阅读说明：本技术 一种抗肝纤维化的药物组合物及其应用 (Anti-hepatic fibrosis pharmaceutical composition and application thereof ) 是由 成秋宸 覃雯 卓朗 于 2019-09-25 设计创作，主要内容包括：本发明公开了抗肝纤维化的药物组合物及其应用,该组合物是由以下重量份的原料药制备而成的制剂：Chitosan 1-5份,Genistein 2-10份,EGCG 3-15份,Taurine 20-100份；本发明的组合物应用在制备抗肝纤维化药物中；该组合物通过多靶点作用肝纤维化通路,提高肝脏细胞抗氧化、抗炎、抗纤维化的能力,延缓或逆转模型动物的肝纤维化进程,无明显肝毒性,质量稳定可控,来源广泛等特点,在抗肝纤维化上有良好的应用前景。(The invention discloses an anti-hepatic fibrosis pharmaceutical composition and application thereof, wherein the composition is a preparation prepared from the following raw material medicines in parts by weight: 1-5 parts of Chitosan, 2-10 parts of Genistein, 3-15 parts of EGCG and 20-100 parts of Taurine; the composition of the invention is applied to the preparation of anti-hepatic fibrosis drugs; the composition has the characteristics of improving the oxidation resistance, anti-inflammation and anti-fibrosis capability of liver cells, delaying or reversing the hepatic fibrosis process of model animals, having no obvious hepatotoxicity, stable and controllable quality, wide sources and the like through a multi-target-point acting hepatic fibrosis pathway, and has good application prospect in resisting hepatic fibrosis.)

1. The anti-hepatic fibrosis pharmaceutical composition is characterized by being a preparation prepared from the following raw material medicines in parts by weight: 1-5 parts of Chitosan, 2-10 parts of Genistein, 3-15 parts of EGCG and 20-100 parts of Taurine.

2. The anti-hepatic fibrosis pharmaceutical composition of claim 1, wherein the composition is prepared from the following raw materials in parts by weight: 2-4 parts of Chitosan, 4-8 parts of Genistein, 6-12 parts of EGCG and 40-80 parts of Taurine.

3. The anti-hepatic fibrosis pharmaceutical composition of claim 1, wherein the composition is prepared from the following raw materials in parts by weight: chitosan 3 parts, Genistein 6 parts, EGCG 9 parts and Taurin 60 parts.

4. The anti-hepatic fibrosis pharmaceutical composition of claim 1, wherein the composition is prepared from raw material drugs as active ingredients and pharmaceutically common adjuvants or auxiliary ingredients, and is in various dosage forms suitable for clinical application.

5. The anti-hepatic fibrosis pharmaceutical composition according to claim 1, wherein the composition is prepared by the following method:

s1: weighing the raw material medicines according to the parts by weight;

S2: the raw material medicines are taken as active ingredients, and are added with auxiliary materials or auxiliary ingredients commonly used in pharmacy to prepare various preparation formulations suitable for clinical application.

6. Use of the pharmaceutical composition according to any one of claims 1-5 as an active ingredient for the preparation of a medicament for treating liver fibrosis.

Technical Field

The invention relates to the technical field of medicines, in particular to an anti-hepatic fibrosis pharmaceutical composition and application thereof.

Background

more than 10% of the world suffer from chronic liver disease, with more than 1 million patients suffering from liver fibrosis and more than 100 million patients dying from liver fibrosis each year. Hepatic fibrosis is the etiology of chronic viral hepatitis, cholestasis, drug-induced liver injury, parasitic infection, chronic alcoholic liver disease and autoimmune hepatitis, acts on the liver, is a compensation reaction in the process of repairing inflammatory injury, and is a necessary way for the progress to cirrhosis. The hepatic fibrosis is considered to have reversible stage, so the hepatic fibrosis becomes the best period of clinical medicine intervention reversion, and the hepatic fibrosis is delayed, prevented, even reversed, and the liver fibrosis has important significance for improving the liver function of a patient, delaying the formation of liver cirrhosis and complications thereof, improving the life quality of the patient and prolonging the life cycle of the patient.

So far, an ideal scheme for treating hepatic fibrosis is still lacking at home and abroad, and an anti-hepatic fibrosis drug approved by the Food and Drug Administration (FDA) is not available. Because the molecular mechanism of hepatic fibrosis is complex, multiple molecular pathways are involved, and a drug with a single target point hardly has good drug effect. Achieving multi-target treatment of liver fibrosis remains a problem that needs to be solved urgently.

Disclosure of Invention

The invention overcomes the technical problems that medicines with single target points hardly have good drug effect because the molecular mechanism of hepatic fibrosis is complex and relates to a plurality of molecular paths in the prior art, provides the application of a natural product pharmaceutical composition in treating hepatic fibrosis, improves the anti-oxidation, anti-inflammation and anti-fibrosis capability of liver cells through multi-target point action of hepatic fibrosis paths, and delays or reverses the hepatic fibrosis process, thereby achieving the purpose of treating hepatic fibrosis.

In order to solve the problems, the invention adopts the following technical scheme:

the anti-hepatic fibrosis pharmaceutical composition is a preparation prepared from the following raw material medicines in parts by weight: 1-5 parts of Chitosan, 2-10 parts of Genistein, 3-15 parts of EGCG and 20-100 parts of Taurine.

Chitosan (Chitosan), Genistein (Genistein), EGCG (gallocatechin gallate) and Taurine (Taurine) in the raw material medicines are natural products; wherein Chitosan is obtained by deacetylating active ingredients extracted from the epidermis of crustacean, Genistein is active ingredients extracted from fructus Sophorae and radix Sophorae Tonkinensis, EGCG is active ingredient extracted from folium Camelliae sinensis, and Taurin is active ingredient extracted from marine fish, and can be synthesized chemically economically; the extraction method of the raw material medicines comprises the following steps: and (3) extracting with alcohol.

In the invention, the composition is a preparation prepared from the following raw material medicines in parts by weight: 2-4 parts of Chitosan, 4-8 parts of Genistein, 6-12 parts of EGCG and 40-80 parts of Taurine.

In the invention, the composition is a preparation prepared from the following raw material medicines in parts by weight: chitosan 3 parts, Genistein 6 parts, EGCG 9 parts and Taurin 60 parts.

In the invention, the composition is prepared from raw material medicines serving as active ingredients and pharmaceutically common auxiliary materials or auxiliary ingredients, and is suitable for various formulations in clinical application; such formulations include, but are not limited to: granule, capsule, tablet, oral liquid, and injection.

In the invention, further, the composition is prepared by the following method:

S1: weighing the raw material medicines according to the parts by weight;

S2: the raw material medicines are taken as active ingredients, and are added with auxiliary materials or auxiliary ingredients commonly used in pharmacy to prepare various preparation formulations suitable for clinical application.

the invention also aims to protect the application of the pharmaceutical preparation which takes the anti-hepatic fibrosis pharmaceutical composition as an active ingredient in preparing anti-hepatic fibrosis drugs.

The pharmaceutically acceptable auxiliary materials of the present invention refer to substances contained in the dosage form in addition to the active ingredients, and include, but are not limited to, fillers (diluents), lubricants (glidants or anti-adherents), dispersants, wetting agents, binders, regulators, solubilizers, antioxidants, bacteriostats, emulsifiers, disintegrants, and the like. The binder comprises syrup, acacia, gelatin, sorbitol, tragacanth, cellulose and its derivatives (such as microcrystalline cellulose, sodium carboxymethylcellulose, ethyl cellulose or hydroxypropyl methylcellulose), gelatin slurry, syrup, starch slurry or polyvinylpyrrolidone; the filler comprises lactose, sugar powder, dextrin, starch and its derivatives, cellulose and its derivatives, inorganic calcium salt (such as calcium sulfate, calcium phosphate, calcium hydrogen phosphate, precipitated calcium carbonate, etc.), sorbitol or glycine, etc.; the lubricant comprises superfine silica gel powder, magnesium stearate, talcum powder, aluminum hydroxide, boric acid, hydrogenated vegetable oil, polyethylene glycol and the like; the disintegrating agent comprises starch and its derivatives (such as sodium carboxymethyl starch, sodium starch glycolate, pregelatinized starch, modified starch, hydroxypropyl starch, corn starch, etc.), polyvinylpyrrolidone or microcrystalline cellulose, etc.; the wetting agent comprises sodium lauryl sulfate, water or alcohol, etc.; the antioxidant comprises sodium sulfite, sodium bisulfite, sodium pyrosulfite, dibutylbenzoic acid, etc.; the bacteriostatic agent comprises 0.5% of phenol, 0.3% of cresol, 0.5% of chlorobutanol and the like; the regulator comprises hydrochloric acid, citric acid, potassium (sodium) hydroxide, sodium citrate, and buffer (including sodium dihydrogen phosphate and disodium hydrogen phosphate); the emulsifier comprises polysorbate-80, sorbitan fatty acid, pluronic F-68, lecithin, soybean lecithin, etc.; the solubilizer comprises Tween-80, bile, glycerol, etc.

the pharmaceutically acceptable auxiliary components have certain physiological activity, but the addition of the components does not change the dominance of the compounds or derivatives in the process of treating diseases, but only plays an auxiliary effect, and the auxiliary effects are only the utilization of the known activity of the components and are auxiliary treatment modes which are conventional in the field of medicine. If the auxiliary components are used in combination with the compound of the present invention, the protection scope of the present invention should still be included.

The applicant, based on many years of medical work experience combined with numerous medical tests, briefly describes the effects of the pharmaceutical components of the present application and the principle of action of the present application in treating liver fibers as follows:

Chitosan (Chitosan) as a biological material has biocompatibility, is non-toxic and non-immunogenic, can inhibit scar formation to different degrees, participates in bile acid metabolism, reduces the absorption of bile acid by organisms, relieves the damage of lipid peroxidation of liver cells to the integrity of mitochondrial membranes, protects liver cell membranes, inhibits the apoptosis of liver cells, repairs liver injury of rats, and accordingly relieves hepatic fibrosis.

Genistein has effects of resisting oxidation, inhibiting immune activation and hepatic stellate cell proliferation, reducing collagen synthesis and extracellular matrix deposition in stellate cells stimulated by TGF-beta 1 in a concentration-dependent manner, synergistically eliminating free radicals by increasing activity and expression of hepatic antioxidant enzyme, reducing expression of alpha-SMA, blocking expression of fibroblast growth factor PDGF, and resisting fibrosis in vitro.

EGCG (gallocatechin gallate) reduces oxidative stress by removing ROS and LPO in HSC cells, inhibits the growth of HSC by inhibiting a Rho signal pathway, can inhibit the generation of collagen and the activity of collagenase to inhibit the synthesis of collagen, and can reduce the expression of MMPs (MMPs), thereby inhibiting hepatic fibrosis.

taurine (Taurine) is a sulfur-containing beta-amino acid, is one of the main components of the rare Chinese medicinal bezoar, is a self-anti-injury substance widely existing in vivo, and can promote bile excretion, inhibit hepatic stellate cells of rats in vitro, inhibit proliferation and collagen synthesis of fibroblasts, and inhibit deposition of extracellular matrix of liver cells of rats so as to relieve the degree of hepatic fibrosis. Research shows that taurine reduces the resistance of blood vessels in the liver by regulating NO signal conduction path, thereby regulating the blood microcirculation of the liver, improving the liver function and inhibiting the liver fibrosis.

Due to the adoption of the technical scheme, the invention at least comprises the following beneficial effects:

(1) The pharmaceutical composition is cut in from the main pathological mechanism of fibrosis, and four natural products of Chitosan (Chitosan), Genistein (Genistein), EGCG (gallocatechin gallate) and Taurine (Taurine) are selected for combination, so as to achieve the purpose of treating hepatic fibrosis by multiple routes and multiple targets; wherein Chitosan has the functions of reducing cholesterol, inhibiting bacteria, preventing and controlling hypertension and good biocompatibility. Genistein has estrogen-like effect of soybean isoflavone, and has effects of resisting oxidation, resisting tumor, inhibiting bacteria, reducing blood lipid, and resisting hepatic fibrosis. EGCG is the most effective active component in green tea catechin extract, is a compound containing multiple phenolic hydroxyl groups, has multiple drug effects of resisting virus, oxidation, arteriosclerosis, thrombosis, angiogenesis, bacteria, inflammation and tumor, and has oxidation resistance higher than that of ascorbic acid. Taurine is an amino acid converted from sulfur-containing amino acid, and has the drug effects of resisting inflammation, reducing blood pressure, reducing blood sugar, resisting arrhythmia, resisting bacteria, enhancing immunity, benefiting gallbladder, strengthening liver and the like; research proves that Chitosan, Genistein, EGCG and Taurine are prepared into a compound, and the compound can inhibit the hyperplasia of lipid storage cells, reduce the synthesis of collagen, promote liver repair, regulate the blood microcirculation of liver and achieve the aim of resisting hepatic fibrosis by the synergistic action of the medicines in the aspects of anti-inflammation, anti-necrosis, liver cell protection and the like.

(2) The invention has the uniqueness that the liver fibrosis pathway is acted by multiple targets, the anti-oxidation, anti-inflammation and anti-fibrosis capability of liver cells is improved, the liver fibrosis process of model animals is delayed or reversed, the liver fibrosis is free from obvious hepatotoxicity, the quality is stable and controllable, the sources are wide, and the like, and the liver fibrosis resistant liver cancer.

(3) When the pharmaceutical composition is applied to the process of treating hepatic fibrosis, the pharmaceutical composition can be compounded with other medicines or medicine carriers to prepare preparations such as granules, capsules, tablets, oral liquid, injection and the like, the proportion of the components forming the preparation has a synergistic effect, the content of active ingredients is high, the use and carrying are convenient, the oral administration and absorption are rapid, the bioavailability is high, and the prevention and treatment effect is obvious through animal test verification.

Drawings

FIG. 1 is a graph showing the effect of CGET on the pathological structure of liver tissue and the degree of liver fibrosis of a liver fibrosis rat through HE staining of liver tissue sections of seven groups of rats;

FIG. 2 shows the effect of CGET on pathological structure of liver tissue and degree of liver fibrosis in rats by Sirius red staining of liver tissue sections of seven groups of rats.

In the figure, a is a control group, B is a model group, C is a drug low-dose group a, D is a drug low-dose group B, E is a drug low-dose group C, F is a drug medium-dose group, and G is a drug high-dose group.

The specific figure analysis is shown in an experimental method.

Detailed Description

The present invention will be further described with reference to examples and tests.