CN101797339A - Synergistic medicinal composition containing oleanolic acid - Google Patents
Synergistic medicinal composition containing oleanolic acid Download PDFInfo
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- CN101797339A CN101797339A CN200910265374A CN200910265374A CN101797339A CN 101797339 A CN101797339 A CN 101797339A CN 200910265374 A CN200910265374 A CN 200910265374A CN 200910265374 A CN200910265374 A CN 200910265374A CN 101797339 A CN101797339 A CN 101797339A
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- Prior art keywords
- grams
- chinese medicine
- hepatitis
- oleanolic acid
- decocting liquid
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 18
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 title claims abstract description 11
- JKLISIRFYWXLQG-UHFFFAOYSA-N Epioleonolsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4CCC3C21C JKLISIRFYWXLQG-UHFFFAOYSA-N 0.000 title claims abstract description 11
- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 title claims abstract description 11
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 229940100243 oleanolic acid Drugs 0.000 title claims abstract description 11
- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 title claims abstract description 11
- 230000002195 synergetic effect Effects 0.000 title abstract description 4
- 239000003814 drug Substances 0.000 claims abstract description 27
- 208000006454 hepatitis Diseases 0.000 claims abstract description 17
- 231100000283 hepatitis Toxicity 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 244000050427 Melilotus officinalis subsp suaveolens Species 0.000 claims description 4
- 235000000839 Melilotus officinalis subsp suaveolens Nutrition 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 238000007654 immersion Methods 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 238000009098 adjuvant therapy Methods 0.000 abstract 1
- 230000001154 acute effect Effects 0.000 description 7
- 206010067125 Liver injury Diseases 0.000 description 6
- 208000002672 hepatitis B Diseases 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000003390 Chinese drug Substances 0.000 description 4
- 206010008909 Chronic Hepatitis Diseases 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 125000000955 oleanolic acid group Chemical group 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 206010019668 Hepatic fibrosis Diseases 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 231100000753 hepatic injury Toxicity 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 206010019799 Hepatitis viral Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000003929 Transaminases Human genes 0.000 description 2
- 108090000340 Transaminases Proteins 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 231100000012 chronic liver injury Toxicity 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 201000001862 viral hepatitis Diseases 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 208000005331 Hepatitis D Diseases 0.000 description 1
- 206010019754 Hepatitis cholestatic Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 231100000439 acute liver injury Toxicity 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 231100000838 cholestatic hepatitis Toxicity 0.000 description 1
- 230000002079 cooperative effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- SPPIIOPGDLITJE-VLQRKCJKSA-N diazanium;(2s,3s,4s,5r,6s)-6-[[(3s,4ar,6ar,6bs,8as,11s,12ar,14ar,14bs)-11-carboxylato-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1h-picen-3-yl]oxy]-5-[(2r,3r,4s,5s,6s)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]oxy-3,4-dihy Chemical compound N.N.O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O SPPIIOPGDLITJE-VLQRKCJKSA-N 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 230000036732 histological change Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000037890 multiple organ injury Diseases 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
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- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a synergistic medicinal composition containing oleanolic acid and traditional Chinese medicinal extractives, as well as an application of the composition in the preparation of medicaments for the adjuvant therapy of hepatitis.
Description
Invention field
The present invention relates to the Pharmaceutical composition formed by oleanolic acid and Chinese medicine extract, and the purposes of said composition in the medicine of preparation adjuvant treating hepatitis.
Background technology
Hepatitis has multiple sorting technique clinically, classifies as (1) nosetiology: viral hepatitis can be divided into five types is first, second, third, fourth, penta.(2) clinical classification can be divided into following a few type: 1. acute anicteric hepatitis, this is a modal type in the viral hepatitis, see with B-mode, third type, hepatitis D more, general this type of hepatitis clinical symptoms is less, and transaminase's elevated levels is lower, and Histological change is light, mortality rate is lower, but the course of disease can be delayed the long period, and " three is slow " characteristics are arranged, and morbidity is slow, recovery is slow, delay also slow (referring to the long meaning slowly); 2. acute icterohepatitis is less relatively compared with anicteric hepatitis, and the state of an illness is a self limiting often, and how good prognosis is, but minority can develop into hepatitis gravis; 3. chronic hepatitis: relevant experts in 1994 propose the name and the suggestion of chronic hepatitis again, with the cause of disease is the diagnosis name that chronic hepatitis is determined on the basis, simultaneously ordered grade scale, formulated standard by stages according to degree of hepatic fibrosis again according to the downright bad order of severity of hepatitis inflammation; 4. hepatitis gravis can be divided into acute heavy type, severe subacute and chronic heavy type again; 5. cholestatic hepatitis.
Wherein hepatitis B is caused by hepatitis B virus, serves as main a kind of infectious disease that also can cause multiple organ injury with the liver inflammatory lesion.China is the most popular country of hepatitis B, reaches more than 35% some local crowd infection rate, and be the most serious infectious disease of current harm people ' s health.According to investigations, China's hepatitis B patient is about 2,700 ten thousand, and annual New Development patient about 9,000,000.
The hepatitis B clinical manifestation is various, easily develops into chronic hepatitis and liver cirrhosis, and a few peoples finally develop into hepatocarcinoma.Hepatic fibrosis is the total pathological change of many chronic hepatopathy evolutions, and the damage of chronic, persistence is the prerequisite that hepatic fibrosis forms.Cause the factor of hepatic injury a lot,, hepatitis B, liver cirrhosis, take some drugs for a long time and can cause acute and chronic liver injury generally because of factors such as medicine, a large amount of ethanol, allergy cause acute liver damage.By reducing detrimental effect to liver function, can adjuvant treating hepatitis.
The medicine that is used for the treatment of the acute and chronic hepatic injury at present, commonly used have oleanolic acid, a diammonium glycyrrhizinate etc.These chemicalses generally have certain side effect, and cause that therapeutic effect at a specified future date is poor, problem such as Strain produces after drug resistance phenomenon, the drug withdrawal relapse rate height.
The curative effect of Chinese medicine hepatitis B is proved by a large amount of clinical trials.Chinese medicine all can be brought into play curative effect preferably at aspects such as antiviral, adjusting immunity of organisms, protection hepatocyte.But Chinese medicine preparation ubiquity onset at present is slow, needs problems such as life-time service.
Therefore, Western medicine and Chinese Medicine and Clavicular need be got up, i.e. synergism is played in Chinese medicine and western medicine combination, solves the problem that above-mentioned Western medicine and Chinese medicine exist in auxiliary treatment all kinds hepatitis separately, produces synergistic therapeutic effect simultaneously.
Summary of the invention
One object of the present invention is to provide the Pharmaceutical composition of being made up of oleanolic acid and a kind of Chinese medicine extract, wherein prepares on the method basis of the Chinese medicine extract of said composition according to embodiment 1 among the Chinese patent CN1049349C, and is as follows:
To get Melilotus suaveolens Ledeb. 9 gram, Herba Abri 9 grams, Herba Artemisiae Scopariae 9 grams, Herba Lysimachiae 6 grams, the Pseudobulbus Bletillae (Rhizoma Bletillae) 3 grams, earlier with Melilotus suaveolens Ledeb. with 10% alcohol water blend immersion 30 minutes, decoct twice then, the filtrate decocting liquid; Other four Chinese medicine mixing and water adding immersion after 30 minutes, is decocted twice, the filtrate decocting liquid; Merge above two decocting liquid, concentrating under reduced pressure, drying gets extract.
One object of the present invention is to provide the purposes of above-mentioned Pharmaceutical composition in preparation auxiliary treatment all kinds hepatitis medicament.
This Chinese medicine the water extracted immersing paste is called " the described Chinese medicine extract of this paper (or above) " hereinafter.
Above-mentioned composition and mixing acceptable accessories can be made acceptable forms clinically, as tablet, capsule, granule, oral liquid, subcutaneous administration preparation, suppository etc.
Pharmacological research
The main pharmacodynamics of Pharmaceutical composition of the present invention studies confirm that it has strong transaminase lowering effect, i.e. function for protecting liver and reducing enzyme activity.
Edit with reference to Zhang Juntian, " modern pharmacology test method " (volume two), combined publication society of China Concord Medical Science University of Beijing Medical University, the 1397-1398 page or leaf, disclosed method in " first segment chmice acute chemical liver injury model ", set up the acute chemical liver injury model of mouse carbon tetrachloride, carry out the pharmacodynamics test of Pharmaceutical composition anti-liver injury of the present invention.
The test grouping:
1 normal control group: animal does not do any processing, and normal physiological saline is irritated stomach;
2 model control group: after the animal model modeling success, normal physiological saline is irritated stomach;
2 pure Chinese drug-treated group: the water extracted immersing paste 1.04g/kg body weight as indicated above
3 oleanolic acid groups: the 10mg/kg body weight is irritated stomach
4 compositions groups: 10mg/kg body weight oleanolic acid+the water extracted immersing paste 1.04g/kg body weight mentioned above is irritated stomach.
Following table has shown the influence of each group to Mouse Liver function leading indicator GOT, GPT.
| Group | Number of animals | GOT (active unit) | GPT (active unit) |
| The normal control group | ??10 | ??20.78±16.75 | ??48.31±17.35 |
| Model control group | ??10 | ??250.76±76.58 | ??306.25±59.47 |
| Pure Chinese drug-treated group | ??10 | ??178.22±60.12 | ??226.99±50.25 |
| The oleanolic acid group | ??10 | ??105.74±36.56 | ??203.71±32.56 |
| The compositions group | ??10 | ??78.41±22.74 | ??100.55±41.68 |
This table shows that all there is significant difference (P＜0.05) in each group (pure Chinese drug-treated group, oleanolic acid group, compositions group) of treatment with model control group, and all there are significant difference (P＜0.05) in compositions group and pure Chinese drug-treated group, compositions group and oleanolic acid group.Show that there are cooperative effect in oleanolic acid and described Chinese medicinal components in the compositions group.
The pharmaceutics test
Can produce the tablet that contains following component in a conventional manner:
Component
The Mg/ sheet
Pharmaceutical composition 200-1000 of the present invention
Corn starch 125.0
Pulvis Talci 75.0
Magnesium stearate 1.0
Wherein compositions is made up of with weight ratio oleanolic acid and Chinese medicine extract mentioned above at 1: 104.
Can produce the capsule that contains following component in a conventional manner:
Component
The Mg/ sheet
Pharmaceutical composition 200-1000 of the present invention
Lactose 10.0
Corn starch 20.0
Talcum 5.0
Wherein compositions is made up of with weight ratio oleanolic acid and Chinese medicine extract mentioned above at 1: 104.
Claims (2)
1. Pharmaceutical composition, it is made up of with weight ratio oleanolic acid and Chinese medicine extract at 1: 104, and described Chinese medicine extract is by following method preparation:
To get Melilotus suaveolens Ledeb. 9 gram, Herba Abri 9 grams, Herba Artemisiae Scopariae 9 grams, Herba Lysimachiae 6 grams, the Pseudobulbus Bletillae (Rhizoma Bletillae) 3 grams, earlier with Melilotus suaveolens Ledeb. with 10% alcohol water blend immersion 30 minutes, decoct twice then, the filtrate decocting liquid; Other four Chinese medicine mixing and water adding immersion after 30 minutes, is decocted twice, the filtrate decocting liquid; Merge above two decocting liquid, concentrating under reduced pressure, drying gets extract.
2. the purposes of compositions as claimed in claim 1 in the medicine of preparation adjuvant treating hepatitis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102653745A CN101797339B (en) | 2009-12-30 | 2009-12-30 | Synergistic medicinal composition containing oleanolic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009102653745A CN101797339B (en) | 2009-12-30 | 2009-12-30 | Synergistic medicinal composition containing oleanolic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101797339A true CN101797339A (en) | 2010-08-11 |
| CN101797339B CN101797339B (en) | 2011-12-21 |
Family
ID=42593280
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009102653745A Expired - Fee Related CN101797339B (en) | 2009-12-30 | 2009-12-30 | Synergistic medicinal composition containing oleanolic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101797339B (en) |
-
2009
- 2009-12-30 CN CN2009102653745A patent/CN101797339B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN101797339B (en) | 2011-12-21 |
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Addressee: Qian Xin Document name: Notification of Passing Preliminary Examination of the Application for Invention |
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| PB01 | Publication | ||
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Addressee: Qian Xin Document name: Notification of Publication and of Entering the Substantive Examination Stage of the Application for Invention |
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| ASS | Succession or assignment of patent right |
Owner name: NINGBO YINZHOU FURUIDA BIOTECHNOLOGY CO., LTD. Free format text: FORMER OWNER: QIAN XIN Effective date: 20111025 |
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| C41 | Transfer of patent application or patent right or utility model | ||
| C53 | Correction of patent of invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Li Gang Inventor after: Qian Xin Inventor before: Qian Xin |
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| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 311203 HANGZHOU, ZHEJIANG PROVINCE TO: 315100 NINGBO, ZHEJIANG PROVINCE Free format text: CORRECT: INVENTOR; FROM: QIAN XIN TO: LI GANG QIAN XIN |
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Effective date of registration: 20111025 Address after: 315100 Zhejiang city of Ningbo province Yinzhou District Zhonggongmiao Street Tiantong Road No. 1388 room 3624 Applicant after: NINGBO YINZHOU FURUIDA BIOTECHNOLOGY Co.,Ltd. Address before: 311203, Hangzhou District, Zhejiang City, Xiaoshan Province South Gate residential area Applicant before: Qian Xin |
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Granted publication date: 20111221 Termination date: 20121230 |