Kidney-nourishing, heat-clearing, dampness-dispelling, and blood stasis-resolving formula and application thereof

Abstract

This invention discloses a formula for nourishing the kidneys, clearing heat, promoting diuresis, and resolving blood stasis, and its application. The formula comprises the following ingredients in parts by weight: Anemarrhena asphodeloides 7-13 parts, Rehmannia glutinosa 7-13 parts, Trionyx sinensis 12-18 parts, Dianthus superbus 7-13 parts, Dendrobium nobile 7-13 parts, Prunus persica 7-13 parts, Trichosanthes kirilowii 9-15 parts, Coptis chinensis 2-7 parts, Phellodendron chinense 7-13 parts, Cinnamomum cassia 2-7 parts, and Plantago asiatica 7-13 parts. This formula, provided by this invention, not only treats polycystic ovary syndrome but also significantly improves quality of life and has a role in preventing and treating depression. The present invention discloses a kidney-nourishing, heat-clearing, dampness-dispelling, and blood stasis-resolving formula and its application. The formula comprises the following raw materials by weight: 7-13 parts of Anemarrhena asphodeloides, 7-13 parts of Rehmannia glutinosa, 12-18 parts of turtle shell, 7-13 parts of Desmodium styracifolium, 7-13 parts of Dendrobium, 7-13 parts of peach kernel, 9-15 parts of Trichosanthes seed, 2-7 parts of Coptis chinensis, 7-13 parts of Phellodendron amurense, 2-7 parts of cinnamon twig, and 7-13 parts of Plantago major. The kidney-nourishing, heat-clearing, dampness-dispelling, and blood stasis-resolving formula provided by this invention is capable of significantly improving the quality of life and preventing depression while treating polycystic ovary syndrome.

Description

[Technical Field]

[0001] This invention relates to the field of traditional Chinese medicine, specifically to a formula for nourishing the kidneys, clearing heat, promoting diuresis, and removing blood stasis, and its application. [Previous Technology]

[0002] Polycystic ovarian syndrome (PCOS) is a common and complex reproductive endocrine and metabolic disease, characterized by infrequent ovulation or anovulation, hyperandrogenemia and polycystic ovarian changes. It has a high risk of serious long-term complications such as diabetes, cardiovascular disease and endometrial cancer. The incidence rate can reach 5%-10% of women of reproductive age. About 50% of infertile patients are related to PCOS, and 90%-95% of infertile women with anovulation have this disease. Patients often seek medical attention due to prolonged menstrual cycles or even amenorrhea or infertility. Menstruation is often a sign for women to self-assess their female physiological health. Abnormal menstruation can easily increase the psychological pressure of patients and aggravate psychological disorders. In addition, external manifestations such as hirsutism, acne, and obesity can also affect the patient's self-confidence, thereby affecting the patient's physical and mental health[1].

[0003] In terms of therapeutics, there is currently no ideal treatment plan for PCOS. Western medicine treatment plans include laparoscopic ovarian puncture, ovulation induction with medication, and anti-androgen drugs and insulin sensitivity enhancement. However, these treatments are mostly staged interventions, and the surgical trauma is significant. The effects of drug treatment are limited, and they do not have a positive preventive effect on the occurrence of long-term complications. In addition, they have drawbacks such as significant side effects, inability to take them for a long time, and high relapse rate after stopping medication. Therefore, they are not the best choice for PCOS patients.

[0004] Traditional Chinese medicine (TCM) believes that the pathogenesis of polycystic ovary syndrome (PCOS) is due to dysfunction of the kidney, liver, and spleen, resulting in phlegm and blood stasis, often manifesting as a deficiency of the root and excess of the branch. The core of TCM treatment for PCOS is syndrome differentiation and treatment based on syndrome differentiation. Common syndrome types include spleen and kidney yang deficiency, phlegm and blood stasis, kidney deficiency and blood stasis, and kidney yin deficiency. Treatment focuses on tonifying the kidney, promoting blood circulation and removing blood stasis, and eliminating dampness and phlegm. A few treatments, based on syndrome differentiation, employ methods to soothe the liver and strengthen the spleen. Medication primarily consists of kidney-yang tonifying drugs, blood-activating and stasis-removing drugs, and phlegm-dampness-resolving drugs. However, TCM alone often struggles to address amenorrhea and menstrual disorders caused by persistent anovulation, hirsutism and acne caused by hyperandrogenemia. Therefore, a treatment model combining TCM with oral contraceptives is frequently used clinically. Because it is difficult to achieve spontaneous ovulation, a treatment model combining TCM with Western ovulation-inducing drugs is often used for those desiring fertility.

[0005] Traditional Chinese medicine currently uses formulas that nourish the kidneys, clear heat, promote diuresis, and remove blood stasis to treat patients with polycystic ovary syndrome (PCOS) of the kidney yin deficiency type. While these methods have achieved some efficacy, as described in CN108403919A, they do not significantly improve quality of life, especially physiological function, job responsibility, emotional job responsibility, social function, and mental health related to depression. Therefore, this invention provides a new formula for nourishing the kidneys, clearing heat, promoting diuresis, and removing blood stasis, which can significantly improve quality of life while treating PCOS.

[0006] References: [1] Liang Ruining, Sun Xueyan, Li Peishuang, et al. Effect of Zishen Qingre Lishi Huayu Decoction on spontaneous ovulation menstruation in patients with polycystic ovary syndrome of kidney yin deficiency [J]. Chinese Journal of Integrated Traditional and Western Medicine, 2021, DOI:10.7661 / j.cjim.20200813.321. [Summary of the Invention]

[0007] Purpose of the invention: The technical problem to be solved by the present invention is to provide a formula for nourishing the kidney, clearing heat, promoting diuresis and removing blood stasis, and its application, in order to address the shortcomings of the prior art.

[0008] In order to solve the above-mentioned technical problems, the present invention discloses the following technical solution:

[0009] In a first aspect, the present invention provides a traditional Chinese medicine composition and a traditional Chinese medicine extract.

[0010] Traditional Chinese medicine (TCM) initially understood polycystic ovary syndrome (PCOS) based on its clinical manifestations, primarily obesity and amenorrhea. TCM believed that "obese people often have phlegm," and the *Jinkui Yaolue* (Essential Prescriptions of the Golden Chamber) stated that "those suffering from phlegm retention should be treated with warming medicines." Furthermore, phlegm and dampness easily obstruct the meridians, leading to phlegm and blood stasis. Therefore, TCM primarily treats PCOS with kidney-yang tonifying drugs, blood-activating and stasis-removing drugs, and phlegm-dampness-resolving drugs. However, after more than 20 years of clinical research, the inventor discovered that while PCOS patients often present with obesity, they also frequently exhibit symptoms of damp-heat, such as acne, dry mouth, oily skin, a pale red or reddish tongue, and a thin, yellow, greasy tongue coating. Based on clinical practice and a study of classical TCM theories, the inventor determined that the pathogenesis of PCOS is mainly kidney yin deficiency, internal damp-heat generation, blood stasis obstructing the meridians, leading to an "overflowing" of blood and qi in the Chong meridian. The main treatment principle is to nourish kidney yin, clear damp heat, and resolve blood stasis and calm the Chong meridian. The method and formula for nourishing kidney yin, clearing damp heat, and resolving blood stasis and calming the Chong meridian were established.

[0011] In this invention, the raw materials in the traditional Chinese medicine composition or extract are Anemarrhena asphodeloides, Rehmannia glutinosa, Trionyx sinensis, Dianthus superbus, Dendrobium nobile, Prunus persica, Trichosanthes kirilowii, Coptis chinensis, Phellodendron chinense, Cinnamomum cassia, and Plantago asiatica.

[0012] The traditional Chinese medicine composition comprises the following raw materials in parts by weight: Anemarrhena asphodeloides 7-13 parts, Rehmannia glutinosa 7-13 parts, Trionyx sinensis 12-18 parts, Dianthus superbus 7-13 parts, Dendrobium nobile 7-13 parts, Prunus persica 7-13 parts, Trichosanthes kirilowii 9-15 parts, Coptis chinensis 2-7 parts, Phellodendron chinense 7-13 parts, Cinnamomum cassia 2-7 parts, and Plantago asiatica 7-13 parts. Further, the raw materials include Glycyrrhiza uralensis, preferably 2-12 parts.

[0013] The herbal extract is prepared from the following raw materials in parts by weight: Anemarrhena asphodeloides 7-13 parts, Rehmannia glutinosa 7-13 parts, Trionyx sinensis 12-18 parts, Dianthus superbus 7-13 parts, Dendrobium nobile 7-13 parts, Prunus persica 7-13 parts, Trichosanthes kirilowii 9-15 parts, Coptis chinensis 2-7 parts, Phellodendron chinense 7-13 parts, Cinnamomum cassia 2-7 parts, and Plantago asiatica 7-13 parts. Further, the raw materials include licorice, preferably 2-12 parts.

[0014] In this traditional Chinese medicine composition and extract, Anemarrhena asphodeloides and Rehmannia glutinosa nourish kidney yin and clear heat and purge fire, serving as the principal herbs; Coptis chinensis and Phellodendron chinense clear heat and dry dampness, Trionyx sinensis nourishes yin, clears heat, softens hardness and dissipates nodules, Dianthus superbus and Prunus persica invigorate blood, remove blood stasis, and regulate menstruation, serving as the assistant herbs; Trichosanthes kirilowii clears heat and resolves phlegm, Dendrobium nobile benefits the stomach, generates fluids, nourishes yin and clears heat, Plantago asiatica clears heat and promotes diuresis, and Cinnamomum cassia calms the surging and descends rebellious qi, all serving as adjuvant herbs; Glycyrrhiza uralensis harmonizes all the herbs, serving as the guiding herb. The entire formula works to nourish kidney yin, clear damp heat, remove blood stasis, and regulate menstruation.

[0015] The effects of these Chinese medicinal herbs are as follows:

[0016] Anemarrhena asphodeloides: It is bitter and cold in nature, and enters the lung, stomach and kidney meridians; its functions are to nourish yin and reduce fire, moisten dryness and lubricate the intestines.

[0017] Rehmannia: This can be a processed product made by mixing raw Rehmannia with rice wine, steaming, and sun-drying. It has a sweet taste and warm nature, and enters the liver and kidney meridians. Its functions include nourishing blood and moisturizing the body, replenishing essence and marrow.

[0018] Turtle shell: Salty and cold in nature, enters the liver and kidney meridians; Efficacy: Nourishes yin and subdues yang, softens hardness and dissipates nodules.

[0019] Dianthus superbus: Bitter and cold in nature, enters the heart and small intestine meridians; Efficacy: promotes urination and relieves strangury, invigorates blood and regulates menstruation.

[0020] Dendrobium: Sweet and slightly cold in nature, enters the stomach and kidney meridians; Efficacy: Nourishes yin and clears heat, benefits the stomach and promotes the production of body fluids;

[0021] Peach kernel: It is bitter and sweet in taste, and neutral in nature. It enters the heart, liver and large intestine meridians. Its functions are to promote blood circulation and remove blood stasis, moisten the intestines and promote bowel movement, and relieve cough and asthma.

[0022] Trichosanthes kirilowii seed: Sweet and cold in nature, it enters the lung, stomach, and large intestine meridians. Efficacy: Moistens the lungs and resolves phlegm, moistens the intestines and promotes bowel movement.

[0023] Coptis chinensis: Bitter and cold in nature, it enters the heart, spleen, stomach, liver, gallbladder, and large intestine meridians. Functions: Clears heat and dries dampness, drains fire and detoxifies.

[0024] Phellodendron bark: Bitter and cold in nature, it enters the kidney, bladder, and large intestine meridians. Functions: Clears heat and dries dampness, drains fire and detoxifies, reduces fever and eliminates steaming sensation.

[0025] Cinnamon Twig: pungent and sweet in taste, warm in nature, enters the lung, heart, and bladder meridians. Functions: induces sweating and relieves muscle tension, warms and unblocks the meridians, assists yang and promotes qi transformation. It calms and relieves rebellious qi, making it an essential medicine for treating rebellious qi.

[0026] Plantago asiatica: Sweet and cold in nature, it enters the liver, kidney, lung, and small intestine meridians. Functions: Clears heat and promotes diuresis, eliminates phlegm, cools the blood, and detoxifies.

[0027] Licorice: Sweet and neutral in nature, it enters the heart, lung, spleen, and stomach meridians. Functions: Tonifies the spleen and replenishes qi, clears heat and detoxifies, and harmonizes the effects of other herbs.

[0028] In some cases, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: Anemarrhena asphodeloides 7-13 parts, Rehmannia glutinosa 7-13 parts, Trionyx sinensis 12-18 parts, Dianthus superbus 7-13 parts, Dendrobium nobile 7-13 parts, Prunus persica 7-13 parts, Trichosanthes kirilowii 9-15 parts, Coptis chinensis 2-7 parts, Phellodendron chinense 7-13 parts, Cinnamomum cassia 2-7 parts, Plantago asiatica 7-13 parts, Glycyrrhiza uralensis 2-12 parts; preferably, the parts by weight of each raw material are as follows: Anemarrhena asphodeloides 8-12 parts, Rehmannia glutinosa 8-12 parts, Trionyx sinensis 13-17 parts, Dianthus superbus 8-12 parts, Dendrobium nobile 8-12 parts, Prunus persica 8-12 parts, Trichosanthes kirilowii 10-14 parts, Coptis chinensis 2-6 parts, Phellodendron chinense 8-12 parts, Cinnamomum cassia 2-7 parts, Plantago asiatica 8-12 parts. The ingredients are: 2-12 parts of licorice; preferably, the weight parts of each ingredient are as follows: 8-12 parts of anemarrhena, 8-12 parts of rehmannia, 13-17 parts of turtle shell, 8-12 parts of dianthus, 8-12 parts of dendrobium, 8-12 parts of peach kernel, 10-14 parts of trichosanthes seed, 2-6 parts of coptis, 8-12 parts of phellodendron, 2-5 parts of cinnamon twig, 8-12 parts of plantain, and 4-10 parts of licorice; preferably, the weight parts of each ingredient are as follows: 10 parts of anemarrhena, 8-12 parts of rehmannia, 13-17 parts of turtle shell, 8-12 parts of dianthus, 8-12 parts of dendrobium, 8-12 parts of peach kernel, 10-14 parts of trichosanthes seed, 2-6 parts of coptis, 8-12 parts of phellodendron, 2-5 parts of cinnamon twig, 8-12 parts of plantain, and 4-10 parts of licorice. One example is: Anemarrhena asphodeloides 10 parts, Rehmannia glutinosa 10 parts, Trionyx sinensis 15 parts, Dianthus superbus 10 parts, Dendrobium nobile 10 parts, Prunus persica 10 parts, Trichosanthes kirilowii 12 parts, Coptis chinensis 3 parts, Phellodendron chinense 10 parts, Cinnamomum cassia 3 parts, Plantago asiatica 10 parts, Glycyrrhiza uralensis 6 parts. Another example is: Anemarrhena asphodeloides 10 parts, Rehmannia glutinosa (processed) 10 parts, vinegar-processed Trionyx sinensis 15 parts, Dianthus superbus 10 parts, Dendrobium nobile 10 parts, Prunus persica 10 parts, Trichosanthes kirilowii 12 parts, Coptis chinensis 3 parts, Phellodendron chinense 10 parts, Cinnamomum cassia 3 parts, Plantago asiatica 10 parts, Glycyrrhiza uralensis 6 parts.

[0029] In some cases, the herbal extract is prepared from raw materials comprising the following parts by weight: Anemarrhena asphodeloides 7-13 parts, Rehmannia glutinosa 7-13 parts, Trionyx sinensis 12-18 parts, Dianthus superbus 7-13 parts, Dendrobium nobile 7-13 parts, Prunus persica 7-13 parts, Trichosanthes kirilowii 9-15 parts, Coptis chinensis 2-7 parts, Phellodendron chinense 7-13 parts, Cinnamomum cassia 2-7 parts, Plantago asiatica 7-13 parts, Glycyrrhiza uralensis 2-12 parts; preferably, the parts by weight of each raw material are as follows: Anemarrhena asphodeloides 8-12 parts, Rehmannia glutinosa 8-12 parts, Trionyx sinensis 13-17 parts, Dianthus superbus 8-12 parts, Dendrobium nobile 8-12 parts, Prunus persica 8-12 parts, Trichosanthes kirilowii 10-14 parts, Coptis chinensis 2-6 parts, Phellodendron chinense 8-12 parts, Cinnamomum cassia 2-7 parts, Plantago asiatica 8- 12. Licorice 2-12 parts; preferably, the weight parts of each raw material are as follows: Anemarrhena 8-12 parts, Rehmannia 8-12 parts, Trionyx 13-17 parts, Dianthus 8-12 parts, Dendrobium 8-12 parts, Peach kernel 8-12 parts, Trichosanthes 10-14 parts, Coptis 2-6 parts, Phellodendron 8-12 parts, Cinnamon twig 2-5 parts, Plantago 8-12 parts, Licorice 4-10 parts; preferably, the weight parts of each raw material are as follows: Anemarrhena 10 parts, Rehmannia 8-12 parts, Trionyx 13-17 parts, Dianthus 8-12 parts, Dendrobium 8-12 parts, Peach kernel 8-12 parts, Trichosanthes 10-14 parts, Coptis 2-6 parts, Phellodendron 8-12 parts, Cinnamon twig 2-5 parts, Plantago 8-12 parts, Licorice 4-10 parts. One example is: Anemarrhena asphodeloides 10 parts, Rehmannia glutinosa 10 parts, Trionyx sinensis 15 parts, Dianthus superbus 10 parts, Dendrobium nobile 10 parts, Prunus persica 10 parts, Trichosanthes kirilowii 12 parts, Coptis chinensis 3 parts, Phellodendron chinense 10 parts, Cinnamomum cassia 3 parts, Plantago asiatica 10 parts, Glycyrrhiza uralensis 6 parts. Another example is: Anemarrhena asphodeloides 10 parts, Rehmannia glutinosa (processed) 10 parts, vinegar-processed Trionyx sinensis 15 parts, Dianthus superbus 10 parts, Dendrobium nobile 10 parts, Prunus persica 10 parts, Trichosanthes kirilowii 12 parts, Coptis chinensis 3 parts, Phellodendron chinense 10 parts, Cinnamomum cassia 3 parts, Plantago asiatica 10 parts, Glycyrrhiza uralensis 6 parts.

[0030] The traditional Chinese medicine composition and the traditional Chinese medicine extract are prepared by the following method: raw materials are weighed according to the following weight proportions, including Anemarrhena asphodeloides, Rehmannia glutinosa, Carapax Trionycis, Dianthus superbus, Dendrobium nobile, Prunus persica, Trichosanthes kirilowii, Coptis chinensis, Phellodendron chinense, Cinnamomum cassia, Plantago asiatica, and further, the raw materials include Glycyrrhiza uralensis. The raw materials are decocted and filtered to obtain a filtrate containing the traditional Chinese medicine composition or the traditional Chinese medicine extract; wherein, the decoction is performed by adding water; preferably, the quality of the water is 8-10 times the quality of the raw materials; preferably, the number of decoctions is 1-3 times; preferably, the total decoction time is 1-3 hours.

[0031] In a second aspect, the present invention provides a method for preparing the traditional Chinese medicine composition and traditional Chinese medicine extract described in the first aspect above.

[0032] The preparation method of the traditional Chinese medicine composition and the traditional Chinese medicine extract includes: weighing raw materials according to the weight parts, the raw materials including Anemarrhena asphodeloides, Rehmannia glutinosa, Carapax Trionycis, Dianthus superbus, Dendrobium nobile, Prunus persica, Trichosanthes kirilowii, Coptis chinensis, Phellodendron chinense, Cinnamomum cassia, Plantago asiatica, and further, the raw materials include Glycyrrhiza uralensis, decocting, filtering, and obtaining a filtrate containing the traditional Chinese medicine composition or the traditional Chinese medicine extract.

[0033] Wherein the decoction is performed by adding water; preferably, the quality of the water is 8-10 times that of the raw material; preferably, the number of decoctions is 1-3 times; preferably, the total decoction time is 1-3 hours.

[0034] In terms of cooperation with manufacturers, the present invention provides a pharmaceutical preparation.

[0035] The traditional Chinese medicine composition and extract obtained by the present invention can also be formulated into various preparations by adding different excipients according to the needs of clinical use and using conventional preparation processes.

[0036] The pharmaceutical preparation includes (i) the traditional Chinese medicine composition or extract described in the first aspect above, or the traditional Chinese medicine composition or extract prepared by the method described in the second aspect above, or a combination of the foregoing; and (ii) pharmaceutically acceptable excipients.

[0037] The pharmaceutical preparation uses the traditional Chinese medicine composition for treating polycystic ovary syndrome as the active ingredient. The pharmaceutical preparation is prepared into a commonly used dosage form in pharmaceuticals using conventional preparation methods in the art.

[0038] The pharmaceutical preparations of the present invention can be prepared by the following method:

[0039] (A) Weigh each of the medicinal materials and mix them to obtain a mixture;

[0040] (B) A pharmaceutically acceptable carrier is added to the mixture, and the mixture is prepared using conventional methods in the art.

[0041] In a fourth aspect, the present invention provides the traditional Chinese medicine composition and extract described in the first aspect above, the traditional Chinese medicine composition and extract prepared by the method described in the second aspect, and the use of the pharmaceutical preparation described in the second aspect in the preparation of products for treating polycystic ovary syndrome and / or depression.

[0042] The product includes pharmaceuticals or health foods.

[0043] Wherein, the treatment of polycystic ovary syndrome is to improve the quality of life while treating polycystic ovary syndrome.

[0044] In a fifth aspect, the present invention provides a medicament for treating polycystic ovary syndrome, wherein the active ingredient of the medicament is the traditional Chinese medicine composition and extract described in the first aspect, the traditional Chinese medicine composition and extract prepared by the method described in the second aspect, or the pharmaceutical preparation described in the present invention in cooperation with a manufacturer.

[0045] In a sixth aspect, the present invention provides a product for treating polycystic ovary syndrome and / or depression, comprising the traditional Chinese medicine composition and extract described in the first aspect above, the traditional Chinese medicine composition and extract prepared by the method described in the second aspect, and the pharmaceutical preparation described in the present invention.

[0046] The product includes pharmaceuticals or health foods.

[0047] The treatment of polycystic ovary syndrome is to improve quality of life while treating polycystic ovary syndrome.

[0048] One example of Rehmannia glutinosa in this invention is processed Rehmannia glutinosa; one example of turtle shell is vinegar-processed turtle shell.

[0049] The dosage of the pharmaceutical preparation described in this invention can be determined based on the amount of drug contained in the final preparation in order to achieve the required effective therapeutic dose and complete the preventive and / or therapeutic effects of this invention.

[0050] The traditional Chinese medicine composition described in this invention is a traditional Chinese medicine composition used to treat polycystic ovary syndrome and / or depression.

[0051] The Chinese herbal extract described in this invention is a Chinese herbal extract used to treat polycystic ovary syndrome and / or depression.

[0052] The pharmaceutical preparation described in this invention is a pharmaceutical preparation for treating polycystic ovary syndrome and / or depression.

[0053] The improvement of quality of life described in this invention includes:

[0054] Increase the scores of any one or more dimensions of the Short Form-36 (SF-36) Health Questionnaire in physical functioning, physiological functioning, bodily pain, general health, vitality, social functioning, emotional functioning, and mental health; and / or, increase the scores of any one or more dimensions of the PCOS Quality of Life Questionnaire (PCOSQ) in body hair, mood, weight, infertility, and menstruation.

[0055] Beneficial effects:

[0056] The kidney-nourishing, heat-clearing, dampness-removing, and blood-stasis-resolving formula provided by this invention can significantly improve the quality of life while treating polycystic ovary syndrome, and also has the effect of preventing and treating depression.

[0057] The kidney-nourishing, heat-clearing, dampness-removing, and blood-stasis-resolving formula provided by this invention can not only help PCOS patients restore ovarian function, promote ovulation, and facilitate pregnancy, but also has few side effects, no drug dependence, and good safety.

[0058] The traditional Chinese medicine composition for treating polycystic ovary syndrome (PCOS) provided by this invention uses inexpensive raw materials, is easy to prepare, convenient to use, has few side effects, and can be taken for a long time. After years of clinical application research, it has shown good efficacy in treating PCOS. Given the large number of people suffering from PCOS and the currently unsatisfactory effects of clinical hormone therapy, the traditional Chinese medicine compound preparation provided by this invention has promising application prospects.

Implementation Method

[0059] Unless otherwise specified, the experimental methods described in the following examples are conventional methods; unless otherwise specified, the reagents and materials can be obtained commercially. Unless otherwise noted, the medicinal materials are all processed Chinese medicinal herbs, which can be obtained from sales companies or processed after obtaining them.

[0060] Example 1: The effect of a kidney-nourishing, heat-clearing, dampness-removing, and blood-stasis-resolving formula on spontaneous ovulatory menstruation in PCOS patients: A multicenter, double-blind, randomized, placebo-controlled trial

[0061] 1.1 Experimental Design

[0062] This study is a multicenter, double-blind, randomized, placebo-controlled trial conducted in accordance with the Declaration of Helsinki and reviewed by the medical ethics committees of the participating institutions.

[0063] 1.2 Subjects

[0064] The subjects were patients with polycystic ovary syndrome (PCOS), and all included patients met the criteria and signed informed consent forms.

[0065] 1.3 Inclusion Criteria

[0066] ① Patients diagnosed with PCOS according to the revised Rotterdam diagnostic criteria: oligomenorrhea (menstrual cycle ≥ 35 days) or amenorrhea (no menstruation for 6 months) are necessary conditions; additional conditions are a. ≥ 12 antral follicles with a diameter less than 10 mm or ovarian volume greater than 10 cm³ as determined by transvaginal / rectal ultrasound; or b. clinical or biochemical hyperandrogenemia (clinical hyperandrogenemia includes hirsutism, acne and androgenic alopecia; biochemical hyperandrogenemia refers to elevated serum testosterone levels).

[0067] ② Patients aged 18-40 who do not currently have fertility requirements.

[0068] ③ Willing to be treated according to the treatment plan specified in this trial.

[0069] 1.4 Exclusion Criteria

[0070] ① Hyperprolactinemia: serum prolactin (PRL) levels ≥25 ng / ml on two separate occasions at least one week apart;

[0071] ② Serum follicle-stimulating hormone (FSH) > 15 IU / L;

[0072] ③ Patients with thyroid disease, serum thyroid-stimulating hormone (TSH) < 0.2 mIU / mL or > 5.5 mIU / mL;

[0073] ④ Poorly controlled type II diabetes patients;

[0074] ⑤ Suspected Cushing's syndrome patient;

[0075] ⑥ Patients suspected of having adrenal or ovarian tumors secreting androgens;

[0076] ⑦ Hypertensive patients with poorly controlled blood pressure, with systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg;

[0077] ⑧ Those who have taken hormones or other medications within the past 3 months, which may affect the results;

[0078] ⑨ Pregnant or lactating women;

[0079] ⑩ Serious or acute diseases of the heart, liver, kidneys, or blood.

[0080] 1.5 Randomization and Blinding

[0081] Eligible participants were randomly assigned in a 1:1 ratio to either the traditional Chinese medicine group or the placebo group. The randomization sequence was generated by computer by independent researchers not involved in treatment, data collection, or evaluation, and each subcenter was provided with a random number and group assignment. The participant's serial number was printed on the outer packaging of the corresponding drug or placebo according to the determined grouping scheme. The study employed a double-blind method; participants, researchers, and physicians were unaware of the intervention. Researchers distributed the study drug, corresponding to the serial number on the packaging, according to the order in which participants were enrolled.

[0082] 1.6 Intervention Measures

[0083] The treatment group (traditional Chinese medicine group) was treated with a traditional Chinese medicine compound formula, Zishen Qingre Lishi Huayu Fang (Nourishing Kidney, Clearing Heat, Promoting Diuresis, and Resolving Blood Stasis Formula). This formula consisted of 12 ingredients: Anemarrhena asphodeloides 10g, Rehmannia glutinosa 10g, Turtle shell (processed with vinegar) 15g, Dianthus superbus 10g, Dendrobium nobile 10g, Prunus persica 10g, Trichosanthes kirilowii 12g, Coptis chinensis 3g, Phellodendron chinense 10g, Cinnamomum cassia 3g, Plantago asiatica 10g, and Glycyrrhiza uralensis 6g. These ingredients were decocted twice with 8 times the amount of water, 1.5 hours per decoction. The control group received a placebo. Both medications were packaged identically and had the same appearance, smell, and color. Subjects took the medication from the first day of enrollment, one prescription dose per day, twice daily, once in the morning and once in the evening, for a total of 3 months.

[0084] 1.7 Outcome Indicators

[0085] The primary outcome measure is the monthly ovulation rate (total number of ovulations per group during the 3-month treatment period / number of samples per group × 3), with ovulation defined as a progesterone level > 3 ng / mL. When basal body temperature measurements show a biphasic temperature pattern, serum progesterone levels are measured after the high temperature has persisted for 2-4 days.

[0086] Secondary outcome measures included: 1) Menstrual conditions, including the number of menstrual cycles and the average number of days of the menstrual cycle during 3 months of treatment. 2) Anthropometric characteristics, including body weight, body mass index, and waist-to-hip ratio. 3) Hair: Assessed using the Ferriman-Gallwey questionnaire, with hair scores on nine body parts (upper lip, chin, chest, arm, upper abdomen, lower abdomen, upper back, lower back, and thigh) ranging from 0 (none) to 4 (equivalent to a hairy man). 4) Acne: Scored using the criteria proposed by Rosenfield, with the nature and number of skin lesions as the scoring criteria, divided into 0 - 5 points. 5) Glucose and lipid metabolism indices, including total cholesterol, triglycerides, fasting blood glucose, insulin, 2-hour blood glucose and insulin levels during an oral glucose tolerance test, and the insulin resistance index calculated according to the formula (Insulin resistance, IR = fasting glucose mmol / l × fasting insulin mIU / L / 22.5). 6) Quality of life: Assessed using the Short Form-36 (SF-36) health questionnaire and the Polycystic Ovary Syndrome Quality of Life Questionnaire (PCOSQ). The SF-36 is the most commonly used general tool for measuring quality of life, consisting of 8 dimensions (physical function, role physical, bodily pain, general health, vitality, social function, role emotional, mental health), a total of 36 items. The score range for each dimension is from 0 to 100, and a higher score indicates better conditions. The PCOSQ is a specific tool for measuring the quality of life in PCOS, consisting of 5 dimensions (hairy body, mood, weight, infertility, menstruation), a total of 26 items. Each item score is selected from 7 options ranging from 1 (always) to 7 (never), and a higher score indicates better function. 7) Adverse events related to the study drug: Record all adverse events occurring during the treatment of the subjects and assess the relevance to the study treatment.

[0087] 1.8 Statistical analysis

[0088] After preliminary pre-studies, we found that the monthly ovulation rate of the traditional Chinese medicine compound Zishen Qingre Lishi Huayu formula in the treatment of PCOS was 40.3%, and the monthly ovulation rate after the placebo acted on PCOS was 15.8%. α is the type I error probability, β is the type II error probability. Considering a 25% dropout rate, it was calculated that 63 eligible subjects needed to be included in each group, and the total sample size of the two groups was 126 cases.

[0089] Data analysis was performed by statisticians who were unclear about the grouping settings. Intention-to-treat (ITT) analysis included all randomized participants, and unobserved outcome events were uniformly recorded as "anovulation". Per-protocol (PP) analysis included participants who received complete intervention treatment, excluding participants who were lost to follow-up, withdrew, discontinued, or intermittently took medication for various reasons. Furthermore, we performed sensitivity analysis, excluding 12 participants with intermittent medication (5 in the control group and 7 in the treatment group) before comparing differences in secondary outcome measures. Normally distributed continuous variables were expressed as mean ± standard deviation, and two independent samples t-tests were used to compare differences between groups. Non-normally distributed continuous variables were expressed as median (interquartiles), and Wilcoxon rank-sum tests were used to compare differences between groups. Categorical variables were expressed as frequency and relative frequency (%), and chi-square tests were used to compare differences between groups. All statistical analyses were performed in SAS 9.4 software, using two-tailed tests. A p-value < 0.05 was considered statistically significant.

[0090] 1.9 Result

[0091] This study included 126 eligible participants, of whom 117 completed all treatments and follow-ups. In the treatment group, 2 participants withdrew midway due to personal reasons, 2 became pregnant, and 2 lost contact. In the control group, 2 participants withdrew due to personal reasons, and 1 became pregnant. In addition, 7 participants in the treatment group interrupted medication during treatment due to home isolation for Covid-19, and 5 participants in the control group interrupted medication during treatment due to home isolation for Covid-19. The baseline characteristics of the two groups before treatment were comparable (see Table 1).

[0092] Regarding ovulation, during the 3-month treatment period, both ITT and PP analyses showed that the monthly spontaneous ovulation rate in the Chinese medicine group was significantly higher than that in the control group (ITT: 36.5% vs. 14.3%, P < 0.001, RR 2.56, 95% CI 1.72 to 3.80; PP: 38.0% vs. 14.6%, P < 0.001, RR 2.61, 95% CI 1.71 to 3.99, see Table 2).

[0093] Regarding menstruation, during the 3-month treatment period, both ITT and PP analyses showed that the number of menstrual periods in the traditional Chinese medicine group was significantly higher than that in the control group (ITT: 27.0% vs. 11.6%, P < 0.001, RR 2.32, 95% CI 1.47 to 3.66; PP: 29.3% vs. 12.1%, P < 0.001, RR 2.42, 95% CI 1.50 to 3.91, see Table 2). The average menstrual cycle length in the traditional Chinese medicine group was shortened by 8.66±28.71 days, which was significantly different from that in the control group (P < 0.001) (see Table 3).

[0094] After 3 months of treatment, there were no significant differences in weight, body mass index, waist-to-hip ratio, and Ferriman-Gallwey hair score between the two groups. The acne score in the traditional Chinese medicine group decreased by 0.6±0.81, which was statistically significant compared with the control group (P < 0.001). There were no statistically significant differences in glucose and lipid metabolism indicators between the two groups (see Table 3).

[0095] Regarding quality of life, after 3 months of treatment, the PCOSQ and SF-36 scores of the traditional Chinese medicine group were significantly higher than baseline. The PCOSQ scores for body hair, mood, menstruation, weight, and infertility in the traditional Chinese medicine group all showed varying degrees of increase compared to the control group (P < 0.001), with the mood score showing the most significant increase (2.13 ± 1.60). The traditional Chinese medicine group also showed significant improvements compared to baseline in SF-36 physiological function, role-physiological function, role-emotional function, social function, mental health, vitality, bodily pain, and overall health, with significant differences compared to the control group (P < 0.001) (see Table 3).

[0096] No drug-related adverse events occurred during the study period, and no abnormalities were found in blood routine tests and liver and kidney function tests after the treatment.

[0097] Table 1 Baseline Characteristics Control group (n=63) Treatment group (n=63) p-value Age (years) 25.6±4.2 24.3±4.4 0.090 Age at menarche (years) 13.1±1.3 13.2±1.2 0.827 Menstrual cycle (days) 59.8±19.3 61.3±19.6 0.667 Weight (kg) 57.0±10.1 55.5±7.9 0.344 Body mass index (kg / m²) 2 ) 22.0±3.5 21.8±2.9 0.721 Waist circumference (cm) 67.0±4.0 66.3±3.7 0.291 Hip circumference (cm) 88.0±2.9 87.2±3.0 0.126 Waist-to-hip ratio 0.8±0.0 0.8±0.0 0.879 hair 5.0 (3.0, 6.0) 5.0 (3.0, 6.0) 0.660 Acne 1.0 (0.0, 2.0) 1.0 (0.0, 2.0) 0.124 Glucose and lipid metabolism Total cholesterol (mmol / L) 1.0 (0.6, 1.3) 0.9 (0.7, 1.3) 0.598 Triglycerides (mmol / L) 4.5±1.0 4.5±0.7 0.992 Fasting blood glucose (mmol / L) 4.8±0.4 4.8±0.4 0.573 Fasting insulin (uIU / ml) 12.1 (8.7, 15.4) 11.5 (8.1, 15.8) 0.779 0.5-hour blood glucose (mmol / L) 7.9±1.7 8.0±1.4 0.854 0.5h insulin (uIU / ml) 89.3±41.4 101.9±46.4 0.110 1-hour blood glucose (mmol / L) 7.6±1.9 7.1±1.4 0.094 1-hour insulin (uIU / ml) 98.7±51.6 96.6±51.8 0.823 2-hour blood glucose (mmol / L) 6.1±1.6 5.7±1.3 0.120 2-hour insulin (uIU / ml) 71.2±51.3 62.6±41.9 0.306 HOMA-IR 2.6 (1.9,3.3) 2.5 (1.7,3.6) 0.620 PCOSQ body hair 3.5±1.2 3.2±1.4 0.289 mood 3.3±1.1 3.0±1.2 0.217 menstruation 3.2±1.0 2.9±1.0 0.135 weight 3±1.1 3.1±1.3 0.557 Infertility 2.9±1.2 3±1.3 0.563 SF-36 Health Questionnaire Physiological functions 55.0 (40.0, 65.0) 55.0 (45.0, 65.0) 0.920 Physiological functions 25.0 (0.0,25.0) 25.0 (0.0,25.0) 0.099 Emotional Function 33.3 (0.0, 66.7) 33.3 (0.0, 33.3) 0.622 social function 37.5 (25.0, 37.5) 37.5 (25.0, 37.5) 0.094 Mental health 40.0 (36.0, 52.0) 36.0 (32.0, 48.0) 0.062 vitality 50.0 (35.0, 55.0) 40.0 (30.0, 55.0) 0.201 Body pain 12.5 (12.5, 25.0) 12.5 (0.0, 25.0) 0.974 Overall health 50.0 (40.0, 55.0) 50.0 (40.0, 60.0) 0.460 Note: Indicators from hair, acne, total cholesterol, fasting insulin, HOMA-IR, and the SF-36 health questionnaire did not conform to a normal distribution and are presented as medians (25th percentile, 75th percentile), using the rank-sum test. Other indicators are presented as mean ± standard deviation, using a two-sample t-test. All p-values ​​were greater than 0.05, indicating that the two groups were comparable at baseline.

[0098] Table 2 Comparison of ovulation rate and menstrual frequency, n (%) index control group Treatment group Absolute danger level (95% CI) Relative risk (95% CI) p-value Intention-to-treat (ITT) analysis Main outcome – ovulation rate 27 (14.29) 69 (36.51) 22.22 (13.74 to 30.71) 2.56 (1.72 to 3.80) <0.001 Secondary outcome – menstrual frequency 22 (11.64) 51 (26.98) 15.34 (7.54 to 23.15) 2.32 (1.47 to 3.66) <0.001 Component set analysis (PP) Main outcome – ovulation rate 24 (14.55) 57 (38.00) 23.45 (14.01 to 32.90) 2.61 (1.71 to 3.99) <0.001 Secondary outcome – menstrual frequency 20 (12.12) 44 (29.33) 17.21 (8.39 to 26.04) 2.42 (1.50 to 3.91) <0.001 Note: 1. In the ITT and PP analyses, n (%) represents the number of times the outcome occurred (frequency), not the sample size. 2. The total sample size for the ITT was 63 participants in the control group and 63 participants in the treatment group. The total sample size for the PP was 55 participants in the control group and 50 participants in the treatment group (excluding all participants who did not receive the complete intervention). 3. The p-value was calculated using the chi-square test.

[0099] Table 3 Comparison of other secondary outcome indicators Difference in effect before and after intervention in the control group Difference in effect before and after intervention in the treatment group p-value Menstrual cycle (days) 15.25±15.70 -8.66±28.71 <0.001 Weight (kg) -0.94±1.73 -0.89±1.78 0.893 Body mass index (kg / m²) 2 ) -0.35±0.7 -0.34±0.68 0.954 Waist circumference (cm) 0.13±0.9 0.12±0.72 0.964 Hip circumference (cm) 0.00±0.00 0.00±0.00 / Waist-to-hip ratio 0.00±0.01 0.00±0.01 0.762 hair 0.00±0.00 -0.18±0.80 0.118 Acne 0.00±0.00 -0.60±0.81 <0.001 Glucose and lipid metabolism Total cholesterol (mmol / L) -0.06±1.09 -0.10±0.60 0.832 Triglycerides (mmol / L) -0.04±1.02 -0.04±0.74 0.994 Fasting blood glucose (mmol / L) 0.03±0.44 0.07±0.67 0.741 Fasting insulin (uIU / ml) -0.21±6.58 0.98±7.70 0.393 0.5-hour blood glucose (mmol / L) -0.20±1.45 0.08±1.48 0.320 0.5h insulin (uIU / ml) 0.16±37.53 -5.47±35.13 0.431 1-hour blood glucose (mmol / L) -0.30±2.22 -0.17±1.97 0.758 1-hour insulin (uIU / ml) -7.36±51.82 -8.38±54.31 0.922 2-hour blood glucose (mmol / L) -0.01±1.81 0.16±1.07 0.547 2-hour insulin (uIU / ml) -1.40±56.05 2.00±47.34 0.739 HOMA-IR -0.02±1.65 0.27±1.78 0.388 PCOSQ body hair 0.25±1.48 1.74±2.07 <0.001 mood 0.26±0.97 2.13±1.60 <0.001 menstruation 0.25±0.90 1.74±1.63 <0.001 weight 0.20±0.78 1.57±1.77 <0.001 Infertility 0.27±1.25 1.72±1.83 <0.001 SF-36 Health Questionnaire Physiological functions 1.64±14.11 29.8±17.17 <0.001 Physiological functions 4.09±26.25 34.00±31.44 <0.001 Emotional Function -8.49±36.41 24.67±37.38 <0.001 social function 2.50±12.59 30.25±25.89 <0.001 Mental health 1.89±10.88 26.72±21.86 <0.001 vitality -1.27±7.71 24.5±19.36 <0.001 Body pain -1.82±11.13 24.25±25.18 <0.001 Overall health 2.82±11.09 18.30±16.56 <0.001 Note: The difference in effect before and after intervention is the difference between each indicator three months later and each indicator at baseline (reflecting the treatment effect). The difference follows a normal distribution (sample size ≥ 50) and is expressed as mean ± standard deviation. A two-sample t-test is used to compare whether there is a difference in the mean difference between the indicators of the treatment group and the control group.

[0100] Example 2

[0101] Formula: 10 parts Anemarrhena asphodeloides, 10 parts Rehmannia glutinosa, 15 parts Vinegar-processed turtle shell, 10 parts Dianthus superbus, 10 parts Dendrobium nobile, 10 parts Prunus persica, 12 parts Trichosanthes kirilowii, 3 parts Coptis chinensis, 10 parts Phellodendron chinense, 3 parts Cinnamomum cassia, 10 parts Plantago asiatica, 6 parts Glycyrrhiza uralensis.

[0102] Preparation process: Weigh each component according to the formula, add water at 8 times the total weight of raw materials, decoct twice, decoct for 1 hour each time, filter to obtain filtrate; concentrate the obtained filtrate to obtain concentrated solution, further concentrate and dry the concentrated solution, and prepare the preparation according to conventional methods.

[0103] Example 3

[0104] Formula: Anemarrhena asphodeloides 8 parts, Rehmannia glutinosa 12 parts, Vinegar-processed turtle shell 13 parts, Dianthus superbus 12 parts, Dendrobium nobile 12 parts, Prunus persica 8 parts, Trichosanthes kirilowii 14 parts, Coptis chinensis 2 parts, Phellodendron chinense 8 parts, Cinnamomum cassia 3 parts, Plantago asiatica 8 parts, Glycyrrhiza uralensis 6 parts.

[0105] Preparation process: Weigh each component according to the formula, add water at 8 times the total weight of raw materials, decoct once for 2 hours, filter to obtain filtrate; concentrate the obtained filtrate to obtain concentrated solution, which can be further concentrated and dried to prepare preparations according to conventional methods.

[0106] Example 4

[0107] Formula: 10 parts Anemarrhena asphodeloides, 10 parts Rehmannia glutinosa, 15 parts Vinegar-processed turtle shell, 10 parts Dianthus superbus, 10 parts Dendrobium nobile, 10 parts Prunus persica, 12 parts Trichosanthes kirilowii, 3 parts Coptis chinensis, 10 parts Phellodendron chinense, 3 parts Cinnamomum cassia, 10 parts Plantago asiatica, 10 parts Glycyrrhiza uralensis.

[0108] Preparation process: Weigh each component according to the formula, add water at 10 times the total weight of raw materials, decoct once for 1.5 hours, filter to obtain filtrate; concentrate the obtained filtrate to obtain concentrated solution, further concentrate and dry the concentrated solution, and prepare the preparation according to conventional methods.

[0109] Example 5

[0110] Formula: 10 parts Anemarrhena asphodeloides, 10 parts Rehmannia glutinosa, 15 parts Vinegar-processed turtle shell, 10 parts Dianthus superbus, 10 parts Dendrobium nobile, 10 parts Prunus persica, 12 parts Trichosanthes kirilowii seed, 3 parts Coptis chinensis, 10 parts Phellodendron chinense, 5 parts Cinnamomum cassia, 10 parts Plantago asiatica, 6 parts Glycyrrhiza uralensis.

[0111] Preparation process: Weigh each component according to the formula, add water at 8 times the total weight of raw materials, decoct twice, decoct for 1 hour each time, filter to obtain filtrate; concentrate the obtained filtrate to obtain concentrated solution, further concentrate and dry the concentrated solution, and prepare the preparation according to conventional methods.

[0112] Example 6

[0113] Formula: Anemarrhena asphodeloides 12 parts, Rehmannia glutinosa 8 parts, Vinegar-processed turtle shell 17 parts, Dianthus superbus 8 parts, Dendrobium nobile 8 parts, Prunus persica 12 parts, Trichosanthes kirilowii 10 parts, Coptis chinensis 6 parts, Phellodendron chinense 12 parts, Cinnamomum cassia 2 parts, Plantago asiatica 12 parts, Glycyrrhiza uralensis 4 parts.

[0114] Preparation process: Weigh each component according to the formula, add water at 10 times the total raw material weight, decoct 3 times, decoct for 1h, 3h and 2h respectively, filter, and combine the filtrates; concentrate the obtained filtrate to obtain concentrated solution, further concentrate and dry the concentrated solution, and prepare the preparation according to conventional methods.

[0115] The products provided in Examples 2-6, like those in Example 1, can significantly improve the quality of life while treating polycystic ovary syndrome and also have the effect of preventing and treating depression.

[0116] Example 7: Case Study on the Effectiveness of Depression Treatment

[0117] Case 1: Ms. Li, 35 years old, with normal menstruation, suffered from severe depression for 7 months, had difficulty falling asleep, felt inferior and hopeless, and often had suicidal thoughts. After taking the medication in Example 1 for 12 weeks, all clinical symptoms disappeared, and the patient's sleep duration was rated as over 7.5 hours per night, with no change in the following six months.

[0118] Case 2: Ms. Chen, 46 years old, with normal menstruation, suffered from severe depression for 12 months, had difficulty falling asleep, felt inferior and hopeless, and often had suicidal thoughts. After taking the traditional Chinese medicine formula in Example 5 for 10 weeks, her clinical symptoms basically disappeared, and she was able to sleep for more than 7 hours every night, with no change in the following year.

[0119] Comparative Example 1:

[0120] 1.1 Treatment methods

[0121] The treatment group received the existing CPOS formula (composition: Anemarrhena asphodeloides 10g, Cornus officinalis 10g, Salvia miltiorrhiza 10g, Prunus persica 10g, Coix lacryma-jobi 15g, Sinapis alba 10g, Phellodendron chinense 10g, Scrophularia ningpoensis 10g, Glycyrrhiza uralensis 6g, 12.6g per packet, containing 45.5g of raw herbs, manufactured by Guangdong Yifang Pharmaceutical Co., Ltd., CPOS formula production batch number: 2014101602). The placebo group received a placebo (composed of starch, pigment, bitter substances, and ginseng flavoring; the CPOS formula and placebo were identical in weight, packaging, appearance, odor, and color, manufactured by Guangdong Yifang Pharmaceutical Co., Ltd., placebo production batch number: 2014101609). One packet was taken twice daily, morning and evening, dissolved in boiling water, for three consecutive months. Throughout the study, patients were required to maintain a normal diet and physical activity, and were not permitted to use any other medications that might affect the results. The observation subject's serial number was printed on the outer packaging of the corresponding drug or analogue according to the group assignment. Researchers then administered the drug according to the serial number, matching the number on the packaging. Neither the researchers nor the patients were aware of their group assignments or the medications they received.

[0122] 1.2 Observation Indicators

[0123] Quality of Life: Assessment was conducted using the PCOS Quality of Life Questionnaire (PCOSQ) and the Short Form-36 (SF-36) Health Questionnaire. The PCOSQ is a specific tool for measuring PCOS quality of life. It consists of five dimensions: body hair, mood, weight, infertility, and menstruation, with a total of 26 items. Each item is scored from 1 (always) to 7 (never), with higher scores indicating better functioning. The SF-36 is the most commonly used general tool for measuring quality of life. It consists of eight dimensions (physiological functioning, role-based physiological functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning, and mental health), with a total of 36 items. Scores for each dimension range from 0 to 100, with higher scores indicating better quality of life.

[0124] 1.3 Statistical Analysis

[0125] Data were processed using SAS 9.4 statistical software. Continuous variables conforming to a normal distribution were expressed as mean ± standard deviation, and differences between groups were compared using a two-sample t-test. Non-normally distributed continuous variables were expressed as median (interquartiles), and differences between groups were compared using a Wilcoxon rank-sum test. Categorical variables were expressed as frequency and relative frequency (%), and differences between groups were compared using a chi-square test. Two-tailed tests were used, and p < 0.05 was considered statistically significant.

[0126] 1.4 Results

[0127] This study included 50 subjects who met the PCOS criteria, of whom 48 completed all treatments and follow-ups. In the control group, 2 subjects withdrew midway due to personal reasons, 1 subject lost contact, and 1 subject withdrew from the trial after discovering hyperthyroidism during treatment. The baseline characteristics of the two groups before treatment were comparable (see Table 4).

[0128] Regarding quality of life, after 3 months of treatment, there were no significant differences between the CPOS formula and the control group in terms of SF-36 physiological function, physiological role, emotional role, social function, mental health, vitality, bodily pain and overall health (P>0.05) (see Table 5).

[0129] Table 4 Baseline Characteristics Control group (n=25) Treatment group (n=25) p-value Age (years) 24.20±3.08 23.20±3.73 0.307 Age at menarche (years) 13.40±1.38 13.04±1.10 0.314 Weight (kg) 55.72±11.23 55.45±8.68 0.926 Body mass index (kg / m²) 2 ) 21.60±3.94 21.43±3.39 0.874 SF-36 Health Questionnaire Physiological functions 91.83±13.99 93.33±10.03 0.635 Physiological functions 71.67±27.65 60.00±35.11 0.158 Emotional Function 67.78±38.64 55.56±38.49 0.225 social function 78.75±20.28 71.67±19.40 0.172 Mental health 69.47±11.91 64.40±17.71 0.199 vitality 56.33±18.66 56.67±18.82 0.945 Body pain 85.00±11.56 84.17±16.72 0.823 Overall health 56.33±21.29 51.67±19.36 0.378 Note: Data are presented as mean ± standard deviation, and a two-sample t-test was used. The test showed that all p-values ​​were greater than 0.05, indicating that the two groups were comparable at baseline.

[0130] Table 5 Comparison of indicators before and after intervention Difference in effect before and after intervention in the control group Difference in effect before and after intervention in the treatment group p-value SF-36 Health Questionnaire Physiological functions -3.39±9.2 -2.17±6.39 0.753 Physiological functions -7.14±27.94 -13.33 ±41.38 0.321 Emotional Function -7.14±45.68 -15.56±42.65 0.771 social function -0.89±17.65 -9.17±16.06 0.995 Mental health 0.57±11.71 -4.40±12.49 0.893 vitality -3.57±16.55 -5.00±12.39 0.609 Body pain 0.45±17.17 0.83±15.02 0.815 Overall health 0.00±15.46 -4.83±16.58 0.983 Note: The difference in effect before and after intervention is the difference between each indicator three months later and each indicator at baseline (reflecting the treatment effect). The difference follows a normal distribution and is expressed as mean ± standard deviation. A two-sample t-test is used to compare whether there is a difference in the mean difference between the indicators of the treatment group and the control group.

[0131] Comparative Example 2:

[0132] In the process of conducting a PCOS study using the oral Chinese medicine formula Nourishing Kidney, Clearing Heat, Promoting Diuresis, Resolving Blood Stasis and Unblocking Collaterals (Chinese Invention No. 201810536499.6), the inventors of this application found that in terms of various quality of life indicators such as physiological function, physiological role, emotional role, social function, mental health, vitality, bodily pain, and overall health, there were no significant differences between the Chinese medicine groups 1 and 2 and the control group.

[0133] The above-described embodiments are merely illustrative of several implementations of the present invention, and their descriptions are relatively specific and detailed. However, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of the present invention should be determined by the appended claims. [Simplified Explanation of the Diagram]

[0134] None

Claims

1. A traditional Chinese medicine composition, characterized in that it is made from the following raw materials in parts by weight: Anemarrhena asphodeloides 7-13 parts, Rehmannia glutinosa 7-13 parts, Trionyx sinensis 12-18 parts, Dianthus superbus 7-13 parts, Dendrobium nobile 7-13 parts, Prunus persica 7-13 parts, Trichosanthes kirilowii 9-15 parts, Coptis chinensis 2-7 parts, Phellodendron chinense 7-13 parts, Cinnamomum cassia 2-7 parts, Plantago asiatica 7-13 parts, Glycyrrhiza uralensis 2-12 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that the weight parts of each raw material are as follows: Anemarrhena asphodeloides 8-12 parts, Rehmannia glutinosa 8-12 parts, Trionyx sinensis 13-17 parts, Dianthus superbus 8-12 parts, Dendrobium nobile 8-12 parts, Prunus persica 8-12 parts, Trichosanthes kirilowii 10-14 parts, Coptis chinensis 2-6 parts, Phellodendron chinense 8-12 parts, Cinnamomum cassia 2-7 parts, Plantago asiatica 8-12 parts, Glycyrrhiza uralensis 2-12 parts.

3. The traditional Chinese medicine composition according to claim 1, characterized in that the weight parts of each raw material are as follows: Anemarrhena asphodeloides 8-12 parts, Rehmannia glutinosa 8-12 parts, Trionyx sinensis 13-17 parts, Dianthus superbus 8-12 parts, Dendrobium nobile 8-12 parts, Prunus persica 8-12 parts, Trichosanthes kirilowii 10-14 parts, Coptis chinensis 2-6 parts, Phellodendron chinense 8-12 parts, Cinnamomum cassia 2-5 parts, Plantago asiatica 8-12 parts, Glycyrrhiza uralensis 4-10 parts.

4. A traditional Chinese medicine extract, characterized in that it is extracted from the following raw materials in parts by weight: Anemarrhena asphodeloides 7-13 parts, Rehmannia glutinosa 7-13 parts, Trionyx sinensis 12-18 parts, Dianthus superbus 7-13 parts, Dendrobium nobile 7-13 parts, Prunus persica 7-13 parts, Trichosanthes kirilowii 9-15 parts, Coptis chinensis 2-7 parts, Phellodendron chinense 7-13 parts, Cinnamomum cassia 2-7 parts, Plantago asiatica 7-13 parts, Glycyrrhiza uralensis 2-12 parts.

5. The herbal extract as described in claim 4, characterized in that the weight parts of each raw material are as follows: Anemarrhena asphodeloides 8-12 parts, Rehmannia glutinosa 8-12 parts, Trionyx sinensis 13-17 parts, Dianthus superbus 8-12 parts, Dendrobium nobile 8-12 parts, Prunus persica 8-12 parts, Trichosanthes kirilowii 10-14 parts, Coptis chinensis 2-6 parts, Phellodendron chinense 8-12 parts, Cinnamomum cassia 2-7 parts, Plantago asiatica 8-12 parts, Glycyrrhiza uralensis 2-12 parts.

6. The herbal extract as described in claim 4, characterized in that the weight parts of each raw material are as follows: Anemarrhena asphodeloides 8-12 parts, Rehmannia glutinosa 8-12 parts, Trionyx sinensis 13-17 parts, Dianthus superbus 8-12 parts, Dendrobium nobile 8-12 parts, Prunus persica 8-12 parts, Trichosanthes kirilowii 10-14 parts, Coptis chinensis 2-6 parts, Phellodendron chinense 8-12 parts, Cinnamomum cassia 2-5 parts, Plantago asiatica 8-12 parts, Glycyrrhiza uralensis 4-10 parts.

7. The herbal extract as described in claim 4, characterized in that the weight parts of each raw material are as follows: Anemarrhena asphodeloides 10 parts, Rehmannia glutinosa 8-12 parts, Trionyx sinensis 13-17 parts, Dianthus superbus 8-12 parts, Dendrobium nobile 8-12 parts, Prunus persica 8-12 parts, Trichosanthes kirilowii 10-14 parts, Coptis chinensis 2-6 parts, Phellodendron chinense 8-12 parts, Cinnamomum cassia 2-5 parts, Plantago asiatica 8-12 parts, Glycyrrhiza uralensis 4-10 parts.

8. The herbal extract as described in claim 4, characterized in that the weight parts of each raw material are as follows: 10 parts of Anemarrhena asphodeloides, 10 parts of Rehmannia glutinosa, 15 parts of Trionyx sinensis, 10 parts of Dianthus superbus, 10 parts of Dendrobium nobile, 10 parts of Prunus persica, 12 parts of Trichosanthes kirilowii, 3 parts of Coptis chinensis, 10 parts of Phellodendron chinense, 3 parts of Cinnamomum cassia, 10 parts of Plantago asiatica, and 6 parts of Glycyrrhiza uralensis.

9. The herbal extract as claimed in claim 4, characterized in that it is prepared by the following method: weighing raw materials according to the weight proportions, decocting, filtering, and obtaining a filtrate containing the herbal extract.

10. A method for preparing a traditional Chinese medicine composition as described in claim 1, characterized in that it comprises: Weigh the raw materials according to the specified weight proportions, decoct them, filter them, and obtain a filtrate containing the Chinese herbal composition.

11. The method for preparing the traditional Chinese medicine composition as described in claim 10, characterized in that the decoction is performed by adding water; the quality of the water is 8-10 times the quality of the raw materials; the number of decoctions is 1-3 times; and the total decoction time is 1-3 hours.

12. A pharmaceutical preparation, characterized in that it comprises (i) a traditional Chinese medicine composition as described in any one of claims 1 to 3, or a traditional Chinese medicine extract as described in any one of claims 4 to 9, or a traditional Chinese medicine composition prepared by the method described in claim 10, or a combination of the foregoing; and (ii) pharmaceutically acceptable excipients.

13. The use of a traditional Chinese medicine composition as described in any one of claims 1 to 3, or a traditional Chinese medicine extract as described in any one of claims 4 to 9, or a traditional Chinese medicine composition prepared by the method described in any one of claims 10 to 14, or a pharmaceutical preparation as described in claim 15, in the preparation of a product for treating polycystic ovary syndrome and / or depression.

14. The application as described in claim 13, wherein the product comprises a drug or a health food.

15. The application as described in claim 13, characterized in that the treatment of polycystic ovary syndrome improves quality of life while treating polycystic ovary syndrome.

16. A product for treating polycystic ovary syndrome and / or depression, characterized in that it comprises a traditional Chinese medicine composition as described in any one of claims 1 to 3, or a traditional Chinese medicine extract as described in any one of claims 4 to 9, or a traditional Chinese medicine composition prepared by the method described in claim 10, or a pharmaceutical preparation as described in claim 12.

17. A medicament for treating polycystic ovary syndrome, characterized in that the medicament uses a traditional Chinese medicine composition as described in any one of claims 1 to 3, or a traditional Chinese medicine extract as described in any one of claims 4 to 9, or a traditional Chinese medicine composition prepared by the method described in claim 10 as an active ingredient.

18. The traditional Chinese medicine composition as claimed in claim 1, characterized in that the Rehmannia glutinosa is prepared Rehmannia glutinosa, and the turtle shell is vinegar-processed turtle shell.

19. The herbal extract as claimed in claim 4, characterized in that the Rehmannia glutinosa is prepared Rehmannia glutinosa and the turtle shell is vinegar-processed turtle shell.