Use of traditional Chinese medicine composition in preparation of medicine for preventing and treating uterine fibroids

Abstract

The present application relates to the technical field of traditional Chinese medicine, and particularly relates to application of a traditional Chinese medicine composition in preparation of a medicine for preventing and treating uterine fibroids. The traditional Chinese medicine composition comprises Gleditsia sinensis L. thorns, giant knotweed, dandelion, Sargentgloryvine stem, radix codonopsis, smilax, red peony root, salvia miltiorrhiza, lindera and corydalis. The traditional Chinese medicine composition can obviously inhibit tumor size of uterine fibroid rats, reduce uterine coefficient, reduce the number and size of myoma, and improve the pathological state of the uterus; and can reduce the content of E2, P and ER in serum, and has a good effect on treating uterine fibroids.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, and particularly relates to application of a traditional Chinese medicine composition in preparation of a medicine for preventing and treating uterine fibroids. BACKGROUND

[0002] Uterine fibroids are the most common benign tumors of female genital organs, which are composed of smooth muscle and connective tissue. They are commonly seen in women aged 30-50 years, and the incidence has gradually increased in recent years. Clinical manifestations include increased menstrual flow, abnormal menstrual period, lower abdominal mass and increased leukorrhea, which greatly affect the work and life of women. Modern medical treatment of the disease mainly relies on drugs and surgical operation, but has many adverse reactions and complications.

[0003] Traditional Chinese medicine believes that the disease is caused by dysfunction of viscera, stagnation of qi, blood stasis, cold coagulation, phlegm obstruction, dampness-heat and deficiency of vital qi, and belongs to the category of "stone mass". Clinical treatment of uterine fibroids mainly relies on promoting blood circulation to remove blood stasis and softening and resolving masses. Modern research shows that traditional Chinese medicine therapy can significantly improve symptoms and has a low incidence of adverse reactions, and has certain advantages in treating the disease. SUMMARY

[0004] Therefore, the present application provides application of a traditional Chinese medicine composition in preparation of a medicine for preventing and treating uterine fibroids.

[0005] Application of the traditional Chinese medicine composition in preparation of the medicine for preventing and treating uterine fibroids;

[0006] The traditional Chinese medicine composition comprises the following raw materials in mass parts, or is made of the following raw materials in mass parts:

[0007] Gleditsia sinensis 8-15 parts, giant knotweed 6-10 parts, dandelion 8-12 parts, caulis sargentodoxae 8-12 parts, radix codonopsis 8-15 parts, smilax 8-15 parts, red peony root 6-10 parts, salvia miltiorrhiza 8-15 parts, lindera 6-10 parts, corydalis 8-12 parts.

[0008] In some specific embodiments, in the traditional Chinese medicine composition, each raw material comprises: Gleditsia sinensis 12 parts, giant knotweed 8 parts, dandelion 9.6 parts, caulis sargentodoxae 9.6 parts, radix codonopsis 12 parts, smilax 12 parts, red peony root 8 parts, salvia miltiorrhiza 12 parts, lindera 8 parts, corydalis 9.6 parts.

[0009] In some specific embodiments, in the traditional Chinese medicine composition, each raw material comprises: Gleditsia sinensis 8 parts, giant knotweed 6 parts, dandelion 8 parts, caulis sargentodoxae 8 parts, radix codonopsis 8 parts, smilax 8 parts, red peony root 6 parts, salvia miltiorrhiza 8 parts, lindera 6 parts, corydalis 8 parts.

[0010] In some specific embodiments, in the traditional Chinese medicine composition, each raw material comprises: Gleditsia sinensis 15 parts, giant knotweed 10 parts, dandelion 12 parts, caulis sargentodoxae 12 parts, radix codonopsis 15 parts, smilax 15 parts, red peony root 10 parts, salvia miltiorrhiza 15 parts, lindera 10 parts, corydalis 12 parts.

[0011] In the present application, the preparation method of the traditional Chinese medicine composition comprises:

[0012] reflux extraction 1-3 times, each time for 0.5-2.5 hours, filter, combine the filtrates to obtain an alcohol extraction liquid;

[0013] reflux decocting 1-4 times, each time for 1-3 hours, filter, combine the filtrates, reduce pressure concentration, add ethanol to reach 60% of the alcohol content, stand for 24-36 hours, collect the alcohol precipitation supernatant;

[0014] combine the alcohol precipitation supernatant and the alcohol extraction liquid, reduce pressure concentration to obtain an extract, add 1-3 times the weight of water of the extract, mix uniformly, stand for 24-36 hours; take the supernatant to dry and crush.

[0015] In the present application, the effective dose of the traditional Chinese medicine composition is 201.6g-403.2g of crude drug per day.

[0016] In the present application, the prevention and treatment comprises at least one of the following:

[0017] reduce the uterine coefficient, reduce the number and size of myoma, improve the uterine pathological state, and reduce the content of estradiol (E2), progesterone (P) and estrogen receptor (ER) in serum.

[0018] The uterine pathological state comprises that the damaged uterus occurs hyperemia, edema and / or hyperplasia.

[0019] Experiments show that the composition can significantly reduce the uterine coefficient of rats with uterine fibroids, improve the uterine color, and reduce the volume of uterine fibroids; can significantly reduce the content of E2, P and ER in serum of rats with uterine fibroids, which indicates that the traditional Chinese medicine composition can reduce the uterine coefficient, reduce the number and size of myoma, improve the uterine pathological state (such as the damaged uterus occurs hyperemia, edema and / or hyperplasia), and has a good therapeutic effect on uterine fibroids.

[0020] The present application also provides a medicine for preventing and treating polycystic ovary, comprising the following raw materials by mass parts, or being made of the following raw materials by mass parts:

[0021] 8-15 parts of Gleditsia sinensis, 6-10 parts of Polygonum cuspidatum, 8-12 parts of Taraxacum mongolicum, 8-12 parts of Sargentodoxa cuneata, 8-15 parts of Codonopsis pilosula, 8-15 parts of Smilax china, 6-10 parts of Red peony root, 8-15 parts of Salvia miltiorrhiza, 6-10 parts of Lindera aggregata, and 8-12 parts of Corydalis tuber.

[0022] According to the above proportion, each raw material is weighed, conventional pharmaceutical adjuvants in the preparation process are added, and conventional pharmaceutical methods in pharmacy are adopted to prepare the required traditional Chinese medicine preparation, including but not limited to granules, capsules, pills, tablets or suppositories.

[0023] The traditional Chinese medicine composition of the present application is prepared from raw materials including Gleditsia sinensis L., giant knotweed, dandelion, Sargentia sargentiana, codonopsis, smilax, red peony root, salvia miltiorrhiza, lindera and corydalis. The present application researches and finds that the traditional Chinese medicine composition can obviously reduce uterine coefficient, reduce the number and size of myoma, and improve the pathological state of uterus; and can reduce the contents of E2, P and ER in serum, and has a good effect of treating uterine fibroids. DETAILED DESCRIPTION

[0024] The present application provides the application of the traditional Chinese medicine composition in the preparation of a medicine for preventing and treating uterine fibroids. Those skilled in the art can refer to the content herein and appropriately improve the process parameters for implementation. It is particularly pointed out that all similar replacements and changes are obvious to those skilled in the art, and they are regarded as included in the present application. The method and application of the present application have been described by preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application herein without departing from the content, spirit and scope of the present application, to implement and apply the present application technology.

[0025] As described above, the present application aims to provide the application of a traditional Chinese medicine composition in the preparation of a medicine for preventing and treating uterine fibroids;

[0026] The traditional Chinese medicine composition includes the following raw materials in mass parts, or is prepared from the following raw materials in mass parts:

[0027] Gleditsia sinensis L. 8-15 parts, giant knotweed 6-10 parts, dandelion 8-12 parts, Sargentia sargentiana 8-12 parts, codonopsis 8-15 parts, smilax 8-15 parts, red peony root 6-10 parts, salvia miltiorrhiza 8-15 parts, lindera 6-10 parts and corydalis 8-12 parts.

[0028] The preparation method of the traditional Chinese medicine composition includes:

[0029] Corydalis, giant knotweed are added with 6-10 times the amount of 60%-80% ethanol, and are refluxed and extracted for 1-3 times, each time for 0.5-2.5 hours, filtered, and the filtrates are combined to obtain an alcohol extract.

[0030] Gleditsia sinensis L., dandelion, Sargentia sargentiana, codonopsis, smilax, red peony root, salvia miltiorrhiza, lindera are added with 10-15 times the amount of water, and are decocted for 1-4 times, each time for 1-3 hours, filtered, the filtrates are combined, concentrated under reduced pressure, ethanol is added to reach an alcohol content of 60%, and the mixture is left to stand for 24-36 hours, and the supernatant of alcohol deposition is collected.

[0031] The alcohol supernatant is combined with the alcohol extract, and concentrated under reduced pressure to obtain an extract, 1-3 times the weight of the extract is added to the water, mixed, and allowed to stand for 24-36 hours; the supernatant is dried, pulverized, and combined with conventional pharmaceutical excipients to form the desired traditional Chinese medicine dosage form using conventional pharmaceutical methods.

[0032] In some embodiments, the method for preparing the traditional Chinese medicine composition comprises:

[0033] Fibraurea, giant knotweed are added to 10 times the amount of 60% ethanol, and reflux extracted 3 times for 1.5 hours each time, filtered, and the filtrate is combined to obtain an alcohol extract;

[0034] Gleditsia sinensis, dandelion, Sargentia, Codonopsis pilosula, Smilax, red peony root, Salvia miltiorrhiza, and Lindera aggregata are added to 10 times the amount of water, decocted 3 times for 1.5 hours each time, filtered, and the filtrate is combined and concentrated under reduced pressure to an extract with a relative density of 1.08-1.12 (60°C-70°C). Ethanol is added to the extract to obtain an alcohol content of 60%, and allowed to stand for 24-36 hours. The alcohol supernatant is combined with the alcohol extract, and concentrated under reduced pressure to an extract with a relative density of 1.04-1.06 (60°C-70°C). 1 times the weight of the extract is added to the water, mixed, and allowed to stand for 24-36 hours. The supernatant is concentrated under reduced pressure to an extract with a relative density of 1.12-1.18 (60°C-70°C), spray dried, pulverized, and combined with an appropriate amount of dextrin and stevioside to form 1000 g of granules.

[0035] Unless otherwise specified, the following experiments are performed according to conventional conditions or manufacturer's recommended conditions, and the raw materials or excipients used, as well as the reagents or instruments used, are conventional products that can be obtained commercially. Unless otherwise specified, all percentages, ratios, proportions, or parts are by weight.

[0036] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as understood by those skilled in the art. In addition, any method and material similar or equivalent to those described can be applied to the present application.

[0037] The present application is further described below in conjunction with examples:

[0038] Preparation of the traditional Chinese medicine composition in Example 1

[0039] The traditional Chinese medicine composition granules are prepared from the following raw materials by weight: Gleditsia sinensis 15 parts, giant knotweed 10 parts, dandelion 12 parts, Sargentia 12 parts, Codonopsis pilosula 15 parts, Smilax 15 parts, red peony root 10 parts, Salvia miltiorrhiza 15 parts, and Lindera aggregata 10 parts.

[0040] The above ten medicinal materials, Polygonum cuspidatum and Corydalis tuber, were extracted with 60% ethanol for 3 times, each time for 1.5 hours, 10 times the amount of solvent. The filtrate was combined and used as the alcohol extract. The remaining eight medicinal materials were decocted with 10 times the amount of water for 3 times, each time for 1.5 hours. The filtrate was combined and concentrated under reduced pressure to a relative density of 1.08-1.12 (60°C-70°C). Ethanol was added to make the alcohol content of the liquid 60%, and the mixture was allowed to stand for 24 to 36 hours. The supernatant was collected and combined with the alcohol extract. The mixture was concentrated under reduced pressure to a relative density of 1.04-1.06 (60°C-70°C). Water was added to make the weight of the extract 1 times, and the mixture was allowed to stand for 24 to 36 hours. The supernatant was collected and concentrated under reduced pressure to a relative density of 1.12-1.18 (60°C-70°C). The extract was spray dried and pulverized to obtain a dry extract powder. Appropriate amounts of dextrin and stevioside were added, and the mixture was dry granulated to prepare 1000g of granules.

[0041] The Chinese medicine composition of Experimental Example 2 has an improving effect on the physiological state of the uterus of a rat uterine fibroid model induced by an estrogen loading method

[0042] 1. Experimental materials

[0043] 1.1 Animals

[0044] 48 SPF female SD rats, 8 weeks old, weighing (200-220) g, purchased from Nanjing Qinglongshan Animal Farm (produced), production license number: SCXK (Zhejiang) 2019-0002.

[0045] 1.2 Drugs

[0046] The Chinese medicine composition prepared in Example 1 was prepared by Jiangsu Kangle Pharmaceutical Co., Ltd. Guizhifuling Capsules were prepared by Jiangsu Kangle Pharmaceutical Co., Ltd.

[0047] 1.3 Instruments

[0048] Refrigerator (Haier Company, model: BCD-51OWDEM); electronic balance (Mettler Toledo, model: ME55 / 02); purified water instrument (Germany Millipore Company, model: Milli-Q Plus); animal weight scale (Shanghai Xiangchuan Electronic Weighing Instrument Co., Ltd., model: ACX-SC-DA); vernier caliper (Deli).

[0049] 2. Dose design

[0050] The unit prescription amount of the traditional Chinese medicine composition is 2051 g of crude drug, and the auxiliary materials are added to obtain 1000 g of finished product. 6 bags (3 times a day, 2 bags each time) are taken every day, which is equivalent to 201.6 g of crude drug per person per day. According to the body surface area conversion method, the equivalent dose of rats is 201.6 g / 60 kg*6.2=20.83 g / kg, which is used as the medium dose. According to the 0.5:1:2 administration method, the low dose is 10.42 g / kg and the high dose is 41.66 g / kg.

[0051] 3. Experimental method

[0052] 48 SD rats were adaptively fed for 7 days with free access to feed and water. They were randomly divided into 6 groups, 8 rats in each group, and the uterine fibroid model was established by estrogen loading method. Except for the blank group, each group of rats was injected with benzoic acid estradiol (0.5 mg / kg) in the medial thigh muscle every day, and progesterone (1 mg / kg) was injected into the other side of the medial thigh at an interval of 1 day. At the same time, the blank group was injected with the same dose of normal saline, and after 5 weeks of modeling, the rat uterus pathology showed that the glandular hyperplasia and muscle fiber hyperplasia were obvious, indicating that the modeling was successful. After the modeling was successful, the Guizhifuling capsule group was given 0.5 g / kg of intragastric administration, and the traditional Chinese medicine composition group was given 41.66 g / kg, 20.83 g / kg, and 10.42 g / kg of intragastric administration at high, medium, and low doses, respectively. The blank and model groups were given the same amount of normal saline by intragastric administration every day.

[0053] Detection index:

[0054] The rat uterus pathology was examined, and the behavior of rats in each group was observed during the modeling period. After 4 weeks of administration, the rat abdominal cavity was opened, the uterus and myoma morphology were observed, the uterus was cut along the bladder connection, the fat was peeled off, and the wet weight was weighed on an electronic balance to calculate the uterus coefficient (uterus weight / rat body weight, mg / g). Under normal circumstances, the ratio of rat uterus weight to body weight, i.e. the uterus coefficient, is constant; when the uterus is damaged and shows hyperemia, edema or hyperplasia, the uterus coefficient increases, and the larger the value, the more severe the damage.

[0055] 4. Statistical method

[0056] The results were statistically processed by t-test.

[0057] 5. Experimental results

[0058] The results show that: after 5 weeks of modeling of uterine fibroids by estrogen loading method, the blank group has no obvious change, the rats in the modeling group have rough hair and are easy to be irritable. The uterus of the blank group rats is in the shape of "Y", and the color and thickness are uniform. The uterus volume of the model group rats is significantly larger than that of the blank group, dark red in color, thick in texture, and individual rats are accompanied by uterine fibroid hyperplasia, indicating the success of modeling. After 4 weeks of administration, the uterus coefficient of the high-dose group of the traditional Chinese medicine composition is significantly lower than that of the model group (***P<0.001, **P<0.01). The uterus volume of the rats in each administration group is slightly larger than that of the blank group, the color is slightly improved, and the volume and number of uterine fibroids are reduced. The results are shown in Table 1.

[0059] Table 1 Effect of traditional Chinese medicine composition on uterus coefficient of each group of rats after modeling n=8

[0060]

[0061]

[0062] Note: compared with the blank group, ## P<0.01; compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0063] 6. Test conclusion

[0064] The estrogen loading method for establishing a uterine fibroid model can evaluate the drug efficacy of drug treatment of uterine fibroids. The uterus coefficient of the high-dose group of the traditional Chinese medicine composition is significantly lower than that of the model group, and the effect of the high-dose group is the best. The uterus volume of the rats in each administration group is slightly larger than that of the blank group, the color is slightly improved, and the volume and number of uterine fibroids are reduced.

[0065] Effect of traditional Chinese medicine composition on serum E2, P and ER levels of estrogen loading method induced rat uterine fibroid model in experimental example 3

[0066] 1. Experimental materials

[0067] 1.1 Animals

[0068] 48 SPF level 8-week-old female SD rats, weighing (200-220) g, purchased from Nanjing Qinglongshan Animal Farm (production), production license number: SCXK (Zhejiang) 2019-0002.

[0069] 1.2 Drugs

[0070] Traditional Chinese medicine composition, prepared according to the method of Example 1, provided by Jiangsu Kangle Pharmaceutical Co., Ltd. Estradiol (E2) ELISA detection kit (enzyme-linked biotechnology, ml002871), estradiol receptor (ER) ELISA detection kit (enzyme-linked biotechnology, ml002869), progesterone (P) ELISA detection kit (enzyme-linked biotechnology, ml002894).

[0071] 1.3 Instruments

[0072] Refrigerator (Haier Company, model: BCD-51OWDEM); electronic balance (Mettler Toledo, model: ME55 / 02); purified water instrument (Milli-Q Plus, Germany); animal weight scale (Shanghai Xiangguan Electronic Weighing Instrument Co., Ltd., model: ACX-SC-DA); multifunctional enzyme microplate reader (Perkin Elmer, model: Inspire).

[0073] 2. Dose design

[0074] The daily dose of the traditional Chinese medicine composition is 2051g of crude drug, plus excipients, to obtain 1000g of finished product, 6 bags are taken per day (twice a day, 3 bags at a time), which is equivalent to 123g of crude drug per person per day. According to the body surface area conversion method, the equivalent dose of rats is 201.6g / 60kg*6.2=20.83g / kg, which is used as the medium dose. According to the 0.5:1:2 dosing method, the low dose is 10.42g / kg and the high dose is 41.66g / kg.

[0075] 3. Experimental method

[0076] Randomly divided into 6 groups, 8 rats in each group, using estrogen loading method to establish uterine fibroid model, the construction method is the same as Example 2. After the model is successfully established, the Cinnamon Poria Capsule group is given intragastrically 0.5g / kg, and the traditional Chinese medicine composition group is given intragastrically at doses of 41.66g / kg, 20.83g / kg, and 10.42g / kg. The blank and model groups are given intragastrically with the same amount of normal saline every day.

[0077] After abdominal aortic anesthesia, blood was taken, centrifuged at 12000r / min for 5min, serum was separated, and the levels of E2, P and ER were detected by enzyme-linked immunosorbent assay (ELISA) using the kit. The operation strictly follows the ELISA kit instructions.

[0078] Detection index:

[0079] Detection of estradiol (E2), progesterone (P), and estrogen receptor (ER) levels in serum.

[0080] 4. Statistical method

[0081] Results The results were statistically processed by t test.

[0082] 5. Experimental results

[0083] Results showed: the results showed that compared with the blank group, the contents of E2, P and ER in the serum of the model group rats were significantly increased (P<0.01), indicating that the modeling was successful. Compared with the model group, the contents of E2, P and ER in the serum of the positive drug group, the low, medium and high dose groups of the traditional Chinese medicine composition were significantly reduced, among which, the differences between the medium and high dose groups of the traditional Chinese medicine composition and the model group had statistical significance (*P<0.05, ****P<0.0001), and the difference between the high dose group and the model group was the largest, and the improvement effect was the most significant. The results are shown in Table 2.

[0084] Table 2 Comparison of E2, P and ER levels in the serum of rats n=8

[0085]

[0086]

[0087] Note: compared with the blank group, # P<0.05, ## P<0.01, ### P<0.001, #### P<0.0001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

[0088] 6. Test conclusion

[0089] After the low, medium and high doses of the traditional Chinese medicine composition were administered, the contents of E2, P and ER in the serum of the rats with uterine fibroids were significantly reduced, among which, the high dose group of the traditional Chinese medicine composition had the best effect, indicating that the traditional Chinese medicine composition had a good regulating effect on the rats with uterine fibroids.

[0090] The above embodiments of the present application are only examples for clearly illustrating the present application, and are not intended to limit the embodiments of the present application. Based on the above description, other different forms of changes or variations can be made by those skilled in the art. Here, all the embodiments are not required to be exhausted. Any modification, equivalent replacement and improvement made within the spirit and principle of the present application should be included in the protection scope of the claims of the present application.

Claims

1. The use of a traditional Chinese medicine composition in the preparation of a medicine for preventing and treating uterine fibroids. The traditional Chinese medicine composition is made from the following raw materials in parts by mass: Gleditsia sinensis 8-15 parts, giant knotweed 6-10 parts, dandelion 8-12 parts, Sargentgloryvine 8-12 parts, codonopsis 8-15 parts, smilax 8-15 parts, red peony root 6-10 parts, salvia 8-15 parts, lindera 6-10 parts, and corydalis 8-12 parts.

2. Use according to claim 1, characterized in that, In the traditional Chinese medicine composition, each raw material is as follows: Gleditsia sinensis 12 parts, giant knotweed 8 parts, dandelion 9.6 parts, Sargentgloryvine 9.6 parts, codonopsis 12 parts, smilax 12 parts, red peony root 8 parts, salvia 12 parts, lindera 8 parts, and corydalis 9.6 parts.

3. Use according to claim 1, characterized in that, In the traditional Chinese medicine composition, each raw material includes: Gleditsia sinensis 8 parts, giant knotweed 6 parts, dandelion 8 parts, Sargentgloryvine 8 parts, codonopsis 8 parts, smilax 8 parts, red peony root 6 parts, salvia 8 parts, lindera 6 parts, and corydalis 8 parts.

4. Use according to claim 1, characterized in that, In the traditional Chinese medicine composition, each raw material is as follows: Gleditsia sinensis 15 parts, giant knotweed 10 parts, dandelion 12 parts, Sargentgloryvine 12 parts, codonopsis 15 parts, smilax 15 parts, red peony root 10 parts, salvia 15 parts, lindera 10 parts, and corydalis 12 parts.

5. The use according to any one of claims 1 to 4, characterized in that, The preparation method of the traditional Chinese medicine composition includes: Corydalis, giant knotweed, and 6-10 times the amount of 60%-80% ethanol are refluxed for 1-3 times, each time for 0.5-2.5 hours, filtered, and the filtrates are combined to obtain an alcohol extract; Gleditsia sinensis, dandelion, Sargentgloryvine, codonopsis, smilax, red peony root, salvia, and lindera are decocted in water for 1-4 times, each time for 1-3 hours, filtered, and the filtrates are combined, concentrated under reduced pressure, and ethanol is added to reach an alcohol content of 60%, and the mixture is left to stand for 24-36 hours, and the supernatant is collected; The supernatant and the alcohol extract are combined, concentrated under reduced pressure to obtain an extract, 1-3 times the weight of water is added, the mixture is stirred, and left to stand for 24-36 hours, and the supernatant is collected, dried, and pulverized.

6. Use according to claim 1, characterized in that, The dosage form of the medicine includes granules, capsules, pills, or tablets.

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