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Application of icariin in preparation of drug for treating dutasteride-induced low-dihydrotestosterone epididymis infertility

A technology of dihydrotestosterone and dutasteride, applied in the field of medicine, can solve the problems of low sperm motility and fertility, abnormal structure and function of the epididymis, and obstacles to sperm maturation, etc.

Inactive Publication Date: 2019-08-13
SHANGHAI INST OF PLANNED PARENTHOOD RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Based on this, the inventor first established a low-androgen epididymal infertility rat model by inducing the dual 5α-reductase inhibitor dutasteride (this technology has been disclosed through the publication of papers, and the method is referring to Example 3). The target of infertility is the epididymis rather than the testis. This model was established by significantly reducing the level of dihydrotestosterone (DHT) in male rats through dutasteride, resulting in a low androgen state in rats, which in turn makes dihydrotestosterone-dependent Abnormalities in the structure and function of the epididymis (rather than the testis), resulting in impaired sperm maturation, resulting in low sperm motility and fertility

Method used

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  • Application of icariin in preparation of drug for treating dutasteride-induced low-dihydrotestosterone epididymis infertility
  • Application of icariin in preparation of drug for treating dutasteride-induced low-dihydrotestosterone epididymis infertility
  • Application of icariin in preparation of drug for treating dutasteride-induced low-dihydrotestosterone epididymis infertility

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Effects of icariin on proliferation of epididymis epithelial cells in male rats

[0053] Experimental Materials

[0054] Fetal bovine serum FBS, DMEM / F12 (1:1) culture medium, and HBSS were purchased from Gibco; trypsin and collagenase were purchased from Sigma; testosterone was purchased from China Resources Zizhu Pharmaceutical Co., Ltd.; CCK-8 was purchased from Dojindo Laboratories; DMSO was purchased from Sigma Company of the United States; icariin, CAS: 489-32-7, was purchased from Cayman Company, with a content of 98%.

[0055] experimental method

[0056] After the epididymis of male rats was digested in two steps with 0.25% trypsin and collagenase (1mg / ml), the rat epididymis epithelial cells were treated in vitro with DMEM / F12 medium (10% fetal bovine serum, 1nmol / L testosterone). Cultivate, establish the in vitro culture method of rat epididymis epithelial cells.

[0057] 0, 0.1, 1, 10, 100 μmol / L icariin acted on rat epididymis epithelial cells cultured i...

Embodiment 2

[0061] Reversal effect of icariin on epididymal epithelial cell apoptosis induced by dutasteride in male rats

[0062] Experimental Materials

[0063] Fetal bovine serum FBS, DMEM / F12 (1:1) culture medium, and HBSS were purchased from Gibco; trypsin and collagenase were purchased from Sigma; testosterone was purchased from China Resources Zizhu Pharmaceutical Co., Ltd.; CCK-8 was purchased from Dojindo Laboratories; DMSO was purchased from Sigma, USA; Dutasteride, CAS: 164656-23-9, was purchased from Hubei Gedian Renfu Pharmaceutical Co., Ltd., with a content of 99%; Icariin, CAS: 489-32-7, was purchased from From Cayman company, the content is 98%.

[0064] experimental method

[0065] After the epididymis of male rats was digested in two steps with 0.25% trypsin and collagenase (1mg / ml), the rat epididymis epithelial cells were treated in vitro with DMEM / F12 medium (10% fetal bovine serum, 1nmol / L testosterone). Cultivate, establish the in vitro culture method of rat epid...

Embodiment 3

[0070] Effects of icariin on sperm maturation and fertility induced by dutasteride in male epididymis infertile rats in vivo

[0071] Experimental Materials

[0072] SD rats were purchased from Shanghai Xipuer-Bikay Experimental Animal Co., Ltd., production license number SCXK (Shanghai): 2013-0016; Dutasteride, CAS: 164656-23-9, were purchased from Hubei Gedian Renfu Pharmaceutical Co., Ltd., content 99%; icariin, CAS: 489-32-7, purchased from Cayman Company, content 98%.

[0073] Drug configuration method:

[0074] Dutasteride: use 0.5% hydroxymethylcellulose sodium (CMC) to suspend and dissolve, the concentration is 2.5mg / ml, and store at 4°C for later use;

[0075] Icariin: Dissolved in 0.5% sodium hydroxymethylcellulose (CMC) containing 0.4% Tween80 at a concentration of 2.5 mg / ml, and stored at 4°C for later use;

[0076] experimental method:

[0077]Give 40mg / kg dutasteride to induce epididymis infertility rats by oral gavage administration, 1 time / day, and give ica...

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Abstract

The invention discloses application of icariin (a compound with a molecular formula C33H40O15) in preparation of a drug for treating dutasteride-induced low-dihydrotestosterone epididymis infertility,and belongs to the technical field of new application of drugs. The low-dihydrotestosterone epididymis infertility is derived from rodents, primates, lagomorphic animals, carnivorous animals and perissodactyl or artiodactyl animals, wherein the involved animals include humans, monkeys, rats, mice, rabbits, cats, dogs, cattle, horses, sheep and pigs. The treatment comprises the step of improving the sperm motility and fertility of animals suffering from dutasteride-induced low-dihydrotestosterone epididymis infertility. The drug comprises a therapeutically effective dose of the compound shownas a formula I and the balance carrier which is pharmaceutically acceptable. The drug can be made into oral preparations, transdermal preparations, injections, suppositories, microspherical slow-release preparations or subcutaneous implants. The drug has the advantages of being safe, effective and high in adaptability.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to the application of icariin in the preparation of a drug for treating dutasteride-induced hypodihydrotestosterone epididymal infertility. Background technique [0002] In recent years, male infertility and its treatment have attracted more and more attention. Due to environmental pollution, long-term trace element deficiency, bad living habits, long-term high stress, excessive smoking, drinking, abuse of hormonal drugs, sexually transmitted diseases and other factors, the reproductive capacity of modern humans, especially males, has shown a significant downward trend. According to statistics, 10% to 20% of married couples are infertile, of which 40% to 70% are caused by the man, and there is an increasing trend year by year. Male reproductive health has become a major issue affecting human reproduction. It is very necessary to carry out the research and treatment of male infertili...

Claims

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Application Information

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IPC IPC(8): A61K31/7048A61P15/00
CPCA61K31/7048A61P15/00
Inventor 谢淑武朱焰李国停钟瑞华杨文捷周洁芸郭湘洁李钊曹灿曹霖
Owner SHANGHAI INST OF PLANNED PARENTHOOD RES
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