WO2012090194A2 - Compositions and methods for treating a skin disorder - Google Patents

Compositions and methods for treating a skin disorder Download PDF

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Publication number
WO2012090194A2
WO2012090194A2 PCT/IL2011/000967 IL2011000967W WO2012090194A2 WO 2012090194 A2 WO2012090194 A2 WO 2012090194A2 IL 2011000967 W IL2011000967 W IL 2011000967W WO 2012090194 A2 WO2012090194 A2 WO 2012090194A2
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Prior art keywords
inula
composition
extract
another embodiment
composition according
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PCT/IL2011/000967
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French (fr)
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WO2012090194A3 (en
Inventor
Galya ABRHAM
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Abrham Galya
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Publication of WO2012090194A2 publication Critical patent/WO2012090194A2/en
Publication of WO2012090194A3 publication Critical patent/WO2012090194A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels

Definitions

  • This invention relates to compositions and methods for treating skin disorders in mammals and more particularly, to compositions and methods for treating viral skin disorders.
  • HSV-2 herpes simplex virus Type 2
  • HSV-2 herpes simplex virus Type 2
  • US 7,083,814 reports that a safe and effective antiviral agent must interrupt the life-cycle of the virus in some manner, such that the virus cannot replicate adequately, and the compound must have negligible or manageable toxicity to the host cells (or patient). In other words, the antiviral agent must be far more toxic to the virus than to the host cell. Another factor which has come to light relates to the long-term side-effects of certain antivirals, as well as the ability of the viruses to adapt or mutate to negate the effect of certain antiviral agents. Alternatively, more general compounds which boost or modulate immune system responses, such as interferons, may be used in combating viral disease, as may vaccines targeted to specific viruses.
  • Inula viscosa (compositae) is known in traditional medicine for a large range of biological activities including antipyretic, anti-bacterial and antifungal activity. Plants from the Compositae family have yielded a wide array of sesquiterpenoids, especially sesquiterpene lactones (SLs), as the main secondary metabolites [Muhammad I et al., 2003]. Two of the sesquiterpene lactones that were published and are well known are: Inuviscolide and Tomentosin. In addition, they exhibits antimicrobial activities [Ali- Shtayeh MS et al., 1998] and even shows cytotoxicity against some cancer cell lines [Woynarowski JM et al., 1981]. Tomentosin has been shown to exhibit fungistatic activity [Cohen Y et al., 2002] and antimalarial activity [Joshi SP et al., 1997].
  • terpenoids represent a chemical defense against environmental stress and provide a repair mechanism for wounds and injuries.
  • effective ingredients in several plant-derived medicinal extracts are also terpenoid compounds of monoterpenoid, sesquiterpenoid, diterpenoid, triterpenoid [A. Salminen et al., 2008].
  • the skin is the largest organ of a mammalian body, serving many important functions, such as regulating body temperature, maintaining water and electrolyte balance, and sensing painful and pleasant stimuli.
  • the skin is adapted to keep dangerous substances from entering the body and provides a shield from the harmful effects of the sun. Any deterioration in skin health may have important consequences on a person's physical and mental health.
  • US 4,254,112 relates to the preparation of an extract of Inula and related species such as Inula viscosa and Inula graveolens (which belong to the family Compositae) which is useful in therapy, in particular as bacteriostatic and fungistatic agent.
  • This extract is useful in the treatment of human beings suffering from infectious diseases.
  • WO9920109A discloses a new sesquiterpene, having the general formula ⁇ 15 ⁇ 20 ⁇ 3. This sesquiterpene was found to possess the property of inhibiting the growth of dermatophytes and particularly of Microsporum canis and Trichophyton rubrum when administered in an adequate dose. This sesquiterpene was obtained from leaves of the plant Inula viscosa. The structural formula of the sesquiterpene and a simple method for its isolation are described.
  • WO03017768A describes infusions of Inula viscosa, and a process to obtain the mentioned infusions by treatment with ethyl alcohol, vegetable oil, or water. The infusions show activity against hematophagic insects, mosquitos, flies, and horseflies.
  • WO05117925 A discloses an Inula viscosa extract for use in treating arthritis and for use an anti-inflammatory, anti-bacterial, anti-fungal, anti-oxidant, anti-yeast agent.
  • the invention further concerns a method for cultivating Inula viscosa plants and an optimized efficient extraction process utilizing ethyl-acetate as the solvent for obtaining an extract characterized by the quantitative presence of carotenoids, flavenoids, tomentosin, sesquiterpene lactones, sterols, and saponins.
  • CN100396295C provides a Chinese medicine for treating viral hepatitides, especially hepatitis A and B, is prepared from Inula flower or its extract or its chemical components and the edible saltpeter.
  • C 1673338A discloses an elecampane detergent, which has in each 1000 g elecampane extract 0.001-950 g, balloonflower root extract 0.001-550 g and Chinese white poplar bark extract 0.001-450 g, except the matrix.
  • the elecampane detergent has excellent skin cleaning and moistening effect, certain germ and virus, especially infectious disease germ and virus, inhibiting and killing effect.
  • the elecampane detergent may be added into detergent, cosmetics, wet towel, toothpaste and other daily used articles to generate skin cleaning, sterilizing and moistening effects.
  • improved methods and compositions are provided for treating viral topical disorders in human patients.
  • cream-based compositions and methods are provided for treating topical disorders related to viral infections.
  • cream-based compositions and methods are provided for treating topical disorders related to Herpes infections.
  • cream-based compositions and methods are provided for treating topical disorders related to Herpes simplex infections.
  • cream-based compositions and methods are provided for treating topical disorders related to Herpes zoster infections.
  • Additional embodiments of the present invention are directed to a novel method for efficient extraction of plant-derived material compounds isolated from Inula viscosa plants.
  • Additional embodiments of the present invention are directed to a novel method for efficient extraction of plant-derived material compounds isolated from herbal plants that contains terpenoids, sesquiterpene lactones, flavones and anti oxidative compounds.
  • compositions of the present invention are directed to a novel method for combination of plant-derived material compounds isolated from Inula viscosa plants with several supplements for more effective and/or synergistic effect.
  • the compositions of the present invention may be formulated with one or more pharmaceutically acceptable carriers to form a topical composition possessing antiviral activity in a form selected from the group consisting of a balm, an ointment, a lotion, a roll-on, a rub, a sticker, a gel, a tincture, a spray and a cream.
  • compositions prepared by the method as described herein.
  • Additional embodiments of the present invention are directed to a topical composition as palliate agent against pain prepared by the methods as described herein.
  • Additional embodiments of the present invention are directed to an oral composition for use in treating autoimmune diseases prepared by the methods described herein.
  • Additional embodiments of the present invention are directed to a topical composition for use in treating pathological conditions, based on over- stimulation of pro-inflammatory cytokines, the composition being prepared as described herein.
  • Additional embodiments of the present invention are directed to a topical composition against blisters that are caused by Herpes simplex virus 3 (HSV3), known commonly as Chickenpox or shingles.
  • HSV3 Herpes simplex virus 3
  • the present invention further provides a topical composition and method for treating warts.
  • compositions for treating a topical disorder associated with a viral infection including at least one of;
  • a plant extract including at least one of tomentosin and inuviscolide
  • a plant cell culture extract including at least one of tomentosin and inuviscolide and
  • the composition the plant extract includes an extract from at least one species selected from the genera Inula, Xanthium and Arnica.
  • the at least one Inula species is selected from Inula acaulis, Inula acervata S.Moore, Inula acinacifolia Gand, Inula acuminata DC, Inula afghanica, Inula anatolica Boiss., Inula auriculata Boiss. & Balansa, Inula bifrons (L.) L., Inula britannica L. - British Yellowhead, Inula Candida (L.) Cass., Inula cappa (Buch.-Ham. ex D.
  • DC Inula caspica Blume, Inula clarkei ( Hookf.) R.R. Stewart, Inula conyzae (Griess.) Meikle - Plougman's-spikenard, Inula crithmoides L. - Golden samphire (syn. Limbarda crithmoides (L.) Dum.), Inula cuspidata, Inula ensifolia L., Inula eupatorioides DC, Inula falconeri Hookf., Inula forrestii, Inula germanica L., Inula grandis Schrenk ex Fisch. & C. A.
  • Inula helenioides DC Inula helenium L.— Elecampane, Inula helianthus-aquatica, Inula helvetica Weber, Inula hirta L., Inula hookeri C B.
  • Inula rhizocephaloides Inula royleana DC. (synonym of Inula racemosa Hookf), Inula rubricaulis, Inula salicina L. - Irish Fleabane, Willowleaf Yellowhead, Inula salsoloides, Inula sericophylla, Inula spiraeifolia L., Inula stewartii Abid & Qaiser, Inula subfloccosa Rech.f, Inula thapsoides Spreng., Inula verbascifolia (Willd.) Hausskn., Inula viscosa and Inula wissmanniana.
  • Inula is also called Dittrichia and/or Cupularia.
  • Inula viscosa is also called Dittrichia viscosa) L.) W. Greuter and/or Cupularia viscosa (L.) Gren. & Godr.
  • the viral infection is selected from the group consisting of HIV, polio virus, hepatitis, herpes viruses, such as HSV-1, HSV-2, HSV-3/VZV, HHV, cytomegalovirus and measles virus, influenza, rhinovirus, parainfluenza, vesicular stomatitis virus (VSV), vaccinia virus (W), encephalitis, African Swine Fever virus and intestine viruses.
  • herpes viruses such as HSV-1, HSV-2, HSV-3/VZV, HHV, cytomegalovirus and measles virus, influenza, rhinovirus, parainfluenza, vesicular stomatitis virus (VSV), vaccinia virus (W), encephalitis, African Swine Fever virus and intestine viruses.
  • the topical disorder is selected from the group consisting of a rash, an allergy, a blister, an abscess, an irritation, a swelling, a coloration, a sore a wart, and a wound.
  • the plant extract is selected from a solvent extract or an aqua extract or a combination of both extracts and a column extract.
  • the composition is a topical composition.
  • the topical composition is selected from the group consisting of a balm, an ointment, a lotion, a roll-on, a rub, a sticker, a gel, a tincture, a spray and a cream.
  • the pharmaceutically acceptable carrier is selected from an aqueous carrier, an oil-based carrier, an emulsion, a cream, a gel and a powder.
  • the composition is an antiviral composition.
  • the composition is an prophylactic antiviral composition.
  • the composition is adapted to act as a palliative agent against pain.
  • the composition is an oral composition.
  • the oral composition is adapted to treat an autoimmune disease.
  • the composition is effective in treating a pathological condition which over-stimulates proinflammatory cytokines.
  • the composition is effective in treating HSV3/VZV-induced blisters.
  • the at least one Inula species includes Inula viscosa. Additionally, according to another embodiment of the present invention, the composition further includes at least one of wheat seed oil, vitamin E, and zinc and other kind of palliate components or natural compounds or synthesized compounds.
  • the composition further includes at least one of; a vegetable oil, a mineral oil, an alcohol, a gel, Aloe vera, paraffin wax, a cream, a stabilizer, a coloring agent, an emulsifier and an Inula viscosa extract.
  • the composition includes both tomentosin and inuviscolide in pharmaceutically effective amounts.
  • a method for treating a topical disorder associated with a viral infection including administering at least one active substance selected from;
  • a plant extract including at least one of tomentosin and inuviscolide
  • a plant cell culture extract including at least one of tomentosin and inuviscolide
  • the plant extract used in the method includes an extract from at least one species selected from the genera Inula, Xanthium and Arnica.
  • the at least one Inula species is selected from Inula acaulis, Inula acervata S.Moore, Inula acinacifolia Gand, Inula acuminata DC, Inula afghanica, Inula anatolica Boiss., Inula auriculata Boiss. & Balansa, Inula bifrons (L.) L., Inula britannica L. - British
  • Inula rhizocephaloides Inula royleana DC. (synonym of Inula racemosa Hookf.), Inula rubricaulis, Inula salicina L. - Irish Fleabane, Willowleaf Yellowhead, Inula salsoloides, Inula sericophylla, Inula spiraeifolia L., Inula stewartii Abid & Qaiser, Inula subfloccosa Rech.f, Inula thapsoides Spreng., Inula verbascifolia (Willd.) Hausskn., Inula viscosa and Inula wissmanniana.
  • the viral infection is selected from the group consisting of HIV, polio virus, RSV, hepatitis, herpes viruses, such as HSV-1, HSV-2, HSV-3, HHV, cytomegalovirus and measles virus, influenza, rhinovirus, parainfluenza, vesicular stomatitis virus (VSV), vaccinia virus (W), encephalitis, Papillomaviruses and African Swine Fever virus.
  • herpes viruses such as HSV-1, HSV-2, HSV-3, HHV, cytomegalovirus and measles virus, influenza, rhinovirus, parainfluenza, vesicular stomatitis virus (VSV), vaccinia virus (W), encephalitis, Papillomaviruses and African Swine Fever virus.
  • the method further includes treating the viral infection.
  • the topical disorder is selected from the group consisting of a rash, an allergy, a blister, an abscess, an irritation, a swelling, a coloration, a sore and a wart.
  • the plant extract is selected from a solvent extract, an aqueous extract, a combination of an organic solvent extract and an aqueous extract, a combination of both extracts and a column extract.
  • the administering step includes administering a topical composition to an afflicted area of skin.
  • the topical composition is selected from the group consisting of a balm, an ointment, a lotion, a roll-on, a rub, a sticker, a gel, a tincture, a spray and a cream.
  • the pharmaceutically acceptable carrier is selected from an aqueous carrier, an oil-based carrier, an emulsion, a cream, a gel and a powder.
  • the method is further adapted to treat pain associated with the topical disorder.
  • the administration is oral.
  • the administration is nasal.
  • the oral method further treats an autoimmune disease.
  • the method is effective in treating a pathological condition which over-stimulates proinflammatory cytokines.
  • the method is effective in treating HSV3 -induced blisters.
  • the at least one Inula species includes Inula viscosa.
  • the at least one active substance is formulated with at least one of wheat seed oil, vitamin E, zinc, other kinds of palliate components, natural compounds or synthesized compounds.
  • the at least one active substance is formulated with at least one of; a vegetable oil, a mineral oil, an alcohol, a gel, Aloe vera, paraffin wax, a cream, a stabilizer, a coloring agent, an emulsifier, and a vitamin.
  • the at least one active substance includes both tomentosin and inuviscolide in pharmaceutically effective amounts.
  • the method further includes:
  • the method further includes waiting for a period of time between step i) and step ii).
  • the period of time is at least twelve hours.
  • steps i) and ii) are each repeated after waiting for an interval of at least twelve hours.
  • the time interval is at least one week.
  • steps i) and ii) are repeated several times, each time after waiting for the duration of the time interval.
  • the method further includes providing the patient with at least one dietary supplement.
  • the at least one dietary supplement is responsive to the results of a blood test of the patient.
  • composition for treating a topical disorder including at least one of;
  • a plant extract including at least one of tomentosin and inuviscolide
  • a plant cell culture extract including at least one of tomentosin and inuviscolide
  • the topical disorder is selected from eczema, an inflammatory disease, acne, a microbial infection, a blistering disease, an itching and non-infectious rash, a skin growth, a parasitic infection, a pigment disorder, a burn, a scar, a chemically-induced disorder, a physically induced disorder and a viral disorder.
  • the itching and non infectious rash is psoriasis.
  • a kit for the treatment of a skin disorder including;
  • the kit includes between about 0.1% to 100% (w/w) of the Inula viscosa extract.
  • the composition includes 0.0001-100% tomentosin and 0.0001-100% inuviscolide.
  • the Inula viscosa extract is obtained by harvesting Inula viscosa plants, drying the harvested plants to obtain a moisture contents of about 0.1% to 100%, grinding the dry biomaterial to powder grain, contacting the powder grain at least one time with ethyl-acetate at elevated temperatures, evaporating the ethyl-acetate and obtaining an extract characterized by its carotenoids, flavenoids, tomentosin, sesquiterpene lactones, sterols, polyphenols and saponins contents.
  • the composition is adapted to act against wounds, including, but not limited to, diabetic wounds, chronic wounds, traumatic wounds, ulcers and pressure sores.
  • the composition is adapted to act against inflammatory skin diseases, including, but not limited to, eczema, atopic dermatitis and seborrhea.
  • the composition is adapted to act against viruses which require at least one of NFKB, ST ATI, CDK and CDC2 cellular proteins for activation thereof.
  • the composition is adapted to act against viruses or viral infections, including, but not limited to, viruses comprising a single strand nucleic acid, viruses comprising a double strand nucleic acid, RNA viruses, DNA viruses, both DNA and RNA viruses and retroviruses.
  • the composition is adapted to act as a palliative against scars or burns.
  • the composition is adapted to act as a peeling agent.
  • the compositions of the present invention may include Inula plants or any other herbal plants containing terpenoids, sesquiterpene lactones, or anti oxidative agents, such as flavones or polyphenols.
  • the present invention further provides a use of at least one of:
  • a plant extract including at least one of tomentosin and inuviscolide
  • a plant cell culture extract including at least one of tomentosin and inuviscolide
  • a pharmaceutically acceptable carrier in the preparation of a medicament for treating a disorder.
  • the present invention further provides at least one of:
  • a plant extract including at least one of tomentosin and inuviscolide
  • a plant cell culture extract including at least one of tomentosin and inuviscolide
  • a pharmaceutically acceptable carrier for use in the preparation of a medicament for treating a disorder.
  • Figs. 1A- ID are images of treatment stages using the compositions of the present invention in treating a sore on a lip induced by HSV-1 with a cream as described in the extract preparation, three times a day: (Fig. 1A) before treatment, (Fig. IB) after 18 hours treatment, (Fig. 1C) after 36 hours treatment, (Fig. ID) after 72 hours treatment, in accordance with an embodiment of the present invention;
  • Figs. 2 A- 2F are images of treatment stages using the compositions of the present invention in treating an abscess with a combined treatment of a tincture and a cream, as described in the extract preparation, four times a day: (Fig. 2A) before treatment, (Fig. 2B) after three days treatment, (Fig. 2C) after four days treatment, (Fig. 2D) after five days treatment, (Fig. 2E) after six days treatment, and (Fig. 2F) after 23 days, in accordance with an embodiment of the present invention;
  • Figs. 3 A- 3C are images of treatment stages using the compositions of the present invention in treating Seborrhea with a cream as described in the extract preparation, twice a day: (Fig. 3A) before treatment, (Fig. 3B) after 48 hours treatment, (Fig. 3C) after 72 hours treatment, in accordance with an embodiment of the present invention;
  • Figs. 4A- 4F are images of tissue culture plates with cells infected with Herpes simplex virus type 3 (HSV3)-4A and 4B controls without treatment; 4C-4E treated with Inula viscosa extract; and 4F treated with Acyclovir, in accordance with an embodiment of the present invention;
  • Figs. 5A- 5C are images of treatment stages using the compositions of the present invention in treating a Herpes simplex 1 (HSV1) with a tincture, as described in the extract preparation, three times a day: (Fig. 5 A) before treatment, (Fig. 5B) after 36 hours treatment, (Fig. 5C) after 48 hours treatment, in accordance with an embodiment of the present invention;
  • HSV1 Herpes simplex 1
  • Figs. 6A-6D are images of treatment stages using the compositions of the present invention in treating a Herpes simplex 1 (HSV1) ) with a tincture as described in the extract preparation, four times a day: (Fig. 6A) before treatment, (Fig. 6B) after 24 hours treatment, (Fig. 6C) after 48 hours treatment, and (Fig. 6D) after 72 hours treatment, in accordance with an embodiment of the present invention;
  • HSV1 Herpes simplex 1
  • Figs. 7A-7D are images of treatment stages using the compositions of the present invention in treating chronic wounds on a heel with a combined treatment of a tincture and a cream, as described in the extract preparation, twice a day - (Fig. 7A) before treatment, (Fig. 7B) after 72 hours treatment, (Fig. 7C) after 5 days' treatment, and (Fig. 7D) after 7 days' treatment, in accordance with an embodiment of the present invention.
  • Figs. 8A-8D are images of treatment stages using the compositions of the present invention in treating viral warts caused by Molluscum contagious virus with a cream as described in the extract preparation twice a day -(Fig. 8A) before treatment, (Fig. 8B) before treatment, (Fig. 8C) after 7 days' treatment, and (Fig. 8D), after one month's treatment, in accordance with an embodiment of the present invention.
  • improved methods and compositions are provided for treating viral topical disorders in human patients.
  • compositions and methods are provided for treating topical disorders related to viral infections.
  • compositions and methods are provided for treating topical disorders related to Herpes infections.
  • compositions and methods are provided for treating topical disorders related to Herpes simplex infections.
  • compositions and methods are provided for treating topical disorders related to Herpes zoster infections.
  • Additional embodiments of the present invention are directed to a novel method for efficient extraction of plant-derived material compounds isolated from Inula viscosa plants.
  • compositions for treating viral disorders and/or topical disorders associated with the viral disorders comprise one or more active ingredients from one or more plant sources.
  • the plant sources may include ground plants or plant parts, plant extracts, plant cell cultures and the like. More particularly, some non-limiting embodiments exemplify the plants are typically from the Inula, Xanthium and Arnica genera
  • Inula is a large genus of about 90 species of flowering plants in the family Asteraceae, native to Europe, Asia and Africa.
  • Inula species include, but are not limited to, Inula acaulis, Inula acervata S.Moore, Inula acinacifolia Gand, Inula acuminata DC, Inula afghanica, Inula anatolica Boiss., Inula auriculata Boiss. & Balansa, Inula bifrons (L.) L., Inula britannica L. - British Yellowhead, Inula Candida (L.) Cass., Inula cappa (Buch.-Ham. ex D.
  • DC Inula caspica Blume, Inula clarkei ( Hookf.) R.R.Stewart, Inula conyzae (Griess.) Meikle— Plougman's-spikenard, Inula crithmoides L. - Golden samphire (syn. Limbarda crithmoides (L.) Dum.), Inula cuspidata, Inula ensifolia L., Inula eupatorioides DC, Inula falconeri Hookf., Inula forrestii, Inula germanica L, Inula grandis Schrenk ex Fisch. & C. A.
  • Inula helenioides DC Inula helenium L. - Elecampane, Inula helianthus-aquatica, Inula helvetica Weber, Inula hirta L., Inula hook ri C. B.
  • Inula rhizocephaloides Inula royleana DC. (synonym of Inula racemosa Hookf), Inula rubricaulis, Inula salicina L. - Irish Fleabane, Willowleaf Yellowhead, Inula salsoloides, Inula sericophylla, Inula spiraeifolia L., Inula stewartii Abid & Qaiser, Inula subfloccosa Rech.f, Inula thapsoides Spreng., Inula verbascifolia (Willd.) Hausskn. and Inula wissmanniana.
  • Some embodiments of the present invention relate to extracts from Inula plants. More particularly, some embodiments relate to the type Inula viscosa plant.
  • the Inula viscosa extract may be used topically or preferably in a formulation comprising suitable excipients.
  • the amount of the Inula viscosa extract in the formulation is about 0.01% to about 100%.
  • the extract is obtained by harvesting the above-ground parts such as, but not limited to: leaves, twigs, bark, flowers, buds, fruits, peels, seeds, roots, rhizomes, tubers, or bulbs.
  • the active ingredient, tomentosin which may be purchased from WuXi AppTec (Tianjin) Co., Ltd. No.41,Kaitai Science & Technology Building 5th Avenue, Tianjin Economic- Technological Development Area (TEDA), Tianjin, China 300457 - catalog number NPT0324- Xanthalongin (Tomentosin).
  • tomentosin is meant CAS no. 33649-15-9 (believed to be of a chemical structure formula ⁇ 5 ⁇ 2 ⁇ 0 3 ).
  • Inuviscolide is meant CAS no. 63109-30-8 (believed to be of a chemical structure formula C 15 H 2 o0 3 ).
  • the active ingredients may be prepared by plant cell culture from Xanthium strumarium or other species, using the method as is described in (Biotechnology and Bioprocess Engineering Volume 6, Number 1, 51-55, 2001 Jae Sung Park, Gi Hwan Yi, Min Hee Nam and Sun Ho Park).
  • the active ingredients may be prepared from Arnica species in accordance with (Willuhn, G.; Herrmann, H. D., 1979: Planta Medica 37(4): 325-332 Composition of Arnica species 12 Communication Xanthalongin, a new xanthanolide from the flowers of Arnica longifolia).
  • viruses tested/to be tested include HIV, polio virus, hepatitis, RSV, Herpes viruses, such as HSV-1, HSV-2, HHV, cytomegalovirus and measles virus, influenza, rhinovirus, parainfluenza, vesicular stomatitis virus (VSV), vaccinia virus (W), encephalitis, Papillomaviruses and African Swine Fever virus.
  • compositions of the present invention may be used, inter alia, for treating a topical disorder associated with a viral infection.
  • the compositions may include at least one or more of, at least two or more of, at least three or more of; at least four or more of, at least five or more of, at least six or more of, or all of:
  • a plant extract including at least one of tomentosin and inuviscolide
  • inuviscolide c) inuviscolide; d) a plant cell culture extract including at least one of tomentosin and inuviscolide
  • compositions of the present invention may be provided in any suitable dosage form.
  • the dosage form is an oral dosage form.
  • Oral dosage forms comprise liquids (spray, solutions, suspensions, and emulsions), semi-solids (pastes), and solids (tablets, capsules, powders, granules, premixes, and medicated blocks).
  • the dosage forms comprising compositions of the present invention comprise at least 0.01-0.1 ⁇ g tomentosin, at least 0.1-1 ⁇ g tomentosin, at least 1-10 ⁇ g tomentosin, at least 10-100 ⁇ g tomentosin, or at least 100-1000 ⁇ g tomentosin, or at least 1000 ⁇ g-1000 mg tomentosin.
  • compositions of the present invention comprise at least 0.01-0.1 ⁇ g inuviscolide, at least 0.1-1 g inuviscolide, at least 1-10 ⁇ g inuviscolide, at least 10-100 ⁇ g inuviscolide, or at least 100-1000 ⁇ g inuviscolide, or at least 1000 ⁇ g-1000 mg inuviscolide.
  • the dosage forms comprising compositions of the present invention comprise at least 0.01-0.1 ⁇ g Inula viscosa dry/liquid extract, at least 0.1-1 ⁇ g Inula viscosa dry/liquid extract, at least 1-10 ⁇ g Inula viscosa dry/liquid extract, at least 10-100 ⁇ g Inula viscosa dry/liquid extract, at least 100-1000 ⁇ g Inula viscosa dry/liquid extract, at least 1-10 mg Inula viscosa dry/liquid extract, or at least 10-100 mg Inula viscosa dry/liquid extract, or at least 100- 1000 mg Inula viscosa dry/liquid extract.
  • a dosage form of the present invention comprises 25-250 ⁇ g tomentosin. In another embodiment, a dosage form of the present invention comprises 100-200 ⁇ g tomentosin. In another, embodiment, a dosage form of the present invention comprises 1-1000 ⁇ g tomentosin. In another, embodiment, a dosage form of the present invention comprises 100-150 ⁇ g tomentosin. In one embodiment, a dosage form of the present invention comprises 25-250 ⁇ g inuviscolide. In another embodiment, a dosage form of the present invention comprises 100-200 g inuviscolide. In another, embodiment, a dosage form of the present invention comprises 1-1000 ⁇ g inuviscolide. In another, embodiment, a dosage form of the present invention comprises 100-150 ⁇ g inuviscolide.
  • oral dosage forms in the art include, WO90/04391, which discloses an oral dosage form of omega-3 polyunsaturated acids to overcome the problems of vascular diseases. It is known to supply said acids in soft gelatine capsule shells.
  • EP 2 240 581 Bl discloses a gelatine capsule for pharmaceutical use with a controlled release of active ingredients and a process for the preparation of said gelatine capsules. During said process xylose is added to the liquid gelatine from which afterwards gelatine capsules are formed. Gelatine capsules manufactured according to the process provide retarded release of active ingredients.
  • US Patent No. 7,264,824 discloses and oral dosage form for food and food supplements, as well as dietetics comprising polyunsaturated acids in a xylose-hardened gelatine capsule with a retarded release time.
  • compositions described herein may be in a suspension, emulsion, solution or spray.
  • a suspension is a coarse dispersion of insoluble drug particles, generally with a diameter exceeding 1 ⁇ , in a liquid (usually aqueous) medium.
  • Suspensions are useful for administering insoluble or poorly soluble drugs/components or in situations when the presence of a finely divided form of the material in the GI tract is required.
  • the taste of most drugs is less noticeable in suspension than in solution, due to the drug being less soluble in suspension.
  • Particle size is an important determinant of the dissolution rate and bioavailability of drugs in suspension.
  • suspensions include surfactants and thickening agents. Surfactants wet the solid particles, thereby ensuring the particles disperse readily throughout the liquid.
  • An emulsion is a system consisting of 2 immiscible liquid phases, one of which is dispersed throughout the other in the form of fine droplets; droplet diameter generally ranges from 0.1-100 ⁇ .
  • the 2 phases of an emulsion are known as the dispersed phase and the continuous phase.
  • Emulsions are inherently unstable and are stabilized through the use of an emulsifying agent, which prevents coalescence of the dispersed droplets.
  • Creaming as occurs with milk, also occurs with pharmaceutical emulsions. However, it is not a serious problem because a uniform dispersion returns upon shaking. Creaming is, nonetheless, undesirable because it is associated with an increased likelihood of the droplets coalescing and the emulsion breaking.
  • Other additives include buffers, antioxidants, and preservatives.
  • Emulsions for oral administration are usually oil (the active ingredient) in water, and facilitate the administration of oily substances such as castor oil or liquid paraffin in a more palatable form.
  • a paste is a 2-component semi-solid in which drug is dispersed as a powder in an aqueous or fatty base.
  • the particle size of the active ingredient in pastes can be as large as 100 ⁇ .
  • the vehicle containing the drug may be water; a polyhydroxy liquid such as glycerin, propylene glycol, or polyethylene glycol; a vegetable oil; or a mineral oil.
  • Other formulation excipients include thickening agents, cosolvents, adsorbents, humectants, and preservatives.
  • the thickening agent may be a naturally occurring material such as acacia or tragacanth, or a synthetic or chemically modified derivative such as xanthum gum or hydroxypropylmethyl cellulose.
  • the degree of cohesiveness, plasticity, and syringeability of pastes is attributed to the thickening agent. It may be necessary to include a cosolvent to increase the solubility of the drug. Syneresis of pastes is a form of instability in which the solid and liquid components of the formulation separate over time; it is prevented by including an adsorbent such as microcrystalline cellulose. A humectant (eg, glycerin or propylene glycol) is used to prevent the paste that collects at the nozzle of the dispenser from forming a hard crust. Microbial growth in the formulation is inhibited using a preservative. It is critical that pastes have a pleasant taste or are tasteless.
  • a tablet consists of one or more active ingredients and numerous excipients and may be a conventional tablet that is swallowed whole, a chewable tablet, or a modified- release tablet (more commonly referred to as a modified-release bolus due to its large unit size).
  • Conventional and chewable tablets are used to administer drugs to dogs and cats, whereas modified-release boluses are administered to cattle, sheep, and goats.
  • the physical and chemical stability of tablets is generally better than that of liquid dosage forms.
  • the main disadvantages of tablets are the bioavailability of poorly water-soluble drugs or poorly absorbed drugs, and the local irritation of the GI mucosa that some drugs may cause.
  • a capsule is an oral dosage form usually made from gelatin and filled with an active ingredient and excipients.
  • Two common capsule types are available: hard gelatin capsules for solid-fill formulations, and soft gelatin capsules for liquid-fill or semi- solid-fill formulations.
  • Soft gelatin capsules are suitable for formulating poorly water- soluble drugs because they afford good drug release and absorption by the GI tract.
  • Gelatin capsules are frequently more expensive than tablets but have some advantages. For example, particle size is rarely altered during capsule manufacture, and capsules mask the taste and odor of the active ingredient and protect photolabile ingredients.
  • a powder is a formulation in which a drug powder is mixed with other powdered excipients to produce a final product for oral administration.
  • Powders have better chemical stability than liquids and dissolve faster than tablets or capsules because disintegration is not an issue. This translates into faster absorption for those drugs characterized by dissolution rate-limited absorption. Unpleasant tastes can be more pronounced with powders than with other dosage forms and can be a particular concern with in-feed powders, in which it contributes to variable ingestion of the dose. Moreover, sick animals often eat less and are therefore not amenable to treatment with in-feed powder formulations.
  • Drug powders are principally used prophylactically in feed, or formulated as a soluble powder for addition to drinking water or milk replacer. Powders have also been formulated with emulsifying agents to facilitate their administration as liquid drenches.
  • a granule is a dosage form consisting of powder particles that have been aggregated to form a larger mass, usually 2-4 mm in diameter. Granulation overcomes segregation of the different particle sizes during storage and/or dose administration, the latter being a potential source of inaccurate dosing. Granules and powders generally behave similarly; however, granules must deaggregate prior to dissolution and absorption.
  • a premix is a solid dosage form in which an active ingredient, such as a coccidiostat, production enhancer, or nutritional supplement, is formulated with excipients.
  • Premix products are mixed homogeneously with feed at rates (when expressed on an active ingredient basis) that range from a few milligrams to -200 g/ton of food/beverage
  • the density, particle size, and geometry of the premix particles should match as closely as possible those of the feed in which the premix will be incorporated to facilitate uniform mixing. Issues such as instability, electrostatic charge, and hygroscopicity must also be addressed.
  • the excipients present in premix formulations include carriers, liquid binders, diluents, anti-caking agents, and anti- dust agents.
  • Carriers such as wheat middlings, soybean mill run, and rice hulls, bind active ingredients to their surfaces and are important in attaining uniform mixing of the active ingredient.
  • a liquid binding agent such as a vegetable oil, should be included in the formulation whenever a carrier is used.
  • Diluents increase the bulk of premix formulations, but unlike carriers, do not bind the active ingredients. Examples of diluents include ground limestone, dicalcium phosphate, dextrose, and kaolin.
  • Caking in a premix formulation may be caused by hygroscopic ingredients and is addressed by adding small amounts of anti-caking agents such as calcium silicate, silicon dioxide, and hydrophobic starch.
  • the dust associated with powdered premix formulations can have serious implications for both operator safety and economic losses, and is reduced by including a vegetable oil or light mineral oil in the formulation. An alternate approach to overcoming dust is to granulate the premix formulation.
  • a medicated block is a compressed feed material that contains an active ingredient, such as a drug, anthelmintic, surfactant (for bloat prevention), or a nutritional supplement, and is commonly packaged in a cardboard box. Ruminants typically have free access to the medicated block over several days, and variable consumption may be problematic. This concern is addressed by ensuring the active ingredient is nontoxic, stable, palatable, and preferably of low solubility.
  • excipients in the formulation modulate consumption by altering the palatability and/or the hardness of the medicated block. For example, molasses increases palatability and sodium chloride decreases it.
  • a binder such as lignin sulfonate
  • the hygroscopic nature of molasses in a formulation may also impact the hardness of medicated blocks and is addressed by using appropriate packaging.
  • the composition of the present invention is in a chewable oral dosage form.
  • the chewable oral dosage form is a chewable tablet.
  • the chewable tablet of the invention is taken slowly by chewing or sucking in the mouth.
  • the chewable tablet of the invention enables the Inula viscosa extracts contained therein to be orally administered without drinking.
  • the composition may comprise any suitable flavor or combination of flavors.
  • composition may further comprise other additives, coloring, and emulsifiers.
  • flavors and additives may be of a natural, semi-synthetic, synthetic source or combinations thereof.
  • the composition further comprises fructose, sorbitol, microcrystalline cellulose, magnesium stearate, or any combination thereof.
  • the composition further comprises chamomile.
  • the composition further comprises ginger.
  • the composition further comprises peppermint.
  • the composition further comprises anise.
  • the composition further comprises fennel.
  • the composition further comprises thyme.
  • the composition further comprises Arsenicum album.
  • the composition further comprises Carbo vegetabilis.
  • the composition further comprises Ignatia, homeopathic ipecac.
  • the composition further comprises Nux vomica.
  • the composition further comprises Zingiber officinale.
  • composition of the present invention is in the form of a chewing gum product.
  • chewing gum compositions contemplated by the present invention comprise all types of sugar and sugarless chewing gums and chewing gum formulations known to those skilled in the art, including regular and bubble gum types.
  • chewing gum compositions of the invention comprise a chewing gum base, a modifier, a bulking agent or sweetener, and one or more other additives such as, flavoring agents, colorants and antioxidants.
  • the modifying agents are used to soften, plasticize and/or compatibilize one or more of the components of the gum base and/or of the formulation as a whole.
  • the present invention provides a soft, chewable dosage form which is pliable and chewy, yet dissolves quickly in the mouth, has a long shelf life, contains little moisture which improves stability and decreases the tendency for the dosage form to dry out, does not require cooking or heating as part of the manufacturing process.
  • the dosage form is used as a matrix for Inula viscosa extracts.
  • the chewable tablet of the invention comprises a metal salt such as calcium, magnesium, aluminum salt, or any mixture thereof.
  • the chewable tablet of the invention comprises hydroxyalkyl cellulose.
  • the chewable tablet of the invention comprises low viscosity hydroxyalkyl cellulose.
  • the chewable tablet of the invention comprises high viscosity hydroxyalkyl cellulose.
  • the chewable tablet of the invention comprises various additives. In another embodiment, the chewable tablet of the invention comprises sweeteners. In another embodiment, the chewable tablet of the invention comprises acidic ingredients. In another embodiment, the chewable tablet of the invention comprises taste correctives. In another embodiment, the chewable tablet of the invention comprises polymeric compounds. In another embodiment, the chewable tablet of the invention comprises essential oils.
  • the chewable tablet of the invention is a soft tablet. In another embodiment, the chewable tablet of the invention is made in a state of soft candy. In another embodiment, the chewable tablet of the invention is made in a state of jelly.
  • the chewable tablet of the invention comprises a core comprising the Inula viscosa extracts of the invention.
  • the chewable tablet of the invention comprises an outer layer wrapping the core which is made up of chewable base such as a gum, a soft candy or a caramel.
  • compositions of the present invention may be provided in any suitable food of a solid, semi-solid or liquid form.
  • the chewable tablet of the invention protects the Inula viscosa extracts that are liable to transform.
  • the chewable tablet of the invention comprises pectin.
  • the chewable tablet of the invention comprises maltitol.
  • the chewable tablet of the invention comprises isomalt.
  • the chewable tablet of the invention comprises liquid glucose.
  • the chewable tablet of the invention comprises sugar.
  • the chewable tablet of the invention comprises citric acid.
  • the chewable tablet of the invention comprises sorbitol.
  • the chewable tablet of the invention comprises a flavoring agent.
  • the chewable tablet of the invention comprises a natural flavoring agent.
  • the chewable tablet of the invention comprises a synthetic flavor. In another embodiment, the chewable tablet of the invention comprises a volatile oil. In another embodiment, the chewable tablet of the invention comprises synthetic flavor oil. In another embodiment, the chewable tablet of the invention comprises a flavoring aromatic. In another embodiment, the chewable tablet of the invention comprises a oleoresin. In another embodiment, the chewable tablet of the invention comprises an extract derived from a plant. In another embodiment, the chewable tablet of the invention comprises an extract derived from a leaf. In another embodiment, the chewable tablet of the invention comprises an extract derived from a flower. In another embodiment, the chewable tablet of the invention comprises an extract derived from a fruit. In another embodiment, the chewable tablet of the invention comprises an extract derived from a stem.
  • the chewable tablet of the invention comprises citrus oil such as but not limited to lime, grapefruit, lemon, or orange.
  • the chewable tablet of the invention comprises fruit essences such as but not limited to apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot or other fruit flavors.
  • the chewable tablet of the invention comprises flavorings such as but not limited to aldehydes and esters such as benzaldehyde (cherry, almond), citral, i.e., alphacitral (lemon, lime), neral, i.e., beta- citral (lemon, lime) decanal (orange, lemon), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), adlehyde C-12 (citrus fruits), tolyl aldehyde (cherry, almond), 2,6- dimethyloctanal (green fruit), and 2-dodecenal (citrus, mandarin), mixtures thereof and the like.
  • aldehydes and esters such as benzaldehyde (cherry, almond), citral, i.e., alphacitral (lemon, lime), neral, i.e., beta- citral (lemon, lime) decanal (orange,
  • the chewable tablet of the invention comprises a gum.
  • the chewable tablet of the invention comprises a soft gum. In another embodiment, the chewable tablet of the invention comprises nougat. In another embodiment, the chewable tablet of the invention comprises soft candy. In another embodiment, the chewable tablet of the invention comprises hard candy. In another embodiment, the chewable tablet of the invention comprises caramel. In another embodiment, the chewable tablet of the invention comprises an enhancing agent of chewing property.
  • sugar used in the present invention may be selected from the group consisting of white sugar, liquid glucose, sorbitol, dextrose, isomalt, liquid maltitol, aspartame and lactose, and this sugar may comprise 30-90 weight % by total weight of the ingredients.
  • the chewable tablet of the invention comprises a sweetener such as but not limited to: glucose (corn syrup), dextrose, invert sugar, fructose, and mixtures thereof (when not used as a carrier); saccharin and its various salts such as the sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Stevia Rebaudiana (Stevioside); chloro derivatives of sucrose such as suralose; sugar alcohols such as sorbitol, mannitol, xylitol, and the like.
  • a sweetener such as but not limited to: glucose (corn syrup), dextrose, invert sugar, fructose, and mixtures thereof (when not used as a carrier); saccharin and its various salts such as the sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Stevia Rebaudiana (Stevioside
  • the chewable tablet of the invention comprises hydrogenated starch hydrolysates and the synthetic sweetener 3,6-dihydro-6-methyl-l-l-l,2,3- oxathiazin-4-one-2,2-dioxide.
  • the chewable tablet of the invention comprises the potassium salt (acesulfame-K), and sodium and calcium salts of 3,6-dihydro-6-methyl-l-l-l,2,3-oxathiazin-4-one-2,2-dioxide.
  • the chewable tablet of the invention comprises other sweeteners known to one of skill in the art.
  • glycerin, lecithin, hydrogenated palm oil or glyceryl monostearate are used as a protecting agent of crystallization of the sugars in 0.02-3.0 weight % by total weight of the ingredients, to prevent adhesion to oral cavity and improve the soft property of the products.
  • isomalt or liquid maltitol are used as an enhancing agent of chewing property.
  • gelatin or arabic gum are used as a keeping agent of hardness and extension property in 0.1-3.0 weight % by total weight of the ingredients.
  • food flavor or a fruits extract; a souring agent such as citric acid are added in adequate amount.
  • a coloring agent such as a food color is optionally added in a small amount.
  • a further embodiment of the present invention includes the use of an effervescent disintegration agent.
  • its action aids in the masking of objectionable taste of the Inula viscosa extract.
  • the effervescent disintegration agent is an acid.
  • the effervescent disintegration agent is citric acid.
  • the effervescent disintegration agent is tartaric acid.
  • the effervescent disintegration agent is malic acid.
  • the effervescent disintegration agent is fumaric acid.
  • the effervescent disintegration agent is adipic acid.
  • the effervescent disintegration agent is succinic acid.
  • the effervescent disintegration agent is at least one base such as but not limited to: carbonate salts, bicarbonate salts and mixtures thereof.
  • the chewable tablet of the invention comprises a crystallization modifier such but not limited to, surfactants (Spans.TM. and Tweens.TM.), dextrose, polyethylene glycol (PEG), polypropylene glycol (PPG), etc. These modifiers generally provide controlled acceleration of crystallization while the matrix is bound. In another embodiment, these crystallization modifiers enhance the formation of a crystalline frame and the conversion of the remaining mass.
  • a crystallization modifier such but not limited to, surfactants (Spans.TM. and Tweens.TM.), dextrose, polyethylene glycol (PEG), polypropylene glycol (PPG), etc.
  • these modifiers generally provide controlled acceleration of crystallization while the matrix is bound.
  • these crystallization modifiers enhance the formation of a crystalline frame and the conversion of the remaining mass.
  • crystallization modifiers are surfactants having a hydrophilic to lipid balance (HLB) of six or greater, i.e., they have the same degree of hydrophilicity as surfactants characterized by degree of HLB.
  • HLB hydrophilic to lipid balance
  • such materials include, but are not limited to anionic, cationic and zwitterionic surfactants as well as neutral materials which have an HLB of six or greater.
  • crystallization modifiers are hydrophilic materials having polyethylene oxide linkages.
  • crystallization modifiers have a molecular weight of at least 100.
  • the chewable tablet of the invention comprises a filler.
  • filler increases the bulk of the tablet.
  • the filler is calcium sulfate, both di- and tri basic, starch, calcium carbonate, microcrystalline cellulose, modified starches, lactose, sucrose, mannitol, sorbitol, or any combination thereof.
  • the chewable tablet of the invention comprises a binder such as but not limited to: starches, pre-gelatinize starches, gelatin, polyvinylpyrrolidone, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, and polyvinylalcohols.
  • a binder such as but not limited to: starches, pre-gelatinize starches, gelatin, polyvinylpyrrolidone, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, and polyvinylalcohols.
  • the chewable tablet of the invention comprises a lubricant such as but not limited to: magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene, monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate and light mineral oil.
  • a lubricant such as but not limited to: magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene, monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate and light mineral oil.
  • the chewable tablet of the invention comprises a dispersion enhancer such as but not limited to: starch, alginic acid, polyvinylpyrrolidones, guar gum, partially hydrolyzed guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants.
  • a dispersion enhancer such as but not limited to: starch, alginic acid, polyvinylpyrrolidones, guar gum, partially hydrolyzed guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants.
  • the chewable tablet of the invention comprises a disintegrant such as but not limited to: Croscarmellose sodium, marketed under the trade name Ac-Di-Sol.
  • the chewable tablet of the invention comprises an absorbent such as but not limited to: maltodextrin.
  • the chewable tablet of the invention comprises an emulsifier such as but not limited to: Mono- and diglycerides, Oleaginous substances such as food oils like Medium, Chain Triglycerides (MCT), and Stearine D 17.
  • the chewable tablet of the invention comprises a water soluble bulking agent such as but not limited to: hydrocolloid thickeners and binders, such as gum arabic, pectins, modified starches, alginates, carrageenans, xanthan gums, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, propylene glycol alginate, polyvinylpyrrolidone (PVP), carboxyvinyl polymers (such as Carbopol.RTM.), polyethylene oxide polymers (such as Polyox.RTM.), sorbitol, xylitol, sucrose, fructose, dextrose, mannitol, starch maltodextrin, corn syrup solids, or combinations thereof.
  • hydrocolloid thickeners and binders such as gum arabic, pectins, modified starches, alginates, carrageenans, xanthan gums, carboxymethylcellulose,
  • the chewable tablet of the invention comprises a water insoluble bulking agent such as but not limited to: talc, dicalcium phosphate, powdered celluloses, microcrystalline celluloses and antacid compounds.
  • a water insoluble bulking agent such as but not limited to: talc, dicalcium phosphate, powdered celluloses, microcrystalline celluloses and antacid compounds.
  • the chewable tablet of the invention comprises Inula viscosa extracts in compressed particles.
  • individual particles are coated with a blend of cellulose acetate or cellulose acetate butyrate and polyvinyl pyrrolidone (USP Povidone or "PVP").
  • the coating provides excellent taste masking while still permitting acceptable bioavailability of the Inula viscosa extracts.
  • the chewable tablet in another embodiment, the chewable tablet.
  • the invention relates to a composition of the invention comprised within chewable and edible soft gelatin capsules, the shells of which comprise gelatin, water, plasticizer and a hydrogenated starch hydrolysate.
  • soft gelatin shell comprises about 10-45% gelatin; about 5-30% water; about 12-35% plasticizer; and about 2-25% of a hydrogenated starch hydrolysate.
  • the shell encloses a soft gelatin capsule fill material.
  • the gelatin may be of Type A, Type B, or a mixture thereof.
  • the present capsule shell further comprises a hydrogenated starch hydrolysate.
  • chewable systems of the invention are preferable for administering the compositions of the invention.
  • the act of chewing increases the surface area of the Inula viscosa extract and increases the rate of absorption by the digestive tract.
  • chewable systems of the invention provide Inula viscosa extract, topically to the mouth or throat areas for both local effects and systemic absorption.
  • compositions that contain Inula viscosa extract for example by mixing, granulating, or tablet-forming processes, is well understood in the art.
  • the Inula viscosa extracts are often mixed with excipients that are pharmaceutically acceptable and compatible with the active ingredient.
  • the active ingredients of compositions of the present invention are mixed with additives customary for this purpose, such as vehicles, stabilizers, or inert diluents, and converted by customary methods into suitable forms for administration, such as tablets, coated tablets, hard or soft gelatin capsules, aqueous, alcoholic or oily solutions.
  • additional methods of administering the compositions of the invention comprise injectable dosage forms.
  • the injectable is administered intraperitonealy.
  • the injectable is administered intramuscularly.
  • the injectable is administered intradermally.
  • the injectable is administered intravenously.
  • the pharmaceutical compositions are administered by intravenous, intra-arterial, or intra-muscular injection of a liquid preparation.
  • suitable liquid formulations include solutions, suspensions, dispersions, spray (liquid under pressure), nasal preparations, emulsions, oils and the like.
  • the pharmaceutical compositions are administered intravenously and are thus formulated in a form suitable for intravenous administration.
  • the pharmaceutical compositions are administered intra-arterially and are thus formulated in a form suitable for intra-arterial administration.
  • the pharmaceutical compositions are administered intra-muscularly and are thus formulated in a form suitable for intra-muscular administration.
  • additional methods of administering the Inula viscosa extracts of the invention comprise dispersions, suspensions or emulsions.
  • the dispersion, suspension or emulsion is administered orally.
  • the solution is administered by infusion.
  • the solution is a solution for inhalation.
  • the pharmaceutical composition is administered as a suppository, for example a rectal suppository or a urethral suppository.
  • the pharmaceutical composition is administered by subcutaneous implantation of a pellet.
  • the pellet provides for controlled release of active compound agent over a period of time.
  • pharmaceutically acceptable carriers for liquid formulations are aqueous or non-aqueous solutions, suspensions, emulsions or oils.
  • non-aqueous solvents are propylene glycol, polyethylene glycol, and injectable organic esters such as ethyl oleate.
  • Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media.
  • oils are those of animal, vegetable, or synthetic origin, for example, peanut oil, soybean oil, olive oil, sunflower oil, fish-liver oil, another marine oil, or a lipid from milk or eggs. Each possibility represents a separate embodiment of the present invention.
  • parenteral vehicles for subcutaneous, intravenous, intraarterial, or intramuscular injection
  • parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's and fixed oils.
  • Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers such as those based on Ringer's dextrose, and the like.
  • sterile liquids such as water and oils, with or without the addition of a surfactant and other pharmaceutically acceptable adjuvants.
  • water, saline, aqueous dextrose and related sugar solutions, and glycols such as propylene glycols or polyethylene glycol are preferred liquid carriers, particularly for injectable solutions.
  • oils are those of animal, vegetable, or synthetic origin, for example, peanut oil, soybean oil, olive oil, sunflower oil, fish-liver oil, another marine oil, or a lipid from milk or eggs. Each possibility represents a separate embodiment of the present invention.
  • the pharmaceutical compositions provided herein are controlled-release compositions, i.e. compositions in which the active compounds are released over a period of time after administration.
  • Controlled- or sustained-release compositions include formulation in lipophilic depots (e.g. fatty acids, waxes, oils).
  • the composition is an immediate-release composition, i.e. a composition in which all the active compound is released immediately after administration. Each possibility represents a separate embodiment of the present invention.
  • the pharmaceutical composition is delivered in a controlled release system.
  • the Inula viscosa extracts, tomentosin and or inuviscolide are administered using intravenous infusion, an implantable osmotic pump, a transdermal patch, liposomes, or other modes of administration.
  • a pump is used (see Langer, supra; Sefton, CRC Crit. Ref. Biomed. Eng. 14:201 (1987); Buchwald et al., Surgery 88:507 (1980); Saudek et al., N. Engl. J. Med. 321:574 (1989).
  • polymeric materials are used; e.g. in microspheres in or an implant.
  • a controlled release system is placed in proximity to the therapeutic target, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138 (1984); and Langer R, Science 249: 1527-1533 (1990).
  • a controlled release system is placed in proximity to the therapeutic target, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138 (1984); and Langer R, Science 249: 1527-1533 (1990).
  • compositions also include, in another embodiment, incorporation of the active materials into or onto particulate preparations of polymeric compounds such as polylactic acid, polglycolic acid, hydrogels, etc, or onto liposomes, microemulsions, micelles, unilamellar or multilamellar vesicles, erythrocyte ghosts, or spheroplasts.)
  • polymeric compounds such as polylactic acid, polglycolic acid, hydrogels, etc, or onto liposomes, microemulsions, micelles, unilamellar or multilamellar vesicles, erythrocyte ghosts, or spheroplasts.
  • particulate compositions coated with polymers e.g. poloxamers or poloxamines
  • polymers e.g. poloxamers or poloxamines
  • the compound coupled to antibodies directed against tissue-specific receptors, ligands or antigens or coupled to ligands of tissue-specific receptors are also included in the present invention.
  • polymers e.g. poloxamers or poloxamines
  • Also comprehended by the invention are compounds modified by the covalent attachment of water-soluble polymers such as polyethylene glycol, copolymers of polyethylene glycol and polypropylene glycol, carboxymethyl cellulose, dextran, polyvinyl alcohol, polyvinylpyrrolidone or polyproline.
  • the modified compounds are known to exhibit substantially longer half-lives in blood following intravenous injection than do the corresponding unmodified compounds (Abuchowski et al., 1981; Newmark et al., 1982; and Katre et al., 1987).
  • Such modifications also increase, in another embodiment, the compound's solubility in aqueous solution, eliminate aggregation, enhance the physical and chemical stability of the compound, and greatly reduce the immunogenicity and reactivity of the compound.
  • the desired in vivo biological activity is achieved by the administration of such polymer-compound abducts less frequently or in lower doses than with the unmodified compound.
  • Each possibility represents a separate embodiment of the present invention.
  • compositions of the present invention may comprise one or more additional components may further include an additional component selected from the group consisting of an anti-static agent, a buffering agent, a bulking agent, a chelating agent, a colorant, a diluent, a dye, an emollient, a fragrance, an occlusive agent, a pH-adjusting agent, a preservative, and at least one vitamin.
  • an additional component selected from the group consisting of an anti-static agent, a buffering agent, a bulking agent, a chelating agent, a colorant, a diluent, a dye, an emollient, a fragrance, an occlusive agent, a pH-adjusting agent, a preservative, and at least one vitamin.
  • compositions of the present invention may comprise one or more additional active agents, selected from the group consisting of active herbal extracts, analgesics, anti-allergic agents, anti-aging agents, anti-bacterials, antibiotic agents, anticancer agents, antidandruff agents, antidepressants, anti-dermatitis agents, anti-edemics, antihistamines, anti-helminths, anti-hyperkeratolyte agents, anti-inflammatory agents, anti-irritants, anti-microbials, anti-mycotics, anti-proliferative agents, antioxidants, anti- wrinkle agents, anti-pruritics, antiseptic agents, antiviral agents, anti-yeast agents, astringents, topical cardiovascular agents, chemotherapeutic agents, corticosteroids, dicarboxylic acids, disinfectants, fungicides, hair growth regulators, hormones, hydroxy acids, immunosuppressants, immunoregulating agents, keratolytic agents, lactams, metals, metal oxides, mitocides
  • the composition may comprise one or more anti-oxidants/radical scavengers.
  • the anti-oxidant/radical scavenger may be selected from butylated hydroxy benzoic acids and their salts, coenzyme Q10, coenzyme A, gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, lipoic acid, amines (e.g., N,N-diethylhydroxylamine, amino-guanidine), sulfhydryl compounds (e.g., glutathione), dihydroxy fumaric acid and its salts, lycine pidolate, arginine pilolate, nordihydroguaiaretic acid, bioflavonoids, curcumin, lysine, methionine, proline, superoxide dismutase, silymarin, tea extracts, grape skin/seed extracts, melanin
  • the composition may comprise one or more additional vitamin extracts selected from vitamin A, any one or more of the vitamin B complex, vitamin D, vitamin K, vitamin E and C.
  • compositions that contain the Inula viscosa extracts of the invention are performed, for example by mixing, granulating, or tablet- forming processes, is well understood in the art.
  • the active therapeutic ingredient is often mixed with excipients that are pharmaceutically acceptable and compatible with the active ingredient.
  • the active compounds are mixed with additives customary for this purpose, such as vehicles, stabilizers, or inert diluents, and converted by customary methods into suitable forms for administration, such as tablets, coated tablets, hard or soft gelatin capsules, aqueous, alcoholic or oily solutions.
  • the active compounds are converted into a solution, suspension, or emulsion, if desired with the substances customary and suitable for this purpose, for example, solubilizers or other substances.
  • the composition may comprise one or more of bran oil, gelatin, glycerin, water, red palm fruit oil and carob extract.
  • the composition may be formulated in the form of a drink or beverage.
  • the composition may be formulated in the form of a sweet, candy, lozenge, chewing gum, toffee, candy bar, chocolate bar, health snack or other appetizing food product.
  • the term “treating” refers to curing a disease. In another embodiment, “treating” refers to preventing a disease. In another embodiment, “treating” refers to reducing the incidence of a disease. In another embodiment, “treating” refers to ameliorating symptoms of a disease. In another embodiment, “treating” refers to inducing remission. In another embodiment, “treating” refers to slowing the progression of a disease.
  • Example 1 Inula viscosa compositions a) Alcoholic Inula viscosa extracts, concentrates, pastes and powders
  • the Inula viscosa extract may be used topically or preferably in a formulation comprising suitable excipients.
  • the amount of the Inula viscosa extract in the formulation is about 0.01% to about 100%.
  • the extract is obtained by harvesting the above-ground parts such as, but not limited to: leaves, twigs, bark, flowers, buds, fruits, peels, seeds, roots, rhizomes, tubers, or bulbs.
  • the parts are homogenized in a blender, for example, with 0-100% ethanol until the mixture is uniform.
  • the homogenate is collected and filtered; the resulting supernatant is an Inula viscosa extract (IVE).
  • the extract may be concentrated by evaporation to form a concentrated extract. Additionally or alternatively it may be concentrated by evaporation until a wet paste, or resin extract forms. Additionally or alternatively an aqueous extract may be concentrated by evaporation and/or lyophilization until a dry powder extract forms, depending on the process conditions.
  • Inula viscosa extract compositions according to the present invention may be used in appropriate formulations comprising wheat seed oil, vitamin E, and zinc.
  • formulations prepared in accordance with the methods described in WO05117925 are prepared in accordance with the methods described in WO05117925.
  • Alcoholic tincture 30g Inula viscosa resin extract were melted and then dissolved in 70 gram alcohol (technical grade alcohol 95%). After stirring for up to 3 hours an Inula viscosa extract formed (in an alcoholic tincture (30% mixture).
  • Aloe vera gel mixture in Inula viscosa tincture - 10 gram of the gel is added to 90 gram of Inula viscosa alcoholic tincture (above), followed by stirring and shaking for up to 3 hours to form a uniform mixture (dispersion) of the tincture in the gel.
  • Vaseline gel comprising Inula viscosa extract
  • Inula Olive oil/Seed oil/canola oil (useful for skin softening, fungal treatment, for skin anti inflammatory, anti oxidant, anti fungus, anti bacteria and anti yeast treatment.
  • 192 gram of olive oil/Seed oil/canola oil were warmed to 55°C.
  • 4 gram of food grade emulsifier Span 80 or equivalent were added to the oil, stirred until uniform blend was reached and kept warm up to 55°C.
  • Inula viscosa extract was warmed up to 50°C, 4 gram of the molten extract were added slowly to the warm oil and vigorously mixed to form a smooth and uniform emulsion.
  • Inula viscosa may be mixed with any other vegetable oil.
  • Example 2 Preparation of an Inula extract cream composition and a solvent extract
  • Fresh leaves of Inula viscosa were collected from a field near Modi'in, Israel. The leaves were ground in a home blender with 70% ethanol until the mixture was uniform. Another option is dry leaves that are soaked in water up to 24 hours (rehydration), then the water are filtered and the leaves are soaked in ethanol for another 24 hours, or dry leaves, that are crushed and soaked in ethanol for another 24 hours. After soaking the leaves are blended. The homogenate was collected and filtered through a gauze pad. Part of the supernatant was collected and stored in a glass bottle at room temperature. The other part of the supernatant was left in an open glass bottle near a window to evaporate. The residue 1-35% (1-35 g to lOOg cream) was mixed with a hand cream that was manufactured comprising the following such as the hand cream commercially available (by the AHAVA Dead Sea Products Ltd or Nivea daily face soft cream).
  • Example 2 The cream of Example 2 was used on a Caucasian male age 62, suffering from an HSV-1 infection on the upper lip.
  • Figs. 1A- ID are images of treatment stages using the compositions of the present invention in treating a sore on a lip induced by HSV-1 with a cream, as described in the extract preparation, three times a day: (Fig. 1A) before treatment, (Fig. IB) after 18 hours treatment, (Fig. 1C) after 36 hours treatment, (Fig. ID) after 72 hours treatment, in accordance with an embodiment of the present invention.
  • the ethanol supernatant prepared hereinabove was used on two Caucasian females age 50-55, who suffer from repeated outbreaks of HSV-3.
  • the symptoms were a red rash on the chest and arms, over-sensitivity around the infected area and an internal pain.
  • the supernatant solution (the ethanol extract of example 1) was smeared on the infected area and overnight the rash was better while the pain and the sensitivity disappeared. After three days of smearing the rash had disappeared too.
  • the symptoms were: a beginning of a red rash on the arms and on the sides of the back and a feel of tingling around the infected area.
  • the solution was smeared on the infected area and overnight the rash and the tingling feeling disappeared. This woman used the ethanol supernatant twice and the results were the same.
  • a young Caucasian female age 35 suffered from an abscess with a severe infection on the chest.
  • Figs. 2A- 2F are images of treatment stages using the compositions of the present invention in treating an abscess: (Fig. 2 A) before treatment, (Fig. 2B) after three days treatment, (Fig. 2C) after four days treatment, (Fig. 2D) after five days treatment, (Fig. 2E) after six days treatment, and (Fig. 2F) after 23 days, in accordance with an embodiment of the present invention.
  • Fig. 2A Prior to this treatment, the doctors recommended four days of antibiotics and then surgery (Fig. 2A). She applied first the ethanol supernatant (from example 1) for two minutes and then afterwards she smeared the on cream (per example 1 hereinabove). She repeated this treatment four times a day. Two days after she began the treatment, the abscess that was originally hard became very soft (Fig. 2B). After additional 24 hours, a small "head” appear on the abscess (Fig. 2C). During the evening of the same day, the abscess exploded and a huge amount of infected fluid burst out. After that, she continued the treatment twice a day. Six days after the beginning of the treatment, only a small wound was left (Fig. 2D). After six months a smaller abscess came back with redness and pain the patient smeared the cream from Example 1 three times a day and after 3 days again, only a small wound was left.
  • a young Caucasian female aged 34 suffers from seborrhea with itching and reddened skin on the forehead.
  • FIGs. 3 A- 1C are images of treatment stages using the compositions of the present invention in treating Seborrhea: (Fig. 3A) before treatment, (Fig. 3B) after 48 hours treatment, (Fig. 3C) after 72 hours treatment, in accordance with an embodiment of the present invention.
  • Example 1 The patient smeared the cream of Example 1 twice a day: once in the morning and once in the evening. A day after she began the treatment the redness was reduced and the itching stopped. After additional 24 hours the affliction almost vanished and after 72 hours, from the beginning of the treatment, the skin went back to normal and not even a small sign was left.
  • Example 8 (a prophetic example)
  • Fresh/dried leaves of Inula viscosa or any other herb that contain sesquiterpene lactones (SLs) are to be collected from a licensed, controlled and supervised habitat.
  • the leaves will be grounded in a blender with 70%- 100% ethanol or in distilled water
  • the mixed homogenate will be collected and filtered through a gauze pad or filtered through Whatman No. 1 filter paper and centrifuged at 20,000 g for 10 min.
  • the aqua supernatant will be dried in a lyophilizer (0.07 mbar, 48 8C) and the ethanolic extraction will be concentrated by evaporator.
  • the resulting resin/powdered extract will designated Inula viscosa ethanol extract or aqueous extract, respectively.
  • the aqua powder will be further extracted in acetonitrile overnight, filtered, and evaporated under reduced pressure.
  • the concentrated ethanolic extract will be purified by a column with a solvent mixture of different polarity.
  • the SLs, Inuviscolide and Tomentosin will be identified by full analysis of the 1H and 13C NMR spectra and by comparison with published data, respectively [Zdero C et al., 1987, Lanzetta R et al., 1991].
  • the purity of the SLs will be greater than 80%.
  • the powder comprising the purified sesquiterpene lactones tomentosin and inuviscolide is then to be mixed with vitamins, ferulic acid, zinc and anti oxidative compounds.
  • Final concentration for treatment of tomentosin in the composition will be 0.1-1% and inuviscolide 0.1-1%.
  • Example 9 (a prophetic example)
  • Fresh leaves/dried of Inula viscosa or any other herb that contain sesquiterpene lactones (SLs) are to be collected from a licensed, controlled and supervised habitat.
  • the leaves will be grounded in a blender with 100% ethanol or in distilled water 1 :5-l :8 (w/v).
  • the mixed homogenate will be collected and filtered through a gauze pad or filtered through Whatman No. 1 filter paper and centrifuged at 20,000 g for 10 min.
  • the aqua supernatant will be dried in a lyophilizer (0.07 mbar, 48 8°C) and the ethanolic extraction will be concentrated by evaporator.
  • the resulting resin/powdered extract will designate Inula viscosa respectively ethanol or watery extract.
  • the resulting resin/powdered extract will be mixed together in different combination ratios ranging from 10% - 90% ethanolic extract to aqueous extract, according to the severity of the medical condition of the patient.
  • Figs. 4A- 4F are images of tissue culture plates with cells infected with Herpes simplex virus type 3 (HSV3)-4A and 4B controls without treatment; 4C-4E treated with Inula viscosa extract; and 4F treated with Acyclovir, in accordance with an embodiment of the present invention;
  • HSV3 Herpes simplex virus type 3
  • the picture demonstrates a tissue culture plate with cells that were infected by herpes virus type 3.
  • the left upper and lower two wells show white spots which represents typical HSV3 plaques.
  • the white spots are typical HSV3 plaques.
  • Those white spots are the exposure of the well bottom, that before was covered with virus infected cells. The virus replication caused cell death and therefore the cells detached and left empty spots.
  • These two wells represent the positive control - cells infected with HSV3 and typical plaques.
  • the middle upper well (Fig. 4C) represents HSV3 infected cells with 0.25 ⁇ g of Inula viscosa extract that was add to their growth medium. In comparison to the positive control, less plaques had grown in this well.
  • the middle lower well (Fig. 4D) represents HSV3 infected cells with 0.5( ⁇ g of Inula viscosa extract which was added to the growth medium. In comparison to the positive control, and to the well with 0.25 ⁇ g Inula viscosa extract (Fig. 4C), even less plaques had grown in this well.
  • the right upper well (Fig. 4E) represents HSV3 infected cells that 1 ⁇ g of Inula viscosa extract, which was added to the growth medium. No plaques had grown or developed in this well.
  • the lower right well represent HSV3 infected cells that ⁇ 0 x,g of Acyclovir was add to their growth medium. This is a positive control for a drug that reduces and prevents HSV3 growth.
  • a Caucasian female age 65 that suffers from outbursts of Herpes Zoster (HSV3) every once in a while, despite taking Acyclovir every outbreak.
  • the outbreaks symptoms include 1 or more red blisters accompanied by itching and either local aches or ache that start at the blister site and continue down the leg nerves (the sensation is of aches within the leg itself).
  • the blisters and their symptoms may last up to 1 week.
  • Inula viscosa extract there was a significant relief in terms of the itching and the redness within 1-3 days.
  • the expected local aches and those that extend into the legs were relieved.
  • the forth outbreak was more difficult and the relief came after two days (36 hours).
  • FIGs. 5 A- 5C are images of treatment stages using the compositions of the present invention in treating a Herpes simplex 1 (HSV1): (Fig. 5 A) before treatment, (Fig. 5B) after 36 hours treatment, (Fig. 5C) after 48 hours treatment, in accordance with an embodiment of the present invention.
  • HSV1 Herpes simplex 1
  • FIG. 5 A A Caucasian male age 25, suffers from an HSV-1 infection on both lips.
  • the male suffers from recurrent outbreaks of labial herpes infections, and is also durable to Zovirax.
  • the left photo (Fig. 5 A) represents two days after the HSV-1 outbreak as the patient suffered from a growing number of cold sores, swelling, redness and pain. 18 hours therafter, he began to use the herbal extract (per Example 1 hereinabove). There was a relief both in pain and in the swelling around the sores (described by the patient. Not represented by a figure). 36 hours after the beginning of the treatment, the middle photo(Fig. 5B), show less infection, significant improvement of the swelling and a coagulate started to appear. After 48 hours the affliction had shrunk (the right photo(Fig. 5C)). On the lower lip, the infection is in a final stage, whereas, on the upper lip, only residues has remained (the right photo).
  • Figs. 6A-6D are images of treatment stages using the compositions of the present invention in treating a Herpes simplex 1 (HSV1): (Fig. 6A) before treatment, (Fig. 6B) after 24 hours treatment, (Fig. 6C) after 48 hours treatment, and (Fig. 6D) after 72 hours treatment, in accordance with an embodiment of the present invention.
  • HSV1 Herpes simplex 1
  • the female suffers from recurrent outbreaks of labial herpes infections, and is also durable to Zovirax.
  • Fig.6A 12 hours after the tingling feeling a cold sore with infection and great pain had appeared (Fig.6B).
  • Fig.6B 12 hours after the tingling feeling a cold sore with infection and great pain had appeared (Fig.6B).
  • the lady started to spread the Inula viscosa extract on the sore and reported that 18 hours from the beginning of the treatment the pain and the discomfort disappear (Fig.6B).
  • 48 hours from the beginning of using Inula viscosa extract the cold sore was fully turned into a coagulate and the swelling was gone (Fig.6C).
  • Fig.6D Another 24 hours later, the coagulate was appeared part of the coagulate fall down (Fig.6D) and 24 hours later the rest of the coagulate fell too (was reported but not pictured).
  • Figs. 7A-7D are images of treatment stages using the compositions of the present invention in treating chronic wounds on a heel- (Fig. 7 A) before treatment, (Fig. 7B) after 72 hours treatment, (Fig. 7C) after 5 days' treatment, and (Fig. 7D) after 7 days' treatment, in accordance with an embodiment of the present invention.
  • FIG. 7A A Caucasian male age 38, suffers in his foot from dry skin that cause cuts, bleeding and great pain throughout walking (Fig. 7A). This male usually treats these wounds with an ointment named "U-Lactin", which hardly helps the healing.
  • Fig. 7B Upon treatment by spreading Inula viscosa extract, after 3 days the dry skin was peeled and a significant relief in pain was reported (Fig. 7B). after 2 more days the bleeding cuts were improved (Fig. 7C), and 2 more days, only residues of the wounds were remained (Fig. 7D).
  • Figs. 8A-8D are images of treatment stages using the compositions of the present invention in treating viral warts caused by Molluscum contagious virus (Fig. 8A) before treatment, (Fig. 8B) before treatment, (Fig. 8C) after 7 days' treatment, and (Fig. 8D) after one month's treatment, in accordance with an embodiment of the present invention.
  • a Caucasian female age 35 suffered from an infection of an intestine virus that cause nausea, stomach aches and diarrhea. After 4 days of sickness she drank an aqua's extract of Inula viscosa. The nausea stopped after two hours and 12 hours later the stomach aches and diarrhea stopped completely.
  • Kaposi's sarcoma-associated herpesvirus induces sustained NF-kappaB activation during de novo infection of primary human dermal microvascular endothelial cells that is essential for viral gene expression.
  • the HIV transactivator TAT binds to the CDK-activating kinase and activates the phosphorylation of the carboxy-terminal domain of RNA polymerase II.

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Abstract

The present invention discloses compositions, methods and kits for treating topical disorders, some of which are associated with a viral infections, the composition comprising at least one of a plant extract comprising at least one of tomentosin and inuviscolide, tomentosin, inuviscolide, a plant cell culture extract comprising at least one of tomentosin and inuviscolide and an Inula viscosa extract and a pharmaceutically acceptable carrier.

Description

COMPOSITIONS AND METHODS FOR TREATING A SKIN
DISORDER
FIELD OF THE INVENTION
This invention relates to compositions and methods for treating skin disorders in mammals and more particularly, to compositions and methods for treating viral skin disorders.
BACKGROUND OF THE INVENTION
There are many reports that many of the viral diseases appear to be spreading: an example is herpes simplex virus Type 2 (HSV-2), the cause of genital herpes. Recent estimates are that more than 1 in 5 Americans age 12 and older tests seropositive for the HSV Type 2, with approximately 1 million new infections each year.
US 7,083,814 reports that a safe and effective antiviral agent must interrupt the life-cycle of the virus in some manner, such that the virus cannot replicate adequately, and the compound must have negligible or manageable toxicity to the host cells (or patient). In other words, the antiviral agent must be far more toxic to the virus than to the host cell. Another factor which has come to light relates to the long-term side-effects of certain antivirals, as well as the ability of the viruses to adapt or mutate to negate the effect of certain antiviral agents. Alternatively, more general compounds which boost or modulate immune system responses, such as interferons, may be used in combating viral disease, as may vaccines targeted to specific viruses.
Inula viscosa (compositae) is known in traditional medicine for a large range of biological activities including antipyretic, anti-bacterial and antifungal activity. Plants from the Compositae family have yielded a wide array of sesquiterpenoids, especially sesquiterpene lactones (SLs), as the main secondary metabolites [Muhammad I et al., 2003]. Two of the sesquiterpene lactones that were published and are well known are: Inuviscolide and Tomentosin. In addition, they exhibits antimicrobial activities [Ali- Shtayeh MS et al., 1998] and even shows cytotoxicity against some cancer cell lines [Woynarowski JM et al., 1981]. Tomentosin has been shown to exhibit fungistatic activity [Cohen Y et al., 2002] and antimalarial activity [Joshi SP et al., 1997].
Traditional medicine has been a fertile source for revealing novel lead molecules for modern drug discovery. In plants, terpenoids represent a chemical defense against environmental stress and provide a repair mechanism for wounds and injuries. Interestingly, effective ingredients in several plant-derived medicinal extracts are also terpenoid compounds of monoterpenoid, sesquiterpenoid, diterpenoid, triterpenoid [A. Salminen et al., 2008].
The skin is the largest organ of a mammalian body, serving many important functions, such as regulating body temperature, maintaining water and electrolyte balance, and sensing painful and pleasant stimuli.
The skin is adapted to keep dangerous substances from entering the body and provides a shield from the harmful effects of the sun. Any deterioration in skin health may have important consequences on a person's physical and mental health.
Several types of skin disorder manifest themselves as rashes and lead to itching. The itching and rashes may develop as the result of infection or irritation or from an immune system reaction. Conventional Western medical practice is to provide topical drugs including corticosteroids and moisturizers. Sometimes phototherapy is used employing ultraviolet light.
US 4,254,112 relates to the preparation of an extract of Inula and related species such as Inula viscosa and Inula graveolens (which belong to the family Compositae) which is useful in therapy, in particular as bacteriostatic and fungistatic agent. This extract is useful in the treatment of human beings suffering from infectious diseases.
WO9920109A discloses a new sesquiterpene, having the general formula ϋ15Η20θ3. This sesquiterpene was found to possess the property of inhibiting the growth of dermatophytes and particularly of Microsporum canis and Trichophyton rubrum when administered in an adequate dose. This sesquiterpene was obtained from leaves of the plant Inula viscosa. The structural formula of the sesquiterpene and a simple method for its isolation are described. WO03017768A describes infusions of Inula viscosa, and a process to obtain the mentioned infusions by treatment with ethyl alcohol, vegetable oil, or water. The infusions show activity against hematophagic insects, mosquitos, flies, and horseflies.
WO05117925 A discloses an Inula viscosa extract for use in treating arthritis and for use an anti-inflammatory, anti-bacterial, anti-fungal, anti-oxidant, anti-yeast agent. The invention further concerns a method for cultivating Inula viscosa plants and an optimized efficient extraction process utilizing ethyl-acetate as the solvent for obtaining an extract characterized by the quantitative presence of carotenoids, flavenoids, tomentosin, sesquiterpene lactones, sterols, and saponins.
CN100396295C provides a Chinese medicine for treating viral hepatitides, especially hepatitis A and B, is prepared from Inula flower or its extract or its chemical components and the edible saltpeter.
C 1673338A discloses an elecampane detergent, which has in each 1000 g elecampane extract 0.001-950 g, balloonflower root extract 0.001-550 g and Chinese white poplar bark extract 0.001-450 g, except the matrix. The elecampane detergent has excellent skin cleaning and moistening effect, certain germ and virus, especially infectious disease germ and virus, inhibiting and killing effect. The elecampane detergent may be added into detergent, cosmetics, wet towel, toothpaste and other daily used articles to generate skin cleaning, sterilizing and moistening effects.
However, there is still a need for improved compositions and methodologies for treating skin disorders.
SUMMARY OF THE INVENTION
It is an object of some aspects of the present invention to provide improved compositions and for treating topical disorders in mammalian subjects.
In some embodiments of the present invention, improved methods and compositions are provided for treating viral topical disorders in human patients.
In other embodiments of the present invention, methods and Inula extract compositions are provided for treating topical disorders.
In additional embodiments of the present invention, cream-based compositions and methods are provided for treating topical disorders related to viral infections.
In further embodiments of the present invention, cream-based compositions and methods are provided for treating topical disorders related to Herpes infections.
In further embodiments of the present invention, cream-based compositions and methods are provided for treating topical disorders related to Herpes simplex infections.
In yet further embodiments of the present invention, cream-based compositions and methods are provided for treating topical disorders related to Herpes zoster infections.
Additional embodiments of the present invention are directed to a novel method for efficient extraction of plant-derived material compounds isolated from Inula viscosa plants.
Further embodiments of the present invention are directed to a novel method for efficient extraction of combinations of plant-derived material compounds isolated from Inula viscosa plants.
Additional embodiments of the present invention are directed to a novel method for efficient extraction of plant-derived material compounds isolated from herbal plants that contains terpenoids, sesquiterpene lactones, flavones and anti oxidative compounds.
Additional embodiments of the present invention are directed to a novel method for combination of plant-derived material compounds isolated from Inula viscosa plants with several supplements for more effective and/or synergistic effect. The compositions of the present invention may be formulated with one or more pharmaceutically acceptable carriers to form a topical composition possessing antiviral activity in a form selected from the group consisting of a balm, an ointment, a lotion, a roll-on, a rub, a sticker, a gel, a tincture, a spray and a cream.
Further embodiments of the present invention are directed to topical antiviral compositions prepared by the method as described herein.
Additional embodiments of the present invention are directed to a topical composition as palliate agent against pain prepared by the methods as described herein.
Additional embodiments of the present invention are directed to an oral composition for use in treating autoimmune diseases prepared by the methods described herein.
Additional embodiments of the present invention are directed to a topical composition for use in treating pathological conditions, based on over- stimulation of pro-inflammatory cytokines, the composition being prepared as described herein.
Additional embodiments of the present invention are directed to a topical composition against blisters that are caused by Herpes simplex virus 3 (HSV3), known commonly as Chickenpox or shingles.
The present invention further provides a topical composition and method for treating warts.
There is thus provided, according to an embodiment of the present invention, a composition for treating a topical disorder associated with a viral infection, the composition including at least one of;
a) a plant extract including at least one of tomentosin and inuviscolide;
b) tomentosin;
c) inuviscolide;
d) a plant cell culture extract including at least one of tomentosin and inuviscolide and
e) an Inula viscosa extract;
f) any other herbal plants that contains terpenoids, sesquiterpene lactones, flavones and anti oxidative agents, and a pharmaceutically acceptable carrier. According to another embodiment of the present invention, the composition the plant extract includes an extract from at least one species selected from the genera Inula, Xanthium and Arnica.
Additionally, according to another embodiment of the present invention, the at least one Inula species is selected from Inula acaulis, Inula acervata S.Moore, Inula acinacifolia Gand, Inula acuminata DC, Inula afghanica, Inula anatolica Boiss., Inula auriculata Boiss. & Balansa, Inula bifrons (L.) L., Inula britannica L. - British Yellowhead, Inula Candida (L.) Cass., Inula cappa (Buch.-Ham. ex D. Don) DC, Inula caspica Blume, Inula clarkei ( Hookf.) R.R. Stewart, Inula conyzae (Griess.) Meikle - Plougman's-spikenard, Inula crithmoides L. - Golden samphire (syn. Limbarda crithmoides (L.) Dum.), Inula cuspidata, Inula ensifolia L., Inula eupatorioides DC, Inula falconeri Hookf., Inula forrestii, Inula germanica L., Inula grandis Schrenk ex Fisch. & C. A. Mey., Inula helenioides DC, Inula helenium L.— Elecampane, Inula helianthus-aquatica, Inula helvetica Weber, Inula hirta L., Inula hookeri C B. Clarke, Inula hupehensis, Inula japonica, Inula koelzii RDawar & Qaiser, Inula lineariifolia Turcz., Inula magnifica, Inula montana L., Inula multicauHs Boiss., Inula nervosa, Inula obtusifolia A.Kern., Inula oculus-christi L., Inula orientalis Lam., Inula pterocaula, Inula racemosa Hookf, Inula rhizocephala Schrenk ex Fisch. & C. A. Mey., Inula rhizocephaloides, Inula royleana DC. (synonym of Inula racemosa Hookf), Inula rubricaulis, Inula salicina L. - Irish Fleabane, Willowleaf Yellowhead, Inula salsoloides, Inula sericophylla, Inula spiraeifolia L., Inula stewartii Abid & Qaiser, Inula subfloccosa Rech.f, Inula thapsoides Spreng., Inula verbascifolia (Willd.) Hausskn., Inula viscosa and Inula wissmanniana.
According to some sources, Inula is also called Dittrichia and/or Cupularia. According to some sources, Inula viscosa is also called Dittrichia viscosa) L.) W. Greuter and/or Cupularia viscosa (L.) Gren. & Godr.
Furthermore, according to another embodiment of the present invention, the viral infection is selected from the group consisting of HIV, polio virus, hepatitis, herpes viruses, such as HSV-1, HSV-2, HSV-3/VZV, HHV, cytomegalovirus and measles virus, influenza, rhinovirus, parainfluenza, vesicular stomatitis virus (VSV), vaccinia virus (W), encephalitis, African Swine Fever virus and intestine viruses. Yet further, according to another embodiment of the present invention, the topical disorder is selected from the group consisting of a rash, an allergy, a blister, an abscess, an irritation, a swelling, a coloration, a sore a wart, and a wound.
Moreover, according to another embodiment of the present invention, the plant extract is selected from a solvent extract or an aqua extract or a combination of both extracts and a column extract.
Additionally, according to another embodiment of the present invention, the composition is a topical composition.
According to another embodiment of the present invention, the topical composition is selected from the group consisting of a balm, an ointment, a lotion, a roll-on, a rub, a sticker, a gel, a tincture, a spray and a cream.
Further, according to another embodiment of the present invention, the pharmaceutically acceptable carrier is selected from an aqueous carrier, an oil-based carrier, an emulsion, a cream, a gel and a powder.
Additionally, according to another embodiment of the present invention, the composition is an antiviral composition.
Additionally, according to another embodiment of the present invention, the composition is an prophylactic antiviral composition.
Yet further, according to another embodiment of the present invention, the composition is adapted to act as a palliative agent against pain.
Alternatively, according to another embodiment of the present invention, the composition is an oral composition.
According to another embodiment of the present invention, the oral composition is adapted to treat an autoimmune disease.
Moreover, according to another embodiment of the present invention, the composition is effective in treating a pathological condition which over-stimulates proinflammatory cytokines.
Additionally, according to another embodiment of the present invention, the composition is effective in treating HSV3/VZV-induced blisters.
Furthermore, according to another embodiment of the present invention, the at least one Inula species includes Inula viscosa. Additionally, according to another embodiment of the present invention, the composition further includes at least one of wheat seed oil, vitamin E, and zinc and other kind of palliate components or natural compounds or synthesized compounds.
According to another embodiment of the present invention, the composition further includes at least one of; a vegetable oil, a mineral oil, an alcohol, a gel, Aloe vera, paraffin wax, a cream, a stabilizer, a coloring agent, an emulsifier and an Inula viscosa extract.
Additionally, according to another embodiment of the present invention, the composition includes both tomentosin and inuviscolide in pharmaceutically effective amounts.
There is thus provided, according to an embodiment of the present invention, a method for treating a topical disorder associated with a viral infection, the method including administering at least one active substance selected from;
a) a plant extract including at least one of tomentosin and inuviscolide;
b) tomentosin;
c) inuviscolide;
d) a plant cell culture extract including at least one of tomentosin and inuviscolide; and
e) an Inula viscosa extract;
to a mammalian subject afflicted with the topical disorder so as to treat the topical disorder.
According to another embodiment of the present invention, the plant extract used in the method includes an extract from at least one species selected from the genera Inula, Xanthium and Arnica.
Furthermore, according to another embodiment of the present invention, the at least one Inula species is selected from Inula acaulis, Inula acervata S.Moore, Inula acinacifolia Gand, Inula acuminata DC, Inula afghanica, Inula anatolica Boiss., Inula auriculata Boiss. & Balansa, Inula bifrons (L.) L., Inula britannica L. - British
Yellowhead, Inula Candida (L.) Cass., Inula cappa (Buch.-Ham. ex D. Don) DC, Inula caspica Blume, Inula clarkei ( Hookf.) R.R.Stewart, Inula conyzae (Griess.) Meikle -
Plougman's-spikenard, Inula crithmoides L. - Golden samphire (syn. Limbarda crithmoides (L.) Dum.), Inula cuspidata, Inula ensifolia L., Inula eupatorioides DC,
Inula falconeri Hookf., Inula forrestii, Inula germanica L., Inula grandis Schrenk ex Fisch. & C. A. Mey., Inula helenioides DC, Inula helenium L. - Elecampane, Inula helianthus-aquatica, Inula helvetica Weber, Inula hirta L, Inula hookeri C. B. Clarke, Inula hupehensis, Inula japonica, Inula koelzii R.Dawar & Qaiser, Inula lineariifolia Turcz., Inula magnifica, Inula montana L., Inula multicaulis Boiss., Inula nervosa, Inula obtusifolia A.Kern., Inula oculus-christi L., Inula orientalis Lam., Inula pterocaula, Inula racemosa Hookf., Inula rhizocephala Schrenk ex Fisch. & C. A. Mey., Inula rhizocephaloides, Inula royleana DC. (synonym of Inula racemosa Hookf.), Inula rubricaulis, Inula salicina L. - Irish Fleabane, Willowleaf Yellowhead, Inula salsoloides, Inula sericophylla, Inula spiraeifolia L., Inula stewartii Abid & Qaiser, Inula subfloccosa Rech.f, Inula thapsoides Spreng., Inula verbascifolia (Willd.) Hausskn., Inula viscosa and Inula wissmanniana.
Additionally, according to another embodiment of the present invention, the viral infection is selected from the group consisting of HIV, polio virus, RSV, hepatitis, herpes viruses, such as HSV-1, HSV-2, HSV-3, HHV, cytomegalovirus and measles virus, influenza, rhinovirus, parainfluenza, vesicular stomatitis virus (VSV), vaccinia virus (W), encephalitis, Papillomaviruses and African Swine Fever virus.
Furthermore, according to another embodiment of the present invention, the method further includes treating the viral infection.
According to another embodiment of the present invention, the topical disorder is selected from the group consisting of a rash, an allergy, a blister, an abscess, an irritation, a swelling, a coloration, a sore and a wart.
Moreover, according to another embodiment of the present invention, the plant extract is selected from a solvent extract, an aqueous extract, a combination of an organic solvent extract and an aqueous extract, a combination of both extracts and a column extract.
Furthermore, according to another embodiment of the present invention, the administering step includes administering a topical composition to an afflicted area of skin.
Additionally, according to another embodiment of the present invention, the topical composition is selected from the group consisting of a balm, an ointment, a lotion, a roll-on, a rub, a sticker, a gel, a tincture, a spray and a cream. Further, according to another embodiment of the present invention, the pharmaceutically acceptable carrier is selected from an aqueous carrier, an oil-based carrier, an emulsion, a cream, a gel and a powder.
Additionally, according to another embodiment of the present invention, the method is further adapted to treat pain associated with the topical disorder.
Furthermore, according to another embodiment of the present invention, the administration is oral.
Furthermore, according to another embodiment of the present invention, the administration is nasal.
Additionally, according to another embodiment of the present invention, the oral method further treats an autoimmune disease.
Furthermore, according to another embodiment of the present invention, the method is effective in treating a pathological condition which over-stimulates proinflammatory cytokines.
Additionally, according to another embodiment of the present invention, the method is effective in treating HSV3 -induced blisters.
Additionally, according to another embodiment of the present invention, the at least one Inula species includes Inula viscosa.
Additionally, according to another embodiment of the present invention, the at least one active substance is formulated with at least one of wheat seed oil, vitamin E, zinc, other kinds of palliate components, natural compounds or synthesized compounds.
Moreover, according to another embodiment of the present invention, the at least one active substance is formulated with at least one of; a vegetable oil, a mineral oil, an alcohol, a gel, Aloe vera, paraffin wax, a cream, a stabilizer, a coloring agent, an emulsifier, and a vitamin.
Furthermore, according to another embodiment of the present invention, the at least one active substance includes both tomentosin and inuviscolide in pharmaceutically effective amounts.
Additionally, according to another embodiment of the present invention, the method further includes:
i) applying the at least one active substance to an area of skin so as to allow at least part of the first composition to start the treatment process; and ii) applying the composition described herein to the area of skin. Furthermore, according to another embodiment of the present invention, the method further includes waiting for a period of time between step i) and step ii).
Additionally, according to another embodiment of the present invention, the period of time is at least twelve hours.
According to another embodiment of the present invention, steps i) and ii) are each repeated after waiting for an interval of at least twelve hours.
Furthermore, according to another embodiment of the present invention, the time interval is at least one week.
Additionally, according to another embodiment of the present invention, steps i) and ii) are repeated several times, each time after waiting for the duration of the time interval.
According to another embodiment of the present invention, the method further includes providing the patient with at least one dietary supplement.
Furthermore, according to another embodiment of the present invention, the at least one dietary supplement is responsive to the results of a blood test of the patient.
There is thus provided, according to another embodiment of the present invention, a composition for treating a topical disorder, the composition including at least one of;
a) a plant extract including at least one of tomentosin and inuviscolide;
b) tomentosin;
c) inuviscolide;
d) a plant cell culture extract including at least one of tomentosin and inuviscolide;
e) an Inula viscosa extract; and
f) a pharmaceutically acceptable carrier.
Furthermore, according to another embodiment of the present invention, the topical disorder is selected from eczema, an inflammatory disease, acne, a microbial infection, a blistering disease, an itching and non-infectious rash, a skin growth, a parasitic infection, a pigment disorder, a burn, a scar, a chemically-induced disorder, a physically induced disorder and a viral disorder.
Additionally, according to another embodiment of the present invention, the itching and non infectious rash is psoriasis. There is thus provided, according to another embodiment of the present invention, a kit for the treatment of a skin disorder including;
a) a composition as described herein; and
b) instructions on how to apply the composition to an area of skin.
Additionally, according to another embodiment of the present invention, the kit includes between about 0.1% to 100% (w/w) of the Inula viscosa extract.
According to another embodiment of the present invention, the composition includes 0.0001-100% tomentosin and 0.0001-100% inuviscolide.
Additionally, according to another embodiment of the present invention, the Inula viscosa extract is obtained by harvesting Inula viscosa plants, drying the harvested plants to obtain a moisture contents of about 0.1% to 100%, grinding the dry biomaterial to powder grain, contacting the powder grain at least one time with ethyl-acetate at elevated temperatures, evaporating the ethyl-acetate and obtaining an extract characterized by its carotenoids, flavenoids, tomentosin, sesquiterpene lactones, sterols, polyphenols and saponins contents.
Additionally, according to another embodiment of the present invention, the composition is adapted to act against wounds, including, but not limited to, diabetic wounds, chronic wounds, traumatic wounds, ulcers and pressure sores.
Furthermore, according to another embodiment of the present invention, the composition is adapted to act against inflammatory skin diseases, including, but not limited to, eczema, atopic dermatitis and seborrhea.
Additionally, according to another embodiment of the present invention, the composition is adapted to act against viruses which require at least one of NFKB, ST ATI, CDK and CDC2 cellular proteins for activation thereof.
Furthermore, according to another embodiment of the present invention, the composition is adapted to act against viruses or viral infections, including, but not limited to, viruses comprising a single strand nucleic acid, viruses comprising a double strand nucleic acid, RNA viruses, DNA viruses, both DNA and RNA viruses and retroviruses.
Furthermore, according to another embodiment of the present invention, the composition is adapted to act as a palliative against scars or burns.
Additionally, according to another embodiment of the present invention, the composition is adapted to act as a peeling agent. Additionally, the compositions of the present invention may include Inula plants or any other herbal plants containing terpenoids, sesquiterpene lactones, or anti oxidative agents, such as flavones or polyphenols.
The present invention further provides a use of at least one of:
a) a plant extract including at least one of tomentosin and inuviscolide;
b) tomentosin;
c) inuviscolide;
d) a plant cell culture extract including at least one of tomentosin and inuviscolide;
e) an Inula viscosa extract; and
f) a pharmaceutically acceptable carrier, in the preparation of a medicament for treating a disorder.
The present invention further provides at least one of:
a) a plant extract including at least one of tomentosin and inuviscolide;
b) tomentosin;
c) inuviscolide;
d) a plant cell culture extract including at least one of tomentosin and inuviscolide;
e) an Inula viscosa extract; and
f a pharmaceutically acceptable carrier, for use in the preparation of a medicament for treating a disorder.
The present invention will be more fully understood from the following detailed description of the preferred embodiments thereof, taken together with the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will now be described in connection with certain preferred embodiments with reference to the following illustrative figures so that it may be more fully understood.
With specific reference now to the figures in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.
Figs. 1A- ID are images of treatment stages using the compositions of the present invention in treating a sore on a lip induced by HSV-1 with a cream as described in the extract preparation, three times a day: (Fig. 1A) before treatment, (Fig. IB) after 18 hours treatment, (Fig. 1C) after 36 hours treatment, (Fig. ID) after 72 hours treatment, in accordance with an embodiment of the present invention;
Figs. 2 A- 2F are images of treatment stages using the compositions of the present invention in treating an abscess with a combined treatment of a tincture and a cream, as described in the extract preparation, four times a day: (Fig. 2A) before treatment, (Fig. 2B) after three days treatment, (Fig. 2C) after four days treatment, (Fig. 2D) after five days treatment, (Fig. 2E) after six days treatment, and (Fig. 2F) after 23 days, in accordance with an embodiment of the present invention;
Figs. 3 A- 3C are images of treatment stages using the compositions of the present invention in treating Seborrhea with a cream as described in the extract preparation, twice a day: (Fig. 3A) before treatment, (Fig. 3B) after 48 hours treatment, (Fig. 3C) after 72 hours treatment, in accordance with an embodiment of the present invention; Figs. 4A- 4F are images of tissue culture plates with cells infected with Herpes simplex virus type 3 (HSV3)-4A and 4B controls without treatment; 4C-4E treated with Inula viscosa extract; and 4F treated with Acyclovir, in accordance with an embodiment of the present invention;
Figs. 5A- 5C are images of treatment stages using the compositions of the present invention in treating a Herpes simplex 1 (HSV1) with a tincture, as described in the extract preparation, three times a day: (Fig. 5 A) before treatment, (Fig. 5B) after 36 hours treatment, (Fig. 5C) after 48 hours treatment, in accordance with an embodiment of the present invention;
Figs. 6A-6D are images of treatment stages using the compositions of the present invention in treating a Herpes simplex 1 (HSV1) ) with a tincture as described in the extract preparation, four times a day: (Fig. 6A) before treatment, (Fig. 6B) after 24 hours treatment, (Fig. 6C) after 48 hours treatment, and (Fig. 6D) after 72 hours treatment, in accordance with an embodiment of the present invention;
Figs. 7A-7D are images of treatment stages using the compositions of the present invention in treating chronic wounds on a heel with a combined treatment of a tincture and a cream, as described in the extract preparation, twice a day - (Fig. 7A) before treatment, (Fig. 7B) after 72 hours treatment, (Fig. 7C) after 5 days' treatment, and (Fig. 7D) after 7 days' treatment, in accordance with an embodiment of the present invention; and
Figs. 8A-8D are images of treatment stages using the compositions of the present invention in treating viral warts caused by Molluscum contagious virus with a cream as described in the extract preparation twice a day -(Fig. 8A) before treatment, (Fig. 8B) before treatment, (Fig. 8C) after 7 days' treatment, and (Fig. 8D), after one month's treatment, in accordance with an embodiment of the present invention. DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
In the detailed description, numerous specific details are set forth in order to provide a thorough understanding of the mvention. However, it will be understood by those skilled in the art that these are specific embodiments and that the present invention may be practiced also in different ways that embody the characterizing features of the invention as described and claimed herein.
It is an object of some aspects of the present invention to provide improved compositions and for treating topical disorders in mammalian subjects.
In some embodiments of the present invention, improved methods and compositions are provided for treating viral topical disorders in human patients.
In other embodiments of the present invention, methods and Inula extract compositions are provided for treating topical disorders.
In additional embodiments of the present invention, compositions and methods are provided for treating topical disorders related to viral infections.
In further embodiments of the present invention, compositions and methods are provided for treating topical disorders related to Herpes infections.
In further embodiments of the present invention, compositions and methods are provided for treating topical disorders related to Herpes simplex infections.
In yet further embodiments of the present invention, compositions and methods are provided for treating topical disorders related to Herpes zoster infections.
Additional embodiments of the present invention are directed to a novel method for efficient extraction of plant-derived material compounds isolated from Inula viscosa plants.
Further embodiments of the present invention are directed to a novel method for efficient extraction of combinations of plant-derived material compounds isolated from Inula viscosa plants. The present invention is directed to compositions for treating viral disorders and/or topical disorders associated with the viral disorders. The compositions comprise one or more active ingredients from one or more plant sources.
The plant sources may include ground plants or plant parts, plant extracts, plant cell cultures and the like. More particularly, some non-limiting embodiments exemplify the plants are typically from the Inula, Xanthium and Arnica genera
Inula is a large genus of about 90 species of flowering plants in the family Asteraceae, native to Europe, Asia and Africa. Inula species include, but are not limited to, Inula acaulis, Inula acervata S.Moore, Inula acinacifolia Gand, Inula acuminata DC, Inula afghanica, Inula anatolica Boiss., Inula auriculata Boiss. & Balansa, Inula bifrons (L.) L., Inula britannica L. - British Yellowhead, Inula Candida (L.) Cass., Inula cappa (Buch.-Ham. ex D. Don) DC, Inula caspica Blume, Inula clarkei ( Hookf.) R.R.Stewart, Inula conyzae (Griess.) Meikle— Plougman's-spikenard, Inula crithmoides L. - Golden samphire (syn. Limbarda crithmoides (L.) Dum.), Inula cuspidata, Inula ensifolia L., Inula eupatorioides DC, Inula falconeri Hookf., Inula forrestii, Inula germanica L, Inula grandis Schrenk ex Fisch. & C. A. Mey., Inula helenioides DC, Inula helenium L. - Elecampane, Inula helianthus-aquatica, Inula helvetica Weber, Inula hirta L., Inula hook ri C. B. Clarke, Inula hupehensis, Inula japonica, Inula koelzii R.Dawar & Qaiser, Inula lineariifolia Turcz., Inula magnifica, Inula montana L., Inula multicaulis Boiss., Inula nervosa, Inula obtusifolia A.Kern., Inula oculus-christi L., Inula orientalis Lam., Inula pterocaula, Inula racemosa Hook , Inula rhizocephala Schrenk ex Fisch. & C A. Mey., Inula rhizocephaloides, Inula royleana DC. (synonym of Inula racemosa Hookf), Inula rubricaulis, Inula salicina L. - Irish Fleabane, Willowleaf Yellowhead, Inula salsoloides, Inula sericophylla, Inula spiraeifolia L., Inula stewartii Abid & Qaiser, Inula subfloccosa Rech.f, Inula thapsoides Spreng., Inula verbascifolia (Willd.) Hausskn. and Inula wissmanniana.
Some embodiments of the present invention relate to extracts from Inula plants. More particularly, some embodiments relate to the type Inula viscosa plant. The Inula viscosa extract may be used topically or preferably in a formulation comprising suitable excipients. The amount of the Inula viscosa extract in the formulation is about 0.01% to about 100%. The extract is obtained by harvesting the above-ground parts such as, but not limited to: leaves, twigs, bark, flowers, buds, fruits, peels, seeds, roots, rhizomes, tubers, or bulbs. According to some further embodiments of the present invention, the active ingredient, tomentosin, which may be purchased from WuXi AppTec (Tianjin) Co., Ltd. No.41,Kaitai Science & Technology Building 5th Avenue, Tianjin Economic- Technological Development Area (TEDA), Tianjin, China 300457 - catalog number NPT0324- Xanthalongin (Tomentosin).
By tomentosin is meant CAS no. 33649-15-9 (believed to be of a chemical structure formula ^5Η2ο03).
By Inuviscolide is meant CAS no. 63109-30-8 (believed to be of a chemical structure formula C15H2o03).
According to some further embodiments of the present invention, the active ingredients may be prepared by plant cell culture from Xanthium strumarium or other species, using the method as is described in (Biotechnology and Bioprocess Engineering Volume 6, Number 1, 51-55, 2001 Jae Sung Park, Gi Hwan Yi, Min Hee Nam and Sun Ho Park).
According to some further embodiments of the present invention, the active ingredients may be prepared from Arnica species in accordance with (Willuhn, G.; Herrmann, H. D., 1979: Planta Medica 37(4): 325-332 Composition of Arnica species 12 Communication Xanthalongin, a new xanthanolide from the flowers of Arnica longifolia).
As to the spectrum of activity of the antiviral compositions of the present invention, many different viruses have been challenged with extracts of whole plants or various plant parts. Some non-limiting examples of viruses tested/to be tested include HIV, polio virus, hepatitis, RSV, Herpes viruses, such as HSV-1, HSV-2, HHV, cytomegalovirus and measles virus, influenza, rhinovirus, parainfluenza, vesicular stomatitis virus (VSV), vaccinia virus (W), encephalitis, Papillomaviruses and African Swine Fever virus.
The compositions of the present invention, may be used, inter alia, for treating a topical disorder associated with a viral infection. The compositions may include at least one or more of, at least two or more of, at least three or more of; at least four or more of, at least five or more of, at least six or more of, or all of:
a) a plant extract including at least one of tomentosin and inuviscolide;
b) tomentosin;
c) inuviscolide; d) a plant cell culture extract including at least one of tomentosin and inuviscolide
e) an Inula viscosa extract;
f) any other herbal plants that contains terpenoids, sesquiterpene lactones and anti oxidative agents, and
g) a pharmaceutically acceptable carrier.
The compositions of the present invention may be provided in any suitable dosage form. According to some embodiments, the dosage form is an oral dosage form. Oral dosage forms comprise liquids (spray, solutions, suspensions, and emulsions), semi-solids (pastes), and solids (tablets, capsules, powders, granules, premixes, and medicated blocks).
According to some embodiments of the present invention, the dosage forms comprising compositions of the present invention, comprise at least 0.01-0.1 μg tomentosin, at least 0.1-1 μg tomentosin, at least 1-10 μg tomentosin, at least 10-100 μg tomentosin, or at least 100-1000 μg tomentosin, or at least 1000 μg-1000 mg tomentosin.
According to some embodiments of the present invention, the compositions of the present invention, comprise at least 0.01-0.1 μg inuviscolide, at least 0.1-1 g inuviscolide, at least 1-10 μg inuviscolide, at least 10-100 μg inuviscolide, or at least 100-1000 μg inuviscolide, or at least 1000 μg-1000 mg inuviscolide.
According to some embodiments of the present invention, the dosage forms comprising compositions of the present invention, comprise at least 0.01-0.1 μg Inula viscosa dry/liquid extract, at least 0.1-1 μg Inula viscosa dry/liquid extract, at least 1-10 μg Inula viscosa dry/liquid extract, at least 10-100 μg Inula viscosa dry/liquid extract, at least 100-1000 μg Inula viscosa dry/liquid extract, at least 1-10 mg Inula viscosa dry/liquid extract, or at least 10-100 mg Inula viscosa dry/liquid extract, or at least 100- 1000 mg Inula viscosa dry/liquid extract.
In one embodiment, a dosage form of the present invention comprises 25-250 μg tomentosin. In another embodiment, a dosage form of the present invention comprises 100-200 μg tomentosin. In another, embodiment, a dosage form of the present invention comprises 1-1000 μg tomentosin. In another, embodiment, a dosage form of the present invention comprises 100-150 μg tomentosin. In one embodiment, a dosage form of the present invention comprises 25-250 μg inuviscolide. In another embodiment, a dosage form of the present invention comprises 100-200 g inuviscolide. In another, embodiment, a dosage form of the present invention comprises 1-1000 μg inuviscolide. In another, embodiment, a dosage form of the present invention comprises 100-150 μg inuviscolide.
Some examples of oral dosage forms in the art include, WO90/04391, which discloses an oral dosage form of omega-3 polyunsaturated acids to overcome the problems of vascular diseases. It is known to supply said acids in soft gelatine capsule shells.
EP 2 240 581 Bl discloses a gelatine capsule for pharmaceutical use with a controlled release of active ingredients and a process for the preparation of said gelatine capsules. During said process xylose is added to the liquid gelatine from which afterwards gelatine capsules are formed. Gelatine capsules manufactured according to the process provide retarded release of active ingredients.
US Patent No. 7,264,824 discloses and oral dosage form for food and food supplements, as well as dietetics comprising polyunsaturated acids in a xylose-hardened gelatine capsule with a retarded release time.
According to some embodiments of the present invention, the compositions described herein may be in a suspension, emulsion, solution or spray.
A suspension is a coarse dispersion of insoluble drug particles, generally with a diameter exceeding 1 μπι, in a liquid (usually aqueous) medium. Suspensions are useful for administering insoluble or poorly soluble drugs/components or in situations when the presence of a finely divided form of the material in the GI tract is required. The taste of most drugs is less noticeable in suspension than in solution, due to the drug being less soluble in suspension. Particle size is an important determinant of the dissolution rate and bioavailability of drugs in suspension. In addition to the excipients described above for solutions, suspensions include surfactants and thickening agents. Surfactants wet the solid particles, thereby ensuring the particles disperse readily throughout the liquid. Thickening agents reduce the rate at which particles settle to the bottom of the container. Some settling is acceptable, provided the sediment can be readily dispersed when the container is shaken. Because hard masses of sediment do not satisfy this criterion, caking of suspensions is not acceptable. An emulsion is a system consisting of 2 immiscible liquid phases, one of which is dispersed throughout the other in the form of fine droplets; droplet diameter generally ranges from 0.1-100 μιη. The 2 phases of an emulsion are known as the dispersed phase and the continuous phase. Emulsions are inherently unstable and are stabilized through the use of an emulsifying agent, which prevents coalescence of the dispersed droplets. Creaming, as occurs with milk, also occurs with pharmaceutical emulsions. However, it is not a serious problem because a uniform dispersion returns upon shaking. Creaming is, nonetheless, undesirable because it is associated with an increased likelihood of the droplets coalescing and the emulsion breaking. Other additives include buffers, antioxidants, and preservatives. Emulsions for oral administration are usually oil (the active ingredient) in water, and facilitate the administration of oily substances such as castor oil or liquid paraffin in a more palatable form.
A paste is a 2-component semi-solid in which drug is dispersed as a powder in an aqueous or fatty base. The particle size of the active ingredient in pastes can be as large as 100 μπι. The vehicle containing the drug may be water; a polyhydroxy liquid such as glycerin, propylene glycol, or polyethylene glycol; a vegetable oil; or a mineral oil. Other formulation excipients include thickening agents, cosolvents, adsorbents, humectants, and preservatives. The thickening agent may be a naturally occurring material such as acacia or tragacanth, or a synthetic or chemically modified derivative such as xanthum gum or hydroxypropylmethyl cellulose. The degree of cohesiveness, plasticity, and syringeability of pastes is attributed to the thickening agent. It may be necessary to include a cosolvent to increase the solubility of the drug. Syneresis of pastes is a form of instability in which the solid and liquid components of the formulation separate over time; it is prevented by including an adsorbent such as microcrystalline cellulose. A humectant (eg, glycerin or propylene glycol) is used to prevent the paste that collects at the nozzle of the dispenser from forming a hard crust. Microbial growth in the formulation is inhibited using a preservative. It is critical that pastes have a pleasant taste or are tasteless.
A tablet consists of one or more active ingredients and numerous excipients and may be a conventional tablet that is swallowed whole, a chewable tablet, or a modified- release tablet (more commonly referred to as a modified-release bolus due to its large unit size). Conventional and chewable tablets are used to administer drugs to dogs and cats, whereas modified-release boluses are administered to cattle, sheep, and goats. The physical and chemical stability of tablets is generally better than that of liquid dosage forms. The main disadvantages of tablets are the bioavailability of poorly water-soluble drugs or poorly absorbed drugs, and the local irritation of the GI mucosa that some drugs may cause.
A capsule is an oral dosage form usually made from gelatin and filled with an active ingredient and excipients. Two common capsule types are available: hard gelatin capsules for solid-fill formulations, and soft gelatin capsules for liquid-fill or semi- solid-fill formulations. Soft gelatin capsules are suitable for formulating poorly water- soluble drugs because they afford good drug release and absorption by the GI tract. Gelatin capsules are frequently more expensive than tablets but have some advantages. For example, particle size is rarely altered during capsule manufacture, and capsules mask the taste and odor of the active ingredient and protect photolabile ingredients.
A powder is a formulation in which a drug powder is mixed with other powdered excipients to produce a final product for oral administration. Powders have better chemical stability than liquids and dissolve faster than tablets or capsules because disintegration is not an issue. This translates into faster absorption for those drugs characterized by dissolution rate-limited absorption. Unpleasant tastes can be more pronounced with powders than with other dosage forms and can be a particular concern with in-feed powders, in which it contributes to variable ingestion of the dose. Moreover, sick animals often eat less and are therefore not amenable to treatment with in-feed powder formulations. Drug powders are principally used prophylactically in feed, or formulated as a soluble powder for addition to drinking water or milk replacer. Powders have also been formulated with emulsifying agents to facilitate their administration as liquid drenches.
A granule is a dosage form consisting of powder particles that have been aggregated to form a larger mass, usually 2-4 mm in diameter. Granulation overcomes segregation of the different particle sizes during storage and/or dose administration, the latter being a potential source of inaccurate dosing. Granules and powders generally behave similarly; however, granules must deaggregate prior to dissolution and absorption.
A premix is a solid dosage form in which an active ingredient, such as a coccidiostat, production enhancer, or nutritional supplement, is formulated with excipients. Premix products are mixed homogeneously with feed at rates (when expressed on an active ingredient basis) that range from a few milligrams to -200 g/ton of food/beverage The density, particle size, and geometry of the premix particles should match as closely as possible those of the feed in which the premix will be incorporated to facilitate uniform mixing. Issues such as instability, electrostatic charge, and hygroscopicity must also be addressed. The excipients present in premix formulations include carriers, liquid binders, diluents, anti-caking agents, and anti- dust agents. Carriers, such as wheat middlings, soybean mill run, and rice hulls, bind active ingredients to their surfaces and are important in attaining uniform mixing of the active ingredient. A liquid binding agent, such as a vegetable oil, should be included in the formulation whenever a carrier is used. Diluents increase the bulk of premix formulations, but unlike carriers, do not bind the active ingredients. Examples of diluents include ground limestone, dicalcium phosphate, dextrose, and kaolin. Caking in a premix formulation may be caused by hygroscopic ingredients and is addressed by adding small amounts of anti-caking agents such as calcium silicate, silicon dioxide, and hydrophobic starch. The dust associated with powdered premix formulations can have serious implications for both operator safety and economic losses, and is reduced by including a vegetable oil or light mineral oil in the formulation. An alternate approach to overcoming dust is to granulate the premix formulation.
A medicated block is a compressed feed material that contains an active ingredient, such as a drug, anthelmintic, surfactant (for bloat prevention), or a nutritional supplement, and is commonly packaged in a cardboard box. Ruminants typically have free access to the medicated block over several days, and variable consumption may be problematic. This concern is addressed by ensuring the active ingredient is nontoxic, stable, palatable, and preferably of low solubility. In addition, excipients in the formulation modulate consumption by altering the palatability and/or the hardness of the medicated block. For example, molasses increases palatability and sodium chloride decreases it. Additionally, the incorporation of a binder such as lignin sulfonate in blocks manufactured by compression or magnesium oxide in blocks manufactured by chemical reaction, increases hardness. The hygroscopic nature of molasses in a formulation may also impact the hardness of medicated blocks and is addressed by using appropriate packaging.
In another embodiment, the composition of the present invention is in a chewable oral dosage form. In another embodiment, the chewable oral dosage form is a chewable tablet. In another embodiment, the chewable tablet of the invention is taken slowly by chewing or sucking in the mouth. In another embodiment, the chewable tablet of the invention enables the Inula viscosa extracts contained therein to be orally administered without drinking.
According to some embodiments of the present invention, the composition may comprise any suitable flavor or combination of flavors.
The composition may further comprise other additives, coloring, and emulsifiers. The flavors and additives may be of a natural, semi-synthetic, synthetic source or combinations thereof.
In another embodiment of the present invention, the composition further comprises fructose, sorbitol, microcrystalline cellulose, magnesium stearate, or any combination thereof. In another embodiment, the composition further comprises chamomile. In another embodiment, the composition further comprises ginger. In another embodiment, the composition further comprises peppermint. In another embodiment, the composition further comprises anise. In another embodiment, the composition further comprises fennel. In another embodiment, the composition further comprises thyme. In another embodiment, the composition further comprises Arsenicum album. In another embodiment, the composition further comprises Carbo vegetabilis. In another embodiment, the composition further comprises Ignatia, homeopathic ipecac. In another embodiment, the composition further comprises Nux vomica. In another embodiment, the composition further comprises Zingiber officinale.
In another embodiment, the composition of the present invention is in the form of a chewing gum product. In another embodiment, chewing gum compositions contemplated by the present invention comprise all types of sugar and sugarless chewing gums and chewing gum formulations known to those skilled in the art, including regular and bubble gum types. In another embodiment, chewing gum compositions of the invention comprise a chewing gum base, a modifier, a bulking agent or sweetener, and one or more other additives such as, flavoring agents, colorants and antioxidants. In another embodiment, the modifying agents are used to soften, plasticize and/or compatibilize one or more of the components of the gum base and/or of the formulation as a whole.
In another embodiment, the present invention provides a soft, chewable dosage form which is pliable and chewy, yet dissolves quickly in the mouth, has a long shelf life, contains little moisture which improves stability and decreases the tendency for the dosage form to dry out, does not require cooking or heating as part of the manufacturing process. In another embodiment, the dosage form is used as a matrix for Inula viscosa extracts.
In another embodiment, the chewable tablet of the invention comprises a metal salt such as calcium, magnesium, aluminum salt, or any mixture thereof. In another embodiment, the chewable tablet of the invention comprises hydroxyalkyl cellulose. In another embodiment, the chewable tablet of the invention comprises low viscosity hydroxyalkyl cellulose. In another embodiment, the chewable tablet of the invention comprises high viscosity hydroxyalkyl cellulose.
In another embodiment, the chewable tablet of the invention comprises various additives. In another embodiment, the chewable tablet of the invention comprises sweeteners. In another embodiment, the chewable tablet of the invention comprises acidic ingredients. In another embodiment, the chewable tablet of the invention comprises taste correctives. In another embodiment, the chewable tablet of the invention comprises polymeric compounds. In another embodiment, the chewable tablet of the invention comprises essential oils.
In another embodiment, the chewable tablet of the invention is a soft tablet. In another embodiment, the chewable tablet of the invention is made in a state of soft candy. In another embodiment, the chewable tablet of the invention is made in a state of jelly.
In another embodiment, the chewable tablet of the invention comprises a core comprising the Inula viscosa extracts of the invention. In another embodiment, the chewable tablet of the invention comprises an outer layer wrapping the core which is made up of chewable base such as a gum, a soft candy or a caramel.
In another embodiment, the compositions of the present invention may be provided in any suitable food of a solid, semi-solid or liquid form.
In another embodiment, the chewable tablet of the invention protects the Inula viscosa extracts that are liable to transform. In another embodiment, the chewable tablet of the invention comprises pectin. In another embodiment, the chewable tablet of the invention comprises maltitol. In another embodiment, the chewable tablet of the invention comprises isomalt. In another embodiment, the chewable tablet of the invention comprises liquid glucose. In another embodiment, the chewable tablet of the invention comprises sugar. In another embodiment, the chewable tablet of the invention comprises citric acid. In another embodiment, the chewable tablet of the invention comprises sorbitol. In another embodiment, the chewable tablet of the invention comprises a flavoring agent. In another embodiment, the chewable tablet of the invention comprises a natural flavoring agent. In another embodiment, the chewable tablet of the invention comprises a synthetic flavor. In another embodiment, the chewable tablet of the invention comprises a volatile oil. In another embodiment, the chewable tablet of the invention comprises synthetic flavor oil. In another embodiment, the chewable tablet of the invention comprises a flavoring aromatic. In another embodiment, the chewable tablet of the invention comprises a oleoresin. In another embodiment, the chewable tablet of the invention comprises an extract derived from a plant. In another embodiment, the chewable tablet of the invention comprises an extract derived from a leaf. In another embodiment, the chewable tablet of the invention comprises an extract derived from a flower. In another embodiment, the chewable tablet of the invention comprises an extract derived from a fruit. In another embodiment, the chewable tablet of the invention comprises an extract derived from a stem.
In another embodiment, the chewable tablet of the invention comprises citrus oil such as but not limited to lime, grapefruit, lemon, or orange. In another embodiment, the chewable tablet of the invention comprises fruit essences such as but not limited to apple, pear, peach, grape, strawberry, raspberry, cherry, plum, pineapple, apricot or other fruit flavors. In another embodiment, the chewable tablet of the invention comprises flavorings such as but not limited to aldehydes and esters such as benzaldehyde (cherry, almond), citral, i.e., alphacitral (lemon, lime), neral, i.e., beta- citral (lemon, lime) decanal (orange, lemon), aldehyde C-8 (citrus fruits), aldehyde C-9 (citrus fruits), adlehyde C-12 (citrus fruits), tolyl aldehyde (cherry, almond), 2,6- dimethyloctanal (green fruit), and 2-dodecenal (citrus, mandarin), mixtures thereof and the like.
In another embodiment, the chewable tablet of the invention comprises a gum.
In another embodiment, the chewable tablet of the invention comprises a soft gum. In another embodiment, the chewable tablet of the invention comprises nougat. In another embodiment, the chewable tablet of the invention comprises soft candy. In another embodiment, the chewable tablet of the invention comprises hard candy. In another embodiment, the chewable tablet of the invention comprises caramel. In another embodiment, the chewable tablet of the invention comprises an enhancing agent of chewing property.
In another embodiment, sugar used in the present invention may be selected from the group consisting of white sugar, liquid glucose, sorbitol, dextrose, isomalt, liquid maltitol, aspartame and lactose, and this sugar may comprise 30-90 weight % by total weight of the ingredients.
In another embodiment, the chewable tablet of the invention comprises a sweetener such as but not limited to: glucose (corn syrup), dextrose, invert sugar, fructose, and mixtures thereof (when not used as a carrier); saccharin and its various salts such as the sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Stevia Rebaudiana (Stevioside); chloro derivatives of sucrose such as suralose; sugar alcohols such as sorbitol, mannitol, xylitol, and the like. In another embodiment, the chewable tablet of the invention comprises hydrogenated starch hydrolysates and the synthetic sweetener 3,6-dihydro-6-methyl-l-l-l,2,3- oxathiazin-4-one-2,2-dioxide. In another embodiment, the chewable tablet of the invention comprises the potassium salt (acesulfame-K), and sodium and calcium salts of 3,6-dihydro-6-methyl-l-l-l,2,3-oxathiazin-4-one-2,2-dioxide. In another embodiment, the chewable tablet of the invention comprises other sweeteners known to one of skill in the art.
In another embodiment, glycerin, lecithin, hydrogenated palm oil or glyceryl monostearate are used as a protecting agent of crystallization of the sugars in 0.02-3.0 weight % by total weight of the ingredients, to prevent adhesion to oral cavity and improve the soft property of the products.
In another embodiment, isomalt or liquid maltitol are used as an enhancing agent of chewing property. In another embodiment, gelatin or arabic gum are used as a keeping agent of hardness and extension property in 0.1-3.0 weight % by total weight of the ingredients. In another embodiment, food flavor or a fruits extract; a souring agent such as citric acid are added in adequate amount. In another embodiment, a coloring agent such as a food color is optionally added in a small amount.
Yet a further embodiment of the present invention includes the use of an effervescent disintegration agent. In another embodiment, its action aids in the masking of objectionable taste of the Inula viscosa extract. In another embodiment, of the present invention the effervescent disintegration agent is an acid. In another embodiment, of the present invention the effervescent disintegration agent is citric acid. In another embodiment, of the present invention the effervescent disintegration agent is tartaric acid. In another embodiment, of the present invention the effervescent disintegration agent is malic acid. In another embodiment, of the present invention the effervescent disintegration agent is fumaric acid. In another embodiment, of the present invention the effervescent disintegration agent is adipic acid. In another embodiment, of the present invention the effervescent disintegration agent is succinic acid. In another embodiment, of the present invention the effervescent disintegration agent is at least one base such as but not limited to: carbonate salts, bicarbonate salts and mixtures thereof.
In another embodiment, the chewable tablet of the invention comprises a crystallization modifier such but not limited to, surfactants (Spans.TM. and Tweens.TM.), dextrose, polyethylene glycol (PEG), polypropylene glycol (PPG), etc. These modifiers generally provide controlled acceleration of crystallization while the matrix is bound. In another embodiment, these crystallization modifiers enhance the formation of a crystalline frame and the conversion of the remaining mass.
In another embodiment, crystallization modifiers are surfactants having a hydrophilic to lipid balance (HLB) of six or greater, i.e., they have the same degree of hydrophilicity as surfactants characterized by degree of HLB. In another embodiment, such materials include, but are not limited to anionic, cationic and zwitterionic surfactants as well as neutral materials which have an HLB of six or greater. In another embodiment, crystallization modifiers are hydrophilic materials having polyethylene oxide linkages. In another embodiment, crystallization modifiers have a molecular weight of at least 100.
In another embodiment, the chewable tablet of the invention comprises a filler. In another embodiment, filler increases the bulk of the tablet. In another embodiment, the filler is calcium sulfate, both di- and tri basic, starch, calcium carbonate, microcrystalline cellulose, modified starches, lactose, sucrose, mannitol, sorbitol, or any combination thereof.
In another embodiment, the chewable tablet of the invention comprises a binder such as but not limited to: starches, pre-gelatinize starches, gelatin, polyvinylpyrrolidone, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, and polyvinylalcohols.
In another embodiment, the chewable tablet of the invention comprises a lubricant such as but not limited to: magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene, monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate and light mineral oil.
In another embodiment, the chewable tablet of the invention comprises a dispersion enhancer such as but not limited to: starch, alginic acid, polyvinylpyrrolidones, guar gum, partially hydrolyzed guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants.
In another embodiment, the chewable tablet of the invention comprises a disintegrant such as but not limited to: Croscarmellose sodium, marketed under the trade name Ac-Di-Sol.
In another embodiment, the chewable tablet of the invention comprises an absorbent such as but not limited to: maltodextrin. In another embodiment, the chewable tablet of the invention comprises an emulsifier such as but not limited to: Mono- and diglycerides, Oleaginous substances such as food oils like Medium, Chain Triglycerides (MCT), and Stearine D 17.
In another embodiment, the chewable tablet of the invention comprises a water soluble bulking agent such as but not limited to: hydrocolloid thickeners and binders, such as gum arabic, pectins, modified starches, alginates, carrageenans, xanthan gums, carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, propylene glycol alginate, polyvinylpyrrolidone (PVP), carboxyvinyl polymers (such as Carbopol.RTM.), polyethylene oxide polymers (such as Polyox.RTM.), sorbitol, xylitol, sucrose, fructose, dextrose, mannitol, starch maltodextrin, corn syrup solids, or combinations thereof.
In another embodiment, the chewable tablet of the invention comprises a water insoluble bulking agent such as but not limited to: talc, dicalcium phosphate, powdered celluloses, microcrystalline celluloses and antacid compounds.
In another embodiment, the chewable tablet of the invention comprises Inula viscosa extracts in compressed particles. In another embodiment, individual particles are coated with a blend of cellulose acetate or cellulose acetate butyrate and polyvinyl pyrrolidone (USP Povidone or "PVP"). In another embodiment, the coating provides excellent taste masking while still permitting acceptable bioavailability of the Inula viscosa extracts. In another embodiment, the chewable tablet.
In another embodiment, the invention relates to a composition of the invention comprised within chewable and edible soft gelatin capsules, the shells of which comprise gelatin, water, plasticizer and a hydrogenated starch hydrolysate. In another embodiment, soft gelatin shell comprises about 10-45% gelatin; about 5-30% water; about 12-35% plasticizer; and about 2-25% of a hydrogenated starch hydrolysate. In another embodiment, the shell encloses a soft gelatin capsule fill material. In another embodiment, the gelatin may be of Type A, Type B, or a mixture thereof. In another embodiment, in order to augment the taste and chewability of the capsule shell, as well as to assist in the rapid dissolution of the shell upon chewing, the present capsule shell further comprises a hydrogenated starch hydrolysate.
In another embodiment, chewable systems of the invention are preferable for administering the compositions of the invention. In another embodiment, the act of chewing increases the surface area of the Inula viscosa extract and increases the rate of absorption by the digestive tract. In another embodiment, chewable systems of the invention provide Inula viscosa extract, topically to the mouth or throat areas for both local effects and systemic absorption.
The preparation of pharmaceutical compositions that contain Inula viscosa extract, for example by mixing, granulating, or tablet-forming processes, is well understood in the art. The Inula viscosa extracts are often mixed with excipients that are pharmaceutically acceptable and compatible with the active ingredient. For oral administration, the active ingredients of compositions of the present invention are mixed with additives customary for this purpose, such as vehicles, stabilizers, or inert diluents, and converted by customary methods into suitable forms for administration, such as tablets, coated tablets, hard or soft gelatin capsules, aqueous, alcoholic or oily solutions.
In another embodiment, additional methods of administering the compositions of the invention comprise injectable dosage forms. In another embodiment, the injectable is administered intraperitonealy. In another embodiment, the injectable is administered intramuscularly. In another embodiment, the injectable is administered intradermally. In another embodiment, the injectable is administered intravenously. Each possibility represents a separate embodiment of the present invention.
In another embodiment, the pharmaceutical compositions are administered by intravenous, intra-arterial, or intra-muscular injection of a liquid preparation. Suitable liquid formulations include solutions, suspensions, dispersions, spray (liquid under pressure), nasal preparations, emulsions, oils and the like. In another embodiment, the pharmaceutical compositions are administered intravenously and are thus formulated in a form suitable for intravenous administration. In another embodiment, the pharmaceutical compositions are administered intra-arterially and are thus formulated in a form suitable for intra-arterial administration. In another embodiment, the pharmaceutical compositions are administered intra-muscularly and are thus formulated in a form suitable for intra-muscular administration.
In another embodiment, additional methods of administering the Inula viscosa extracts of the invention comprise dispersions, suspensions or emulsions. In another embodiment, the dispersion, suspension or emulsion is administered orally. In another embodiment, the solution is administered by infusion. In another embodiment, the solution is a solution for inhalation. Each possibility represents a separate embodiment of the present invention.
In another embodiment, the pharmaceutical composition is administered as a suppository, for example a rectal suppository or a urethral suppository. In another embodiment, the pharmaceutical composition is administered by subcutaneous implantation of a pellet. In another embodiment, the pellet provides for controlled release of active compound agent over a period of time. Each possibility represents a separate embodiment of the present invention.
In other embodiments, pharmaceutically acceptable carriers for liquid formulations are aqueous or non-aqueous solutions, suspensions, emulsions or oils. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, and injectable organic esters such as ethyl oleate. Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media. Examples of oils are those of animal, vegetable, or synthetic origin, for example, peanut oil, soybean oil, olive oil, sunflower oil, fish-liver oil, another marine oil, or a lipid from milk or eggs. Each possibility represents a separate embodiment of the present invention. In another embodiment, parenteral vehicles (for subcutaneous, intravenous, intraarterial, or intramuscular injection) include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's and fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers such as those based on Ringer's dextrose, and the like. Examples are sterile liquids such as water and oils, with or without the addition of a surfactant and other pharmaceutically acceptable adjuvants. In general, water, saline, aqueous dextrose and related sugar solutions, and glycols such as propylene glycols or polyethylene glycol are preferred liquid carriers, particularly for injectable solutions. Examples of oils are those of animal, vegetable, or synthetic origin, for example, peanut oil, soybean oil, olive oil, sunflower oil, fish-liver oil, another marine oil, or a lipid from milk or eggs. Each possibility represents a separate embodiment of the present invention.
In another embodiment, the pharmaceutical compositions provided herein are controlled-release compositions, i.e. compositions in which the active compounds are released over a period of time after administration. Controlled- or sustained-release compositions include formulation in lipophilic depots (e.g. fatty acids, waxes, oils). In another embodiment, the composition is an immediate-release composition, i.e. a composition in which all the active compound is released immediately after administration. Each possibility represents a separate embodiment of the present invention.
In another embodiment, the pharmaceutical composition is delivered in a controlled release system. In another embodiment, the Inula viscosa extracts, tomentosin and or inuviscolide are administered using intravenous infusion, an implantable osmotic pump, a transdermal patch, liposomes, or other modes of administration. In another embodiment, a pump is used (see Langer, supra; Sefton, CRC Crit. Ref. Biomed. Eng. 14:201 (1987); Buchwald et al., Surgery 88:507 (1980); Saudek et al., N. Engl. J. Med. 321:574 (1989). In another embodiment, polymeric materials are used; e.g. in microspheres in or an implant. In yet another embodiment, a controlled release system is placed in proximity to the therapeutic target, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138 (1984); and Langer R, Science 249: 1527-1533 (1990). Each possibility represents a separate embodiment of the present invention. The compositions also include, in another embodiment, incorporation of the active materials into or onto particulate preparations of polymeric compounds such as polylactic acid, polglycolic acid, hydrogels, etc, or onto liposomes, microemulsions, micelles, unilamellar or multilamellar vesicles, erythrocyte ghosts, or spheroplasts.) Such compositions will influence the physical state, solubility, stability, rate of in vivo release, and rate of in vivo clearance. Each possibility represents a separate embodiment of the present invention.
Also included in the present invention are particulate compositions coated with polymers (e.g. poloxamers or poloxamines) and the compound coupled to antibodies directed against tissue-specific receptors, ligands or antigens or coupled to ligands of tissue-specific receptors. Each possibility represents a separate embodiment of the present invention.
Also comprehended by the invention are compounds modified by the covalent attachment of water-soluble polymers such as polyethylene glycol, copolymers of polyethylene glycol and polypropylene glycol, carboxymethyl cellulose, dextran, polyvinyl alcohol, polyvinylpyrrolidone or polyproline. The modified compounds are known to exhibit substantially longer half-lives in blood following intravenous injection than do the corresponding unmodified compounds (Abuchowski et al., 1981; Newmark et al., 1982; and Katre et al., 1987). Such modifications also increase, in another embodiment, the compound's solubility in aqueous solution, eliminate aggregation, enhance the physical and chemical stability of the compound, and greatly reduce the immunogenicity and reactivity of the compound. In another embodiment, the desired in vivo biological activity is achieved by the administration of such polymer-compound abducts less frequently or in lower doses than with the unmodified compound. Each possibility represents a separate embodiment of the present invention.
The compositions of the present invention may comprise one or more additional components may further include an additional component selected from the group consisting of an anti-static agent, a buffering agent, a bulking agent, a chelating agent, a colorant, a diluent, a dye, an emollient, a fragrance, an occlusive agent, a pH-adjusting agent, a preservative, and at least one vitamin.
The compositions of the present invention may comprise one or more additional active agents, selected from the group consisting of active herbal extracts, analgesics, anti-allergic agents, anti-aging agents, anti-bacterials, antibiotic agents, anticancer agents, antidandruff agents, antidepressants, anti-dermatitis agents, anti-edemics, antihistamines, anti-helminths, anti-hyperkeratolyte agents, anti-inflammatory agents, anti-irritants, anti-microbials, anti-mycotics, anti-proliferative agents, antioxidants, anti- wrinkle agents, anti-pruritics, antiseptic agents, antiviral agents, anti-yeast agents, astringents, topical cardiovascular agents, chemotherapeutic agents, corticosteroids, dicarboxylic acids, disinfectants, fungicides, hair growth regulators, hormones, hydroxy acids, immunosuppressants, immunoregulating agents, keratolytic agents, lactams, metals, metal oxides, mitocides, neuropeptides, non-steroidal anti-inflammatory agents, oxidizing agents, photodynamic therapy agents, retinoids, sanatives, scabicides, self tanning agents, skin whitening agents, vasoconstrictors, vasodilators, vitamin extracts, Inula viscosa extract derivatives and wound healing agents.
According to some embodiments, the composition may comprise one or more anti-oxidants/radical scavengers. The anti-oxidant/radical scavenger may be selected from butylated hydroxy benzoic acids and their salts, coenzyme Q10, coenzyme A, gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, lipoic acid, amines (e.g., N,N-diethylhydroxylamine, amino-guanidine), sulfhydryl compounds (e.g., glutathione), dihydroxy fumaric acid and its salts, lycine pidolate, arginine pilolate, nordihydroguaiaretic acid, bioflavonoids, curcumin, lysine, methionine, proline, superoxide dismutase, silymarin, tea extracts, grape skin/seed extracts, melanin, and rosemary extracts.
According to some embodiments, the composition may comprise one or more additional vitamin extracts selected from vitamin A, any one or more of the vitamin B complex, vitamin D, vitamin K, vitamin E and C.
The preparation of pharmaceutical compositions that contain the Inula viscosa extracts of the invention are performed, for example by mixing, granulating, or tablet- forming processes, is well understood in the art. The active therapeutic ingredient is often mixed with excipients that are pharmaceutically acceptable and compatible with the active ingredient. For oral administration, the active compounds are mixed with additives customary for this purpose, such as vehicles, stabilizers, or inert diluents, and converted by customary methods into suitable forms for administration, such as tablets, coated tablets, hard or soft gelatin capsules, aqueous, alcoholic or oily solutions. For parenteral administration, the active compounds are converted into a solution, suspension, or emulsion, if desired with the substances customary and suitable for this purpose, for example, solubilizers or other substances.
According to some additional embodiments, the composition may comprise one or more of bran oil, gelatin, glycerin, water, red palm fruit oil and carob extract.
According to some further embodiments, the composition may be formulated in the form of a drink or beverage.
According to some further embodiments, the composition may be formulated in the form of a sweet, candy, lozenge, chewing gum, toffee, candy bar, chocolate bar, health snack or other appetizing food product.
Each of the above additives, excipients, formulations and methods of administration represents a separate embodiment of the present invention.
In one embodiment, the term "treating" refers to curing a disease. In another embodiment, "treating" refers to preventing a disease. In another embodiment, "treating" refers to reducing the incidence of a disease. In another embodiment, "treating" refers to ameliorating symptoms of a disease. In another embodiment, "treating" refers to inducing remission. In another embodiment, "treating" refers to slowing the progression of a disease.
Example 1 -Inula viscosa compositions a) Alcoholic Inula viscosa extracts, concentrates, pastes and powders
Some embodiments of the present invention relate to alcoholic extracts from
Inula plants. More particularly, some embodiments relate to the type Inula viscosa plant. The Inula viscosa extract may be used topically or preferably in a formulation comprising suitable excipients. The amount of the Inula viscosa extract in the formulation is about 0.01% to about 100%. The extract is obtained by harvesting the above-ground parts such as, but not limited to: leaves, twigs, bark, flowers, buds, fruits, peels, seeds, roots, rhizomes, tubers, or bulbs. The parts are homogenized in a blender, for example, with 0-100% ethanol until the mixture is uniform. The homogenate is collected and filtered; the resulting supernatant is an Inula viscosa extract (IVE). The extract may be concentrated by evaporation to form a concentrated extract. Additionally or alternatively it may be concentrated by evaporation until a wet paste, or resin extract forms. Additionally or alternatively an aqueous extract may be concentrated by evaporation and/or lyophilization until a dry powder extract forms, depending on the process conditions.
Inula viscosa extract compositions according to the present invention may be used in appropriate formulations comprising wheat seed oil, vitamin E, and zinc.
b) Inula viscosa formulations
According to further embodiments, formulations prepared in accordance with the methods described in WO05117925.
c) Inula viscosa alcoholic tincture
An alcoholic tincture of Inula viscosa ethanol extract for topical disorders associated with viral infections. Alcoholic tincture: 30g Inula viscosa resin extract were melted and then dissolved in 70 gram alcohol (technical grade alcohol 95%). After stirring for up to 3 hours an Inula viscosa extract formed (in an alcoholic tincture (30% mixture).
d) Aloe vera gel containing Inula viscosa extract
Aloe vera gel mixture in Inula viscosa tincture:- 10 gram of the gel is added to 90 gram of Inula viscosa alcoholic tincture (above), followed by stirring and shaking for up to 3 hours to form a uniform mixture (dispersion) of the tincture in the gel.
e) Vaseline gel comprising Inula viscosa extract
Preparation of Inula viscosa extract 10% in petroleum Vaseline:- Weigh 90 gram of petroleum Vaseline, add 10 gram of Inula viscosa extract, stir until even texture and color is obtained.
f) Olive oil/ Seed oil/canola oil emulsion comprising Inula viscosa extract
Inula Olive oil/Seed oil/canola oil (useful for skin softening, fungal treatment, for skin anti inflammatory, anti oxidant, anti fungus, anti bacteria and anti yeast treatment. 192 gram of olive oil/Seed oil/canola oil were warmed to 55°C. 4 gram of food grade emulsifier Span 80 or equivalent were added to the oil, stirred until uniform blend was reached and kept warm up to 55°C. Inula viscosa extract was warmed up to 50°C, 4 gram of the molten extract were added slowly to the warm oil and vigorously mixed to form a smooth and uniform emulsion. In a similar manner Inula viscosa may be mixed with any other vegetable oil. Example 2 Preparation of an Inula extract cream composition and a solvent extract
Extraction procedure
Fresh leaves of Inula viscosa were collected from a field near Modi'in, Israel. The leaves were ground in a home blender with 70% ethanol until the mixture was uniform. Another option is dry leaves that are soaked in water up to 24 hours (rehydration), then the water are filtered and the leaves are soaked in ethanol for another 24 hours, or dry leaves, that are crushed and soaked in ethanol for another 24 hours. After soaking the leaves are blended. The homogenate was collected and filtered through a gauze pad. Part of the supernatant was collected and stored in a glass bottle at room temperature. The other part of the supernatant was left in an open glass bottle near a window to evaporate. The residue 1-35% (1-35 g to lOOg cream) was mixed with a hand cream that was manufactured comprising the following such as the hand cream commercially available (by the AHAVA Dead Sea Products Ltd or Nivea daily face soft cream).
Example 3 -HSV-1 COLD SORE TREATMENT
- The cream of Example 2 was used on a Caucasian male age 62, suffering from an HSV-1 infection on the upper lip.
Reference is now made to Figs. 1A- ID, which are images of treatment stages using the compositions of the present invention in treating a sore on a lip induced by HSV-1 with a cream, as described in the extract preparation, three times a day: (Fig. 1A) before treatment, (Fig. IB) after 18 hours treatment, (Fig. 1C) after 36 hours treatment, (Fig. ID) after 72 hours treatment, in accordance with an embodiment of the present invention.
When the patient was infected, he used Zovirax for 4 days but the affliction got worse. Thereafter, he stopped using Zovirax and starts to use the cream of Example 2 containing the Inula extract (Fig. 1A). Approximately eighteen hours after the first use the pain had subsided (Fig. IB), less infection was seen, the swelling was better and a new coagulate started to appear. After 36 hours the affliction had shrunk (Fig. 1C).
After 72 hours only a small coagulate was seen (Fig. ID). Example 4 -HSV-3 RASH TREATMENT
The ethanol supernatant prepared hereinabove was used on two Caucasian females age 50-55, who suffer from repeated outbreaks of HSV-3. In one female, the symptoms were a red rash on the chest and arms, over-sensitivity around the infected area and an internal pain. The supernatant solution (the ethanol extract of example 1) was smeared on the infected area and overnight the rash was better while the pain and the sensitivity disappeared. After three days of smearing the rash had disappeared too. In the other female, the symptoms were: a beginning of a red rash on the arms and on the sides of the back and a feel of tingling around the infected area. The solution was smeared on the infected area and overnight the rash and the tingling feeling disappeared. This woman used the ethanol supernatant twice and the results were the same.
Example 5 - ABSCESS TREATMENT
A young Caucasian female age 35, suffered from an abscess with a severe infection on the chest.
Reference is now made to Figs. 2A- 2F, which are images of treatment stages using the compositions of the present invention in treating an abscess: (Fig. 2 A) before treatment, (Fig. 2B) after three days treatment, (Fig. 2C) after four days treatment, (Fig. 2D) after five days treatment, (Fig. 2E) after six days treatment, and (Fig. 2F) after 23 days, in accordance with an embodiment of the present invention.
Prior to this treatment, the doctors recommended four days of antibiotics and then surgery (Fig. 2A). She applied first the ethanol supernatant (from example 1) for two minutes and then afterwards she smeared the on cream (per example 1 hereinabove). She repeated this treatment four times a day. Two days after she began the treatment, the abscess that was originally hard became very soft (Fig. 2B). After additional 24 hours, a small "head" appear on the abscess (Fig. 2C). During the evening of the same day, the abscess exploded and a huge amount of infected fluid burst out. After that, she continued the treatment twice a day. Six days after the beginning of the treatment, only a small wound was left (Fig. 2D). After six months a smaller abscess came back with redness and pain the patient smeared the cream from Example 1 three times a day and after 3 days again, only a small wound was left.
Example 7 -SEBORRHEA TREATMENT
A young Caucasian female aged 34, suffers from seborrhea with itching and reddened skin on the forehead.
Reference is now made to Figs. 3 A- 1C, which are images of treatment stages using the compositions of the present invention in treating Seborrhea: (Fig. 3A) before treatment, (Fig. 3B) after 48 hours treatment, (Fig. 3C) after 72 hours treatment, in accordance with an embodiment of the present invention.
The patient smeared the cream of Example 1 twice a day: once in the morning and once in the evening. A day after she began the treatment the redness was reduced and the itching stopped. After additional 24 hours the affliction almost vanished and after 72 hours, from the beginning of the treatment, the skin went back to normal and not even a small sign was left.
Example 8 (a prophetic example)
Fresh/dried leaves of Inula viscosa or any other herb that contain sesquiterpene lactones (SLs) are to be collected from a licensed, controlled and supervised habitat.
The leaves will be grounded in a blender with 70%- 100% ethanol or in distilled water
1:8 (w/v). The mixed homogenate will be collected and filtered through a gauze pad or filtered through Whatman No. 1 filter paper and centrifuged at 20,000 g for 10 min. The aqua supernatant will be dried in a lyophilizer (0.07 mbar, 48 8C) and the ethanolic extraction will be concentrated by evaporator. The resulting resin/powdered extract will designated Inula viscosa ethanol extract or aqueous extract, respectively. The aqua powder will be further extracted in acetonitrile overnight, filtered, and evaporated under reduced pressure. The acetonitrile extract will be separated by thin layer chromatography (TLC) into two main SLs components: Tomentosin (Rf = 0.88) and
Inuviscolide (Rf = 0.725) using the solvent system benzene/ methanol (3:1). The concentrated ethanolic extract will be purified by a column with a solvent mixture of different polarity. The SLs, Inuviscolide and Tomentosin will be identified by full analysis of the 1H and 13C NMR spectra and by comparison with published data, respectively [Zdero C et al., 1987, Lanzetta R et al., 1991]. The purity of the SLs will be greater than 80%.
The powder comprising the purified sesquiterpene lactones tomentosin and inuviscolide is then to be mixed with vitamins, ferulic acid, zinc and anti oxidative compounds. Final concentration for treatment of tomentosin in the composition will be 0.1-1% and inuviscolide 0.1-1%.
Example 9 (a prophetic example)
Fresh leaves/dried of Inula viscosa or any other herb that contain sesquiterpene lactones (SLs) are to be collected from a licensed, controlled and supervised habitat. The leaves will be grounded in a blender with 100% ethanol or in distilled water 1 :5-l :8 (w/v). The mixed homogenate will be collected and filtered through a gauze pad or filtered through Whatman No. 1 filter paper and centrifuged at 20,000 g for 10 min. The aqua supernatant will be dried in a lyophilizer (0.07 mbar, 48 8°C) and the ethanolic extraction will be concentrated by evaporator. The resulting resin/powdered extract will designate Inula viscosa respectively ethanol or watery extract. The resulting resin/powdered extract will be mixed together in different combination ratios ranging from 10% - 90% ethanolic extract to aqueous extract, according to the severity of the medical condition of the patient.
Example 10- HSV-3/VZV in vitro assay
Reference is now made to Figs. 4A- 4F, which are images of tissue culture plates with cells infected with Herpes simplex virus type 3 (HSV3)-4A and 4B controls without treatment; 4C-4E treated with Inula viscosa extract; and 4F treated with Acyclovir, in accordance with an embodiment of the present invention;
The picture demonstrates a tissue culture plate with cells that were infected by herpes virus type 3. The left upper and lower two wells (Figs. 4A and 4B) show white spots which represents typical HSV3 plaques. The white spots are typical HSV3 plaques. Those white spots are the exposure of the well bottom, that before was covered with virus infected cells. The virus replication caused cell death and therefore the cells detached and left empty spots. These two wells represent the positive control - cells infected with HSV3 and typical plaques.
The middle upper well (Fig. 4C) represents HSV3 infected cells with 0.25μg of Inula viscosa extract that was add to their growth medium. In comparison to the positive control, less plaques had grown in this well.
The middle lower well (Fig. 4D) represents HSV3 infected cells with 0.5(^g of Inula viscosa extract which was added to the growth medium. In comparison to the positive control, and to the well with 0.25 μg Inula viscosa extract (Fig. 4C), even less plaques had grown in this well.
The right upper well (Fig. 4E) represents HSV3 infected cells that 1 μg of Inula viscosa extract, which was added to the growth medium. No plaques had grown or developed in this well.
The lower right well represent HSV3 infected cells that \0 x,g of Acyclovir was add to their growth medium. This is a positive control for a drug that reduces and prevents HSV3 growth.
Conclusions: these images demonstrate the influence of Inula viscosa extract in a dose dependent manner on HSV3. The HSV3 inhibitory concentration by Inula viscosa extract is much lower compared to the Acyclovir inhibitory concentration.
Example 11- HSV3 infection
A Caucasian female age 65, that suffers from outbursts of Herpes Zoster (HSV3) every once in a while, despite taking Acyclovir every outbreak. The outbreaks symptoms include 1 or more red blisters accompanied by itching and either local aches or ache that start at the blister site and continue down the leg nerves (the sensation is of aches within the leg itself). The blisters and their symptoms may last up to 1 week. In contrast, upon treatment by spreading Inula viscosa extract, there was a significant relief in terms of the itching and the redness within 1-3 days. The expected local aches and those that extend into the legs were relieved. In the first 3 outbreaks the pain, redness and blisters were relived after one night (12-18 hours). The forth outbreak was more difficult and the relief came after two days (36 hours).
Example 12- HSV-1 infection
Reference is now made to Figs. 5 A- 5C, which are images of treatment stages using the compositions of the present invention in treating a Herpes simplex 1 (HSV1): (Fig. 5 A) before treatment, (Fig. 5B) after 36 hours treatment, (Fig. 5C) after 48 hours treatment, in accordance with an embodiment of the present invention.
A Caucasian male age 25, suffers from an HSV-1 infection on both lips. The male suffers from recurrent outbreaks of labial herpes infections, and is also durable to Zovirax. The left photo (Fig. 5 A) represents two days after the HSV-1 outbreak as the patient suffered from a growing number of cold sores, swelling, redness and pain. 18 hours therafter, he began to use the herbal extract (per Example 1 hereinabove). There was a relief both in pain and in the swelling around the sores (described by the patient. Not represented by a figure). 36 hours after the beginning of the treatment, the middle photo(Fig. 5B), show less infection, significant improvement of the swelling and a coagulate started to appear. After 48 hours the affliction had shrunk (the right photo(Fig. 5C)). On the lower lip, the infection is in a final stage, whereas, on the upper lip, only residues has remained (the right photo).
Example 13- HSV-1 infection
Reference is now made to Figs. 6A-6D, which are images of treatment stages using the compositions of the present invention in treating a Herpes simplex 1 (HSV1): (Fig. 6A) before treatment, (Fig. 6B) after 24 hours treatment, (Fig. 6C) after 48 hours treatment, and (Fig. 6D) after 72 hours treatment, in accordance with an embodiment of the present invention.
A Caucasian female age 24, suffers from an HSV-1 infection on the upper lip.
The female suffers from recurrent outbreaks of labial herpes infections, and is also durable to Zovirax. At the beginning the young lady reported a tingling in her upper lip which represents a budding of a new herpes cold sore (Fig.6A). 12 hours after the tingling feeling a cold sore with infection and great pain had appeared (Fig.6B). At that point, the lady started to spread the Inula viscosa extract on the sore and reported that 18 hours from the beginning of the treatment the pain and the discomfort disappear (Fig.6B). 48 hours from the beginning of using Inula viscosa extract, the cold sore was fully turned into a coagulate and the swelling was gone (Fig.6C). Another 24 hours later, the coagulate was appeared part of the coagulate fall down (Fig.6D) and 24 hours later the rest of the coagulate fell too (was reported but not pictured).
Example 14- Chronic wound healing
Reference is now made to Figs. 7A-7D, which are images of treatment stages using the compositions of the present invention in treating chronic wounds on a heel- (Fig. 7 A) before treatment, (Fig. 7B) after 72 hours treatment, (Fig. 7C) after 5 days' treatment, and (Fig. 7D) after 7 days' treatment, in accordance with an embodiment of the present invention.
A Caucasian male age 38, suffers in his foot from dry skin that cause cuts, bleeding and great pain throughout walking (Fig. 7A). This male usually treats these wounds with an ointment named "U-Lactin", which hardly helps the healing. Upon treatment by spreading Inula viscosa extract, after 3 days the dry skin was peeled and a significant relief in pain was reported (Fig. 7B). after 2 more days the bleeding cuts were improved (Fig. 7C), and 2 more days, only residues of the wounds were remained (Fig. 7D).
Example 15- Viral warts caused by Molluscum contaeious virus
Reference is made to Figs. 8A-8D, which are images of treatment stages using the compositions of the present invention in treating viral warts caused by Molluscum contagious virus (Fig. 8A) before treatment, (Fig. 8B) before treatment, (Fig. 8C) after 7 days' treatment, and (Fig. 8D) after one month's treatment, in accordance with an embodiment of the present invention.
A young female child age 18 months, suffered from viral warts at her buttocks.
One of the warts began to grow without control and looked like a benign tumor (Figs.
8A and B). The doctor treatment was to sting the wart with liquid nitrogen, a treatment that causes great pain for a while. At that point the wart was spread with Inula viscosa extract for 7 days and the wart began to shrink (Fig. 8C). A month of treatment for 3 days a week caused a significant shrinkage until the blister was dried and almost undetectable (Fig. 8D).
Example 16-intestinal virus
A Caucasian female age 35, suffered from an infection of an intestine virus that cause nausea, stomach aches and diarrhea. After 4 days of sickness she drank an aqua's extract of Inula viscosa. The nausea stopped after two hours and 12 hours later the stomach aches and diarrhea stopped completely.
The references cited herein teach many principles that are applicable to the present invention. Therefore the full contents of these publications are incorporated by reference herein where appropriate for teachings of additional or alternative details, features and/or technical background.
It is to be understood that the invention is not limited in its application to the details set forth in the description contained herein or illustrated in the drawings. The invention is capable of other embodiments and of being practiced and carried out in various ways. Those skilled in the art will readily appreciate that various modifications and changes can be applied to the embodiments of the invention as hereinbefore described without departing from its scope, defined in and by the appended claims.
References
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Claims

CLAIMS:
1. A composition for treating a topical disorder associated with a viral infection, the composition comprising at least one of:
a) a plant extract comprising at least one of tomentosin and inuviscolide;
b) tomentosin;
c) inuviscolide;
d) a plant cell culture extract comprising at least one of tomentosin and inuviscolide and
e) an Inula viscosa extract; and
a pharmaceutically acceptable carrier.
2. A composition according to claim 1, wherein said plant extract comprises an extract from at least one species selected from the genera Inula, Xanthium and Arnica.
3. A composition according to claim 2, wherein said at least one Inula species is selected from Inula acaulis, Inula acervata S.Moore, Inula acinacifolia Gand, Inula acuminata DC, Inula afghanica, Inula anatolica Boiss., Inula auriculata Boiss. & Balansa, Inula bifrons (L.) L., Inula britannica L.— British Yellowhead, Inula Candida (L.) Cass., Inula cappa (Buch.-Ham. ex D. Don) DC, Inula caspica Blume, Inula clarkei ( Hookf.) R.R.Stewart, Inula conyzae (Griess.) Meikle - Plougman's-spikenard, Inula crithmoides L.— Golden samphire (syn. Limbarda crithmoides (L.) Dum.), Inula cuspidata, Inula ensifolia L, Inula eupatorioides DC, Inula falconeri Hookf., Inula forrestii, Inula germanica L., Inula grandis Schrenk ex Fisch. & C. A. Mey., Inula helenioides DC, Inula helenium L. - Elecampane, Inula helianthus-aquatica, Inula helvetica Weber, Inula hirta L., Inula hookeri C. B. Clarke, Inula hupehensis, Inula japonica, Inula koelzii KDawar & Qaiser, Inula lineariifolia Turcz., Inula magnifica, Inula montana L., Inula multicaulis Boiss., Inula nervosa, Inula obtusifolia A.Kern., Inula oculus-christi L., Inula orientalis Lam., Inula pterocaula, Inula racemosa Hookf, Inula rhizocephala Schrenk ex Fisch. & C. A. Mey., Inula rhizocephaloides, Inula royleana DC. (synonym of Inula racemosa Hookf), Inula rubricaulis, Inula salicina L. — Irish Fleabane, Willowleaf Yellowhead, Inula salsoloides, Inula sericophylla, Inula spiraeifolia L, Inula stewartii Abid & Qaiser, Inula subfloccosa Rech.f, Inula thapsoides Spreng., Inula verbascifolia (Willd.) Hausskn., Inula viscosa and Inula wissmanniana.
4. A composition according to claim 1, wherein said viral infection is selected from the group consisting of HIV, polio virus, hepatitis, Herpes viruses, such as HSV-1, HSV-2, HSV-3, HHV, cytomegalovirus and measles virus, influenza, rhinovirus, parainfluenza, vesicular stomatitis virus (VSV), vaccinia virus (W), encephalitis, Papillomaviruses and African Swine Fever virus.
5. A composition according to claim 1, wherein said topical disorder is selected from the group consisting of a rash, an allergy, a blister, an abscess, an irritation, a swelling, a coloration, a sore and a wart.
6. A composition according to claim 1, wherein said plant extract is selected from a solvent extract, an aqueous extract, an organic solvent extract, an organic and aqueous solvent mixture extracts, a column extract, a combination with other herbal plants extracts and combinations thereof.
7. A composition according to claim 1, wherein the composition is a topical composition.
8. A composition according to claim 7, wherein said topical composition is selected from the group consisting of a balm, an ointment, a lotion, a roll-on, a rub, a sticker and a cream.
9. A composition according to claim 1, wherein said pharmaceutically acceptable carrier is selected from an aqueous carrier, an oil-based carrier, an emulsion, a cream, a gel and a powder.
10. A composition according to claim 1, wherein said composition is an antiviral composition.
11. A composition according to claim 1 , wherein said composition is adapted to act as a palliative agent against pain.
12. A composition according to claim 1, wherein said composition is an oral composition.
13. A composition according to claim 12, wherein said oral composition is adapted to treat an autoimmune disease.
14. A composition according to claim 1, wherein said composition is effective in treating a pathological condition which over-stimulates pro-inflammatory cytokines.
15. A composition according to claim 1, wherein said composition is effective in treating HSV 3 -induced blisters.
16. A composition according to claim 3, wherein said at least one Inula species comprises Inula viscosa.
17. A composition according to claim 1, further comprising at least one of wheat seed oil, vitamin E, and zinc.
18. A composition according to claim 1, further comprising at least one of: a vegetable oil, a mineral oil, an alcohol, a gel, Aloe vera, paraffin wax, a cream, a stabilizer, a coloring agent, an emulsifier and a vitamin.
19. A composition according to claim 1, comprising both tomentosin and inuviscolide in pharmaceutically effective amounts.
20. A composition according to claim 19, wherein said pharmaceutically effective amount of tomentosin is in a range of 0.1 μg to 10
21. A composition according to claim 19, wherein said pharmaceutically effective amount of inuviscolide is in a range of 0.1 μg to 10
22. A method for treating a topical disorder associated with a viral infection, the method comprising administering at least one active substance selected from:
a) a plant extract comprising at least one of tomentosin and inuviscolide;
b) tomentosin;
c) inuviscolide;
d) a plant cell culture extract comprising at least one of tomentosin and inuviscolide;
e) an Inula viscosa extract; and
a pharmaceutically acceptable carrier to a mammalian subject afflicted with said topical disorder so as to treat said topical disorder.
23. A method according to claim 22, wherein said plant extract comprises an extract from at least one species selected from the genera Inula, Xanthium and Arnica.
24. A method according to claim 23, wherein said at least one Inula species is selected from Inula acaulis, Inula acervata S.Moore, Inula acinacifoUa Gand, Inula acuminata DC, Inula afghanica, Inula anatolica Boiss., Inula auriculata Boiss. &
Balansa, Inula bifrons (L.) L., Inula britannica L.— British Yellowhead, Inula Candida
(L.) Cass., Inula cappa (Buch.-Ham. ex D. Don) DC, Inula caspica Blume, Inula clarkei ( Hookf.) R.R. Stewart, Inula conyzae (Griess.) Meikle— Plougman's-spikenard,
Inula crithmoides L.— Golden samphire (syn. Limbarda crithmoides (L.) Dum.), Inula cuspidata, Inula ensifolia L, Inula eupatorioides DC, Inula falconeri Hookf, Inula forrestii, Inula germanica L., Inula grandis Schrenk ex Fisch. & C. A. Mey., Inula helenioides DC, Inula helenium L.— Elecampane, Inula helianthus-aquatica, Inula helvetica Weber, Inula hirta L., Inula hookeri C. B. Clarke, Inula hupehensis, Inula japonica, Inula koelzii R.Dawar & Qaiser, Inula lineariifolia Turcz., Inula magnifica, Inula montana L., Inula multicaulis Boiss., Inula nervosa, Inula obtusifolia A.Kern., Inula oculus-christi L., Inula orientalis Lam., Inula pterocaula, Inula racemosa Hookf., Inula rhizocephala Schrenk ex Fisch. & C. A. Mey., Inula rhizocephaloides, Inula royleana DC. (synonym of Inula racemosa Hookf.), Inula rubricaulis, Inula salicina L. - Irish Fleabane, Willowleaf Yellowhead, Inula salsoloides, Inula sericophylla, Inula spiraeifolia L., Inula stewartii Abid & Qaiser, Inula subfloccosa Rech.f, Inula thapsoides Spreng., Inula verbascifolia (Willd.) Hausskn., Inula viscosa and Inula wissmanniana.
25. A method according to claim 22, wherein said viral infection is selected from the group consisting of HIV, polio virus, hepatitis, Herpes viruses, such as HSV-1, HSV-2, HSV-3, HHV, cytomegalovirus and measles virus, influenza, rhinovirus, parainfluenza, vesicular stomatitis virus (VSV), vaccinia virus (VV), encephalitis, Papillomaviruses and African Swine Fever virus.
26. A method according to claim 25, wherein said method further comprises treating said viral infection.
27. A method according to claim 22, wherein said topical disorder is selected from the group consisting of a rash, an allergy, a blister, an abscess, an irritation, a swelling, a coloration, a sore and a wart.
28. A method according to claim 22, wherein said plant extract is selected from a solvent extract or an aqua extract or the combination of both extracts and a column extract.
29. A method according to claim 22, wherein said administering step comprises administering a topical composition to an afflicted area of skin.
30. A method according to claim 29, wherein said topical composition is selected from the group consisting of a balm, an ointment, a lotion, a roll-on, a rub, a sticker and a cream.
31. A method according to claim 22, wherein said pharmaceutically acceptable carrier is selected from an aqueous carrier, an oil-based carrier, an emulsion, a cream, a gel and a powder.
32. A method according to claim 22, wherein said method is further adapted to treat pain associated with said topical disorder.
33. A method according to claim 22, wherein said administration is oral.
34. A method according to claim 33, wherein said oral method further treats an autoimmune disease such as psoriasis.
35. A method according to claim 22, wherein said method is effective in treating a pathological condition which over-stimulates pro-inflammatory cytokines.
36. A method according to claim 22, wherein said method is effective in treating HSV 3 -induced blisters.
37. A method according to claim 24, wherein said at least one Inula species comprises Inula viscosa.
38. A method according to claim 22, said at least one active substance is formulated with at least one of wheat seed oil, vitamin E, and zinc.
39. A method according to claim 22, wherein said at least one active substance is formulated with at least one of: a vegetable oil, a mineral oil, an alcohol, a gel, Aloe vera, paraffin wax, a cream, a stabilizer, a coloring agent, an emulsifier and a Inula viscosa extract.
40. A method according to claim 22, wherein said at least one active substance comprises both tomentosin and inuviscolide in pharmaceutically effective amounts.
41. A method according to claim 40, wherein said pharmaceutically effective amount of tomentosin is in a range of 0.1 μg to 10 μg.
43. A method according to claim 40, wherein said pharmaceutically effective amount of inuviscolide is in a range of 0.1 μg to 10 μg.
44. A method of treating a disorder comprising administering a composition according to any of claims 1 to 21 to a mammalian subject afflicted with said disorder so as to treat said disorder.
45. A method according to claim 44, comprising:
i) applying said at least one active substance to an area of skin so as to allow at least part of a first composition to start a treatment process; and
ii) applying the composition according to any of claims 1 to 21 to said area of skin.
46. A method according to claim 45, further comprising waiting for a period of time between step i) and step ii).
47. A method according to claim 46, wherein the period of time is at least twelve hours.
48. A method according to claim 45, wherein steps i) and ii) are each repeated after waiting for an interval of at least twelve hours.
49. A method according to claim 46, wherein the period of time is at least one week.
50. A method according to claim 45, wherein steps i) and ii) are repeated several times, each time after waiting for the duration of the time interval.
51. A composition for treating a topical disorder, the composition comprising at least one of:
a) a plant extract comprising at least one of tomentosin and inuviscolide;
b) tomentosin;
c) inuviscolide;
d) a plant cell culture extract comprising at least one of tomentosin and inuviscolide; and
e) an Inula viscosa extract.
52. A composition according to claim 51, wherein the topical disorder is selected from acne, a microbial infection, a blistering disease, an itching and noninfectious rash, a skin growth, a parasitic infection, a pigment disorder, a burn, a scar, a chemically-induced disorder, a physically induced disorder and a viral disorder.
53. A composition according to claim 52, wherein the itching and non infectious rash is psoriasis.
54. A kit for the treatment of a skin disorder comprising:
a) a composition according to any of claims 1 to 21 and 51-53; and
b) instructions on how to apply the composition to an area of skin.
55. A kit according to claim 54, comprising at least one of:
a) between about 0.01% to 50% (w/w) of said Inula viscosa extract; b) at least one other herbal plant extract containing sesquiterpene lactones or polyphenols; and
c) at least one antioxidant selected from flavones and polyphenols.
56. A kit according to claim 54, wherein said composition comprises 0.1%- 0.5% tomentosin and 0.1%-0.5% inuviscolide.
57. A composition according to claim 1 , wherein said composition is adapted to act against diabetic wounds.
58. A composition according to any of claims 1 -21 , wherein said composition is adapted to act as a palliative agent against scars or burns.
59. A composition according to any of claims 1 -21 , wherein said composition is adapted to act as a peeling agent.
60. A composition according to any of claims 1 -21 and 51-53, wherein said composition is adapted to treat an inflammatory skin disease.
61. A composition according to claim 60, wherein said inflammatory skin disease is selected from eczema, atopic dermatitis and seborrhea.
62. A composition according to any of claims 1 -21 and 51 -53, wherein said composition is adapted to have antiviral activity against a virus which requires at least one of NFKB CDK and CDC2 cellular proteins for activation thereof.
63. A composition according to any of claims 1 -21 and 51 -53, wherein said composition is adapted to have antiviral against a virus or viral infection.
64. A composition according to claim 60, wherein said virus is selected from a virus comprising a single strand nucleic acid, a virus comprising a double strand nucleic acid, an RNA virus, a DNA virus, a both DNA and RNA virus and a retrovirus.
65. Use of a composition according to any of claims 1 -21 and 51 -53 in the preparation of a medicament for treating a disorder.
1/8
Herpes -HS VI
Herpes
infection
of
After 18
hours
ing
After 36 f hours ion
After 72
hours
Figure imgf000056_0001
FIG.1 2/8
Figure imgf000057_0001
FIG. 2
Figure imgf000058_0001
After 48 hours
Figure imgf000058_0002
After 72 hours
Figure imgf000058_0003
FIG.3
Figure imgf000059_0001
Figure imgf000060_0001
Figure imgf000060_0002
Figure imgf000060_0003
6/8
Figure imgf000061_0001
7/8
Figure imgf000062_0001
FIG. 7
8/8
Figure imgf000063_0001
PCT/IL2011/000967 2010-12-29 2011-12-28 Compositions and methods for treating a skin disorder WO2012090194A2 (en)

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