Pharmaceutical compositions and dosage forms for the treatment of gout

Abstract

The present application relates to a kind of pharmaceutical compositions for treating gout, comprising three groups of active ingredients and adjuvant, wherein the first group of active ingredients has the effect of inhibiting the generation of uric acid, including one or more of Cordyceps militaris, celery seed, galangal, chicory;The second group of active ingredients has the effect of accelerating the excretion of uric acid, including one or more of corn silk, Gyrinopsys pentaphylla, dandelion, coix seed, lotus leaf, Poria cocos, marine fish oligopeptide;The third group of active ingredients has the effect of relieving inflammatory pain, including one or more of Ampelopsis brevifolia leaf, papaya, radix puerariae.The pharmaceutical composition can be made into granules, tablets and other dosage forms, with good drug efficacy, convenient to take, no obvious toxic and side effects and other advantages.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of traditional Chinese medicine, in particular, to a pharmaceutical composition for treating gout. BACKGROUND

[0002] Gout is the second largest metabolic disease in China, characterized by elevated uric acid levels, with a global prevalence of about 10%, and the incidence rate is increasing year by year and showing a trend of younger age. Its pathological mechanism is the deposition of intrarticular monosodium urate crystals to induce inflammation, release interleukins, tumor necrosis factor and other inflammatory mediators, and trigger an inflammatory cascade, resulting in symptoms such as joint redness, heat and pain. Gout can recur, leading to joint dislocation or pathological fracture, often accompanied by kidney disease and various chronic diseases such as hypertension, diabetes, hyperlipidemia, etc., which seriously endanger human health.

[0003] According to different clinical stages of gout treatment, commonly used drugs are divided into two categories: controlling acute arthritis symptoms and anti-hyperuricemia, among which anti-hyperuricemia can be divided into inhibiting uric acid generation and promoting uric acid excretion. The drugs for controlling acute arthritis symptoms can reduce the pain of joint local by inhibiting the chemotaxis, adhesion and phagocytosis of inflammatory cells, and inhibiting the release of inflammatory factors, including colchicine, non-steroidal anti-inflammatory drugs, glucocorticoids, etc.; the drugs for inhibiting uric acid generation can reduce uric acid by inhibiting xanthine oxidase, including allopurinol, febuxostat, etc.; the drugs for promoting uric acid excretion can increase the excretion of urate by inhibiting the active reabsorption of urate in the renal tubule, including benzbromarone, probenecid, etc.

[0004] However, these common clinical drugs show certain toxic and side effects in treatment. Among the drugs for controlling acute arthritis symptoms, colchicine and non-steroidal anti-inflammatory drugs can cause adverse gastrointestinal reactions such as abdominal pain, nausea, vomiting, etc., and long-term use of colchicine can even cause aplastic anemia. Among the drugs for inhibiting uric acid generation, allopurinol often causes adverse reactions such as skin rash, diarrhea, abdominal pain, low fever, kidney damage, etc., and febuxostat often causes abnormal liver function, diarrhea, headache, muscle and skeletal system and connective tissue diseases. Among the drugs for promoting uric acid excretion, benzbromarone and probenecid can cause varying degrees of gastrointestinal reactions such as nausea, vomiting, fullness in the stomach, etc.

[0005] In addition to the above common drugs, there are also some imported uric acid-lowering health foods on the domestic market, such as celery seed capsules, sour cherry capsules, black cherry tablets, etc., but the prices are expensive. There are also products such as Poria cocos mulberry root and pueraria tea bags, gardenia and chicory tea, etc. to relieve gout, but they have the shortcomings of single dosage form and slow effect. SUMMARY

[0006] The first aspect of the present application provides a pharmaceutical composition for treating gout, which can be prepared into granules, tablets and the like, and has the advantages of good drug efficacy, no obvious toxic and side effects and the like.

[0007] The pharmaceutical composition provided in the present application comprises three groups of active ingredients and excipients, wherein the first group of active ingredients comprises one or more of Cordyceps militaris, celery seeds, Alpinia officinarum and chicory; the second group of active ingredients comprises one or more of corn silk, Ginkgo leaves, dandelion, coix seed, lotus leaves, Poria cocos and marine fish oligopeptide; and the third group of active ingredients comprises one or more of Ampelopsis aconitifolia leaves, papaya and radix puerariae.

[0008] In some embodiments, the excipients comprise one or more of a binder, a flavoring agent, a lubricant and an antioxidant.

[0009] Optionally, the binder comprises one or more of sugar syrup, malt dextrin, hydroxypropyl methylcellulose, sodium carboxymethylcellulose and pregelatinized starch, and preferably malt dextrin.

[0010] Optionally, the flavoring agent comprises one or more of maltitol, sucralose, erythritol and steviol glycoside.

[0011] Optionally, the lubricant comprises one or more of magnesium stearate, talc, colloidal silicon dioxide and polyethylene glycol, and preferably magnesium stearate.

[0012] Optionally, the antioxidant comprises one or more of citric acid, DL-malic acid and ascorbic acid.

[0013] The second aspect of the present application provides a granule for treating gout, which comprises the pharmaceutical composition of the first aspect, i.e. three groups of active ingredients and excipients, wherein the excipients comprise a binder and a flavoring agent.

[0014] In some embodiments, the first group of active ingredients accounts for 17-48% in the granule by mass percentage, the second group of active ingredients accounts for 8-38% in the granule by mass percentage, and the third group of active ingredients accounts for 2.2-11% in the granule by mass percentage.

[0015] The third aspect of the present application provides a tablet for treating gout, which comprises the pharmaceutical composition of the first aspect, i.e. three groups of active ingredients and excipients, wherein the excipients comprise a binder, a flavoring agent, a lubricant and an antioxidant.

[0016] In some embodiments, the first group of active ingredients accounts for 30-55% in the tablet by mass percentage, the second group of active ingredients accounts for 4-16% in the tablet by mass percentage, and the third group of active ingredients accounts for 4-16% in the tablet by mass percentage.

[0017] The fourth aspect of the present application provides a preparation method of the granules of the second aspect of the present application, comprising the following steps:

[0018] The active ingredient raw materials are dried, crushed, dissolved and centrifuged respectively, and then the filtrate is concentrated and dried to obtain the active ingredient water extract;

[0019] The active ingredient water extract is mixed, granulated in a sterile environment, dried, and packaged to obtain the granules.

[0020] The fifth aspect of the present application provides a preparation method of the tablets of the third aspect of the present application, comprising the following steps:

[0021] The active ingredient raw materials are dried, crushed, dissolved and centrifuged respectively, and then the filtrate is concentrated and dried to obtain the active ingredient water extract;

[0022] The active ingredient water extract is mixed, granulated in a sterile environment, dried, and packaged to obtain the granules. DETAILED DESCRIPTION

[0023] Reference will now be made in detail to the embodiments of the present application, one or more examples of which are set forth below. Each example is provided by way of explanation of the present application, not limitation of the present application. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made in the present application without departing from the scope or spirit of the present application. For example, features illustrated or described as part of one embodiment, can be used with another embodiment to yield a still further embodiment.

[0024] Thus, it is intended that the present application cover modifications and variations of this application provided they come within the scope of the appended claims and their equivalents. Other objects, features, and aspects of the present application are disclosed in or are apparent from the following detailed description of the application. It is to be understood by the skilled artisan that the discussion below is a description of exemplary embodiments only, and is not intended as limiting the broader aspects of the present application.

[0025] In the present application, the technical features described in an open way include both the closed technical solution consisting of the listed features and the open technical solution containing the listed features.

[0026] In the present application, when a numerical interval is involved, the numerical interval is considered to be continuous and includes the minimum value and the maximum value of the range and each value between the minimum value and the maximum value, unless otherwise specified. Further, when a range is referred to as an integer, each integer between the minimum value and the maximum value of the range is included. In addition, when multiple ranges are provided to describe a feature or a characteristic, the ranges can be combined. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all sub-ranges subsumed therein.

[0027] In this document, the unit related to the data range, if only with the unit after the right end point, indicates that the units of the left end point and the right end point are the same. For example, 1 ~ 10 mm indicates that the units of the left end point "1" and the right end point "10" are both mm (millimeter).

[0028] In addition, the specific conditions not indicated in the embodiments are carried out according to the conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products that can be obtained by purchase.

[0029] The pharmaceutical composition of the present application can be used for treating gout, and can be prepared into granules, tablets and other dosage forms, and has the advantages of good drug efficacy, no obvious toxic and side effects, etc. The pharmaceutical composition of the present application comprises three groups of active ingredients and excipients, wherein the first group of active ingredients comprises one or more of Cordyceps militaris, celery seeds, galangal and chicory; the second group of active ingredients comprises one or more of corn silk, lophatherum gracile, dandelion, coix seed, lotus leaf, poria cocos and marine fish oligopeptide; the third group of active ingredients comprises one or more of Ampelopsis aconitifolia, papaya and radix puerariae, and the excipients comprise one or more of binding agents, flavoring agents, lubricants and antioxidants. The pharmaceutical composition of the present application combines the three groups of active ingredients to treat gout, can effectively inhibit the generation of uric acid, accelerate the excretion of uric acid while relieving the pain caused by inflammation, and can also reduce the toxic and side effects.

[0030] Specifically, each component in the first group of active ingredients has the effect of inhibiting the generation of uric acid from purine. Taking Cordyceps militaris as an example, Cordyceps militaris contains nucleoside compounds, Cordyceps polysaccharides, cordycepin and other bioactive ingredients, has the effects of improving liver function and regulating purine metabolism, and can reduce the levels of creatinine, urea nitrogen and uric acid in the serum of hyperuricemia and the activity of xanthine oxidase.

[0031] Each component in the second group of active ingredients has the effect of accelerating the excretion of uric acid. Taking corn silk as an example, corn silk is the female flower style of the plant Zea mays, contains polyglucose, flavonoids, alkaloids and other bioactive ingredients, has the pharmacological effects of diuresis, blood pressure reduction, blood sugar reduction and liver protection, and the total flavonoids in corn silk accelerate the excretion of uric acid by reducing the reabsorption of uric acid by HK-2 cells.

[0032] Each component in the third group of active ingredients has the effect of relieving inflammatory pain. Taking radix puerariae as an example, its main active ingredient is isoflavone, which can play an anti-inflammatory role by affecting immune cells, inflammatory factors and signal pathways. Therefore, the present application combines the three groups of active ingredients together to achieve the therapeutic effect of reducing the concentration of uric acid in the body and relieving inflammatory pain.

[0033] In some embodiments, the binder comprises one or more of sugar syrup, malt dextrin, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, pregelatinized starch, preferably malt dextrin.

[0034] In some embodiments, the flavoring agent comprises one or more of maltitol, sucralose, erythritol, steviol glycoside.

[0035] In some embodiments, the lubricant comprises one or more of magnesium stearate, talc, colloidal silicon dioxide, polyethylene glycol, preferably magnesium stearate.

[0036] In some embodiments, the antioxidant comprises one or more of citric acid, DL-malic acid, ascorbic acid.

[0037] A second aspect of the present application is to provide a granule for treating gout, comprising the pharmaceutical composition of the first aspect, specifically, the first group of active ingredients comprises one or more of Cordyceps militaris, celery seeds, Alpinia officinarum, chicory, the second group of active ingredients comprises one or more of corn silk, Ginkgo biloba, dandelion, coix seed, lotus leaf, Poria cocos, marine fish oligopeptide, the third group of active ingredients comprises one or more of Ampelopsis brevifolia, papaya, pueraria, and the excipients comprise a binder and a flavoring agent.

[0038] The pharmaceutical composition is made into a granule dosage form, compared with common liquid dosage forms such as oral liquids, the additives are relatively less, there are no obvious toxic side effects, and it is easy to transport and carry. In some embodiments, the first group of active ingredients accounts for 17-48% in the granule by mass percentage, the second group of active ingredients accounts for 8-38% in the granule by mass percentage, the third group of active ingredients accounts for 2.2-11% in the granule by mass percentage, and the rest is the binder and the flavoring agent.

[0039] The binder has the effect of increasing viscosity and dispersibility, and the mass percentage in the granule is 20-30%.

[0040] The flavoring agent accounts for 15.02-20.06% in the granule by mass percentage.

[0041] A third aspect of the present application is to provide a tablet for treating gout, comprising the pharmaceutical composition of the first aspect, specifically, the first group of active ingredients comprises one or more of Cordyceps militaris, celery seeds, Alpinia officinarum, chicory, the second group of active ingredients comprises one or more of corn silk, Ginkgo biloba, dandelion, coix seed, lotus leaf, Poria cocos, marine fish oligopeptide, the third group of active ingredients comprises one or more of Ampelopsis brevifolia, papaya, pueraria, and the excipients comprise a binder, a flavoring agent, a lubricant, and an antioxidant.

[0042] The pharmaceutical composition is made into a tablet form, and compared with common solid dosage forms such as capsules and pills, the cost of batch production is relatively low. In some embodiments, the first group of active ingredients accounts for 30-55% in the tablet by mass percentage, the second group of active ingredients accounts for 4-16% in the tablet by mass percentage, the third group of active ingredients accounts for 4-16% in the tablet by mass percentage, and the rest is adhesive, flavoring agent, lubricant and antioxidant.

[0043] The mass percentage of the adhesive in the tablet is 15-25%.

[0044] The mass percentage of the flavoring agent in the tablet is 15.01-26%.

[0045] The mass percentage of the lubricant in the tablet is 0.5-1%, which has the effect of reducing sticking and making the surface of the tablet smooth.

[0046] The mass percentage of the antioxidant in the tablet is 0.2-2%.

[0047] The fourth aspect of the present application provides a preparation method of the granules of the present application, comprising the following steps:

[0048] After the active ingredient raw materials are dried, crushed, dissolved and centrifuged, the filtrate is concentrated and dried to obtain the active ingredient water extract;

[0049] The active ingredient water extract is mixed, granulated in a sterile environment, dried, and packaged to obtain the granules.

[0050] Optionally, when preparing the active ingredient water extract, the drying can use a drying machine, the temperature can be set to 50-80℃, and the time can be set to 2-4h; the crushing can use a 10-mesh traditional Chinese medicine crusher, and the granules with a particle size of 1-10mm are selected after crushing for 1-5min; the solvent in the dissolving process is pure water, the mass-volume ratio of the active ingredient powder to water is 1:8-10 (g / mL), the temperature is controlled at 60-80℃, and the extraction is performed for 2-4h; the centrifugation can use a centrifugal concentrator, the speed can be set to 1000-3000rpm, the temperature can be set to 50-60℃, and the time can be set to 10-30min; the concentration can use a high-efficiency concentrator, the temperature can be set to 50-70℃, the vacuum pressure can be set to -0.06 to -0.09Mpa, and the concentration is performed until the solid content is 15-20%; and the drying can use a spray dryer, the inlet air temperature can be set to 160-190℃, and the outlet air temperature can be set to 70-90℃.

[0051] The granules prepared by spray drying are sieved with a 40-mesh sieve to obtain granules with a particle size of 40-80 meshes.

[0052] The packaging can use a powder packaging machine for quantitative packaging.

[0053] The fifth aspect of the present application provides a method for preparing a tablet, comprising the following steps:

[0054] The active ingredient raw material is dried, crushed, dissolved and centrifuged, and then the filtrate is concentrated and dried to obtain an active ingredient water extract.

[0055] The active ingredient water extract is mixed, granulated in a sterile environment, tableted, packaged, and a tablet is obtained.

[0056] Optionally, when preparing the active ingredient water extract, drying can be performed using an oven, the temperature can be set to 50-80℃, and the time can be set to 2-4h; crushing can be performed using a 10-mesh traditional Chinese medicine crusher, and the granules with a particle size of 1-10mm are screened after crushing for 1-5min using a 10-mesh screen; the solvent in the dissolving process is pure water, the mass / volume ratio of the active ingredient powder to water is 1:8-10 (g / mL), the temperature is controlled at 60-80℃, and the extraction is performed for 2-4h; centrifugation can be performed using a centrifugal concentrator, the speed can be set to 1000-3000rpm, the temperature can be set to 50-60℃, and the time can be set to 10-30min; concentration can be performed using a high-efficiency concentrator, the temperature can be set to 50-70℃, the vacuum pressure can be set to -0.06 to -0.09Mpa, and the concentration is performed until the solid content is 15-20%; and drying can be performed using a spray dryer, the inlet air temperature can be set to 160-190℃, and the outlet air temperature can be set to 70-90℃.

[0057] The granules prepared by spray drying are screened using a 40-mesh screen to obtain granules with a particle size of 40-80 mesh.

[0058] Tableting can be performed using a tablet press, and the pressure can be set to 40-100N.

[0059] The embodiments of the present application will be described in detail below with reference to the examples. In the following examples, the raw materials used are commercially available products, unless otherwise specified.

[0060] Example 1

[0061] This example provides a granule, and first, an active ingredient water extract is prepared:

[0062] Take Cordyceps militaris, celery seeds, chicory, corn silk, marine fish oligopeptide, lophatherum gracile, pueraria, poria cocos, galangal, papaya into the dryer and dry for 2h, take out and put into 10 mesh traditional Chinese medicine crusher, crush for 2min, then screen the particle size of 1-10mm granules through 10 mesh screen. Take 100g of each active ingredient granules, add 1000ml of pure water, extract at 70℃ for 3h, then put into the centrifugal concentrator, the speed is 2000rpm, the temperature is 50℃, take out after 30min. Put the filtrate into the high-efficiency concentrator, set the temperature to 60℃, and the vacuum pressure to-0.08Mpa. Concentrate to a solid content of 18%. Take out and put into the spray dryer, the inlet air temperature is 180℃, and the outlet air temperature is 80℃. Cordyceps militaris water extract 60g, celery seed water extract 55g, chicory water extract 68g, corn silk water extract 65g, marine fish oligopeptide water extract 45g, lophatherum gracile water extract 48g, pueraria water extract 38g, poria cocos water extract 46g, galangal water extract 50g, papaya water extract 42g are obtained respectively.

[0063] Then prepare granules:

[0064] Weigh the components according to the proportion, in mass percentage, Cordyceps militaris water extract accounts for 10%, celery seed water extract accounts for 10%, chicory water extract accounts for 8%, galangal water extract accounts for 3%, corn silk water extract accounts for 6%, marine fish oligopeptide water extract accounts for 6%, lophatherum gracile water extract accounts for 5%, poria cocos water extract accounts for 3%, pueraria water extract accounts for 5%, papaya water extract accounts for 0.5%. The adjuvants include binders and flavorings, among which the binder is malt dextrin, accounting for 25%, and the flavorings are maltitol and sucralose, maltitol accounting for 18.45% and sucralose accounting for 0.05%.

[0065] Mix the active ingredient water extract, binder and flavoring evenly in a sterile environment, put the mixture into the granulator for 10min at a speed of 120rpm; after granulation, put it into the dryer and dry at 60℃ for 2h; take it out and put it into the powder packaging machine for quantitative packaging, get granules, the granules are 10g / bag.

[0066] Example 2

[0067] This example provides a kind of granules, first adopt the same method as in example 1 to prepare active ingredient water extract; Then prepare granules:

[0068] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 15%, the water extract of celery seed accounts for 15%, the water extract of chicory accounts for 10%, the water extract of high-quality ginger accounts for 8%, the water extract of corn silk accounts for 2%, the water extract of marine fish oligopeptide accounts for 2%, the water extract of Ginkgo biloba accounts for 2%, the water extract of Poria cocos accounts for 2%, the water extract of Pueraria accounts for 2%, and the water extract of papaya accounts for 0.2%. The adjuvants include a binder and a flavoring agent, wherein the binder is malt dextrin, accounting for 30%, and the flavoring agent is maltitol and sucralose, wherein maltitol accounts for 11.74% and sucralose accounts for 0.06%.

[0069] In a sterile environment, the active ingredient water extract, the binder and the flavoring agent are uniformly mixed, the mixture is put into a granulator for 15 minutes at a speed of 100 rpm; after granulation, it is put into a drying machine and dried at 80℃ for 2 hours; after taking out, it is put into a powder dispenser for quantitative packaging, and a granule is obtained, which is 10g / bag.

[0070] Example 3

[0071] This example provides a granule, which is prepared by first preparing an active ingredient water extract by the same method as in Example 1; and then preparing a granule:

[0072] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 5%, the water extract of celery seed accounts for 5%, the water extract of chicory accounts for 5%, the water extract of high-quality ginger accounts for 2%, the water extract of corn silk accounts for 10%, the water extract of marine fish oligopeptide accounts for 10%, the water extract of Ginkgo biloba accounts for 10%, the water extract of Poria cocos accounts for 8%, the water extract of Pueraria accounts for 2%, and the water extract of papaya accounts for 0.2%. The adjuvants include a binder and a flavoring agent, wherein the binder is malt dextrin, accounting for 26.74%, and the flavoring agent is maltitol and sucralose, wherein maltitol accounts for 15% and sucralose accounts for 0.06%.

[0073] In a sterile environment, the active ingredient water extract, the binder and the flavoring agent are uniformly mixed, the mixture is put into a granulator for 8 minutes at a speed of 130 rpm; after granulation, it is put into a drying machine and dried at 60℃ for 4 hours; after taking out, it is put into a powder dispenser for quantitative packaging, and a granule is obtained, which is 10g / bag.

[0074] Example 4

[0075] This example provides a granule, which is prepared by first preparing an active ingredient water extract by the same method as in Example 1; and then preparing a granule:

[0076] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 10%, the water extract of celery seed accounts for 10%, the water extract of chicory accounts for 5%, the water extract of high-quality ginger accounts for 5%, the water extract of corn silk accounts for 6%, the water extract of marine fish oligopeptide accounts for 6%, the water extract of Ginkgo biloba accounts for 4%, the water extract of Poria cocos accounts for 4%, the water extract of Pueraria accounts for 10%, and the water extract of papaya accounts for 1%. The adjuvants include a binder and a flavoring agent, wherein the binder is malt dextrin, accounting for 20%, and the flavoring agent is maltitol and sucralose, maltitol accounting for 18.96% and sucralose accounting for 0.04%.

[0077] In a sterile environment, the active ingredient water extract, the binder and the flavoring agent are mixed uniformly, and the mixture is put into a granulator for 8 min at a speed of 130 rpm; after granulation, it is put into a drying machine and dried at 60℃ for 3h; after taking out, it is put into a powder dispenser for quantitative packaging, and a granule is obtained, which is 10g / bag.

[0078] The formulations of examples 1-4 are shown in table 1.

[0079] Table 1: Components and their contents of examples 1-4

[0080]

[0081]

[0082] Example 5

[0083] This example provides a tablet, which is prepared by first preparing the active ingredient water extract:

[0084] Cordyceps militaris, celery seeds, chicory, coix seed, corn silk, Ampelopsis brevifolia leaves, and Pueraria are put into a drying machine and dried for 2h, then taken out and put into a 10-mesh traditional Chinese medicine crusher, crushed for 2min, and sieved through a 10-mesh sieve to obtain granules with a particle size of 1-10mm. 100g of each active ingredient granule is taken, and 900mL of pure water is added, and extracted at 60℃ for 4h, then put into a centrifugal concentrator at a speed of 2000rpm and a temperature of 50℃, and taken out after 30min. The filtrate is taken and put into a high-efficiency concentrator, the temperature is set to 70℃, and the vacuum pressure can be set to-0.09Mpa, and concentrated to a solid content of 20%. Take out and put into a spray dryer, wherein the inlet air temperature is 190℃ and the outlet air temperature is 85℃, and Cordyceps militaris water extract 60g, celery seed water extract 55g, chicory water extract 68g, coix seed water extract 48g, corn silk water extract 65g, Ampelopsis brevifolia leaf water extract 45g, and Pueraria water extract 38g are obtained respectively.

[0085] Then the tablet is prepared:

[0086] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 16%, the water extract of celery seed accounts for 15%, the water extract of chicory accounts for 10%, the water extract of coix seed accounts for 5%, the water extract of corn silk accounts for 5%, the water extract of Ampelopsis aconitifolia accounts for 5%, and the water extract of pueraria accounts for 4%. The auxiliary materials include adhesive, flavoring agent, lubricant and antioxidant, wherein the adhesive is malt dextrin, accounting for 20%; the flavoring agent is erythritol and stevioside, erythritol accounting for 18% and stevioside accounting for 0.25%; the lubricant is magnesium stearate, accounting for 1%; and the antioxidant is citric acid and DL-malic acid, citric acid accounting for 0.5% and DL-malic acid accounting for 0.25%.

[0087] In a sterile environment, the active ingredient water extract, adhesive, flavoring agent, lubricant and antioxidant are mixed uniformly, and the mixture is put into a granulator for 10 minutes at a speed of 120 rpm; after granulation, it is put into a tablet press with a pressure of 40 N; and then it is packaged after being taken out, to obtain tablets, which are 1 g / tablet.

[0088] Example 6

[0089] This example provides a tablet, which is prepared by first preparing the active ingredient water extract by the same method as in Example 5, and then preparing the tablet:

[0090] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 15%, the water extract of celery seed accounts for 10%, the water extract of chicory accounts for 5%, the water extract of coix seed accounts for 2%, the water extract of corn silk accounts for 2%, the water extract of Ampelopsis aconitifolia accounts for 8%, and the water extract of pueraria accounts for 8%. The auxiliary materials include adhesive, flavoring agent, lubricant and antioxidant, wherein the adhesive is malt dextrin, accounting for 22.9%; the flavoring agent is erythritol and stevioside, erythritol accounting for 25% and stevioside accounting for 1%; the lubricant is magnesium stearate, accounting for 0.5%; and the antioxidant is citric acid and DL-malic acid, citric acid accounting for 0.5% and DL-malic acid accounting for 0.1%.

[0091] In a sterile environment, the active ingredient water extract, adhesive, flavoring agent, lubricant and antioxidant are mixed uniformly, and the mixture is put into a granulator for 12 minutes at a speed of 100 rpm; after granulation, it is put into a tablet press with a pressure of 60 N; and then it is packaged after being taken out, to obtain tablets, which are 1 g / tablet.

[0092] Example 7

[0093] This example provides a tablet, which is prepared by first preparing the active ingredient water extract by the same method as in Example 5, and then preparing the tablet:

[0094] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 15%, the water extract of celery seed accounts for 10%, the water extract of chicory accounts for 5%, the water extract of coix seed accounts for 8%, the water extract of corn silk accounts for 8%, the water extract of Ampelopsis aconitifolia accounts for 2%, and the water extract of pueraria accounts for 2%. The auxiliary materials include adhesive, flavoring agent, lubricant and antioxidant, wherein the adhesive is malt dextrin, accounting for 25%; the flavoring agent is erythritol and stevioside, erythritol accounting for 21.2% and stevioside accounting for 1%; the lubricant is magnesium stearate, accounting for 0.8%; and the antioxidant is citric acid and DL-malic acid, citric acid accounting for 1% and DL-malic acid accounting for 1%.

[0095] In a sterile environment, the active ingredient water extract, adhesive, flavoring agent, lubricant and antioxidant are mixed uniformly, and the mixture is put into a granulator for 8 minutes at a speed of 130 rpm; after granulation, it is put into a tablet press with a pressure of 50 N; and then packaging is performed to obtain tablets, and the tablets are 1.5 g / tablet.

[0096] Example 8

[0097] The present embodiment provides a tablet, which is prepared by first preparing the active ingredient water extract by the same method as in Example 5; and then preparing the tablet:

[0098] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 15%, the water extract of celery seed accounts for 10%, the water extract of chicory accounts for 5%, the water extract of coix seed accounts for 8%, the water extract of corn silk accounts for 8%, the water extract of Ampelopsis aconitifolia accounts for 8%, and the water extract of pueraria accounts for 8%. The auxiliary materials include adhesive, flavoring agent, lubricant and antioxidant, wherein the adhesive is malt dextrin, accounting for 15%; the flavoring agent is erythritol and stevioside, erythritol accounting for 21.7% and stevioside accounting for 0.1%; the lubricant is magnesium stearate, accounting for 0.6%; and the antioxidant is citric acid and DL-malic acid, citric acid accounting for 0.1% and DL-malic acid accounting for 0.5%.

[0099] In a sterile environment, the active ingredient water extract, adhesive, flavoring agent, lubricant and antioxidant are mixed uniformly, and the mixture is put into a granulator for 12 minutes at a speed of 100 rpm; after granulation, it is put into a tablet press with a pressure of 70 N; and then packaging is performed to obtain tablets, and the tablets are 1.5 g / tablet.

[0100] Example 9

[0101] The present embodiment provides a tablet, which is prepared by first preparing the active ingredient water extract by the same method as in Example 5; and then preparing the tablet:

[0102] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 20%, the water extract of celery seed accounts for 20%, the water extract of chicory accounts for 15%, the water extract of coix seed accounts for 2%, the water extract of corn silk accounts for 2%, the water extract of Ampelopsis aconitifolia accounts for 2%, and the water extract of pueraria accounts for 2% by mass percentage. The auxiliary materials include adhesive, flavoring agent, lubricant and antioxidant, wherein the adhesive is malt dextrin, accounting for 18.9%; the flavoring agent is erythritol and steviol glycoside, erythritol accounting for 15% and steviol glycoside accounting for 0.1%; the lubricant is magnesium stearate, accounting for 1%; and the antioxidant is citric acid and DL-malic acid, citric acid accounting for 1% and DL-malic acid accounting for 1%.

[0103] In a sterile environment, the active ingredient water extract, adhesive, flavoring agent, lubricant and antioxidant are mixed uniformly, and the mixture is put into a granulator for 15 min at a speed of 100 rpm; after granulation, it is put into a tablet press with a pressure of 100 N; and then it is packaged after being taken out, to obtain tablets, which are 2 g / tablet.

[0104] The formulations of examples 5-9 are shown in table 2.

[0105] Table 2: Components and their contents of examples 5-9

[0106]

[0107]

[0108] Comparative example 1

[0109] This comparative example provides a granule, which is prepared by first preparing the active ingredient water extract by the same method as example 1; and then preparing the granule:

[0110] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 10%, the water extract of celery seed accounts for 10%, the water extract of chicory accounts for 8%, and the water extract of high-quality ginger accounts for 3% by mass percentage. The auxiliary materials include adhesive and flavoring agent, wherein the adhesive is malt dextrin, accounting for 50.5%, and the flavoring agent is maltitol and sucralose, maltitol accounting for 18.45% and sucralose accounting for 0.05%.

[0111] In a sterile environment, the active ingredient water extract, adhesive and flavoring agent are mixed uniformly, and the mixture is put into a granulator for 10 min at a speed of 120 rpm; after granulation, it is put into a drying machine and dried at 60°C for 4 h; and then it is quantitatively packaged after being taken out and put into a powder dispenser, to obtain a granule.

[0112] Comparative example 2

[0113] This comparative example provides a granule, which is prepared by first preparing the active ingredient water extract by the same method as example 1; and then preparing the granule:

[0114] The components are weighed according to the proportion, and the corn stigma water extract accounts for 6%, the marine fish oligopeptide water extract accounts for 6%, the water extract of Ginkgo biloba accounts for 5%, and the water extract of Poria cocos accounts for 3% by mass percentage. The adjuvants include binders and flavoring agents, wherein the binder is malt dextrin, accounting for 61.5%, and the flavoring agent is maltitol and sucralose, maltitol accounting for 18.45% and sucralose accounting for 0.05%.

[0115] In a sterile environment, the active ingredient water extract, the binder and the flavoring agent are mixed uniformly, and the mixture is put into a granulator for 12 min at a speed of 100 rpm; after granulation, it is put into a drying machine and dried at 80℃ for 2h; after taking out, it is put into a powder dispenser for quantitative packaging, and the granules are obtained.

[0116] Comparative Example 3

[0117] This comparative example provides a granule. First, the active ingredient water extract is prepared by the same method as Example 1; then the granule is prepared:

[0118] The components are weighed according to the proportion, and the corn stigma water extract accounts for 6%, the marine fish oligopeptide water extract accounts for 6%, the water extract of Ginkgo biloba accounts for 5%, and the water extract of Poria cocos accounts for 3% by mass percentage. The adjuvants include binders and flavoring agents, wherein the binder is malt dextrin, accounting for 61.5%, and the flavoring agent is maltitol and sucralose, maltitol accounting for 18.45% and sucralose accounting for 0.05%.

[0119] In a sterile environment, the active ingredient water extract, the binder and the flavoring agent are mixed uniformly, and the mixture is put into a granulator for 12 min at a speed of 100 rpm; after granulation, it is put into a drying machine and dried at 80℃ for 2h; after taking out, it is put into a powder dispenser for quantitative packaging, and the granules are obtained.

[0120] The formulations of Comparative Examples 1-3 are shown in Table 3.

[0121] Table 3: Components and contents of Comparative Examples 1-3

[0122]

[0123]

[0124] Comparative Example 4

[0125] This comparative example provides a tablet. First, the active ingredient water extract is prepared by the same method as Example 5; then the tablet is prepared:

[0126] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 16%, the water extract of celery seed accounts for 15%, and the water extract of chicory accounts for 10% in terms of mass percentage. The adjuvants include binders, flavoring agents, lubricants and antioxidants, wherein the binder is malt dextrin, accounting for 39%; the flavoring agent is erythritol and stevioside, erythritol accounting for 18% and stevioside accounting for 0.25%; the lubricant is magnesium stearate, accounting for 1%; and the antioxidant is citric acid and DL-malic acid, citric acid accounting for 0.5% and DL-malic acid accounting for 0.25%.

[0127] In a sterile environment, the active ingredient water extract, the binder, the flavoring agent, the lubricant and the antioxidant are mixed uniformly, and the mixture is put into a granulator for 10 minutes at a speed of 120 rpm; after granulation, it is put into a tablet press with a pressure of 40 N; and then it is packaged after being taken out, to obtain tablets.

[0128] Comparative Example 5

[0129] This comparative example provides a tablet, which is prepared by first preparing an active ingredient water extract by the same method as in Example 5; and then preparing a tablet:

[0130] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 16%, the water extract of celery seed accounts for 15%, and the water extract of chicory accounts for 10% in terms of mass percentage. The adjuvants include binders, flavoring agents, lubricants and antioxidants, wherein the binder is malt dextrin, accounting for 39%; the flavoring agent is erythritol and stevioside, erythritol accounting for 18% and stevioside accounting for 0.25%; the lubricant is magnesium stearate, accounting for 1%; and the antioxidant is citric acid and DL-malic acid, citric acid accounting for 0.5% and DL-malic acid accounting for 0.25%.

[0131] In a sterile environment, the active ingredient water extract, the binder, the flavoring agent, the lubricant and the antioxidant are mixed uniformly, and the mixture is put into a granulator for 10 minutes at a speed of 120 rpm; after granulation, it is put into a tablet press with a pressure of 40 N; and then it is packaged after being taken out, to obtain tablets.

[0132] Comparative Example 6

[0133] This comparative example provides a tablet, which is prepared by first preparing an active ingredient water extract by the same method as in Example 5; and then preparing a tablet:

[0134] The components are weighed according to the proportion, and the water extract of Cordyceps militaris accounts for 16%, the water extract of celery seed accounts for 15%, and the water extract of chicory accounts for 10% in terms of mass percentage. The adjuvants include binders, flavoring agents, lubricants and antioxidants, wherein the binder is malt dextrin, accounting for 39%; the flavoring agent is erythritol and stevioside, erythritol accounting for 18% and stevioside accounting for 0.25%; the lubricant is magnesium stearate, accounting for 1%; and the antioxidant is citric acid and DL-malic acid, citric acid accounting for 0.5% and DL-malic acid accounting for 0.25%.

[0135] The active ingredient water extract, adhesive, flavoring agent, lubricant and antioxidant are mixed uniformly under aseptic environment, and the mixture is put into a granulator for 12 min at a rotation speed of 100 rpm. After granulation, the mixture is put into a tablet press at a pressure of 100 N. After taking out, the mixture is packaged to obtain tablets.

[0136] The formulations of Comparative Examples 4 to 6 are shown in Table 4.

[0137] Table 4: Components and their contents of Comparative Examples 4 to 6

[0138]

[0139] Experimental Example: Mouse experiment on the effect of the pharmaceutical composition on the treatment of gout

[0140] The granules prepared by the method of Example 1 are added to physiological saline respectively, and stirred until dissolved completely to prepare a drug solution with a content of 1 mg / mL for standby. The tablets prepared by the method of Example 5 are added to physiological saline respectively, and stirred until dissolved completely to prepare a drug solution with a content of 1 mg / mL for standby.

[0141] SPF level mice, half male and half female, weighing 18 to 22 g, are adaptively fed for one week, and then randomly divided into 5 groups, including 1 group of blank group, 1 group of model group and 3 groups of administration groups, 10 mice in each group. Except for the blank group, all mice are injected with sodium urate crystals into the ankle joint cavity, and the injection amount is 250 mg / kg, so as to induce and construct an acute gouty arthritis mouse model. The blank group and the model group of mice are given physiological saline by gavage at a dose of 10 mL / kg, and the 1st and 2nd administration groups of mice are given drugs by gavage at a dose of 10 mL / kg, and the drug solutions prepared by the methods of Example 1 and Example 5 are used respectively. The 3rd administration group of mice is given allopurinol tablets by gavage at a dose of 10 mg / kg. After 7 days of continuous administration, the mice are sacrificed 1 hour after the administration on the 8th day, and the blood is taken from the orbital venous plexus, and the supernatant is taken after standing for 20 min and centrifugation for 20 min at a rotation speed of 3000 rpm. The serum uric acid level is determined by phosphotungstic acid method using a kit provided by Nanjing Jiancheng Biological Engineering Institute; the IL-1β level is determined by enzyme-linked immunosorbent assay using a kit provided by Nanjing Jiancheng Biological Engineering Institute, and IL-1β is a biochemical factor related to inflammation in serum. The determination results are shown in Table 5.

[0142] Table 5: Determination values of blood uric acid and IL-1β

[0143]

[0144] The results in Table 5 show that the blood uric acid and IL-1β levels of the model group mice are higher than those of the blank group, which is caused by the injection of sodium urate; the blood uric acid of the administration group mice is lower than that of the model group, and the IL-1β levels of the administration group (Example 1) and the administration group (Example 5) are lower than that of the administration group (allopurinol), indicating that the active ingredient for relieving inflammatory pain in the pharmaceutical composition of the application can exert the anti-inflammatory effect compared with the commercial drug exemplified by allopurinol tablets.

[0145] The technical features of the above-described embodiments can be combined arbitrarily, and for the sake of brevity, all possible combinations of the technical features in the above-described embodiments are not described, however, as long as the combinations of the technical features do not contradict each other, they should be considered as the scope of the description.

[0146] The above-described embodiments only express several implementation manners of the application, the description is more specific and detailed, but it should not be understood as a limitation on the scope of the patent. It should be pointed out that for ordinary skilled persons in the art, several modifications and improvements can be made without departing from the concept of the application, which are all within the protection scope of the application. Therefore, the protection scope of the patent of the application should be subject to the appended claims.

Claims

1. A pharmaceutical composition for treating gout, characterized in that, It contains three groups of active ingredients and excipients. The first group of active ingredients consists of Cordyceps militaris, celery seed, galangal, and chicory; the second group of active ingredients consists of corn silk, Lophatherum gracile, Poria cocos, and marine fish oligopeptides; and the third group of active ingredients consists of papaya and kudzu root. By mass percentage, the first group of active ingredients accounts for 17-48%, the second group of active ingredients accounts for 8-38%, and the third group of active ingredients accounts for 2.2-11%.

2. The pharmaceutical composition according to claim 1, characterized in that, The excipients include one or more of the following: adhesives, flavoring agents, lubricants, and antioxidants.

3. The pharmaceutical composition according to claim 2, characterized in that, The binder includes one or more of syrup, maltodextrin, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, and pregelatinized starch; the flavoring agent includes one or more of maltitol, sucralose, erythritol, and steviol glycosides.

4. The pharmaceutical composition according to claim 2, characterized in that, The lubricant includes one or more of magnesium stearate, talc, colloidal silica, and polyethylene glycol; the antioxidant includes one or more of citric acid, DL-malic acid, and ascorbic acid.

5. A granule for treating gout, characterized in that, The pharmaceutical composition of claim 1 includes excipients including binders and flavoring agents.

6. A tablet for treating gout, characterized in that, The pharmaceutical composition comprising the claims of claim 1, wherein the excipients include binders, flavoring agents, lubricants, and antioxidants.

7. The tablet according to claim 6, characterized in that, By mass percentage, the first group of active ingredients accounts for 30-55%, the second group of active ingredients accounts for 4-16%, and the third group of active ingredients accounts for 4-16%.

8. A method for preparing a granule for treating gout as described in claim 5, characterized in that, Includes the following steps: After drying, pulverizing, dissolving and centrifuging the active ingredient raw materials, the filtrate was concentrated and dried to obtain the water extract of the active ingredient. The active ingredients are mixed with water extracts, granulated under sterile conditions, dried, and packaged to obtain granules.

9. A method for preparing a tablet according to claim 6 or 7, characterized in that, Includes the following steps: After drying, pulverizing, dissolving and centrifuging the active ingredient raw materials, the filtrate was concentrated and dried to obtain the water extract of the active ingredient. The active ingredients are mixed with water extracts, granulated, compressed, and packaged under sterile conditions to obtain tablets.

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