Traditional Chinese medicine composition for treating or improving hypoovarian reserve function and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating or improving hypoovarian reserve function and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition comprises the following components in parts by weight: angelica sinensis, parched white paeony root, parasitic loranthus, dodder, roasted rhizoma atractylodis macrocephalae, ligusticum wallichii, herba lycopi, albizia flower and honey-fried licorice root. And after ovulation, morinda officinalis and glossy privet fruit are added. The formula provided by the invention complies with the natural law of human bodies, and according to the growth of qi and blood, yin and yang, nourishing blood, activating blood and tonifying kidney, yin and yang are tonified without stagnation, and blood stasis is removed without hurting healthy qi; meanwhile, the traditional Chinese medicine is used for strengthening the root of acquired days, quieting the main internal organs, combining dynamic and static, regulating qi-blood yin-yang balance and taking the balance as a period. The invention further provides application of the composition or the traditional Chinese medicine extract or the traditional Chinese medicine preparation in preparation of a medicine for treating or improving ovarian reserve hypofunction.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating or improving diminished ovarian reserve of kidney deficiency and blood stasis type and application thereof. BACKGROUND

[0002] With the development of global economy and the change of women's social role, the delay of reproductive age has become a modern trend, leading to a common challenge in clinical reproductive medicine-diminished ovarian reserve (DOR). Due to the decrease in the number and / or quality of oocytes, the risk of miscarriage and fetal chromosomal abnormalities increases significantly, and even if assisted reproductive technology (ART) is applied for procreation treatment, there are problems such as fewer oocytes, higher cycle cancellation rate and lower clinical pregnancy rate. If not intervened in time, not only the fertility of patients will decrease, but also the risk of osteoporosis, bone fracture and cardiovascular events will increase in the long term, which seriously affects the quality of life of patients. How to restore the ovarian function of DOR patients, improve the quality of oocytes of patients and enhance the ovarian response of patients with poor ovarian response is one of the problems to be solved in the field of reproduction, but there is no exact and effective method to improve the reproductive outcome of DOR patients at present.

[0003] The methods currently adopted to improve the ovarian function and fertility of patients include hormone replacement therapy, dehydroepiandrosterone therapy, ovulation induction therapy, immunotherapy and assisted reproductive technology therapy. However, some patients have concerns about the adverse reactions and risks of hormones, and the acceptance is poor, and there are also limitations in the treatment of tumor, hormone resistance, obesity and other groups. Therefore, it is of important clinical and social significance to find a safe and effective treatment method to improve the ovarian reserve function and oocyte quality of DOR patients and improve their fertility.

[0004] CN114177256A discloses a traditional Chinese medicine composition for treating diminished ovarian reserve and application thereof, which comprises the following components in parts by weight: Xianlingpi 10-20 parts, Xianmao 10-20 parts, Baguantian 10-20 parts, Lujiaogao 5-10 parts, Zixieche 5-10 parts, Gouqizi 15-20 parts, Shudig 10-20 parts, Shengdi 10-20 parts, Huangbai 5-15 parts, Xiangfu 10-20 parts, Yimucao 15-20 parts, Danggui 10-20 parts, Honghua 10-20 parts, Sanlieng 10-20 parts, Lulutong 10-20 parts, Juren 10-20 parts and Gancao 5-10 parts. The composition can effectively treat diminished ovarian reserve, improve female ovarian function, improve ovarian reserve capacity, promote follicular development and ovulation; but the composition is only suitable for DOR patients of kidney deficiency type, and a large dose of blood-activating drugs of multiple flavors is used.

[0005] CN115779035A discloses a traditional Chinese medicine composition for treating or improving decreased ovarian reserve function, and a preparation method and application thereof, wherein the traditional Chinese medicine composition comprises the following raw materials: North Shashen, vinegar turtle plate, wine female privet fruit, angelica, prepared rehmannia, wine cornus officinalis, cuscuta, medlar, wine cistanche, polygonatum, white peony root, vinegar cyperus rotundus, mulberry. The traditional Chinese medicine composition can improve the ovarian reserve function and follicle maturation and development of DOR, can significantly increase the AFC and serum AMH, HIF-1α, VEGF, Ang-1 and Ang-2 levels, and reduce FSH, FSH / LH; and promote the increase of the number of follicles at all levels, the improvement of ovarian atrophy, the neat arrangement of granulosa cells, and the increase of vascular distribution in DOR mice; at the same time, promote the expression of SIRT1, VEGF, HIF-1α, Ang-1, Ang-2 proteins in the ovaries of DOR mice, and inhibit the expression of NF-kB, to improve the ovarian reserve function, but the composition is suitable for DOR patients with liver and kidney yin deficiency.

[0006] CN116942758A discloses a traditional Chinese medicine composition for improving decreased ovarian reserve function, which is prepared from the following raw materials: white hoelen 8-16 parts, prepared rehmannia 8-16 parts, raw rehmannia 8-16 parts, herba epimedii 5-13 parts, deer horn cream 6-14 parts, female privet fruit 5-13 parts, purple quartz 11-19 parts, radix morindae officinalis 5-13 parts, radix ophiopogonis 5-13 parts, cornus officinalis 2-10 parts, turtle shell 5-13 parts, radix scrophulariae 2-10 parts, angelica 8-16 parts, chuanxiong 8-16 parts, radix sargentodoxae 11-19 parts, and white peony root 5-13 parts. Animal experiments have proved that the traditional Chinese medicine composition can effectively improve the ovarian function of DOR model mice, and the traditional Chinese medicine composition is reasonable in compatibility and has no toxic side effects, but the composition has no attention to the changes of blood before and after ovulation in women. SUMMARY

[0007] The inventors of the present application found in long-term clinical practice that patients with mixed deficiency and excess are more common. Modern people like cold and lack of exercise, and the kidney yang is damaged and cannot warm the uterus. Cold evil is generated inside, which hinders the movement of blood in the uterus. Blood cannot be generated, blood stagnation, and blood cannot fill the blood sea on time, so menstrual delay, menstrual volume and other menstrual diseases are seen. Blood stagnation affects the connection between organs, and essence and blood cannot nourish the kidney, leading to imbalance between yin and yang, and further aggravating the loss of the kidney.

[0008] According to the clinical actual situation, the inventors of the present application propose to simplify the traditional Chinese medicine regulation method into two stages of before ovulation and after ovulation. Before ovulation, kidney-tonifying and blood-activating drugs are used. It should be noted that if the patient has a large amount of menstruation, a large amount of blood-activating drugs should not be used, and the blood should be adjusted. After ovulation, kidney essence is supplemented, and flower drugs are added to promote follicular development and discharge.

[0009] Women take blood as the basis, and menstruation, belt, fetus and production all rely on the transformation of blood. Blood stasis hinders the normal circulation of qi and blood. If qi and blood are not unobstructed, the kidney will be deficient. Therefore, kidney deficiency and blood stasis influence each other and cause each other. Therefore, in the treatment of kidney deficiency and blood stasis type DOR, not only should the kidney be supplemented, but also the blood should be nourished. Therefore, the inventors of the present application take nourishing blood and invigorating blood, tonifying kidney and filling essence as the treatment principle, and propose the present application.

[0010] The present application provides a traditional Chinese medicine composition, which comprises the following components in parts by weight: Angelica 6-12 parts, fried white peony root 6-15 parts, taxillus 9-15 parts, semen cuscutae 6-12 parts, fried atractylodes 6-20 parts, chuanxiong 3-10 parts, lycianthes 6-12 parts, albizia flower 5-15 parts, and fried licorice 2-10 parts.

[0011] In an embodiment of the present application, the traditional Chinese medicine composition comprises the following components in parts by weight: Angelica 10 parts, fried white peony root 10 parts, taxillus 12 parts, semen cuscutae 12 parts, fried atractylodes 10 parts, chuanxiong 4 parts, lycianthes 10 parts, albizia flower 12 parts, and fried licorice 6 parts.

[0012] In the present application, the traditional Chinese medicine composition further comprises the following components in parts by weight: Radix Morindae Officinalis 3-15 parts and Ligustri Lucidi Fructus 6-12 parts.

[0013] In an embodiment of the present application, the traditional Chinese medicine composition comprises the following components in parts by weight: Angelica 10 parts, fried white peony root 10 parts, taxillus 12 parts, semen cuscutae 12 parts, fried atractylodes 10 parts, chuanxiong 4 parts, lycianthes 10 parts, albizia flower 12 parts, and fried licorice 6 parts.

[0014] The present application further provides a traditional Chinese medicine extract, which is extracted from medicinal materials comprising the following components in parts by weight: Angelica 10 parts, fried white peony root 10 parts, taxillus 12 parts, semen cuscutae 12 parts, fried atractylodes 10 parts, chuanxiong 4 parts, lycianthes 10 parts, albizia flower 12 parts, and fried licorice 6 parts.

[0015] In an embodiment of the present application, the medicinal materials in the group A comprise the following components in parts by weight: Angelica 10 parts, fried white peony root 10 parts, taxillus 12 parts, semen cuscutae 12 parts, fried atractylodes 10 parts, chuanxiong 4 parts, lycianthes 10 parts, albizia flower 12 parts, and fried licorice 6 parts.

[0016] In the present application, the medicinal materials of the traditional Chinese medicine extract further comprise Radix Morindae Officinalis 3-15 parts and Ligustri Lucidi Fructus 6-12 parts.

[0017] In an embodiment of the present application, the medicinal materials comprise the following components in parts by weight: Angelica 10 parts, fried white peony root 10 parts, taxillus 12 parts, semen cuscutae 12 parts, fried atractylodes 10 parts, chuanxiong 4 parts, lycianthes 10 parts, albizia flower 12 parts, and fried licorice 6 parts.

[0018] In this invention, the extraction method is decoction.

[0019] In one embodiment of the present invention, the herbal extract is obtained by the following operation: the herbs are mixed, soaked in water (preferably for 0.5 h), ensuring that the water level is more than 2 cm above the herbs, brought to a boil over high heat and then simmered over low heat (preferably for 30 min), the decoction is collected and filtered; the residue is added to water, brought to a boil over high heat and then simmered over low heat (preferably for 30 min), the decoction is collected and filtered; the decoctions after the two filtrations are combined to obtain the aqueous decoction.

[0020] The present invention also provides a traditional Chinese medicine preparation comprising the above-mentioned traditional Chinese medicine composition and / or the above-mentioned traditional Chinese medicine extract.

[0021] The dosage forms of the traditional Chinese medicine preparations include one of the following: decoction, granules, capsules, pills, powders, tablets, and oral liquids.

[0022] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition, the above-mentioned traditional Chinese medicine extract, or the above-mentioned traditional Chinese medicine preparation in the preparation of a medicament for treating or improving ovarian reserve deficiency.

[0023] The ovarian reserve decline mentioned above is a type of ovarian reserve decline due to kidney deficiency and blood stasis.

[0024] In one embodiment of the present invention, the above-mentioned traditional Chinese medicine composition, extract or preparation is used in the preparation of a medicament for treating or improving pre-ovulatory ovarian reserve.

[0025] In one embodiment of the present invention, the above-mentioned traditional Chinese medicine composition, extract or preparation is used in the preparation of a medicament for treating or improving post-ovulation ovarian reserve.

[0026] Compared with the prior art, the beneficial effects achieved by the present invention are:

[0027] In this invention, most of the herbs in the formula belong to the liver and kidney meridians, as the liver and kidneys share a common origin. The *Clinical Guidelines and Medical Cases* points out that women's constitution is primarily governed by the liver, which stores blood, and the normal function of the liver in regulating blood flow affects the fullness of the blood. Angelica sinensis invigorates blood and also nourishes blood; stir-fried white peony root nourishes blood and softens the liver. These two herbs act as the principal ingredients, dispersing blood stasis without harming the foundation of qi and blood. Loranthus parasiticus and Cuscuta chinensis both nourish the liver and kidneys; both are neutral in nature. Stir-fried Atractylodes macrocephala is a key herb for strengthening the spleen, tonifying the kidneys and spleen, assisting the principal ingredients as the assistant ingredients. Ligusticum chuanxiong and Lycopus lucidus invigorate blood and remove blood stasis; Albizia julibrissin calms the mind; these three herbs harmonize blood and regulate the heart as the adjuvant ingredients. Prepared licorice root assists the spleen-strengthening effect of stir-fried Atractylodes macrocephala and also harmonizes the other herbs as the guiding ingredients.

[0028] The application focuses on the changes of qi and blood before and after ovulation of women, and simplifies the traditional Chinese medicine regulation method into two stages of before ovulation and after ovulation. Before ovulation, the emphasis is on regulating qi and blood, and in the post-ovulation period, yin is strong and yang is born, and the balance gradually shifts to yang, and yin and yang are both strong. At this time, add Ba Ji Tian and Nu Zhen Zi, yin and yang are both supplemented, and the supplement is not greasy. The whole prescription conforms to the natural law of the human body, and according to the growth and decline of qi and blood, yin and yang, it realizes the combination of nourishing blood and activating blood and supplementing kidney and filling essence, yin and yang are both supplemented, and the supplement is not stagnated, and the stagnation of blood does not harm the normal, and at the same time, it is combined with the main part of the five internal organs and six viscera, and the balance of qi and blood, yin and yang is adjusted, and the period is and, and it is suitable for improving the ovarian reserve function of DOR patients with kidney deficiency and blood stasis. DETAILED DESCRIPTION

[0029] The application will be further described below in conjunction with specific embodiments, but the application is not limited to the following embodiments.

[0030] Clinical research: observation of the efficacy of the drug combination of the application on DOR

[0031] 1. Data and methods

[0032] 1.1 General data

[0033] The case data came from patients who met the criteria of kidney deficiency and blood stasis type DOR treated in the gynecology department of Guang'anmen Hospital of China Academy of Chinese Medical Sciences from December 2022 to September 2023.

[0034] This study adopted a randomized controlled study, and was divided into a test group of 28 cases, with an average age of (34.36±2.71) years old, BMI: (21.79±2.27) kg / m 2 , disease duration: 2(1.00, 2.75) years; and a control group of 29 cases, with an average age of (34.07±2.54) years old, BMI: (22.28±2.45) kg / m 2 , disease duration: 2(1.00, 3.00) years. There was no significant difference in age, body mass index, and disease duration between the two groups (P>0.05), and they were comparable.

[0035] 1.2 Diagnostic criteria

[0036] 1.2.1 Western diagnostic criteria for decreased ovarian reserve

[0037] According to the diagnostic criteria in the 2022 “Clinical Diagnosis and Treatment Expert Consensus on Decreased Ovarian Reserve”, any two of them can be diagnosed.

[0038] (1) AMH: AMH <1.1 ng / ml;

[0039] (2) AFC: AFC on both sides of the ovary <5;

[0040] (3) Basal FSH: basal FSH≥10 IU / L for two consecutive menstrual cycles;

[0041] 1.2.2 TCM syndrome differentiation criteria for DOR of kidney deficiency and blood stasis type

[0042] Reference to the Guiding Principle of Clinical Research for New Drugs of Traditional Chinese Medicine and the standard of oligoamenorrhea, postmenopausal, and infertility of kidney deficiency and blood stasis syndrome.

[0043] Main symptoms: ① Menstrual cycle is delayed or menstrual flow is scanty, color is pale and quality is thin or color is purple with blood clots; ② Infertility.

[0044] Secondary symptoms: ③ Lumbago and soreness of knees, thirst and unwilling to drink; ④ Dizziness and tinnitus, hot flashes and sweating, irritability, and pain in the lower abdomen.

[0045] Tongue and pulse: tongue is pale or purple with blood clots, pulse is deep and thin or slow and astringent.

[0046] Main symptoms and secondary symptoms each meet one or more, combined with tongue and pulse, can be diagnosed.

[0047] 1.3 Inclusion criteria

[0048] (1) Age 20-40 years old;

[0049] (2) Meet the Western medical diagnostic criteria for DOR;

[0050] (3) Meet the TCM diagnostic criteria for kidney deficiency and blood stasis syndrome;

[0051] (4) Patients who voluntarily participate in this study and sign the informed consent form.

[0052] 1.4 Exclusion criteria

[0053] (1) Combined with reproductive tract developmental abnormalities, reproductive system tuberculosis, Asherman syndrome, polycystic ovary syndrome, thyroid disease, empty sella syndrome, central nervous system tumor, breast cancer, estrogen and progesterone-dependent tumor, ovarian resistance syndrome, etc;

[0054] (2) Combined with severe diseases of cardiovascular, cerebrovascular, liver, kidney and hematopoietic system, diabetes or abnormal blood sugar;

[0055] (3) Unexplained vaginal bleeding;

[0056] (4) Untreated endometrial hyperplasia;

[0057] (5) Used other drugs to treat this disease within the last 3 months, which is related or conflicts with the drugs used in this study;

[0058] (6) Patients with suspected pregnancy, pregnancy, and lactation;

[0059] (7) Allergic to the study drug.

[0060] 1.5 Treatment method

[0061] Treatment group: Take the drug combination of the application: Angelica 10g, Fried White Peony 10g, Taxillus 12g, Dodder 12g, Fried Atractylodes 10g, Chuanxiong 4g, Lantana 10g, Albizia Flower 12g, Fried Licorice 6g; add Radix Morindae Officinalis 10g and Ligustri Lucidi Fructus 10g after ovulation. Method of taking: 1 dose per day, decocted with water for 2 times, about 300ml in total, 150ml per time, taken 30 minutes after breakfast and dinner, 28 days as a complete course of treatment, take for 3 courses in succession, do not stop taking medicine during menstruation, and strictly use contraception during the taking of medicine. The decoction pieces are provided by the Chinese Medicine Shop of Guang'anmen Hospital.

[0062] Control group: Take Femoston treatment (manufacturer: Abbott-Biologicals-B.V, registration certificate number H20150346). Method of use: take 1 white tablet (containing estradiol 1mg) per day for the first 14 days, and take 1 gray tablet (containing estradiol 1mg and dydrogesterone 10mg) per day for the next 14 days, 28 days as a complete course of treatment, take for 3 courses in succession, and strictly use contraception during the taking of medicine.

[0063] Among the subjects in the two groups, amenorrhea patients are given progesterone capsules, taken orally for 5 consecutive days, 2 times a day, 100mg each time, and the amount of vaginal bleeding is like menstruation, then the treatment course is started.

[0064] 1.6 Observation index

[0065] (1) Detect the levels of AMH, FSH, E2, and LH in the peripheral blood of patients in the two groups on the 2nd-4th day of menstruation before and after treatment.

[0066] (2) Observe the number of antral follicles in the ovaries of patients in the two groups before and after treatment. Perform transvaginal ultrasound (transrectal ultrasound for those who do not have sexual life) examination before and after treatment to evaluate and record.

[0067] (3) Observe the TCM syndrome efficacy of patients in the two groups after treatment. The TCM syndrome score includes the scores of symptoms such as soreness of waist and knees, dizziness and tinnitus, hot flashes, decreased sexual desire, chest tightness, and abdominal distension and pain. Patients in the two groups fill out the TCM syndrome score table before and after treatment, and the changes in TCM symptom scores are statistically analyzed and recorded for 2 times. Efficacy index (N) = [(pre-treatment score - post-treatment score) / pre-treatment score] x 100%; cured: menstruation returns to normal, and clinical discomfort symptoms basically disappear, N≥95%; markedly effective: menstruation is significantly improved and close to normal, and clinical discomfort symptoms are relieved, 70%≤N<95%; effective: menstruation is improved compared with before treatment, and clinical discomfort symptoms are reduced, 30%≤N<70%; ineffective: menstruation does not return to normal, and clinical discomfort symptoms do not change significantly, N<30%.

[0068] (4) Safety observation: Patients in the two groups were examined for liver and kidney function, blood routine, urine routine before and after treatment. And record whether the two groups of patients have adverse reactions during medication, such as allergy, headache, nausea and vomiting, breast pain, record adverse reaction events and measures taken.

[0069] 1.7 Clinical efficacy criteria

[0070] Cure: FSH value, AMH value, AFC number returned to normal range;

[0071] Marked effect: FSH value, AMH value, AFC number at least one returned to normal range;

[0072] Effective: FSH value, AMH value, AFC number did not return to normal range, but at least one index improved by ≥30%;

[0073] Invalid: FSH value, AMH value, AFC number improved by <30% or aggravated.

[0074] 1.8 Statistical method

[0075] SPSS-26.0 software was used for statistical analysis of the research data. The rate (%) was used for count data; chi-square test was used for four table data; rank sum test was used for rank data. If it does not conform to the normal distribution, use the median and quartile to describe, and use non-parametric test for statistical analysis; if it conforms to the normal distribution, use mean ± standard deviation for description, and use t test for analysis. The test level α=0.05, two-sided test was used, P<0.05 was considered to have statistically significant difference.

[0076] 2. Results

[0077] 2.1 Serum FSH level

[0078] There was no statistically significant difference in serum FSH level between the two groups before treatment (P>0.05), which was comparable. After treatment, the serum FSH levels of the two groups were lower than before, and the difference was statistically significant (P=0.000). Comparison between groups, the serum FSH levels of the test group and the control group after treatment had no statistically significant difference (P>0.05), which indicated that the application and femotinol could improve the serum FSH level, and the treatment effect was equivalent. See Table 1.

[0079] Table 1 Comparison of serum FSH values of the two groups (mIU / mL),

[0080] Before treatment After treatment t P Test group (N=28) 16.33±6.47 9.22±3.06 6.056 0.000 Control group (N=29) 16.23±5.31 10.79±6.04 5.323 0.000 t 0.066 -1.235 P 0.948 0.222

[0081] Note: The data conforms to the normal distribution, t test is used.

[0082] 2.2 Serum LH levels

[0083] Before treatment, the serum LH levels of the two groups of patients before treatment had no statistically significant difference (P>0.05), and were comparable. After treatment, the serum LH levels of the two groups of patients were decreased compared with before, and the difference was statistically significant (P<0.05). Comparison between groups, the serum LH levels of the test group and the control group after treatment had no statistically significant difference (P>0.05), indicating that the application and fenmtol can improve the serum LH level, and the treatment effects are equivalent. See Table 2.

[0084] Table 2 Comparison of serum LH values (mIU / mL) of the two groups of patients M (P 25 , P 75 )

[0085] Before treatment After treatment Z P Test group (N=28) 4.99(3.59，10.01) 4.69(3.32，5.55) -3.006 0.003 Control group (N=29) 5.43(3.80，10.15) 4.70(3.37，5.88) -2.926 0.003 Z -0.607 -0.431 P 0.544 0.666

[0086] Note: The data do not conform to normal distribution, and non-parametric test is used.

[0087] 2.3 Serum E2 level

[0088] Before treatment, the serum E2 levels of the two groups of patients before treatment had no statistically significant difference (P>0.05), and were comparable. After treatment, the serum E2 levels of the two groups of patients were decreased compared with before, and the difference was statistically significant (P<0.05). Comparison between groups, the serum E2 levels of the test group and the control group after treatment had no statistically significant difference (P>0.05), indicating that the application and fenmtol can improve the serum E2 level, and the treatment effects are equivalent. See Table 3.

[0089] Table 3 Comparison of serum E2 values (pg / ml) of the two groups of patients before and after treatment M (P 25 , P 75 )

[0090] Before treatment After treatment Z P Test group (N=28) 29.60(21.95，55.31) 45.67(35.99，74.75) -2.459 0.014 Control group (N=29) 33.70(22.80，43.75) 50.00(36.85，120.50) -2.173 0.030 Z -1.285 -0.710 P 0.199 0.477

[0091] Note: The data do not conform to normal distribution, and non-parametric test is used.

[0092] 2.4 Serum AMH value

[0093] Before treatment, the serum AMH levels of the two groups of patients before treatment had no statistically significant difference (P>0.05), and were comparable. After treatment, the serum AMH levels of the test group were significantly increased (P<0.05), and the serum AMH levels of the control group had no obvious change (P>0.05). After treatment, the serum AMH levels of the test group were significantly higher than those of the control group (P<0.05), indicating that the serum AMH value of the test group after treatment has a significant increase, and the treatment effect of the control group on the serum AMH value is not obvious, and the improvement effect of the application on the AMH level is obviously better than that of fenmtol. See Table 4.

[0094] Table 4 Comparison of serum AMH values (ng / ml) of two groups before and after treatment within groups, M(P 25 , P 75 )

[0095] Before treatment After treatment Z P Test group (N=28) 0.57(0.23，0.80) 1.09(0.56，1.55) -3.849 0.000 Control group (N=29) 0.21(0.06，0.57) 0.20(0.08，0.58) -0.592 0.554 Z -1.940 -4.671 P 0.052 0.000

[0096] Note: The data do not conform to normal distribution, non-parametric test is adopted.

[0097] 2.5 AFC number

[0098] Before treatment, the number of pre-AFC of patients in two groups had no statistically significant difference (P>0.05), and was comparable. After treatment, the number of AFC of patients in two groups was increased, and the difference was statistically significant (P<0.05). After treatment, the number of AFC of patients in the test group was significantly higher than that in the control group (P<0.05), which indicated that the number of AFC of patients treated by the application and fentanyl was obviously increased, and the improvement effect of the application was more obvious, as shown in Table 5.

[0099] Table 5 Comparison of AFC number (piece) of two groups before and after treatment within groups, M(P 25 , P 75 )

[0100] Before treatment After treatment Z P Test group (N=28) 4.00(3.00，5.75) 7.00(6.00，8.75) -4.406 0.000 Control group (N=29) 5.00(3.00，6.00) 5.00(4.00，7.00) -3.224 0.001 Z -0.561 -2.640 P 0.575 0.008

[0101] Note: The data do not conform to normal distribution, non-parametric test is adopted.

[0102] 2.6 TCM syndrome score

[0103] Before treatment, the TCM syndrome scores of patients in two groups were compared, and the difference was not statistically significant (P>0.05), and was comparable. After treatment, the TCM syndrome scores of patients in two groups were decreased, and the difference was statistically significant (P<0.05), and the improvement of the test group was better than that of the control group, and the difference was statistically significant (P<0.05), which indicated that the application and fentanyl could reduce the TCM syndrome scores of patients, and improve the clinical symptoms of patients, and the improvement effect of the application on TCM syndrome score was better than that of fentanyl. See Table 6.

[0104] Table 6 Comparison of TCM syndrome scores of two groups before and after treatment within groups

[0105]

[0106] Note: The data before treatment conform to normal distribution, t test is adopted; the data after treatment do not conform to normal distribution, non-parametric test is adopted.

[0107] After treatment, 3 patients (10.71%) were cured, 11 patients (39.29%) were markedly effective, 13 patients (46.43%) were effective, and 1 patient (3.57%) was ineffective in the test group; 1 patient (3.45%) was cured, 6 patients (20.69%) were markedly effective, 19 patients (65.52%) were effective, and 3 patients (10.34%) were ineffective in the control group. The total effective rate of TCM syndrome was 96.43% in the test group and 89.66% in the control group; according to the statistical results, the patients cured and markedly effective accounted for 50% of the total number of patients in the test group; in comparison, there were 7 patients cured and markedly effective in the control group, accounting for only 24.14%. The difference was statistically significant (P<0.05) by non-parametric test, indicating that the effect of improving TCM symptoms of the application was significantly better than that of fentanyl, as shown in Table 7.

[0108] Table 7 Comparison of TCM syndrome effect difference (n, %)

[0109]

[0110] Note: Non-parametric test is used for one-way ordered RxC table data.

[0111] 2.7 Evaluation of clinical efficacy

[0112] The number of cured, markedly effective, effective, and ineffective patients in the test group after treatment was 4, 18, 5, and 1, respectively; and that in the control group was 3, 15, 10, and 1, respectively. The total effective rate of the test group was 96.43%, and that of the control group was 96.55%. There was no statistically significant difference (P>0.05) by non-parametric test, indicating that both the application and fentanyl had high clinical efficacy, and the treatment effects were equivalent, as shown in Table 8.

[0113] Table 8 Comparison of clinical efficacy difference (n, %)

[0114]

[0115] Note: This table is a one-way ordered RxC table, and non-parametric test is used to compare the difference between the two groups.

[0116] 2.8 Safety observation

[0117] Before and after treatment, there were no obvious abnormalities in liver and kidney function, blood routine, and urine routine of all patients, and no adverse events occurred in all patients.

[0118] Although the application has been described in detail in the foregoing with general description and specific embodiments, some modifications or improvements can be made on the basis of the application, which is obvious to those skilled in the art. Therefore, these modifications or improvements made on the basis of not deviating from the spirit of the application are within the scope of the application claimed.

Claims

1. A traditional Chinese medicine composition comprising the following components in parts by weight: Angelica sinensis 6-12 parts, stir-fried Paeonia lactiflora 6-15 parts, Taxillus chinensis 9-15 parts, Cuscuta chinensis 6-12 parts, stir-fried Atractylodes macrocephala 6-20 parts, Ligusticum chuanxiong 3-10 parts, Lycopus lucidus 6-12 parts, Albizia julibrissin 5-15 parts, and prepared Glycyrrhiza uralensis 2-10 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition also includes the following components in parts by weight: Morinda officinalis 3-15 parts and Ligustrum lucidum 6-12 parts.

3. A traditional Chinese medicine extract, obtained by extracting the following medicinal materials in parts by weight: Angelica sinensis 6-12 parts, stir-fried white peony root 6-15 parts, Taxillus chinensis 9-15 parts, Cuscuta chinensis 6-12 parts, stir-fried Atractylodes macrocephala 6-20 parts, Ligusticum chuanxiong 3-10 parts, Lycopus lucidus 6-12 parts, Albizia julibrissin flower 5-15 parts, and prepared licorice root 2-10 parts.

4. The traditional Chinese medicine extract according to claim 3, characterized in that, The medicinal materials also include: 3-15 parts of Morinda officinalis and 6-12 parts of Ligustrum lucidum.

5. The traditional Chinese medicine extract according to claim 3 or 4, characterized in that, The extraction method is water decoction.

6. A traditional Chinese medicine preparation comprising the traditional Chinese medicine composition according to claim 1 or 2 and / or the traditional Chinese medicine extract according to claim 3 or 4.

7. The traditional Chinese medicine preparation according to claim 6, characterized in that, The dosage forms of the traditional Chinese medicine preparations include one of the following: decoction, granules, capsules, pills, powders, tablets, and oral liquids.

8. The use of the traditional Chinese medicine composition according to claim 1 or 2, the traditional Chinese medicine extract according to claim 3 or 4, or the traditional Chinese medicine preparation according to claim 6 or 7 in the preparation of a medicament for treating or improving ovarian reserve deficiency.

9. The application according to claim 8, characterized in that, The ovarian reserve decline mentioned above is a type of ovarian reserve decline due to kidney deficiency and blood stasis.

10. The application according to claim 8, characterized in that, The medications mentioned are pre-ovulation medications and post-ovulation medications.

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