CN102060904B - Celosia argentea L. saponin compounds and application thereof - Google Patents
Celosia argentea L. saponin compounds and application thereof Download PDFInfo
- Publication number
- CN102060904B CN102060904B CN 201010545566 CN201010545566A CN102060904B CN 102060904 B CN102060904 B CN 102060904B CN 201010545566 CN201010545566 CN 201010545566 CN 201010545566 A CN201010545566 A CN 201010545566A CN 102060904 B CN102060904 B CN 102060904B
- Authority
- CN
- China
- Prior art keywords
- celosin
- feather cockscomb
- group
- glycosides
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Abstract
The invention relates to the technical field of medicine, in particular to Celosia argentea L. total saponin III and Celosia argentea L. saponin novel compounds (Celosin C1, Celosin D1, Celosin E, Celosin F and Celosin G) which are extracted from Celosia argentea L. The chemical structural formulas of the five Celosia argentea L. saponin compounds are shown in the specification. Animal experiments prove that the Celosia argentea L. total saponin III and Celosia argentea L. saponin novel compounds (C1, D1, E, F and E) are have activity of preventing and treating hepatopathy, heart cerebrovascular diseases, metabolic disease, dementia, tristimania or angst, and the compounds provided by the invention are simple in preparation method and low in cost. The invention provides new medicament sources for hepatopathy heart cerebrovascular disease, metabolic disease, dementia, tristimania or angst.
Description
Technical field
The present invention relates to medical technical field, is a kind of feather cockscomb total saponins III extract and 5 new compound feather cockscombs of feather cockscomb saponins glycosides C that extracts from the dry mature seed Semen Celosiae (Semen Celosiae) of feather cockscomb (Celosia argentea L.)
1(Celosin C
1), feather cockscomb glycosides D
1(Celosin D
1), Celosin E (Celosin E), Celosin F (Celosin F) and Celosin G (Celosin G) and prevent and treat application in hepatopathy, cardiovascular and cerebrovascular disease, metabolic disease, dementia, depression or the anxiety medicine in preparation.
Background technology
Semen Celosiae (Semen Celosiae) is the dry mature seed of Amaranthaceae (Amaranthcea) feather cockscomb (Celosia argentea L.).The Semen Celosiae bitter, cold nature has clearing liver, effect hot, hypotensive, anti-inflammatory makes eye bright, dispels the wind.Be usually used in the treatment of conjunctival congestion with pain and swelling of the eye, keratitis, nebula, iridocyclitis, dizzy, skin wind-heat itch, mange.The inventor has separated from Semen Celosiae and has obtained saponin component Celosin A, glycosides B, glycosides C and glycosides D, and applied for patent (seeing ZL200610026789.3 and 200910053042.0 for details), so far there are no extracts feather cockscomb total saponins III and is separated to feather cockscomb glycosides C from Semen Celosiae
1, feather cockscomb glycosides D
1, Celosin E, Celosin F, Celosin G report.
Summary of the invention
The new Celosia argentea L. saponin compounds feather cockscomb glycosides C that the invention provides a kind of feather cockscomb total saponins III that from Semen Celosiae, extracts and from Semen Celosiae extract, be separated to
1, D
1, E, F and G, and with them for the preparation of the purposes of preventing and treating hepatopathy, cardiovascular and cerebrovascular disease, metabolic disease, dementia, depression or anxiety disease.5 Celosia argentea L. saponin compounds feather cockscomb glycosides C
1(Celosin C
1), feather cockscomb glycosides D
1(Celosin D
1), Celosin E (Celosin E), Celosin F (Celosin F) and Celosin G (Celosin G) chemical structural formula be as follows:
R
1 R
2 R
3 R
4 R
5 R
6 R
7
CelosinC
1 H OH COOH CH
3 H (CH
3)
2 fuc-rha-glc-xyl
CelosinD
1 H OH COOH CH
3 H (CH
3)
2 fuc-rha-glc-xyl-ara
Celosin E OH glcA CH
3 CH
3 H (CH
3)
2 CH
3
Celosin F OH xyl CH
3 COOH CH
3 ＝CH
2 COOH
Celosin G H glc CH
3 CH
3 H (CH
3)
2 fuc-rha-glcA
The preparation method of feather cockscomb total saponins III extract of the present invention and 5 new compounds is as follows:
1. prepare the feather cockscomb total saponins:
Semen Celosiae is pulverized rear water or the routinely diacolation extraction of 30%～70% aqueous ethanol, the extracting solution concentrating under reduced pressure gets concentrated solution, concentrated solution passes through AB-8, D101 or NKA-9 macroporous resin column, successively water, 30% ethanol, 45% ethanol, 60% ethanol and 95% ethanol gradient elution, collect respectively 30%, 45% and 60% ethanol eluate, with elutriant difference concentrating under reduced pressure, drying, get successively feather cockscomb total saponins I, feather cockscomb total saponins II and feather cockscomb total saponins III.
2. prepare Celosia argentea L. saponin compounds feather cockscomb glycosides C
1, D
1, E, F, G
(1) feather cockscomb total saponins I is carried out silica gel column chromatography, with chloroform-methanol (30: 1～1: 1) solvent systems gradient elution, again elutriant is carried out separation and purification by high-speed counter-current chromatograph, use methylene dichloride: methyl alcohol: propyl carbinol: water=4: 3: 0.3: 2+0.4% Glacial acetic acid solvent systems gets Celosin E, Celosin F and Celosin G.(2) feather cockscomb total saponins III is carried out silica gel column chromatography, with methylene chloride-methanol-water (9: 1: 0.1～7: 3: 0.3) solvent systems gradient elution, again elutriant is carried out separation and purification by high-speed counter-current chromatograph, use propyl carbinol: ethyl acetate: methyl alcohol: water=3.5: 3.5: 0.6: 10+0.5% Glacial acetic acid solvent systems gets feather cockscomb glycosides C
1With feather cockscomb glycosides D
1
Through pharmacology and pharmacodynamic experiment, extract feather cockscomb total saponins III of the present invention or compound feather cockscomb glycosides C
1, D
1, that E, F or G all have the hepatopathy of control, cardiovascular and cerebrovascular disease, metabolic disease, dementia, depression or anxiety is active.These diseases comprise fatty liver, liver injury, hepatic fibrosis, liver cirrhosis, coronary heart disease, myocardial infarction, myocardial ischemia, cerebral ischemia, cerebral infarction, cerebral apoplexy, diabetes, hyperinsulinemia, insulin resistance disease, obesity, diabetes intolerance, hyperlipidemia.
Extract feather cockscomb total saponins III of the present invention and compound feather cockscomb glycosides C
1, D
1, E, F, G preparation method be simple, with low cost.The present invention provides new medicament sources for preventing and treating hepatopathy, cardiovascular and cerebrovascular disease, metabolic disease, dementia, depression or anxiety.
Embodiment
Now in conjunction with the embodiments the present invention is described in detail.
Embodiment 1. preparation feather cockscomb total saponins III and compound feather cockscomb glycosides C
1, D
1, E, F, G
Get the Semen Celosiae 50kg of Hui nationality, pulverize, after soaking 24 hours with 50L hydroecium temperature, extract with 20L speed diacolation hourly, regather 250L water percolate, the extracting solution concentrating under reduced pressure gets concentrated solution, concentrated solution is by the AB-8 macroporous resin column, successively water, 30% ethanol, 45% ethanol, 60% ethanol and 95% ethanol gradient elution, collect respectively the ethanol eluate of 30% ethanol, 45% ethanol and 60% and concentrating under reduced pressure, drying, successively feather cockscomb total saponins I 55g, feather cockscomb total saponins II 25g and feather cockscomb total saponins III 150g.Wherein, feather cockscomb total saponins II main component is Celosin A, feather cockscomb B, feather cockscomb C and feather cockscomb D, (seeing ZL200610026789.3 and 200910053042.0 for details, lower same).
Feather cockscomb total saponins I is carried out silica gel column chromatography, with chloroform-methanol (30: 1～1: 1) solvent systems gradient elution, again this elutriant is used methylene dichloride: methyl alcohol: propyl carbinol: water=4: 3: 0.3: 2+0.4% Glacial acetic acid solvent systems carries out separation and purification by high-speed counter-current chromatograph, obtains respectively Celosin E 1.3g, Celosin F 2.4g and Celosin G 2.1g.
Feather cockscomb total saponins III is carried out silica gel column chromatography, with methylene chloride-methanol-water (9: 1: 0.1～7: 3: 0.3) solvent systems wash-out, again with the high-speed counter-current chromatograph separation and purification of this elutriant, the solvent systems that adopts is: ethyl acetate: propyl carbinol: methyl alcohol: water=3.5: 3.5: 0.6: 10+0.5% acetic acid obtains respectively feather cockscomb glycosides C
115.3g and feather cockscomb glycosides D
17.9g;
Embodiment 2. preparation feather cockscomb total saponins III and compound feather cockscomb glycosides C
1, D
1, E, F, G
Get the Semen Celosiae 50kg of Hui nationality, pulverize, with 50L50% aqueous ethanol soaking at room temperature after 24 hours, extract with 20L speed diacolation hourly, regather 250L water percolate, the extracting solution concentrating under reduced pressure gets concentrated solution, concentrated solution is by the D101 macroporous resin column, successively water, 30% ethanol, 45% ethanol, 60% ethanol and 95% ethanol gradient elution, collect respectively the ethanol eluate of 30% ethanol, 45% ethanol and 60% and concentrating under reduced pressure, drying, successively feather cockscomb total saponins I 155g, feather cockscomb total saponins II 125g and feather cockscomb total saponins III270g.
The method for preparing Celosin E, F and G by feather cockscomb total saponins I obtains respectively Celosin E 4.5g, Celosin F 3.8g and Celosin G 4.7g with embodiment 1.
Prepare feather cockscomb glycosides C by feather cockscomb total saponins III
1And D
1Method with embodiment 1, obtain respectively feather cockscomb glycosides C
125.3g and feather cockscomb glycosides D
118.9g;
Embodiment 3. preparation feather cockscomb total saponins III and compound feather cockscomb glycosides C
1, D
1, E, F, G
Get the Semen Celosiae 50kg of Hui nationality, pulverize, with 50L70% aqueous ethanol soaking at room temperature after 24 hours, extract with 20L speed diacolation hourly, regather 250L water percolate, the extracting solution concentrating under reduced pressure gets concentrated solution, concentrated solution is by the NKA-9 macroporous resin column, successively water, 30% ethanol, 45% ethanol, 60% ethanol and 95% ethanol gradient elution, collect respectively the ethanol eluate of 30% ethanol, 45% ethanol and 60% and concentrating under reduced pressure, drying, successively feather cockscomb total saponins I 95g, feather cockscomb total saponins II 75g and feather cockscomb total saponins III 150g.
The method for preparing Celosin E, F and G by feather cockscomb total saponins I obtains respectively Celosin E 3.5g, Celosin F 2.8g and Celosin G 3.7g with embodiment 1.
Prepare feather cockscomb glycosides C by feather cockscomb total saponins III
1And D
1Method with embodiment 1, obtain respectively feather cockscomb glycosides C
121.3g and feather cockscomb glycosides D
112.9g;
Structural Identification
1. feather cockscomb glycosides C
1
White powder, m.p.:240～243 ℃, molecular formula is C
53H
82O
24, HR-TOF-MS:m/z1101.5114[M-H]
-(Calcd.1101.5118), determine that compound molecular weight is 1102.UV (MeOH) shows that compound is without obvious uv-absorbing.Nuclear magnetic resonance data sees Table 1.
H spectrum by table 1 can infer that with the C spectrum this compound is Pentacyclic triterpene saponins compounds.
This compound with trifluoroacetic acid hydrolysis after, adopt GC-MS to analyze, structure shows in the sugared position of this saponin(e and has D-husband sugar, L-rhamnosyl, D-Glucose and D-wood sugar.In HMBC spectrum, 180.8 carbonyl carbon and 53.1 quaternary carbon all with the methyl hydrogen coupling of 2.05 (3H, s), show that this methyl and carbonyl all are connected on 4 the quaternary carbon; 173.5 carbonyl carbon and 52.7 tertiary carbon hydrogen coupling is arranged, illustrate 25 for carboxyl; 6.09 it is relevant that the sugared terminal hydrogen of (d, J=8.5Hz) and 176.8 carbonyl carbon have, and shows that two sugar in the compound are to be connected on 28 of aglycon; 6.44 (1H, s) sugared terminal hydrogen has relevant with 74.3 carbon, 5.10 (d, J=5.5Hz) sugared terminal hydrogen has relevant with 85.5 carbon, 5.25 (1H, s) sugared terminal hydrogen has relevant with 107.8 carbon, by further doing the GC-MS experiment, further confirmed the kind of four kinds of sugar, last result shows: the kind of four sugar in this compound and the order of connection are β-D-xylopyranosyl (1 → 2)-β-D-glucopyranosyl (1 → 4)-α-L-rhamnopyranosyl (1 → 2)-β-D-pyrans husband glycosyls.The contrast Oleanolic Acid
13C-NMR composes data, compound
13C-NMR spectrum and reference (Chen Dechang. carbon spectrum and the application in the herbal medicine chemistry [M] thereof. Beijing: People's Health Publisher, 1991:319-320, down together) data of report are basically identical, so determine the aglycon structure of compound are: 23,25-dicarboxyl-Oleanolic Acid.
Comprehensive above the analysis, the structure of determining compound is: 23,25-dicarboxyl-28-O-[β-D-xylopyranosyl (1 → 2)-β-D-glucopyranosyl (1 → 4)-α-L-rhamnopyranosyl (1 → 2)-β-D-pyrans husband glycosyl]-Oleanolic Acid.Be a new compound, called after feather cockscomb glycosides C
1
2. feather cockscomb glycosides D
1
White powder, m.p.:236～239 ℃, molecular formula is C
58H
90O
28, HR-TOF-MS:m/z 1257.5514[M+Na]
+(Calcd.1257.5516), determine that compound molecular weight is 1234.UV (MeOH) shows that compound is without obvious uv-absorbing.Nuclear magnetic resonance data sees Table 1
H spectrum by table 1 can infer that with the C spectrum this compound is Pentacyclic triterpene saponins compounds.
This compound with trifluoroacetic acid hydrolysis after, adopt GC-MS to analyze, structure shows that the sugared position of this saponin(e exists D-husband sugar, L-rhamnosyl, D-Glucose, D-wood sugar and D-R.
By with glycosides C
1Spectrogram relatively, find that the displaced phase of corresponding carbon of two saponin(es is similar, parent nucleus is the same, just this saponin(e will have more a sugar, is D-R.
In sum, the structure of determining compound is: 23,25-dicarboxyl-28-O-[β-D-arabopyranose base (1 → 2)-β-D-xylopyranosyl (1 → 2)-β-D-glucopyranosyl (1 → 4)-α-L-rhamnopyranosyl (1 → 2)-β-D-pyrans husband glycosyl]-Oleanolic Acid, be new compound, called after feather cockscomb glycosides D
1
Table 1 feather cockscomb glycosides C
1, D
1 1H,
13C-NMR data (C
5D
5N+D
2O, δ, ppm)
3 Celosin Es
White powder, m.p.:235～237 ℃, molecular formula is C
36H
54O
12, HR-TOF-MS:m/z 679.3675[M+H]
+(Calcd.679.3694), determine that compound molecular weight is 678.UV (MeOH) shows that compound is without obvious uv-absorbing.Nuclear magnetic resonance data sees Table 2, table 3.
H spectrum by table 2 can infer that with the C spectrum of table 3 this compound is Pentacyclic triterpene saponins compounds.
This compound with trifluoroacetic acid hydrolysis after, adopt GC-MS to analyze, structure shows that the sugared position of this saponin(e is glucuronic acid.In the HMBC spectrum, 182.2,181.76,175.5 carbonyl carbon respectively with 1.38 (s), 2.76 (s), 4.27 (s) have coupling; Determining of the link position of sugar is according to hydrogen related 4.44 (d, the J=7.5) of end group carbon and 3 tertiary carbons of parent nucleus coupling to be arranged; Determining of parent nucleus position of double bond is that hydrogen according to 12,13 olefinic carbon and 2.76 (s) and 0.96 (s) is relevant.The contrast Oleanolic Acid
13C-NMR composes data, compound
13The data of C-NMR spectrum and reference report are basically identical, so determine the aglycon structure of compound are: 23,25-dicarboxyl-volatile oil.
Comprehensive above the analysis, determine that the structure of compound is: 23,25-dicarboxyl-3-O-beta d glucopyranosiduronic acid base-volatile oil is a new compound, the called after Celosin E.
3 Celosin Fs
White powder, m.p.:225～227 ℃, molecular formula is C
35H
50O
12, HR-TOF-MS:m/z 661.3255[M-H]
-(Calcd.661.3224), determine that compound molecular weight is 662.UV (MeOH) shows that compound is without obvious uv-absorbing.Nuclear magnetic resonance data sees Table 2, table 3.
H spectrum by table 2 can infer that with the C spectrum of table 3 this compound is Pentacyclic triterpene saponins compounds.
This compound with trifluoroacetic acid hydrolysis after, adopt GC-MS to analyze, structure shows that the sugared position of this saponin(e is wood sugar.In the HMBC spectrum, 181.1,181.9,182.1 carbonyl carbon respectively with 2.75 (d, J=11), 2.03 (s), 1.30 (s) have coupling; Determining of the link position of sugar is according to hydrogen related 4.31 (d, the J=7.5) of end group carbon and 3 tertiary carbons 86.7 of parent nucleus coupling to be arranged; Determining of parent nucleus position of double bond is that olefinic carbon hydrogen 5.23 (s) according to 12 is relevant with 18 tertiary carbon 43.0.The contrast urson
13C-NMR composes data, compound
13C-NMR spectrum and reference report (Li Kaiquan. Chen Wu. Xiong Xiaojuan, Deng. the chemistry of ursonic acid, pharmacology and Clinical advances. Chinese patent medicine, 2002,24 (9): data 709-710.) are basically identical, so determine the aglycon structure of compound be: 20,30-alkene-23,26-dicarboxyl-urson.
Comprehensive above the analysis, determine that the structure of compound is: 20,30-alkene-23,26-dicarboxyl-3-O-β-D-xylopyranosyl-urson is a new compound, the called after Celosin F.
4 Celosin Gs
White powder, m.p.:239～241 ℃, molecular formula is C
53H
80O
25, HR-TOF-MS:m/z 1139.5248[M+Na]
+(Calcd.1139.5250), determine that compound molecular weight is 1116.UV (MeOH) shows that compound is without obvious uv-absorbing.Nuclear magnetic resonance data sees Table 2, table 3.
H spectrum by table 2 can infer that with the C spectrum of table 3 this compound is Pentacyclic triterpene saponins compounds.
This compound with trifluoroacetic acid hydrolysis after, adopt GC-MS to analyze, structure shows that the sugared position of this saponin(e is D-husband sugar, L-rhamnosyl, D-Glucose aldehydic acid and D-Glucose.In the HMBC spectrum, 180.3,176.8,170.8 carbonyl carbon respectively with 2.07 (s), 2.17 (s), 4.13 (s) have coupling; Determining of the link position of sugar is with 3 tertiary carbons 86.3 and 28 carbonyl carbon 176.8 of parent nucleus coupling to be arranged respectively according to hydrogen related 5.28 (d, J=7.5), 6.11 (d, the J=8) of end group carbon; 6.47 it is relevant that the sugared terminal hydrogen of (1H, s) and 74.3 carbon have, it is relevant that the sugared terminal hydrogen of 5.10 (d, J=7.5Hz) and 85.5 carbon have, the contrast Oleanolic Acid
13C-NMR composes data, compound
13The data of C-NMR spectrum and reference report are basically identical, so determine the aglycon structure of compound are: 23-carboxyl-Oleanolic Acid.
Comprehensive above the analysis, the structure of determining compound is: 23-carboxyl-3-O-β-D-glucopyranosyl-28-O-beta d glucopyranosiduronic acid base (1 → 4)-α-L-rhamnopyranosyl (1 → 2)-β-D-pyrans husband glycosyl-Oleanolic Acid, be a new compound, the called after Celosin G.
Table 2 Celosin E, F, G's
1H-NMR data (MeOD, δ (ppm), J (Hz))
| The hydrogen spectrum | E | F | G |
| 1 | 1.93(d，J＝13.5) | 1.18(d，J＝6.5) | 1.35(s) |
| 2 | 4.27(s) | 4.18(S) | 2.11(m) |
| 3 | 4.07(s) | 3.98(S) | 4.80(d，J＝3.5) |
| 4 | - | - | - |
| 5 | 1.50(s) | 1.48(m) | 2.15(m) |
| 6 | 1.65(s) | 1.06(s) | 1.86(m) |
| 7 | 1.07(s) | 2.03(m) | 1.8 |
| 8 | - | - | - |
| 9 | 2.76(s) | 2.43(s) | 1.82(m) |
| 10 | - | - | - |
| 11 | 1.77(m) | 1.62(m) | 2.17(m) |
| 12 | 5.11(s) | 5.23(s) | 5.5(s) |
| 13 | - | - | - |
| 14 | - | - | - |
| 15 | 1.52(s) | 1.19(d，J＝6.5) | 1.35(s) |
| 16 | 1.50(s) | 1.44(m) | 2.11(m) |
| 17 | - | - | - |
| 18 | - | 2.61(d，J＝4) | 3.18(d，J＝4) |
| 19 | 1.17(s) | 2.43(s) | 1.82(m) |
| 20 | - | - | - |
| 21 | 1.41(s) | 1.18(s) | 1.49(d，J＝9) |
| 22 | - | 2.75(d，J＝11) | 2.17(m) |
| 23 | - | - | - |
| 24 | 1.38(s) | 1.30(s) | 2.07(s) |
| 25 | - | 1.18(s) | 1.65(s) |
| 26 | 0.65(s) | - | 1.07(s) |
| 27 | 0.96(s) | 0.72(s) | 1.33(s) |
| 28 | 1.16(s) | - | - |
| 29 | 1.60(s) | 1.09(s) | 1.00(s) |
| 30 | 1.50(s) | 4.51(s) | 2.17(m) |
| 3-O-glcA | |||
| 1 | 4.44(d，J＝7.5) | ||
| 2 | 3.32(m) | ||
| 3 | 3.45(m) | ||
| 4 | 4.20(s) | ||
| 5 | 3.55(m) | ||
| 6 | |||
| 3-O-xyl | |||
| 1 | 4.31(d，J＝7.5) | ||
| 2 | 3.19(m) | ||
| 3 | 3.25(m) | ||
| 4 | 3.39(m) | ||
| 5 | 3.45(m) | ||
| 3-O-glc | |||
| 1 | 5.28(d，J＝7.5) | ||
| 2 | 4.01(m) | ||
| 3 | 4.24(m) | ||
| 4 | 4.02(m) | ||
| 5 | 4.26(m) | ||
| 6 | 4.32(m) | ||
| 28-O-Fuc | |||
| 1 | 6.11(d，J＝8) | ||
| 2 | 4.71(m) | ||
| 3 | 4.24(m) | ||
| 4 | 4.02(m) | ||
| 5 | 4.77(m) |
| 6 | 1.65(s) | ||
| Fuc-2-Rha | |||
| 1 | 6.47(s) | ||
| 2 | 4.91(s) | ||
| 3 | 4.77(m) | ||
| 4 | 4.40(m) | ||
| 5 | 4.85(s) | ||
| 6 | 1.77(d，J＝6) | ||
| Rha-4-glcA | |||
| 1 | 5.10(d，J＝7.5) | ||
| 2 | 4.13(d，J＝5.5) | ||
| 3 | 4.01(m) | ||
| 4 | 4.26(m) | ||
| 5 | 4.13(d，J＝5.5) | ||
| 6 |
Table 3 Celosin E, F, G's
13C-NMR data (MeOD, δ (ppm), J (Hz))
| The carbon spectrum | E | F | G |
| 1 | 45.1 | 44.9 | 44.6 |
| 2 | 70.9 | 71.3 | 32.5 |
| 3 | 86.9 | 86.7 | 86.3 |
| 4 | 53.6 | 53.6 | 53.1 |
| 5 | 53.3 | 53.3 | 52.8 |
| 6 | 28.9 | 21.9 | 21.2 |
| 7 | 30.9 | 31.1 | 46.4 |
| 8 | 37.6 | 37.7 | 40.3 |
| 9 | 42.9 | 43.0 | 48.9 |
| 10 | 41.0 | 41.2 | 37.0 |
| 11 | 24.8 | 24.4 | 23.8 |
| 12 | 123.6 | 124.3 | 122.9 |
| 13 | 145.5 | 144.8 | 144.9 |
| 14 | 43.2 | 43.3 | 42.4 |
| 15 | 21.9 | 30.7 | 46.4 |
| 16 | 47.4 | 39.3 | 32.5 |
| 17 | 47.7 | 47.9 | 47.2 |
| 18 | 49.8 | 49.1 | 42.3 |
| 19 | 35.1 | 43.0 | 46.5 |
| 20 | 31.8 | 149.9 | 31.1 |
| 21 | 33.8 | 33.8 | 34.4 |
| 22 | 34.0 | 42.9 | 28.4 |
| 23 | 182.2 | 182.1 | 180.3 |
| 24 | 14.2 | 13.9 | 14.3 |
| 25 | 181.7 | 17.3 | 17.0 |
| 26 | 18.0 | 181.9 | 17.6 |
| 27 | 26.8 | 17.8 | 26.2 |
| 28 | 17.3 | 181.1 | 176.8 |
| 29 | 33.9 | 26.7 | 33.4 |
| 30 | 24.3 | 107.5 | 23.9 |
| 3-O-glcA | |||
| 1 | 105.5 | ||
| 2 | 75.2 | ||
| 3 | 77.8 | ||
| 4 | 70.6 | ||
| 5 | 73.8 | ||
| 6 | 178.5 | ||
| 3-O-xyl | |||
| 1 | 105.5 | ||
| 2 | 75.0 | ||
| 3 | 77.5 | ||
| 4 | 73.5 | ||
| 5 | 62.9 | ||
| 3-O-glc | |||
| 1 | 106.2 | ||
| 2 | 75.0 | ||
| 3 | 77.7 | ||
| 4 | 78.6 | ||
| 5 | 71.1 | ||
| 6 | 67.6 | ||
| 28-O-Fuc | |||
| 1 | 94.9 | ||
| 2 | 74.3 | ||
| 3 | 76.7 | ||
| 4 | 73.3 | ||
| 5 | 72.5 | ||
| 6 | 17.0 | ||
| Fuc-2-Rha | |||
| 1 | 101.5 | ||
| 2 | 71.9 | ||
| 3 | 72.5 | ||
| 4 | 85.5 | ||
| 5 | 70.9 | ||
| 6 | 18.7 | ||
| Rha-4-glcA | |||
| 1 | 107.8 | ||
| 2 | 76.4 | ||
| 3 | 75.0 | ||
| 4 | 71.1 | ||
| 5 | 78.9 | ||
| 6 | 170.7 |
The pharmacological effect test
One, the compounds of this invention is to the preventive and therapeutic effect of hepatopathy
The provide protection of the acute liver that () tetracol phenixin is caused
1. experimental animal and method:
90 of Kunming mouses (the The 2nd Army Medical College animal center provides), mean random is divided into 9 groups, is respectively: Normal group, model control group, positive controls (positive control drug is Biphenylylmethylcarbinol, and is lower same), feather cockscomb glycosides C
1Group (1#, lower same), feather cockscomb glycosides D
1Group (2#, lower with), Celosin E group (3#, lower with), Celosin F group (4#, lower with), Celosin G group (5#, lower with) and feather cockscomb total saponins III group (6#, lower together).
Medicine is made into the aqueous solution, presses Mouse Weight gastric infusion (together lower), positive control drug Biphenylylmethylcarbinol dosage is 200mg/kg, feather cockscomb total saponins III and compound feather cockscomb glycosides C
1, D
1, E, F, G dosage be respectively 4mg/Kg, the gavage volume is 0.2ml/10g, Normal group and the isopyknic distilled water of model control group gavage, gavage is 7 days continuously.Except Normal group, all the other each group 1h abdominal injection 0.1% tetracol phenixin 10ml/kg after administration in the 7th day, each group is plucked the eyeball blood sampling after 18 hours, and is centrifugal, get serum, measure aspartic transaminase (AST), alanine aminotransferase (ALT).The results are shown in Table 4.
Table 4 the compounds of this invention causes the provide protection blood parameters of liver injury to tetracol phenixin
Compare with model control group:
*P＜0.01
By as seen from Table 4, feather cockscomb glycosides C
1, D
1, E, F, G or feather cockscomb total saponins III successive administration 7 days, can obviously suppress AST, ALT that tetracol phenixin causes and raise, its effect approaches with Normal group, and significantly better than the positive drug Biphenylylmethylcarbinol.
(2) to the therapeutic action of fatty liver
1, laboratory animal and method:
110 of Wister rats, body weight 180-230g is divided into two groups at random, and first group 10, be the Normal group group, give normal feed; All the other 100 is second group, gives routinely high lipid food after 60 days, puts to death wherein 10, does the hepatic pathology section, determine that Models of Fatty Liver is set up after, be divided at random more following 9 groups, model control group continues to give high lipid food; Non-treatment group, animal change the food normal diet; Feather cockscomb glycosides C
1Group (1#), feather cockscomb glycosides D
1Group (2#), Celosin E group (3#), Celosin F group (4#), Celosin G group (5#) and feather cockscomb total saponins III group (6#), animal all changes the food normal diet, and dosage is 8mg/Kg/d, successive administration 30 days.
2, observation index:
A body weight: in the time of 0,30,60,90 day, weigh respectively;
B blood parameters: Serum ALT, AST, serum total cholesterol, triglyceride level;
The c pathological examination: paraffin section, HE dyeing, observe fatty liver and inflammation degree of necrosis.
The results are shown in Table 5, table 6, table 7.
The variation of blood fat in each experimental group animal serum of table 5
Compare with model control group,
*P＜0.01
The variation of each experimental group animal serum transaminase content of table 6
Compare with model control group,
*P＜0.01
The degree (%) of each experimental group animal livers steatosis of table 7
By table 5,6,7 as seen, administration 30 days, feather cockscomb glycosides C
1, D
1, E, F, G or feather cockscomb total saponins III can obviously reduce cholesterol and triglyceride level in the serum, effectively alleviates the fatty liver sex change that high lipid food causes, improves the hepatic disorder that causes because of steatosis.
(3) to tetracol phenixin (CCl
4) therapeutic action of the rat chronic hepatic fibrosis brought out
1, laboratory animal and method:
180 of male Wister rats are divided into 9 groups at random, 20 every group, are respectively Normal group, model control group, positive controls, and feather cockscomb glycosides C
1(1#), D
1(2#), E (3#), F (4#), G (5#) and feather cockscomb total saponins III (6#) group.Except Normal group, all the other each treated animals are the CCl of subcutaneous injection 10% weekly all
4(5ml/Kg) 2 times, totally 12 weeks; From start injection CCl
4Rise, press the drug dose administration every day 1 time, in totally 12 weeks, administering mode: gastric infusion, dosage: positive drug Biphenylylmethylcarbinol 160mg/Kg/d, extract of the present invention and compound are 8mg/Kg/d.
2, observation index:
A. after 12 weeks of administration, press the content that the ELSA kit method is measured the amino transaminase (AST) of aspartic acid in the serum, the amino transaminase (ALT) of L-Ala, total serum protein (TP), microalbumin (ALB);
B. get hepatic tissue, press the ELSA kit method measure oxyproline (HP)), III Collagen Type VI propetide (PIIIP)), the content of IV Collagen Type VI (CIV);
C. get hepatic tissue, the pathology histological examination is done in HE dyeing, calculates collagen volume fraction (CVF).
The results are shown in Table 8, table 9, table 10.
Table 8 the compounds of this invention is to CCl
4Due to the rat chronic liver injury after the impact of liver function
Compare with model control group,
*P＜0.01
Table 9 the compounds of this invention is to CCl
4Due to the impact of rat chronic liver injury heptic fibrosis
Compare with model control group,
*P＜0.01
Table 10 the compounds of this invention is to CCl
4Due to the rat chronic liver injury after the impact of collagen volume fraction
Compare with model control group,
*P＜0.01
By table 8,9,10 as seen, feather cockscomb glycosides C
1, D
1, E, F, G or feather cockscomb total saponins III be to CCl
4Due to the rat chronic hepatic fibrosis obvious therapeutic action is arranged.
Two, the cardiovascular and cerebrovascular activity of the compounds of this invention
(1) to Racemic isoproterenol (ISO) to the therapeutic action of myocardial ischemia in rats
1, laboratory animal and method
64 of Healthy female SD rats are equally divided into 8 groups at random, are respectively Normal group, model control group and medicine group of the present invention.Normal group and model control group be gavage equal-volume physiological saline respectively, the other gavage feather cockscomb of drug component glycosides C
1(1#), D
1(2#), E (3#), F (4#), G (5#) and feather cockscomb total saponins III (6#), dosage is 8mg/Kg/d, successive administration three days.Model control group and drug component not after second day and administration in the 3rd day 1h by body weight subcutaneous injection ISO 1ml/Kg, the physiological saline of the capacity such as Normal group subcutaneous injection, record respectively gave before the tested medicine on the 3rd day and give ISO for the second time after the electrocardiogram(ECG of 30min, measure the J point value, calculate the absolute value that gives respectively to organize behind the ISO displacement of rat J point.Rat aorta is taken a blood sample centrifugal separation plasma behind the anticoagulant heparin, serum lactic dehydrogenase in the spectrophotometry blood plasma (LDH) activity unit after having surveyed electrocardiogram(ECG.Each administration group statistics and model group are relatively carried out the t-check.The LDH calculation formula is as follows:
The results are shown in Table 11, table 12.
Table 11 the compounds of this invention is on the impact (n=8) of myocardial ischemia in rats J point displacement due to the ISO
Compare with model control group,
*P＜0.05,
*P＜0.01,
Table 12 the compounds of this invention is on the impact (n=8) of ISO rat LDH activity unit
Compare with model control group,
*P＜0.05,
*P＜0.01,
By table 11,12 as seen, feather cockscomb glycosides C
1, D
1, E, F, G or feather cockscomb total saponins III myocardial ischemia in rats that ISO is caused has significant restraining effect, and can alleviate the damage of ischemic myocardium, therefore myocardial ischemia had significant protective effect.
(2) the compounds of this invention is to the provide protection of rat coronary artery caused by ligature acute myocardial ischemia
1, laboratory animal and method
Get 80 of healthy SD rats about body weight 200g, male and female half and half, be divided at random 8 groups: model control group (physiological saline 10ml/kg/d), positive controls (Proprasylyte 8mg/Kg/d), medicine group of the present invention (dosage is 8mg/Kg/d).All samples is through gastric infusion, and the administration volume is 10ml/kg, every day 1 time, continuous 2 days.
1h after the last administration, abdominal injection 12% Chloral Hydrate 3ml/kg anaesthetizes, the record normal ECG, chest unhairing, sterilization, along the about 2cm of left mid-clavicular line longitudinal incision skin, at the 4th or the 5th intercostal blunt separation flesh layer, open the thoracic cavity, cut off pericardium, the light right side thorax of pressing is extruded heart, behind ligation arteria coroaria sinistra in coronary vein place between right side circular cone and the left auricle of heart, heart is put back to the thoracic cavity, fully discharge air in the thoracic cavity, sew up and close thoracic cavity, respirator assisted respiartion, frequency 20 times/minutes, Tidal volume 5ml.At once, 1h, 24h, 48h trace respectively one section electrocardiogram(ECG after ligation, and in 24h, 48h difference gavage medicine 1# to 6# and physiological saline, dosage 8mg/Kg/d.
Behind coronary ligation 50h, rat is anaesthetized again, takes out rapidly heart, uses normal saline flushing, removes blood stains, rejects the non-cardiac muscular tissues such as blood vessel, fat, sucks moisture with thieving paper, claims whole-heartedly weight in wet base.Along coronary sulcus excision atrium, stay ventricle, weigh, along coronary sulcus from the apex of the heart to heart base portion 4 of parallel myocardium sheets with ventricular muscles crosscut Cheng Houyue 0.1cm, clean with normal saline flushing, myocardium sheet is placed in 0.1% the N-BT solution, the 15min that under 37 ℃ of water bath condition, dyes, unnecessary dyestuff is removed in immediately water flushing after the dyeing.Infarcted region is not painted, and non-infarcted region is dyed blueness by N-BT solution.Cut off infarcted myocardium, claim weight in wet base, account for whole-heartedly with the infarcted region weight in wet base that the per-cent of weight in wet base represents myocardial infarct size, the results are shown in Table 13.
Table 13 the compounds of this invention causes the impact (n=10) of Model Rats with Acute Myocardial Ischemia ischemic scope on coronary artery ligation
Compare with model control group,
*P＜0.01
By as seen from Table 13, feather cockscomb glycosides C
1, D
1, E, F, G or feather cockscomb total saponins III can reduce the tissue necrosis that myocardial ischemia causes very significantly, ischemia group is woven with significant protective effect, effect and positive control drug
Proprasylyte approaches.
(3) the compounds of this invention is to the provide protection of focal brain ischemia-reperfusion injury in rats
1. experimental animal and method:
Get totally 72 of male SD rats, be divided at random 9 groups, every group 8, the 1st group is sham operated rats, the 2nd group is model group (injection equal-volume physiological saline), the 3rd group of positive medicine nimotop injection group (Bayer A.G's production), dosage 8mg/Kg/d, the the 4th to 9 group is that feather cockscomb 1# to 6# organizes, and dosage all is 8mg/Kg/d.Administration time is later on tail vein injection after 1 hour of models of cerebral ischemia-reperfusion injury modeling success.
Line bolt model with reference to Longa EZ report prepares models of cerebral ischemia-reperfusion injury (Longa EZ, et al:Reversable middle cerebral artery occlusion without craniectomy in rat.Stroke, 1989,20:84).Ischemic poured into to break end after 24 hours in 2 hours again gets brain, TTC dyeing is left and taken sample and is carried out cerebral infarct volume and measure and (see the Zhang Juntian chief editor for details: modern pharmacology experimental methodology, the 1241st page, combined publication society of China Concord Medical Science University of Beijing Medical University, October in 1998 the 1st edition).
The results are shown in Table 14.
Table 14 the compounds of this invention is to the provide protection of focal brain ischemia-reperfusion injury in rats
Compare with model group,
*P＜0.05,
*P＜0.01
By as seen from Table 14, feather cockscomb glycosides C
1, D
1, E, F, G or feather cockscomb total saponins III have stronger provide protection to focal brain ischemia-reperfusion injury in rats.
Three, the compounds of this invention is to the preventive and therapeutic effect of metabolic disease
1, laboratory animal and method:
Get body weight and be 90 of the rats of 180～240g, male and female half and half are left and taken 10 at random as Normal group, and all the other are experimental group.After the experimental group rat fasting 12, with abdominal cavity, lower-left disposable injection streptozotocin (STZ, u s company) 65mg/Kg (is dissolved in PH4.5,0.1mmol/L citrate buffer), control group is injected isometric citrate buffer, inject after 48 hours, the glucose in urine of all blood sugar concentration＞13mmol/L is strong positive person, and occur drinking more, many foods, the diuresis person is diabetes model, diabetes rat is divided into 7 groups more at random, every group 10, diabetic model group, the compounds of this invention feather cockscomb 1# to 6# treatment group, control group and model group are fed and are raised normal diet, except freely drinking water, every day is with distilled water gavage (2ml/d).The compounds of this invention feather cockscomb 1# to 6# organizes, and every rat is 4 weeks of gavage according to dosage, during standard feed and drinking-water unrestricted, after 4 weeks, with Sodital anesthesia, heart extracting blood detects Biochemical Index: the whole blood blood sugar detection: the afterbody 20 μ L that take a blood sample, measure by blood glucose meter with blood sugar test paper.
The results are shown in Table 15
Table 15 the compounds of this invention is on the impact of experimental diabetic rats blood sugar
Compare with model group,
*P＜0.01
By as seen from Table 15, feather cockscomb glycosides C
1, D
1, E, F, G or feather cockscomb total saponins III have obvious hypoglycemic activity.
Four, the compounds of this invention is to the therapeutic action of dementia
1.MORRIS water maze method
1.1 animal and method
The MORRIS water maze laboratory: 90 of SD rats (being provided by the The 2nd Army Medical College Experimental Animal Center), be divided at random 9 groups, be respectively blank group, model group, positive controls and feather cockscomb 1# to 6# medicine group.Its empty group and model group are with 0.5% Xylo-Mucine gavage, and the positive controls gavage gives Hup A 4mg/kg, and medicine group of the present invention is pressed the 8mg/kg gastric infusion, every day 2 times, totally 8 days.After for the first time administration every day 1 hour, begin to carry out the MORRIS water maze training.Experiment allows rat free swimming 2 minutes to adapt to surrounding environment the day before yesterday, from first day, train every day 4 times, select at random a place of entry at every turn, rat is put into water towards pool wall, observe and record route map and the required time (latent period) that rat sought and climbed up platform.4 trained rat, need it is caused platform if rat was not found platform in 120 seconds respectively from four different place of entry entry.At this moment be designated as 120 seconds latent period, trained the interval 60 seconds at every turn, continuous 7 days.After the last administration in the 8th day 1 hour, blank group rats by intraperitoneal injection physiological saline 1ml/kg, all the other respectively organize rats by intraperitoneal injection scopolamine hydrobromide 2mg/kg.Every rear 25min of rat injection end is fixed into water spot by one and is put in the water towards pool wall, observes and record the time (latent period) that it is sought platform route and finds platform.
Keep away dark experiment: 90 of SD rats, be divided at random 9 groups by the aforementioned groupings method, wherein blank group and model group are with 0.5% Xylo-Mucine gavage, the control group gavage gives Hup A 4mg/kg, medicine group of the present invention is pressed the 8mg/kg gastric infusion, every day 2 times, totally 8 days.1 hour begins training after the last administration in the 8th day, except the blank group, and every group of rat 25min abdominal injection scopolamine hydrobromide 2.0mg/kg before training, blank group is physiological saline 1.0ml/kg.During training rat put into first case endoadaptation 3min, plugged then places animal back and to keep away the bright chamber of camera bellows to the hole, observes animal and enters first the total degree (number of times of making a mistake) that enters the darkroom in time (latent period) in darkroom and the 5min.Repeated to keep away dark experimental implementation on the 9th day and record latent period and the number of making mistakes as the memory indexs, the results are shown in Table 16 and table 17.
Table 16 is respectively organized the latent period that rat seeks platform
*P＜0.05,
*Compare with model group P＜0.01
Table 17 is respectively organized rat and is made a mistake number of times and latent period relatively
Compare with model group,
*P＜0.05,
*P＜0.01
By table 16,17 as seen, feather cockscomb glycosides C
1, D
1, E, F, G or feather cockscomb total saponins III can obviously improve the learning and memory function of dementia rats, and dementia is had certain preventive and therapeutic action.
Five, the antidepressant of the compounds of this invention or anxiety are active
1, laboratory animal and method
Method by Zhang Juntian chief editor " modern pharmacology experimental technique " (first volume) the 104th page is carried out.Mouse (Kunming kind, male, 20-23 restrains) is put into 10 centimetres of the depth of waters, and the graduated cylinder that water temperature is 25 ± 1 ℃ (20 centimetres high, 14 cm diameters) went swimming makes it produce the feared state of mind, takes out after 5 minutes, and 32 ℃ lower to hairy dried.Give respectively the laboratory animal gastric infusion in 24 hours, again mouse is put into above-mentioned environment, measure mouse and in 6 minutes rear 4 minutes, keeps the motionless time of swimming, with the shortening of the dead time standard as judgement medicine antidepressant effect.This tests 10 of every group of mouse.1. the blank group gives the physiological saline with drug study group equivalent; 2. positive controls gives medicine fluorine west tincture, and dosage is 6mg/Kg; 3. feather cockscomb 1# to 6# of the present invention, dosage all are 4mg/Kg, the same time in 24 hours after each is organized administration time and is that mouse is hairy and does.Route of administration is divided into gastric infusion three times, and gastric infusion carries out the forced swimming experiment after 60 minutes the last time, the results are shown in Table 18.
Table 18 saponins compound is on the result that affects of mouse forced swimming experiment behavior
Compare with the blank group
*P＜0.05,
*P＜0.01
By as seen from Table 18, feather cockscomb glycosides C
1, D
1, E, F, G or feather cockscomb total saponins III all can significantly reduce the mouse forced swimming dead time, shows that the compounds of this invention all has significant antidepressant activity.
Above-mentioned each experiment shows that it is active that the compounds of this invention has the hepatopathy of control, cardiovascular and cerebrovascular disease, metabolic disease, dementia, depression or anxiety, so can be used for preparing the medicine of preventing and treating hepatopathy, cardiovascular and cerebrovascular disease, metabolic disease, dementia, depression or anxiety.
Claims (2)
1. Celosia argentea L. saponin compounds feather cockscomb glycosides C
1(Celosin C
1), feather cockscomb glycosides D
1(Celosin D
1), Celosin E (Celosin E), Celosin G (Celosin G), it is characterized in that chemical structural formula is as follows:
2. the described Celosia argentea L. saponin compounds feather cockscomb of claim 1 glycosides C
1, feather cockscomb glycosides D
1, Celosin E, Celosin G prevent and treat application in hepatopathy, cardiovascular and cerebrovascular disease, metabolic disease, dementia, depression or the anxiety medicine in preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010545566 CN102060904B (en) | 2010-11-16 | 2010-11-16 | Celosia argentea L. saponin compounds and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010545566 CN102060904B (en) | 2010-11-16 | 2010-11-16 | Celosia argentea L. saponin compounds and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102060904A CN102060904A (en) | 2011-05-18 |
| CN102060904B true CN102060904B (en) | 2013-04-03 |
Family
ID=43996423
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010545566 Active CN102060904B (en) | 2010-11-16 | 2010-11-16 | Celosia argentea L. saponin compounds and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102060904B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105669793B (en) * | 2015-12-30 | 2018-08-03 | 上海市奉贤区中心医院 | Oleanane-type triterpene saponin class compound, preparation method and its application |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100429219C (en) * | 2006-05-23 | 2008-10-29 | 中国人民解放军第二军医大学 | Celosia argentea suponin compound and its pharmaceutical use |
| CN101570561B (en) * | 2009-06-15 | 2011-09-14 | 中国人民解放军第二军医大学 | Novel Celosia argentea saponins compounds and application thereof |
-
2010
- 2010-11-16 CN CN 201010545566 patent/CN102060904B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN102060904A (en) | 2011-05-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100429219C (en) | Celosia argentea suponin compound and its pharmaceutical use | |
| Witthawaskul et al. | Acute and subacute toxicities of the saponin mixture isolated from Schefflera leucantha Viguier | |
| CN102391346B (en) | A kind of volatile oil saponins compound and uses thereof | |
| CN107890470A (en) | A kind of preparation method of the effective constituents of steroid saponin containing trilliaceae tablet and its application in various kinds of drug is prepared | |
| CN105722519A (en) | Composition containing a borage officinalis extract for alleviating, preventing, or treating metabolic diseases | |
| CN101570561B (en) | Novel Celosia argentea saponins compounds and application thereof | |
| CN104663975A (en) | Acanthopanax health tea for decreasing sugar and lipid and preparation method for acanthopanax health tea | |
| CN103919854B (en) | Application of butterflybush flower and extract thereof to preparation of medicament | |
| CN104387438B (en) | New triterpene saponin componds Herba Celosiae argenteae glycosides L in Semen Celosiae and its medical application | |
| CN104523742B (en) | A kind of polysaccharide composition and its application with protect liver and raising immunization | |
| CN102283913B (en) | Radix aconiti carmichaeli extract and application thereof | |
| CN102060904B (en) | Celosia argentea L. saponin compounds and application thereof | |
| CN103463409B (en) | Traditional Chinese medicine formula for treating heart qi deficiency | |
| CN107912773A (en) | A kind of preparation for being used to alleviate physical fatigue | |
| Tao et al. | Effects of polysaccharides extracted from zhu zi shen (rhizoma panacis majoris) on oxidative stress and hemodynamics in rats with adriamycin-induced chronic heart failure | |
| CN104341478B (en) | Triterpene saponin componds feather cockscomb glycosides K and its medical application in the seed of feather cockscomb | |
| CN103083429B (en) | Blood fat-reducing traditional Chinese medicine formula | |
| CN101804083B (en) | Application of pollen pini and extract thereof in treating inflammatory bowel disease and method for preparing extract | |
| CN101618095B (en) | Application of effective parts of Chinese dates and hawthorns in aspect of preparing medicine with activities of lowering blood fat and resisting oxidation | |
| CN105025910A (en) | Pharmaceutical composition and functional food for prevention or treatment of diabetic complications or angioedema comprising natural extract | |
| CN104740054B (en) | A kind of pharmaceutical composition for preventing and treating myocardial ischemia and its production and use | |
| CN104027363B (en) | A method of extracting an alpha-glucosidase inhibitor from phellinus pini | |
| CN106109767A (en) | A kind of compound preparation preventing and treating non-alcohol fatty liver | |
| CN102716182B (en) | A kind of be used for the treatment of non-alcoholic fatty liver disease Semen Cassiae extract, preparation method and pharmacy application thereof | |
| CN102293847A (en) | Chinese medicinal composition for treating constipation, acne and hyperlipidemia, and preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |