Classical prescription for treating hypoovarian reserve function

Abstract

The invention relates to the technical field of traditional Chinese medicines, and discloses a classic prescription for treating hypoovarian reserve function, which is prepared from the following raw materials: 30 to 40g of Chinese yam, 20 to 30g of semen cuscutae, 10 to 20g of fructus lycii, 10 to 15g of radix achyranthis bidentatae, 10 to 20g of codonopsis pilosula, 10 to 20g of poria cocos, 20 to 30g of malt, 10 to 15g of angelica sinensis and 10 to 30g of radix puerariae. The classical prescription for treating the hypoovarian reserve function has a positive curative effect, and modern network pharmacology also scientifically proves that active ingredients such as quercetin, daidzein, kaempferol and the like contained in the kidney-tonifying and menstruation-regulating prescription are flavonoid compounds from the aspect of action mechanism, so that the prescription has very good anti-inflammatory and anti-oxidative stress ovarian protection effects; the application range is wide, clinical manifestations of patients with the ovarian reserve function decline are generally hypomenorrhea, menoxenia, amenorrhea, infertility or perimenopausal symptoms, and the kidney tonifying and menstruation regulating prescription has a certain regulating effect on the hypomenorrhea.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, in particular to a classical prescription for treating diminished ovarian reserve. BACKGROUND

[0002] Diminished ovarian reserve (DOR) refers to the decrease in the number and / or quality of oocytes in the ovary of a female, which is manifested as the decline in female reproductive capacity. DOR is an early stage of ovarian function decline, and if not actively intervened, it will develop into premature ovarian failure in 1-6 years. In recent years, with the increase of female family and social pressure, its incidence has been increasing year by year and showing a trend of younger age. And DOR is relatively insidious, and patients are often diagnosed due to irregular menstruation, infertility and other diseases, which can easily delay the treatment opportunity and seriously endanger the psychological and reproductive health of women.

[0003] At present, hormone replacement therapy is commonly used in clinical western medicine, which has been proved to significantly improve the clinical symptoms of DOR and restore ovulation, etc. However, long-term use of hormones alone can cause adverse reactions such as breast pain and vaginal bleeding in patients, and increase the risk of breast cancer and endometrial cancer. SUMMARY

[0004] The present application provides a classical prescription for treating diminished ovarian reserve, which has the advantages of good anti-inflammatory, antioxidant stress and ovarian protection, and solves the problems raised in the above background.

[0005] The present application provides the following technical scheme: a classical prescription for treating diminished ovarian reserve, which is composed of the following raw materials: yam 30-40g, cuscuta 20-30g, medlar 10-20g, huaiyikun 10-15g, radix codonopsis 10-20g, tuckahoe 10-20g, malt 20-30g, angelica 10-15g, kudzu root 10-30g.

[0006] Preferably, it is composed of the following raw materials: yam 30g, cuscuta 20g, medlar 10g, huaiyikun 10g, radix codonopsis 10g, tuckahoe 10g, malt 20g, angelica 10g, kudzu root 10g, 1 dose / d.

[0007] Preferably, the decoction method of the decoction is as follows:

[0008] Step S1: Before decoction, the above-mentioned traditional Chinese medicine decoction pieces are soaked in a ceramic vessel with cold water, the liquid level is preferably 2cm higher than the decoction pieces, and after soaking for 30min;

[0009] Step S2: quickly boil with strong fire, and then maintain for about 15-20min with weak fire;

[0010] Step S3: filter the juice while hot, then re-boil with water for 2 times;

[0011] Step S4: finally, mix the 1000ml of the medicine obtained by 3 times of boiling, and then take it;

[0012] Method of taking medicine: 150ml, 3 times a day, after meal.

[0013] Preferably, the preparation method of the powder: mix the above traditional Chinese medicines, use a traditional Chinese medicine crusher to crush, and pass through a 100 mesh sieve to obtain fine powder;

[0014] Method of taking medicine: 10g, 2 times a day, soak in 100ml of water for 10 minutes, and then take it.

[0015] Preferably, the preparation method of the pill is as follows:

[0016] Step S1: mix the above traditional Chinese medicines, use a traditional Chinese medicine crusher to crush, and pass through a 100 mesh sieve to obtain fine powder;

[0017] Step S2: heat the honey to boiling, the color becomes dark, and the viscosity is strong, then heat it to a light red color with a glossy foam on the surface, when the white silk is not strong, turn off the fire, and then cool it to obtain the refined honey;

[0018] Step S3: 30g of refined honey is used to make small honey pills for every 100g of fine powder;

[0019] Method of taking medicine: 8g, 2 times a day, take it with warm water after meal.

[0020] The present application has the following beneficial effects:

[0021] 1、①The curative effect is positive, and modern network pharmacology also scientifically proves from the mechanism that the active ingredients such as quercetin, daidzein and kaempferol in the kidney-tonifying and menstruation-regulating formula are flavonoids, which have good anti-inflammatory and antioxidant stress ovarian protection effects;

[0022] ②The application range is wide, and the clinical manifestations of patients with decreased ovarian reserve function are usually oligomenorrhea, oligomenorrhea, amenorrhea, infertility or perimenopausal symptoms, and the kidney-tonifying and menstruation-regulating formula has certain regulating effects on them;

[0023] ③The economic nature is high, the present application uses the following traditional Chinese medicines: yam, cuscuta, medlar, huaiyin, radix ginseng, tuckahoe, malt, angelica, and radix puerariae; all of them are clinically used traditional Chinese medicines, and the price of the whole set of traditional Chinese medicines is different, and the price is about 10-40 yuan, and according to the feedback of the patients, 1-3 doses can obtain good therapeutic effect, the economic nature is high, and the economic pressure of the patients can be reduced.

[0024] ④For Chinese patent medicines, the formula has the advantages of flexible addition and subtraction.

[0025] 2. The classic prescription for treating diminished ovarian reserve has good therapeutic effect in practice, has few side effects, relatively low price, can be taken for a long time and other advantages, and has wide application prospect in gynecological diseases. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 Comparison of TCM symptom scores of the two groups of patients schematic diagram;

[0027] Figure 2 schematic diagram for comparing the clinical effects of the two groups of patients;

[0028] Figure 3 Comparison of serum FSH, E2 and LH levels of the two groups of patients schematic diagram;

[0029] Figure 4 Comparison of serum GDF9 and BMP45 levels of the two groups of patients schematic diagram. DETAILED DESCRIPTION

[0030] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the protection scope of the present application.

[0031] The theory of traditional Chinese medicine believes that "the kidney stores essence and governs reproduction". The essence stored in the kidney is the premise and basis for the function of the kidney governing reproduction. The essence stored in the kidney includes the essence of predestination and the essence of postnatals. The essence of predestination, as its name implies, is received from parents and comes from predestination, which is the essence for reproduction. "The spirit of the pivot: the meridians" says, "people are born first, and then the essence is formed", which shows that the essence of predestination is the original material of life, forms the embryo, and is stored in the kidney, which has the function of guiding the growth and development and reproduction of the human body. Under the nourishment of the essence of postnatals, it is constantly filled and can better play the key role of reproductive function. Western medicine believes that the occurrence of oocytes is the primary and important link in the process of human reproduction, and the development of follicles is started by multiple factors including the hypothalamic-pituitary-ovarian axis, ovarian endocrine and paracrine factors and many other regulations. Therefore, it can be considered that oocytes and follicles are the manifestation of the essence of reproduction, and the generation of oocytes and the development of follicles are closely related to whether the kidney essence is sufficient. The essence of the kidney is transformed into follicles, and the kidney yin essence and blood nourish oocytes. Deficiency of kidney essence is the basic pathogenesis of the generation and development of oocytes and follicles. Normal menstruation is the external manifestation of the normal development, maturation and discharge of oocytes, and is also the prerequisite for the formation of fetal pregnancy. Tianqi, which Zhang Jingyue called "invisible water", is the essence of yin and essence, which is directly related to reproductive function. It is directly related to the rise and fall of kidney essence, which is "to" the puberty and "exhausted" in the menopausal period. Modern medical scholars believe that Tianqi is a trace amount of substance that cannot be seen with the naked eye but objectively exists in the human body. Western medicine divides the female life cycle into different periods according to the occurrence, development, maturation and decline of ovarian function, which is very consistent with the rise and fall of Tianqi in the Canon of Internal Medicine, suggesting that the connotation of Tianqi includes ovarian function, and Tianqi should be a kind of substance related to reproduction, such as endocrine hormone. Chong is the blood sea, and the uterus is the place of fetus, both of which are closely related to the reproductive organs and sexual function, and their functions should include the function of gonads. Therefore, it is believed that the kidney-Tianqi-chongren can coordinate the uterus to ensure normal menstruation and reproductive function, which is fundamentally related to the functional status of kidney essence. Therefore, it is believed that the kidney-Tianqi-chongren-uterus axis of traditional Chinese medicine and the hypothalamic-pituitary-ovarian axis of modern medicine have a wonderful coincidence, although the theoretical systems are different, but the understanding of the mechanism of human reproductive function regulation has a high consistency. At the same time, it further proves that the deficiency of kidney essence, the kidney failing to store essence and the disorder of reproductive axis are the basic pathogenesis of the occurrence of ovarian reserve dysfunction.

[0032] Please refer to Figures 1-4 A classical prescription for treating ovarian reserve dysfunction, which is composed of the following raw materials: Shanyao 30-40g, Tusizi 20-30g, Gouqi 10-20g, Huai Niuxi 10-15g, Dangshen 10-20g, Fuling 10-20g, Maidu 20-30g, Dangui 10-15g, Gegen 10-30g.

[0033] The following raw materials are used: 30g of Chinese yam, 20g of Chinese dodder, 10g of Chinese wolfberry, 10g of Huaiyishen, 10g of Codonopsis pilosula, 10g of Poria cocos, 20g of malt, 10g of angelica, and 10g of kudzu root, 1 dose per day.

[0034] If cold and fear, add Herba Epimedii and Ba Ji Tian to warm the kidney and assist Yang; if the waist and legs are sore, add fried Eucommia ulmoides and Morinda officinalis to tonify the kidney and strengthen the waist; if dizziness and tinnitus, add Schisandra chinensis and Astragalus complanatus to astringe essence and nourish marrow; if there is chest pain, breast distension, and abdominal distension and pain, add Fructus Meliae, Radix Bupleuri, and Lignum Aquilariae Resinatum to regulate Qi and relieve pain. The author has used the kidney-tonifying and menstruation-regulating prescription to treat patients with ovarian reserve function decline due to deficiency of the kidney and deficiency of Qi and blood for more than ten years, and has obtained good feedback. After treatment, the scores of symptoms such as soreness of the waist and knees, five-center heat, dizziness, tinnitus, and hot flashes, the levels of serum FSH and LH, and the level of E2 were significantly reduced, and the ovarian reserve function was significantly improved. The treatment has a significant effect and is worthy of clinical reference.

[0035] The decoction is prepared by the following method:

[0036] Step S1: Before decoction, the above-mentioned traditional Chinese medicine decoction pieces are soaked in a ceramic vessel with cold water. The liquid level should be about 2cm higher than the decoction pieces. After soaking for 30 minutes,

[0037] Step S2: Boil rapidly with strong fire, and then change to medium heat for about 15-20 minutes.

[0038] Step S3: Filter the medicine juice while it is hot, and then decoct with water for another two times.

[0039] Step S4: Finally, mix about 1000ml of the medicine juice obtained by decoction for three times, and then take it.

[0040] Method of taking medicine: 150ml per time, three times a day, and take it after meals.

[0041] The preparation method of the powder is as follows: mix the above-mentioned traditional Chinese medicines, crush them with a traditional Chinese medicine crusher, and pass the fine powder through a 100-mesh sieve.

[0042] Method of taking medicine: 10g per time, two times a day, and take it after soaking in about 100ml of water for 10 minutes.

[0043] The preparation method of the pill is as follows:

[0044] Step S1: Mix the above-mentioned traditional Chinese medicines, crush them with a traditional Chinese medicine crusher, and pass the fine powder through a 100-mesh sieve.

[0045] Step S2: Heat the honey to boiling, and change to medium heat until the color becomes dark, the viscosity is strong, and there is no white silk. Then, turn off the heat. After cooling, the honey is ready.

[0046] Step S3: 100 g of fine powder was made into small pill with 30 g of refined honey;

[0047] Method of taking: 2 times a day, about 8 g each time, after meals with warm water.

[0048] The Bushen Tiaojing Decoction has good therapeutic effect in the clinical treatment of premature ovarian failure, has the advantages of few side effects, relatively low price, and can be taken for a long time, etc. It has a broad application prospect in gynecological diseases. The following cases are listed to illustrate the effect of the Bushen Tiaojing Decoction in the treatment of decreased ovarian reserve function:

[0049] Materials and Methods

[0050] 1.1 General information

[0051] A total of 116 patients with decreased ovarian reserve function (DOR) were collected, all of whom were admitted to the Department of Gynecology and Obstetrics of the Affiliated Hospital of North Sichuan Medical College from February 2013 to February 2015. They were all patients with deficiency of kidney and deficiency of blood and qi according to TCM syndrome differentiation. They were randomly divided into control group and comprehensive group, 58 cases in each group. The control group was 23-38 years old, with an average of (31.79±4.36) years old; the age of menarche was 12.5-16 years old, with an average of (14.57±1.82) years old; the time of amenorrhea was 0.6-2.2 years, with an average of (1.58±0.17) years; 8 cases of primary infertility, 50 cases of delivery history. The comprehensive group was 24-39 years old, with an average of (32.42±4.49) years old; the age of menarche was 12-16.5 years old, with an average of (14.49±1.77) years old; the time of amenorrhea was 0.7-2.4 years, with an average of (1.62±0.19) years; 9 cases of primary infertility, 49 cases of delivery history. The difference between the two groups in age, menarche time, amenorrhea time and other general conditions was not statistically significant, and they were comparable.

[0052] 1.2 Diagnostic criteria

[0053] 1.2.1 The diagnostic criteria for DOR were developed according to relevant literature such as “Chinese Gynecology and Obstetrics” (second edition) edited by Cao Zeyi, “Chinese Expert Consensus on Clinical Diagnosis and Treatment of Premature Ovarian Insufficiency”, “Bologna Conference Standard of European Human Assisted Reproduction Association” and “Hormone Supplement Consensus of Premature Ovarian Insufficiency”:

[0054] ①Measurement on the 2nd-4th day of menstrual cycle, at least 2 times, interval 4 weeks. Total number of bilateral AFC <6 or bFSH >10 IU / L or E2 >292.8 pmol / L (i.e. 80 pg / ml) (any of the above conditions meets one of them);

[0055] ②AMH≤1.1 ng / ml.

[0056] 1.2.2 Diagnosis criteria of deficiency of kidney and deficiency of qi and blood Refer to the standard of "Guiding principles for clinical research on new drugs of traditional Chinese medicine".

[0057] ① Main symptoms: soreness of waist and knees, pale complexion, delayed menarche, less menstrual flow and amenorrhea gradually;

[0058] ② Secondary symptoms: fatigue, listlessness, tinnitus, deafness, insomnia and amnesia. Pale tongue with white fur, weak pulse. Definite diagnosis requires 2 items of main symptoms combined with secondary symptoms, and tongue and pulse.

[0059] 1.3 Inclusion criteria

[0060] ① Meet the diagnostic criteria of DOR;

[0061] ② Meet the diagnostic criteria of deficiency of kidney and deficiency of qi and blood;

[0062] ③ Not treated with relevant preparations of traditional Chinese medicine in recent period;

[0063] ④ 20-40 years old;

[0064] ⑤ All patients have obtained informed consent and signed the informed consent form.

[0065] 1.4 Exclusion criteria

[0066] ① Amenorrhea caused by other reasons (such as bilateral oophorectomy, gynecological organic lesions, etc.);

[0067] ② Combined with severe diseases of cardiovascular, cerebrovascular, liver, kidney and endocrine system, etc.;

[0068] ③ Patients with mental illness;

[0069] ④ Participate in other clinical trials at the same time;

[0070] ⑤ Do not cooperate with medication during the treatment period.

[0071] 1.5 Treatment method

[0072] 1.5.1 The experimental group was treated with Bushen Tiaojing Decoction, which was composed of Shanyao 30g, Tusizi 20g, Gouqi 10g, Huai Niuxi 10g, Dangshen 10g, Fuling 10g, Maidan 20g, Dangui 10g, Gegen 10g, 1 dose / d, decocted with conventional water, taken orally in the morning and evening, and stopped during menstrual period. The treatment of two groups was 20d for 1 course, and continuous treatment for 3 courses.

[0073] 1.5.2 The control group was treated with Femoston (ABBV, import drug registration certificate number: H20150345), 1 tablet / time, 1 time / d, for 28d, continuous treatment for 3 courses.

[0074] 1.6 Observation index

[0075] ① Comparison of TCM symptom scores between the two groups before and after treatment, referring to the quantification table of kidney deficiency and Qi and blood insufficiency in the "Guiding Principles for Clinical Research of New Chinese Medicines". The evaluation indicators include: soreness of waist and knees, fatigue, dizziness, tinnitus, insomnia and forgetfulness. The symptoms are graded into none (0 points), mild (1 point), moderate (2 points) and severe (3 points).

[0076] ② Serum FSH, E2, and LH were measured in the two groups before and after treatment. About 3 mL of venous blood was drawn in the morning on an empty stomach and tested by enzyme-linked immunosorbent assay (ELISA) before and after treatment. For those in the menstrual cycle, the test was performed on days 1 to 3 of the cycle. The FSH kit was used (Shanghai Jianglai Biotechnology Co., Ltd., batch number A20985); the E2 kit was used (Shanghai Gaochuang Chemical Technology Co., Ltd., batch number CSB-E05108h); and the LH kit was used (Shanghai Fanke Biotechnology Co., Ltd., batch number FK-F8250).

[0077] ③ The serum levels of growth differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15) in the two groups were determined by ELISA before and after treatment. The GDF-9 kit was used (Shanghai Yuanmu Biotechnology Co., Ltd., batch number YMY9626); the BMP-15 kit was used (Nanjing Saihongrui Biotechnology Co., Ltd., batch number E92107Hu).

[0078] 1.7 The efficacy evaluation criteria were established with reference to the "Standards for Diagnosis and Efficacy of Traditional Chinese Medicine Diseases and Syndromes." Clinical cure: Menstruation resumes after treatment, maintaining normal menstruation for more than three cycles, and complete disappearance of clinical symptoms. Improvement: Menstruation resumes after treatment, but the menstrual cycle is not normal, and clinical symptoms are alleviated. Ineffectiveness: Menstruation does not resume after treatment, and clinical symptoms do not improve.

[0079] 1.8 Statistical analysis SPSS 17.0 statistical analysis software was used for data analysis. Measurement data were expressed as x ± s. The t-test was used for comparison between groups. The chi-square test was used to analyze measurement data. P < 0.05 was considered statistically significant.

[0080] 2 Results

[0081] 2.1 Comparison of TCM symptom scores between the two groups After treatment, the scores of TCM symptoms in both groups were significantly reduced (P < 0.01); after treatment, the scores of TCM symptoms in the comprehensive group were significantly lower than those in the control group, and the difference was statistically significant (P < 0.01). Figure 1 .

[0082] 2.2 Comparison of clinical efficacy between the two groups The total effective rate of the comprehensive group was 94.83%, and that of the control group was 81.03%. The comprehensive group was significantly higher than the control group, and the difference was statistically significant (P < 0.05). Figure 2 .

[0083] 2.3 Comparison of serum FSH, E2 and LH levels between the two groups of patients The serum FSH and LH levels of the two groups of patients were significantly decreased after treatment, and the E2 level was increased (P<0.01). After treatment, the serum FSH and LH levels of the comprehensive group were lower than those of the control group, and the E2 level was higher than that of the control group, with a statistically significant difference (P<0.01), as shown in Table 2. Figure 3 .

[0084] 2.4 Comparison of serum GDF-9 and BMP-15 levels between the two groups of patients The serum GDF-9 and BMP-15 levels of the two groups of patients were significantly increased after treatment (P<0.01). After treatment, the serum GDF-9 and BMP-15 levels of the comprehensive group were significantly higher than those of the control group, with a statistically significant difference (P<0.01), as shown in Table 3. Figure 4 .

[0085] It should be noted that the relational terms herein such as first and second and the like are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any such actual relationship or order between such entities or actions. Moreover, the terms "comprises", "comprising", or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but can include other elements not expressly listed or inherent to such process, method, article, or apparatus.

[0086] Although embodiments of the present application have been shown and described, it is to be understood that various modifications, substitutions, alternatives, and variations can be made in the embodiments without departing from the spirit and scope of the present application as defined by the appended claims and their equivalents.

Claims

1. A classic prescription for treating diminished ovarian reserve function, characterized in that: It is composed of the following raw materials: 30-40g of yam, 20-30g of dodder seed, 10-20g of wolfberry, 10-15g of Chinese clematis, 10-20g of Codonopsis pilosula, 10-20g of Poria cocos, 20-30g of malt, 10-15g of Chinese angelica, and 10-30g of Pueraria root.

2. A classic prescription for treating diminished ovarian reserve function according to claim 1, characterized in that: It is composed of the following ingredients: 30g of yam, 20g of dodder seed, 10g of wolfberry, 10g of Chinese clematis, 10g of Codonopsis pilosula, 10g of Poria cocos, 20g of malt, 10g of Chinese angelica, and 10g of Pueraria root.

3. A classic prescription for treating diminished ovarian reserve function according to claim 1, characterized in that: The decoction method is: Step S1: Before decocting, the above-mentioned Chinese herbal medicine slices are placed in a ceramic container and soaked in cold water, preferably with the liquid surface covering the slices by about 2 cm, for 30 minutes; Step S2: Bring to a boil quickly over high heat, then switch to low heat and maintain for about 15 to 20 minutes; Step S3: Filter the medicinal juice while it is hot, and then add water and boil it again for 2 more times; Step S4: Finally, the 1000 ml of medicinal solution obtained by the three decoctions is mixed and taken; Dosage: Take 150ml three times a day, warm after meals.

4. A classic prescription for treating diminished ovarian reserve function according to claim 1, characterized in that: Preparation method of powder: Mix the above Chinese medicines, crush them using a Chinese medicine grinder, and pass through a 100-mesh sieve to obtain fine powder; Dosage: Take 10g twice a day, add 100ml of boiling water and soak for 10 minutes, then drink warm.

5. A classic prescription for treating diminished ovarian reserve function according to claim 1, characterized in that: Preparation method of pills: Step S1: Mix the above Chinese medicines, crush them using a Chinese medicine grinder, and sieve them through a 100-mesh sieve to obtain fine powder; Step S2: Heat the honey until it boils, becomes darker in color, and becomes viscous. Then, reduce heat and heat until light red, shiny foam appears. When it is sticky but no white threads are present, turn off the heat and allow the honey to cool. Step S3: For every 100g of fine powder, 30g of refined honey is used to make small honey pills; Dosage: Twice a day, about 8g each time, take with warm water after meals.

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