CN109106917B - Application of traditional Chinese medicine composition in preparation of acute liver injury medicine - Google Patents
Application of traditional Chinese medicine composition in preparation of acute liver injury medicine Download PDFInfo
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- CN109106917B CN109106917B CN201811313771.0A CN201811313771A CN109106917B CN 109106917 B CN109106917 B CN 109106917B CN 201811313771 A CN201811313771 A CN 201811313771A CN 109106917 B CN109106917 B CN 109106917B
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- corydalis saxicola
- saxicola bunting
- zedoary turmeric
- turmeric oil
- total alkaloids
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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)
- A61K36/66—Papaveraceae (Poppy family), e.g. bloodroot
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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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
According to the invention, corydalis saxicola bunting and curcuma zedoaria are innovatively combined, in order to further increase curative effect and reduce administration dosage, effective parts are respectively taken for combination, namely corydalis saxicola bunting total alkaloids and zedoary turmeric oil are combined, effective proportion (corydalis saxicola bunting total alkaloids: zedoary turmeric oil is 1: 2-2.67) and optimal proportion (corydalis saxicola bunting total alkaloids: zedoary turmeric oil is 1:2.67) are preferably selected through orthogonal experiments and pharmacodynamic experiments. The result shows that the corydalis saxicola bunting total alkaloids and the zedoary turmeric oil are compatible, the protective effect of the corydalis saxicola bunting total alkaloids on the acute liver injury of the mouse is simultaneously obviously better than that of the corydalis saxicola bunting total alkaloids or the zedoary turmeric oil which are used independently, and the proportion of the two effective parts is not simple superposition of drug effects, but has obvious synergistic effect.
Description
Technical Field
The invention relates to the field of traditional Chinese medicine compounds, in particular to application of a traditional Chinese medicine composition in preparation of a medicine for treating acute liver injury.
Background
China is a high-prevalence area of viral hepatitis, about 1.2 billion chronic Hepatitis B (HBV) infected people exist, and according to latest data, the number of worldwide liver cancer and cirrhosis deaths is increasing, and the death rate is high because liver cancer can be diagnosed only at the end stage. The liver is the largest parenchymal organ in the abdominal cavity, is responsible for important physiological functions of the human body, causes liver dysfunction due to various reasons, causes various liver diseases, and is the basis of acute liver failure, and the liver failure is finally caused by severe or continuous liver injury. Hepatic fibrosis is the inevitable stage of chronic liver disease progressing to cirrhosis, and is manifested by excessive abnormal deposition of Extracellular matrix (ECM) components in the liver, and is a reversible process, so it is very critical to intervene in therapy.
Zedoary turmeric is a traditional Chinese medicine for promoting blood circulation and removing blood stasis, has the effects of improving microcirculation, improving local anoxia state, inhibiting in vivo fibroblast collagen synthesis and the like, is commonly used for treating abdominal mass in traditional Chinese medicine, and has positive effects of preventing primary liver cancer and liver function damage and reducing hepatic fibrosis caused by chemotherapy. One of seven medicinal materials in the anti-hepatic fibrosis compound preparation anti-fibrosis and anti-cirrhosis granules is zedoary. The zedoary turmeric oil is the extracted Chinese medicinal volatile oil, and researches show that the zedoary turmeric oil can inhibit the expression of IL-6 and TIMP of hepatic stellate cells to enhance ECM degradation, and simultaneously the zedoary turmeric oil can inhibit the expression of TGF-beta and P450 of the hepatic stellate cells to reduce ROS synthesis and lipid peroxidation, and inhibit the activation of the hepatic stellate cells and the synthesis of ECM. Therefore, the zedoary turmeric oil has good treatment effect on liver diseases.
In addition, Corydalis saxicola bunting is a whole plant of Corydalis saxicola bunting of Papaveraceae, has effects of clearing heat and detoxicating, promoting diuresis, relieving pain and stopping bleeding, and is commonly used for treating diseases such as hepatitis and hemorrhoid hemorrhage. The research shows that the corydalis saxicola bunting extract has a protective effect on mouse liver injury caused by CCl4, the corydalis saxicola bunting total alkaloid has an improvement effect on immune liver injury, and the obvious anti-hepatic fibrosis effect of the corydalis saxicola bunting total alkaloid is also proved by modern research institutes. Corydalis saxicola bunting has been developed into corydalis saxicola bunting injection which is a Chinese patent medicine for strengthening body resistance, clearing heat and removing toxicity and is used for treating acute and chronic hepatitis with syndrome of dampness-heat in liver and gallbladder. Therefore, the corydalis saxicola bunting total alkaloids also have good treatment effect on liver diseases.
Disclosure of Invention
The purpose of the invention is as follows:
based on the technical points, corydalis saxicola bunting and curcuma zedoary are innovatively combined, in order to further increase the curative effect and reduce the administration dosage, effective parts are respectively taken for combination, namely corydalis saxicola bunting total alkaloids and zedoary turmeric oil are combined for combination, the optimal combination proportion is preferably selected through orthogonal experiments and pharmacodynamics experiments, and the result shows that the corydalis saxicola bunting total alkaloids and the zedoary turmeric oil are combined for combination, the protective effect on the acute liver injury of mice is simultaneously and obviously superior to the independent use of the corydalis saxicola bunting total alkaloids or the zedoary turmeric oil, and the proportion of the two effective parts is not the simple superposition of the drug effect, but has obvious synergistic effect.
The technical scheme is as follows:
the invention provides an application of a traditional Chinese medicine composition in preparing a medicine for treating acute liver injury, which is characterized by comprising the following components in part by weight: the corydalis saxicola bunting total alkali and the zedoary turmeric oil are prepared according to the following weight ratio: corydalis saxicola bunting total alkali: zedoary turmeric oil is 1: 2-2.67.
As a further improvement of the invention, the corydalis saxicola bunting total alkali and the zedoary turmeric oil are prepared according to the following weight ratio: the corydalis saxicola bunting total alkali and the zedoary turmeric oil are prepared according to the following weight ratio: corydalis saxicola bunting total alkali: zedoary turmeric oil 1: 2.67.
Advantageous effects
According to the invention, corydalis saxicola bunting and curcuma zedoaria are innovatively combined, in order to further increase curative effect and reduce administration dosage, effective parts are respectively taken for combination, namely corydalis saxicola bunting total alkaloids and zedoary turmeric oil are combined, effective proportion (corydalis saxicola bunting total alkaloids: zedoary turmeric oil is 1: 2-2.67) and optimal proportion (corydalis saxicola bunting total alkaloids: zedoary turmeric oil is 1:2.67) are preferably selected through orthogonal experiments and pharmacodynamic experiments. The result shows that the corydalis saxicola bunting total alkaloids and the zedoary turmeric oil are compatible, the protective effect of the corydalis saxicola bunting total alkaloids on the acute liver injury of the mouse is simultaneously obviously better than that of the corydalis saxicola bunting total alkaloids or the zedoary turmeric oil which are used independently, and the proportion of the two effective parts is not simple superposition of drug effects, but has obvious synergistic effect.
Detailed Description
The present invention will be further illustrated with reference to the following examples, which are not intended to limit the scope of the invention.
Example 1: preparation of effective part
Corydalis saxicola bunting total alkali: taking a proper amount of corydalis saxicola bunting decoction pieces, extracting with acid water to obtain corydalis saxicola bunting total alkaloid crude extract, extracting with alcohol, concentrating, and repeatedly performing acid dissolution and alkali precipitation to obtain corydalis saxicola bunting total alkaloid with total alkaloid content of over 50% by ultraviolet detection.
Zedoary volatile oil: referring to the volatile oil determination method A under the item (appendix X D) of the determination of the volatile oil of zedoary turmeric in the first part of China pharmacopoeia of 2015 edition: the volatile oil in the curcuma zedoary decoction pieces is extracted by a steam distillation method, which is specifically implemented as follows: the curcuma zedoary decoction pieces are crushed and sieved by a No. 4 sieve, 8 times of water is added for about 6 hours of extraction, and the extraction rate is 1 to 2 percent.
Example 2 screening of optimal compatibility ratio of corydalis saxicola bunting total alkaloids and zedoary turmeric oil
1. Uniform design grouping
The total alkaloids of corydalis saxicola and zedoary turmeric oil are respectively 25-125 mg/kg-1And 25 to 200mg/kg-15 doses were selected as 5 levels (Table 1) from the above, according to the uniform design Table U5(54) Grouping was performed (table 2).
TABLE 1 two drugs level settings
TABLE 2 Uniform design U5(54) Factor level meter
2. Animal molding and administration method
By using CCl4Acute liver injury experimental model: 80 Kunming mice and males are selected and respectively arranged according to the uniformly designed test group, and animals are randomly grouped according to body weight, and each group comprises 10 animals.
The administration scheme is as follows: according to the uniform design table (table 2), animals are given different drugs, the gavage is given 0.2mL/10g, the normal group is given isovolumetric solvent (0.5% CMC-Na solution), the positive control group is given bifendate solution, 100 mg.kg < -1 >, the administration is carried out once a day, the continuous gavage is carried out for 7 days, and after the last administration, the animals are injected with 0.1% CCl in the abdominal cavity410ml.kg-1, after fasting for 16h, taking at least 0.5mL of blood from eyeball and placing in 1.5mL centrifuge tube, centrifuging at 3000r/min for 10min to prepare serum, centrifuging to separate serum for detecting alanine amino transferase (ALT), aspartic acid amino transferase (AST) and total bileActivity of bilirubin (TBIL).
3. Analysis of results
The results were analyzed using Excel analysis software, all data are expressed in x ± s, and the difference in variation between groups and between groups was examined by t (table 3).
TABLE 3 Effect of different compatibility ratios on serum indices of mice
Δ p < 0.01 (compared to blank control group), Δ p < 0.05 (compared to model group), and Δ p < 0.01.
The experimental results in table 3 show that: the serum ALT, AST and TBIL of the carbon tetrachloride model group is obviously increased compared with the normal group (P)<0.01), indicating that molding was successful. The two effective components can reduce ALT, AST and TBIL levels in serum in different compatibility proportion groups, and each index has significant difference (P) compared with model group<0.05) to prompt that the total alkaloids of corydalis saxicola is 25-125 mg/kg-125-200 mg/kg of zedoary turmeric oil-1Within range of compatibility to CCl4The liver of the mouse with the injury has obvious protective effect, and the curative effects are sequenced according to the following sequence: c>A≈D>B ≈ E, i.e.: group (corydalis saxicola bunting total alkali/mg kg)-1Zedoary turmeric oil/mg/kg-1)＝C(75、125)>A(125、150)≈D(50、100)>B(100、50)≈E(25、25)。
Example 3 verification of drug efficacy of corydalis saxicola bunting total alkaloids and zedoary turmeric oil
Using CCL4An acute liver injury experimental model is verified, and the protection effect of the compound with the optimal compatibility proportion (the compatibility in group 3 in example 2) on the acute liver injury of a mouse is verified, and the compound is compared with the single corydalis saxicola bunting total alkaloids and the single curcuma zedoary volatile oil.
60 ICR mice were randomized into 6 groups, each consisting of: the blank control group, the model group, the corydalis saxicola bunting total alkaloids group, the zedoary turmeric oil group, the compatibility group (C) and the bifendate group, the molding and administration methods are the same as those described in example 2, the administration dosage of the corydalis saxicola bunting total alkaloids group and the zedoary turmeric oil group is the same as the total amount of the medicines in the compatibility group, namely 275mg/kg, and the results are shown in Table 4:
TABLE 4 verification test of optimum compatibility
Δ p < 0.01 (compared to blank control group), Δ p < 0.05 (compared to model group), and Δ p < 0.01.
The results in table 4 show that the drug effect of the drug combination group selected in example 2 (the corydalis saxicola bunting total alkaloids and the zedoary turmeric oil are respectively administered in a 75mg/kg and 200mg/kg drug combination) is significantly better than that of the drug combination group using corydalis saxicola bunting total alkaloids or the zedoary turmeric oil alone, and the difference is significant (p is less than 0.05), which indicates that the drug combination of the corydalis saxicola bunting total alkaloids and the zedoary turmeric oil has significant synergistic effect and better liver protection effect.
Claims (2)
1. An application of a traditional Chinese medicine composition in preparing a medicine for treating acute liver injury is characterized in that: the traditional Chinese medicine composition is prepared from corydalis saxicola bunting total alkali and zedoary turmeric oil according to the following weight ratio: corydalis saxicola bunting total alkali: zedoary turmeric oil is 1: 2-2.67.
2. The use of claim 1, wherein: the traditional Chinese medicine composition is prepared from corydalis saxicola bunting total alkali and zedoary turmeric oil according to the following weight ratio: corydalis saxicola bunting total alkali: zedoary turmeric oil 1: 2.67.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1453277A (en) * | 2003-05-19 | 2003-11-05 | 吴梅春 | Meadowrueleaf corydalis general alkaloid and its prepn and application |
| CN101229235A (en) * | 2008-01-11 | 2008-07-30 | 南京弘景医药科技有限公司 | Process for preparing corydalis saxicola bunting total alkali |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1453277A (en) * | 2003-05-19 | 2003-11-05 | 吴梅春 | Meadowrueleaf corydalis general alkaloid and its prepn and application |
| CN101229235A (en) * | 2008-01-11 | 2008-07-30 | 南京弘景医药科技有限公司 | Process for preparing corydalis saxicola bunting total alkali |
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