Application of traditional Chinese medicine composition in preparation of medicine for preventing and treating dysmenorrhea

By using traditional Chinese medicine compositions to regulate hormone and neurotransmitter levels, the problem of dysmenorrhea treatment was solved, and the symptoms of primary and cold blood stasis type dysmenorrhea were significantly alleviated.

CN119607058APending Publication Date: 2025-03-14JIANGSU KANION PHARMA CO LTD
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Patent Information

Application Number
CN202510154190.0
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-02-12
Publication Date
2025-03-14

AI Technical Summary

Technical Problem

The prior art is difficult to effectively solve the treatment of dysmenorrhea, especially primary dysmenorrhea and cold blood stasis type dysmenorrhea.

Method used

The levels of estrogen and neurotransmitters are adjusted through specific preparation methods and dosage forms to relieve dysmenorrhea and dysfunction.

Benefits of technology

It significantly reduced the serum estradiol level in primary dysmenorrhea rats, increased serum progesterone level, and increased plasma β-endorphin level; it reduced the levels of luteinizing hormone and follicle-stimulating hormone in cold-coagulant blood stasis dysmenorrhea rats, and relieved the symptoms of dysmenorrhea.

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Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to application of a traditional Chinese medicine composition in preparation of a medicine for preventing and treating dysmenorrhea. The invention provides application of a traditional Chinese medicine composition in preparation of a medicine for preventing and treating dysmenorrhea. The traditional Chinese medicine composition comprises pseudo-ginseng, ligusticum wallichii, corydalis tuber, radix paeoniae alba, radix achyranthis bidentatae, rhizoma cibotii, cooked rhubarb and radix angelicae pubescentis. The traditional Chinese medicine composition can remarkably reduce the serum E2 level of rats with primary dysmenorrhea, increase the serum PROG level and improve the plasma beta-EP level; and the contents of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) of a rat with cold coagulation and blood stasis type dysmenorrhea are remarkably reduced. And the preparation method of the compound combination medicine for treating dysmenorrhea is simple, rapid, efficient and easy to operate. The prepared capsules, tablets, granules, pills, injections and the like are convenient to carry and take.
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Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to the application of a traditional Chinese medicine composition in the preparation of medicines for preventing and treating dysmenorrhea. Background Art

[0002] Dysmenorrhea refers to pain in the lower abdomen or waist, or even lumbar spine, during and before and after menstruation. It occurs every time during the menstrual cycle, and in severe cases, it can be accompanied by nausea and vomiting, cold sweats, cold hands and feet, and even fainting, which affects work and life.

[0003] At present, clinical dysmenorrhea is often divided into primary and secondary types. Primary dysmenorrhea refers to those without obvious lesions in the reproductive organs, so it is also called functional dysmenorrhea, which is more common in adolescent girls, unmarried people and married people without children. This type of dysmenorrhea can be relieved or disappear after normal delivery. Secondary dysmenorrhea is mostly caused by organic lesions in the reproductive organs. This disease is a common disease in gynecological clinics. According to relevant surveys, the incidence of dysmenorrhea is 33.19%.

[0004] In traditional Chinese medicine, dysmenorrhea is called "menstrual abdominal pain". It can be divided into deficiency and excess, and clinically it can be divided into four syndromes: qi stagnation and blood stasis, cold and dampness coagulation, qi and blood deficiency, and dampness and heat. Traditional Chinese medicine believes that menstrual fluid comes from the kidneys, which means that menstrual disorders are directly related to kidney function, and are also related to the spleen, liver, qi and blood, Chong Mai, Ren Mai, and uterus. Dysmenorrhea is mainly caused by kidney qi deficiency, insufficient qi and blood, and pressure from all aspects, which makes liver qi stagnate, resulting in poor circulation of qi and blood, causing dysmenorrhea. Therefore, the treatment of regulating menstruation focuses on tonifying the kidney, strengthening the spleen, soothing the liver, and regulating qi and blood.

[0005] The treatment options for dysmenorrhea mainly include drug therapy, non-drug therapy and surgical treatment. Drug therapy mainly relieves dysmenorrhea by analgesia and regulating hormone levels; non-drug therapy includes physical therapy such as exercise, hot compress, massage, etc.; in secondary dysmenorrhea, if the cause is clear and severe, surgical treatment may be required. In recent years, with the deepening of medical research, the treatment options for dysmenorrhea are also constantly evolving. The field of traditional Chinese medicine should also actively intervene in the work of dysmenorrhea and develop prescriptions for the symptoms. Summary of the invention

[0006] In view of this, the technical problem to be solved by the present invention is to provide an application of a traditional Chinese medicine composition in the preparation of a drug for preventing and treating dysmenorrhea.

[0007] The invention provides application of a traditional Chinese medicine composition in preparing a medicine for preventing and treating dysmenorrhea.

[0008] In the present invention, the Chinese medicine composition comprises the following raw materials in parts by weight: 100-400 parts of Panax notoginseng, 200-500 parts of Chuanxiong, 200-500 parts of Corydalis, 200-500 parts of White Peony, 200-500 parts of Achyranthes, 100-400 parts of Cibotium barometz, 100-400 parts of Rhubarb and 100-400 parts of Angelica dahurica.

[0009] In some embodiments, the Chinese medicine composition is made of the following raw materials in parts by weight: 335 parts of Panax notoginseng, 445 parts of Chuanxiong, 445 parts of Corydalis yanhusuo, 445 parts of white peony root, 445 parts of Achyranthes bidentata, 335 parts of Cibotium barometz, 335 parts of Rhubarb and 335 parts of Angelica dahurica.

[0010] In the present invention, the preparation method of the Chinese medicine composition as mentioned above comprises:

[0011] (1) Divide Panax notoginseng into two equal parts, one of which is made into coarse powder and the other into fine powder;

[0012] (2) Grind Corydalis yanhusuo, Chuanxiong and Angelica dahurica into coarse powder, combine with coarse powder of Panax notoginseng, and percolate with 4-8 times the amount of 65%-85% ethanol to make a fluid extract;

[0013] (3) Soak white peony root, Achyranthes bidentata, Cibotium barometz and cooked rhubarb in water and boil them 1-2 times, each time for 30-90 minutes. Concentrate the extract to a relative density of 1.15-1.20 at 50°C, add ethanol to make the alcohol content reach 60%-90%, refrigerate for more than 24 hours, filter, recover ethanol from the filtrate and concentrate it to a relative density of 1.15-1.20, add ethanol to make the alcohol content reach 60%-90%, refrigerate for more than 24 hours, filter, recover ethanol from the filtrate and concentrate it;

[0014] (4) Adding the fluid extract of step (2) to the product prepared in step (3), recovering ethanol and concentrating to a thick paste, drying, adding Panax notoginseng fine powder and mixing evenly to prepare a Chinese medicine composition.

[0015] In some embodiments, step (2) of the method for preparing the traditional Chinese medicine composition comprises: grinding Corydalis yanhusuo, Chuanxiong rhizome and Angelica pubescens into coarse powder, combining the powder with Panax notoginseng coarse powder, and percolating with 6 times the amount of 75% ethanol to prepare a fluid extract.

[0016] In some embodiments, step (3) of the method for preparing the Chinese medicine composition comprises: soaking white peony root, Achyranthes bidentata, Cibotium barometz and cooked rhubarb in water and then boiling for 60 minutes, concentrating the extract to a relative density of 1.15-1.20 at 50°C, adding ethanol to make the alcohol content reach 60%, refrigerating for more than 24 hours, filtering, recovering ethanol from the filtrate and concentrating it to a relative density of 1.15-1.20 at 50°C, adding ethanol to make the alcohol content reach 80%, refrigerating for more than 24 hours, filtering, recovering ethanol from the filtrate and concentrating it.

[0017] In some embodiments, the preparation method further comprises: step (5): adding conventional excipients to the traditional Chinese medicine composition of step (4) to prepare a clinically acceptable dosage form.

[0018] Preferably, step (5) of the preparation method is: after crushing the Chinese medicine composition of step (4), adding an appropriate amount of starch, granulating with 10% polyacrylic acid No. 4 resin, and encapsulating.

[0019] In the present invention, the prevention and treatment includes regulating the estrogen level and / or regulating the neurotransmitter level.

[0020] Dysmenorrhea is inextricably linked to changes in the levels of hormones related to females. Among them, the six female hormones (including testosterone, estradiol, progesterone, luteinizing hormone, prolactin and follicle-stimulating hormone) are hormones closely related to female reproductive health and menstrual cycle, and also affect the occurrence of dysmenorrhea. The present invention has experimentally found that the Chinese medicine composition as described above has a significant effect on the level of female hormones. In a specific embodiment, the female hormone includes at least one of progesterone, estradiol, luteinizing hormone and / or follicle-stimulating hormone. The regulation includes increasing the level of PROG and reducing the levels of E2, FSH and / or LH.

[0021] In a specific embodiment, the neurotransmitter is β-endorphin. Endorphin is an endogenous analgesic substance with activity similar to that of morphine. It is present in the nerve fibers of the endometrium, uterine cavity fluid, glandular epithelium and uterine muscle, and participates in the regulatory activities of the reproductive endocrine system. Progesterone can promote the secretion of endorphins, while estradiol can inhibit the promoting effect of progesterone on endorphins. The analgesic effect of endorphins may be related to the relief of reproductive-related pain such as dysmenorrhea. In the present invention, the regulation includes increasing the level of β-endorphin.

[0022] In the present invention, the dysmenorrhea is primary dysmenorrhea or cold stagnation and blood stasis type dysmenorrhea.

[0023] In a specific embodiment, for primary dysmenorrhea, the aforementioned Chinese medicine composition can regulate the levels of serum E2, PROG and plasma β-EP. The regulation includes increasing the level of PROG, decreasing the level of E2 and / or increasing the level of β-EP.

[0024] In a specific embodiment, for dysmenorrhea of ​​cold stagnation and blood stasis type, the Chinese medicine composition as described above can regulate the levels of LH and FSH in serum. The regulation includes reducing the levels of FSH and / or LH.

[0025] Furthermore, the present invention also provides a drug for preventing and treating dysmenorrhea, which comprises the following raw materials in parts by weight, or is made from the following raw materials in parts by weight:

[0026] 100~400 parts of Panax notoginseng, 200~500 parts of Chuanxiong, 200~500 parts of Corydalis, 200~500 parts of White Peony Root, 200~500 parts of Achyranthes Bidentata, 100~400 parts of Cibotium barometz, 100~400 parts of Rhubarb and 100~400 parts of Angelica dahurica.

[0027] The dosage form of the drug is tablet, capsule, granule, pill, injection, decoction, suspension, dispersant, syrup, suppository, gel, aerosol, patch or oral solution.

[0028] The medicine also includes other active ingredients that can treat and / or improve dysmenorrhea. The other active ingredients that can treat and / or improve dysmenorrhea include but are not limited to Panax notoginseng dysmenorrhea capsules and / or Leonurus granules.

[0029] Furthermore, the present invention also provides a method for preventing and treating dysmenorrhea, which comprises administering the above-mentioned drug. The administration method of the present invention includes but is not limited to oral administration and / or injection.

[0030] The invention provides an application of a Chinese medicine composition in preparing a drug for preventing and treating dysmenorrhea, wherein the Chinese medicine composition comprises Panax notoginseng, Chuanxiong, Corydalis, White Peony, Achyranthes, Cibotium barometz, Rheum officinale and Angelica dahurica. The Chinese medicine composition can significantly reduce the serum E2 level of rats with primary dysmenorrhea, increase the serum PROG level, and improve the plasma β-EP level; and significantly reduce the serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) content of rats with cold coagulation and blood stasis type dysmenorrhea. Moreover, the preparation method of the compound combination drug for treating dysmenorrhea is simple, rapid, efficient and easy to operate. The prepared capsules, tablets, granules, pills, injections and the like are easy to carry and convenient to take. DETAILED DESCRIPTION

[0031] The present invention provides the use of a Chinese medicine composition in the preparation of a drug for preventing and treating dysmenorrhea. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It should be particularly noted that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application of this article without departing from the content, spirit and scope of the present invention to realize and apply the technology of the present invention.

[0032] The following experiments, if no specific conditions are specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The APIs or excipients, reagents or instruments used, if the manufacturer is not specified, are all conventional products that can be purchased commercially. Unless otherwise specified, all percentages, ratios, proportions or parts are by weight.

[0033] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention. The present invention is further described below in conjunction with the embodiments:

[0034] Example 1 Preparation of Chinese medicine composition

[0035] Panax notoginseng 335g, Ligusticum chuanxiong 445g, Corydalis 445g, White Peony 445g, Achyranthes bidentata 445g, Cibotium barometz 335g, Rhubarb 335g, Angelica dahurica 335g.

[0036] Take half of the above eight ingredients and grind them into fine powder, and store them in another container; grind the other half of the Panax notoginseng into coarse powder. Grind Corydalis, Chuanxiong, and Angelica dahurica into coarse powder, combine them with the coarse powder of Panax notoginseng, and percolate with 6 times the amount of 75% ethanol to make a fluid extract; soak white peony root, Achyranthes bidentata, Cibotium barometz and cooked rhubarb in water and boil for 60 minutes, concentrate the extract to a relative density of 1.15-1.20 at 50°C, add ethanol to make the alcohol content reach 60%, refrigerate for more than 24 hours, filter, recover ethanol from the filtrate and concentrate it to a relative density of 1.15-1.20 at 50°C, add ethanol to make the alcohol content reach 80%, refrigerate for more than 24 hours, filter, recover ethanol from the filtrate and concentrate it to an appropriate volume, add the above fluid extract, recover ethanol and concentrate it to a thick paste, dry, add Panax notoginseng fine powder, mix well, grind, add appropriate amount of starch, granulate with 10% polyacrylic acid No. 4 resin, and encapsulate to make 1000 capsules.

[0037] Experimental Example 2 Therapeutic effect of Chinese medicine composition on primary dysmenorrhea rat model

[0038] 1. Experimental Materials

[0039] 1.1 Animals

[0040] 60 female SD rats, SPF grade, weighing 200-220 g, were purchased from Hangzhou Medical College.

[0041] Breeding environment: room temperature 20~26℃, relative humidity controlled at 40~70%, and breeding density of 5 per cage.

[0042] 1.2 Drugs

[0043] The Chinese medicine composition was prepared according to the method of Example 1 and provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd.; diethylstilbestrol injection (batch number: H11020965, Beijing Shuanghe Pharmaceutical Co., Ltd.); oxytocin injection (batch number: H32024725, Greenfield Pharmaceutical Co., Ltd.); sodium pentobarbital (batch number: 211122, Beijing Chemical Reagent Company); progesterone (Progesterone, PROG) radioimmunoassay kit (item number: PP773, Biyuntian Biotechnology Co., Ltd.), estradiol (Estradiol, E2) radioimmunoassay kit (item number: E-OSEL-R0001, Elabscience Company), β-endorphin (Plasma β-endorphin, β-EP) radioimmunoassay kit (Cat. No.: E-EL-R0105, Elabscience); Tianqi Tongmeng Capsule (Batch No.: Z20055369, Jiangxi Yaodu Renhe Pharmaceutical Co., Ltd.); Normal saline (Batch No.: 2101282721, Chenxin Pharmaceutical Co., Ltd.).

[0044] 1.3 Instruments

[0045] Electronic balance (Mettler Toledo, model: ME55); purified water instrument (Millipore, Germany, model: Milli-Q Plus); animal weight scale (Shanghai Xiangchuan Electronic Scale Co., Ltd., model: CX-SC-DA); refrigerated centrifuge (Beijing Baiyang Centrifuge Co., Ltd., model: BY-220A); microplate reader (MeiGu Molecular Instrument (Shanghai) Co., Ltd., model: FlexStation3).

[0046] 2. Dosage design

[0047] The daily dosage of the Chinese medicine composition is 30.72g of crude drug / day. According to the body surface area conversion method, the equivalent dose for rats is 30.72g / 60kg×6.25=3.2g of crude drug / kg. According to the 1 / 2:1:2 dosing method, the low dose is 1.6g of crude drug / kg, the medium dose is 3.2g of crude drug / kg, and the high dose is 6.4g of crude drug / kg. Oral administration, 10mL / kg, once a day.

[0048] The daily dosage of Panax notoginseng dysmenorrhea capsule suspension is 6g / day. According to the body surface area conversion method, the equivalent dose for rats is 6g / 60kg×6.25=0.6g / kg.

[0049] 3. Experimental Methods

[0050] 3.1 Primary dysmenorrhea rat model

[0051] 60 rats were randomly divided into normal control group, model control group, positive drug group, high, medium and low dose groups of Chinese medicine composition, with 10 rats in each group. Except for the blank group, rats in the other groups were subcutaneously injected with diethylstilbestrol every day for 10 consecutive days, with a dose of 0.5 mg / kg on the 1st and 10th days and 0.25 mg / kg on the 2nd to 9th days. During this period, the blank group and the model group were gavaged with an equal volume of normal saline every day, the positive drug group was gavaged with 0.6 g / kg of Tianqi Tongmeng Capsule Suspension, and the low, medium and high dose groups of Chinese medicine composition were gavaged with 1.6 g crude drug / kg, 3.2 g crude drug / kg, and 6.4 g crude drug / kg, respectively, once a day.

[0052] Except for the blank group, the corresponding drugs were gavaged on the 10th day, and 2U of oxytocin was injected intraperitoneally in each group of rats 45 minutes later. 1 hour after the administration of oxytocin, the rats were anesthetized by intraperitoneal injection of 2% sodium pentobarbital (2mL / kg), 3mL of blood was collected by carotid artery cannulation, 1mL of blood was injected into a centrifuge tube (without anticoagulant), and the blood was allowed to stand until coagulation. After equilibrium, it was centrifuged at 3000r / min for 10min, and the serum was separated. The serum E2 and serum PROG levels were determined by radioimmunoassay; 2mL of blood was quickly injected into an anticoagulant tube containing aprotinin and ethylenediaminetetraacetic acid (EDTA) and mixed, and immediately centrifuged at 3000r / min for 10min. The plasma was placed in a 20℃ refrigerator for testing, and the plasma β-EP level obtained after centrifugation was detected by radioimmunoassay.

[0053] 3.2 Related detection indicators

[0054] The levels of E2, PROG in serum and β-EP in plasma of rats.

[0055] 4. Statistical methods

[0056] The statistical software package Graphpad prism 8 was used for statistics. The experimental data were expressed as mean ± standard deviation (X ± SD). The t-test was used for comparison between two groups, and one-way ANOVA was used for comparison between multiple groups. P < 0.05 indicated that the data were statistically significant.

[0057] 5. Experimental Results

[0058] Compared with the normal control group, the serum E2 of the rats in the model group was significantly increased (P<0.001); the serum PROG level and plasma β-EP were significantly decreased (P<0.001, P<0.001), indicating that the model was successfully established. After 10 days of administration, compared with the model group, the serum E2 level of the positive drug group and the high and medium dose groups of the Chinese medicine combination was significantly reduced (P<0.001, P<0.001, P<0.05); the serum PROG level of the positive drug group and the high and medium dose groups of the Chinese medicine combination was significantly increased (P<0.001, P<0.001, P<0.01); the plasma β-EP level of the positive drug group and the high dose of the Chinese medicine combination was significantly increased (P<0.01, P<0.001). The results are shown in Table 1.

[0059] Table 1 Results of E2, PROG and β-EP test in rats of each group ( ±S)

[0060]

[0061] Note: Compared with the blank group, #P<0.05, ##P<0.01, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0062] 6. Experimental conclusion

[0063] 6.4g crude drug / kg of the Chinese herbal composition can significantly reduce the serum E2 level, increase the serum PROG level, and improve the plasma β-EP level in the primary dysmenorrhea model of rats; 3.2g crude drug / kg of the Chinese herbal composition can significantly reduce the serum E2 level and increase the serum PROG level in the primary dysmenorrhea model of rats, indicating that the Chinese herbal composition has the effect of relieving pain, and the Chinese herbal composition has a certain therapeutic effect on the primary dysmenorrhea rat model.

[0064] Experimental Example 3 Therapeutic effect of Chinese medicine composition on rat model of dysmenorrhea caused by cold stagnation and blood stasis

[0065] 1. Experimental Materials

[0066] 1.1 Animals

[0067] 60 female SD rats, SPF grade, weighing 200-220 g, were purchased from Hangzhou Medical College.

[0068] Breeding environment: room temperature 20~26℃, relative humidity controlled at 40~70%, and breeding density of 5 per cage.

[0069] 1.2 Drugs

[0070] The Chinese medicine composition was prepared according to the method of Example 1 and provided by Jiangsu Kangyuan Pharmaceutical Co., Ltd.; estradiol benzoate injection (Shanghai General Pharmaceutical Co., Ltd., batch number H31021114); oxytocin injection (Greenfield Pharmaceutical Co., Ltd., batch number H32024725); motherwort granules (Beijing Tongrentang Natural Medicine Tangshan Co., Ltd., batch number: Z13020660); luteinizing hormone (Luteinizing hormone, LH) enzyme-linked immunosorbent assay kit (Shanghai Jianglai Biotechnology Co., Ltd., item number: JL11706); follicle-stimulating hormone (Follicle-stimulating hormone, FSH) enzyme-linked immunosorbent assay kit (Shanghai Jianglai Biotechnology Co., Ltd., item number: JL13251); isoflurane (Shenzhen Ruiwode Life Science Co., Ltd., item number: R510-22-10).

[0071] 1.3 Instruments

[0072] Electronic balance (Mettler Toledo, model: ME55 / 02); refrigerated centrifuge (Beijing Baiyang Centrifuge Co., Ltd., model: BY-R20); animal weight scale (Shanghai Xiangchuan Electronic Scale Co., Ltd., model: CX-SC-DA); ELISA reader (MeiGu Molecular Instrument (Shanghai) Co., Ltd., model: FlexStation3).

[0073] 2. Dosage design

[0074] The daily dosage of the Chinese medicine composition is 30.72g of crude drug / day. According to the body surface area conversion method, the equivalent dose for rats is 30.72g / 60kg×6.25=3.2g of crude drug / kg. According to the 1 / 2:1:2 dosing method, the low dose is 1.6g of crude drug / kg, the medium dose is 3.2g of crude drug / kg, and the high dose is 6.4g of crude drug / kg. Oral administration, 10mL / kg, once a day.

[0075] The daily dosage of Leonurus granules in the positive control group was 30 g / day. According to the body surface area conversion method, the equivalent dose for rats was 30 g / 60 kg × 6.25 = 3.1 g / kg.

[0076] 3. Experimental Methods

[0077] 3.1 Establishment of rat model of dysmenorrhea caused by cold coagulation and blood stasis

[0078] After one week of adaptive feeding of rats, 60 rats were randomly divided into a blank group, a model group, a positive control group, and a high, medium, and low dose group of the Chinese medicine composition, with 10 rats in each group. The rats were placed in an ice water bath for 20 minutes every day. Except for the blank group, the remaining rats were injected with estradiol benzoate for 14 consecutive days. The dose on the 1st and 14th days was 0.5 mg / 200 g, and the dose for the rest of the time was 0.2 mg / 200 mg. On the 13th day, the rats were subcutaneously injected with epinephrine hydrochloride (8 μg / kg) twice, with an interval of 2 hours. After the second injection of epinephrine hydrochloride, the rats were placed in ice water for 5 minutes. 40 minutes after the last administration, oxytocin (2U / 100g) was injected intraperitoneally, and blood was collected from the abdominal aorta of the rats after isoflurane anesthesia.

[0079] 3.2 Grouping and Dosing

[0080] The rats were given drugs by gavage on the 3rd day after the injection of estradiol benzoate. The positive control group was given 3.1 g / kg of Leonurus granules, and the low-, medium- and high-dose groups of the Chinese medicine composition were given 1.6 g / kg, 3.2 g / kg and 6.4 g / kg, respectively. The blank group and the model group were gavaged with an equal volume of distilled water, respectively. The drugs were given by gavage once a day for 11 consecutive days.

[0081] 3.3 Related indicator measurement

[0082] ELISA kits were used to detect the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in serum.

[0083] 4. Statistical methods

[0084] The statistical software package Graphpad prism 8 was used for statistics. The experimental data were expressed as mean ± standard deviation (X ± SD). The t-test was used for comparison between two groups, and one-way ANOVA was used for comparison between multiple groups. P < 0.05 indicated that the data were statistically significant.

[0085] 5. Experimental Results

[0086] Compared with the normal group, the FSH and LH levels of the model group rats were significantly increased (P<0.001), indicating that the model was successfully established. After 11 days of administration, the FSH levels of the positive control group, the high-dose group of the Chinese medicine composition and the medium-dose group were lower than those of the model group, with significant differences (P<0.001, P<0.001, P<0.01); the LH levels of the positive control group, the high-dose group of the Chinese medicine composition and the medium-dose group were lower than those of the model group, with extremely significant differences (P<0.001), and the low-dose group of the Chinese medicine composition was lower than that of the model group, with significant differences (P<0.01). The results are shown in Table 2.

[0087] Table 2 Effects on serum LH and FSH in rats with dysmenorrhea model of cold stagnation and blood stasis ( ±S)

[0088]

[0089] Note: Compared with the blank group, #P<0.05, ##P<0.01, ###P<0.001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0090] 6. Experimental conclusion

[0091] The Chinese medicine composition of 6.4g crude drug / kg and 3.2g crude drug / kg can significantly reduce FSH and LH in rats with cold coagulation and blood stasis type dysmenorrhea, indicating that the Chinese medicine composition can regulate physiological hormone levels to relieve dysmenorrhea symptoms, and the Chinese medicine composition has a certain therapeutic effect on the rat model of cold coagulation and blood stasis type dysmenorrhea

[0092] The above are only preferred embodiments of the present invention. It should be pointed out that, for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. Application of the Chinese medicine composition in the preparation of drugs for preventing and treating dysmenorrhea; The Chinese medicine composition comprises the following raw materials in parts by weight: 100-400 parts of Panax notoginseng, 200-500 parts of Chuanxiong, 200-500 parts of Corydalis, 200-500 parts of White Peony, 200-500 parts of Achyranthes, 100-400 parts of Cibotium barometz, 100-400 parts of Rhubarb and 100-400 parts of Angelica dahurica.

2. The use according to claim 1, characterized in that: The Chinese medicine composition is prepared from the following raw materials in parts by weight: 335 parts of Panax notoginseng, 445 parts of Chuanxiong, 445 parts of Corydalis yanhusuo, 445 parts of white peony root, 445 parts of Achyranthes bidentata, 335 parts of Cibotium barometz, 335 parts of Rheum officinale and 335 parts of Angelica dahurica.

3. The use according to claim 1 or 2, characterized in that: The preparation method of the Chinese medicine composition comprises: (1) Divide Panax notoginseng into two equal parts, one of which is made into coarse powder and the other into fine powder; (2) Grind Corydalis yanhusuo, Chuanxiong and Angelica dahurica into coarse powder, combine with coarse powder of Panax notoginseng, and percolate with 4-8 times the amount of 65%-85% ethanol to make a fluid extract; (3) Soak white peony root, Achyranthes bidentata, Cibotium barometz and Rhubarb in water and boil for 1-2 times, each time for 30-90 minutes. Concentrate the extract to a relative density of 1.15-1.20 at 50°C, add ethanol to make the alcohol content reach 60%-90%, refrigerate for more than 24 hours, filter, recover ethanol from the filtrate and concentrate it to a relative density of 1.15-1.20, add ethanol to make the alcohol content reach 60%-90%, refrigerate for more than 24 hours, filter, recover ethanol from the filtrate and concentrate it; (4) Adding the fluid extract of step (2) to the product prepared in step (3), recovering ethanol and concentrating to a thick paste, drying, adding Panax notoginseng fine powder and mixing evenly to prepare a Chinese medicine composition.

4. The use according to claim 3, characterized in that: Step (2) comprises: grinding Corydalis yanhusuo, Chuanxiong and Angelica pubescens into coarse powder, combining the powder with Panax notoginseng coarse powder, and percolating with 6 times the amount of 75% ethanol to prepare a fluid extract; Step (3) comprises: soaking white peony root, Achyranthes bidentata, Cibotium barometz and Rhubarb in water and then boiling for 60 minutes, concentrating the extract to a relative density of 1.15-1.20 at 50°C, adding ethanol to make the alcohol content reach 60%, refrigerating for more than 24 hours, filtering, recovering ethanol from the filtrate and concentrating it to a relative density of 1.15-1.20 at 50°C, adding ethanol to make the alcohol content reach 80%, refrigerating for more than 24 hours, filtering, recovering ethanol from the filtrate and concentrating it.

5. The use according to any one of claims 1 to 4, characterized in that: The prevention and treatment include regulating estrogen levels and / or regulating neurotransmitter levels.

6. The use according to claim 5, characterized in that: The female hormone includes at least one of progesterone, estradiol, luteinizing hormone and / or follicle stimulating hormone.

7. The use according to claim 5, characterized in that: The neurotransmitter is beta-endorphin.

8. The use according to any one of claims 1 to 7, characterized in that: The dysmenorrhea is primary dysmenorrhea or cold stagnation and blood stasis type dysmenorrhea.

9. A drug for preventing and treating dysmenorrhea, characterized in that: The invention comprises the following raw materials in parts by weight, or is made from the following raw materials in parts by weight: 100~400 parts of Panax notoginseng, 200~500 parts of Chuanxiong, 200~500 parts of Corydalis, 200~500 parts of White Peony Root, 200~500 parts of Achyranthes Bidentata, 100~400 parts of Cibotium barometz, 100~400 parts of Rhubarb and 100~400 parts of Angelica dahurica.

10. The drug according to claim 9, characterized in that It also includes other active ingredients that have the function of treating and / or improving dysmenorrhea.