Traditional Chinese medicine composition for polycystic ovarian syndrome lipid metabolism disorder and application

Abstract

The invention provides a traditional Chinese medicine composition for polycystic ovarian syndrome lipid metabolism disorder and application. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 125 to 500 parts of rhizoma atractylodis macrocephalae, 75 to 300 parts of radix bupleuri, 150 to 600 parts of herba artemisiae scopariae, 75 to 300 parts of fructus gardeniae, 125 to 500 parts of fructus citri sarcodactylis, 50 to 200 parts of fried semen ziziphi spinosae, 50 to 200 parts of fructus schizandrae, 75 to 300 parts of herba sedi and 75 to 300 parts of raw liquorice root. The traditional Chinese medicine composition disclosed by the invention is reasonable in proportion, can improve the reproductive function and lipid metabolism disorder of a mouse model with polycystic ovarian syndrome, and can improve the levels of triglyceride, cholesterol, free fatty acid and the like in HepG2 cell supernatant induced by DHT (docosahexaenoic acid). The traditional Chinese medicine composition disclosed by the invention is supported by a solid traditional Chinese medicine gynecologic classic theory and clinical and laboratory data, is definite in clinical curative effect, free of toxic and side effects and safe to take, and can be applied to preparation of medicines for treating polycystic ovarian syndrome lipid metabolism disorder.

Description

Technical Field

[0001] The invention belongs to a Chinese medicine composition, and relates to a Chinese medicine composition for treating lipid metabolism disorder in polycystic ovary syndrome. The Chinese medicine composition can be used in preparing a medicine for treating lipid metabolism disorder in polycystic ovary syndrome. Background Art

[0002] Polycystic ovary syndrome (PCOS) is a common reproductive endocrine and metabolic disease characterized by anovulatory menstruation, hyperandrogenism and insulin resistance, affecting the reproductive health of 4%-21% of women of childbearing age. PCOS women have defective fat storage capacity. Compared with non-PCOS women, the number of adipocytes in the abdomen and buttocks of PCOS women is significantly increased, and the expression of genes involved in lipid accumulation and angiogenesis is significantly reduced. The dynamic balance of lipid metabolism is a necessary basis for promoting follicular growth and development and maintaining endocrine homeostasis. Lipids participate in follicular development and regulate oocyte maturation, playing an important role in female reproductive function. Lipids accumulated in oocytes and granulosa cells are used throughout the process of oocyte maturation and early embryonic development, providing important energy support for them. The occurrence and development of PCOS is usually accompanied by abnormalities in lipid metabolism, amino acid metabolism and sugar metabolism, a process called metabolic reprogramming. Among them, abnormal lipid metabolism, as the most common metabolic disorder in PCOS, is most closely related to the pathogenesis of PCOS. Studies have confirmed that the disorder of gene expression levels related to lipid metabolism and changes in DNA methylation in PCOS ovarian granulosa cells affect granulosa cell function and oocyte quality, and play an important role in the pathogenesis of PCOS. Studies have found that the transcriptome expression profile of PCOS ovarian granulosa cells has changed significantly, and the expression of multiple lipid metabolism-related genes has been abnormal; enrichment analysis has found that these changes are mainly concentrated in metabolism-related signaling pathways, especially lipid metabolism signaling pathways. It can be seen that maintaining the homeostasis of lipid metabolism is of great significance to improving PCOS follicle development disorders.

[0003] The symptoms and signs of PCOS are scattered in the medical classics of all dynasties, and many doctors have their own theories. For example, "Ming Wan's Gynecology" says: "Only those who are fat and plump are full of fat, and the door of the Yuan room is not open; those who carry phlegm, phlegm is stagnant, and the waves of the sea of ​​blood do not flow... It is turbid, it is leukorrhea, it is amenorrhea, and it is a disease of childlessness." Another example is "Zhu Danxi's Heart Method" explains that women are fat, and they eat rich food, the spleen is not healthy and healthy, the function of raising the clear and lowering the turbid is not performed, the water and grain essence and the water are blocked, and the phlegm is generated internally. The phlegm is sticky and moves with the air. After stagnation, it is stuck and difficult to move, and strange diseases are rampant in the blocked places. If it fills the skin, it will cause obesity. If it blocks the triple burner, the metabolism will be poor. If it blocks the Chongren and Ren meridians, it will not move or transform, which will cause abnormal menstruation, PCOS ovarian polycystic pathological changes, ovarian capsule thickening, and it is difficult to capture sperm and become pregnant. Obesity is one of the main symptoms of PCOS. According to the Chinese medicine theory that "fat people have more phlegm", excessive accumulation of phlegm, fat, etc. causes bloated body and obesity. The expanded lipids in adipose tissue under pathological conditions are considered to be phlegm, water, dampness and the like in Chinese medicine theory. Phlegm, dampness and fat membranes are blocked and accumulated in the uterus, and Chong and Ren meridians are blocked, leading to abnormal ovarian storage and discharge, causing ovulation disorders and infertility. This prescription is based on the principle of strengthening the spleen and soothing the liver, clearing away dampness and heat, and supplemented with Qi. Atractylodes macrocephala, Bupleurum chinense and Artemisia capillaris are the main herbs, which can invigorate the spleen and soothe the liver, clear away dampness and heat, so as to improve the lipid metabolism disorder of PCOS and improve the quality of follicles, providing the power and material basis for correcting ovulation disorders; Gardenia jasminoides, Citron and stir-fried Ziziphus jujuba seeds are the assistant herbs, which can enhance the functions of clearing away heat and dampness, soothing the liver and relieving depression, and at the same time regulating qi and harmonizing the middle; Schisandra chinensis, Herba schisandrae and raw licorice are the adjuvant herbs, which can invigorate qi and produce body fluid, eliminate dampness and clear heat, replenish qi and invigorate the spleen, and further promote the development and maturation of follicles. Summary of the invention

[0004] The invention aims to provide a traditional Chinese medicine composition for treating lipid metabolism disorder in polycystic ovary syndrome. The composition comprises the following components per 1000 dosage units: 125-500 parts of atractylodes macrocephala, 75-300 parts of bupleurum, 150-600 parts of capillaris, 75-300 parts of gardenia, 125-500 parts of citron, 50-200 parts of stir-fried spiny jujube seeds, 50-200 parts of schisandra chinensis, 75-300 parts of scutellaria baicalensis and 75-300 parts of raw liquorice.

[0005] The weight of the above components is calculated based on the crude drug. Each portion can be 1g, or kilograms or tons. If grams are used as the unit, the formula composition can be made into 1000 doses of pharmaceutical preparations. The 1000 doses refer to the finished pharmaceutical preparations, such as 1000g of granules, etc., which can also be made into large packages as granules, such as 100-500 bags, specifically 100 bags, 125 bags, 200 bags, 250 bags, 500 bags, etc., each bag can be used as a single dose.

[0006] The above composition can be made into a preparation with a dosage of 50-1000 times. For example, as a granule, it can be made into 125 bags, 1-2 bags can be taken each time, and a total of 62.5-125 times can be taken.

[0007] The above composition is based on weight ratio, which can be increased or decreased according to the corresponding proportion during production. For example, large-scale production can be measured in kilograms or tons, and small-scale production can also be measured in milligrams. The weight can be increased or decreased, but the weight ratio of the raw medicinal materials in each component remains unchanged.

[0008] The Chinese medicine composition with the above ratio can be prepared into any preparation form suitable for medical use by adding appropriate excipients as needed. The preparation can be a variety of suitable dosage forms such as capsules, granules, tablets, powders, etc.

[0009] Another object of the present invention is to provide the use of the traditional Chinese medicine composition in the preparation of a drug for treating lipid metabolism disorders in polycystic ovary syndrome.

[0010] The Chinese medicine composition provided by the present invention can significantly improve the estrous cycle of testosterone-induced mice, the number of corpora lutea in ovarian tissue, and the blood sugar level. It can also significantly improve the lipid deposition in liver tissue and the level of liver oxidative stress, and the blood lipid level and testosterone level in the blood of mice are also significantly improved, indicating that the Chinese medicine composition can improve the reproductive function and lipid metabolism disorders of the polycystic ovary syndrome mouse model.

[0011] The Chinese medicine composition provided by the present invention can significantly improve the levels of triglycerides, cholesterol, free fatty acids, etc. in the supernatant of HepG2 cells induced by DHT. Oil red staining and oxidative stress marker ROS staining also confirmed the results in animal experiments, and within a certain concentration range, the effect is dose-dependent, and the higher the drug concentration, the better the effect.

[0012] The benefits of the present invention are as follows: (1) the Chinese medicine composition of the present invention has a reasonable composition ratio, and is supported by solid classical theories of TCM gynecology and clinical and laboratory data; (2) the Chinese medicine composition of the present invention has a definite clinical efficacy, has no toxic side effects, is safe to take, and can be used in the preparation of drugs for treating lipid metabolism disorders in polycystic ovary syndrome; (3) the Chinese medicine composition of the present invention has less medicinal taste, is easy to control quality, and is low in cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1.Network pharmacology analysis results. In the figure: A. Venn diagram of PCOS, MAFLD, and QUF10; B. PPI network; C. Molecular docking analysis result heat map; D. MCC, MNC and Degree analysis network; E. 3D and 2D diagrams of the TOP5 molecular docking of SRD5A1 and QUF10; PCOS polycystic ovary syndrome, MAFLD metabolic fatty liver, QUF10 traditional Chinese medicine composition, PPI protein-protein interaction.

[0014] Figure 2 .KEGG and GO analysis. In the figure: A. The top 20 KEGG pathways; B. The top 10 GO enriched pathways of biological processes, cellular components, and molecular functions.

[0015] Figure 3 .Ideas for animal experiment design.

[0016] Figure 4 .The regulatory effect of the Chinese medicine composition on lipid metabolism was verified by animal models. In the figure: A. The estrus cycle pattern of the three groups; B. The results of HE staining of the ovaries and the comparison of the percentage of total follicles in the three groups; C. Typical pictures of HE staining, oil red staining and ROS staining of the liver of the three groups of animals; D. Comparison of intraperitoneal glucose tolerance test (OGTT) and glucose levels at 6 time points in each group of mice; E. Fasting blood glucose level; F. Testosterone levels in the blood of the three groups; G. Blood lipid levels of the three groups of animals. Abbreviation: QUF10 This Chinese medicine composition, PCOS polycystic ovary syndrome, HE hematoxylin-eosin staining, PAF preantral and early antral follicles, AF preantral follicles, CF cystic follicles, CL corpus luteum, D estrus, P proestrus, E estrus, M metestrus, TC total cholesterol, TG triglycerides, LDL low-density lipoprotein, HDL high-density lipoprotein, ROS reactive oxygen species, ns had no significant difference. #Comparison between PCOS group and QUF10 group, p<0.05; *Comparison between control group and PCOS group, p<0.05. **p<0.01, ****p<0.0001.

[0017] Figure 5.The cell model was used to verify the regulatory effect of the Chinese medicine composition on ovarian granulosa cells and liver lipid metabolism. In the figure: A. CCK-8 analysis was used to screen the concentration of QUF10; B. TC, TG, free cholesterol, and cholesterol ester levels in the supernatant of HepG2 cell culture fluid; F. ROS staining and flow cytometry analysis of KGN cell lines by DHT (50uM / L) and three concentrations of QUF10 (1, 5, 10mg / mL); G. Oil red, ROS staining, and apoptosis analysis of HepG2 cell lines by DHT (100uM / L) and three concentrations of QUF10 (1, 5, 10mg / mL). The data represent at least three independent experiments and are expressed as mean ± standard deviation. There was no statistically significant difference in DHT, dihydrotestosterone, QUF10, this Chinese medicine composition, TC, total cholesterol, TG, triglycerides, ROS, KGN ovarian granulosa cell line, HepG2 human liver cancer cell line, ROS, and ns. ROS staining images were magnified 40 times, and Oil Red was magnified 20 times. ***p<0.05, p<0.01, ****p<0.001, p<0.0001. DETAILED DESCRIPTION

[0018] The present invention is further described by specific examples.

[0019] Example 1 Preparation of granules of the present invention The drug composition consists of: 125g of Atractylodes macrocephala, 75g of Bupleurum chinense, 150g of Artemisia capillaris, 75g of Gardenia jasminoides, 125g of Citron, 50g of stir-fried Ziziphus jujuba seeds, 50g of Schisandra chinensis, 75g of Herba Creepers, and 75g of raw Licorice root.

[0020] Preparation method: (1) The above nine herbs, Atractylodes macrocephala, Bupleurum chinense, Artemisia capillaris, Gardenia jasminoides, Citron, stir-fried Ziziphus jujuba seeds, Schisandra chinensis, Herba schisandrae, and raw Licorice are extracted with 10 times the amount of 70% ethanol and refluxed for 1.0 hour. Extract twice in total, combine the extracts, and recover the ethanol. Concentrate under reduced pressure at 60°C to a relative density of 1.05 (measured at 30°C), and centrifuge at 14,000 rpm in a tubular centrifuge to remove impurities. Combine the centrifuge liquid with the alcohol-extracted liquid, and concentrate under reduced pressure at 60°C to a relative density of 1.15 (measured at 60°C). Use a spray dryer (control the spray speed at 2000 ml / min, the air inlet temperature at 140°C, and the air outlet temperature at 85°C) to prepare an extract powder; (2) Add 0.75 g of dextrin and 1 g of powdered sugar to 1 g of dry paste powder, mix, moisten and granulate with 85% ethanol, dry the wet granules (air temperature 50°C), and shape the granules to prepare 1000 doses of granules.

[0021] Example 2 Preparation of tablets of the present invention The drug composition consists of: 125g of Atractylodes macrocephala, 75g of Bupleurum chinense, 150g of Artemisia capillaris, 75g of Gardenia jasminoides, 125g of Citron, 50g of stir-fried Ziziphus jujuba seeds, 50g of Schisandra chinensis, 75g of Herba Creepers, and 75g of raw Licorice root.

[0022] Preparation method: (1) The above nine herbs, Atractylodes macrocephala, Bupleurum chinense, Artemisia capillaris, Gardenia jasminoides, Citron, stir-fried Ziziphus jujuba seeds, Schisandra chinensis, Herba schisandrae, and raw Licorice are extracted with 10 times the amount of 70% ethanol and refluxed for 1.0 hour. Extract twice in total, combine the extracts, and recover the ethanol. Concentrate under reduced pressure at 60°C to a relative density of 1.05 (measured at 30°C), and centrifuge at 14,000 rpm in a tubular centrifuge to remove impurities. Combine the centrifuge liquid with the alcohol-extracted liquid, and concentrate under reduced pressure at 60°C to a relative density of 1.15 (measured at 60°C). Use a spray dryer (control the spray speed at 2000 ml / min, the air inlet temperature at 140°C, and the air outlet temperature at 85°C) to prepare an extract powder; (2) Add 495 g of lactose, 45 g of protein sugar, and 50 ml of 90-95% ethanol to 1 g of dry powder to prepare granules. Add 30 g of magnesium stearate to the dry granules, mix well, and press into tablets to prepare 1000 tablets.

[0027] Example 3 Preparation of capsules of the present invention The drug composition consists of: 125g of Atractylodes macrocephala, 75g of Bupleurum chinense, 150g of Artemisia capillaris, 75g of Gardenia jasminoides, 125g of Citron, 50g of stir-fried Ziziphus jujuba seeds, 50g of Schisandra chinensis, 75g of Herba Creepers, and 75g of raw Licorice root.

[0028] Preparation method: (1) The above nine herbs, Atractylodes macrocephala, Bupleurum chinense, Artemisia capillaris, Gardenia jasminoides, Citron, stir-fried Ziziphus jujuba seeds, Schisandra chinensis, Herba schisandrae, and raw Licorice are extracted with 10 times the amount of 70% ethanol and refluxed for 1.0 hour. Extract twice in total, combine the extracts, and recover the ethanol. Concentrate under reduced pressure at 60°C to a relative density of 1.05 (measured at 30°C), and centrifuge at 14,000 rpm in a tubular centrifuge to remove impurities. Combine the centrifuge liquid with the alcohol-extracted liquid, and concentrate under reduced pressure at 60°C to a relative density of 1.15 (measured at 60°C). Use a spray dryer (control the spray speed at 2000 ml / min, the air inlet temperature at 140°C, and the air outlet temperature at 85°C) to prepare an extract powder; (2) Grind the above dry extract into fine powder, put it into capsules, and make 1000 capsules.

[0029] Example 4 Preparation of granules of the present invention The medicinal composition consists of: 250g of Atractylodes macrocephala, 150g of Bupleurum chinense, 300g of Artemisia capillaris, 150g of Gardenia jasminoides, 250g of Citron, 100g of stir-fried Ziziphus jujuba seeds, 100g of Schisandra chinensis, 150g of Herba Creepers, and 150g of raw Licorice root.

[0030] Preparation method: (1) The above nine herbs, Atractylodes macrocephala, Bupleurum chinense, Artemisia capillaris, Gardenia jasminoides, Citron, stir-fried Ziziphus jujuba seeds, Schisandra chinensis, Herba schisandrae, and raw liquorice were extracted with 10 times the amount of 70% ethanol and refluxed for 1.0 hour. Extract twice in total, combine the extracts, and recover the ethanol. Concentrate under reduced pressure at 60°C until the relative density of the drug solution is 1.05 (measured at 30°C), and use a tubular centrifuge at 14,000 rpm to remove impurities. The centrifuge liquid is combined with the alcohol-extracted drug solution, and concentrated under reduced pressure at 60°C until the relative density of the drug solution is 1.15 (measured at 60°C). Use a spray dryer (control the spray speed to 2000 ml / min, the air inlet temperature to 140°C, and the air outlet temperature to 85°C) to prepare an extract powder; (2) Add 0.75 g of dextrin and 1 g of powdered sugar to 1 g of dry paste powder, mix, moisten and granulate with 85% ethanol, dry the wet granules (air temperature 50°C), and shape the granules to prepare 1000 doses of granules.

[0031] Example 5 Preparation of tablets of the present invention The medicinal composition consists of: 250g of Atractylodes macrocephala, 150g of Bupleurum chinense, 300g of Artemisia capillaris, 150g of Gardenia jasminoides, 250g of Citron, 100g of stir-fried Ziziphus jujuba seeds, 100g of Schisandra chinensis, 150g of Herba Creepers, and 150g of raw Licorice root.

[0032] Preparation method: (1) The above nine herbs, Atractylodes macrocephala, Bupleurum chinense, Artemisia capillaris, Gardenia jasminoides, Citron, stir-fried Ziziphus jujuba seeds, Schisandra chinensis, Herba schisandrae, and raw liquorice were extracted with 10 times the amount of 70% ethanol and refluxed for 1.0 hour. Extract twice in total, combine the extracts, and recover the ethanol. Concentrate under reduced pressure at 60°C until the relative density of the drug solution is 1.05 (measured at 30°C), and use a tubular centrifuge at 14,000 rpm to remove impurities. The centrifuge liquid is combined with the alcohol-extracted drug solution, and concentrated under reduced pressure at 60°C until the relative density of the drug solution is 1.15 (measured at 60°C). Use a spray dryer (control the spray speed to 2000 ml / min, the air inlet temperature to 140°C, and the air outlet temperature to 85°C) to prepare an extract powder; (2) Add 495 g of lactose, 45 g of protein sugar, and 50 ml of 90-95% ethanol to 1 g of dry powder to prepare granules. Add 30 g of magnesium stearate to the dry granules, mix well, and press into tablets to prepare 1000 tablets.

[0033] Example 6 Preparation of capsules of the present invention The medicinal composition consists of: 250g of Atractylodes macrocephala, 150g of Bupleurum chinense, 300g of Artemisia capillaris, 150g of Gardenia jasminoides, 250g of Citron, 100g of stir-fried Ziziphus jujuba seeds, 100g of Schisandra chinensis, 150g of Herba Creepers, and 150g of raw Licorice root.

[0034] Preparation method: (1) The above nine herbs, Atractylodes macrocephala, Bupleurum chinense, Artemisia capillaris, Gardenia jasminoides, Citron, stir-fried Ziziphus jujuba seeds, Schisandra chinensis, Herba schisandrae, and raw liquorice were extracted with 10 times the amount of 70% ethanol and refluxed for 1.0 hour. Extract twice in total, combine the extracts, and recover the ethanol. Concentrate under reduced pressure at 60°C until the relative density of the drug solution is 1.05 (measured at 30°C), and use a tubular centrifuge at 14,000 rpm to remove impurities. The centrifuge liquid is combined with the alcohol-extracted drug solution, and concentrated under reduced pressure at 60°C until the relative density of the drug solution is 1.15 (measured at 60°C). Use a spray dryer (control the spray speed to 2000 ml / min, the air inlet temperature to 140°C, and the air outlet temperature to 85°C) to prepare an extract powder; (2) Grind the above dry extract into fine powder, put it into capsules, and make 1000 capsules.

[0035] Example 7 Preparation of granules of the present invention The medicinal composition consists of: 500g of Atractylodes macrocephala, 300g of Bupleurum chinense, 600g of Artemisia capillaris, 300g of Gardenia jasminoides, 500g of Citron, 200g of stir-fried Semen Ziziphi spinulosae, 200g of Schisandra chinensis, 300g of Herba Creepers, and 300g of raw Licorice.

[0036] Preparation method: (1) The above nine herbs, Atractylodes macrocephala, Bupleurum chinense, Artemisia capillaris, Gardenia jasminoides, Citron, stir-fried Ziziphus jujuba seeds, Schisandra chinensis, Herba schisandrae, and raw liquorice were extracted with 10 times the amount of 70% ethanol and refluxed for 1.0 hour. Extract twice in total, combine the extracts, and recover the ethanol. Concentrate under reduced pressure at 60°C until the relative density of the drug solution is 1.05 (measured at 30°C), and use a tubular centrifuge at 14,000 rpm to remove impurities. The centrifuge liquid is combined with the alcohol-extracted drug solution, and concentrated under reduced pressure at 60°C until the relative density of the drug solution is 1.15 (measured at 60°C). Use a spray dryer (control the spray speed to 2000 ml / min, the air inlet temperature to 140°C, and the air outlet temperature to 85°C) to prepare an extract powder; (2) Add 0.75 g of dextrin and 1 g of powdered sugar to 1 g of dry paste powder, mix, moisten and granulate with 85% ethanol, dry the wet granules (air temperature 50°C), and shape the granules to prepare 1000 doses of granules.

[0037] Example 8 Preparation of tablets of the present invention The medicinal composition consists of: 500g of Atractylodes macrocephala, 300g of Bupleurum chinense, 600g of Artemisia capillaris, 300g of Gardenia jasminoides, 500g of Citron, 200g of stir-fried Semen Ziziphi spinulosae, 200g of Schisandra chinensis, 300g of Herba Creepers, and 300g of raw Licorice.

[0038] Preparation method: (1) The above nine herbs, Atractylodes macrocephala, Bupleurum chinense, Artemisia capillaris, Gardenia jasminoides, Citron, stir-fried Ziziphus jujuba seeds, Schisandra chinensis, Herba schisandrae, and raw liquorice were extracted with 10 times the amount of 70% ethanol and refluxed for 1.0 hour. Extract twice in total, combine the extracts, and recover the ethanol. Concentrate under reduced pressure at 60°C until the relative density of the drug solution is 1.05 (measured at 30°C), and use a tubular centrifuge at 14,000 rpm to remove impurities. The centrifuge liquid is combined with the alcohol-extracted drug solution, and concentrated under reduced pressure at 60°C until the relative density of the drug solution is 1.15 (measured at 60°C). Use a spray dryer (control the spray speed to 2000 ml / min, the air inlet temperature to 140°C, and the air outlet temperature to 85°C) to prepare an extract powder; (2) Add 495 g of lactose, 45 g of protein sugar, and 50 ml of 90-95% ethanol to 1 g of dry powder to prepare granules. Add 30 g of magnesium stearate to the dry granules, mix well, and press into tablets to prepare 1000 tablets.

[0039] Example 9 Preparation of capsules of the present invention The medicinal composition consists of: 500g of Atractylodes macrocephala, 300g of Bupleurum chinense, 600g of Artemisia capillaris, 300g of Gardenia jasminoides, 500g of Citron, 200g of stir-fried Semen Ziziphi spinulosae, 200g of Schisandra chinensis, 300g of Herba Creepers, and 300g of raw Licorice.

[0040] Preparation method: (1) The above nine herbs, Atractylodes macrocephala, Bupleurum chinense, Artemisia capillaris, Gardenia jasminoides, Citron, stir-fried Ziziphus jujuba seeds, Schisandra chinensis, Herba schisandrae, and raw liquorice were extracted with 10 times the amount of 70% ethanol and refluxed for 1.0 hour. Extract twice in total, combine the extracts, and recover the ethanol. Concentrate under reduced pressure at 60°C until the relative density of the drug solution is 1.05 (measured at 30°C), and use a tubular centrifuge at 14,000 rpm to remove impurities. The centrifuge liquid is combined with the alcohol-extracted drug solution, and concentrated under reduced pressure at 60°C until the relative density of the drug solution is 1.15 (measured at 60°C). Use a spray dryer (control the spray speed to 2000 ml / min, the air inlet temperature to 140°C, and the air outlet temperature to 85°C) to prepare an extract powder; (2) Grind the above dry extract into fine powder, put it into capsules, and make 1000 capsules.

[0041] Example 10 Clinical study:

[0042] 1. General Information 32 patients with polycystic ovary syndrome and lipid metabolism disorders were selected, and heart, brain, kidney, metabolic and endocrine diseases were excluded. The diagnostic criteria and syndrome differentiation criteria were formulated according to the "Standards for Diagnosis and Efficacy of TCM Diseases and Syndromes" issued by the State Administration of Traditional Chinese Medicine;

[0043] 2. Diagnosis and efficacy evaluation criteria

[0044] (1) Western medicine diagnostic criteria: Two of the three symptoms are sufficient to diagnose PCOS, and other diseases that may cause similar clinical manifestations need to be excluded: A. Oligovulation or anovulation: Oligovulation refers to less than 8 ovulations per year, and anovulation refers to no menstruation for more than 6 months; B. Hyperandrogenemia and / or signs of hyperandrogenism: Hyperandrogenism is manifested by elevated serum total testosterone or free testosterone levels. Signs of hyperandrogenism include hirsutism, acne, etc. C. Polycystic ovarian changes: Ultrasound examination shows that one or both ovaries have ≥12 follicles with a diameter of 2-9 mm, or the ovarian volume is ≥10 ml.

[0045] Lipid metabolism disorders: It is mainly detected by testing the lipid components in the blood, including total cholesterol (TC) exceeding 5.2mmol / L, triglycerides (TG) exceeding 1.7mmol / L, high-density lipoprotein below 1.1mmol / L, low-density lipoprotein (LDL-C) exceeding 3.5mmol / L, etc.

[0046] (2) TCM diagnostic criteria: Late menstruation, scanty menstruation, or infrequent menstruation, or even amenorrhea, or heavy metrorrhagia; hirsutism, acne, or obesity; fond of fatty, sweet, and alcoholic foods, fatigue, limb fatigue, abdominal distension, dizziness, back pain, dry mouth but no desire to drink; loose stools or constipation, yellowish urine, heavy vaginal discharge, and occasional vulvar itching; pale tongue with thick, greasy coating, and deep pulse.

[0047] The above menstrual disorders are necessary, and the other 4 items can be diagnosed.

[0048] 3. Treatment Methods The 20 cases in the treatment group took the medicine prepared in Example 4 of the present invention orally on the basis of lifestyle adjustment, twice a day, 4 weeks as a course of treatment, and 3 courses of treatment were performed. The 12 cases in the control group only underwent lifestyle adjustment.

[0049] 4. Treatment Outcomes Compared with 12 patients who only adjusted their lifestyle, the menstrual cycle of 20 patients in the treatment group was significantly regular after taking the Chinese medicine composition orally according to the prescribed method. At the same time, compared with the control group, the TC level (P = <0.05), TG level (P = <0.05), and LDL-C level (P = <0.05) were significantly reduced (Table 1). No increase in transaminase and blood creatinine was observed during the course of medication, and the patients did not complain of adverse reactions such as muscle pain and gastrointestinal tract.

[0050] Table 1: Changes in blood lipid levels after three courses of oral administration of the Chinese medicine composition Note: *<0.05vs. control group

[0051] Example 11 Experimental Study

[0052] 1. Network pharmacology methods and results:

[0053] After removing duplicate genes from the database and literature, the disease had only 181 common genes with QUF10 ( Figure 1 A). The hue and size of the nodes in the PPI network represent the degree of the nodes. The darker the color and the larger the size, the greater the importance in the network. Therefore, TP53, AKT1, STAT3, JUN and ESR1 are the top 5 potential targets of QUF10 for the treatment of PCOS-related MAFLD ( Figure 1 B). Quercetin, kaempferol, isopurpurine, resveratrol and dihydroberberine were the top 5 important components among all the chemical components detected in QUF10, and the best binding sites of the more important proteins in the PPI network were selected as ligands for their molecular docking analysis (Table 2). Higher absolute values ​​indicate greater ligand-receptor interactions, among which the steroid 5α-reductase 1 (SRD5A1) protein model had the highest docking score with the top 5 components of QUF10. Figure 1 C shows the complete 3D and 2D results of SRD5A1. The purple arrows in the 2D picture indicate that most of the ligands are connected to SRD5A1 through hydrogen bonds.

[0054] To determine Figure 1 The potential biological activities and related mechanisms of the common genes in the three parts of A were analyzed by KEGG and GO. A total of 162 KEGG pathways, 271 GO-biological process (BP) pathways, 35 GO-cellular component (CC) pathways, and 68 GO-molecular function (MF) pathways were enriched. Figure 2 As shown in A and 2B, the potential mechanism may be related to abnormal lipid and endocrine metabolism and related pathways (possibly AGE-RAGE and PI3K-Akt signaling pathways). Proliferation, apoptosis, response to xenobiotic stimulation, and inflammatory response may be the main pathological processes of QUF10 changes in PCOS women.

[0055] Table 2. Molecular docking scores of QUF10 TOP5 active ingredients and targets Quercetin Kaempferol Isocordyline Resveratrol Dihydroberberine SRD5A1 -7.759 -7.78 -6.739 -7.995 -7.459 AKR1B1 -7.665 -7.103 -6.582 -6.023 -6.9 ADORAI -7.303 -7.833 -5.602 -7.085 -5.733 ESR1 -8.756 -8.855 -6.599 -8.345 0 MMP12 -7.88 -7.038 -7.07 -3.456 -6.523 AKT1 -7.084 -7.954 -6.483 -3.96 -5.134 TP53 -6.138 -5.783 -4.742 -4.638 -5.057 CA12 -5.702 -5.949 -4.852 -5.74 -3.98 EGFR -6.001 -5.708 -4.531 -4.798 -4.531 TNF -5.512 -4.578 -6.296 -3.965 -4.342 STAT3 -5.021 -5.297 -5.153 -4.35 -4.679 IL2 -5.545 -5.415 -4.407 -3.678 -3.718 CDK2 -5.181 -5.108 -3.888 -3.614 -4.093 IL6 -5.073 -4.573 -4.319 -3.87 -3.054 PTGS2 -6.919 -6.674 -6.202 0 0 MAPK1 0 -3.295 -6.116 0 0 JUN -4.008 -3.252 0 -1.75 0 NOTE: Higher absolute values ​​of the docking scores indicate greater ligand-receptor interaction.

[0056] 1. Animal Experimental Methods Three-week-old C57 mice were randomly divided into three groups, with 8-10 mice in each group, and the treatment methods were as follows: Control group: subcutaneous injection of sesame oil for 21 days and intragastric administration of normal saline; PCOS group: continuous subcutaneous injection of dehydroepiandrosterone (DHEA, 6 mg / 100 g / body weight) for 21 days; PCOS+TCM group: Dehydroepiandrosterone (DHEA, 6 mg / 100 g / body weight) was injected subcutaneously for 21 days continuously. The volume of the TCM composition administered to the mice was calculated according to the body surface area. The mice were administered intragastrically for 21 days (e.g. Figure 3 ).

[0057] 2. Animal Experiment Results The Chinese medicine composition can significantly improve the estrous cycle of testosterone-induced mice ( Figure 4 A), the number of corpora lutea in ovarian tissue ( Figure 4 B), and blood sugar levels ( Figure 4 D and 4E). Further analysis of the liver tissue of mice revealed that the Chinese medicine composition significantly improved lipid deposition in liver tissue and the level of liver oxidative stress ( Figure 4 C), blood lipid levels and testosterone levels in mice were also significantly improved ( Figure 4 F and 4G), indicating that the Chinese medicine composition can improve the reproductive function and lipid metabolism disorders of the polycystic ovary syndrome mouse model.

[0058] 3. Cell Experiment Methods A cell model of PCOS combined with lipid metabolism disorder was established using dihydrotestosterone (DHT)-induced ovarian granulosa cell line (KGN) and liver cell line (HepG2).

[0059] 4. Cell Experiment Results First, the appropriate concentration of DHT and the administration concentration of the Chinese medicine composition were screened out by cell proliferation experiment ( Figure 5 A). The Chinese medicine composition can significantly improve the levels of triglycerides, cholesterol, free fatty acids, etc. in the supernatant of HepG2 cells induced by DHT ( Figure 5 BE). Oil red staining and oxidative stress marker ROS staining also confirmed the results of animal experiments. Within a certain concentration range, the effect is dose-dependent, and the higher the drug concentration, the better the effect ( Figure 5 F and 5G).

Claims

1. A Chinese medicine composition for treating lipid metabolism disorder in polycystic ovary syndrome, characterized in that: The composition of each 1000 dosage units is composed of: 125-500 parts of Atractylodes macrocephala, 75-300 parts of Bupleurum chinense, 150-600 parts of Artemisia capillaris, 75-300 parts of Gardenia jasminoides, 125-500 parts of Citron, 50-200 parts of stir-fried Ziziphus jujuba seeds, 50-200 parts of Schisandra chinensis, 75-300 parts of Herba schisandrae, and 75-300 parts of raw Licorice, and the weight of each component is calculated based on the raw drug.

2. Use of a Chinese medicine composition according to claim 1 in preparing a drug for treating lipid metabolism disorders in polycystic ovary syndrome.

3. The use of a Chinese medicine composition according to claim 2, characterized in that: The drug preparation form of the composition and excipients is capsule, granule, tablet or powder.

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