Application of traditional Chinese medicine composition in preparing medicine for preventing and treating polycystic ovary syndrome

Abstract

This invention relates to the field of traditional Chinese medicine technology, and more particularly to the application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and treatment of polycystic ovary syndrome (PCOS). The traditional Chinese medicine composition includes Gleditsia sinensis thorns, Polygonum cuspidatum, Taraxacum mongolicum, Sargentodoxa cuneata, Codonopsis pilosula, Smilax china, Paeonia lactiflora, Salvia miltiorrhiza, Lindera strychnifolia, and Corydalis yanhusuo. Experiments show that this traditional Chinese medicine composition can significantly inhibit the increase of ovarian weight in PCOS rats; and can reduce the levels of luteinizing hormone and testosterone in the serum of PCOS rats, exhibiting a good therapeutic effect on PCOS.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to the application of traditional Chinese medicine compositions in the preparation of drugs for the prevention and treatment of polycystic ovary syndrome. Background Technology

[0002] Polycystic ovary syndrome (PCOS) is a common and complex endocrine and metabolic disorder in women of reproductive age. It is characterized by chronic anovulation (disordered or absent ovulation) and hyperandrogenemia (excessive production of male hormones in the woman's body). The main clinical manifestations include irregular menstrual cycles, infertility, hirsutism, and / or acne. It is the most common female endocrine disorder, with a high incidence rate among women of reproductive age, severely impacting female fertility.

[0003] The cause of PCOS is unknown, and there is no effective cure. Treatment is mainly symptomatic and requires long-term health management. Most experts believe that insulin resistance is a key factor in its pathogenesis and is related to multiple pathological processes such as autophagy, oxidative stress, and mitochondrial dysfunction. First-line drugs for this disease, such as birth control pills and insulin sensitizers, are off-label symptomatic treatments and have problems such as narrow applicability and numerous adverse reactions.

[0004] In Traditional Chinese Medicine (TCM), PCOS falls under the categories of "delayed menstruation" and "infertility." Most TCM practitioners believe its pathogenesis is rooted in kidney deficiency, with phlegm-dampness and blood stasis as secondary symptoms. Treatment often employs methods such as warming the kidneys and strengthening the spleen, resolving phlegm and removing blood stasis. TCM's syndrome differentiation and treatment approach has advantages such as holistic regulation, multi-stage intervention, and multi-target therapy, and is expected to bring more benefits to PCOS patients. Summary of the Invention

[0005] In view of this, the present invention provides the application of a traditional Chinese medicine composition in the preparation of a medicament for the prevention and treatment of polycystic ovary syndrome.

[0006] The application of the traditional Chinese medicine composition of the present invention in the preparation of a drug for the prevention and treatment of polycystic ovary syndrome;

[0007] The traditional Chinese medicine composition comprises, or is made from, the following raw materials in parts by weight:

[0008] 8-15 parts of Gleditsia sinensis thorns, 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 Paeonia lactiflora, 8-15 parts of Salvia miltiorrhiza, 6-10 parts of Lindera strychnifolia, and 8-12 parts of Corydalis yanhusuo.

[0009] In some specific implementation schemes, the raw materials in the traditional Chinese medicine composition include: 12 parts of Gleditsia sinensis thorns, 8 parts of Polygonum cuspidatum, 9.6 parts of Taraxacum mongolicum, 9.6 parts of Sargentodoxa cuneata, 12 parts of Codonopsis pilosula, 12 parts of Smilax china, 8 parts of Paeonia lactiflora, 12 parts of Salvia miltiorrhiza, 8 parts of Lindera strychnifolia, and 9.6 parts of Corydalis yanhusuo.

[0010] In some specific implementation schemes, the raw materials in the traditional Chinese medicine composition include: 8 parts of Gleditsia sinensis thorns, 6 parts of Polygonum cuspidatum, 8 parts of Taraxacum mongolicum, 8 parts of Sargentodoxa cuneata, 8 parts of Codonopsis pilosula, 8 parts of Smilax china, 6 parts of Paeonia lactiflora, 8 parts of Salvia miltiorrhiza, 6 parts of Lindera strychnifolia, and 8 parts of Corydalis yanhusuo.

[0011] In some specific implementation schemes, the raw materials in the traditional Chinese medicine composition include: 15 parts of Gleditsia sinensis thorns, 10 parts of Polygonum cuspidatum, 12 parts of Taraxacum mongolicum, 12 parts of Sargentodoxa cuneata, 15 parts of Codonopsis pilosula, 15 parts of Smilax china, 10 parts of Paeonia lactiflora, 15 parts of Salvia miltiorrhiza, 10 parts of Lindera strychnifolia, and 12 parts of Corydalis yanhusuo.

[0012] In this invention, the preparation method of the traditional Chinese medicine composition includes:

[0013] Add 6-10 times the amount of 60%-80% ethanol to Corydalis yanhusuo and Polygonum cuspidatum, reflux and extract 1-3 times, 0.5-2.5 hours each time, filter, combine the filtrates to obtain the ethanol extract;

[0014] Add 10 to 15 times the amount of water to the following herbs and decoct 1 to 4 times, each time for 1 to 3 hours: soapberry thorns, dandelion, large blood vine, codonopsis, smilax, red peony root, salvia miltiorrhiza, and lindera root. Filter the decoction, combine the filtrates, concentrate under reduced pressure, let stand for 24 to 36 hours, and collect the supernatant after alcohol precipitation.

[0015] The supernatant of the alcohol precipitation was combined with the alcohol extract and concentrated under reduced pressure to obtain an extract. Water of 1-3 times the weight of the extract was added and mixed well. Ethanol was added until the alcohol content reached 60%. The mixture was allowed to stand for 24-36 hours. The supernatant was then dried and pulverized.

[0016] In this invention, the effective dosage of the traditional Chinese medicine composition is 201.6g to 403.2g of raw herbs per day.

[0017] In this invention, the prevention and control measures include at least one of the following: 1) to 2)

[0018] 1) Reduce luteinizing hormone and / or testosterone levels;

[0019] 2) Inhibit weight gain and / or inhibit ovarian weight gain.

[0020] In some embodiments, the luteinizing hormone and testosterone are luteinizing hormone and testosterone in serum.

[0021] This invention also provides a drug for the prevention and treatment of polycystic ovary syndrome, characterized in that it comprises, or is made from, the following raw materials in parts by weight:

[0022] 8-15 parts of Gleditsia sinensis thorns, 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 Paeonia lactiflora, 8-15 parts of Salvia miltiorrhiza, 6-10 parts of Lindera strychnifolia, and 8-12 parts of Corydalis yanhusuo.

[0023] After weighing the raw materials according to the above proportions, add them to the conventional pharmaceutical excipients used in traditional Chinese medicine preparations, and use conventional pharmaceutical methods in pharmaceutics to prepare the required traditional Chinese medicine preparations, including but not limited to granules, capsules, pills, tablets and suppositories.

[0024] This invention provides the application of a traditional Chinese medicine composition in the preparation of drugs for the prevention and treatment of polycystic ovary syndrome (PCOS). The composition includes Gleditsia sinensis thorns, Polygonum cuspidatum, Taraxacum mongolicum, Sargentodoxa cuneata, Codonopsis pilosula, Smilax china, Paeonia lactiflora, Salvia miltiorrhiza, Lindera strychnifolia, and Corydalis yanhusuo. Experiments show that this composition can significantly inhibit the increase in ovarian weight in PCOS rats and reduce the levels of luteinizing hormone and testosterone in the serum of PCOS rats, demonstrating a good therapeutic effect on PCOS. Detailed Implementation

[0025] This invention provides the application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and treatment of polycystic ovary syndrome. Those skilled in the art can refer to the content of this document and appropriately modify the process parameters to achieve the desired result. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in this invention. The methods and applications of this invention have been described through preferred embodiments, and those skilled in the art can obviously make modifications or appropriate alterations and combinations to the methods and applications described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.

[0026] As mentioned above, the present invention aims to provide an application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and treatment of polycystic ovary syndrome;

[0027] The traditional Chinese medicine composition comprises, or is made from, the following raw materials in parts by weight:

[0028] 8-15 parts of Gleditsia sinensis thorns, 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 Paeonia lactiflora, 8-15 parts of Salvia miltiorrhiza, 6-10 parts of Lindera strychnifolia, and 8-12 parts of Corydalis yanhusuo.

[0029] In this invention, the preparation method of the traditional Chinese medicine composition includes:

[0030] Add 6-10 times the amount of 60%-80% ethanol to Corydalis yanhusuo and Polygonum cuspidatum, reflux and extract 1-3 times, 0.5-2.5 hours each time, filter, combine the filtrates to obtain the ethanol extract;

[0031] Add 10-15 times the amount of water to the following herbs and decoct 1-4 times, 1-3 hours each time: Gleditsia sinensis thorns, dandelion, Sargentodoxa cuneata, Codonopsis pilosula, Smilax china, Paeonia lactiflora, Salvia miltiorrhiza, and Lindera strychnifolia. Filter the decoction, combine the filtrates, concentrate under reduced pressure, add ethanol until the alcohol content reaches 60%, let stand for 24-36 hours, and collect the supernatant of the alcohol precipitation.

[0032] The supernatant of the alcohol precipitation was combined with the alcohol extract and concentrated under reduced pressure to obtain an extract. Water of 1-3 times the weight of the extract was added and mixed well, and the mixture was allowed to stand for 24-36 hours. The supernatant was dried, pulverized, and conventional pharmaceutical excipients were added. The required traditional Chinese medicine dosage form was prepared using conventional methods in pharmaceutics.

[0033] In some specific embodiments, the preparation method of the traditional Chinese medicine composition specifically includes:

[0034] Corydalis rhizome and Polygonum cuspidatum were extracted by reflux with 10 times the amount of 60% ethanol three times, each time for 1.5 hours. The extracts were filtered and the filtrates were combined to obtain the alcohol extract.

[0035] Gleditsia sinensis thorns, dandelion, Sargentodoxa cuneata, Codonopsis pilosula, Smilax china, Paeonia lactiflora, Salvia miltiorrhiza, and Lindera strychnifolia are decocted three times with 10 times the amount of water, each time for 1.5 hours. The decoction is filtered, and the filtrates are combined and concentrated under reduced pressure to an extract with a relative density of 1.08-1.12 (60℃-70℃). Ethanol is added to make the alcohol content of the decoction reach 60%, and the mixture is allowed to stand for 24 to 36 hours. The supernatant of the alcohol precipitation is collected and combined with the alcohol extract, and concentrated under reduced pressure to an extract with a relative density of 1.04-1.06 (60℃-70℃). Water with an equal weight of the extract is added and mixed well. The mixture is allowed to stand for 24 to 36 hours, and the supernatant is collected and concentrated under reduced pressure to an extract with a relative density of 1.12-1.18 (60℃-70℃). The extract is spray-dried, pulverized, and a dry powder is obtained. An appropriate amount of dextrin and steviol glycosides are added, and the mixture is dry-granulated to produce 1000g granules.

[0036] Unless otherwise specified, all experiments in the following experiments were conducted under standard conditions or conditions recommended by the manufacturer. Active pharmaceutical ingredients (APIs) or excipients, as well as reagents or instruments whose manufacturers are not specified, are all commercially available products. Unless otherwise stated, all percentages, ratios, proportions, or parts are by weight.

[0037] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as are familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to this invention.

[0038] Example 1: Preparation of the Traditional Chinese Medicine Composition

[0039] The granules of this traditional Chinese medicine composition are made from the following raw materials in parts by weight: 15 parts of Gleditsia sinensis thorns, 10 parts of Polygonum cuspidatum, 12 parts of Taraxacum mongolicum, 12 parts of Sargentodoxa cuneata, 15 parts of Codonopsis pilosula, 15 parts of Smilax china, 10 parts of Paeonia lactiflora, 15 parts of Salvia miltiorrhiza, 10 parts of Lindera strychnifolia, and 12 parts of Corydalis yanhusuo.

[0040] For the above ten medicinal materials, polygonum cuspidatum and rhizoma corydalis are reflux-extracted with 10 times the amount of 60% ethanol for 3 times, 1.5 hours each time, filtered, and the filtrates are combined to obtain an ethanol extract for standby; the remaining eight medicinal materials are decocted with 10 times the amount of water for 3 times, 1.5 hours each time, filtered, and the filtrates are combined and concentrated under reduced pressure to an extract with a relative density of 1.08 - 1.12 (60℃ - 70℃). Ethanol is added to make the ethanol content in the medicinal liquid reach 60%, and it is allowed to stand for 24 to 36 hours. The supernatant of ethanol precipitation is taken and combined with the ethanol extract, and then concentrated under reduced pressure to an extract with a relative density of 1.04 - 1.06 (60℃ - 70℃). Water equal to the weight of the extract is added and mixed evenly, allowed to stand for 24 to 36 hours, the supernatant is taken, and concentrated under reduced pressure to an extract with a relative density of 1.12 - 1.18 (60℃ - 70℃), spray-dried, pulverized to obtain dry extract powder, appropriate amount of dextrin and stevioside are added, and granulated by dry granulation to prepare 1000 g of granules, thus obtaining the product.

[0041] Effect of the traditional Chinese medicine composition in Example 2 on improving body weight and ovarian weight of rats with polycystic ovary syndrome

[0042] 1. Experimental materials

[0043] 1.1 Animals

[0044] 40 SPF-grade 8-week-old female SD rats, with a body weight of (180 - 200) g, purchased from Hangzhou Medical College (production), production license number: SCXK(Zhe)2019 - 0002.

[0045] 1.2 Drugs

[0046] The traditional Chinese medicine composition prepared in Example 1, Jiangsu Kanion Pharmaceutical Co., Ltd.

[0047] 1.3 Instruments

[0048] Refrigerator (Haier Co., model: BCD-216SZ); electronic balance (Sartorius Scientific Instruments Co., model: BSA224S-CW); purified water instrument (Millipore Corporation, Germany, model: Milli-QPlus); animal weighing scale (Shanghai Xiangchuan Electronic Weighing Apparatus Co., Ltd., model: ACX-SC-DA).

[0049] 2. Dosage design

[0050] The unit prescription amount of the traditional Chinese medicine composition is 5599 g of crude drug. With excipients added, 1000 g of the finished product is obtained. 6 bags are taken every day (twice a day, 3 bags each time), which is equivalent to 201.6 g of crude drug taken per person per day. According to the body surface area conversion method, the equivalent dose for rats is 201.6 g / 60 kg * 6.2 = 20.83 g / kg, and this dose is used as the medium dose. According to the dosing method of 0.5:1:2, the low dose is 10.42 g / kg and the high dose is 41.66 g / kg.

[0051] 3. Experimental Methods

[0052] Rats were acclimatized for 3 days with free access to feed and water. They were randomly divided into a control group and a model group. Rats in the model group were administered 1 mg / kg letrozole daily by gavage, while the control group received an equal volume of purified water. The modeling period was 21 days. On day 21, successfully modeled rats were divided into four groups: a model control group, and groups with low, medium, and high doses of the traditional Chinese medicine combination (10.42 g / kg, 20.83 g / kg, and 41.66 g / kg), each with 8 rats. The control and model groups received an equal volume of purified water, while the other groups received the corresponding drug solution by gavage for 7 consecutive days. Rats were then sacrificed, and blood and ovaries were collected.

[0053] Detection indicators: Ovarian weight was measured 35 days after modeling to assess the success of the polycystic ovary syndrome model.

[0054] 4. Statistical Methods

[0055] The results were statistically analyzed using t-tests.

[0056] 5. Experimental Results

[0057] The results showed that there were no significant changes in the blank control group. In the model group, rats administered 1 mg / kg letrozole by gavage for 21 days showed significantly increased body weight and ovarian weight compared to the blank control group (P<0.0001), indicating successful model establishment. Seven days after administration, the body weight and ovarian weight of rats in the low, medium, and high dose groups of the traditional Chinese medicine composition were significantly reduced compared to the model group (***P<0.001, **P<0.01, *P<0.05). The results are shown in Table 1.

[0058] Table 1. Effects of traditional Chinese medicine compositions on body weight and ovarian weight of rats in each group after modeling ( n=8)

[0059]

[0060] Note: Compared with the blank control group #### P<0.0001; compared with the model group, *P<0.05, **P<0.01, ****P<0.0001.

[0061] 6. Experimental Conclusions

[0062] Rats' body weight and ovarian weight can be used to assess the establishment of a polycystic ovary syndrome (PCOS) model. After administration of the traditional Chinese medicine composition at low, medium, and high doses, the rats' body weight and the weight of both ovaries were significantly reduced compared to the model group. Example 3: Effects of the traditional Chinese medicine composition on serum hormone levels in rats with PCOS.

[0063] 1. Experimental Materials

[0064] 1.1 Animals

[0065] Forty SPF-grade 8-week-old female SD rats, weighing (180 - 200) g, were purchased from Hangzhou Medical College (producer), with the production license number: SCXK(Zhe)2019 - 0002.

[0066] 1.2 Drugs

[0067] The traditional Chinese medicine composition was prepared according to the method of Example 1 and provided by Jiangsu Kanion Pharmaceutical Co., Ltd.

[0068] 1.3 Instruments

[0069] Refrigerator (Haier Co., model: BCD-216SZ); electronic balance (Sartorius Scientific Instruments Co., model: BSA224S-CW); multi-functional microplate reader (MD Co., USA, model: Flexstation 3); animal weighing scale (Shanghai Xiangchuan Electronic Weighing Instrument Co., Ltd., model: ACX-SC-DA); luteinizing hormone and testosterone ELISA kits (elabscience Co., USA).

[0070] 2. Dosage Design

[0071] The daily dosage of the traditional Chinese medicine composition was 5599 g of crude drug. With excipients added, 1000 g of the finished product was obtained. Six bags were taken every day (twice a day, three bags each time), which was equivalent to 201.6 g of crude drug per person per day. According to the body surface area conversion method, the equivalent dosage for rats was 201.6 g / 60 kg * 6.2 = 20.83 g / kg, and this dosage was used as the medium dosage. According to the 0.5:1:2 dosing method, the low dosage was 10.42 g / kg and the high dosage was 41.66 g / kg.

[0072] 3. Experimental Methods

[0073] After the ovarian weight measurement in Example 1, the rat blood was centrifuged at a rate of 12000 r / min for 5 min, and the supernatant was stored in a -80°C refrigerator. The ELISA kits for luteinizing hormone and testosterone were used to detect the hormone levels in the serum. The operation was carried out strictly in accordance with the kit instructions.

[0074] Detection Index: Determination of hormone levels in the serum.

[0075] 4. Statistical Methods

[0076] The results were statistically processed using the t-test.

[0077] 5. Experimental Results

[0078] The results showed that, compared with the blank control group, the serum levels of luteinizing hormone (LH) and testosterone in the model group rats were significantly increased (P<0.0001), indicating successful model establishment. Compared with the model group, the levels of LH and testosterone were significantly decreased after administration of the traditional Chinese medicine composition at low, medium, and high doses (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001), with the high-dose group showing the greatest difference and the most significant improvement. These results indicate that the traditional Chinese medicine composition has a good therapeutic effect on hormone levels in rats with polycystic ovary syndrome. The results are shown in Table 2.

[0079] Table 2 Comparison of luteinizing hormone and testosterone levels in rat serum ( n=8)

[0080]

[0081] Note: Compared with the blank control group #### P<0.0001; compared with the model group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

[0082] 6. Experimental Conclusions

[0083] After administration of low, medium, and high doses of the traditional Chinese medicine composition, the serum levels of luteinizing hormone and testosterone in rats with polycystic ovary syndrome decreased, indicating that the traditional Chinese medicine composition has a good therapeutic effect on rats with polycystic ovary syndrome.

[0084] The above embodiments of the present invention are merely examples to clearly illustrate the present invention and are not intended to limit the implementation of the present invention. Those skilled in the art can make other variations or modifications based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. Application of traditional Chinese medicine compositions in the preparation of drugs for the prevention and treatment of polycystic ovary syndrome; The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 8-15 parts of Gleditsia sinensis thorns, 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 Paeonia lactiflora, 8-15 parts of Salvia miltiorrhiza, 6-10 parts of Lindera strychnifolia, and 8-12 parts of Corydalis yanhusuo.

2. The application according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 12 parts of Gleditsia sinensis thorns, 8 parts of Polygonum cuspidatum, 9.6 parts of Taraxacum mongolicum, 9.6 parts of Sargentodoxa cuneata, 12 parts of Codonopsis pilosula, 12 parts of Smilax china, 8 parts of Paeonia lactiflora, 12 parts of Salvia miltiorrhiza, 8 parts of Lindera strychnifolia, and 9.6 parts of Corydalis yanhusuo.

3. The application according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 8 parts of Gleditsia sinensis thorns, 6 parts of Polygonum cuspidatum, 8 parts of Taraxacum mongolicum, 8 parts of Sargentodoxa cuneata, 8 parts of Codonopsis pilosula, 8 parts of Smilax china, 6 parts of Paeonia lactiflora, 8 parts of Salvia miltiorrhiza, 6 parts of Lindera strychnifolia, and 8 parts of Corydalis yanhusuo.

4. The application according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15 parts of Gleditsia sinensis thorns, 10 parts of Polygonum cuspidatum, 12 parts of Taraxacum mongolicum, 12 parts of Sargentodoxa cuneata, 15 parts of Codonopsis pilosula, 15 parts of Smilax china, 10 parts of Paeonia lactiflora, 15 parts of Salvia miltiorrhiza, 10 parts of Lindera strychnifolia, and 12 parts of Corydalis yanhusuo.

5. The application according to any one of claims 1 to 4, characterized in that, The preparation method of the traditional Chinese medicine composition includes: Add 6-10 times the amount of 60%-80% ethanol to Corydalis yanhusuo and Polygonum cuspidatum, reflux and extract 1-3 times, 0.5-2.5 hours each time, filter, combine the filtrates to obtain the ethanol extract; Add 10-15 times the amount of water to the following herbs and decoct 1-4 times, 1-3 hours each time: Gleditsia sinensis thorns, dandelion, Sargentodoxa cuneata, Codonopsis pilosula, Smilax china, Paeonia lactiflora, Salvia miltiorrhiza, and Lindera strychnifolia. Filter the decoction, combine the filtrates, concentrate under reduced pressure, add ethanol until the alcohol content reaches 60%, let stand for 24-36 hours, and collect the supernatant of the alcohol precipitation. The supernatant of the alcohol precipitation was combined with the alcohol extract and concentrated under reduced pressure to obtain an extract. Water of 1-3 times the weight of the extract was added and mixed well. The mixture was allowed to stand for 24-36 hours. The supernatant was then dried and pulverized.

6. The application according to claim 1, characterized in that, The dosage forms of the drug include granules, capsules, pills, or tablets.

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