Traditional Chinese medicine granules for rheumatism diseases and preparation method of traditional Chinese medicine granules

Abstract

The invention provides traditional Chinese medicine granules for rheumatism diseases and a preparation method thereof, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine granules for rheumatism diseases comprise traditional Chinese medicine components and auxiliary materials, the traditional Chinese medicine components comprise notopterygium root, radix angelicae pubescentis, ligusticum, radix saposhnikoviae, honey-fried licorice root, fructus viticis and ligusticum wallichii; the auxiliary materials comprise a filling agent, an adhesive, a solubilizer and a disintegrating agent; the mass ratio of the traditional Chinese medicine components to the auxiliary materials is (20-60): (40-80). The traditional Chinese medicine granule provided by the invention can be used for treating rheumatism diseases, and has higher bioavailability and long shelf life.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and relates to a traditional Chinese medicine granule for rheumatic diseases, and specifically relates to a traditional Chinese medicine granule for rheumatic diseases and a preparation method thereof. Background Art

[0002] Qianghuo Shengshi Decoction is composed of Qianghuo, Duhuo, Ligusticum chuanxiong, Saposhnikovia divaricata, Zhigancao, Vitex manji and Chuanxiong, which has the effects of dispelling wind, eliminating dampness and relieving pain. It is mainly used to treat rheumatism in the surface, shoulder and back pain that cannot be turned back, headache and heaviness, waist and spine pain, difficulty turning, white tongue coating and floating pulse. It is clinically used to treat rheumatoid arthritis, rheumatoid arthritis, osteoporosis, ankylosing spondylitis and other rheumatism in the surface. In the prescription, Qianghuo and Duhuo are both the main herbs, both of which are pungent, pungent, warm and dry. They are pungent and dispersing wind, bitter and drying, and warm and cold-dispersing. Therefore, they can dispel wind and dampness and unclog the joints. Among them, Qianghuo is good at dispelling rheumatism in the upper part of the body, while Duhuo is good at dispelling rheumatism in the lower part of the body. The combination of the two herbs can disperse rheumatism from top to bottom of the body, unclog the joints and stop pain. The assistant herbs are Fangfeng and Ligusticum chuanxiong, which enter the Taiyang meridian, dispel wind and dampness, and are good at stopping headaches. The herbs are assisted by Chuanxiong to promote blood circulation and qi, dispel wind and stop pain, and Vitex manji dispels wind and stops pain. Licorice is used to harmonize the various herbs.

[0003] Chinese herbal decoction is the earliest and most widely used dosage form in clinical application of traditional Chinese medicine. It has the advantages of rapid onset, easy absorption and strong effect, and occupies an important position in clinical application of traditional Chinese medicine. The preparation method of Qianghuo Shengshi Decoction adopts a water decoction process to prepare a Chinese herbal decoction for consumption. However, Chinese herbal decoction has certain limitations during use, such as inconvenience in carrying, difficulty in accurate dosage control, cumbersome decoction process, short storage time, inconvenience in taking, etc. Therefore, it is necessary to make it into a Chinese herbal preparation that is easy to carry and has good stability.

[0004] Journal article (Sun Hongshan. Study on the preparation process and quality evaluation of Qianghuo Shengshi Drop Pills. 2020) Based on the decoction Qianghuo Shengshi Decoction, Qianghuo Shengshi Drop Pills were developed to improve the limitations of the decoction, increase the solubility of poorly soluble drugs, improve bioavailability and stability, make the drug effect rapid, and expand the scope of application. However, the drop pills have the defects of poor heat resistance, easy hygroscopic deterioration, local irritation, small dosage, high storage requirements, and inconvenience in taking.

[0005] Granules are a modern form of Chinese medicine preparations that have the advantages of being easy to carry, easy to take, and stable. They are made of drugs and suitable excipients into dry granular preparations with a certain particle size to ensure the fluidity, lubricity, compressibility of the granules and the disintegration of the finished product.

[0006] The invention patent with the publication number CN115814100A discloses a special auxiliary material for Chinese medicine granules and a preparation method thereof, wherein the special auxiliary material for Chinese medicine granules comprises the following raw materials in parts by weight: 10-15 parts of anhydrous glucose, 55-65 parts of anhydrous sodium sulfate, 15-25 parts of sodium chloride, 4-6 parts of magnesium sulfate heptahydrate, 2-5 parts of yellow dextrin and 0.02-0.04 parts of disodium edetate. The preparation method of the special auxiliary material for Chinese medicine granules comprises the following steps: taking anhydrous glucose, anhydrous sodium sulfate, sodium chloride, magnesium sulfate heptahydrate, and disodium edetate in parts by weight, crushing and grinding and sieving yellow dextrin, and then placing in a stirring mixing tank for stirring, and mixing evenly to obtain the special auxiliary material for Chinese medicine granules. The Chinese medicine granule special excipient increases the adaptability of active pharmaceutical ingredients, especially Chinese patent medicines and compound preparations. After the Chinese medicine granule special excipient is simply treated, it can be mixed with Chinese medicine extracts for granulation. Compared with the general Chinese medicine granule excipient, the Chinese medicine granule special excipient has low viscosity and good fluidity, can be better mixed, has a high granulation yield, does not need to be repeatedly granulated, does not need to add ethanol during granulation, can avoid the problem of ethanol residue in the preparation process of Chinese patent medicine, and the process of the present invention is simple, controllable, does not require special equipment, has low production cost, and is suitable for industrial production. However, it is not disclosed that the Chinese medicine granule special excipient is used in the compounding of the effective ingredients of Qianghuo Shengshi Decoction.

[0007] None of the above technologies discloses the preparation of granules based on Qianghuo Shengshi Decoction. In order to further improve the defects of Qianghuo Shengshi Decoction such as inconvenient to carry, short storage time, and inconvenient to take, it is urgently necessary to provide a Chinese medicine granule to treat rheumatic diseases, improve water solubility, improve bioavailability, and have higher oral compliance. Summary of the invention

[0008] The present invention aims at the problems existing in the prior art and provides a Chinese medicine granule for rheumatic diseases and a preparation method thereof. The present invention adopts Chinese medicine ingredients consisting of Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Radix Glycyrrhizae Preparata, Fructus Viticis and Rhizoma Chuanxiong as active ingredients, further compounding auxiliary materials to prepare Chinese medicine granules, which can be used to treat rheumatic diseases, improve water solubility and bioavailability, and have high oral compliance.

[0009] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0010] In a first aspect, the present invention provides a Chinese medicine granule for rheumatic diseases, characterized in that it comprises Chinese medicine ingredients and excipients;

[0011] The Chinese medicinal ingredients are obtained by water extraction and concentration of Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Radix fangfeng, Radix glycyrrhizae, Fructus viticis and Rhizoma chuanxiong;

[0012] The auxiliary materials include fillers, binders, solubilizers and disintegrants;

[0013] The mass ratio of the traditional Chinese medicine components to the auxiliary materials is 20-60:40-80.

[0014] Preferably, the mass ratio of the traditional Chinese medicine ingredients to the excipients is 40-60:40-60.

[0015] Among the traditional Chinese medicine ingredients, the mass ratio of Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Radix Glycyrrhizae Preparata, Fructus Viticis and Rhizoma Chuanxiong is 5-10:5-10:2-4:2-4:2-4:1-3:0.5-2, preferably 6:6:3:3:3:2:1.5.

[0016] Preferably, the auxiliary materials include the following components in percentage by weight:

[0017] 60-85% filler, 2-15% binder, 0.5-15% solubilizer and 5-20% disintegrant.

[0018] More preferably, the auxiliary material includes the following components in percentage by weight:

[0019] 70-75% filler, 3-10% binder, 5-15% solubilizer and 8-20% disintegrant.

[0020] In one embodiment, the auxiliary material includes the following components in percentage by weight:

[0021] 60-85% filler, 2-10% binder, 0.5-10% solubilizer and 12.5-20% disintegrant.

[0022] In one embodiment, the auxiliary material includes the following components in percentage by weight:

[0023] 70-75% filler, 3% binder, 5-7% solubilizer and 17-20% disintegrant.

[0024] The filler is selected from one or more of starch, lactose, microcrystalline cellulose, mannitol, calcium hydrogen phosphate, calcium carbonate and magnesium aluminum silicate, preferably starch, lactose and magnesium aluminum silicate in a mass ratio of 1-4:1-4:1-2, more preferably starch, lactose and magnesium aluminum silicate in a mass ratio of 2:2:1.

[0025] The binder is selected from one or more of povidone, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, gum arabic, sucrose, and dextrin, preferably povidone, hydroxypropyl methylcellulose, and dextrin in a mass ratio of 1-2:1-2:1, and more preferably povidone, hydroxypropyl methylcellulose, and dextrin in a mass ratio of 1:2:1.

[0026] The solubilizer is selected from one or more of β-cyclodextrin and its derivatives and polysorbate 80, and the β-cyclodextrin and its derivatives include one or more of β-cyclodextrin, hydroxypropyl-β-cyclodextrin and sulfobutyl ether-β-cyclodextrin. Preferably, the solubilizer is selected from β-cyclodextrin and polysorbate 80, and more preferably, the solubilizer is selected from β-cyclodextrin and polysorbate 80 in a mass ratio of 1:1.

[0027] The disintegrant is selected from one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch, preferably cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1-3, and more preferably cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1.

[0028] Preferably, the auxiliary material further comprises a wetting agent, and the wetting agent comprises one or both of water and ethanol, preferably one or both of water and ethanol.

[0029] In a second aspect, the present invention provides a method for preparing the Chinese medicine granules described in the above technical solution, comprising the following steps:

[0030] S1: decoct and extract Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Radix Angelicae Pubescentis, Fructus Viticis and Rhizoma Chuanxiong, filter, take the filtrate, concentrate and dry to obtain an extract, which is the traditional Chinese medicine ingredient;

[0031] S2: Mix the Chinese medicinal ingredients and auxiliary materials and granulate them to prepare Chinese medicinal granules.

[0032] Preferably, in step S1, firstly, Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Radix Glycyrrhizae, Fructus viticis and Rhizoma Chuanxiong are crushed and soaked in water for 0.5-2h, then decocted in water for extraction, the number of decoctions is 1-4 times, each time for 1-3h, the amount of water used for each decoction is 5-10 times the total amount of Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Glycyrrhiza uralensis, Fructus viticis and Rhizoma Chuanxiong, filtered, the filtrate is taken, combined and concentrated and dried to obtain an extract, which is a traditional Chinese medicine ingredient, and the relative density of the extract at 60°C is 1.1-1.3.

[0033] Preferably, in step S2, the extract obtained in step S1 is powdered, excipients are added, mixed and granulated, and dried to prepare the Chinese medicine granules.

[0034] Compared with the prior art, the present invention has the following beneficial effects:

[0035] Firstly, the present invention adopts the Chinese medicinal ingredients consisting of Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Radix Angelicae Pubescentis, Fructus Viticis and Rhizoma Chuanxiong as active ingredients, and further compound auxiliary materials to prepare Chinese medicinal granules, which can be used to treat rheumatic diseases. The Chinese medicinal granules are easy to carry, convenient to take and have higher bioavailability.

[0036] Secondly, the present invention selects the Chinese medicine ingredients and excipients in a mass ratio of 20-60:40-80, and further selects the filler, binder, solubilizer and disintegrant in a suitable ratio, so that the obtained Chinese medicine granules have higher bioavailability, good water solubility and long shelf life. DETAILED DESCRIPTION

[0037] It is worth noting that, unless otherwise specified, the raw materials used in the present invention are all common commercially available products, and their sources are not specifically limited.

[0038] The following sources of raw materials are provided for illustrative purposes:

[0039] Notopterygium root: purchased from Anhui Xuanji Food Co., Ltd., production batch number 20240988;

[0040] Angelica dahurica: purchased from Shaanxi Shangluo Panlong Botanical Pharmaceutical Co., Ltd., production batch number 20241296;

[0041] Ligusticum chuanxiong: purchased from Anhui Jiuzhizhen Pharmaceutical Co., Ltd., production batch number 20240903;

[0042] Saposhnikovia divaricata: purchased from Shaanxi Shangluo Panlong Botanical Pharmaceutical Co., Ltd., production batch number 20241136;

[0043] Roasted licorice root: purchased from Shaanxi Shangluo Panlong Botanical Pharmaceutical Co., Ltd., production batch number 20241183;

[0044] Vitex rotundifolia: purchased from Anhui Jiuzhizhen Pharmaceutical Co., Ltd., production batch number 20241039;

[0045] Chuanxiong: purchased from Shaanxi Shangluo Panlong Botanical Pharmaceutical Co., Ltd., production batch number 20241186.

[0046] Basic Example 1

[0047] Preparation of Chinese herbal medicine ingredients:

[0048] Take 6 parts of Notopterygium wilfordii, 6 parts of Angelica dahurica, 6 parts of Ligusticum chuanxiong, 6 parts of Radix Angelicae Pubescentis, 2 parts of Fructus Viticis and 1.5 parts of Rhizoma Chuanxiong, mix them, grind Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, add water for soaking, the soaking time is 0.5h, then decoct in water, the number of decoctions is 3 times, each time for 2h, the amount of water used for each decoction is 8 times the total amount of Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Glycyrrhiza uralensis, Fructus Viticis and Rhizoma Chuanxiong, filter after decoction, take the filtrate, combine the three filtrates, concentrate and dry to obtain an extract, which is the traditional Chinese medicine ingredient, and the relative density of the extract at 60°C is 1.12.

[0049] Example 1

[0050] The composition of the Chinese medicine granules is: 5g of Chinese medicine ingredients and 6g of auxiliary materials. The mass percentage of each component in the auxiliary materials is as follows:

[0051] 72% filler, 6% binder, 10% solubilizer and 12% disintegrant.

[0052] The filler is starch, lactose and magnesium aluminum silicate in a mass ratio of 2:2:1;

[0053] The binder is povidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 1:2:1;

[0054] The solubilizer is β-cyclodextrin and polysorbate 80 in a mass ratio of 1:1;

[0055] The disintegrant is cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1.

[0056] The preparation method of the Chinese medicine granules for rheumatic diseases is specifically the following steps:

[0057] The extract obtained in Basic Example 1 was powdered, and then a solubilizer, a filler, a binder and a disintegrant were added and mixed evenly, and an appropriate amount of water was added, and granulated by wet granulation, dried, dried in a fluidized bed at 55° C. for 0.5 hours, granulated, and passed through a 40-mesh sieve to obtain Chinese medicine granules.

[0058] Example 2

[0059] The composition of the Chinese medicine granules is: 5g of Chinese medicine ingredients and 6g of excipients. The mass percentage of each component in the excipients is as follows:

[0060] 70% filler, 3% binder, 7% solubilizer and 20% disintegrant.

[0061] The filler is starch, lactose and magnesium aluminum silicate in a mass ratio of 2:2:1;

[0062] The binder is povidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 1:2:1;

[0063] The solubilizer is β-cyclodextrin and polysorbate 80 in a mass ratio of 1:1;

[0064] The disintegrant is cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1.

[0065] The preparation method of the Chinese medicine granules for rheumatic diseases is specifically the following steps:

[0066] The extract obtained in Basic Example 1 was powdered, and then a solubilizer, a filler, a binder and a disintegrant were added and mixed evenly, and an appropriate amount of water was added, and granulated by wet granulation, dried, dried in a fluidized bed at 55° C. for 0.5 hours, granulated, and passed through a 40-mesh sieve to obtain Chinese medicine granules.

[0067] Example 3

[0068] The composition of the Chinese medicine granules is: 5g of Chinese medicine ingredients and 6g of excipients. The mass percentage of each component in the excipients is as follows:

[0069] 75% filler, 3% binder, 5% solubilizer and 17% disintegrant.

[0070] The filler is starch, lactose and magnesium aluminum silicate in a mass ratio of 2:2:1;

[0071] The binder is povidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 1:2:1;

[0072] The solubilizer is β-cyclodextrin and polysorbate 80 in a mass ratio of 1:1;

[0073] The disintegrant is cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1.

[0074] The preparation method of the Chinese medicine granules for rheumatic diseases is specifically the following steps:

[0075] The extract obtained in Basic Example 1 was powdered, and then a solubilizer, a filler, a binder and a disintegrant were added and mixed evenly, and an appropriate amount of water was added, and granulated by wet granulation, dried, dried in a fluidized bed at 55° C. for 0.5 hours, granulated, and passed through a 40-mesh sieve to obtain Chinese medicine granules.

[0076] Example 4

[0077] The composition of the Chinese medicine granules is: 5g of Chinese medicine ingredients and 6g of excipients. The mass percentage of each component in the excipients is as follows:

[0078] 85% filler, 2% binder, 0.5% solubilizer and 12.5% ​​disintegrant.

[0079] The filler is starch, lactose and magnesium aluminum silicate in a mass ratio of 2:2:1;

[0080] The binder is povidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 1:2:1;

[0081] The solubilizer is β-cyclodextrin and polysorbate 80 in a mass ratio of 1:1;

[0082] The disintegrant is cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1.

[0083] The preparation method of the Chinese medicine granules for rheumatic diseases is specifically the following steps:

[0084] The extract obtained in Basic Example 1 was powdered, and then a solubilizer, a filler, a binder and a disintegrant were added and mixed evenly, and an appropriate amount of water was added, and granulated by wet granulation, dried, dried in a fluidized bed at 55° C. for 0.5 hours, granulated, and passed through a 40-mesh sieve to obtain Chinese medicine granules.

[0085] Example 5

[0086] The composition of the Chinese medicine granules is: 5g of Chinese medicine ingredients and 6g of excipients. The mass percentage of each component in the excipients is as follows:

[0087] 60% filler, 10% binder, 10% solubilizer and 20% disintegrant.

[0088] The filler is starch, lactose and magnesium aluminum silicate in a mass ratio of 2:2:1;

[0089] The binder is povidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 1:2:1;

[0090] The solubilizer is β-cyclodextrin and polysorbate 80 in a mass ratio of 1:1;

[0091] The disintegrant is cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1.

[0092] The preparation method of the Chinese medicine granules for rheumatic diseases is specifically the following steps:

[0093] The extract obtained in Basic Example 1 was powdered, and then a solubilizer, a filler, a binder and a disintegrant were added and mixed evenly, and an appropriate amount of water was added, and granulated by wet granulation, dried, dried in a fluidized bed at 55° C. for 0.5 hours, granulated, and passed through a 40-mesh sieve to obtain Chinese medicine granules.

[0094] Example 6

[0095] The composition of the Chinese medicine granules is: 2g of Chinese medicine ingredients and 8g of auxiliary materials. The mass percentage of each component in the auxiliary materials is as follows:

[0096] 72% filler, 6% binder, 10% solubilizer and 12% disintegrant.

[0097] The filler is starch, lactose and magnesium aluminum silicate in a mass ratio of 2:2:1;

[0098] The binder is povidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 1:2:1;

[0099] The solubilizer is β-cyclodextrin and polysorbate 80 in a mass ratio of 1:1;

[0100] The disintegrant is cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1.

[0101] The preparation method of the Chinese medicine granules for rheumatic diseases is specifically the following steps:

[0102] The extract obtained in Basic Example 1 was powdered, and then a solubilizer, a filler, a binder and a disintegrant were added and mixed evenly, and an appropriate amount of water was added, and granulated by wet granulation, dried, dried in a fluidized bed at 55° C. for 0.5 hours, granulated, and passed through a 40-mesh sieve to obtain Chinese medicine granules.

[0103] Example 7

[0104] The composition of the Chinese medicine granules is: 6g of Chinese medicine ingredients and 4g of excipients. The mass percentage of each component in the excipients is as follows:

[0105] 72% filler, 6% binder, 10% solubilizer and 12% disintegrant.

[0106] The filler is starch, lactose and magnesium aluminum silicate in a mass ratio of 2:2:1;

[0107] The binder is povidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 1:2:1;

[0108] The solubilizer is β-cyclodextrin and polysorbate 80 in a mass ratio of 1:1;

[0109] The disintegrant is cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1.

[0110] The preparation method of the Chinese medicine granules for rheumatic diseases is specifically the following steps:

[0111] The extract obtained in Basic Example 1 was powdered, and then a solubilizer, a filler, a binder and a disintegrant were added and mixed evenly, and an appropriate amount of water was added, and granulated by wet granulation, dried, dried in a fluidized bed at 55° C. for 0.5 hours, granulated, and passed through a 40-mesh sieve to obtain Chinese medicine granules.

[0112] Example 8

[0113] The composition of the Chinese medicine granules is: 5g of Chinese medicine ingredients and 6g of excipients. The mass percentage of each component in the excipients is as follows:

[0114] 72% filler, 6% binder, 10% solubilizer and 12% disintegrant.

[0115] The filler is starch, lactose and magnesium aluminum silicate in a mass ratio of 4:4:1;

[0116] The binder is povidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 2:2:1;

[0117] The solubilizer is β-cyclodextrin and polysorbate 80 in a mass ratio of 2:1;

[0118] The disintegrant is cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:3.

[0119] The preparation method of the Chinese medicine granules for rheumatic diseases is specifically the following steps:

[0120] The extract obtained in Basic Example 1 was powdered, and then a solubilizer, a filler, a binder and a disintegrant were added and mixed evenly, and an appropriate amount of water was added, and granulated by wet granulation, dried, dried in a fluidized bed at 55° C. for 0.5 hours, granulated, and passed through a 40-mesh sieve to obtain Chinese medicine granules.

[0121] Example 9

[0122] The composition of the Chinese medicine granules is: 5g of Chinese medicine ingredients and 6g of excipients. The mass percentage of each component in the excipients is as follows:

[0123] 72% filler, 6% binder, 10% solubilizer and 12% disintegrant.

[0124] The filler is starch, lactose and magnesium aluminum silicate in a mass ratio of 1:1:1;

[0125] The binder is povidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 2:1:1;

[0126] The solubilizer is β-cyclodextrin and polysorbate 80 in a mass ratio of 1:2;

[0127] The disintegrant is cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1.

[0128] The preparation method of the Chinese medicine granules for rheumatic diseases is specifically the following steps:

[0129] The extract obtained in Basic Example 1 was powdered, and then a solubilizer, a filler, a binder and a disintegrant were added and mixed evenly, and an appropriate amount of water was added, and granulated by wet granulation, dried, dried in a fluidized bed at 55° C. for 0.5 hours, granulated, and passed through a 40-mesh sieve to obtain Chinese medicine granules.

[0130] Comparative Example 1

[0131] The difference from Example 1 is that the composition of the Chinese medicine granules is: 7g of Chinese medicine ingredients and 3g of auxiliary materials, and the rest is the same as Example 1, and the Chinese medicine granules are prepared.

[0132] Comparative Example 2

[0133] The difference from Example 1 is that the "6% binder" is replaced by the "filler" with the same mass percentage, and the rest is the same as Example 1 to prepare the Chinese medicine granules.

[0134] Comparative Example 3

[0135] The difference from Example 1 is that the "10% solubilizer" is replaced with the "disintegrant" of the same mass percentage, and the rest is the same as Example 1 to prepare the Chinese medicine granules.

[0136] Comparative Example 4

[0137] The difference from Example 1 is that "starch, lactose and magnesium aluminum silicate in a mass ratio of 2:2:1" is replaced by "starch and lactose in a mass ratio of 2:2", and the rest is the same as Example 1 to prepare Chinese medicine granules.

[0138] Comparative Example 5

[0139] The difference from Example 1 is that "1:2:1 of povidone, hydroxypropyl methylcellulose and dextrin" is replaced by "1:1:6 of povidone, hydroxypropyl methylcellulose and dextrin", and the rest is the same as Example 1 to prepare Chinese medicine granules.

[0140] Comparative Example 6

[0141] The difference from Example 1 is that "β-cyclodextrin and polysorbate 80 in a mass ratio of 1:1" is replaced by "β-cyclodextrin", and the rest is the same as Example 1 to prepare Chinese medicine granules.

[0142] Comparative Example 7

[0143] The difference from Example 1 is that "cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1" is replaced by "cross-linked polyvinylpyrrolidone", and the rest is the same as Example 1 to prepare Chinese medicine granules.

[0144] Test Example 1

[0145] Chinese medicine granules for the treatment of rheumatic diseases

[0146] 1. Materials and methods

[0147] 1.1 Experimental animals

[0148] Three-month-old SPF-grade SD female rats (purchased from Shanghai Slake Experimental Animal Co., Ltd.) were adaptively raised for 7 days, with free access to food and water, and randomly divided into a normal group, a model group, a positive drug group, a basic example 1-1 group, a basic example 1-2 group, a basic example 1-3 group, a basic example 1-4 group, an example 1-9 group, and a comparative example 1-7 group, with 10 rats in each group.

[0149] 1.2 Test methods

[0150] Modeling: Except for the normal control group, rats in other groups were subcutaneously injected with 0.1 mL of Freund's complete adjuvant (10 mg / mL) at the plantar level of the left hind paw to induce inflammation, while the normal group was injected with an equal amount of normal saline.

[0151] Administration: After the modeling was completed, the Basic Example 1-1 group, the Basic Example 1-2 group, the Basic Example 1-3 group, and the Basic Example 1-4 group were gavaged with 0.5 mg / kg, 0.22 mg / kg, 0.66 mg / kg, and 0.77 mg / kg of the Chinese medicine component prepared in the Basic Example 1 group, respectively, and the Example 1-9 group and the Comparative Example 1-7 group were gavaged with 1.1 mg / kg of the Chinese medicine granules prepared in the corresponding group, the normal group and the model group were given an equal volume of distilled water, and the positive drug group was given 0.5 mg / kg of methotrexate, once a day for 14 consecutive days.

[0152] 2. Test results

[0153] 2.1 Plantar swelling:

[0154] After the administration, the thickness of the left hind paw of the rats was measured and the degree of paw swelling was calculated.

[0155] Swelling degree = (C t C0) / C0, C0 represents the thickness of the forefoot causing inflammation, C t Indicates the thickness of the plantar fossa after inflammation.

[0156] The results are shown in Table 1.

[0157] The results in Table 1 show that:

[0158] After modeling, the swelling of the paws of rats in the model group was significantly increased compared with that in the normal group.

[0159] After drug administration, compared with the model group, the swelling of the paws of the rats in the basic example 1-1 group, the basic example 1-2 group, the basic example 1-3 group, the basic example 1-4 group, the positive drug group, the example 1-9 group and the comparative example 1-7 group all decreased significantly, which shows that the Chinese medicine component as the main active ingredient can reduce the swelling of the paws of the rats and relieve inflammation in the rats. Among them, the example 1 group has the best ability to reduce the swelling of the paws of the rats.

[0160] Comparing the basic example 1-1 group and the example 2 group, the basic example 1-2 group and the example 6 group, the basic example 1-3 group and the example 7 group, the basic example 1-4 group and the comparative example 1 group, the Chinese medicine component at the same dose, the Chinese medicine component is added with excipients to prepare granules, and the effect of treating rat foot swelling is significantly improved. This shows that after adding appropriate excipients to the Chinese medicine component to prepare granules, the efficacy of the Chinese medicine component can be effectively improved and the bioavailability can be improved.

[0161] Comparing Example 1, Examples 6-7 and Comparative Example 1, the swelling degree of the paws of rats in Comparative Example 1 was significantly improved, which indicates that in the preparation process of the Chinese medicine granules, the mass ratio of the Chinese medicine ingredients and the excipients can be more effectively reduced under the conditions of 20-60:40-80 to relieve inflammation in rats.

[0162] Comparing Example 1 with Comparative Examples 2-3, the swelling degree of the paws of rats in Comparative Examples 2-3 was significantly increased, which indicates that the use of adhesives and solubilizers in the preparation of Chinese medicine granules can more effectively reduce the swelling degree of the paws of rats and relieve inflammation in rats.

[0163] Comparing Example 1, Examples 8-9 and Comparative Examples 4-7, the swelling degree of the paw of the rats in Comparative Examples 4-7 was significantly improved, which indicates that in the preparation process of the traditional Chinese medicine granules, the filler composed of starch, lactose and magnesium aluminum silicate, the binder composed of polyvidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 1-2:1-2:1, the solubilizer composed of β-cyclodextrin and polysorbate 80, and the disintegrant composed of cross-linked polyvidone and low-substituted hydroxypropyl cellulose can more effectively reduce the swelling degree of the paw of the rats and relieve inflammation in the rats.

[0164] Comparing Examples 1-5, it was found that the rat paw swelling degree of Example 1-3 was lower than that of Example 4-5. The results showed that in the preparation process of the Chinese medicine granules, the mass percentage of each component in the excipients is preferably: 70-75% filler, 3-10% binder, 5-15% solubilizer and 8-20% disintegrant, and most preferably 72% filler, 6% binder, 10% solubilizer and 12% disintegrant.

[0165] Table 1 Rat paw swelling

[0166] Group Plantar swelling Normal group 0.05±0.01 Model Group <![CDATA[0.57±0.02 ### ]]> Positive drug group <![CDATA[0.26±0.04 ** ]]> Basic Example 1-1 Group <![CDATA[0.33±0.01 * ]]> Basic Example 1-2 Group <![CDATA[0.50±0.08 * ]]> Basic Example 1-3 Groups <![CDATA[0.25±0.02 ** ]]> Basic Examples 1-4 <![CDATA[0.18±0.02 *** ]]> Example 1 Group <![CDATA[0.11±0.02 *** ]]> Example 2 Group <![CDATA[0.19±0.03 *** ]]> Example 3 Group <![CDATA[0.20±0.04 *** ]]> Example 4 Group <![CDATA[0.25±0.03 ** ]]> Example 5 Group <![CDATA[0.22±0.01 ** ]]> Example 6 Group <![CDATA[0.33±0.04 * ]]> Example 7 Group <![CDATA[0.13±0.02 *** ]]> Example 8 Group <![CDATA[0.16±0.01 *** ]]> Example 9 Group <![CDATA[0.14±0.01 ** ]]> Comparative Example 1 <![CDATA[0.25±0.06 **+++ ]]> Comparative Example 2 <![CDATA[0.26±0.05 **+++ ]]> Comparative Example 3 <![CDATA[0.31±0.07 *+++ <!-- 8 -->]]> Comparative Example 4 <![CDATA[0.20±0.05 ***+++ ]]> Comparative Example 5 <![CDATA[0.17±0.04 ***++ ]]> Comparative Example 6 <![CDATA[0.25±0.04 **+++ ]]> Comparative Example 7 <![CDATA[0.19±0.03 ***++ ]]>

[0167] ### p<0.001, vs normal group; * p<0.05, ** p<0.01, *** p<0.001, vs model group; ++ p<0.01, +++ p<0.001, vs Example 1 group.

[0168] 2.2 Rat arthritis index:

[0169] After the last administration, the primary lesions on the inflamed side of each group of rats were observed, and the arthritis index of the rats was calculated.

[0170] The criteria for determining the arthritis index are as follows:

[0171] 0 points = normal;

[0172] 1 point = mild but noticeable swelling or redness of the ankle or wrist, or noticeable swelling or redness limited to individual fingers, regardless of the number of fingers affected;

[0173] 2 points = moderate redness and swelling of the ankle or wrist;

[0174] 3 points = severe redness and swelling of the entire paw including the finger;

[0175] 4 points = maximal inflammation of the limb, involving multiple joints.

[0176] Add up the scores for the left and right paw joints.

[0177] The results are shown in Table 2.

[0178] The results in Table 2 show that after modeling, the arthritis index of rats in the model group was significantly increased compared with that in the normal group.

[0179] After drug administration, compared with the model group, the arthritis index of rats in the basic example 1-1 group, the basic example 1-2 group, the basic example 1-3 group, the basic example 1-4 group, the positive drug group, the example 1-9 group and the comparative example 1-7 group all decreased significantly, indicating that the Chinese medicine component as the main active ingredient can relieve arthritis in rats. Among them, the example 1 group has the best ability to reduce arthritis in rats.

[0180] Comparing the basic example 1-1 group and the example 2 group, the basic example 1-2 group and the example 6 group, the basic example 1-3 group and the example 7 group, the basic example 1-4 group and the comparative example 1 group, the Chinese medicine components are added with excipients to prepare granules at the same dose, and the effect of treating arthritis in rats is significantly improved. This shows that after adding appropriate excipients to the Chinese medicine components to prepare granules, the efficacy of the Chinese medicine components can be effectively improved and the bioavailability can be improved.

[0181] Comparing Example 1, Examples 6-7 and Comparative Example 1, the arthritis index of the rats in Comparative Example 1 was significantly improved, which indicates that in the preparation process of the Chinese medicine granules, the mass ratio of the Chinese medicine ingredients to the excipients can be more effectively reduced in the condition of 20-60:40-80, which is the best.

[0182] Comparing Example 1 with Comparative Examples 2-3, the arthritis index of the rats in Comparative Examples 2-3 was significantly improved, which indicates that the use of a binder and a solubilizer in the preparation of the traditional Chinese medicine granules can more effectively alleviate arthritis in rats.

[0183] Comparing Example 1, Examples 8-9 and Comparative Examples 4-7, the arthritis index of the rats in Comparative Examples 4-7 was significantly improved, which indicates that in the preparation process of the traditional Chinese medicine granules, the use of fillers composed of starch, lactose and magnesium aluminum silicate, binders composed of polyvidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 1-2:1-2:1, solubilizers composed of β-cyclodextrin and polysorbate 80, and disintegrants composed of cross-linked polyvidone and low-substituted hydroxypropyl cellulose can more effectively relieve arthritis in rats.

[0184] Comparing Examples 1-5, it was found that the rat arthritis index of Example 1-3 was lower than that of Example 4-5. The results showed that in the preparation process of the Chinese medicine granules, the mass percentage of each component in the excipients is preferably: 70-75% filler, 3-10% binder, 5-15% solubilizer and 8-20% disintegrant, and most preferably 72% filler, 6% binder, 10% solubilizer and 12% disintegrant.

[0185] Table 2 Arthritis index of rats

[0186]

[0187]

[0188] ### p<0.001, vs normal group; * p<0.05, ** p<0.01, *** p<0.001, vs model group; + p<0.05, ++ p<0.01, vs Example 1 group.

[0189] 2.3 Levels of inflammatory factors TNF-α and IL-1β in serum:

[0190] After the last administration, the rats were anesthetized, blood was collected from the abdominal aorta, and serum was collected to test the levels of TNF-α and IL-1β according to the instructions of the kit.

[0191] The results are shown in Table 3.

[0192] The results in Table 3 show that after modeling, the levels of TNF-α and IL-1β in the model group rats were significantly increased compared with those in the normal group.

[0193] After drug administration, compared with the model group, the TNF-α and IL-1β levels of rats in the basic example 1-1 group, the basic example 1-2 group, the basic example 1-3 group, the basic example 1-4 group, the positive drug group, the example 1-9 group and the comparative example 1-7 group were significantly reduced, which shows that the Chinese medicine ingredients as the main active ingredients can reduce the TNF-α and IL-1β levels of rats and relieve inflammation in rats. Among them, the example 1 group has the best ability to reduce the levels of TNF-α and IL-1β.

[0194] Comparing the basic example 1-1 group and the example 2 group, the basic example 1-2 group and the example 6 group, the basic example 1-3 group and the example 7 group, the basic example 1-4 group and the comparative example 1 group, the Chinese medicine components are added with excipients to prepare granules at the same dose, and the effect of treating the TNF-α and IL-1β levels of rats is significantly improved. This shows that after adding appropriate excipients to the Chinese medicine components to prepare granules, the efficacy of the Chinese medicine components can be effectively improved and the bioavailability can be improved.

[0195] Comparing Example 1, Examples 6-7 and Comparative Example 1, the TNF-α and IL-1β levels of rats in Comparative Example 1 were significantly increased, which indicates that in the preparation process of Chinese medicine granules, the mass ratio of Chinese medicine ingredients and excipients under the conditions of 20-60:40-80 can more effectively reduce the TNF-α and IL-1β levels of rats and relieve inflammation in rats.

[0196] Comparing Example 1 with Comparative Examples 2-3, the TNF-α and IL-1β levels of rats in Comparative Examples 2-3 were significantly increased, which indicates that in the preparation process of Chinese medicine granules, the use of binders and solubilizers can more effectively reduce the TNF-α and IL-1β levels of rats and relieve inflammation in rats.

[0197] Comparing Example 1, Examples 8-9 and Comparative Examples 4-7, the TNF-α and IL-1β levels of rats in Comparative Examples 4-7 were significantly improved, which indicates that in the preparation process of the traditional Chinese medicine granules, the use of fillers composed of starch, lactose and magnesium aluminum silicate, binders composed of polyvidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 1-2:1-2:1, solubilizers composed of β-cyclodextrin and polysorbate 80, and disintegrants composed of cross-linked polyvidone and low-substituted hydroxypropyl cellulose can more effectively reduce the levels of TNF-α and IL-1β in rats and relieve inflammation in rats.

[0198] Comparing Examples 1-5, it was found that the rat TNF-α and IL-1β levels of Examples 1-3 were lower than those of Examples 4-5. The results showed that in the preparation process of Chinese medicine granules, the mass percentage of each component in the excipients is preferably: 70-75% filler, 3-10% binder, 5-15% solubilizer and 8-20% disintegrant, and the most preferred is 72% filler, 6% binder, 10% solubilizer and 12% disintegrant.

[0199] Table 3 TNF-α and IL-1β levels in rats

[0200]

[0201]

[0202] ### p<0.001, vs normal group; * p<0.05, ** p<0.01, *** p<0.001, vs model group; + p<0.05, ++ p<0.01, vs Example 1 group.

[0203] Test Example 2

[0204] Under non-stirring conditions, the dissolution conditions of the Chinese medicine granules prepared in Examples 1-9 and Comparative Examples 1-7 at 30s, 2min, and 5min when dissolved in cold water.

[0205] The results are shown in Table 4.

[0206] The results in Table 4 show that the Chinese medicine granules of Examples 1-9 have good solubility in cold water.

[0207] Table 4 Dissolution of Chinese medicine granules in cold water

[0208]

[0209]

[0210] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A Chinese medicine granule for rheumatic diseases, characterized in that: Including Chinese herbal medicine ingredients and excipients; The Chinese medicinal ingredients are obtained by water extraction and concentration of Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Radix fangfeng, Radix glycyrrhizae, Fructus viticis and Rhizoma chuanxiong; The auxiliary materials include fillers, binders, solubilizers and disintegrants; The mass ratio of the traditional Chinese medicine components to the auxiliary materials is 20-60:40-80.

2. The Chinese medicine granules according to claim 1, characterized in that: The mass ratio of the traditional Chinese medicine ingredients to the auxiliary materials is 40-60:40-60.

3. The Chinese medicine granules according to claim 1, characterized in that: Among the traditional Chinese medicine ingredients, the mass ratio of Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Radix Glycyrrhizae Preparata, Fructus Viticis Manni and Rhizoma Chuanxiong is 5-10:5-10:2-4:2-4:2-4:1-3:0.5-2.

4. The Chinese medicine granules according to claim 3, characterized in that: Among the traditional Chinese medicine ingredients, the mass ratio of Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Radix Glycyrrhizae Preparata, Fructus Viticis Manni and Rhizoma Chuanxiong is 6:6:3:3:3:2:1.

5.

5. The Chinese medicine granules according to claim 1, characterized in that: The auxiliary materials include the following components in percentage by weight: 60-85% filler, 2-15% binder, 0.5-15% solubilizer and 5-20% disintegrant.

6. The Chinese medicine granules according to claim 5, characterized in that: The auxiliary materials include the following components in percentage by weight: 70-75% filler, 3-10% binder, 5-15% solubilizer and 8-20% disintegrant.

7. The Chinese medicine granules according to claim 5, characterized in that: The filler is selected from one or more of starch, lactose, microcrystalline cellulose, mannitol, calcium hydrogen phosphate, calcium carbonate and magnesium aluminum silicate; The binder is selected from one or more of povidone, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, gum arabic, sucrose, and dextrin; The solubilizing agent is selected from one or more of β-cyclodextrin and its derivatives and polysorbate 80; the β-cyclodextrin and its derivatives are selected from one or more of β-cyclodextrin, hydroxypropyl-β-cyclodextrin and sulfobutyl ether-β-cyclodextrin; The disintegrant is selected from one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch.

8. The Chinese medicine granules according to claim 7, characterized in that: The filler is starch, lactose and magnesium aluminum silicate in a mass ratio of 1-4:1-4:1-2; The binder is povidone, hydroxypropyl methylcellulose and dextrin in a mass ratio of 1-2:1-2:1; The solubilizing agent is selected from β-cyclodextrin and polysorbate 80; The disintegrant is cross-linked polyvinylpyrrolidone and low-substituted hydroxypropyl cellulose in a mass ratio of 1:1-3.

9. The Chinese medicine granules according to claim 5, characterized in that: The auxiliary material also includes a wetting agent, and the wetting agent includes one or two of water and ethanol.

10. The method for preparing the Chinese medicine granules according to any one of claims 1 to 9, characterized in that: The following steps are involved: S1: decoct and extract Notopterygium wilfordii, Angelica dahurica, Ligusticum chuanxiong, Radix Angelicae Pubescentis, Fructus Viticis and Rhizoma Chuanxiong, filter, take the filtrate, concentrate and dry to obtain an extract, which is the traditional Chinese medicine ingredient; S2: Mix the Chinese medicinal ingredients and auxiliary materials and granulate them to prepare Chinese medicinal granules.

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