CN-122005541-A - Use of dihydroartemisinin in preparation of medicine for preventing, delaying and/or treating ovarian aging and related diseases thereof

Abstract

The invention relates to application of dihydroartemisinin in preparation of a medicament for preventing, delaying and/or treating ovarian aging and related diseases thereof. The present invention for the first time has found that dihydroartemisinin is effective in the prevention, delay and/or treatment of ovarian aging, which includes ovarian fibrosis and the resulting age-related fertility decline. Dihydroartemisinin remarkably improves the structure and function of ovaries through multi-target synergistic effects of adjusting reproductive endocrine, inhibiting senescence-associated phenotype, resisting ovarian fibrosis and the like, and is particularly characterized by recovering estrus cycle, increasing weight of ovaries, and increasing ovulation quantity and litter size. In addition, the invention also proves that the dihydroartemisinin has the potential of preventing fertility from decreasing in a middle-aged model, has good safety, does not damage main organs and reproductive organs, has normal liver and kidney function indexes, and provides a new strategy for clinically intervening ovarian aging.

Inventors

• YU YANG
• GU MENGQING
• LI JIALIN
• ZENG ZHONGHONG

Assignees

• 北京大学第三医院（北京大学第三临床医学院）

Dates

Publication Date

20260512

Application Date

20260312

Claims (10)

1. 1. Use of dihydroartemisinin or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the prevention, delay and/or treatment of ovarian aging and related diseases.
2. 2. The use according to claim 1, wherein the dihydroartemisinin or a pharmaceutically acceptable salt thereof is the only active ingredient in the medicament.
3. 3. Use according to claim 1, wherein the medicament further comprises other active ingredients for preventing, delaying and/or treating ovarian aging and related diseases.
4. 4. The use according to any one of claims 1 to 3, wherein the ovarian failure is a natural decline in ovarian function associated with aging.
5. 5. Use according to any one of claims 1 to 4, wherein the prevention, delay and/or treatment of ovarian aging is selected from one or both of the following: (1) Preventing, delaying and/or treating ovarian fibrosis; (2) Preventing, delaying and/or treating female age-related fertility decline.
6. 6. The use of claim 5, wherein the prevention, delay and/or treatment of ovarian fibrosis is manifested as a reduction of collagen deposition in ovarian tissue.
7. 7. Use according to claim 5, wherein the prevention, delay and/or treatment of female age-related fertility decline is manifested by one or more of the following: (a) Increasing ovarian weight; (b) Increasing the number of ovulations; (c) Increasing the number of live products; (d) Increasing the proportion of individuals with fertility; (e) Recovering the regular estrus cycle.
8. 8. The use according to any one of claims 1 to 7, wherein the medicament further comprises a pharmaceutically acceptable adjuvant.
9. 9. The use according to claim 8, wherein the pharmaceutically acceptable excipients are selected from one or more of carriers, surfactants, preservatives, antioxidants, hardeners, thickeners and absorption promoters.
10. 10. Use according to any one of claims 1 to 9, wherein the dosage form of the medicament is selected from one or more of suppositories, tablets, capsules, granules, drops and injections, preferably injections.

Description

Use of dihydroartemisinin in preparation of medicine for preventing, delaying and/or treating ovarian aging and related diseases thereof Technical Field The invention belongs to the technical field of medicine application. In particular, the invention relates to the use of dihydroartemisinin in the preparation of a medicament for the prevention, delay and/or treatment of ovarian aging and related diseases. Background The ovaries, which are the earliest organs of female reproductive system with reduced function, typically accelerate significantly after age 30, are characterized by reduced number of oocytes and reduced quality, which in turn results in an irreversible decrease in female fertility with age. With the widespread delay of female fertility age worldwide, age-related infertility has become a major clinical problem to be solved urgently in the reproductive medicine field. The molecular mechanisms of ovarian aging are extremely complex involving interactions of multiple signaling pathways such as telomere depletion, oxidative stress imbalance, accumulation of advanced glycation end products, DNA damage accumulation, chronic low-grade inflammation, and mitochondrial dysfunction. However, there is still a lack of a strictly validated safety intervention in the current clinical practice that can effectively delay or even reverse the decline of ovarian function. Of note, recent studies have revealed that ovarian aging is often accompanied by the occurrence of tissue fibrosis. Significant increases in collagen fiber deposition were observed in ovarian tissue in both natural postmenopausal women and reproductive aging animal models, suggesting that fibrosis may be one of the important pathological features of hypoovariance. Fibrosis is essentially due to the continued activation of fibroblasts, resulting in excessive deposition of extracellular matrix and abnormal proliferation of connective tissue, thereby destroying normal organ structure and function. Fibrosis has been shown to trigger progressive dysfunction and even organ failure in organs such as the lung, liver, etc., but in the area of ovarian aging, studies on fibrosis remain in the initiation phase. The existing anti-fibrosis drugs in global scale mainly comprise pirfenidone and nidazole, and the pirfenidone and the nidazole can delay the fibrosis progress of partial organs (such as lung) by inhibiting inflammatory signal pathways, but the curative effect is mainly reflected in delaying the course of disease rather than reversing formed fibrosis lesions, and the safety and organ specificity of long-term application are still limited. Furthermore, the occurrence mechanism and pathological characteristics of fibrosis are significantly different among different organs, for example, heart fibrosis mainly relates to factors such as pressure load, ischemia injury and the like, and mainly comprises reactive fibrosis, while ovarian fibrosis is a progressive pathological change under the combined action of multiple factors such as chronic inflammation, oxidative stress, hormone level change and the like in the aging process. Fibrosis of different organs has significant differences in cell sources, signaling pathways, microenvironment regulation, etc., which makes it difficult to directly infer an effective anti-fibrosis strategy for one organ to other organs. Up to now, no clinical therapeutic drug specific to ovarian fibrosis has been developed. Therefore, the development of a medicine capable of effectively preventing, delaying or even reversing the ovarian aging is not only an urgent need for coping with the increasingly serious age-related fertility problems in the global scope, but also a major break opening for filling the blank of the current anti-fibrosis treatment in the field of reproductive systems. Disclosure of Invention In view of the above problems, it is an object of the present invention to provide a medicament for preventing, delaying and/or treating ovarian aging and related diseases. The inventor finds that Dihydroartemisinin (DHA) can effectively prevent, delay and/or treat ovarian aging, comprises ovarian fibrosis and age-related fertility decline caused by ovarian fibrosis, has the potential of preventing fertility decline, is good in safety, does not damage main organs and reproductive organs, and provides a new strategy for clinically intervening in ovarian aging. Thus, the invention provides the use of dihydroartemisinin in the preparation of a medicament for the prevention, delay and/or treatment of ovarian aging and related diseases thereof. The above object of the present invention is achieved by providing the following technical solutions: the invention provides application of dihydroartemisinin or pharmaceutically acceptable salt thereof in preparation of medicines for preventing, delaying and/or treating ovarian aging and related diseases thereof. According to some embodiments of the invention, the dihydroartemisinin or a p