A traditional Chinese medicine composition for improving polycystic ovary syndrome

Abstract

This invention discloses a traditional Chinese medicine composition for improving polycystic ovary syndrome (PCOS). The raw materials of this composition comprise the following components by weight: Cuscuta chinensis 5-20 parts, Lycium barbarum 5-20 parts, Angelica sinensis 5-20 parts, Morus alba 5-20 parts, Salvia miltiorrhiza 5-25 parts, Gardenia jasminoides 5-10 parts, Paeonia suffruticosa 5-20 parts, Cyperus rotundus 5-20 parts, Pinellia ternata 5-20 parts, Abrus precatorius 5-20 parts, and Glycyrrhiza uralensis 5-10 parts. This traditional Chinese medicine composition can significantly improve ovarian morphology, promote the recovery of the estrous cycle, increase luteinizing hormone levels, and decrease testosterone levels, providing a new and effective drug option for the clinical treatment of PCOS.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine composition for improving polycystic ovary syndrome. Background Technology

[0002] Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in women of reproductive age. Its clinical manifestations are highly heterogeneous, often characterized by ovulation disorders, hyperandrogenemia / hyperandrogenism, and polycystic ovarian morphology. It is frequently accompanied by insulin resistance, obesity, lipid metabolism abnormalities, and chronic low-grade inflammation. Statistics show that the prevalence of PCOS in women of reproductive age is approximately 5%-10%, accounting for about 75% of anovulatory infertility, seriously affecting women's reproductive health and quality of life.

[0003] Traditional Chinese medicine (TCM) treatment of PCOS has unique advantages. It can improve endocrine and metabolic disorders, promote follicle development and ovulation through multi-target and multi-pathway holistic regulation, with fewer adverse reactions. However, existing patented TCM compound formulas still have room for further optimization in their combination. In particular, for the complex pathogenesis of PCOS patients, which often involves both "liver meridian stagnation and heat" and "phlegm-dampness obstruction," current technologies lack synergistic formulations that can simultaneously address liver stagnation, phlegm-resolving and dampness-eliminating, and kidney-tonifying and blood-activating effects. While some compound formulas contain liver-soothing and phlegm-resolving herbs, they often use Poria cocos to strengthen the spleen and eliminate dampness, resulting in a weaker effect in clearing liver meridian stagnation and heat, making it difficult to comprehensively improve the hyperandrogenemia and metabolic disorders in PCOS patients.

[0004] Therefore, developing a traditional Chinese medicine composition that closely addresses the core pathogenesis of PCOS—kidney deficiency and liver stagnation, phlegm and blood stasis—and possesses the effects of tonifying the kidney and soothing the liver, promoting blood circulation and removing blood stasis, clearing heat and dampness and resolving phlegm, with significant synergistic effects, is of great clinical significance and market value. Summary of the Invention

[0005] The primary objective of this invention is to overcome the shortcomings and deficiencies of existing technologies and provide a traditional Chinese medicine composition for improving polycystic ovary syndrome (PCOS). This traditional Chinese medicine composition closely addresses the core pathogenesis of PCOS, namely kidney deficiency and liver stagnation, phlegm and blood stasis, and possesses the effects of tonifying the kidney and soothing the liver, promoting blood circulation and removing blood stasis, clearing heat and dampness and resolving phlegm. Moreover, this combination of traditional Chinese medicines exhibits significant synergistic effects and has important clinical significance and market value.

[0006] Another object of the present invention is to provide the application of the said traditional Chinese medicine composition.

[0007] The objective of this invention is achieved through the following technical solution:

[0008] A traditional Chinese medicine composition for improving polycystic ovary syndrome, wherein the raw materials of the traditional Chinese medicine composition comprise the following components in parts by weight: Cuscuta chinensis 5-20 parts, Lycium barbarum 5-20 parts, Angelica sinensis 5-20 parts, Morus alba 5-20 parts, Salvia miltiorrhiza 5-25 parts, Gardenia jasminoides 5-10 parts, Paeonia suffruticosa 5-20 parts, Cyperus rotundus 5-20 parts, Pinellia ternata 5-20 parts, Abrus precatorius 5-20 parts, and Glycyrrhiza uralensis 5-10 parts.

[0009] Preferably, the raw material composition of the traditional Chinese medicine composition comprises the following components in parts by weight: Cuscuta chinensis 10±1g, Lycium barbarum 10±1g, Angelica sinensis 10±1g, Morus alba 10±1g, Salvia miltiorrhiza 15±2g, Gardenia jasminoides 6±0.5g, Paeonia suffruticosa 10±1g, Cyperus rotundus 10±1g, Pinellia ternata 10±1g, Abrus precatorius 10±1g, and Glycyrrhiza uralensis 6±0.5g.

[0010] More preferably, the raw material composition of the traditional Chinese medicine composition comprises the following components in parts by weight: 10g of Cuscuta chinensis, 10g of Lycium barbarum, 10g of Angelica sinensis, 10g of Morus alba, 15g of Salvia miltiorrhiza, 6g of Gardenia jasminoides, 10g of Paeonia suffruticosa, 10g of Cyperus rotundus, 10g of Pinellia ternata, 10g of Abrus precatorius, and 6g of Glycyrrhiza uralensis.

[0011] The aforementioned traditional Chinese medicine composition can significantly improve ovarian morphology in PCOS patients or animals, increase luteinizing hormone levels, and promote the recovery of the estrous cycle.

[0012] Preferably, the animal is a mouse.

[0013] The preparation method of the traditional Chinese medicine composition includes the following steps: adding 8 to 12 times the amount of water to the raw material and decocting for 1 to 2 hours, then filtering and concentrating to obtain the final product.

[0014] Preferably, the amount of water used is 10 times that of the raw material.

[0015] Preferably, the decoction is performed twice, for one hour each time, and the filtrates are combined after filtration.

[0016] Preferably, the concentration is to concentrate to half of the original volume.

[0017] The application of the aforementioned traditional Chinese medicine composition in the preparation of a drug for improving polycystic ovary syndrome (PCOS).

[0018] The application of the aforementioned traditional Chinese medicine composition in the preparation of a medicine for restoring the estrous cycle in patients or animals with polycystic ovary syndrome (PCOS).

[0019] The application of the traditional Chinese medicine composition in the preparation of a drug for reducing the number of cystic follicles in the ovaries of polycystic ovary syndrome (PCOS).

[0020] The application of the traditional Chinese medicine composition in the preparation of a drug for regulating reproductive endocrine indicators of polycystic ovary syndrome (PCOS), wherein the reproductive endocrine indicators include luteinizing hormone levels and / or serum testosterone levels.

[0021] Preferably, the reproductive endocrine indicators for regulating polycystic ovary syndrome (PCOS) include increasing luteinizing hormone levels and / or decreasing testosterone levels.

[0022] The drug comprises the above-mentioned traditional Chinese medicine composition (as the active ingredient) and a pharmaceutically acceptable carrier.

[0023] The drug can be manufactured into clinically acceptable dosage forms such as granules, pills, capsules, tablets, oral liquids, decoctions, powders, injections (powder injections), or syrups according to conventional processes; preferably, it is an oral preparation.

[0024] This invention is based on Traditional Chinese Medicine (TCM) theory, targeting the core pathogenesis of polycystic ovary syndrome (PCOS) characterized by kidney deficiency, liver stagnation, and phlegm-blood stasis. The formula uses Cuscuta chinensis, Lycium barbarum, and Morus alba as the principal herbs to tonify the kidneys and replenish essence; Cyperus rotundus and Angelica sinensis as the assistant herbs to soothe the liver and nourish blood; Salvia miltiorrhiza, Paeonia suffruticosa, and Gardenia jasminoides to invigorate blood circulation, remove blood stasis, and clear stagnation and heat; and Pinellia ternata and Abrus precatorius to resolve phlegm, promote diuresis, clear the liver, and detoxify, serving as adjuvant herbs; and Glycyrrhiza uralensis as the guiding herb to harmonize the effects of all the herbs. The entire formula works synergistically to tonify the kidneys, soothe the liver, invigorate blood circulation, remove blood stasis, clear heat, promote diuresis, and resolve phlegm.

[0025] Validated using a dehydroepiandrosterone (DHEA)-induced PCOS mouse model, the formula of this invention can effectively restore the estrous cycle, reduce the number of cystic follicles in the ovaries, increase the number of corpora lutea, and significantly improve serum testosterone levels in PCOS model mice. This invention, through the specific combination of *Abrus precatorius*, *Pinellia ternata*, and *Cyperus rotundus*, enhances the effect of clearing heat from the liver meridian while resolving phlegm and dampness. It shows a synergistic effect in improving hyperandrogenemia and polycystic ovarian changes, with no obvious toxic side effects, providing a new and effective drug option for the clinical treatment of polycystic ovary syndrome.

[0026] The present invention has the following advantages and effects compared with the prior art:

[0027] 1. Significant Synergistic Effect: This invention, through the specific combination of *Abrus precatorius* with *Pinellia ternata* and *Cyperus rotundus*, breaks through the limitations of the traditional phlegm-resolving combination of *Cyperus rotundus*, *Pinellia ternata*, and *Poria cocos*. *Abrus precatorius* readily enters the liver meridian, clearing heat, promoting diuresis, and detoxifying. When combined with *Pinellia ternata*, it enhances the effect of clearing stagnant heat in the liver meridian while resolving phlegm and promoting diuresis; when combined with *Cyperus rotundus*, it assists in its ability to soothe the liver and relieve stagnation. The three herbs work synergistically to exert multiple effects of "phlegm-soothing the liver-clearing heat," more comprehensively addressing the complex pathogenesis of PCOS where stagnant heat in the liver meridian and internal obstruction of phlegm and dampness coexist.

[0028] 2. Outstanding Pharmacodynamic Effects: Animal experiments showed that the herbal composition of this invention significantly improved ovarian morphology in PCOS model mice, increased luteinizing hormone levels, and promoted the recovery of the estrous cycle. Compared with the positive control drug (DHEA + metformin), this invention is more effective in improving polycystic ovarian changes.

[0029] 3. Broad clinical application prospects: This invention provides a new traditional Chinese medicine formula for the clinical treatment of PCOS, which is especially suitable for PCOS patients with the syndrome of kidney deficiency and liver stagnation, phlegm and blood stasis, and has important social and economic benefits. Attached Figure Description

[0030] Figure 1 This is a schematic diagram of the modeling and drug administration scheme in Embodiment 1 of the present invention.

[0031] Figure 2 The image shows the H&E staining results of the ovaries of experimental mice in the model group and control group in Example 1 of this invention.

[0032] Figure 3 This is a diagram of the estrous cycle of experimental mice in the model group and control group in Example 1 of the present invention.

[0033] Figure 4 This is a quantitative analysis diagram of cystic follicles in the model group and control group experimental mice in Example 1 of the present invention.

[0034] Figure 5 This is a quantitative analysis diagram of the corpus luteum in the model group and control group experimental mice in Example 1 of the present invention.

[0035] Figure 6 This is a graph showing the quantitative analysis of testosterone in the model group and control group mice in Example 1 of the present invention. Detailed Implementation

[0036] The present invention will be further described in detail below with reference to embodiments, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the experimental methods, reagents and raw materials used in the following embodiments are all conventional methods, reagents and raw materials. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0037] Example 1: Preparation of an animal model of polycystic ovary syndrome (PCOS)

[0038] 1. Materials and Methods

[0039] 1.1 Animals

[0040] Three-week-old female C57BL / 6 mice were purchased from the Guangdong Provincial Laboratory Animal Center and housed under standard specific pathogen-free (SPF) conditions with free access to food and water. After a 7-day acclimatization period, the mice were included in the experiment. Mice were randomly assigned to experimental groups. Body weight, estrous cycle, histological parameters, and molecular markers were assessed at pre-defined time points.

[0041] 1.2 Drugs

[0042] Composition and preparation of the traditional Chinese medicine composition (DOSE): Cuscuta chinensis 10g, Lycium barbarum 10g, Angelica sinensis 10g, Morus alba 10g, Salvia miltiorrhiza 15g, Gardenia jasminoides 6g, Paeonia suffruticosa 10g, Cyperus rotundus 10g, Pinellia ternata 10g, Abrus precatorius 10g, Glycyrrhiza uralensis 6g. Purchase 50 doses of raw herbs. Add 10 times the amount of water to all the raw herbs and decoct twice, 1 hour each time. Combine the filtrates and concentrate to half the original volume. Bottle, seal, and store at -20℃ for later use.

[0043] 1.3 Conventional Feed

[0044] Maintenance diet for mice (Beijing Huafukang Biotechnology Co., Ltd.)

[0045] 2. Modeling and Dosing Protocol

[0046] like Figure 1 As shown, 4-week-old female C57BL / 6 mice were randomly divided into 5 groups (n=3 per group): control group, DHEA model group, DHEA + low-dose CPLT group, DHEA + high-dose CPLT group, and DHEA + metformin group.

[0047] Except for the control group, mice in the other groups were injected subcutaneously into the back of the neck daily with dehydroepiandrosterone (DHEA, 6 mg / 100 g body weight / day, dissolved in a mixture of 5% (v / v) anhydrous ethanol and 95% (v / v) sesame oil) for 21 consecutive days to establish a PCOS model; mice in the control group were injected only with an equal volume of solvent (sesame oil) daily.

[0048] Simultaneously with model establishment, mice in the DHEA+LOW DOSE and DHEA+HIGH DOSE groups were administered 100 μL or 200 μL of CPLT via oral gavage daily, respectively. The DHEA+MET group was administered metformin (200 mg / kg) via gavage daily, while the DHEA model group and control group were administered the same volume of solvent via gavage daily. All interventions lasted for 21 days.

[0049] Following the last administration, the estrous cycle of mice in each group was monitored for 8 consecutive days. Mice were then sacrificed, and blood and ovarian tissue were collected for subsequent assays.

[0050] 3. Observation Indicators and Methods

[0051] The PCOS-like phenotype is defined based on a combination of the following characteristics: weight gain, estrous cycle irregularities, an increased number of cystic follicles and a decreased corpus luteum in the ovary, and abnormal serum hormone profiles.

[0052] 3.1 Ovarian H&E

[0053] After bilateral ovarian harvesting, surrounding adipose tissue was carefully removed, and the ovaries were fixed with 4% paraformaldehyde. Following routine dehydration and paraffin embedding, serial sections were prepared at a thickness of 4–5 μm. Sections were stained with hematoxylin and eosin (H&E) and observed under a light microscope. Results are as follows: Figure 2 As shown, after modeling, this traditional Chinese medicine formula can significantly improve DHEA-induced ovarian cystic changes.

[0054] 3.2 Erosive Cycle

[0055] During the designated observation period, vaginal cytology was performed at the same time every day for 8 consecutive days. The specific procedure was as follows: The vagina was gently rinsed with 20 μL of sterile saline, and the collected cell suspension was spread onto a glass slide and fixed with 4% paraformaldehyde for 20 minutes. The slides were then stained with hematoxylin and eosin (H&E). The relative proportions of nucleated epithelial cells, keratinized epithelial cells, and leukocytes were observed under a light microscope to determine the estrous cycle stages (proestrus, estrus, resting phase, and anestrus). Irregular or absent phase transitions were considered estrous cycle disorder. Results are as follows: Figure 3 As shown, this traditional Chinese medicine formula can significantly restore the DHEA-induced estrous cycle.

[0056] 3.3 Cystic follicles

[0057] After bilateral ovarian harvesting, surrounding adipose tissue was carefully removed, and the ovaries were fixed with 4% paraformaldehyde. Following routine dehydration and paraffin embedding, serial sections were prepared at a thickness of 4–5 μm. Sections were stained with hematoxylin and eosin (H&E) and observed under a light microscope. Cystic follicles were defined as follicular structures with thin walls, significantly reduced or absent granulosa cell layers, and enlarged antral cavities. To avoid duplicate counting, sections were selected at predetermined intervals (one section every 50–100 μm). Results are as follows: Figure 4 As shown, after modeling, this traditional Chinese medicine formula can significantly reduce the number of cystic follicles.

[0058] 3.4 Corpus luteum

[0059] After final processing, mice were euthanized according to the experimental protocol. Whole blood samples were collected, allowed to coagulate at room temperature, and then centrifuged to separate serum (4℃, 3000×g, 15 min). Serum samples were stored at -80℃ until detection. Luteinizing hormone levels were measured using a commercially available ELISA kit strictly according to the instructions. All samples were tested within the same batch or after batch effect correction to reduce inter-test variability. Results are as follows: Figure 5 As shown, after modeling, this traditional Chinese medicine formula can significantly increase the level of luteinizing hormone.

[0060] 3.5 Testosterone

[0061] After final processing, mice were euthanized according to the experimental protocol. Whole blood samples were collected, allowed to coagulate at room temperature, and then centrifuged to separate serum (4℃, 3000×g, 15 minutes). Serum samples were stored at -80℃ until detection. Serum testosterone levels were measured using a commercially available ELISA kit strictly according to the instructions. All samples were tested within the same batch or batch-effect corrected to reduce inter-test variability. Results are as follows: Figure 6 As shown, after modeling, this traditional Chinese medicine formula can significantly reduce testosterone levels.

[0062] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for improving polycystic ovary syndrome, characterized in that, The raw materials of the aforementioned traditional Chinese medicine composition comprise the following components by weight: Cuscuta chinensis 5-20 parts, Lycium barbarum 5-20 parts, Angelica sinensis 5-20 parts, Morus alba 5-20 parts, Salvia miltiorrhiza 5-25 parts, Gardenia jasminoides 5-10 parts, Paeonia suffruticosa 5-20 parts, Cyperus rotundus 5-20 parts, Pinellia ternata 5-20 parts, Abrus precatorius 5-20 parts, and Glycyrrhiza uralensis 5-10 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The raw materials of the aforementioned traditional Chinese medicine composition include the following components in parts by weight: Cuscuta chinensis 10±1g, Lycium barbarum 10±1g, Angelica sinensis 10±1g, Morus alba 10±1g, Salvia miltiorrhiza 15±2g, Gardenia jasminoides 6±0.5g, Paeonia suffruticosa 10±1g, Cyperus rotundus 10±1g, Pinellia ternata 10±1g, Abrus precatorius 10±1g, and Glycyrrhiza uralensis 6±0.5g.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The raw materials of the aforementioned traditional Chinese medicine composition include the following components in parts by weight: Cuscuta chinensis 10g, Lycium barbarum 10g, Angelica sinensis 10g, Morus alba 10g, Salvia miltiorrhiza 15g, Gardenia jasminoides 6g, Paeonia suffruticosa 10g, Cyperus rotundus 10g, Pinellia ternata 10g, Abrus precatorius 10g, and Glycyrrhiza uralensis 6g.

4. The method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, The process includes the following steps: adding the raw drug to 8 to 12 times the amount of water and decocting for 1 to 2 hours, then filtering and concentrating to obtain the final product.

5. The method for preparing the traditional Chinese medicine composition according to claim 4, characterized in that: The amount of water used is 10 times that of the raw drug; The decoction is performed twice, for one hour each time; The concentration mentioned refers to concentrating the volume to half of its original volume.

6. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for improving polycystic ovary syndrome and restoring the estrous cycle in patients or animals with polycystic ovary syndrome.

7. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for reducing the number of cystic follicles in the ovaries of polycystic ovary syndrome.

8. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for regulating reproductive endocrine indicators in polycystic ovary syndrome, characterized in that: The reproductive endocrine indicators include luteinizing hormone levels and / or serum testosterone levels.

9. The application according to claim 8, characterized in that: The aforementioned indicators for regulating reproductive endocrine function in polycystic ovary syndrome include increasing luteinizing hormone levels and / or decreasing testosterone levels.

10. The application according to any one of claims 6 to 9, characterized in that: The drug also includes pharmaceutically acceptable carriers.

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