Application of traditional Chinese medicine composition in preparation of medicine for treating endometriosis

Abstract

The invention belongs to the technical field of medicines, and particularly relates to application of a traditional Chinese medicine composition in preparation of a medicine for treating endometriosis. The traditional Chinese medicine composition is prepared from the following raw materials: 1-25 parts of fried peach kernel, 2-40 parts of fried myrrh, 2-40 parts of radix salviae miltiorrhizae, 2-20 parts of radix paeoniae rubra, 2-20 parts of safflower, 2-30 parts of herba lycopi, 2-20 parts of fried cowherb seed, 2-30 parts of spina gleditsiae, 2-60 parts of herba patriniae, 2-60 parts of dandelion, 1-25 parts of szechwan chinaberry fruit, 2-40 parts of radix angelicae, 2-40 parts of pyrrosia lingua and 1-20 parts of fructus lycii. The traditional Chinese medicine composition has a remarkable curative effect on endometriosis, has no toxic or side effect, and provides an important clinical value for overcoming the defects of few Chinese patent medicine varieties and poor curative effect in the current market.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicine, and particularly relates to the application of a traditional Chinese medicine composition in the preparation of a medicament for treating endometriosis. Background Art

[0002] Endometriosis (EMT) refers to the growth and infiltration of endometrial tissue (glands and stroma) in locations outside the endometrium. Repeated bleeding can form nodules and masses, causing pain. It can affect any part of the body, but the vast majority is located in pelvic organs and peritoneum, with the ovaries and uterosacral ligaments being the most common. The specific cause of endometriosis is not yet clear, but it may be related to retrograde menstruation, genetic factors, immune factors, inflammatory factors, etc.

[0003] The symptoms of endometriosis are closely related to the menstrual cycle and mainly include: ⑴ Pain: 70% - 80% of endometriosis patients have varying degrees of pelvic pain, including dysmenorrhea, non-menstrual abdominal pain, dyspareunia, and defecation pain, etc. Dysmenorrhea is the most typical symptom and mostly the first symptom, usually gradually worsening. ⑵ Abnormal menstruation: 15% - 30% of patients have symptoms such as increased menstrual volume, prolonged menstrual period, or continuous menstruation. ⑶ Infertility: The incidence of infertility in endometriosis patients is 30% - 50%, and among women with infertility, approximately 20% - 50% are endometriosis patients. ⑷ Pelvic mass: When the ovarian endometriotic cyst is relatively large, a mass adhered to the uterus can be palpated during a gynecological examination. Additionally, if the endometrium implants in the intestine, bladder, ureter, or even the lungs and pleura, etc., it will also cause corresponding symptoms, such as menstrual blood in the stool, menstrual blood in the urine, hydronephrosis of the ureter, hemoptysis during menstruation, pneumothorax during menstruation, etc.

[0004] Endometriosis is a chronic disease that requires long-term management. Currently, common treatment methods include: drug suppression of ovarian function to prevent the growth and activity of endometrial implants, conservative surgery to remove as much endometriotic tissue as possible, combined application of the first two treatments, and total hysterectomy, usually with the ovaries and fallopian tubes removed simultaneously. Surgical treatment may lead to a decline in ovarian reserve function, infertility, menstrual changes, or even premature menopause, etc., and there is a certain risk of recurrence after surgery. Drug treatment includes: estrogen suppression, gonadotropin-releasing hormone agonists or antagonists, androgens, and progestins, but all have certain side effects. For example, the side effects of estrogen suppression include abdominal distension, breast tenderness, liver and kidney function damage, high recurrence rate, breakthrough bleeding, and deep vein thrombosis, etc.

[0005] The advantage of traditional Chinese medicine lies in that it can relieve the pain brought by surgery and the harm of western medicine hormones to the body. Through the advantages of overall conditioning, personalized treatment and few side effects, traditional Chinese medicine can effectively relieve symptoms, prevent recurrence, and improve the quality of life of patients, fundamentally solving the problem. Therefore, it is imperative to develop traditional Chinese medicine drugs for the treatment of endometriosis.

[0006] Qianliexin Capsule is an existing drug for the treatment of chronic prostatitis and improvement of symptoms of prostatic hyperplasia caused by blood stasis condensation and damp-heat pouring downward. It is composed of stir-fried peach kernels, stir-fried myrrh, salvia miltiorrhiza, red peony root, safflower, eupatorium japonicum, stir-fried semen vaccariae, gleditsia sinensis spine, patrinia scabiosaefolia, dandelion, toosendan fruit, angelica dahurica, pyrrosia lingua, and wolfberry fruit. There is no report on its use for the treatment of endometriosis. Summary of the Invention

[0007] In order to solve the above problems, the present invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for the treatment of endometriosis. This traditional Chinese medicine composition has significant curative effect on endometriosis and no toxic side effects, providing important clinical value for making up for the shortage of varieties and poor curative effect of traditional Chinese patent medicines for this treatment on the current market, and also expanding the new use of the traditional Chinese medicine formula used in Qianliexin Capsule.

[0008] The present invention provides the following technical solutions: An application of a traditional Chinese medicine composition in the preparation of a drug for the treatment of endometriosis, wherein the traditional Chinese medicine composition is made from the following raw materials in parts by weight: Stir-fried peach kernels 1-25 parts, stir-fried myrrh 2-40 parts, salvia miltiorrhiza 2-40 parts, red peony root 2-20 parts, safflower 2-20 parts, eupatorium japonicum 2-30 parts, stir-fried semen vaccariae 2-20 parts, gleditsia sinensis spine 2-30 parts, patrinia scabiosaefolia 2-60 parts, dandelion 2-60 parts, toosendan fruit 1-25 parts, angelica dahurica 2-40 parts, pyrrosia lingua 2-40 parts, wolfberry fruit 1-20 parts.

[0009] Furthermore, the preparation method of the traditional Chinese medicine composition is as follows: Take the above-mentioned parts by weight of stir-fried myrrh, gleditsia sinensis spine, and angelica dahurica, and pulverize them into fine powder; the remaining 11 raw materials are decocted with water 2-4 times, each time for 0.5-2 hours. Combine the extraction liquids, filter, concentrate the filtrate into a thick paste, add the above-mentioned fine powder, dry, continue to pulverize into fine powder, mix evenly, and finally process it into an oral preparation to obtain.

[0010] Furthermore, the oral preparation is powder, capsule, tablet, granule or pill.

[0011] Furthermore, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of stir-fried peach kernels, 15 parts of stir-fried myrrh, 15 parts of salvia miltiorrhiza, 15 parts of red peony root, 15 parts of safflower, 15 parts of lycopus lucidus, 15 parts of stir-fried semen vaccariae, 15 parts of gleditsia sinensis thorn, 50 parts of patrinia scabiosaefolia, 50 parts of dandelion, 15 parts of toosendan fruit, 15 parts of angelica dahurica, 25 parts of pyrrosia lingua, 15 parts of wolfberry fruit.

[0012] The beneficial effects of the present invention include but are not limited to: In the traditional Chinese medicine composition of the present invention, stir-fried peach kernels, stir-fried myrrh, salvia miltiorrhiza, red peony root, safflower, gleditsia sinensis thorn, lycopus lucidus, and stir-fried semen vaccariae together serve as the monarch drugs, jointly exerting the effects of promoting blood circulation to remove blood stasis and dissipating swelling and relieving pain; supplemented by dandelion, patrinia scabiosaefolia, and pyrrosia lingua as the ministerial drugs, mainly clearing damp-heat; assisted by wolfberry fruit to tonify the kidney and replenish essence; angelica dahurica and toosendan fruit regulate qi and dredge the meridians, guiding all the drugs to reach the affected area, serving as the adjuvant drugs. The whole formula of this traditional Chinese medicine composition is compatibly formulated, with the effects of promoting blood circulation to remove blood stasis, detoxifying and dissipating swelling, regulating qi and relieving pain, and tonifying the kidney and replenishing essence, and has remarkable curative effects on female endometriosis. As a drug currently only used for improving the symptoms of chronic prostatitis and prostatic hyperplasia, the research on the application of the present invention has important clinical significance for expanding the new uses of this drug formula. Specific embodiments

[0013] To clearly illustrate the technical features of this solution, the present invention will be elaborated in detail through specific embodiments below. The scope of the present invention is not limited to the following embodiments. Professionals in the field can understand that various changes and modifications can be made to the present invention without departing from the spirit and scope of the present invention. Example 1

[0014] This example is a hard capsule preparation of the traditional Chinese medicine composition of the present invention.

[0015] The prescription is: 500 g of stir-fried myrrh, 500 g of gleditsia sinensis thorn, 500 g of angelica dahurica powder, 500 g of stir-fried peach kernels, 500 g of salvia miltiorrhiza, 500 g of red peony root, 500 g of safflower, 500 g of lycopus lucidus, 500 g of stir-fried semen vaccariae, 1666 g of patrinia scabiosaefolia, 1666 g of dandelion, 500 g of toosendan fruit, 833 g of pyrrosia lingua, 500 g of wolfberry fruit.

[0016] The preparation method is as follows: Take 500 g of stir-fried myrrh, 500 g of gleditsia sinensis thorn, and 500 g of angelica dahurica powder, crush them into fine powder, and set aside; separately take 500 g of stir-fried peach kernels, 500 g of salvia miltiorrhiza, 500 g of red peony root, 500 g of safflower, 500 g of lycopus lucidus, 500 g of stir-fried semen vaccariae, 1666 g of patrinia scabiosaefolia, 1666 g of dandelion, 500 g of toosendan fruit, 833 g of pyrrosia lingua, 500 g of wolfberry fruit, mix them, add 65 L of water and decoct for 2 times, each time for 1 hour. Combine the extraction liquids, filter, concentrate the filtrate into a thick paste, add the above-mentioned reserved fine powder, dry, crush into fine powder, sieve, make into fine powder, mix evenly, and fill into clear capsules to make hard capsules.

[0017] Dosage and Administration: Oral administration. Take 4 - 6 capsules each time, three times a day; or as prescribed by a doctor. Example 2

[0018] This example is the pill preparation of the traditional Chinese medicine composition of the present invention.

[0019] Prescription: Myrrha (parched) 400g, Gleditsiae Spina 400g, Radix Angelicae Dahuricae powder 400g, Persicae Semen (parched) 500g, Salviae Miltiorrhizae Radix 500g, Paeoniae Radix Rubra 500g, Carthami Flos 500g, Lycopi Herba 500g, Vaccariae Semen (parched) 500g, Patriniae Herba 1666g, Taraxaci Herba 1666g, Meliae Toosendan Fructus 500g, Pyrrosiae Folium 833g, Lycii Fructus 500g.

[0020] Preparation method: Take Myrrha (parched) 400g, Gleditsiae Spina 400g, Radix Angelicae Dahuricae powder 400g, and crush them into fine powder for standby; take another Persicae Semen (parched) 500g, Salviae Miltiorrhizae Radix 500g, Paeoniae Radix Rubra 500g, Carthami Flos 500g, Lycopi Herba 500g, Vaccariae Semen (parched) 500g, Patriniae Herba 1666g, Taraxaci Herba 1666g, Meliae Toosendan Fructus 500g, Pyrrosiae Folium 833g, Lycii Fructus 500g, mix them, add 65L of water for decoction, decoct for 2 times, 1 hour each time, combine the extraction liquids, filter, concentrate the filtrate into a thick paste, add the above - mentioned standby fine powder, dry, crush into fine powder, sieve, make it into fine powder, mix well, and make pills with water to form pill preparations.

[0021] Dosage and Administration: Oral administration. Take 20 - 30 pills each time, three times a day; or as prescribed by a doctor. Example 3

[0022] This example is the tablet of the traditional Chinese medicine composition of the present invention.

[0023] Prescription: Myrrha (parched) 500g, Gleditsiae Spina 500g, Radix Angelicae Dahuricae powder 500g, Persicae Semen (parched) 400g, Salviae Miltiorrhizae Radix 400g, Paeoniae Radix Rubra 400g, Carthami Flos 400g, Lycopi Herba 400g, Vaccariae Semen (parched) 400g, Patriniae Herba 1500g, Taraxaci Herba 1500g, Meliae Toosendan Fructus 400g, Pyrrosiae Folium 800g, Lycii Fructus 400g.

[0024] Preparation method: Take Myrrha (parched) 500g, Gleditsiae Spina 500g, Radix Angelicae Dahuricae powder 500g, and crush them into fine powder for standby; take another Persicae Semen (parched) 400g, Salviae Miltiorrhizae Radix 400g, Paeoniae Radix Rubra 400g, Carthami Flos 400g, Lycopi Herba 400g, Vaccariae Semen (parched) 400g, Patriniae Herba 1500g, Taraxaci Herba 1500g, Meliae Toosendan Fructus 400g, Pyrrosiae Folium 800g, Lycii Fructus 400g, mix them, add 65L of water for decoction, decoct for 2 times, 1 hour each time, combine the extraction liquids, filter, concentrate the filtrate into a thick paste, add the above - mentioned standby fine powder and soluble starch, and make tablets.

[0025] Dosage and Administration: Oral administration. Take 4 - 6 tablets each time, three times a day; or as prescribed by a doctor.

[0026] The fine powders of the medicaments prepared in the above Examples 1-3 were respectively taken for animal experimental studies.

[0027] The following is an experimental study and verification of the effect of the drug prepared by the present invention in treating endometriosis through an animal experiment on an endometriosis model.

[0028] I. Test drugs 1.1 Traditional Chinese medicine compositions Example 1, Example 2, and Example 3, corresponding to the medicament prescriptions and preparation methods of the aforementioned Examples 1, 2, and 3 respectively. The fine powders sieved from Examples 1 and 2 and the fine powder of the drug before tabletting in Example 3 were taken.

[0029] 1.2 Control drug: Guizhi Fuling Capsule.

[0030] II. Experimental study on endometriosis in rats 2.1 Experimental animals 60 healthy female SD rats, weighing 250±20 g.

[0031] 2.2 Experimental grouping After 3 days of adaptive feeding of the experimental animals, 10 were randomly selected as the blank control group; the remaining 50 were used for modeling, and the animals after successful modeling were divided into a model group, a traditional Chinese medicine composition Example 1 group, a traditional Chinese medicine composition Example 2 group, a traditional Chinese medicine composition Example 3 group, and a Guizhi Fuling Capsule control group.

[0032] 2.3 Modeling One day before modeling, each rat was subcutaneously injected with estradiol benzoate at 0.1 mg / kg•d. The rats were anesthetized by intraperitoneal injection of 20% urethane (4 ml / kg). After shaving the lower abdomen, it was disinfected with 75% alcohol. A longitudinal incision about 2 cm was made in the middle of the lower abdomen to expose the uterus. The ovarian end of the right side was ligated, and a uterine segment about 1.5 cm long at the distal end of the right uterine horn was ligated and then cut off, and placed in a petri dish containing sterile normal saline. Two pieces of uterine tissue (including the muscular layer) of 5 mm×5 mm were cut, with the serosa facing the peritoneum and the mucosa facing the abdominal cavity, and the four corners were fixed to the abdominal wall muscles on both sides of the incision with 6-0 non-absorbable sutures, and the abdominal incision was continuously sutured layer by layer, and the abdomen was routinely closed. Pay attention to observing the breathing and heartbeat of the rats and wait for them to wake up naturally. After the operation, penicillin was intramuscularly injected to prevent infection for 3 days, and estradiol benzoate at 0.1 mg / kg•d was injected on the second day after the operation, once every three days for a total of 5 times.

[0033] 2.4 Drug administration On the 15th day after surgery, the animals with successful modeling were randomly divided into 5 groups, namely the model group, the traditional Chinese medicine composition example 1 group (1.6 g / kg; equivalent to 5.215 g / kg of crude drug content), the traditional Chinese medicine composition example 2 group (1.6 g / kg; equivalent to 5.215 g / kg of crude drug content), the traditional Chinese medicine composition example 3 group (1.6 g / kg; equivalent to 5.215 g / kg of crude drug content), and the Guizhi Fuling Capsule control group (0.25 g / kg). Drugs with corresponding concentrations were prepared and administered by gavage at a dose of 1.0 ml / 100 g. The blank control group was gavaged with 1.0 ml / 100 g of distilled water; the administration was continued for 30 days.

[0034] After the administration ended, all rats were anesthetized with ether, the abdominal cavity was opened, the growth of the ectopic endometrial lesions was observed, and the length, width, and thickness of the ectopic endometrium were measured and recorded. The ectopic volume was calculated, and the capillary vessels and adhesion conditions of the ectopic tissue were recorded. The ectopic tissue together with the adjacent adhered tissue was cut and fixed in 10% formaldehyde for pathological examination and immunohistochemical detection of the expression of CD34. The ovaries were dissected and weighed, and the organ coefficient (ovary weight / rat body weight × 100%, %) was calculated.

[0035] Steps of immunohistochemical staining: The paraffin sections were routinely dewaxed and hydrated, 4% hydrogen peroxide was added dropwise and left for 20 min, the antigen was repaired by heating for 30 min, rinsed with PBS phosphate buffer for 3 min × 3 times, the primary antibody (1:50) was added dropwise and incubated overnight at 4°C, rinsed with PBS for 3 min × 3 times, incubated with the secondary antibody for 20 min, rinsed with PBS for 3 min × 3 times, developed with DBA, counterstained with hematoxylin, and sealed with neutral gum. Observation was carried out under a microscope. After staining, randomly select 400-fold microscopic fields of view of the sections of each experimental animal for observation and counting. The reading of the slides refers to the Formwitz scoring method. Taking the cells in the middle of the section as the base number 100%, according to the percentage of receptor-positive cells and the staining depth, it is divided into four grades: - grade (negative): positive cells < 25% (1 point) or no staining (1 point); + grade (weak positive): positive cells 25% - 50% (2 points), positive staining is yellow and relatively clear (2 points); ++ grade (positive): positive cells 51% - 75% (3 points), positive staining is brown-yellow and clear (3 points); +++ grade (strong positive): positive cells > 75% (4 points), cytoplasm is brown (4 points); the product of the two scores is used as the final score.

[0036] 2.5 Data statistical method The statistical analysis of the data was performed using SPSS 17.0 statistical software, and the results were expressed as mean ± standard deviation ( ), and the t-test was used.

[0037] 2.6 Test results of the traditional Chinese medicine composition of the present invention on rat endometriosis 2.6.1 Effects on the body weight and ovarian coefficient of rats, and the results are shown in Table 1.

[0038]

[0039] 2.6.2 Comparison of the growth of endometriotic lesions, and the results are shown in Table 2.

[0040] After the animals were sacrificed, laparotomy was performed to observe the appearance, and the height of the cystic fluid in the ectopic lesions of each group was measured with a caliper. The growth of the bilateral ectopic lesions was divided into 4 grades: (1) Atrophy or no growth (-): The ectopic lesion shrank or was accompanied by a yellowish color, or only the ectopic lesion was present but there was no fluid accumulation; (2) Low growth (+): There was a small amount of fluid in the ectopic lesion; (3) Moderate growth (++): There was cystic fluid in the ectopic lesion, but the height of the accumulated fluid < 2 mm; (4) Good growth (+++): The height of the cystic fluid in the ectopic lesion ≥ 2 mm.

[0041]

[0042] 2.6.3 Observation of the vascular richness of endometriotic lesions, and the results are shown in Table 3.

[0043] Grading criteria: (1) Relatively rich blood vessels in the ectopic lesion (+++); (2) Less blood vessel distribution in the ectopic lesion (++); (3) Basically no blood vessel distribution in the ectopic lesion (+); (4) No blood vessel distribution in the ectopic tissue (-).

[0044]

[0045] 2.6.4 Observation of the adhesion of endometriotic lesions, and the results are shown in Table 4.

[0046] Grading criteria: (1) High adhesion of the ectopic tissue to the intestinal mucosa or other tissues (+++), and covered with adipose tissue; (2) Mild adhesion of the ectopic tissue to other tissues, and covered with a little adipose tissue (++); (3) Basically no adhesion of the ectopic tissue, or it can be easily separated by gentle peeling (+); (4) No adhesion appears in the ectopic tissue (-).

[0047]

[0048] 2.6.5 Observation and comparison of the area and volume of endometriotic lesions, and the results are shown in Table 5.

[0049]

[0050] 2.6.6 Changes in the expression of CD34 in endometriotic lesions, and the results are shown in Table 6.

[0051]

[0052] 2.6.7 Comparison of the lesion degree of uterine ectopic endometrial tissue, and the results are shown in Table 7.

[0053]

[0054] III. Experimental Study on Endometriosis in Mice 3.1 Experimental animals: 80 female Kunming mice, weighing 25 ± 2 g.

[0055] 3.2 Experimental grouping Randomly select 12 as the blank control group; the remaining 68 are used for modeling, and after successful modeling, the animals are divided into a model group, a traditional Chinese medicine composition Example 1 group, a traditional Chinese medicine composition Example 2 group, a traditional Chinese medicine composition Example 3 group, and a Guizhi Fuling Capsule group.

[0056] 3.3 Modeling Two days before modeling, intramuscularly inject estradiol benzoate at 0.05 mL / mouse / day. On the 3rd day, except for the 12 in the normal control group, the remaining 68 animals are modeled. Intraperitoneally inject 10% urethane for anesthesia at 25 mL / kg, fix on the operating table, and disinfect the abdomen; open the abdominal cavity, ligate both sides of the left uterine ovarian end and vaginal end of the mouse, cut it off, longitudinally cut it into 2 pieces (5 mm × 5 mm), and sew it on both sides of the abdominal wall. Three days after the operation, intraperitoneally inject penicillin at 1.7 million U / kg every day. After the operation, intramuscularly inject estradiol benzoate at 0.05 mL / mouse / time, twice, to promote the growth of ectopic endometrium.

[0057] 3.4 Administration In the 2nd week of the experiment, the successfully modeled animals are randomly divided into 5 groups, namely the model group, the traditional Chinese medicine composition Example 1 group (1.6 g / kg; equivalent to containing 5.215 g / kg of crude drug), the traditional Chinese medicine composition Example 2 group (1.6 g / kg; equivalent to containing 5.215 g / kg of crude drug), the traditional Chinese medicine composition Example 3 group (1.6 g / kg; equivalent to containing 5.215 g / kg of crude drug), and the Guizhi Fuling Capsule group (1.6 g / kg). The test samples of each group are prepared into corresponding drug concentrations and administered by gavage at 0.2 mL / 10 g. The blank control group and the model group are respectively given an equal amount of distilled water, and administered continuously for 5 weeks.

[0058] 30 minutes after the last administration, the animals are sacrificed by cervical dislocation, fixed on the operating table, the hair is shaved, the abdomen is disinfected, the abdominal cavity is opened, the growth of ectopic endometrial lesions is observed, and the length, width, and thickness of the ectopic endometrium are measured and recorded. The uterus and ectopic tissues together with the adjacent tissues with adhesions are cut off and fixed in 10% formaldehyde for pathological examination and immunohistochemical detection of the expression of CD34 and VEGF. Weigh the weight of the ovaries and calculate the organ coefficient (ovary weight / mouse weight × 100%, %).

[0059] Immunohistochemical staining procedure: Paraffin sections were routinely dewaxed and hydrated, 4% hydrogen peroxide was dropped and placed for 20 min, antigen was repaired by heating for 30 min, rinsed with PBS phosphate buffer for 3 min × 3 times, primary antibodies (VEGF 1:50, CD34 1:50) were dropped, incubated overnight at 4°C, rinsed with PBS for 3 min × 3 times, secondary antibody was incubated for 20 min, rinsed with PBS for 3 min × 3 times, DBA was used for color development, counterstained with hematoxylin and sealed with neutral gum, and observed under a microscope. After staining, randomly select representative 400-fold microscopic fields of view from the sections of each experimental animal for observation and counting. The reading of the slides refers to the Formwitz scoring method. Taking the cells in the middle of the section as the base number of 100%, it is divided into four grades according to the percentage of receptor-positive cells and the staining depth: - grade (negative): positive cells < 25% (1 point) or no staining (1 point); + grade (weakly positive): positive cells 25% - 50% (2 points), positive staining is yellow and relatively clear (2 points); ++ grade (positive): positive cells 51% - 75% (3 points), positive staining is brownish yellow and clear (3 points); +++ grade (strongly positive): positive cells > 75% (4 points), cytoplasm is brown (4 points); the product of the two scores is used as the final score.

[0060] 3.5 Statistical method for data The statistical analysis of the data was performed using SPSS 17.0 statistical software, and the results were expressed as mean ± standard deviation ( ), and t-test was used.

[0061] 3.6 Research results of the composition of the present invention on endometriosis in mice 3.6.1 Effect on the body weight of mice, and the results are shown in Table 8.

[0062]

[0063] 3.6.2 Effect on the ectopic endometrial lesions of mice, and the results are shown in Table 9.

[0064]

[0065] 3.6.3 Effect on the ovarian coefficient of endometriosis mice, and the results are shown in Table 10.

[0066]

[0067] 3.6.4 Expression of CD34 and VEGF in the endometrial ectopic lesions of mice, and the results are shown in Table 11.

[0068]

[0069] 3.6.5 Histopathological observation of the ectopic endometrial tissue of mice by the composition of the present invention, and the results are shown in Table 12.

[0070]

[0071] The experimental results showed that the traditional Chinese medicine compositions of Examples 1, 2, and 3 could inhibit the growth of endometriotic tissues in rats, and the degree and scope of pseudo-glands and inflammatory cell infiltration in the ectopic endometrium of rats were alleviated compared with the model group; the immunohistochemical results showed that the positive expression in the endometriosis model group of rats was significantly higher than that in the blank control group, and the difference was statistically significant (P < 0.05); compared with the model group, although the expression of CD34 in the traditional Chinese medicine compositions of Examples 1, 2, and 3 showed a downward trend, there was no significant difference, and there was also no significant difference in the Cinnamon Twig and Poria group compared with the model group (P > 0.05).

[0072] The positive expression in the endometriosis model group of mice was significantly higher than that in the blank control group (P < 0.05); compared with the model group, there was no significant difference in the positive expression in the Cinnamon Twig and Poria group compared with the model group, and the expression of CD34 in the treatment groups of the traditional Chinese medicine compositions of Examples 1, 2, and 3 was significantly lower than that in the model group (P < 0.05), suggesting that the traditional Chinese medicine compositions of Examples 1, 2, and 3 could reduce the expression of CD34 in the endometrial transplantation tissues of experimental animals; the expression of VEGF in the traditional Chinese medicine compositions of Examples 1, 2, and 3 groups decreased significantly (P < 0.05), suggesting that the traditional Chinese medicine compositions of Examples 1, 2, and 3 groups could reduce the expression level of VEGF in the endometriotic tissues of mice.

[0073] The experiment found that the ovarian coefficient in the endometriosis model group of rats was significantly higher than that in the normal control group (P < 0.01). After the drug treatment, the ovarian coefficients of the experimental animals in each group decreased. The ovarian coefficients of the experimental animals in the traditional Chinese medicine compositions of Examples 1, 2, and 3 groups were significantly lower than those in the model group (P < 0.01), and there was no significant difference compared with the blank control group (P > 0.05).

[0074] The experiment found that the ovarian coefficient in the endometriosis model group of mice decreased compared with the normal control group, and the traditional Chinese medicine compositions of Examples 1, 2, and 3 groups and the positive control group increased to varying degrees.

[0075] In summary, the traditional Chinese medicine compositions of Examples 1, 2, and 3 have a certain therapeutic effect on experimental endometriosis in rats and mice.

[0076] IV. Preliminary Toxicity Study The acute toxicity test showed that the sample of Example 1 was given to mice at 13 g / kg / time, that is, the single dose was more than 100 times the daily dose of a human (70 kg). It was administered by gavage 3 times within 24 hours and observed for one week. No abnormalities were found, and no animal deaths occurred. According to the requirements of the tolerance test, when mice can tolerate 60 - 100 times the adult dose, it can be considered that the tolerance test is qualified. The powder dosage of Example 1 far exceeds the above requirements, so it can be considered that this traditional Chinese medicine composition is relatively safe.

[0077] The long-term toxicity test showed that the samples of Example 1 were administered to three groups of mice A, B, and C at 0.65 g / 100 g, 0.39 g / 100 g, and 0.13 g / 100 g respectively, which were equivalent to 50 times, 30 times, and 10 times the human dosage. During the 180 days of continuous administration, no abnormalities were found in the appearance and activities of the animals. The body weights of the animals in each group continued to increase. At the end of the experiment, the body weights of the large (Group A), medium (Group B), small (Group C) dose groups and the control group increased by 249.5 g, 240.0 g, 232.0 g, and 226.5 g respectively compared with before administration. The difference was extremely significant (P < 0.001) when compared before and after administration, but there was no difference between groups (P > 0.05), indicating that the test sample did not affect the food intake and weight gain of the animals under the experimental conditions. At the end of the experiment, no abnormalities were found during macroscopic observation during dissection, and no pathological changes related to the test sample were found in the pathological microscopic examination of important organs (heart, liver, lung, kidney, testis, ovary, etc.), indicating that the traditional Chinese medicine composition was relatively safe.

[0078] As described above, the above are only examples of the present application. The protection scope of the present application is not limited by these specific examples, but is determined by the claims of the present application. For those skilled in the art, various changes and modifications can be made to the present application. Any modification, equivalent replacement, improvement, etc. made within the technical idea and principle of the present application shall be included within the protection scope of the present application.

Claims

1. Use of a Chinese medicine composition in the preparation of a drug for treating endometriosis, wherein the Chinese medicine composition is made of the following raw materials in parts by weight: 1-25 parts of stir-fried peach kernels, 2-40 parts of stir-fried myrrh, 2-40 parts of salvia miltiorrhiza, 2-20 parts of red peony root, 2-20 parts of safflower, 2-30 parts of zedoaria, 2-20 parts of stir-fried fenugreek, 2-30 parts of gleditsia spinosa, 2-60 parts of patrinia herb, 2-60 parts of dandelion, 1-25 parts of toosendan fruit, 2-40 parts of angelica dahurica, 2-40 parts of pyrrosia, and 1-20 parts of wolfberry fruit.

2. The use according to claim 1, characterized in that: The preparation method of the Chinese medicine composition is as follows: Take the above-mentioned parts by weight of stir-fried myrrh, sapodilla thorns and angelica dahurica, and grind them into fine powder; add water to the remaining 11 raw materials and boil them for 2 to 4 times, each time for 0.5 to 2 hours, combine the extracts, filter, concentrate the filtrate into a thick paste, add the above-mentioned fine powder, dry, continue to grind into fine powder, mix well, and finally process it into an oral preparation to obtain.

3. The use according to claim 1 or 2, characterized in that: The oral preparation is powder, capsule, tablet, granule or pill.

4. The use according to claim 1 or 2, characterized in that: The Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of stir-fried peach kernels, 15 parts of stir-fried myrrh, 15 parts of salvia miltiorrhiza, 15 parts of red peony root, 15 parts of safflower, 15 parts of herba zedoariae, 15 parts of stir-fried vaccariae, 15 parts of gleditsia spinosa, 50 parts of herba patriniae, 50 parts of herba dandelions, 15 parts of fructus toosendan, 15 parts of the angelica dahurica, 25 parts of pyrrosia, and 15 parts of fructus wolfberries.

Images