US-12622890-B2 - Use of the active compound in the prevention or treatment of ovarian dysfunction diseases

Abstract

Use of the active compound in the present disclosure for the prevention or treatment of ovarian dysfunction disease. In particular, the present disclosure relates to the use of a compound shown in Formula I or a pharmaceutically acceptable salt thereof in the treatment or prevention of ovarian dysfunction disease, wherein R1 and R2 are each independently selected from H, C1-C6 alkyl, C1-C6 alkenyl, and C1-C6 alkynyl. The present disclosure also relates to the use of a compound shown in said Formula I or a pharmaceutically acceptable salt thereof, in combination with hyodeoxycholic acid or a pharmaceutically acceptable salt thereof, in the treatment or prevention of ovarian dysfunction disease. The present disclosure also relates to compositions comprising a compound shown in said Formula I or a pharmaceutically acceptable salt thereof and/or hyodeoxycholic acid or a pharmaceutically acceptable salt thereof.

Inventors

• Cuiling Lu
• Tao Jiang
• Yanxiao YI

Assignees

• INSTITUTE OF BIOPHYSICS, CHINESE ACADEMY OF SCIENCES

Dates

Publication Date

20260512

Application Date

20220902

Priority Date

20220427

Claims (13)

1. 1 . A method of treatment or prevention of ovarian dysfunction diseases comprising administering a compound of Formula I or a pharmaceutically acceptable salt thereof wherein: R1 and R2 are each independently selected from H, C1-C6 alkyl group, C1-C6 alkenyl group or C1-C6 alkyne group; administering hyodeoxycholic acid or its pharmaceutically acceptable salt; and wherein the ovarian dysfunction diseases are treated.
2. 2 . The method of claim 1 , wherein R1 and R2 are each independently selected from the H or C1-C6 alkyl groups.
3. 3 . The method of claim 1 , wherein the ovarian dysfunction diseases is selected from the group consisting of premature ovarian insufficiency, premature ovarian failure, diminished ovarian reserve, poor ovarian response, early menopause, impaired ovarian function, insufficient ovarian function, lowered ovarian function.
4. 4 . The method of claim 1 , wherein the ovarian dysfunction disease is caused by genetic factors, iatrogenic factors, immunologic factors, environmental factors, physical advanced age, and a combination thereof.
5. 5 . The method of claim 1 wherein the compound shown in Formula I or a pharmaceutically acceptable salt thereof is administered simultaneously or sequentially with hyodeoxycholic acid or a pharmaceutically acceptable salt thereof.
6. 6 . A composition for the prevention or treatment of ovarian disorders, which is characterized in that wherein the composition comprises a compound of Formula I or a pharmaceutically acceptable salt thereof, and hyodeoxycholic acid and a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently selected from H, C1-C6 alkyl group, C1-C6 alkenyl group or C1-C6 alkyne group; and hyodeoxycholic acid; and a pharmaceutically acceptable excipient.
7. 7 . The composition of claim 6 , wherein R1 and R2 are each independently selected from H or C1-C6 alkyl groups.
8. 8 . The composition of claim 6 , wherein the composition is in the form of a tablet, capsule, solution, granule, pill, powder, ointment, elixir, suspension, dust, injection, suppository, cream, spray or patch.
9. 9 . The method of claim 1 , wherein R1 and R2 are each independently selected from the H or C1-C5 alkyl groups.
10. 10 . The method of claim 1 , wherein R1 and R2 are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, and n-pentyl groups.
11. 11 . The method of claim 3 , wherein further comprises the administration of hyodeoxycholic acid or its pharmaceutically acceptable salt to relieve oxidative stress damage, restore sex hormone secretion, and restore ovulation.
12. 12 . The composition of claim 7 , wherein R1 and R2 are each independently selected from the H or C1-C5 alkyl groups.
13. 13 . The composition of claim 11 , wherein R1 and R2 are each independently selected from H, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, and n-pentyl groups.

Description

This application is the National Stage filing under 35 U.S.C. 371 of International Application No. PCT/CN2022/116863, filed Sep. 2, 2022, which claims the benefit of Chinese Provisional Application No. 202210453982.4, filed Apr. 27, 2022. The disclosures of each of these applications are incorporated herein by reference. TECHNICAL FIELD The invention relates to methods and drugs for preventing or treating ovarian dysfunction diseases. BACKGROUND OF THE INVENTION The ovary is an important reproductive and endocrine organ of female animals. Its functions include ovulation and secretion of hormones (such as steroid hormones, estrogen and progesterone). When the ovarian function is dysregulated, such as abnormal follicle maturation or reduced secretion of steroid hormones, a series of ovarian dysfunction diseases will be triggered, such as follicle development, maturation or ovulation failure, patients may suffer from infertility, spontaneous abortion and premature senescence, and also affect the endocrine function of the ovary. At present, hormone replacement therapy and assisted reproduction therapy are the main treatments of ovarian dysfunction diseases. Hormone replacement therapy can effectively improve estrogen and serum FSH level in short-term, but with more side effects and contraindications, such as gastrointestinal discomfort, weight gain, increased risk of endometrial cancer, breast cancer and other gynecological cancers. Use of estrogen can also increase the risk of venous thrombosis with poor long-term curative effect. At the same time, clinically, patients have a certain psychological burden for hormone therapy or refuse to use hormone therapy. Assisted reproductive therapy, is expensive and mostly unavailable for patients who are anovulation or ovulating sparsely. Importantly, there are no clear and effective strategies to prevent and delay ovarian dysfunction diseases. Therefore, it is urgent to find a new drug with obvious effect and low side effects for the prevention or treatment of ovarian dysfunction diseases. THE INVENTION CONTENTS To address one of the above technical problems, this disclosure provided drugs and methods for the treatment or prevention of ovarian dysfunction diseases. After treatment with drugs in this disclosure, ovarian function can be effectively restored, and follicle development and ovulation can be promoted. According to one aspect of this disclosure, the application of the compounds shown in Formula I or their pharmaceutically acceptable salts in the treatment or prevention of ovarian dysfunction diseases is provided, Among them, R1 and R2 are each independently selected from H, C1-C6 alkyl group, C1-C6 alkenyl group and C1-C6 alkyne group. According to some embodiments, R1 and R2 can be each independently selected from H. According to some embodiments, R1 and R2 can be each independently selected from branched or straight chain C1-C6 alkyl groups. According to specific embodiments, R1 and R2 can be each independently selected from branched or straight chain C1-C5 alkyl groups. According to specific embodiments, R1 and R2 can be each independently selected from branched or straight chain C1-C4 alkyl groups. According to specific embodiments, R1 and R2 can be each independently selected from branched or straight chain C1-C3 alkyl groups. According to specific embodiments, R1 and R2 can be each independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, or n-pentyl groups. According to some embodiments, R1 and R2 can be each independently selected from the branched or straight chain C1-C6 alkenyl groups. According to specific embodiments, R1 and R2 can be each independently selected from the branched or straight chain C1-C5 alkenyl groups. According to specific embodiments, R1 and R2 can be each independently selected from branched or straight chain C1-C4 alkenyl groups. According to specific embodiments, R1 and R2 can be each independently selected from branched or straight C1-C3 alkenyl groups. According to specific embodiments, R1 and R2 can be each independently selected from vinyl, propylene, butenyl, or pentenyl groups. According to some embodiments, R1 and R2 can be each independently selected from branched or straight C1-C6 alkynyl groups. According to specific embodiments, R1 and R2 can be each independently selected from the branched or straight C1-C5 alkyne group. According to specific embodiments, R1 and R2 can be each independently selected from branched or straight C1-C4 alkyne groups. According to specific embodiments, R1 and R2 can be each independently selected from branched or straight C1-C3 alkyne groups. According to specific embodiments, R1 and R2 can be each independently selected from acetylene, propylene, or butyne groups. According to some embodiments, R1 and R2 can be the same or different. According to some embodiments, the ovarian dysfunction diseases may include, but are not limited to, premature ovarian