CN101856397B - Medicinal composition for treating hepatitis B and preparation method thereof - Google Patents
Medicinal composition for treating hepatitis B and preparation method thereof Download PDFInfo
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- CN101856397B CN101856397B CN2009100816292A CN200910081629A CN101856397B CN 101856397 B CN101856397 B CN 101856397B CN 2009100816292 A CN2009100816292 A CN 2009100816292A CN 200910081629 A CN200910081629 A CN 200910081629A CN 101856397 B CN101856397 B CN 101856397B
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- silymarin
- rhizoma cimicifugae
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Abstract
The invention discloses a medicinal composition for treating hepatitis B and a preparation method thereof. The medicinal composition consists of total saponin of cimicifuga dahurica, silymarin, a pharmaceutically acceptable carrier, and an excipient. Pharmacological and pharmacodynamic experiments prove that: the medicinal composition has anti-viral effect and injury protection effect, and has the characteristics of small dosage, exact curative effect, and the like.
Description
Technical field
Content of the present invention relates to a kind of pharmaceutical composition of treating hepatitis B and preparation method thereof, belongs to technical field of Chinese medicines.
Background technology
Hepatitis B is claimed hepatitis B (abbreviation hepatitis B) again, is due to the hepatitis b virus infection (HBV).
The pathogenesis that causes chronic viral hepatitis B mainly is because the intravital virus of acute viral hepatitis patient fails to be eliminated and body autoimmune function obstacle for a long time.Hepatitis B patient's persistent infection is the basic reason of lesion growth, and there are long, defectives such as side effect is big, easy recurrence, expense height of cycle in present main antiviral drugs, can not satisfy clinical requirement.But the employing Comprehensive Treatment comprises and regulates body's immunity, antiviral, the liver protecting function, improves symptom, prevents more scientific and effective of traditional Chinese medicine therapy such as hepatic fibrosis.Market still lacks and has the medicine that antivirus action simultaneously has the treatment hepatitis B of hepatoprotective effect again.
Rhizoma Cimicifugae is the dry rhizome of ranunculaceae plant Rhizoma Cimicifugae, Xingan's Rhizoma Cimicifugae and big SANYE Rhizoma Cimicifugae.Function with the rash delivered, heat-clearing and toxic substances removing, elevate a turnable ladder yang-energy.
The Rhizoma Cimicifugae total saponins is the effective site that obtains with modern extraction and separation technology by in the Rhizoma Cimicifugae, has the inside and outside antivirus action of significant body, can contain the hepatitis B state of an illness deterioration.
Herba Silybi mariani is the dry mature fruit of feverfew Herba Silybi mariani Silybum marianum (L.) Gaertn..Has heat-clearing and toxic substances removing, the effect of 'Shugan Lidan '.Cure mainly dampness-heat in the liver and gallbladder. hypochondriac pain, jaundice.
Silymarin is the general name by the effective ingredient of extraction separation in the Herba Silybi mariani dry seed; Be widely used in the acute and chronic hepatitis of treatment in recent years; Liver cirrhosis and treating liver injury have the protection liver plasma membrane, promote the hepatocyte reparative regeneration, control hepatoprotective effects such as liver tissues inflammatory reaction, anti-hepatic fibrosis.Although silymarin has the incomparable advantage of medicine of other treatment hepatitis B, at anti-virus aspect, a little less than the effect relative thin.
Therefore to have the medicine that antivirus action has hepatoprotective effect simultaneously again be to solve the intractable effective ways of hepatitis B in research.
Summary of the invention
The objective of the invention is to disclose a kind of pharmaceutical composition of treating hepatitis B and preparation method thereof.
The present invention is used to treat hepatitis B with Rhizoma Cimicifugae total saponins and two kinds of component reasonable compatibilities of silymarin, and said composition possesses antivirus action and injury protection effect simultaneously.
The present invention seeks to realize through following technical scheme:
Active ingredient in pharmaceutical percentage by weight of the present invention consists of:
Rhizoma Cimicifugae total saponins 10～60%, silymarin 40～90%.
Active ingredient in pharmaceutical of the present invention, preferred weight percent is following:
Rhizoma Cimicifugae total saponins 15～40%, silymarin 60～85%.
Active ingredient in pharmaceutical of the present invention, optimum weight percentage ratio is following:
Rhizoma Cimicifugae total saponins 23.1%, silymarin 76.9%.
Get above-mentioned active component, add adjuvant pharmaceutically commonly used in right amount, process drug combination preparation, comprise oral formulations or lyophilized injectable powders such as granule, pill, capsule, tablet, oral liquid.
This pharmaceutical composition is with low cost, easy to use, prescription science, determined curative effect.
Following experimental example and embodiment further prove but are not limited to the present invention.
Experimental example 1: the inhibitory action of extracorporeal antivirus effect effect-HBsAg, HBeAg secretion and HBV-DNA are duplicated
1. pair cell toxicity test: with 0.06% trypsin the 2.2.15 cell is dispersed into the individual cells suspension, using the DMEM that contains 10% hyclone to cultivate and being made into concentration is 3 * 10
5The cell suspension of/mL is pressed the 0.1mL/ hole and is divided kind in 96 orifice plates, puts 37 ℃, saturated humidity, 5%CO
2Cultivate in the incubator, change pastille culture fluid 0.1mL/ hole behind the 2d, each concentration four hole.The pharmaceutical composition medicinal liquid is made serial doubling dilution become following 8 concentration, 2000,1000,500,250,125,62.5,31.3,15.6 μ g/mL.Continue to cultivate, and establish the contrast that does not add medicine; Collect supernatant behind the 6d, survey drug cell toxicity, calculate the poisonous concentration (TC of half with mtt assay
50), maximal non-toxic concentration (TC
0).
2. to HBeAg, HBsAg inhibition test: cell is handled, and inoculation is cultivated the same; Dosage from 500 μ g/mL to extending below; Establish the blank that does not add medicine simultaneously, the medicine contrast of same concentrations silymarin and Rhizoma Cimicifugae total saponins, the positive drug contrast of lamivudine 8 μ g/mL.The ELISA method is measured HBSAg, HBeAg after collecting supernatant afterwards.Calculate suppression ratio, calculate medium effective concentration (IC
50).
3. result:
3.1 the toxic action of pair cell: measure the external TC of pharmaceutical composition through mtt assay to the 2.2.15 cell
50=491.2 μ g/mL, TC
0=125 μ g/mL; The external TC of Rhizoma Cimicifugae total saponins to the 2.2.15 cell
50=485.5 μ g/mL, TC
0=125 μ g/mL; The external TC of silymarin to the 2.2.15 cell
50=354.0 μ g/mL, TC
0=250 μ g/mL; The result sees table 1.
3.2 to HBeAg, HBsAg inhibitory action: pharmaceutical composition all has remarkable inhibitory action and is good dose-effect relationship HBsAg and HBeAg more than 31.3 μ g/mL concentration, and effect is superior to the Rhizoma Cimicifugae total saponins or silymarin uses separately.The result sees table 2,3.
The external toxicity of table 1 pharmaceutical composition to the 2.2.15 cell
Compare with matched group:
*P＜0.05;
*P＜0.01
The external inhibitory action of table 2 pharmaceutical composition to 2.2.15 cell HBeAg
Compare with the blank group:
*P＜0.05;
*P＜0.01
The external inhibitory action of table 3 pharmaceutical composition to 2.2.15 cell HBsAg
Compare with matched group:
*P＜0.05;
*P＜0.01
Experimental example 2: the interior resisting virus of pharmaceutical composition is active-to the therapeutical effect of duck hepatitis-B model
1. divide into groups and administration
The male Shanghai of 1 age in days sheldrake after animal bought back the back adaptability and feed 2d, is selected congenital natural infection DHBV person as animal for research with the DHBV dna probe of digoxigenin labeled through the dot blot hybridization detection.DHBV infects duckling and divides 6 groups to carry out Drug therapy test, 6 every group: model control group (DHBV), pharmaceutical composition 20mg/kg at random; 40mg/kg, 80mg/kg group, Rhizoma Cimicifugae total saponins 80mg/kg group; Silymarin 80mg/kg group, lamivudine 10mg/kg group, oral administration; Be total to 10d every day 2 times, and model control group (DHBV) is with the physiologic saline for substitute medicine.In preceding 1 day of administration (T0), medication the 5th day (T5) after medication the 10th day (T10) and the drug withdrawal the 3rd day (P3), is got blood from duck lower limb shin vein, separation of serum, and-70 ℃ of preservations are to be checked.
2.DHBV-DNA detection method
It is clear to get above-mentioned Sanguis Anas domestica to be checked, presses nick translation test kit operating instruction, uses
32The P labelling is made probe, and 40pL serum is put on nitrocellulose membrane, carries out dot blot hybridization, and autoradiograph sheet speckle detects OD value (optical filter is 490nm) on ELIASA, represent virus load indirectly with the OD value, with t check carrying out statistical analysis.
3. result:
The result shows: DHBV DNA titre held stationary state after the lamivudine group medication, there is not tangible ascendant trend, and serum DHBVDNA titre and model group relatively have significant difference, and DHBV DNA has certain rise trend after the drug withdrawal; Serum DHBV DNA titre held stationary state after the pharmaceutical composition medication, serum DHBV DNA titre and model group relatively have significant difference, no tangible rise trend after the drug withdrawal.Rhizoma Cimicifugae total saponins 80mg/kg relatively has significant difference from the 5th day beginning serum DHBV DNA titre and model group, and DHBV DNA has certain rise trend after the drug withdrawal; Silymarin does not show DHBV DNA is had a significant effect.Show that pharmaceutical composition has the obvious suppression effect to the propagation of DHBV virus, effect is superior to the Rhizoma Cimicifugae total saponins or silymarin uses separately.The result sees table 4.
Table 4 pharmaceutical composition is to the influence of the clear DHBV DNA of Sanguis Anas domestica titre
Compare with model control group:
*P＜0.05
*P＜0.01; With before the administration relatively:
△P＜0.05
△ △P＜0.01
Experimental example 3: pharmaceutical composition is to CCl
4Cause the protective effect of rat chronic hepatic injury
Get 60 of rats, the male and female dual-purpose, except that 10 of normal control groups, all the other animals are pressed the 0.5mL/100g body weight, the CCL of lumbar injection 10%
4, 2 times weekly.GPT in the serum is measured in 2 all posterior orbit blood samplings; Removal GPT content is lower than the animal of 100 karmen units; All the other animals are evenly divided 5 groups according to GPT content: model group, bifendate 30mg/kg group, pharmaceutical composition 25mg/kg, 50mg/kg; The 100mg/kg group is established Rhizoma Cimicifugae total saponins 100mg/kg and silymarin 100mg/kg group simultaneously as contrast.Grouping and medication are with 3.1.Each group of back of dividing into groups still continues the CCL with lumbar injection 10%
4Modeling, 2 times weekly, continuous 8 weeks.The administration group begins gastric infusion simultaneously, and every day, dose gave for 2 times, continuous 8 weeks.Normal control group intraperitoneal injection of saline under square one is given distilled water with the filling stomach.Observe following index: weigh the record death condition weekly; Per 2 weeks are detected GPT content in the serum; Measure the content of GPT, GOT, ALP, ALB, TP, TBIL in the serum respectively at 6 weeks, the blood sampling of 8 weeks after the administration; Pathologic finding.
The result shows: to the influence of rat blood serum biochemical indicator: pharmaceutical composition 50mg/kg, and the 100mg/kg group can obviously reduce serum alt content in administration the 6th all beginnings; Pharmaceutical composition 50mg/kg, 100mg/kg administration the 6th week beginning, 25mg/kg administration the 8th all beginnings can obviously reduce AST content in the serum; Pharmaceutical composition group 50mg/kg, the 6th week of 100mg/kg administration can be reduced the content of TBIL in the serum (STB).The pharmaceutical composition effect is superior to the Rhizoma Cimicifugae total saponins or silymarin uses separately, and the result sees table 5.
Table 5 pharmaceutical composition is to the protective effect of rat chronic hepatic injury
6 weeks
8 weeks
Compare with the normal control group
##Compare with model control group P＜0.01:
*P＜0.01
*P＜0.05
Pathological examination shows: after HE dyeing, administration various dose group and the fibroplasia of model group comparison hepatic tissue, the inflammatory cell infiltration of portal area, nodular formation all have the trend that alleviates, and the liver tissue lesions of especially big or middle dose groups obviously is better than model group.Administration various dose group hepatic tissue interstitial fibers VG dyeing is the weak positive after GA dyeing, and pharmaceutical composition group and other administration group hepatic tissue fibroplasia appear significantly weak positive.The hepatic pathology grading adopts rank test to carry out statistical procedures, with model group significant difference (P＜0.05) is arranged relatively.
The specific embodiment
Following embodiment all can realize the effect of above-mentioned experimental example.
Embodiment 1 tablet
Silymarin 110g
Rhizoma Cimicifugae total saponins 33g
Get Rhizoma Cimicifugae total saponins, silymarin and 257g starch, mixing, with 80% alcohol granulation, drying, tabletting is processed 1000 in tablet.
Embodiment 2: capsule
Silymarin 85g
Rhizoma Cimicifugae total saponins 58g
Get Rhizoma Cimicifugae total saponins, silymarin and 257g starch, mixing is processed capsule.
Embodiment 3: pill
Silymarin 122g
Rhizoma Cimicifugae total saponins 21g
Get the used adjuvant commonly used of Rhizoma Cimicifugae total saponins, silymarin and pill, adopt conventional method to process pill.
Embodiment 4: granule
Silymarin 95g
Rhizoma Cimicifugae total saponins 48g
Get the used adjuvant commonly used of Rhizoma Cimicifugae total saponins, silymarin and granule, adopt conventional method to process granule.
Embodiment 5: oral liquid
Silymarin 118g
Rhizoma Cimicifugae total saponins 25g
Get the used adjuvant commonly used of Rhizoma Cimicifugae total saponins, silymarin and oral liquid, adopt conventional method to process oral liquid.
Embodiment 6: lyophilized injectable powder
Silymarin 100g
Rhizoma Cimicifugae total saponins 43g
Get Rhizoma Cimicifugae total saponins, silymarin and conventional adjuvant, adopt conventional method to process lyophilized injectable powder.
Claims (6)
1. pharmaceutical composition of treating hepatitis B is by forming as the Rhizoma Cimicifugae total saponins of active component and silymarin and pharmaceutically acceptable carrier and excipient.
2. a kind of pharmaceutical composition of treating hepatitis B as claimed in claim 1 is characterized in that described active constituents of medicine percentage by weight is:
Rhizoma Cimicifugae total saponins 10～60%, silymarin 40～90%.
3. a kind of pharmaceutical composition of treating hepatitis B as claimed in claim 2 is characterized in that described active constituents of medicine percentage by weight is:
Rhizoma Cimicifugae total saponins 15～40%, silymarin 60～85%.
4. a kind of pharmaceutical composition of treating hepatitis B as claimed in claim 3 is characterized in that described active constituents of medicine percentage by weight is:
Rhizoma Cimicifugae total saponins 23.1%, silymarin 76.9%.
5. like the arbitrary said pharmaceutical composition of claim 1-4, wherein pharmaceutical composition is peroral dosage form or lyophilized injectable powder.
6. like the arbitrary said pharmaceutical composition of claim 1-4, wherein pharmaceutical composition is granule, pill, capsule, tablet, oral liquid or lyophilized injectable powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100816292A CN101856397B (en) | 2009-04-07 | 2009-04-07 | Medicinal composition for treating hepatitis B and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100816292A CN101856397B (en) | 2009-04-07 | 2009-04-07 | Medicinal composition for treating hepatitis B and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN101856397A CN101856397A (en) | 2010-10-13 |
| CN101856397B true CN101856397B (en) | 2012-07-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100816292A Expired - Fee Related CN101856397B (en) | 2009-04-07 | 2009-04-07 | Medicinal composition for treating hepatitis B and preparation method thereof |
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|---|---|
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0919227A1 (en) * | 1997-12-01 | 1999-06-02 | Gerhard Dr. Gergely | Effervescent preparation contianing a plant extract |
| CN1589858A (en) * | 2003-08-27 | 2005-03-09 | 于水 | New use of cimicifuga root and its affective part monomer in treating hepatitis B and its preparation method |
-
2009
- 2009-04-07 CN CN2009100816292A patent/CN101856397B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0919227A1 (en) * | 1997-12-01 | 1999-06-02 | Gerhard Dr. Gergely | Effervescent preparation contianing a plant extract |
| CN1589858A (en) * | 2003-08-27 | 2005-03-09 | 于水 | New use of cimicifuga root and its affective part monomer in treating hepatitis B and its preparation method |
Non-Patent Citations (2)
| Title |
|---|
| 王伯祥等.肝胆病常用中药的研究概况.《中医肝胆病学》.中国医药科技出版社,1993,第60-158页. * |
| 项中等.中药治疗乙型肝炎的进展.《广州医药》.广州市医药卫生科技情报站,1987,第18卷(第4期),54-56. * |
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| CN101856397A (en) | 2010-10-13 |
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Granted publication date: 20120725 Termination date: 20180407 |