A composition for improving ovarian reserve function and regulating menstruation and use thereof

Abstract

The present application relates to a composition for improving ovarian reserve function and regulating menstruation and application thereof, the composition comprising ginsenoside CK, ergothioneine, coenzyme Q10, pyrroloquinoline quinone, angelica extract and dendrobium officinale extract. The composition provided by the present application has synergistic effects of the components, can repair ovarian mitochondria, restore NAD + , protect granulosa cells, supply blood to uterus, nourish yin and moisten dryness in the reproductive system, improve ovarian reserve function in multiple dimensions, regulate menstrual cycle, menstrual period and menstrual volume.

Description

Technical Field

[0001] This invention relates to the field of ovarian health care technology, and more particularly to a composition for improving ovarian reserve function and regulating menstruation and its application. Background Technology

[0002] Decreased ovarian reserve (DOR) is characterized by decreased anti-Müllerian hormone (AMH), reduced antral follicle count, menstrual cycle irregularities (shortened or irregular), and decreased menstrual flow. Its core pathology includes: ① Oocyte mitochondrial dysfunction leading to insufficient ATP supply, increased meiotic errors, and decreased oocyte quality; ② Ovarian NAD... + Levels decline sharply with age (ovarian NAD+) + One of the fastest-deteriorating organs), leading to the decline of metabolic function of ovarian granulosa cells; ③ Accelerated apoptosis of ovarian granulosa cells leads to increased follicular atresia and faster depletion of the follicular pool; ④ Insufficient blood supply to the endometrium and restricted endometrial growth lead to reduced menstrual flow; ⑤ Ovarian "yin deficiency" state (insufficient tissue water, microcirculatory disorders, chronic oxidative stress) leads to the deterioration of the follicular development microenvironment and decreased follicular fluid quality, affecting oocyte maturation.

[0003] Existing methods of hormone replacement therapy (HRT) or dehydroepiandrosterone (DHEA) supplementation raise concerns about hormone dependence, breast cancer risk, and long-term safety. CN117815260A discloses a preparation for improving ovarian reserve function and its preparation method. The preparation, by weight, comprises: 12-24 parts of Poria cocos polysaccharide, 9-18 parts of oxalic acid, 9-18 parts of fucoxanthin, 15-30 parts of allicin, 5-10 parts of nicotinamide mononucleotide, and 3-9 parts of coenzyme Q10. CN118104819A discloses a composition for enhancing ovarian function, its preparation method, and its application. The composition for ovarian health, by weight, comprises: 2-7 parts of coenzyme Q10, 3-15 parts of pine bark extract, 0-2 parts of soybean germ extract, 20-35 parts of yeast extract, and 1-7 parts of Pleurotus ostreatus extract. The effectiveness of these compositions in improving ovarian reserve function requires further improvement.

[0004] Therefore, providing a safe, non-hormonal approach to improve ovarian reserve and regulate menstruation from multiple dimensions has promising application prospects. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a composition for improving ovarian reserve function and regulating menstruation, and its application. The components in the composition provided by this invention have synergistic effects, contributing to ovarian mitochondrial repair and NAD+ regulation. + It improves ovarian reserve function in multiple dimensions, including restoration, protection of granulosa cells, uterine blood supply, and nourishing and moisturizing the reproductive system, and regulates menstrual cycle, menstrual period and menstrual flow.

[0006] To achieve this objective, the present invention adopts the following technical solution: In a first aspect, the present invention provides a composition for improving ovarian reserve function and regulating menstruation, the composition comprising ginsenoside CK, ergothionein (EGT), coenzyme Q10 (CoQ10), pyrrolizinone (PQQ), Angelica sinensis extract and Dendrobium officinale extract.

[0007] In this invention, CoQ10 directly increases mitochondrial ATP production in oocytes, improving oocyte quality. Multiple randomized controlled trials (RCTs) in the IVF field have confirmed that CoQ10 can improve ovarian responsiveness (increased oocyte retrieval), improve embryo quality (increased rate of high-quality embryos), and increase clinical pregnancy rates. EGT restores ovarian NAD through the CSE / H2S / cGPDH pathway. + Levels, addressing ovarian NAD + The problem of rapid decline in ovarian function. EGT is actively taken up by ovarian tissue via the OCTN1 transporter, protecting the integrity of the oocyte mitochondrial membrane. Ginsenoside CK, through LKB1 / AMPK activation, restores energy metabolism and survival signals in ovarian granulosa cells, reduces granulosa cell apoptosis, and delays follicular atresia. Ginsenoside CK, through CALM, maintains ER calcium homeostasis, protects SIRT1 protein integrity, and maintains the ovarian microenvironment. Angelica sinensis extract is a classic traditional Chinese medicine for "tonifying blood and regulating menstruation." It contains ligustilide, which promotes endometrial angiogenesis and endometrial repair, improving menstrual flow; ferulic acid, which has antioxidant properties and protects ovarian tissue; and Angelica sinensis polysaccharides, which promote ovarian granulosa cell proliferation and estradiol secretion. PQQ, through CREB / PGC-1α, promotes mitochondrial biogeneration in oocytes, replenishing the declining number of mitochondria. Dendrobium officinale extract has "yin-nourishing and kidney-tonifying" effects and is rich in Dendrobium officinale polysaccharides and other effective components. Dendrobium officinale polysaccharides increase the water and hyaluronic acid content in follicular fluid, improving the follicular development microenvironment. The "yin-nourishing and dryness-moistening" effects of Dendrobium officinale directly correspond to the "yin deficiency" state of ovarian tissue in DOR, promoting follicle development and egg maturation.

[0008] The six components in this invention have synergistic effects, and can repair ovarian mitochondria and NAD+. + It improves ovarian reserve function in multiple dimensions, including restoration, protection of granulosa cells, uterine blood supply, and nourishing and moisturizing the reproductive system, and regulates menstrual cycle, menstrual period and menstrual flow.

[0009] Preferably, the composition comprises, by weight parts, 1-30 parts of ginsenoside CK (e.g., 1 part, 5 parts, 10 parts, 20 parts, 25 parts, 30 parts, etc.), 5-100 parts of ergothionein (e.g., 5 parts, 10 parts, 20 parts, 50 parts, 80 parts, 100 parts, etc.), and coenzyme Q10. 10-300 parts (e.g., 10, 50, 100, 150, 200, 250, 300 parts, etc.), 1-50 parts of pyrroloquinoline quinone (e.g., 1, 10, 20, 30, 40, 50 parts, etc.), 10-300 parts of Angelica sinensis extract (e.g., 10, 50, 100, 200, 250, 300 parts, etc.), and 20-400 parts of Dendrobium officinale extract (e.g., 20, 50, 100, 200, 300, 400 parts, etc.).

[0010] Preferably, the composition comprises, by weight parts, 5-20 parts of ginsenoside CK, 20-80 parts of ergothionein, 50-200 parts of coenzyme Q10, 10-40 parts of pyrroloquinoline quinone, 50-200 parts of Angelica sinensis extract, and 50-300 parts of Dendrobium officinale extract.

[0011] Preferably, the coenzyme Q10 includes reduced coenzyme Q10 and / or oxidized coenzyme Q10.

[0012] In a second aspect, the present invention provides the use of the composition for improving ovarian reserve and regulating menstruation according to the first aspect in the preparation of products for improving ovarian reserve and regulating menstruation.

[0013] Preferably, the amount of the composition added to the product is 5-70 wt% (e.g., 5 wt%, 10 wt%, 20 wt%, 30 wt%, 40 wt%, 50 wt%, 60 wt%, 70 wt%, etc.).

[0014] Thirdly, the present invention provides an oral formulation comprising the composition and excipients described in the first aspect for improving ovarian reserve function and regulating menstruation.

[0015] Preferably, the excipients include any one or a combination of at least two of the following: solvent, carrier, excipient, filler, binder, wetting agent, disintegrant, emulsifier, cosolvent, solubilizer, osmotic pressure regulator, surfactant, coating material, colorant, pH adjuster, antioxidant, antibacterial agent, or buffer.

[0016] Preferably, the dosage form of the oral preparation includes capsules, tablets, powders, granules, solid beverages, or gummies.

[0017] Compared with the prior art, the present invention has at least the following beneficial effects: The composition provided by this invention promotes ovarian mitochondrial repair and NAD+. + CoQ10 improves ovarian reserve function in multiple dimensions, including restoration, granulosa cell protection, uterine blood supply, and nourishing the reproductive system. It directly increases mitochondrial ATP in oocytes, improving egg quality, while EGT restores ovarian NAD through a novel pathway. + The composition contains ginsenoside CK, which restores granulosa cell metabolism and reduces follicular atresia; Angelica sinensis extract, which promotes endometrial repair and blood supply and improves menstrual flow; Dendrobium officinale, which "nourishes yin and tonifies the kidneys" and improves the follicular development microenvironment; and Dendrobium officinale polysaccharides, which improve follicular fluid quality. The composition provided by this invention does not contain exogenous estrogen and can avoid the risks of breast cancer and thrombosis associated with HRT. Attached Figure Description

[0018] Figure 1 This is a graph showing the effect of the test substance on serum AMH in mice.

[0019] Figure 2 This is a graph showing the effect of the test substance on serum inhibin B in mice.

[0020] Figure 3 This is a graph showing the effect of the test substance on serum FSH in mice. Detailed Implementation

[0021] To facilitate understanding of the present invention, the following embodiments are provided. Those skilled in the art should understand that these embodiments are merely illustrative and should not be construed as limiting the scope of the invention.

[0022] The raw materials used in the following examples are as follows: The manufacturer of ginsenoside CK was Guangzhou Qingnang Biotechnology Co., Ltd., and the product number was QNCPYL227S. The coenzyme Q10 is cocrystal reduced coenzyme Q10 (panthenol), purchased from Cocrystal Health Industry (Zhejiang) Co., Ltd., with product number Q083; The Angelica sinensis extract was purchased from Guangdong Qingyunshan Pharmaceutical Co., Ltd., with product number C060401-06. The Dendrobium officinale extract was purchased from Guangdong Qingyunshan Pharmaceutical Co., Ltd., with product number C101805-03. All other raw materials are ordinary commercially available products.

[0023] Example 1 This embodiment provides a composition for improving ovarian reserve function and regulating menstruation, comprising, by weight parts, 10 parts of ginsenoside CK, 50 parts of ergothionein, 100 parts of coenzyme Q10, 30 parts of pyrroloquinoline quinone, 100 parts of Angelica sinensis extract, and 200 parts of Dendrobium officinale extract.

[0024] Example 2 This embodiment provides a composition for improving ovarian reserve function and regulating menstruation, comprising, by weight parts, 5 parts of ginsenoside CK, 80 parts of ergothionein, 50 parts of coenzyme Q10, 40 parts of pyrroloquinoline quinone, 50 parts of Angelica sinensis extract, and 300 parts of Dendrobium officinale extract.

[0025] Example 3 This embodiment provides a composition for improving ovarian reserve function and regulating menstruation, comprising, by weight parts: 20 parts ginsenoside CK, 20 parts ergothionein, 200 parts coenzyme Q10, 10 parts pyrroloquinoline quinone, 200 parts Angelica sinensis extract, and 50 parts Dendrobium officinale extract.

[0026] Example 4 This embodiment provides a composition for improving ovarian reserve function and regulating menstruation, comprising, by weight parts, 1 part of ginsenoside CK, 100 parts of ergothionein, 10 parts of coenzyme Q10, 50 parts of pyrroloquinoline quinone, 10 parts of Angelica sinensis extract and 400 parts of Dendrobium officinale extract.

[0027] Example 5 This embodiment provides a composition for improving ovarian reserve function and regulating menstruation, comprising, by weight parts, 30 parts of ginsenoside CK, 5 parts of ergothionein, 300 parts of coenzyme Q10, 1 part of pyrroloquinoline quinone, 300 parts of Angelica sinensis extract, and 20 parts of Dendrobium officinale extract.

[0028] Comparative Example 1 This comparative example provides a composition for improving ovarian reserve function and regulating menstruation. The only difference between this composition and Example 1 is that it does not contain ginsenoside CK, while other parameters remain unchanged.

[0029] Comparative Example 2 This comparative example provides a composition for improving ovarian reserve and regulating menstruation. The only difference between this composition and Example 1 is that it does not contain ergothioneine, while other parameters remain the same.

[0030] Comparative Example 3 This comparative example provides a composition for improving ovarian reserve function and regulating menstruation. The only difference between this composition and Example 1 is that it does not contain coenzyme Q10, while other parameters remain the same.

[0031] Comparative Example 4 This comparative example provides a composition for improving ovarian reserve and regulating menstruation. The only difference between this composition and Example 1 is that it does not contain pyrroloquinoline quinone, while other parameters remain unchanged.

[0032] Comparative Example 5 This comparative example provides a composition for improving ovarian reserve function and regulating menstruation. The only difference between this composition and Example 1 is that it does not contain Angelica sinensis extract, while other parameters remain unchanged.

[0033] Comparative Example 6 This comparative example provides a composition for improving ovarian reserve function and regulating menstruation. The only difference between this composition and Example 1 is that it does not contain Dendrobium officinale extract, while other parameters remain unchanged.

[0034] Test case VCD-induced mouse model of decreased ovarian reserve during perimenopause (indicators: serum anti-Müllerian hormone (AMH), inhibin B, and follicle-stimulating hormone (FSH)). (1) Experimental animals: 8-week-old female ICR mice, weighing 20-25g, were acclimatized for one week before the experiment was conducted. The experimental environment temperature was 25±1℃ and the humidity was 50%±10%.

[0035] (2) Animal grouping and treatment: Sample group: 4-vinylcyclohexene diepoxide (VCD) was used to establish the model, dissolved in sesame oil, and injected intraperitoneally at a dose of 160 mg / kg for 4 consecutive weeks, once a day; at the same time, the composition provided in the examples and comparative examples was administered by gavage at a dose of 50 mg / kg for 6 consecutive weeks, once a day. Model control group: VCD modeling, administered physiological saline at the same volume as the composition by gavage; Normal control group: Intraperitoneal injection of an equal volume of sesame oil and gavage administration of an equal volume of physiological saline as the composition; Each group contains 10 mice.

[0036] (3) Test method: After the 6th week of the experiment, blood was collected from the orbital venous plexus of mice. After standing at room temperature for 30 minutes, the blood was centrifuged at 3000 rpm for 15 minutes to separate the serum. The levels of AMH, inhibin B, and FSH were detected by ELISA.

[0037] The test results are summarized as follows: Figures 1-3 As shown in the figures, , , The numbers indicate that compared with the model control group, p < 0.05, p < 0.01, and p < 0.001; #, ##, and ### indicate that compared with Example 1, p < 0.05, p < 0.01, and p < 0.001.

[0038] pass Figures 1-3 It can be seen that, compared with the mice in the model control group, the mice using the compositions provided in Examples 1-5 of the present invention showed an increase in AMH and inhibin B and a decrease in FSH, indicating that the compositions provided by the present invention have the effect of improving ovarian reserve function and regulating menstruation.

[0039] The comparison between Examples 1 and Examples 4-5 shows that by optimizing the proportion of each component in the composition, the present invention further improves various indicators in mice, indicating that the optimized composition has a better effect on improving ovarian reserve function and regulating menstruation.

[0040] The comparison between Example 1 and Comparative Examples 1-6 shows that when any component of the composition of the present invention is missing, its effect on improving various indicators in mice decreases. This indicates that the components in the composition provided by the present invention play a role from multiple dimensions and have a synergistic effect on improving ovarian reserve function and regulating menstruation.

[0041] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A composition for improving ovarian reserve function and regulating menstruation, characterized in that, The composition includes ginsenoside CK, ergothionein, coenzyme Q10, pyrrolidinequinoline quinone, angelica extract, and dendrobium officinale extract.

2. The composition according to claim 1, characterized in that, The composition comprises, by weight parts, 1-30 parts of ginsenoside CK, 5-100 parts of ergothionein, 10-300 parts of coenzyme Q10, 1-50 parts of pyrroloquinoline quinone, 10-300 parts of Angelica sinensis extract, and 20-400 parts of Dendrobium officinale extract.

3. The composition according to claim 2, characterized in that, The composition comprises, by weight parts, 5-20 parts of ginsenoside CK, 20-80 parts of ergothionein, 50-200 parts of coenzyme Q10, 10-40 parts of pyrroloquinoline quinone, 50-200 parts of Angelica sinensis extract, and 50-300 parts of Dendrobium officinale extract.

4. The composition according to any one of claims 1-3, characterized in that, The coenzyme Q10 includes reduced coenzyme Q10 and / or oxidized coenzyme Q10.

5. The use of the composition for improving ovarian reserve and regulating menstruation according to any one of claims 1-4 in the preparation of products for improving ovarian reserve and regulating menstruation.

6. The application according to claim 5, characterized in that, The amount of the composition added to the product is 5-70 wt%.

7. An oral preparation, characterized in that, The oral formulation comprises the composition and excipients for improving ovarian reserve and regulating menstruation as described in any one of claims 1-4.

8. The oral formulation according to claim 7, characterized in that, The excipients include any one or a combination of at least two of the following: solvent, carrier, excipient, filler, binder, wetting agent, disintegrant, emulsifier, cosolvent, solubilizer, osmotic pressure regulator, surfactant, coating material, colorant, pH adjuster, antioxidant, antibacterial agent, or buffer.

9. The oral formulation according to claim 7 or 8, characterized in that, The dosage forms of the oral preparations include capsules, tablets, powders, granules, solid beverages, or gummies.

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