A composition for treating infertility caused by polycystic ovary syndrome and use thereof

Abstract

The application provides a composition for treating infertility caused by polycystic ovary syndrome, which is composed of traditional Chinese medicines and western medicines. The traditional Chinese medicines are prepared from raw medicinal materials in the following proportions by weight: 5-13 parts of donkey-hide gelatin, 9-21 parts of prepared rehmannia, 5-13 parts of angelica, 9-21 parts of semen cuscutae, 5-13 parts of ligustrum lucidum ait, 5-13 parts of codonopsis pilosula, 5-13 parts of white atractylodes rhizome, 9-21 parts of polygonatum, 5-13 parts of rhizoma caryophylli, and 5-13 parts of chuanxiong. The western medicine is letrozole. The application also provides the use of the composition. The advantage of the application is that clinical and animal experiments have confirmed that the effect of letrozole combined with the traditional Chinese medicine decoction of the application on treating infertility caused by polycystic ovary syndrome is better, and the ovulation rate and pregnancy rate are significantly improved, so the application is worth promoting.

Description

[Technical Field]

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a composition for treating infertility caused by polycystic ovary syndrome and its application. [Background Technology]

[0002] Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by hyperandrogenemia, ovulation disorders, and polycystic ovaries. The incidence of PCOS is relatively high in adolescent and reproductive-age women, approximately 5%–10%, and about 75% in women with anovulatory infertility, reaching over 85% in women with hirsutism. About one-quarter of patients in infertility clinics are diagnosed with PCOS, and approximately 20%–50% of patients requiring assisted reproductive technology (ART) have PCOS.

[0003] Obese individuals account for approximately 60% to 70% of those with PCOS. Influenced by factors such as obesity, changes in human diet and lifestyle, the incidence of PCOS is showing an upward trend year by year! The immediate harms of PCOS include menstrual disorders, infertility, hirsutism, acne, and obesity, and it is prone to long-term complications such as endometrial cancer, breast cancer, diabetes, arteriosclerosis, and coronary heart disease.

[0004] Currently, due to the unknown cause of polycystic ovary syndrome (PCOS), clinical treatment mainly focuses on comprehensive therapies such as hormone therapy, lacking specific treatment methods. To date, no drug has been able to effectively treat PCOS and achieve long-term remission. Therefore, the improvement and innovation of drugs for treating PCOS combined with infertility is an urgent problem to be solved.

[0005] The literature (China Association of Traditional Chinese Medicine, 2015, 15th National Academic Conference of Gynecology of Traditional Chinese Medicine) published a "Clinical Analysis of 76 Cases of Infertility Caused by Polycystic Ovary Syndrome Treated with Integrated Traditional Chinese and Western Medicine": Both groups received routine clomiphene treatment, i.e., clomiphene 50mg once daily for 5 consecutive days starting from the 5th day of the menstrual cycle. The treatment group received additional traditional Chinese medicine treatment, mainly based on tonifying the kidney and strengthening the spleen, supplemented by soothing the liver. The herbal composition was: Angelica sinensis 15g, Rehmannia glutinosa 15g, Paeonia lactiflora 10g, Rubus idaeus 15g, Cuscuta chinensis 15g, Ligustrum lucidum 15g, Cornus officinalis 10g, Morus alba 15g, Dioscorea opposita 15g, Codonopsis pilosula 30g, Atractylodes macrocephala 15g, Cyperus rotundus 10g. Modifications: For those with significant liver stagnation, add 10g of Curcuma longa and 10g of Litchi chinensis seed; for those with significant blood stasis, add 15g of Angelica sinensis, 15g of Salvia miltiorrhiza, 30g of Spatholobus suberectus, and 15g of Leonurus japonicus; for those with significant phlegm-dampness, add 10g of Poria cocos, 15g of Benincasa hispida peel, 10g of Amomum villosum, 10g of Magnolia officinalis, and 15g of Coix lacryma-jobi. Chinese patent document CN202310062554.3 discloses "A traditional Chinese medicine composition with the effect of improving endometrial receptivity and its application," which consists of the following raw materials in parts by weight: Cuscuta chinensis, Taxillus chinensis, Codonopsis pilosula, Astragalus membranaceus, Eucommia ulmoides, Dipsacus asper, Scutellaria baicalensis, Paeonia lactiflora, Atractylodes macrocephala (fried), Cyperus rotundus (processed), Colla corii asini, Glycyrrhiza uralensis (processed), Lycium barbarum, Rubus idaeus, Amethyst, Nelumbo nucifera, Rehmannia glutinosa (processed), Epimedium brevicornu, Polygonatum sibiricum (processed with wine), Pseudostellaria heterophylla, Ligustrum lucidum (processed with wine), Hirudo medicinalis, Cervi cornu colla, Salvia miltiorrhiza, and Angelica sinensis. The results confirmed that the traditional Chinese medicine composition provided by this invention can simultaneously treat infertility, threatened abortion, miscarriage, and recurrent miscarriage, and has the characteristics of low treatment cost, good efficacy, high cure rate, low recurrence rate, and few toxic side effects, as well as improving endometrial receptivity. Chinese patent document CN201911002376.5 discloses "A compound traditional Chinese medicine preparation for regulating menstruation and beautifying the complexion," which is composed of the following raw materials in parts by weight: donkey-hide gelatin, licorice root, processed Polygonatum sibiricum, kudzu root, processed Polygala tenuifolia, Leonurus japonicus, Achyranthes bidentata, Salvia miltiorrhiza, Eucommia ulmoides, Dipsacus asper, processed Cyperus rotundus, rose, yam, Poria cocos, Atractylodes macrocephala, Codonopsis pilosula, mulberry, wolfberry, processed Cuscuta chinensis, processed Ligustrum lucidum, processed Rehmannia glutinosa, Paeonia lactiflora, Ligusticum chuanxiong, Angelica sinensis, and deer antler. The results confirmed that the combined effects of these herbs in this invention tonify the kidneys, regulate menstruation, benefit the liver, and beautify the complexion.

[0006] Currently, there are no reports regarding the composition of the present invention for treating infertility caused by polycystic ovary syndrome and its application. [Summary of the Invention]

[0007] The purpose of this invention is to address the shortcomings of existing technologies by providing a traditional Chinese medicine composition for treating infertility caused by polycystic ovary syndrome.

[0008] Another object of the present invention is to provide a use for the above-mentioned traditional Chinese medicine composition.

[0009] Another object of the present invention is to provide a pharmaceutical composition for treating infertility caused by polycystic ovary syndrome.

[0010] Another object of the present invention is to provide a use of the above-described pharmaceutical composition.

[0011] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0012] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating infertility caused by polycystic ovary syndrome, which is made from the following raw materials in parts by weight: 5-13 parts of donkey-hide gelatin, 9-21 parts of prepared rehmannia root, 5-13 parts of angelica root, 9-21 parts of dodder seed, 5-13 parts of privet fruit, 5-13 parts of codonopsis root, 5-13 parts of atractylodes rhizome, 9-21 parts of polygonatum rhizome, 5-13 parts of cyperus rhizome, and 5-13 parts of chuanxiong rhizome.

[0013] Preferably, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 7-11 parts of donkey-hide gelatin, 12-18 parts of prepared rehmannia root, 7-11 parts of angelica root, 12-18 parts of dodder seed, 7-11 parts of privet fruit, 7-11 parts of codonopsis root, 7-11 parts of atractylodes rhizome, 15 parts of polygonatum rhizome, 7-11 parts of cyperus rhizome, and 7-11 parts of chuanxiong rhizome.

[0014] More preferably, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 9 parts donkey-hide gelatin, 15 parts prepared rehmannia root, 9 parts angelica root, 15 parts dodder seed, 9 parts privet fruit, 9 parts codonopsis root, 9 parts atractylodes rhizome, 15 parts polygonatum rhizome, 9 parts cyperus rhizome, and 9 parts chuanxiong rhizome.

[0015] Secondly, the present invention provides the use of any of the above-described traditional Chinese medicine compositions in the preparation of a drug for treating infertility caused by polycystic ovary syndrome.

[0016] The dosage form of the traditional Chinese medicine composition is decoction, granules, tablets, capsules, oral liquid, mixture, or syrup.

[0017] Thirdly, the present invention provides a pharmaceutical composition for treating infertility caused by polycystic ovary syndrome, the pharmaceutical composition comprising any of the above-described traditional Chinese medicine compositions and letrozole.

[0018] Fourthly, the present invention provides the use of the compositions described above in the preparation of a medicament for treating infertility caused by polycystic ovary syndrome.

[0019] The advantages of this invention are:

[0020] 1. The herbal composition of this invention conforms to the principle of "principal, assistant, adjuvant, and guide" in traditional Chinese medicine formulation. The principal ingredients are donkey-hide gelatin, prepared rehmannia root, and angelica root, which nourish blood and replenish essence. The assistant ingredients are dodder seed, privet fruit, codonopsis root, atractylodes rhizome, and polygonatum rhizome, which tonify both the spleen and kidneys, replenish qi, nourish yin, and warm yang. The adjuvant ingredients are cyperus rhizome and chuanxiong rhizome, which invigorate blood and remove blood stasis. The entire formula works synergistically to nourish blood and yin, tonify the kidneys and spleen, and invigorate blood and remove blood stasis.

[0021] 2. Experiments have confirmed that the combination of LE and this traditional Chinese medicine decoction is more effective in treating infertility caused by PCOS, with significantly improved ovulation and pregnancy rates, and is worthy of promotion.

Detailed Implementation Methods

[0022] The specific embodiments provided by the present invention will be described in detail below.

[0023] Example 1: Preparation of a Traditional Chinese Medicine Composition for Treating Infertility Caused by Polycystic Ovary Syndrome (Part 1)

[0024] 9 parts donkey-hide gelatin, 15 parts prepared rehmannia root, 9 parts angelica root, 15 parts dodder seed, 9 parts privet fruit, 9 parts codonopsis root, 9 parts atractylodes rhizome, 15 parts polygonatum rhizome, 9 parts cyperus rhizome, and 9 parts chuanxiong rhizome.

[0025] Example 2: Preparation of a Traditional Chinese Medicine Composition for Treating Infertility Caused by Polycystic Ovary Syndrome (Part Two)

[0026] 9 parts donkey-hide gelatin, 12 parts prepared rehmannia root, 11 parts angelica root, 9 parts dodder seed, 13 parts privet fruit, 9 parts codonopsis root, 7 parts atractylodes rhizome, 18 parts polygonatum rhizome, 5 parts cyperus rhizome, and 13 parts chuanxiong rhizome.

[0027] Example 3: Preparation of a Traditional Chinese Medicine Composition for Treating Infertility Caused by Polycystic Ovary Syndrome (Part 3)

[0028] 7 parts donkey-hide gelatin, 18 parts prepared rehmannia root, 5 parts angelica root, 21 parts dodder seed, 9 parts privet fruit, 7 parts codonopsis root, 11 parts atractylodes rhizome, 9 parts polygonatum rhizome, 13 parts cyperus rhizome, and 9 parts chuanxiong rhizome.

[0029] Example 4: Preparation of a Traditional Chinese Medicine Composition for Treating Infertility Caused by Polycystic Ovary Syndrome (Part 4)

[0030] 11 parts donkey-hide gelatin, 9 parts prepared rehmannia root, 13 parts angelica root, 15 parts dodder seed, 7 parts privet fruit, 11 parts codonopsis root, 95 parts atractylodes rhizome, 21 parts polygonatum rhizome, 9 parts cyperus rhizome, and 7 parts chuanxiong rhizome.

[0031] Example 5: Preparation of a Traditional Chinese Medicine Composition for Treating Infertility Caused by Polycystic Ovary Syndrome (Part 5)

[0032] 5 parts donkey-hide gelatin, 21 parts prepared rehmannia root, 9 parts angelica root, 12 parts dodder seed, 11 parts privet fruit, 5 parts codonopsis root, 13 parts atractylodes rhizome, 15 parts polygonatum rhizome, 7 parts cyperus rhizome, and 11 parts chuanxiong rhizome.

[0033] Example 6: Preparation of a Traditional Chinese Medicine Composition for Treating Infertility Caused by Polycystic Ovary Syndrome (VI)

[0034] 13 parts donkey-hide gelatin, 15 parts prepared rehmannia root, 7 parts angelica root, 18 parts dodder seed, 5 parts privet fruit, 13 parts codonopsis root, 9 parts atractylodes rhizome, 12 parts polygonatum rhizome, 11 parts cyperus rhizome, and 5 parts chuanxiong rhizome.

[0035] Example 7: Preparation of a Traditional Chinese Medicine Composition for Treating Infertility Caused by Polycystic Ovary Syndrome (VII)

[0036] 9 parts donkey-hide gelatin, 18 parts prepared rehmannia root, 5 parts angelica root, 21 parts dodder seed, 9 parts privet fruit, 7 parts codonopsis root, 11 parts atractylodes rhizome, 9 parts polygonatum rhizome, 13 parts cyperus rhizome, and 9 parts chuanxiong rhizome.

[0037] Example 8: Preparation of a Traditional Chinese Medicine Composition for Treating Infertility Caused by Polycystic Ovary Syndrome (Part 8)

[0038] 7 parts donkey-hide gelatin, 9 parts prepared rehmannia root, 13 parts angelica root, 15 parts dodder seed, 7 parts privet fruit, 11 parts codonopsis root, 95 parts atractylodes rhizome, 21 parts polygonatum rhizome, 9 parts cyperus rhizome, and 7 parts chuanxiong rhizome.

[0039] Example 9: Preparation of a Traditional Chinese Medicine Composition for Treating Infertility Caused by Polycystic Ovary Syndrome (IX)

[0040] 11 parts donkey-hide gelatin, 21 parts prepared rehmannia root, 9 parts angelica root, 12 parts dodder seed, 11 parts privet fruit, 5 parts codonopsis root, 13 parts atractylodes rhizome, 15 parts polygonatum rhizome, 7 parts cyperus rhizome, and 11 parts chuanxiong rhizome.

[0041] Example 10: Preparation of a Traditional Chinese Medicine Composition for Treating Infertility Caused by Polycystic Ovary Syndrome (X)

[0042] 5 parts donkey-hide gelatin, 15 parts prepared rehmannia root, 7 parts angelica root, 18 parts dodder seed, 5 parts privet fruit, 13 parts codonopsis root, 9 parts atractylodes rhizome, 12 parts polygonatum rhizome, 11 parts cyperus rhizome, and 5 parts chuanxiong rhizome.

[0043] Example 11: Preparation of a Traditional Chinese Medicine Composition for Treating Infertility Caused by Polycystic Ovary Syndrome (XI)

[0044] 13 parts donkey-hide gelatin, 12 parts prepared rehmannia root, 11 parts angelica root, 9 parts dodder seed, 13 parts privet fruit, 9 parts codonopsis root, 7 parts atractylodes rhizome, 18 parts polygonatum rhizome, 5 parts cyperus rhizome, and 13 parts chuanxiong rhizome.

[0045] It should be noted that the method of use for the combination is as follows: the traditional Chinese medicine combination should be taken from the fifth day of menstruation, one dose per day, divided into two doses, for two consecutive weeks; the combined Western medicine (letrozole) should be taken from the fifth day of menstruation, one tablet (2.5mg) once a day, for five consecutive days.

[0046] Example 12: Preparation of a traditional Chinese medicine composition tablet / capsule for treating infertility caused by polycystic ovary syndrome.

[0047] Take any one of the traditional Chinese medicine compositions described in Examples 1-11, add 9-11 times the amount of water, decoct for 2-3.5 hours, and filter out the decoction. Add another 9 times the amount of water, decoct for 2.5 hours, filter out the decoction, combine the two decoctions, let stand, filter out the supernatant, concentrate, cool, add 3 times the amount of alcohol as the concentrate, stir and let it precipitate overnight. Take the supernatant, concentrate to a thick extract; add pharmaceutical excipients, vacuum dry, pulverize and granulate, and compress into tablets or capsules.

[0048] Example 13: Preparation of Traditional Chinese Medicine Composition Granules for Treating Infertility Caused by Polycystic Ovary Syndrome

[0049] Take any one of the traditional Chinese medicine compositions described in Examples 1-11, add 8-10 times the amount of water, decoct for 3 hours, and filter out the decoction. Add another 10 times the amount of water, decoct for 2.5 hours, filter out the decoction, combine the two decoctions, let stand, filter out the supernatant, concentrate, cool, add 2 times the amount of alcohol to the concentrate, stir and let it precipitate overnight. Take the supernatant, concentrate to a thick extract; add appropriate pharmaceutical excipients, granulate, dry, granulate, and package into 15g / bags.

[0050] Example 14: Preparation of a traditional Chinese medicine composition / oral liquid / syrup for treating infertility caused by polycystic ovary syndrome

[0051] Take any one of the traditional Chinese medicine compositions described in Examples 1-11, add 8-11 times the amount of water, decoct for 3 hours, and filter out the decoction. Add another 8 times the amount of water, decoct for 3 hours, filter out the decoction, combine the two decoctions, let stand, filter out the supernatant, concentrate, cool, add 3.5 times the amount of alcohol as the concentrate, stir and let it precipitate overnight. Take the supernatant, concentrate it to a thick extract; add appropriate pharmaceutical excipients to prepare a compound, oral liquid or syrup.

[0052] Example 15 Clinical Trial

[0053] 1. Research Data

[0054] 1.1 Research Subjects

[0055] 100 PCOS infertile patients from our outpatient clinic.

[0056] 1.2 Inclusion criteria: ① PCOS patients who meet the Rotterdam diagnostic criteria, have normal sexual activity, and have been married for 1 year or more without pregnancy; ② Age 20-40 years.

[0057] 1.3 Exclusion criteria: ① Male reproductive dysfunction; ② Infertility due to other causes, such as blocked fallopian tubes or abnormal development of reproductive organs; ③ Allergy to or contraindication to the drugs used in this study.

[0058] 1.4 Grouping: 100 infertile patients with PCOS were randomly divided into a control group and an experimental group, with 50 patients in each group.

[0059] 1.5 Treatment Methods

[0060] (1) Control group: Letrozole. Start taking it on the fifth day of menstruation, once a day, one tablet (2.5mg) each time, for 5 consecutive days.

[0061] (2) Experimental group: Letrozole + Chinese herbal decoction (15g Rehmannia glutinosa, 9g Angelica sinensis, 15g Cuscuta chinensis, 9g Ligustrum lucidum, 9g Codonopsis pilosula, 9g Atractylodes macrocephala, 15g Polygonatum sibiricum, 9g Cyperus rotundus, 9g Ligusticum chuanxiong, decocted in water and taken orally, with 9g of donkey-hide gelatin powder added. Start taking it on the fifth day of menstruation, one dose per day, divided into two doses, for two consecutive weeks).

[0062] 1.6 Observation Indicators

[0063] The study compared the follicular development, maturation days, number of mature follicles, ovulation rate, pregnancy rate, hormone levels before and after treatment, and endometrial thickness before and after treatment on days 12-20 of the menstrual cycle between the two groups of patients.

[0064] 1.7 Statistical Methods

[0065] SPSS 26.0 software was used for statistical analysis, and the quantitative data were analyzed using... The following statements indicate that the means between two groups are compared using a t-test or a rank-sum test; count data are expressed as percentages, and the rates between two groups are compared using a chi-square test, with P < 0.05 indicating a statistically significant difference.

[0066] 2. Results

[0067] 2.1 The diameter of follicles in the experimental group was larger than that in the control group, and the difference was statistically significant (P<0.05), as shown in Table 1.

[0068] Table 1 Comparison of follicle diameter (mm) on days 12-16 of the menstrual cycle between the two groups of patients.

[0069]

[0070] 2.2 The experimental group had a shorter follicle maturation time, a greater number of mature follicles, and higher ovulation and pregnancy rates than the control group. All differences were statistically significant (P<0.05), as shown in Table 2.

[0071] Table 2 Comparison of follicular maturation days, number of mature follicles, ovulation rate, and pregnancy rate between the two groups of patients.

[0072]

[0073] 2.3 Before treatment (blood was drawn on day 3 of menstruation), there were no statistically significant differences in the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) between the two groups (P > 0.05). After treatment (blood was drawn on day 21 of menstruation), the levels of LH, FSH, E2, and P increased in both groups; compared with the control group, the increase was more significant in the experimental group, and the difference between the two groups was statistically significant (P < 0.05), as shown in Table 3.

[0074] Table 3 Comparison of LH, FSH, E2, P, etc. between the two groups of patients

[0075]

[0076] 2.4 The endometrial thickness (on the day of HCG injection) in the experimental group was higher than that in the control group, and the difference was statistically significant (P<0.05), as shown in Table 4.

[0077] Table 4 Comparison of endometrial thickness between the two groups of patients

[0078]

[0079] 3. Conclusion

[0080] The combination of LE and this traditional Chinese medicine decoction is more effective in treating infertility caused by PCOS, with significantly improved ovulation and pregnancy rates, and is worth promoting.

[0081] Example 16 Animal Experiment

[0082] 1. Experimental Materials

[0083] 1.1 Animals

[0084] Ninety healthy, clean-grade female SD rats aged 70 days, weighing 220-250g, were purchased from Shanghai Xipu-Bikai Experimental Animal Co., Ltd.

[0085] 1.2 Drugs

[0086] Treatment group 1 preparation: letrozole + traditional Chinese medicine decoction (15g Rehmannia glutinosa, 9g Angelica sinensis, 15g Cuscuta chinensis, 9g Ligustrum lucidum, 9g Codonopsis pilosula, 9g Atractylodes macrocephala, 15g Polygonatum sibiricum, 9g Cyperus rotundus, 9g Ligusticum chuanxiong, decocted in water and taken orally, then 9g of donkey-hide gelatin powder was added).

[0087] Treatment Group 2 Preparation: Letrozole + Traditional Chinese Medicine Decoction (18g Rehmannia glutinosa, 5g Angelica sinensis, 21g Cuscuta chinensis, 9g Ligustrum lucidum, 7g Codonopsis pilosula, 11g Atractylodes macrocephala, 9g Polygonatum sibiricum, 13g Cyperus rotundus, 9g Ligusticum chuanxiong, decocted in water and taken orally, with 7g of donkey-hide gelatin powder added);

[0088] Treatment Group 3 Preparation: Simple Chinese herbal decoction (15g Rehmannia glutinosa, 9g Angelica sinensis, 15g Cuscuta chinensis, 9g Ligustrum lucidum, 9g Codonopsis pilosula, 9g Atractylodes macrocephala, 15g Polygonatum sibiricum, 9g Cyperus rotundus, 9g Ligusticum chuanxiong, decocted in water and taken orally, with 9g of donkey-hide gelatin powder added);

[0089] Preparation of control group 1: Letrozole + Chinese herbal decoction (15g Rehmannia glutinosa, 9g Angelica sinensis, 15g Eucommia ulmoides, 9g Ligustrum lucidum, 9g Codonopsis pilosula, 9g Dioscorea opposita, 15g Polygonatum sibiricum, 9g Morus alba, 9g Ligusticum chuanxiong, decocted in water and taken orally, with 9g of donkey-hide gelatin powder added);

[0090] Control group 2 preparation: letrozole + traditional Chinese medicine decoction (18g Rehmannia glutinosa, 5g Angelica sinensis, 21g Cuscuta chinensis, 9g Lilium brownii, 7g Ziziphus jujuba, 11g Atractylodes macrocephala, 9g Ophiopogon japonicus, 13g Cyperus rotundus, 9g Curcuma longa, decocted in water and taken orally, with 7g of donkey-hide gelatin powder added);

[0091] Control group 3 preparation: simple Chinese herbal decoction (15g Rehmannia glutinosa, 9g Angelica sinensis, 15g Eucommia ulmoides, 9g Ligustrum lucidum, 9g Codonopsis pilosula, 9g Dioscorea opposita, 15g Polygonatum sibiricum, 9g Morus alba, 9g Ligusticum chuanxiong, decocted in water and taken orally, with 9g of donkey-hide gelatin powder added);

[0092] Control group: physiological saline;

[0093] Model group: physiological saline.

[0094] 1.3 Main Reagents and Instruments

[0095] Glucose, neutral insulin injection, and human chorionic gonadotropin (HCG) for injection were provided by Shanghai First Maternity and Infant Hospital; radioimmunoassay kits for serum testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and insulin (INS) were provided by Beijing Northern Biotechnology Research Institute; the rat anti-Müllerian hormone (AMH) ELISA kit was provided by Guangzhou Darui Antibody Engineering Technology Co., Ltd.; and the ELISA kits for IGF-I, TGF-β1, and TNF-α were provided by Wuhan Boster Biological Engineering Co., Ltd.

[0096] 2. Methods

[0097] 2.1 Animal Modeling

[0098] Ten rats were randomly selected as the control group.

[0099] The remaining rats were modeled using the Poretsky method with modifications: except for the control group, all rats were subcutaneously injected with HCG 3.0 IU twice daily for 9 days; INS (human insulin injection) was started at 0.5 IU / day from day 1 to 11, gradually increasing to 6.0 IU / day, and maintained at 6.0 IU / day from day 12 until day 22, thus establishing an INS+HCG-induced PCOS-induced ovulation disorder rat model. During the modeling period, all groups received 5% glucose solution as their daily drinking water to prevent hypoglycemic shock, while the control group received the same volume of physiological saline subcutaneously during the same period. On day 23, blood was collected from the retro-orbital vein of the model rats to measure serum T and INS levels. In the control group, serum T and INS levels were within the normal range, and all vaginal smears showed complete estrous cycles; in the model rats, vaginal smears showed no complete estrous cycles and elevated serum T and INS levels, indicating successful establishment of the PCOS-induced ovulation disorder rat model. Seventy rats that successfully developed the model were selected based on their serum T and INS levels and were randomly divided into three treatment groups (groups 1, 2, and 3), three control groups (groups 1, 2, and 3), and a model group (group 10 rats in each group).

[0100] 2.2 Experimental Scheme

[0101] Treatment groups 1 and 2, and control groups 1 and 2, all received a combination of traditional Chinese medicine decoction and Western medicine. The traditional Chinese medicine decoction was administered by gavage at a dose of 17.16 g / kg, and the Western medicine at a dose of 2.5 mg / kg. Treatment group 3 and control group 3 rats received the decoction via gavage. The blank group and model group rats were administered 1 ml / 100 g body weight of physiological saline by gavage daily, once a day for 14 consecutive days.

[0102] 2.3 Observation Indicators

[0103] After the last administration, the rats were fasted overnight. Blood was collected from the inguinal vein the next day, and serum was separated. E2, T, LH, FSH, and INS were measured by radioimmunoassay; AMH, IGF-I, TGF-β1, and TNF-α were measured by ELISA.

[0104] 2.4 Statistical Methods

[0105] Statistical analysis was performed using SPSS 26.0 software. Data are presented as mean ± standard deviation. The data are presented in the table. One-way ANOVA was used for pairwise comparisons among multiple groups. Before data testing, tests for normality and homogeneity of variance were performed. Data that did not conform to a normal distribution underwent logarithmic or square root transformation. If the data still showed a skewed distribution after transformation, a nonparametric test was used. P < 0.05 was considered statistically significant.

[0106] 3. Results

[0107] 3.1 Effects of serum T, LH and FSH in rats.

[0108] As shown in Table 5, after drug administration, the serum T, LH, FSH, and AMH levels in the model group rats were significantly higher than those in the blank group (P<0.05). Compared with the model group, the serum T and LH levels in treatment groups I and II were significantly lower (P<0.01); the serum T and LH levels in treatment group III were significantly lower (p<0.05); the serum FSH and AMH levels in treatment groups I and II were significantly lower (P<0.01); the serum FSH and AMH levels in treatment group III were lower (P<0.05); the T, LH, FSH, and AMH levels in control group I, II, and III rats also decreased, but there was no significant difference (p>0.05).

[0109] Table 5 Effects of serum T, LH, FSH, and AMH in rats

[0110]

[0111] Note: * Compared with the control group, P<0.05; # Compared with the model group (P<0.01, P<0.05).

[0112] 3.2 Effects of serum E2 and INS in rats

[0113] As shown in Table 6, the serum E2 level in the model group was significantly lower and the INS level was significantly higher than that in the control group (P<0.05). Compared with the model group, the serum E2 level in rats 1, 2, and 3 of the treatment group was significantly higher (P<0.05), and the serum INS level in rats 1, 2, and 3 of the treatment group was significantly lower, with the decrease being particularly significant in rats 1 and 2 of the treatment group (P<0.01); the serum E2 and INS levels in rats 1, 2, and 3 of the control group showed no significant changes (p>0.05).

[0114] Table 6. Effects of serum E2 and INS in rats

[0115]

[0116] Note: * Compared with the control group, P<0.05; # Compared with the model group (P<0.01, P<0.05).

[0117] 3.3 Effects of serum IGF-I, TGF-β, and TNF-α in rats

[0118] As shown in Table 7, compared with the blank group, the serum levels of IGF-I and TGF-β1 in the model group rats were decreased, while the TNF-α level was increased (P<0.05). Compared with the model group, the serum TGF-β1 levels in rats in groups I, II, and III of the treatment group were increased (P<0.05 or P<0.01), with the increase being particularly significant in groups I and II of the treatment group (P<0.01). The serum IGF-I levels in rats in groups I, II, and III of the treatment group were significantly higher than those in the model group (P<0.05). The serum TNF-α levels in the treatment group rats were lower than those in the model group (P<0.05 or P<0.01), with the decrease being particularly significant in groups I and II of the treatment group (P<0.01). Compared with the model group, the serum levels of IGF-I and TGF-β1 in rats in groups I, II, and III of the control group were increased, while the TNF-α level was decreased, but there were no significant differences (P>0.05).

[0119] Table 7 Effects of serum IGF-I, TGF-β, and TNF-α in rats

[0120]

[0121] Note: * Compared with the control group, P<0.05; # Compared with the model group (P<0.01, P<0.05).

[0122] The results showed that treatment groups one and two were the most effective in treating infertility caused by PCOS, followed by treatment group three. Control groups one, two, and three did not show significant therapeutic effects on the disease.

[0123] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several improvements and additions without departing from the method of the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating infertility caused by polycystic ovary syndrome, characterized in that, It is made from the following raw materials in parts by weight: donkey-hide gelatin 5-13 parts, prepared rehmannia root 9-21 parts, angelica root 5-13 parts, dodder seed 9-21 parts, privet fruit 5-13 parts, codonopsis root 5-13 parts, atractylodes rhizome 5-13 parts, polygonatum rhizome 9-21 parts, cyperus rhizome 5-13 parts, and chuanxiong rhizome 5-13 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, It is made from the following raw materials in parts by weight: 7-11 parts donkey-hide gelatin, 12-18 parts prepared rehmannia root, 7-11 parts angelica root, 12-18 parts dodder seed, 7-11 parts privet fruit, 7-11 parts codonopsis root, 7-11 parts atractylodes rhizome, 15 parts polygonatum rhizome, 7-11 parts cyperus rhizome, and 7-11 parts chuanxiong rhizome.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, It is made from the following raw materials in parts by weight: 9 parts donkey-hide gelatin, 15 parts prepared rehmannia root, 9 parts angelica root, 15 parts dodder seed, 9 parts privet fruit, 9 parts codonopsis root, 9 parts atractylodes rhizome, 15 parts polygonatum rhizome, 9 parts cyperus rhizome, and 9 parts chuanxiong rhizome.

4. The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a drug for treating infertility caused by polycystic ovary syndrome.

5. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The dosage form of the traditional Chinese medicine composition is decoction, granules, tablets, capsules, mixture, or syrup.

6. A pharmaceutical composition for treating infertility caused by polycystic ovary syndrome, characterized in that, The pharmaceutical composition comprises the traditional Chinese medicine composition according to any one of claims 1-3 and letrozole.

7. The use of the pharmaceutical composition of claim 6 in the preparation of a medicament for treating infertility caused by polycystic ovary syndrome.

Images