A kind of anti-hepatic fibrosis composition and its application

A liver fibrosis and compound technology, applied in the field of medicine, can solve problems such as gastrointestinal reactions, achieve clear mechanism, enhance therapeutic effect, and reduce the degree of liver fibrosis

Active Publication Date: 2022-06-07
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, with the gradual and in-depth research on the mechanism of liver fibrosis, it is found that if one wants to block or even reverse the development of liver fibrosis in the stage of liver fibrosis, it is impossible to achieve only one method or one pathogenic pathway. The clinical application of flavonoid lignans alone requires long-term use and causes some side effects such as gastrointestinal reactions
[0003] At present, there is no internationally recognized drug that is safe, effective, liver-targeted, and long-term tolerated by the FDA for the treatment of liver fibrosis. The treatment of liver fibrosis is limited to controlling the etiology, including hepatitis B and C Main antiviral therapy and continuous anti-inflammatory therapy, etc.

Method used

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  • A kind of anti-hepatic fibrosis composition and its application
  • A kind of anti-hepatic fibrosis composition and its application
  • A kind of anti-hepatic fibrosis composition and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Silybin and Leoceque compositions for the treatment of liver fibrosis model mice

[0030]In addition to the normal control group, the mice with successful molding were randomly divided into model control group (Model-control), silybin group (6mg / kg, iv), Leocerin group (1mg / kg, iv), silybin and Leoceque composition group, each experimental group of 6 mice, given once a day, administered for 4 weeks, a total of 28 times, and recorded mouse weight changes during the experiment. The dosage administered in the composition group is consistent with the dose of each drug in the monotherapy group. All groups of mice were administered until the last day of the experiment, weighed 12 h in advance and fasted and did not tolerate water. After peeling off the large lobes of the liver, wash them with pre-chilled normal saline, take roughly the same parts in 4% paraformaldehyde solution and fix them, and then perform embedding, sectioning and Sirius red staining.

[0031] as Figure 1-5 As...

Embodiment 2

[0033] Silybin and Leocetin anti-hepatic fibrosis dose screening study

[0034] The molded animals after 4 weeks of liver fibrosis molding were randomly divided into four groups, the module group, silybin 6mg / kg + leocerin 0.5mg / kg group, silybin 6mg / kg + leosixin 1mg / kg group, silybin 1mg / kg + leosique 1mg / kg group, each group of 6 mice, respectively, the concentration of silybin 6mg / kg + liosic 0.5mg / kg, silybin 1mg / kg + liosicin 1mg / kg, silybin 6mg / kg, silybin 6mg / kg respectively, respectively, the concentration of silybin 6mg / kg + silybin 0.5mg / kg, silybin 1mg / kg, silybin 6mg / kg Kg + Leocet 1 mg / kg three groups of suspension drug solution, tail vein administration, every 3 days to administer once, a total of 10 times. After the end of administration, the liver lobe was peeled off and washed with pre-cooled normal saline, and after fixation of roughly the same part in 4% paraformaldehyde solution, it was embedded, sliced and stained with Sirius red, and positive area analysi...

Embodiment 3

[0037] Drug carrier-loaded silybin and leoceque compositions for the treatment of liver fibrosis

[0038] Preparation of PAMAM micelles of silybin: weigh silybin 6mg, add 0.6mL of methanol, ultrasonically dissolve to make a methanol solution of silybin, dissolve PAMAM 15mg in 1.5mL of double distilled water to form a carrier solution, add the methanol solution of silybin to the carrier solution dropwise, and stir for 3h after the completion of the drops. Dialysis in a dialysis bag (MWCO= 1000) for 24h, 3000 rpm centrifugation for 10min, take the supernatant lyophilized, that is, the PAMAM micelle of silybin.

[0039] PAMAM micelle preparation of Liosicine: According to the PAMAM micelle preparation method of silybin, replace "silybin 6mg" with "Leosimine 1mg", that is, The PAMAM micelle of Leosilana.

[0040] MPP micelle preparation of silybin: weigh silybin 6mg, add methanol 0.6mL, ultrasonically dissolve to make a methanol solution of silybin, dissolve mPP 20mg in 2mL double dis...

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Abstract

The invention discloses an anti-hepatic fibrosis composition and its application, belonging to the technical field of medicine. Composition of flavonoid lignan compound and soluble guanylate cyclase agonist can improve liver fibrosis in mice in thioacetamide liver fibrosis model. The present invention better cures liver fibrosis or provides another feasible option for treating liver fibrosis, and improves the prognosis or quality of life of patients.

Description

Technical field [0001] The present invention belongs to the field of medical technology, specifically relates to a pharmaceutical composition and its application in the preparation of hepatic fibrosis therapeutic drugs. Background [0002] Liver disease is a major health problem worldwide, with 4.6% of liver disease deaths and 62.6% of global liver disease deaths in the Asia-Pacific region, which accounts for more than half of the global population, in 2015. Liver damage can be caused by a variety of liver diseases, including chronic hepatitis B virus infection, chronic hepatitis C virus infection, and alcoholic, nonalcoholic fatty liver disease. Liver fibrosis is caused by abnormal proliferation and deposition of fibrous connective tissue in the liver during post-injury repair, and the deposited collagen fibers constitute a barrier for drug delivery, preventing drug delivery to damaged cells and making it difficult to repair damage, resulting in liver fibrosis further developing...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K31/357A61K31/506A61K38/10A61P1/16
CPCA61K45/00A61K31/357A61K31/506A61K38/10A61P1/16A61K2300/00Y02A50/30
Inventor 姚静崔琴乔佳男
Owner CHINA PHARM UNIV
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