CN-121987758-A - Application of SS-31 in preparation of fertility improving drugs

Abstract

The invention relates to an application of SS-31 in preparation of a medicament for improving fertility, and belongs to the technical field of medicaments. The use of SS-31 in the manufacture of a medicament for improving fertility, including the use of SS-31 in the manufacture of a medicament for improving mitochondrial function and metabolism to increase fertility in a mammal and/or a human. The invention uses intraperitoneal injection of SS-31 to prove that the invention can precisely reverse the ovarian mitochondrial dysfunction and oxidative stress of the aged mice, remodel the follicular microenvironment and obviously restore the fertility potential, and in addition, the invention draws a molecular roadmap for remedying the fertility of the aged mice by the SS-31 for the first time, namely, takes the dynamic imaging of an ovarian single cell transcriptome and living cells as an entry point, and the SS-31 plays the protection effect through a mitochondrial-VEGF axis. Not only lays a theoretical foundation for the clinical transformation of SS-31, but also provides a verifiable new paradigm for targeting mitochondrial-VEGF interactive regulation and control and delaying reproductive aging.

Inventors

• SUN SHAOCHEN
• ZHANG HAOLIN
• WANG YUE

Assignees

• 南京农业大学

Dates

Publication Date

20260508

Application Date

20260105

Claims (3)

1. The application of SS-31 in preparing medicine for improving fertility is characterized by comprising the application of SS-31 in preparing medicine for improving mitochondrial function and metabolism, optimizing oocyte quality, activating ovarian potential and improving mammal fertility.
2. 2. The use of SS-31 in the manufacture of a medicament for improving fertility, according to claim 1, comprising the use of SS-31 in the manufacture of a medicament for treating a decrease in fertility in a senescent mammal.
3. 3. The method of claim 2, wherein the fertility-improving agent is SS-31, and wherein the fertility-improving agent is SS-31.

Description

Application of SS-31 in preparation of fertility improving drugs Technical Field The invention relates to an application of SS-31 in preparation of a medicament for improving fertility, and belongs to the technical field of medicaments. Background The traditional definition of advanced parturients (AMA) is that the age is more than or equal to 35 years old, and the main basis is that the abortion and the risk of fetal chromosomal aneuploidies in this age group are significantly increased. Statistics have shown that miscarriages from aneuploidy occur more frequently in women over 40 years old than young women. Age-related reduced oocyte quality is a key indicator of ovarian aging. Failure of cytoplasmic maturation by aging is associated with mitochondrial dysfunction, altered mitochondrial biogenesis, altered mitochondrial morphology, distribution, activity and kinetics, smooth endoplasmic reticulum deformity and calcium interference, and altered cytoskeleton. Many studies have shown that age-related changes in oocyte energy metabolism may affect oocyte quality. Mitochondria are key organelles that provide energy for ovum maturation, fertilization, and embryo development. Mitochondrial dysfunction can trigger oxidative stress, which in turn can lead to nuclear DNA and mitochondrial damage, insufficient intracellular energy supply, imbalance in calcium homeostasis, and abnormal meiotic spindles, ultimately potentially leading to ovum aneuploidy. In recent years, with the continuous intensive research on mitochondrial biogenesis, morphology and function and dynamic changes thereof in disease states, mitochondrial targeting drugs have been rapidly developed. These include nicotinamide mononucleotide (NMN, which supplements the pool of NAD +), mitochondrial targeting protectants (such as MitoQ), antioxidant coenzyme Q10, and the mitochondrial permeability transition pore inhibitor cyclosporin A. However, traditional mitochondrial targeting drugs are still limited in clinical application due to their inability to be efficiently absorbed by mitochondria in vivo and their high toxicity. D-Arg-Dmt-Lys-Phe-NH2 (also known as MTP-131, ELAMIPRETIDE and Bendavia, collectively referred to as SS-31) is an aromatic cationic tetrapeptide which can penetrate cell membranes and has a molecular weight of 639.8 g/mol and consists of a series of small molecule water-soluble peptides. SS-31 has the advantages of small volume, easy synthesis, easy dissolution in water, difficult degradation by peptidase and the like, so that the solid-phase peptide is very stable in solution. Under physiological pH conditions, SS-31 carries 3 positive charges, selectively concentrates on the inner mitochondrial membrane through electrostatic and hydrophobic interactions, combines with cardiolipin in mitochondria, stabilizes the integrity of the mitochondrial membrane, improves the efficiency of electron transfer chains, and reduces the generation of mitochondrial ROS. Furthermore, SS-31 is not dependent on mitochondrial energy and membrane potential and is absorbed by cells in an unsaturated manner without receptor or transporter mediation. It accumulates mainly in the intragranular membrane of the line, does not transport into the mitochondrial matrix even at very high concentrations, and has no effect on normal mitochondria, and is therefore considered relatively safe. However, SS-31 is easily hydrolyzed by protease in vivo, thus resulting in short half-life and needs frequent administration for maintenance, and in addition, the mitochondrial function can be rapidly improved after a single injection of SS-31, but the long-term anti-aging effect has not been confirmed. Disclosure of Invention The invention aims at overcoming the defects in the prior art, and provides an application of SS-31 in preparing a medicament for improving fertility, which provides a novel safe medicament for improving the fertility of aged mammals. The invention solves the technical problems by the following technical scheme that the invention firstly provides the application of SS-31 in preparing the medicine for improving fertility, including the application of SS-31 in preparing the medicine for improving mitochondrial function and metabolism, optimizing oocyte quality, activating ovarian potential and improving mammal fertility. The invention further provides the use of SS-31 in the manufacture of a medicament for treating reduced fertility in a senescent mammal. The invention still further provides the use of SS-31 in the manufacture of a medicament for treating aging oocytes in a mammal suffering from reproductive aging. The application potential of the SS-31 peptide (D-Arg-Dmt-Lys-Phe-NH 2) in preparing medicines for treating the oocytes with aging related to reproductive aging is demonstrated by experiments. It was demonstrated that Vascular Endothelial Growth Factor (VEGF) expression was significantly increased in mice ovaries in the reproductive senescence model