A traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome, preparation and use

Abstract

The application provides a traditional Chinese medicine composition for adjusting metabolism of polycystic ovary syndrome, a preparation and purposes, which is prepared from the following raw medicinal materials in a proportion by weight: Radix Rehmanniae Preparata 25-35 parts, Radix Paeoniae Alba 25-35 parts, Rhizoma Atractylodis Macrocephalae 25-35 parts, Radix Salviae Miltiorrhizae 25-35 parts, Radix Morindae Officinalis 25-35 parts, Fructus Corni 10-20 parts, Rhizoma Pinelliae Praeparatum 10-20 parts and Pericarpium Citri Reticulatae 10-20 parts. The eight kinds of traditional Chinese medicines are compatible with each other, and the effects of tonifying kidney and essence, invigorating spleen and drying dampness are achieved. The present application can reduce serum androgen, restore the level of estrus cycle, promote ovulation and effectively improve reproductive function. The clinical application practice shows that no intolerable side effect is found.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome, a preparation and a use. BACKGROUND

[0002] Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in women of childbearing age, and the clinical incidence is increasing year by year, accounting for about 15% to 18% of women of childbearing age. The main features of PCOS are anovulation, hyperandrogenism and polycystic-like performance of the ovary, often accompanied by obesity, insulin resistance, abnormal glucose and lipid metabolism, increased oxidative stress and subclinical chronic inflammation, which significantly increase the risk of metabolic syndrome, type 2 diabetes, long-term cardiovascular disease and endometrial cancer. Although the occurrence and development of PCOS are related to genetic factors and environmental factors, the specific pathogenesis is still unclear.

[0003] Hyperandrogenism, as one of the main clinical features of PCOS, is also one of the important diagnostic conditions of PCOS. Related studies have shown that high androgen has the ability to inhibit folliculogenesis and ovum development, and at the same time affects the periodic ovulation of the ovary and the secretion of sex hormones, leading to decreased endometrial receptivity and causing low pregnancy rate and high abortion rate, thereby affecting the reproductive ability of women of childbearing age. In addition, excessive androgen can cause abnormal sex differentiation such as female pseudohermaphroditism in the fetal period; male external genitalia and appearance masculinization in childhood; no menstrual onset or menstrual disorder, amenorrhea, infertility, hirsutism, acne and baldness, etc. after puberty. In addition, clinical studies have also shown that PCOS patients with high androgen performance have a significantly higher risk of metabolic and cardiovascular complications than PCOS patients without high androgen performance.

[0004] In recent years, a large amount of experimental data has shown that reducing the serum androgen level of patients can effectively improve the polycystic ovary, anovulation, abnormal glucose and lipid metabolism and high androgen-related performance of PCOS. However, there are very limited drugs that can be used to treat PCOS in clinical practice at present, and the side effects caused by these drugs are obvious. For example, the commonly used anti-androgen drug ethinyl estradiol cyproterone acetate tablets (Diane-35) can effectively improve diseases such as acne, hair loss, hirsutism and polycystic ovary syndrome caused by excessive androgen, but long-term use will increase the burden on the cardiovascular system, endocrine system, digestive system and urogenital system, causing symptoms such as nausea, vomiting, elevated blood pressure, edema, venous thrombosis and the like in patients.

[0005] The current clinical anti-androgen therapy usually needs 3-6 months, mainly adopts oral short-acting contraceptive, spironolactone, flutamide, finasteride and dexamethasone for treatment. However, oral contraceptive can cause irregular vaginal bleeding, nausea, vomiting, breast pain and other side effects; spironolactone needs to be taken continuously for 6 months when used as anti-androgen therapy, and long-term medication can not only increase the social and economic burden, but also bring breast pain, menstrual disorders, headache, polyuria and hyperkalemia to patients; flutamide has liver toxicity, and the effectiveness and safety of medication are questioned; dexamethasone is mainly used for treating PCOS patients with high androgen from adrenal glands, and has limitation. In addition, the drugs for treating insulin resistance, such as metformin and lipid-lowering drugs, such as statins, are not ideal for reducing androgen levels and improving ovulation, and whether they are beneficial for long-term treatment still needs to be further verified through strict experimental design and large sample research. Therefore, the present application provides a traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome, which can improve the safety of medication, reduce serum androgen levels and improve symptoms related to polycystic ovary syndrome. SUMMARY

[0006] In order to solve the problems of side effects caused by existing anti-androgen drugs and PCOS drugs, the purpose of the present application is to provide a traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome, preparation and use.

[0007] To achieve the above-mentioned purpose, the technical scheme of the present application is as follows.

[0008] A traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome is prepared from the following raw medicinal materials in a certain weight ratio:

[0009] 25-35 parts of Radix Rehmanniae Preparata, 25-35 parts of Radix Paeoniae Alba, 25-35 parts of Rhizoma Atractylodis Macrocephalae, 25-35 parts of Radix Salviae Miltiorrhizae, 25-35 parts of Radix Morindae Officinalis, 10-20 parts of Fructus Corni, 10-20 parts of Rhizoma Pinelliae with Ginger, and 10-20 parts of Pericarpium Citri Reticulatae.

[0010] Further, the following raw medicinal materials in a certain weight ratio are used:

[0011] 25-30 parts of Radix Rehmanniae Preparata, 25-30 parts of Radix Paeoniae Alba, 25-30 parts of Rhizoma Atractylodis Macrocephalae, 25-30 parts of Radix Salviae Miltiorrhizae, 25-30 parts of Radix Morindae Officinalis, 10-15 parts of Fructus Corni, 10-15 parts of Rhizoma Pinelliae with Ginger, and 10-15 parts of Pericarpium Citri Reticulatae.

[0012] Further, the following raw medicinal materials in a certain weight ratio are used:

[0013] 30 parts of Radix Rehmanniae Preparata, 30 parts of Radix Paeoniae Alba, 30 parts of Rhizoma Atractylodis Macrocephalae, 30 parts of Radix Salviae Miltiorrhizae, 30 parts of Radix Morindae Officinalis, 15 parts of Fructus Corni, 15 parts of Rhizoma Pinelliae with Ginger, and 15 parts of Pericarpium Citri Reticulatae.

[0014] The effects of each active ingredient in the raw medicinal materials of the present application are as follows:

[0015] Rehmannia: sweet, warm, liver and kidney; function of nourishing yin and blood, benefit essence marrow.

[0016] White Peony Root: bitter, spicy, liver and spleen; function of blood regulating menstruation, astringe Yin to stop sweating, softening the liver pain, liver Yang.

[0017] White Atractylodes: bitter, sweet, warm, spleen and stomach; function of spleen, dry wet water, stop sweating, an embryo.

[0018] Salvia: bitter, cold, heart and liver; function of activating blood and removing blood stasis, through the pain, clear heart, blood and abscess.

[0019] Ba Ji Tian: spicy, sweet, warm, kidney and liver; function of kidney Yang, strong bones, wind and dampness.

[0020] Dogwood: sour, astringent, warm, liver and kidney; function of liver and kidney, astringent and solid.

[0021] Ginger Pinellia: spicy, warm, spleen, stomach and lung; function of dry wet phlegm, descending adverse vomiting, phlegm.

[0022] Dried Orange Peel: bitter, spicy, warm, lung and spleen; function of regulating qi and spleen, dry wet phlegm.

[0023] In the present application, Rehmannia and Ba Ji Tian are the monarch drugs, Rehmannia is the main drug for tonifying kidney Yin, which has the effect of tonifying blood and nourishing Yin, benefiting essence and filling marrow. "Yang is born and Yin grows", so Rehmannia is combined with Ba Ji Tian to warm the kidney and strengthen Yang.

[0024] Dogwood, White Peony Root and White Atractylodes are the minister drugs, Dogwood can nourish liver and kidney and fill essence and blood. In this way, essence and blood are abundant, liver and kidney are nourished, and Chong and Ren are regulated. White Peony Root "has cold and bitter acid, enters the liver and blood, benefits blood and nourishes Yin, tonifies blood and nourishes meridians, astringes Yin to harmonize Ying and Wei", so White Peony Root is used to assist the monarch drug Rehmannia to tonify Yin in the blood. White Atractylodes tonifies Qi and invigorates the spleen, dries dampness and promotes water. The three drugs are used together to tonify the kidney and nourish Yin, invigorate the spleen and dry dampness.

[0025] Salvia, Ginger Pinellia and Dried Orange Peel are the auxiliary drugs, Salvia activates blood and removes blood stasis to remove blood stasis. Ginger Pinellia dries wet phlegm to enhance the dry wet spleen function of White Atractylodes. Dried Orange Peel regulates Qi, which means "Qi is smooth and phlegm is self-dissolved".

[0026] The above eight kinds of traditional Chinese medicines are combined, which complement each other, and have the effects of tonifying kidney and benefiting essence, invigorating the spleen and drying dampness.

[0027] The traditional Chinese medicine composition of the present application can be prepared by various methods according to the needs on the basis of the above raw materials. For example, traditional water decoction method can be selected.

[0028] Further, the preparation of the traditional Chinese medicine composition is as follows:

[0029] Mixing Rehmanniae Radix Praeparata, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Radix Salviae Miltiorrhizae, Radix Morindae Officinalis, Fructus Corni, Rhizoma Pinelliae, Pericarpium Citri Reticulatae to obtain a raw material mixture, decocting the raw material mixture with water for 1-3 times, and combining the decocting liquid to obtain the product.

[0030] Further, the mass ratio of water to the raw material mixture is 5-10:1. The amount of water added each time can be adjusted according to actual conditions, and it is appropriate that the liquid level submerges the raw medicinal materials. According to the weight ratio of raw materials: Rehmanniae Radix Praeparata 30g, Radix Paeoniae Alba 30g, Rhizoma Atractylodis Macrocephalae 30g, Radix Salviae Miltiorrhizae 30g, Radix Morindae Officinalis 30g, Fructus Corni 15g, Rhizoma Pinelliae 15g, Pericarpium Citri Reticulatae 15g, the most suitable amount in the present application is 1500mL of water added for the first time, and 1000mL of water added for the second time.

[0031] Further, the decocting time each time is 1-2h.

[0032] The present application also provides a traditional Chinese medicine preparation comprising a therapeutically effective amount of the traditional Chinese medicine composition of claim 1.

[0033] The traditional Chinese medicine composition of the present application is added with different auxiliary materials according to the needs of clinical use, and is processed into various oral preparations including granules, pills, capsules, tablets, powders, pastes and oral liquid preparations by using conventional preparation processes. Of course, the traditional Chinese medicine preparation of the present application is not limited to granules, pills, capsules, tablets, powders, pastes and oral liquid preparations. The dosage of the traditional Chinese medicine composition of the present application can be determined according to the amount of the drug contained in the final preparation to achieve a therapeutically effective dose and complete the prophylactic and / or therapeutic effects of the present application.

[0034] The present application also provides the use of the traditional Chinese medicine composition in the preparation of a medicine for regulating the metabolism of polycystic ovary syndrome.

[0035] The present application also provides the use of the traditional Chinese medicine composition in the preparation of a medicine for reducing the androgen level in female animals, promoting ovulation or promoting pregnancy.

[0036] The present application has the following beneficial effects:

[0037] 1. In the traditional Chinese medicine composition of the present invention, Rehmannia glutinosa and Morinda officinalis are the principal herbs. Rehmannia glutinosa is an essential herb for tonifying kidney yin, and has the effects of nourishing blood and yin, replenishing essence and marrow. "Yang generates yin," so Rehmannia glutinosa is combined with Morinda officinalis to warm the kidney and strengthen yang. Cornus officinalis, Paeonia lactiflora, and Atractylodes macrocephala are the assistant herbs. Cornus officinalis can nourish the liver and kidney and replenish essence and blood. With abundant essence and blood, the liver and kidney are nourished, and the Chong and Ren meridians are regulated. Paeonia lactiflora is "cold and bitter, enters the blood part of the liver meridian, nourishes blood and yin, replenishes blood and nourishes the meridians, and astringes yin to harmonize the Ying and Wei." Therefore, Paeonia lactiflora is used to assist the principal herb Rehmannia glutinosa to achieve the effect of nourishing yin in the blood. Atractylodes macrocephala tonifies qi and strengthens the spleen, dries dampness and promotes diuresis. The three herbs combined tonify the kidney and nourish yin, strengthen the spleen and dry dampness. This formula uses Danshen (Salvia miltiorrhiza), ginger-processed Pinellia ternata, and tangerine peel as adjuvant herbs. Danshen invigorates blood circulation and promotes menstruation to remove blood stasis; ginger-processed Pinellia ternata dries dampness and resolves phlegm, enhancing the dampness-drying and spleen-strengthening effects of Atractylodes macrocephala; and tangerine peel regulates Qi, embodying the principle of "when Qi flows smoothly, phlegm naturally dissipates." These eight herbs complement each other, working synergistically to tonify the kidneys and replenish essence, strengthen the spleen, and dry dampness. Animal studies have confirmed that this formula, while lowering serum androgen levels, restores estrous cycle levels, promotes ovulation, and effectively improves reproductive function.

[0038] 2. The traditional Chinese medicine formula of this invention has the effect of reducing androgen levels in female animals. By affecting testosterone synthesis in the ovary, it regulates hormone levels, improves ovulation and restores the estrous cycle, and alleviates symptoms related to polycystic ovary syndrome. Clinical application practice shows that no intolerable side effects have been found. Therefore, overall, as a clinical drug, the traditional Chinese medicine formula of this invention has ideal safety. Attached Figure Description

[0039] Figure 1 This describes the effect of the traditional Chinese medicine composition of Example 1 on improving the estrous cycle in PCOS mice.

[0040] Figure 2 This describes the effect of the traditional Chinese medicine composition in Example 1 on the morphology of ovarian tissue in PCOS mice.

[0041] Figure 3 This describes the effect of the traditional Chinese medicine composition in Example 1 on improving serum hormone levels in PCOS mice.

[0042] Figure 4 This describes the effect of the traditional Chinese medicine composition of Example 1 on improving the expression of serum inflammatory factors in PCOS mice.

[0043] Figure 5 This describes the effect of the traditional Chinese medicine composition of Example 1 on the expression of genes related to androgen synthesis and metabolism in PCOS mice.

[0044] Figure 6 This is the total ion chromatogram (negative mode) of the traditional Chinese medicine preparation made from the traditional Chinese medicine composition of Example 1.

[0045] Figure 7This is the total ion chromatogram (positive mode) of the traditional Chinese medicine preparation made from the traditional Chinese medicine composition of Example 1. Detailed Implementation

[0046] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0047] Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0048] The formulation of this invention conforms to the principle of "principal, assistant, adjuvant and guide" in traditional Chinese medicine. The following traditional Chinese medicines used in this invention interact and complement each other to exert their synergistic therapeutic effects. The components of the traditional Chinese medicine raw materials used have mutually intertwined, mutually promoting and synergistic effects.

[0049] The raw materials (or medicinal materials) used in this invention can all be purchased from ordinary pharmacies or Chinese herbal medicine sales companies, and their specifications comply with national pharmaceutical standards or relevant regulations such as the Chinese Pharmacopoeia. Unless otherwise specified, all medicinal materials used are processed Chinese herbal medicine slices, which may also be obtained and then processed.

[0050] In this invention, "patient" refers to a person suffering from a disease, a wild animal, or a livestock. Wild animals are animals in their natural state that have not been domesticated. Livestock are animals raised artificially for food, such as rabbits, horses, cattle, sheep, dogs, rats, and hamsters. Mammals, especially humans, are preferred as "patients" for diagnosis.

[0051] All the Chinese medicinal materials used in the following embodiments of the present invention are ordinary commercially available products, and their specifications comply with the corresponding national pharmaceutical standards or relevant regulations such as the Chinese Pharmacopoeia. All the Chinese medicinal materials are processed medicinal slices, and the following Chinese medicinal materials—Rehmannia glutinosa (processed), Paeonia lactiflora (white peony root), Atractylodes macrocephala (white atractylodes rhizome), Salvia miltiorrhiza (salvia miltiorrhiza), Morinda officinalis (morinda officinalis), Cornus officinalis (cornus fruit), Pinellia ternata (processed with ginger), and Citrus reticulata (tangerine peel)—were provided by the First Affiliated Hospital of Guangzhou Medical University.

[0052] Example 1

[0053] A traditional Chinese medicine composition for regulating metabolism in polycystic ovary syndrome is made from the following raw materials in the indicated weight ratios:

[0054] Prepared Rehmannia Root 30g, White Peony Root 30g, Atractylodes Rhizome 30g, Salvia Root 30g, Morinda Root 30g, Cornus Fruit 15g, Ginger-processed Pinellia Rhizome 15g, Tangerine Peel 15g.

[0055] The preparation of the traditional Chinese medicine composition is as follows:

[0056] Mix Rehmanniae Radix Praeparatae, Radix Paeoniae Albae, Rhizoma Atractylodis Macrocephalae, Radix Salviae Miltiorrhizae, Radix Morindae Officinalis, Fructus Corni, Rhizoma Pinelliae, Pericarpium Citri Reticulatae to obtain a raw material mixture, and decoct the raw material mixture by adding water twice, each time for 1.5 h (start timing after bubbling and boiling), and filter with gauze after each decocting, and combine the decocting liquid to obtain the product. The mass ratio of water to the raw material mixture is 10:1 in the first decocting. The mass ratio of water to the raw material mixture is 8:1 in the second decocting.

[0057] Example 2

[0058] A traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome is prepared from the following raw medicinal materials in the following proportions by weight:

[0059] Rehmanniae Radix Praeparatae 25 g, Radix Paeoniae Albae 25 g, Rhizoma Atractylodis Macrocephalae 25 g, Radix Salviae Miltiorrhizae 25 g, Radix Morindae Officinalis 25 g, Fructus Corni 14 g, Rhizoma Pinelliae 14 g, Pericarpium Citri Reticulatae 15 g.

[0060] The traditional Chinese medicine composition is prepared as follows:

[0061] Mix Rehmanniae Radix Praeparatae, Radix Paeoniae Albae, Rhizoma Atractylodis Macrocephalae, Radix Salviae Miltiorrhizae, Radix Morindae Officinalis, Fructus Corni, Rhizoma Pinelliae, Pericarpium Citri Reticulatae to obtain a raw material mixture, and decoct the raw material mixture by adding water twice, each time for 2 h, and combine the decocting liquid to obtain the product. The mass ratio of water to the raw material mixture is 7.7:1 in the first decocting. The mass ratio of water to the raw material mixture is 5.1:1 in the second decocting.

[0062] Example 3

[0063] A traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome is prepared from the following raw medicinal materials in the following proportions by weight:

[0064] Rehmanniae Radix Praeparatae 28 g, Radix Paeoniae Albae 28 g, Rhizoma Atractylodis Macrocephalae 28 g, Radix Salviae Miltiorrhizae 28 g, Radix Morindae Officinalis 28 g, Fructus Corni 16 g, Rhizoma Pinelliae 15 g, Pericarpium Citri Reticulatae 15 g.

[0065] The traditional Chinese medicine composition is prepared as follows:

[0066] Mix Rehmanniae Radix Praeparatae, Radix Paeoniae Albae, Rhizoma Atractylodis Macrocephalae, Radix Salviae Miltiorrhizae, Radix Morindae Officinalis, Fructus Corni, Rhizoma Pinelliae, Pericarpium Citri Reticulatae to obtain a raw material mixture, and decoct the raw material mixture by adding water twice, each time for 2 h, and combine the decocting liquid to obtain the product. The mass ratio of water to the raw material mixture is 7.7:1 in the first decocting. The mass ratio of water to the raw material mixture is 5.1:1 in the second decocting.

[0067] Example 4

[0068] A traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome is prepared from the following raw medicinal materials in the following proportions by weight:

[0069] Radix Rehmanniae Preparata 33g, Radix Paeoniae Alba 33g, Rhizoma Atractylodis Macrocephalae 33g, Radix Salviae Miltiorrhizae 33g, Radix Morindae Officinalis 33g, Fructus Corni 18g, Rhizoma Pinelliae Preparatum 16g, Pericarpium Citri Reticulatae 18g.

[0070] The preparation of the traditional Chinese medicine composition is as follows:

[0071] Mix Radix Rehmanniae Preparata, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Radix Salviae Miltiorrhizae, Radix Morindae Officinalis, Fructus Corni, Rhizoma Pinelliae Preparatum and Pericarpium Citri Reticulatae to obtain a raw material mixture, add water to the raw material mixture and decoct twice, each time for 2 hours, combine the decocted liquid to obtain the traditional Chinese medicine composition. The mass ratio of water to the raw material mixture is 7.7:1 in the first decoction, and 5.1:1 in the second decoction.

[0072] Example 5

[0073] A traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome is prepared from the following raw medicinal materials in a certain proportion by weight:

[0074] Radix Rehmanniae Preparata 35g, Radix Paeoniae Alba 35g, Rhizoma Atractylodis Macrocephalae 35g, Radix Salviae Miltiorrhizae 35g, Radix Morindae Officinalis 35g, Fructus Corni 20g, Rhizoma Pinelliae Preparatum 20g, Pericarpium Citri Reticulatae 20g.

[0075] The preparation of the traditional Chinese medicine composition is as follows:

[0076] Mix Radix Rehmanniae Preparata, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Radix Salviae Miltiorrhizae, Radix Morindae Officinalis, Fructus Corni, Rhizoma Pinelliae Preparatum and Pericarpium Citri Reticulatae to obtain a raw material mixture, add water to the raw material mixture and decoct twice, each time for 2 hours, combine the decocted liquid to obtain the traditional Chinese medicine composition. The mass ratio of water to the raw material mixture is 7.7:1 in the first decoction, and 5.1:1 in the second decoction.

[0077] Example 6

[0078] A traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome is prepared from the following raw medicinal materials in a certain proportion by weight:

[0079] Radix Rehmanniae Preparata 25g, Radix Paeoniae Alba 25g, Rhizoma Atractylodis Macrocephalae 25g, Radix Salviae Miltiorrhizae 25g, Radix Morindae Officinalis 25g, Fructus Corni 10g, Rhizoma Pinelliae Preparatum 10g, Pericarpium Citri Reticulatae 10g.

[0080] The preparation of the traditional Chinese medicine composition is as follows:

[0081] Mix Radix Rehmanniae Preparata, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Radix Salviae Miltiorrhizae, Radix Morindae Officinalis, Fructus Corni, Rhizoma Pinelliae Preparatum and Pericarpium Citri Reticulatae to obtain a raw material mixture, add water to the raw material mixture and decoct twice, each time for 2 hours, combine the decocted liquid to obtain the traditional Chinese medicine composition. The mass ratio of water to the raw material mixture is 7.7:1 in the first decoction, and 5.1:1 in the second decoction.

[0082] Example 7

[0083] A traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome is prepared from the following raw medicinal materials in a certain proportion by weight:

[0084] Radix Rehmanniae Preparata 31g, Radix Paeoniae Alba 31g, Rhizoma Atractylodis Macrocephalae 31g, Radix Salviae Miltiorrhizae 31g, Radix Morindae Officinalis 31g, Fructus Corni 16g, Rhizoma Pinelliae Preparatum 15g, Pericarpium Citri Reticulatae 18g.

[0085] The traditional Chinese medicine composition is prepared as follows:

[0086] The Radix Rehmanniae Preparata, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Radix Salviae Miltiorrhizae, Radix Morindae Officinalis, Fructus Corni, Rhizoma Pinelliae Preparatum and Pericarpium Citri Reticulatae are mixed to obtain a raw material mixture, and water is added to the raw material mixture for decocting three times, each time for 1h, and the decocting liquid is obtained by combining. The mass ratio of water to the raw material mixture is 10:1 in the first decocting, 7:1 in the second decocting and 5:1 in the third decocting.

[0087] Example 8

[0088] A traditional Chinese medicine composition for regulating metabolism of polycystic ovary syndrome is prepared from the following raw medicinal materials in a certain proportion by weight:

[0089] Radix Rehmanniae Preparata 27g, Radix Paeoniae Alba 27g, Rhizoma Atractylodis Macrocephalae 27g, Radix Salviae Miltiorrhizae 27g, Radix Morindae Officinalis 27g, Fructus Corni 13g, Rhizoma Pinelliae Preparatum 13g, Pericarpium Citri Reticulatae 13g.

[0090] The traditional Chinese medicine composition is prepared as follows:

[0091] The Radix Rehmanniae Preparata, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Radix Salviae Miltiorrhizae, Radix Morindae Officinalis, Fructus Corni, Rhizoma Pinelliae Preparatum and Pericarpium Citri Reticulatae are mixed to obtain a raw material mixture, and water is added to the raw material mixture for decocting three times, each time for 1h, and the decocting liquid is obtained by combining. The mass ratio of water to the raw material mixture is 10:1 in the first decocting, 7:1 in the second decocting and 5:1 in the third decocting.

[0092] The traditional Chinese medicine composition of Examples 1-8 has a parallel effect on regulating metabolism of polycystic ovary syndrome, and therefore, the effect of the traditional Chinese medicine composition of Example 1 is taken as an example to illustrate the effect.

[0093] I. Inhibition of the traditional Chinese medicine composition on the increase of serum androgen level, improvement of polycystic-like changes in ovary and estrous cycle in PCOS mouse model.

[0094] 1.1. Experimental animals

[0095] 8-week-old C57BL / 6J mice were provided by the Guangdong Experimental Animal Center, SPF level. Animal license number: SYXK(Yue)2020-0227. Animals were housed in separate cages, had free access to water and food, and the humidity in the laboratory was maintained at 40%-70%, with a temperature control of 18-22℃. 12 hours of light and 12 hours of darkness alternated, keeping the environment quiet. After the mice were routinely acclimated for 7 days, modeling, grouping, and experiments were started. The mouse feed, bedding, and all experimental conditions were provided by the Respiratory Disease Key Laboratory of Guangzhou Medical University. The experimental operation process strictly followed the relevant regulations of the Animal Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (Ethical Review Approval Number: FJTCM IACUC2020096) and the "Guidelines for the Treatment of Laboratory Animals".

[0096] 1.2. Drugs, reagents, and main instruments

[0097] Traditional Chinese medicine preparation raw materials (Example 1): Radix Rehmanniae Preparata 30g, Radix Paeoniae Alba 30g, Atractylodes Macrocephala Koidz 30g, Salvia Miltiorrhiza Bunge 30g, Radix Morindae Officinalis 30g, Fructus Corni 15g, Rhizoma Pinelliae Preparatum 15g, Pericarpium Citri Reticulatae 15g (provided by the First Affiliated Hospital of Guangzhou Medical University).

[0098] Dihydrotestosterone (DHT, from Simga, USA, A8380).

[0099] Sesame oil (from Acros organics, Belgium, CAS9008-74-0).

[0100] Benzyl benzoate (from Simga, USA, B6630).

[0101] Blood glucose meter 7600P and matching blood glucose test paper from Bayer.

[0102] Follicle-stimulating hormone (FSH) kit, luteinizing hormone (LH) kit, testosterone (T) kit, and ELISA kit were all provided by Elabscience Co., Ltd.

[0103] 1.3. Experimental methods

[0104] 1.3.1. Animal model establishment method and grouping

[0105] 7-week-old C57 female mice were randomly divided into 2 groups after 1 week of acclimation: control group and PCOS group.

[0106] Vaginal epithelial cell smear (hereinafter referred to as "vaginal smear") test: On the workbench, the mouse tail was lifted up, physiological saline was repeatedly injected into the vaginal orifice with a pipette, and then evenly coated on the glass slide. After the glass slide was dried, H&E staining was performed, and the epithelial cell morphology was observed under a microscope.

[0107] One week after the vaginal smear test, mating experiments were performed. Female mice in proestrus and estrus were caged with male mice overnight. The next morning, the female mice were examined for tampons. If a tampon was found, it was recorded as E1. The tampon is a white plug formed by the coagulation of semen in the vagina after mating in mice. The white plug blocks the vagina to prevent backflow of semen. This white plug structure is called a tampon. The tampon of a mouse is relatively firm and can remain in the vagina for a long time.

[0108] Pregnancy androgen exposure: E16-18 (i.e. 16-18 days after E1 was found) subcutaneous injection of 100 μL solution on the nape of the mouse, wherein (1) the control group mice were subcutaneously injected with 100 μL of a mixture of sesame oil / benzyl benzoate (90 μL of sesame oil and 10 μL of benzyl benzoate) on the nape; (2) the PCOS group mice were subcutaneously injected with 100 μL of DHT-sesame oil / benzyl benzoate mixture (250 μg of DHT (dihydrotestosterone) dissolved in 90 μl of sesame oil and 10 μl of benzyl benzoate) on the nape. Injection was performed once. The control group mice and the PCOS group mice were raised in a standardized SPF level experimental animal room.

[0109] Successful establishment of mouse PCOS model (referred to as F1): The vaginal smear of the PCOS group mice showed persistent post-estrus and inter-estrus, indicating that the mouse PCOS model was successfully established.

[0110] Since PCOS is hereditary, the modeling object is the maternal C57 mice. The offspring of the maternal mice are PCOS models (F1).

[0111] 1.3.2, Preparation of traditional Chinese medicine preparation

[0112] Preparation of traditional Chinese medicine preparation: 30g of Radix Rehmanniae Preparata, 30g of Radix Paeoniae Alba, 30g of Atractylodes Macrocephala Koidz, 30g of Salvia Miltiorrhiza Bge, 30g of Morindae Radicis, 15g of Fructus Corni, 15g of Rhizoma Pinelliae Preparatum, and 15g of Pericarpium Citri Reticulatae were weighed. The mixture was decocted according to the method of Example 1. The decoction conditions were as follows: extraction times: 2 times, extraction temperature: 100°C, extraction time of the first and second times: 1.5h / 1.5h (timing started after bubbling and boiling), water addition multiples of the first and second times: 10 times / 8 times, filtration methods of the first and second times: gauze filtration; the decoction liquid was obtained; then the decoction liquid was concentrated to a drug concentration of 3.9g / mL, and was then divided into glass bottles after high-pressure sterilization, and was stored at -20°C for standby use. The concentration was 3.9g / mL, and the dosage was 0.3mL Bid per mouse (the mouse dosage was 2 times the human conventional dosage based on body weight).

[0113] 1.3.3, Animal grouping and intervention

[0114] F1 intervention group: F1 (PCOS model) mice were weaned at 21 days after birth (recorded as P21), and the mice were randomly divided into three groups: control group, PCOS group, and PCOS + traditional Chinese medicine group. At P63 (63 days after birth), 300 μL was administered intragastrically, twice a day.

[0115] (1) Control group: 300 μL of distilled water was administered intragastrically, twice a day.

[0116] (2) PCOS group: 300 μL of distilled water was administered intragastrically, twice a day.

[0117] (3) PCOS + traditional Chinese medicine group: 300 μL of traditional Chinese medicine preparation (3.9 g / mL) was administered intragastrically, twice a day.

[0118] Continuous intragastric administration for 3 months, and on the last 10 days of each month, continuous vaginal smears were observed for three groups of mice in the same time period.

[0119] 1.4, Detection index

[0120] 1.4.1, Estrous cycle detection

[0121] Continuous vaginal smears were performed on the last 10 days of each month of treatment, and mouse vaginal epithelial cell smears were observed to determine the estrous cycle.

[0122] After the above 1.3.3 treatment for three months, the mice were taken for continuous vaginal epithelial cell smears for 10 days, and the continuous keratinization of vaginal epithelial cells was observed. The simple process is as follows: on the workbench, the mouse tail was lifted up, and physiological saline was repeatedly injected into the vaginal orifice and evenly coated on the glass slide. After the glass slide was dried, H&E staining was performed, and the epithelial cell morphology was observed under a microscope.

[0123] 1.4.2, glucose tolerance test

[0124] ① At 22 weeks of age, the mice were fasted for one day, and the next morning, tail vein blood was collected, and the fasting blood glucose value (FPG) was measured using a Bayer blood glucose meter (7600P type).

[0125] ② Oral glucose: 2 g / kg of 20% glucose (from Simga Company, USA, G7021) was administered.

[0126] ③ Monitor blood glucose value: tail blood was collected to measure blood glucose values at 0, 15, 30, 60, and 120 min after injection.

[0127] ④ Software analysis: EXCEL statistical software was used to analyze and compare the area under the curve (AUC).

[0128] 1.4.3, Morphological observation of ovarian tissue

[0129] After the 23-week mice were sacrificed after anesthesia, one ovary was taken out and fixed in 10% paraformaldehyde solution. After good fixation, the specimen was trimmed, dehydrated, paraffin-embedded, and sliced at the maximum diameter plane of the ovary as the detection surface. After H&E staining, the slice was sealed, observed under a microscope, and photographed.

[0130] 1.4.4, Sex hormone level detection

[0131] After 3 months of the above 1.3.3 treatment, blood was taken from the orbital venous plexus, and after standing at room temperature for 1 h, it was centrifuged at 3000 rpm, 4℃ for 15 min, and the upper phase serum was taken. Enzyme-linked immunosorbent assay (ELISA) was used to detect follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T).

[0132] 1.4.5, Statistical processing

[0133] SPSS22.0 statistical analysis software was used for analysis, and Graph pad Prism9 was used for drawing. The data of this experiment were all measurement data, and the normally distributed data were described as mean ± standard deviation , and the non-normal data were described as median. Repeated measurement data such as body weight and blood glucose were analyzed by repeated measurement test, and measurement data of different time and different groups were analyzed by factor analysis. The measurement data of the three groups of mice met the requirements of normal distribution and homogeneity of variance, and were analyzed by one-way ANOVA, and pairwise comparison was performed; otherwise, non-parametric test of k independent samples was used, and pairwise comparison was performed. The results were considered statistically significant when P<0.05.

[0134] 1.5, Results

[0135] 1.5.1, Effect of traditional Chinese medicine formula on estrous cycle of PCOS mice

[0136] The presence of estrous cycle can reflect the ovulation of mice, and the estrous cycle of PCOS mice generally appears to be stagnant, suggesting that ovulation is abnormal. Figure 1is the improvement effect of the traditional Chinese medicine composition of Example 1 on the estrous cycle of PCOS mice, (A) is the estrous cycle curve of the control group of mice; (B) is the estrous cycle curve of the PCOS group of mice; (C) is the estrous cycle curve of the PCOS+traditional Chinese medicine group of mice in the first month of treatment; (D) is the estrous cycle curve of the PCOS+traditional Chinese medicine group of mice in the second month of treatment; (E) is the estrous cycle curve of the PCOS+traditional Chinese medicine group of mice in the third month of treatment. Among them, the vertical coordinate Estrous Cycle Stage represents the estrous cycle; the horizontal coordinate DAYS represents the number of days. P is the proestrus stage; E is the estrus stage; M is the metestrus stage; and D is the diestrus stage.

[0137] As shown in Figure 1 , the vaginal smear test of estrous cycle found that the vaginal epithelial cell smear of the control (Control) group ( Figure 1 (A)) showed periodic changes, and the cycle was generally 4-5 days. In the detection of 10 consecutive days, the vaginal smear of the PCOS group ( Figure 1 (B)) of mice showed obvious persistent keratinization of epithelial cells or cycle arrest. With the prolongation of treatment time, the PCOS+traditional Chinese medicine group ( Figure 1 (E)) of mice showed obvious active cycle, and the regularity was significantly restored. Therefore, it is proved that the traditional Chinese medicine composition of Example 1 can effectively restore the estrous cycle level after continuous treatment of PCOS mice for three months.

[0138] 1.5.2, improvement effect of the traditional Chinese medicine prescription on the ovarian tissue morphology of PCOS mice

[0139] Figure 2 is the improvement effect of the traditional Chinese medicine composition of Example 1 on the ovarian tissue morphology of PCOS mice. (A) is a micrograph of the morphology of the ovarian (ovary) tissue pathological section of the control group of mice; (B) is a micrograph of the morphology of the ovarian tissue pathological section of the PCOS group of mice; (C) is a micrograph of the morphology of the ovarian tissue pathological section of the PCOS+traditional Chinese medicine group of mice.

[0140] As shown in Figure 2 , the number of follicles at all levels of the ovary of the control group of mice was rich, the development was normal, the granulosa cell arrangement was neat and dense, and a small amount of follicles were expanded. The PCOS group of mice showed more follicles with cystic expansion, and the connective tissue arrangement was loose. The granulosa cell layer was reduced by 2-3 layers, and the membrane cell layer was thickened. The number of follicles at all levels of the PCOS+traditional Chinese medicine group was rich, and a small amount of follicles were expanded. Therefore, it is proved that the traditional Chinese medicine composition of Example 1 can effectively improve the ovarian tissue morphology of PCOS mice.

[0141] 1.5.3, influence of the traditional Chinese medicine prescription on the serum hormone level of PCOS mice

[0142] The serum hormone levels directly reflect the influence of PCOS on the reproductive capacity of the mice, as shown in Figure 3 Figure 3 is a comparison of the improvement of the serum hormone levels of the PCOS mice by the traditional Chinese medicine composition of Example 1. (A) is a Testosterone (T) column chart of the control group, the PCOS group and the PCOS+traditional Chinese medicine group of mice. (B) is an FSH (follicle-stimulating hormone) column chart of the control group, the PCOS group and the PCOS+traditional Chinese medicine group of mice. (C) is an LH (luteinizing hormone) column chart of the control group, the PCOS group and the PCOS+traditional Chinese medicine group of mice. (D) is an LH / FSH column chart of the control group, the PCOS group and the PCOS+traditional Chinese medicine group of mice.

[0143] As shown in Figure 3 , the T and LH / FSH levels in the PCOS group are significantly higher than those in the control group and the PCOS+traditional Chinese medicine group (P<0.05); the LH / FSH level in the PCOS+traditional Chinese medicine group is higher than that in the control group (P<0.05). This shows that the traditional Chinese medicine composition of Example 1 can reduce the serum androgen and regulate the serum hormone levels of the PCOS mice by affecting the testosterone synthesis, thereby improving the symptoms related to polycystic ovary syndrome.

[0144] 1.5.4. Influence of the traditional Chinese medicine prescription on the expression of serum inflammatory factors of the PCOS mice

[0145] The expression of the serum inflammatory factors shows the influence of PCOS on the inflammation in the mice, as shown in Figure 4 Figure 4 is a comparison of the improvement of the serum inflammatory factor expression of the PCOS mice by the traditional Chinese medicine composition of Example 1. (A) is an mRNA fold change column chart of the serum inflammatory factor Il1b of the control group, the PCOS group and the PCOS+traditional Chinese medicine group of mice. (B) is an mRNA fold change column chart of the serum inflammatory factor Il6 of the control group, the PCOS group and the PCOS+traditional Chinese medicine group of mice. (C) is an mRNA fold change column chart of the serum inflammatory factor Tnf of the control group, the PCOS group and the PCOS+traditional Chinese medicine group of mice. (D) is an mRNA fold change column chart of the serum inflammatory factor Il10 of the control group, the PCOS group and the PCOS+traditional Chinese medicine group of mice. (E) is an mRNA fold change column chart of the serum inflammatory factor Il33 of the control group, the PCOS group and the PCOS+traditional Chinese medicine group of mice.

[0146] As shown in Figure 4 ​​As shown, the expression of serum inflammatory factors Il1b, Il6, and Tnf in the PCOS group reveals the effect of PCOS on inflammation in mice. The gene expression of Il1b, Il6, Tnf, Il10, and Il33 in the PCOS group was significantly higher than that in the control group and the PCOS+traditional Chinese medicine group (P<0.05). The gene expression of Il1b and Tnf in the PCOS+traditional Chinese medicine group was significantly lower than that in the control group (P<0.05); the gene expression of Il6, Il10, and Il33 in the PCOS+traditional Chinese medicine group was significantly lower than that in the PCOS group (P<0.05). This indicates that the traditional Chinese medicine composition of Example 1 of this invention can reduce the expression of serum inflammatory factors in PCOS mice.

[0147] 1.5.5 Effects of Traditional Chinese Medicine Formulas on Glucose Metabolism in PCOS Mice

[0148] Glucose metabolism reflects insulin resistance in mice, such as Figure 5 As shown. Figure 5 This is a comparison of the effects of the traditional Chinese medicine composition of Example 1 on the expression of androgen-related genes in PCOS mice.

[0149] like Figure 5 As shown, the AUC of blood glucose time in the PCOS + traditional Chinese medicine group was lower than that in the PCOS group (P<0.05).

[0150] II. Chemical Composition Analysis of Traditional Chinese Medicine Formulas

[0151] The chemical composition analysis of the traditional Chinese medicine formula was performed by gas chromatography-mass spectrometry (GC-MS).

[0152] 2.1 Instruments and Analytical Conditions

[0153] 2.1.1 Instruments

[0154] Agilent 6545 time-of-flight mass spectrometer, C18 column (2.1×150mm, 1.8μm).

[0155] 2.1.2 Analytical Conditions and Methods

[0156] The carrier gas was helium (99.999%), the flow rate was 1.0 mL / min, and the injection volume was 1.0 μL. The injection port temperature was 150 °C, held for 2 min, and then increased to 300 °C at 15 °C / min and stabilized for 5 min.

[0157] 2.1.3 Mass Spectrometry Conditions

[0158] The ionization method is an EI source with an ionization energy of 70 electron volts and a scanning range of 50–1700 m / z.

[0159] Dual AJS ESI; Gas Temp: 320 °C; Gas Flow: 8 L / min; Nebulizer: 45 psi; Sheath Gas Temp: 350 °C; Sheath Gas Flow: 11 L / min.

[0160] VCap: 3500 V; Nozzle Voltage: 500 V / 1000 V; Fragmentor: 130 V.

[0161] 2.1.4. Liquid chromatography conditions

[0162] Column: Agilent C18 column (2.1 x 150 mm, 1.8 μm), column temperature: 40 °C.

[0163] Mobile phase A: 0.1% formic acid water, mobile phase B: methanol.

[0164] Flow rate: 0.4 mL / min, injection volume: 1 μL.

[0165] Gradient elution program: 0-1 min, 15% B; 1-5 min, 15%-30% B; 5-30 min, 30%-70% B; 30-35 min, 70%-95% B; 35-45 min, 95% B.

[0166] 2.2. Preparation of test solution

[0167] The traditional Chinese medicine composition of Example 1 of the present application was extracted according to the method of 1.3.2 to prepare a traditional Chinese medicine preparation. Specifically, 30 g of Radix Rehmanniae Preparata, 30 g of Radix Paeoniae Alba, 30 g of Radix Atractylodis Macrocephalae, 30 g of Radix Salviae Miltiorrhizae, 30 g of Radix Morindae Officinalis, 15 g of Fructus Corni, 15 g of Rhizoma Pinelliae Praeparatum, and 15 g of Pericarpium Citri Reticulatae were weighed. The mixture was decocted according to the method of Example 1, and the decocting conditions were as follows: extraction times: 2 times, extraction temperature: 100 °C, extraction time of the first and second times: 1.5 h / 1.5 h (the time was counted after the boiling began), water addition amount of the first and second times: 10 times / 8 times, and filtration mode of the first and second times: gauze filtration. The decocting liquid was obtained. Then, the decocting liquid was concentrated to a drug concentration of 3.9 g / mL, and was then divided into glass bottles which had been sterilized by autoclaving, and was stored at -20 °C for standby use.

[0168] Preparation of test solution: 1 mL of the traditional Chinese medicine preparation (3.9 g / mL) was taken, and mobile phase A (0.1% formic acid water) was added. The mixture was ultrasonically extracted for 40 min, 40% methanol was added to make up to 50 mL, and the mixture was filtered through a 0.22 μm microporous filter. The filtrate was used as the test solution (for use in liquid chromatography-mass spectrometry analysis).

[0169] 2.3, detection results

[0170] The test sample solution was subjected to liquid chromatography-mass spectrometry analysis (UPLC-MS / MS) using the above mass spectrometry and chromatography conditions, and the chemical components of the traditional Chinese medicine preparation were detected and analyzed, as shown in Table 1 and Figures 6-7 .

[0171] Figure 6 is a total ion chromatogram (negative mode) of the traditional Chinese medicine preparation prepared from the traditional Chinese medicine composition of Example 1. Figure 7 is a total ion chromatogram (positive mode) of the traditional Chinese medicine preparation prepared from the traditional Chinese medicine composition of Example 1.

[0172] Table 1 Analysis of chemical components of traditional Chinese medicine prescription

[0173]

[0174]

[0175]

[0176] The results in Table 1 and Figures 6-7 The analysis of the results shows that the chemical component analysis of the traditional Chinese medicine composition by mass spectrometry analysis can obtain that the main effective components of the traditional Chinese medicine composition are composed of quinine acid, malic acid, citric acid, pyroglutamic acid, gallic acid, etc. Figures 6-7 The positive and negative ion chromatograms also verify the traditional Chinese medicine composition of the traditional Chinese medicine composition.

[0177] The above is only a preferred embodiment of the present application and is not intended to limit the present application. Any modification, equivalent replacement and improvement within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A traditional Chinese medicine composition for regulating metabolism in polycystic ovary syndrome, characterized in that, Made from the following raw materials in the indicated weight ratios: Prepared Rehmannia Root 25-35 parts, White Peony Root 25-35 parts, Atractylodes Rhizome 25-35 parts, Salvia Root 25-35 parts, Morinda Root 25-35 parts, Cornus Fruit 10-20 parts, Ginger-processed Pinellia Rhizome 10-20 parts, Tangerine Peel 10-20 parts.

2. The traditional Chinese medicine composition for regulating metabolism in polycystic ovary syndrome according to claim 1, characterized in that, Made from the following raw materials in the indicated weight ratios: Prepared Rehmannia Root 25-30 parts, White Peony Root 25-30 parts, Atractylodes Rhizome 25-30 parts, Salvia Root 25-30 parts, Morinda Root 25-30 parts, Cornus Fruit 10-15 parts, Ginger-processed Pinellia Rhizome 10-15 parts, Tangerine Peel 10-15 parts.

3. The traditional Chinese medicine composition for regulating metabolism in polycystic ovary syndrome according to claim 2, characterized in that, Made from the following raw materials in the indicated weight ratios: Prepared Rehmannia Root 30 parts, White Peony Root 30 parts, Atractylodes Rhizome 30 parts, Salvia Root 30 parts, Morinda Root 30 parts, Cornus Fruit 15 parts, Ginger-processed Pinellia Rhizome 15 parts, Tangerine Peel 15 parts.

4. The traditional Chinese medicine composition for regulating metabolism in polycystic ovary syndrome according to claim 1, characterized in that, The preparation of this traditional Chinese medicine composition is as follows: Take Rehmannia glutinosa, Paeonia lactiflora, Atractylodes macrocephala, Salvia miltiorrhiza, Morinda officinalis, Cornus officinalis, Pinellia ternata, and Citrus reticulata to obtain a raw material mixture. Add water to the raw material mixture and decoct it 1 to 3 times. Combine the decoction liquids to obtain the final product.

5. The traditional Chinese medicine composition for regulating metabolism in polycystic ovary syndrome according to claim 4, characterized in that, The mass ratio of water to raw material mixture is 5 to 10:

1.

6. The traditional Chinese medicine composition for regulating metabolism in polycystic ovary syndrome according to claim 4, characterized in that, Each simmering time is 1 to 2 hours.

7. A traditional Chinese medicine preparation, characterized in that, The traditional Chinese medicine preparation is made from a therapeutically effective amount of the traditional Chinese medicine composition as described in claim 1.

8. The use of the traditional Chinese medicine composition according to any one of claims 1 to 6 in the preparation of a drug for regulating metabolism in polycystic ovary syndrome.

9. The use of the traditional Chinese medicine composition according to claim 8 in the preparation of a drug for regulating metabolism in polycystic ovary syndrome, characterized in that, Prepare drugs to reduce androgen levels in female animals, promote ovulation, or promote conception.

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