CN113876864A

CN113876864A - Pharmaceutical composition for treating infertility and preparation method and application thereof

Info

Publication number: CN113876864A
Application number: CN202111389080.0A
Authority: CN
Inventors: 高敬书; 王宇
Original assignee: Heilongjiang University of Chinese Medicine
Current assignee: Heilongjiang University of Chinese Medicine
Priority date: 2021-11-22
Filing date: 2021-11-22
Publication date: 2022-01-04
Anticipated expiration: 2041-11-22
Also published as: CN113876864B

Abstract

The invention discloses a pharmaceutical composition for treating infertility, which comprises 0.02-0.04 part of a compound in a formula I, 0.01-0.04 part of chlorogenic acid, 0.08-0.12 part of herba patriniae extract and 0.08-0.12 part of epicatechin, and is prepared into the pharmaceutical composition for use. Experiments show that the medicinal composition of the compound shown in the formula I, the chlorogenic acid, the patrinia extract and the epicatechin have the synergistic effect of the components, can dredge salpingemphraxis caused by inflammation, and has a treatment effect on infertility.

Description

Pharmaceutical composition for treating infertility and preparation method and application thereof

Technical Field

The invention belongs to the field of pharmaceutical composition preparations, and particularly relates to a pharmaceutical composition for treating infertility.

Background

Infertility is a difficult and complicated disease which is concerned all over the world, is one of the common gynecological diseases, is relatively intractable in treatment, and is a medical problem which needs to be solved urgently. As the oviduct plays an important role in picking up the ovum and transporting the ovum, the sperm and the embryo, and is also a place where sperm capacitation and sperm and egg meet and fertilize, the mucous membrane of the oviduct is easily damaged by infection and operation, further cilia disappear, the peristaltic disorder is caused, and even the oviduct is blocked or adhered to the surrounding tissues, and the unobstructed function of the oviduct is influenced. The obstruction or the blockage of the fallopian tube is an important reason for female infertility, and the infertility caused by the fallopian tube obstruction caused by salpingitis is called salpingitis obstructive infertility. Most of western medicine treatment adopts the endoscopic interventional therapy such as the tubal catheter guide wire dilatation and the like, the cost is high, the wound is large, the recurrence is easy, the readhesion in the tubal cavity is easy to cause, the wound of the drug treatment is small, the toxic and side effect is small, the curative effect is high, the readhesion rate is low, the advantages are obvious, and the focus of the current medical field is provided.

The traditional Chinese medicine treatment is generally based on pharmacology of promoting blood circulation to remove blood stasis, clearing and activating the channels and collaterals, assisting pregnancy and preventing miscarriage, is comprehensively treated by adding and subtracting medicines according to specific type dialectics, assisting with a plurality of methods of traditional Chinese medicine external application, acupuncture and moxibustion, traditional Chinese medicine example introduction and the like, reflects the characteristic of complementary advantages of the traditional Chinese medicine on the adding and subtracting medicines, and improves the normal intrauterine pregnancy rate while weakening the clinical risk. However, the therapeutic diagnosis and the therapeutic effect judgment standards of the traditional Chinese medicine are lack of uniformity, and the clinical treatment period is relatively long. Therefore, new medicines need to be further researched on the aspect of treating the infertility caused by oviduct obstruction so as to better exert the advantages of no wound, small toxic and side effects and definite curative effect in the disease treatment by the medicines, and the further research on the medicines with definite infertility treatment, small adverse reaction and low recurrence rate is necessary. Therefore, the invention further develops and prepares the pharmaceutical composition with good curative effect, small side effect, safety and effectiveness.

Disclosure of Invention

The invention aims to seek a medicinal composition with good curative effect, small side effect, safety and effectiveness, thereby providing a medicinal composition for treating infertility and a preparation method and application thereof.

The pharmaceutical composition for treating infertility consists of a compound shown as a formula I, chlorogenic acid, a herba patriniae extract and epicatechin,

wherein, the structure of the compound of formula I is as follows

The pharmaceutical composition for treating infertility comprises the following raw materials in parts by weight: 0.02-0.04 part of compound of formula I, 0.01-0.04 part of chlorogenic acid, 0.08-0.12 part of herba patriniae extract and 0.08-0.12 part of epicatechin.

More preferably, the pharmaceutical composition for treating infertility comprises the following raw materials in parts by weight: 0.02-0.03 part of compound of formula I, 0.02-0.03 part of chlorogenic acid, 0.10-0.12 part of herba Patriniae extract and 0.08-0.1 part of epicatechin.

More preferably, the pharmaceutical composition for treating infertility comprises the following raw materials in parts by weight: 0.02 part of compound of formula I, 0.03 part of chlorogenic acid, 0.1 part of herba patriniae extract and 0.08 part of epicatechin.

The pharmaceutical composition for treating infertility is prepared by the following method: pulverizing herba Patriniae, defatting with 8 times of petroleum ether under reflux for 2 times (1 hr each time), soaking in 16 times of water at 85 deg.C for 3 times (2 hr each time), mixing the medicinal liquids, filtering, and concentrating.

The invention also provides a pharmaceutical preparation containing the medicament for treating infertility as an active ingredient, and the pharmaceutical preparation is prepared into common pharmaceutical dosage forms such as oral liquid, powder, granules, capsules, tablets, pills and the like by adopting the conventional preparation method in the field. Preferably tablet, oral liquid, buccal tablet, chewable tablet, and powder.

The pharmaceutical preparation can also comprise a medically acceptable carrier, and the sum of the weight of the medicinal material components accounts for 1 to 99.9 percent of the total weight of the medicine; more preferably, the sum of the weight of the medicinal material components accounts for 10 to 80 percent of the total weight of the medicament; further preferably, the sum of the weight of the medicinal material components accounts for 30-60% of the total weight of the medicament.

The invention also provides application of the pharmaceutical composition in preparing a medicament for treating infertility, and the pharmaceutical composition can be used for treating infertility caused by salpingitis induced salpingemphraxis.

The compound with the structure shown in the formula I is a known flavonoid compound, and is a compound separated from an ethanol extract of phellodendron amurense serving as a genuine herb in Heilongjiang province and obtained by purification. Phellodendron amurense is a larch of phellodendron genus of Rutaceae family, the bark is grayish brown to black gray, and the inner layer of the bark is usually processed and used as a medicine, which is bitter in taste and cold in nature and has the functions of clearing heat and removing toxicity, purging fire and drying dampness. The compound with the structure shown in the formula I is a phellodendron amurense dry leaf extract, the English name of the phellodendron amurense dry leaf extract is (2S) -5-Hydroxy-2- (4-hydroxyphenyl) -8- (3-methyl-2-buten-1-yl) -4-oxo-3, 4-dihydro-2H-chromen-7-yl beta-D-glucopyranoside, the common name is Phellodenin F, and the structural formula is as follows:

the extraction method comprises drying cortex Phellodendri, extracting under reflux with 8 times of 95% ethanol for 2 times (each time for 2 hr), and concentrating under reflux to obtain brown extract. Dispersing the extract in water, filtering, passing the filtrate through Diaion HP-20 macroporous adsorbent resin, eluting with 50% ethanol, separating with silica gel column (80-100 mesh), eluting with chloroform-methanol 15: 1, and purifying with Sephadex LH-20 to obtain compound of formula I with potential antiinflammatory and antioxidant effects. The chlorogenic acid is an important pharmacodynamic component in the Chinese medicinal sargentgloryvine stem, has the effects of clearing heat and removing toxicity, and promoting blood circulation and dispelling wind, and researches show that the chlorogenic acid can directly act on bacterial cell walls to inhibit the synthesis of the bacterial cell walls, so that the chlorogenic acid has wide antibacterial activity. The patrinia distillation liquid part has strong bacteriostatic activity on escherichia coli, streptococcus and staphylococcus aureus in vitro, so the patrinia distillation liquid part is extracted by water decoction, and the patrinia extract is obtained by the specific method that patrinia is crushed, 8 times of petroleum ether is added for reflux and degreasing for 2 times, 1 hour each time, 3 times of soaking at the temperature of 85 ℃ in 16 times of water for 2 hours each time, liquid medicine is combined, and the liquid medicine is filtered and concentrated. The epicatechin is a natural plant flavanol compound, is white crystal, is easy to dissolve in water and methanol, exists in a large number of foods and Chinese medicinal materials, has the functions of resisting oxidation, removing free radicals, enhancing metabolism, regulating immunity, resisting tumors and the like, and has various other physiological activities, such as the effects of reducing fat and blood sugar, preventing cardiovascular diseases, resisting inflammation, protecting nerves, inhibiting bacteria and the like. The raw materials of the invention all belong to natural plant medicines as raw materials, and the process is carried outThe medicine composition is prepared by compatibility through experiments for years, is scientific and reasonable, discovers that the components of the medicine composition taking the compound shown in the formula I, the chlorogenic acid, the patrinia extract and the epicatechin as main components are mutually synergistic through pharmacological experiments, utilizes the comprehensive effects of the components, and treats the oviduct obstructive infertility by dissipating blood stasis, diminishing inflammation and inhibiting the development of inflammatory factors, and has no toxic or side effect and no dependence.

The composition of the pharmaceutical composition is obtained by screening in a large amount, the preparation of the pharmaceutical composition is optimized by optimization treatment, and in order to achieve optimization, the inventor performs a large amount of work, and compared experiments, screening experiments and animal experiments prove that the preparation has a remarkable effect on treating infertility compared with the prior art, and compared with the prior art, the pharmaceutical composition has prominent substantial specificity and remarkable progress.

Detailed Description

The following examples are given for the purpose of illustrating the present invention, and the detailed embodiments and specific procedures are given for the purpose of illustrating the present invention, but the scope of the present invention is not limited to the following examples.

Example 1

A pharmaceutical composition for the treatment of infertility is prepared by pulverizing compound of formula I0.03 g, chlorogenic acid 0.02g, herba Patriniae extract 0.1g, and epicatechin 0.08g, and mixing.

Example 2

A pharmaceutical composition for the treatment of infertility is prepared from compound of formula I0.02 g, chlorogenic acid 0.03g, herba Patriniae extract 0.11g, and epicatechin 0.08g by pulverizing and mixing.

Example 3

A pharmaceutical composition for the treatment of infertility is prepared by pulverizing and mixing 0.03g of compound of formula I, 0.02g of chlorogenic acid, and 0.1g of herba Patriniae extract.

Example 4

A pharmaceutical composition for the treatment of infertility is prepared by pulverizing compound of formula I0.03 g, herba Patriniae extract 0.10g, and epicatechin 0.08g, and mixing.

Example 5

A pharmaceutical composition for the treatment of infertility is prepared by pulverizing compound of formula I0.03 g, chlorogenic acid 0.02g, and epicatechin 0.08g, and mixing.

Example 6

A pharmaceutical composition for the treatment of infertility is prepared by pulverizing compound of formula I0.08 g and chlorogenic acid 0.15g, and mixing.

Example 7

A pharmaceutical composition for the treatment of infertility is prepared from herba Patriniae extract 0.10g and epicatechin 0.13g by pulverizing and mixing.

Example 8

A pharmaceutical composition for the treatment of infertility is prepared from 0.03g of compound of formula I.

Experimental example 1 pharmacodynamic test of the drug of the present invention for infertility

(1) And (3) experimental modeling: 240 Wistar female rats were adaptively fed for one week, randomly divided into 20 normal groups and 220 modeling groups. The rat of the model group is fasted for 12 hours without water prohibition, 10 percent chloral hydrate is used for intraperitoneal injection, the rat is fixed on an operation table after about 5 minutes of anesthesia effect, after abdomen hair shearing, alcohol and iodophor are disinfected, the central incision of the lower abdomen is 0.8-1cm long, the uterus, the fallopian tube and the ovary are exposed, 0.1mL of bacterial suspension (diluted by sterile saline with the concentration of 3 x 10 and 10) is injected at the position of the uterus close to the fallopian tube according to the direction from the fallopian tube to the ovary (the bacterial suspension is diluted by escherichia coli, staphylococcus aureus and hemolytic streptococcus according to the ratio of 2: 1⁹one/mL), the muscle layer and the skin are sutured in sequence after injection, and the rat cage is placed after alcohol disinfection for natural revival. After the molding operation, 1 rat is randomly sacrificed from the molding rats on the 5 th, 10 th, 15 th and 20 th days respectively for pathological observation, and the observation proves that the rat is marked by adhesion, stiffness and obstruction of the oviduct cavity after 20 days, and the molding is successful.

(2) Grouping experiments: the successfully molded 200 rats were randomly divided into 10 groups of 20 rats each as a model group, a positive group and each group of examples 1 to 8, and were subjected to constant volume intragastric administration on the 20 th day after molding. The normal saline is perfused into a model group, 0.03g/ml (radix bupleuri, angelica, rehmannia root, red paeony root, safflower, peach seed, fructus aurantii, liquorice, ligusticum wallichii, radix achyranthis bidentatae and platycodon grandiflorum) of the blood stasis removing tablet is administrated into a positive group, 0.03g/ml of the medicines in the examples 1 to 8 are respectively administrated into the groups from the example 8, and the groups are perfused into the stomach according to the volume of 1ml/100g after conversion according to the specific gravity of a human and a mouse. The normal group without molding was perfused with equal volume of normal saline. All groups of rats were gavaged 1 time a day for 30 consecutive days.

(3) The experimental method comprises the following steps: at 15 days and 30 days after administration, 1.5-2h, 5 rats were respectively anesthetized with chloral hydrate, and the two fallopian tubes were removed of excess adipose tissue for observation. The visual observation of normal group has clear tissue structure of fallopian tube, unobstructed lumen, abundant cilia, tight intercellular connection, and no fibrous tissue proliferation and inflammatory cell infiltration. The model group has the effects of thickened tube wall, reduced tube cavity, adhesion of cilia, fibrous tissue proliferation and blood vessel expansion on day 15, obvious thickened tube wall, obviously reduced tube cavity, thickened cilia and obviously increased fibrous tissue on day 30, and chronic inflammatory cell infiltration can be seen. Each administration group had uniform thickness of oviduct on day 15, and had different degrees of adhesion with surrounding tissues and different degrees of hydrocele.

5ml of abdominal aorta blood is taken, the contents of IL-1 and TNF-alpha in serum are detected by a double antibody sandwich ELISA method, and the experimental results are shown in Table 1. The expression of the oviduct EGFR and ICAM-1 proteins is detected by an immunohistochemical SABC method, and the experimental results are shown in Table 2. After blood is taken and anticoagulant is added, a full-automatic blood viscosity instrument is adopted to detect the rheological indexes of blood, including whole blood viscosity, erythrocyte rigidity index, erythrocyte aggregation index and hematocrit, and the experimental result is shown in table 3.

Table 1 effect of each group of drugs on IL-1, TNF- α levels in rat serum (x ± S, pg/ml, n ═ 5)

Because IL-1, TNF-alpha is one of the main signs of inflammatory reaction, have many biological activities, play a certain role in the development process of chronic inflammation pathophysiology, can finally cause local tissue adhesion and granulation fibrous tissue growth of organism, IL-1, TNF-alpha content increase apparently in the blood serum of oviduct of inflammation injury, have shown that it participates in chronic inflammatory reaction of oviduct, reduce IL-1, TNF-alpha content can further treat inflammatory obstructive infertility. The experimental results in Table 1 show that the IL-1 and TNF-alpha contents in the model group are obviously increased compared with the IL-1 and TNF-alpha contents in the normal control group, which indicates that the mixed bacteria liquid molding can increase the IL-1 and TNF-alpha contents in blood to cause infertility. The IL-1 and TNF-alpha contents in the groups 1-8 and the positive group are obviously different from those in the normal control group and the model group, wherein the IL-1 and TNF-alpha contents in the groups 3-8 are obviously reduced, which indicates that the examples 3-8 can treat infertility by reducing the IL-1 and TNF-alpha contents. The IL-1 and TNF-alpha contents of the groups 1-2 and the positive administration group are remarkably reduced, which shows that the infertility can be treated by reducing the IL-1 and TNF-alpha contents of the groups 1-2 and the positive administration group. By comparing the data of examples 1-2, the positive group and examples 3-8, it can be further demonstrated that the treatment effect on infertility by decreasing the levels of IL-1 and TNF- α is stronger in the examples 1-2 and the positive administration group than in the examples 3-8.

TABLE 2 Effect of each group of drugs on the expression levels of EGFR and ICAM-1 proteins in rat oviduct (x. + -.S, n. gtoreq.5)

Since the EGFR epidermal growth factor receptor is generally present in epidermal cells and stromal cells and has a prominent effect in the processes of regulating cell growth and tissue repair, the EGFR distribution in normal oviducts is related to the differentiation degree of the oviduct epithelium, and the high expression of the EGFR enhances the reactivity of the epidermal cells to the growth factor, promotes the epidermal cells to be combined with the receptor to form a compound, influences the proliferation and differentiation process of the oviduct epithelium, promotes inflammation to be further aggravated, and thus causes infertility. The cell adhesion molecule ICAM-1 belongs to glycoprotein expressed on the cell surface, is rarely shown under normal conditions, and is obviously increased after being stimulated by IL-1 and TNF-alpha, and the increase of the expression can promote or intensify the generation of inflammation and increase the adhesion among cells. According to the experimental results shown in Table 2, ICAM-1 expression is not found in the oviduct epithelial cells of the normal group, and the EGFR protein and ICAM-1 expression of the model group is obviously increased compared with the EGFR protein and ICAM-1 expression of the normal control group, so that the mixed bacterial liquid molding can increase the EGFR protein and ICAM-1 expression in the oviduct epithelial cells to cause infertility. The EGFR protein and ICAM-1 expression in the groups 1-8 and the positive group are obviously different from those in the normal control group and the model group, wherein the EGFR protein and ICAM-1 expression in the groups 3-8 are obviously reduced, which shows that the examples 3-8 can treat infertility by reducing the EGFR protein and ICAM-1 expression. The EGFR protein and ICAM-1 expressions in the groups 1-2 and the positive administration group were significantly reduced, which demonstrates that the infertility treatment by reducing the EGFR protein and ICAM-1 expressions in the groups 1-2 and the positive administration group was possible. By comparing the data of examples 1 to 2, the positive group and examples 3 to 8, it can be further understood that the therapeutic effect on infertility exerted by the reduction of the expression of EGFR protein and ICAM-1 in examples 1 to 2 and the group administered positively is stronger than that of the drugs in examples 3 to 8.

TABLE 3 Effect of each group of drugs on the hemorheological index of rats (x. + -. S, n ═ 5)

The whole blood viscosity, the erythrocyte rigidity index, the erythrocyte aggregation index, the hematocrit and the like belong to hemorheology indexes and can be used as important bases for evaluating the blood viscosity, and the indexes are improved to a certain extent in an oviduct inflammatory obstructive infertility rat model. The experimental results shown in table 3 show that the whole blood viscosity, the erythrocyte rigidity index, the erythrocyte aggregation index and the erythrocyte volume of the model group rat are all obviously increased, which indicates that the modeling is successful. The hemorheology indexes of all treatment groups are obviously reduced compared with that of a model group, and the whole blood viscosity, the erythrocyte rigidity index, the erythrocyte aggregation index and the hematocrit in the examples 1-8 groups and the positive group are obviously different from those of a normal control group and the model group, wherein the whole blood viscosity, the erythrocyte rigidity index, the erythrocyte aggregation index and the hematocrit content in the examples 3-8 groups are obviously reduced, which indicates that the examples 3-8 can treat infertility by reducing the whole blood viscosity, the erythrocyte rigidity index, the erythrocyte aggregation index and the hematocrit. The whole blood viscosity, the erythrocyte rigidity index, the erythrocyte aggregation index and the hematocrit of the groups 1-2 and the positive administration group are obviously reduced, which shows that the infertility of the groups 1-2 and the positive administration group can be treated by reducing the whole blood viscosity, the erythrocyte rigidity index, the erythrocyte aggregation index and the hematocrit. By comparing the data of examples 1 to 2, the positive group and examples 3 to 8, it can be further explained that the treatment effect of infertility of examples 1 to 2 and the group administered positively is stronger than that of the drugs of examples 3 to 8 by lowering the whole blood viscosity, the erythrocyte rigidity index, the erythrocyte aggregation index and the hematocrit.

The remaining 10 rats in each group were placed in 2 male rats each, and were housed in the same cage for 30 days, and the pregnancy of each group was observed separately, and the results are shown in Table 4.

Table 4 effect of each group of drugs on conception rate of rats (x ± S, n ═ 10)

After the completion of the gavage, the pregnancy rate of each group of rats is compared, and the results show that the pregnancy rate of the normal group is 100%, the pregnancy rate of the model group is only 10%, the pregnancy rates of the experimental examples 1-8 and the positive groups are respectively 30% -90% different, and the results further show that the cure rate of the treatment of the inflammatory obstructive infertility of the groups 1-2 and the positive groups reaches more than 60%, and the treatment effect is obviously superior to the action effect of the groups 3-8. Meanwhile, the data show that the compatibility of various medicinal raw materials in the medicament is excellent, the compatibility is not good, and the combination of various medicinal raw materials produces an obvious synergistic technical effect.

Experimental example 2 clinical trial of infertility by the drug of the present invention

(1) Grouping: 100 patients with fallopian tube obstructive infertility are confirmed by hysterosalpingography, wherein 26 cases of primary infertility and 74 cases of secondary infertility are confirmed; 51 cases of bilateral obstruction of the fallopian tube, 35 cases of bilateral obstruction and bilateral obstruction, and 14 cases of unilateral obstruction and contralateral obstruction; the patients are 22-42 years old, the disease course is 1-5 years old, and the patients are randomly divided into 2 groups, wherein 60 cases of treatment groups and 40 cases of control groups have no obvious difference in age, sterility age, fallopian tube patency and the like.

(2) Treatment criteria were: and (3) healing: the uterus oviduct contrast proves the smoothness. The method has the following advantages: hysterosalpingography indicates that the fallopian tube is obstructed or the blocked part is reduced. And (4) invalidation: the fallopian tubes remain occluded. The control group is administered with ZHONG SHI XUE FU ZHU YU PIAN (blood stasis removing tablet), which is prepared from bupleuri radix, radix Angelicae sinensis, rehmanniae radix, radix Paeoniae Rubra, Carthami flos, semen Persicae, fructus Aurantii, Glycyrrhrizae radix, rhizoma Ligustici Chuanxiong, Achyranthis radix, and radix Platycodi; the experimental group was administered with the drug prepared in example 1 of the present invention, and 3 months was one treatment course.

(3) The results are shown in Table 5.

TABLE 5 comparison of two groups of treatment effects and conception rate within 1 year

As can be seen from the results in Table 5, the cure rate and the total effective rate of the experimental group are significantly higher than those of the control group, and the experimental group has significant advantages in terms of the number of patients who visit and have a pregnancy within one year.

It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.

Claims

1. A pharmaceutical composition for treating infertility is characterized by comprising a compound of formula I, chlorogenic acid, herba Patriniae extract and epicatechin, wherein the compound of formula I has the following structure

2. The pharmaceutical composition according to claim 1, comprising the following raw materials in parts by weight: 0.02-0.04 part of compound of formula I, 0.01-0.04 part of chlorogenic acid, 0.08-0.12 part of herba patriniae extract and 0.08-0.12 part of epicatechin.

3. The pharmaceutical composition according to any one of claims 1-2, comprising the following raw materials in parts by weight: 0.02-0.03 part of compound of formula I, 0.02-0.03 part of chlorogenic acid, 0.10-0.12 part of herba Patriniae extract and 0.08-0.1 part of epicatechin.

4. The pharmaceutical composition according to any one of claims 1 to 3, comprising the following raw materials in parts by weight: 0.02 part of compound of formula I, 0.03 part of chlorogenic acid, 0.1 part of herba patriniae extract and 0.08 part of epicatechin.

5. The method for preparing a pharmaceutical composition according to any one of claims 1-4, wherein the compound of formula I, chlorogenic acid, herba Patriniae extract, epicatechin are mixed and dispersed.

6. The pharmaceutical preparation prepared from the pharmaceutical composition according to any one of claims 1 to 5, wherein the pharmaceutical preparation is prepared into pharmaceutically common dosage forms, such as oral liquid, powder, granules, capsules, tablets, pills and the like, preferably tablets, oral liquid, buccal tablets, chewable tablets and powder, by adopting a conventional preparation method in the field.

7. The pharmaceutical preparation of claim 6, further comprising a pharmaceutically acceptable carrier, wherein the total weight of the medicinal materials accounts for 1-99.9% of the total weight of the pharmaceutical preparation; more preferably, the sum of the weight of the medicinal material components accounts for 10 to 80 percent of the total weight of the medicament; further preferably, the sum of the weight of the medicinal material components accounts for 30-60% of the total weight of the medicament.

8. Use of a pharmaceutical composition according to any one of claims 1 to 7 for the treatment of infertility.

9. The use according to claim 8, wherein the infertility is infertility caused by salpingemphraxis due to salpingitis.