Ureuqing tablet and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and relates to uremia clearing tablets and a preparation method thereof. The uremia clearing tablet is prepared from the following raw materials in parts by mass, the traditional Chinese medicine composition is prepared from the following raw materials: 40 parts of rheum officinale, 36 parts of liquorice, 160 parts of astragalus membranaceus, 120 parts of white mulberry root-bark, 80 parts of radix sophorae flavescentis, 120 parts of codonopsis pilosula, 200 parts of bighead atractylodes rhizome, 200 parts of poria cocos, 120 parts of radix paeoniae alba, 1000 parts of chrysanthemum, 200 parts of prepared fleece flower root, 120 parts of ligusticum wallichii, 200 parts of salvia miltiorrhiza, 80 parts of ginger processed pinellia, 200 parts of plantain herb, 60 parts of radix bupleuri, 400 to 600 parts of pregelatinized starch, 100 to 200 parts of hydroxypropyl-beta-cyclodextrin, 80 to 150 parts of co-treatment substance, 70 to 100 parts of low-substituted hydroxypropyl cellulose and 10 to 15 parts of anhydrous calcium hydrogen phosphate. 5-8 parts of fumaric acid and 22-32 parts of a lubricant; the uremia clearing tablet provided by the invention is good in formability, short in disintegration time limit and good in stability under the condition of no coating.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines and relates to a urea-clearing tablet and a preparation method thereof. Background Art

[0002] Chronic renal failure (CRF) is a common kidney disease characterized by a gradual decline in renal function, eventually leading to uremia.

[0003] In the field of traditional Chinese medicine, Urea Clear is a commonly used Chinese patent medicine, which is composed of 16 herbs such as rhubarb, astragalus, atractylodes, mulberry bark, tuckahoe, chuanxiong, and salvia miltiorrhiza. It has the effects of clearing the bowels and reducing turbidity, strengthening the spleen and removing dampness, and promoting blood circulation and removing blood stasis. It is used for patients with chronic renal failure, azotemia and early uremia, and those with spleen deficiency and turbidity and spleen deficiency and blood stasis according to TCM dialectical analysis. It can reduce creatinine and urea nitrogen, stabilize renal function, and delay dialysis time. It also has a certain effect on improving renal anemia, increasing blood calcium, and reducing blood scales.

[0004] However, the current clinical dosage form of Urea Clear is mainly granules, which need to be taken with water. For some patients, especially the elderly and children, it is inconvenient to take, which affects the patient's compliance. Tablets are more convenient to take than granules, so it is very necessary to develop Urea Clear tablets.

[0005] The Chinese patent with the publication number CN1672709A in the prior art discloses a urea-clearing tablet, the main ingredients of which are: rhubarb, licorice, astragalus, mulberry bark, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, poria, white peony root, chrysanthemum, processed polygonum multiflorum, chuanxiong, salvia miltiorrhiza, ginger pinellia, plantain, bupleurum. The auxiliary materials are appropriate. The preparation method is: take 2-3% of rhubarb, licorice, and bupleurum by weight, 6-8% of astragalus, mulberry bark, codonopsis pilosula, white peony root, chuanxiong, 2-5% of sophora flavescens, chrysanthemum, ginger pinellia, atractylodes macrocephala, poria, processed polygonum multiflorum, salvia miltiorrhiza, and plantain by weight. The above medicinal materials are boiled in water for 3 times, the first time for 3 hours, the second and third times for 2 hours each time, the decoction is combined, concentrated into a clear paste with a relative density of 1.25 (measured at 80°C), dried into a dry paste, crushed into fine powder, passed through a 120-mesh sieve, and set aside. Mix the dry paste powder with appropriate amount of auxiliary materials, granulate and dry. Press the granules into plain tablets or film-coat them. The urea-clearing tablets are composed of drugs and fillers, which are easy to carry, small in dosage and convenient to take.

[0006] However, compared with granules, tablets have defects such as poor solubility and long disintegration time, and the above technical solution does not address this problem. Summary of the invention

[0007] The object of the present invention is to provide a urea-clearing tablet and a preparation method thereof. The urea-clearing tablet provided by the present invention has good formability, a short disintegration time and good long-term stability without coating.

[0008] The first aspect of the present invention provides a urea-clearing tablet, which comprises, by weight, 40 parts of rhubarb, 36 parts of liquorice, 160 parts of astragalus, 120 parts of mulberry bark, 80 parts of sophora flavescens, 120 parts of codonopsis pilosula, 200 parts of atractylodes macrocephala, 200 parts of tuckahoe, 120 parts of white peony root, 1000 parts of chrysanthemum, 200 parts of processed Polygonum multiflorum, 120 parts of ligusticum chuanxiong, 200 parts of salvia miltiorrhiza, 80 parts of ginger pinellia, 200 parts of plantain, 60 parts of bupleurum, 400-600 parts of pregelatinized starch, 100-200 parts of hydroxypropyl-β-cyclodextrin, 80-150 parts of co-processed product, 70-100 parts of low-substituted hydroxypropyl cellulose, 10-15 parts of anhydrous calcium hydrogen phosphate, 5-8 parts of fumaric acid, and 22-32 parts of lubricant.

[0009] In some preferred embodiments, the co-processed product is a mixture of a microcrystalline cellulose colloidal silicon dioxide co-processed product and a microcrystalline cellulose lactose co-processed product, and the mass ratio of the two is 1-3:4-8, preferably 1.5-2.5:5-7, and further preferably 2:6.

[0010] The inventors unexpectedly discovered during the research and development process that mixing a mixture of a co-processed product of microcrystalline cellulose colloidal silicon dioxide and a co-processed product of microcrystalline cellulose lactose with a clear paste, and then drying, crushing, and making a dry powder, and directly tableting, can improve the tableting effect of the urea-clearing tablet. The obtained urea-clearing tablets have low friability and no cracking phenomenon; and have a good disintegration rate, especially after long-term storage. Still have a good disintegration rate.

[0011] In some preferred embodiments, the microcrystalline cellulose colloidal silicon dioxide co-processed product is produced by Zhuhai Dongchen Pharmaceutical Co., Ltd. TMS series products are preferred TMS 635.

[0012] In some preferred embodiments, the microcrystalline cellulose lactose co-processed product is produced by Zhuhai Dongchen Pharmaceutical Co., Ltd. TMC series products are preferred TMC-935.

[0013] In some preferred embodiments, the mass ratio of the pregelatinized starch, hydroxypropyl-β-cyclodextrin, co-processed product and low-substituted hydroxypropyl cellulose is 23-27:6-9:5-7:4-5, preferably 24-26:7-8:5.5-6.5:4.2-4.7, and further preferably 25:8:6:4.5.

[0014] The application of Chinese patent medicines with Chinese herbal medicine extracts as active ingredients as tablets is limited by the poor fluidity and compressibility of Chinese herbal medicine extracts. The inventors found through creative research and development that when pregelatinized starch, hydroxypropyl-β-cyclodextrin, co-processed product and low-substituted hydroxypropyl cellulose are added to the present invention and the mass ratio is controlled to be 23-27:6-9:5-7:4-5, the pregelatinized starch, hydroxypropyl-β-cyclodextrin, co-processed product and low-substituted hydroxypropyl cellulose work together to achieve a good tableting effect, and the obtained urea-clearing tablets have low friability and no cracking phenomenon; and the disintegration and stability are also improved. At the same time, it was unexpectedly found that when the hydroxypropoxy content of the low-substituted hydroxypropyl cellulose is 10-12.9% and the average particle size is 40-45μm, the effect is better.

[0015] In some preferred embodiments, the low-substituted hydroxypropyl cellulose has a hydroxypropoxy content of 10-12.9% and an average particle size of 40-45 μm.

[0016] In some preferred embodiments, the mass ratio of anhydrous calcium hydrogen phosphate to fumaric acid is 12-14:6-7, preferably 12.5-13.5:6.5, and further preferably 13:6.5.

[0017] The inventors found during the research and development process that the urea-clearing tablets obtained without coating have good tableting effect and disintegration speed, but their water content and microbial content increase rapidly after long-term storage. In order to solve this technical problem, the present invention creatively adds anhydrous calcium hydrogen phosphate and fumaric acid. Under a specific ratio, the two work together not only to avoid the increase of water content and microbial content after long-term storage, but also to further improve the tableting effect.

[0018] In a preferred embodiment, the raw materials of the Urea Clearing Tablets include, by weight: 40 parts of rhubarb, 36 parts of liquorice, 160 parts of astragalus, 120 parts of mulberry bark, 80 parts of sophora flavescens, 120 parts of Codonopsis pilosula, 200 parts of Atractylodes macrocephala, 200 parts of Poria, 120 parts of white peony root, 1000 parts of chrysanthemum, 200 parts of processed Polygonum multiflorum, 120 parts of Chuanxiong, 200 parts of Salvia miltiorrhiza, 80 parts of Pinellia ternata, 200 parts of Plantago, 60 parts of Bupleurum, 500 parts of pregelatinized starch, 160 parts of hydroxypropyl-β-cyclodextrin, 120 parts of co-processed product, 90 parts of low-substituted hydroxypropyl cellulose, 13 parts of anhydrous calcium hydrogen phosphate, 6.5 parts of fumaric acid, and 28 parts of lubricant.

[0019] In some preferred embodiments, the lubricant includes at least one of magnesium stearate, calcium stearate, hard sodium fumarate, colloidal silicon dioxide, and talc, preferably magnesium stearate.

[0020] The second aspect of the present invention provides a method for preparing the above-mentioned Urea Clearing Tablets, comprising the following steps:

[0021] S1. Add water to rhubarb, licorice, astragalus, mulberry bark, sophora flavescens, codonopsis, atractylodes, poria, white peony root, chrysanthemum, processed Polygonum multiflorum, ligusticum chuanxiong, salvia miltiorrhiza, ginger pinellia, plantain, and bupleurum, and boil three times, combine the filtrate, filter, and concentrate the filtrate into a clear paste, mix the clear paste with the co-processed product, dry, and crush to obtain a dry powder;

[0022] S2. Evenly mix the dry powder, pregelatinized starch, hydroxypropyl-β-cyclodextrin, low-substituted hydroxypropyl cellulose, anhydrous calcium hydrogen phosphate, fumaric acid and lubricant, and press into tablets.

[0023] Preferably, the first and second decoction times are 1.5-2.5 h, and the third decoction time is 0.5-1.5 h.

[0024] Most preferably, the first and second decoction times are 2 hours, and the third decoction time is 1 hour.

[0025] Preferably, the filtrate is concentrated to a clear paste having a relative density of 1.25 (80° C.).

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] 1. The present invention adopts pregelatinized starch, hydroxypropyl-β-cyclodextrin, co-processed product, and low-substituted hydroxypropyl cellulose (hydroxypropoxy content is 10-12.9%, and average particle size is 40-45 μm) in a specific proportion. Through the joint action, the tableting effect is good, and the obtained urea-clearing tablets have low friability and no fragmentation phenomenon; and the disintegration and stability are also improved.

[0028] 2. The microcrystalline cellulose colloidal silicon dioxide co-processed product and the microcrystalline cellulose lactose co-processed product of the present invention work together to improve the tableting effect of the urea-clearing tablets while obtaining urea-clearing tablets with good disintegration rate, especially after long-term storage, the urea-clearing tablets still have a good disintegration rate, thereby ensuring the disintegration stability of the urea-clearing tablets during long-term storage.

[0029] 3. The present invention adopts a specific ratio of anhydrous calcium hydrogen phosphate, fumaric acid and pregelatinized starch, hydroxypropyl-β-cyclodextrin, co-processed product and low-substituted hydroxypropyl cellulose to jointly improve the tableting effect and the long-term stability of the urea-clearing tablets without coating (low hygroscopicity and microbial content meeting the standards). DETAILED DESCRIPTION

[0030] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is only an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the invention of the present invention based on the disclosed content, and they should also fall within the scope of the present invention.

[0031] When the embodiments give numerical ranges, it should be understood that, unless otherwise specified in the present invention, both endpoints of each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as those generally understood by those skilled in the art. In addition to the specific methods, equipment, and materials used in the embodiments, according to the grasp of the prior art by those skilled in the art and the record of the present invention, any methods, equipment, and materials of the prior art similar or equivalent to the methods, equipment, and materials described in the embodiments of the present invention can also be used to realize the present invention.

[0032] The present invention will be further described below by way of specific embodiments.

[0033] The source information of the raw materials involved in the following examples or comparative examples is shown in Table 1:

[0034] Table 1

[0035]

[0036]

[0037] Example 1

[0038] A urea-clearing tablet, comprising the following raw materials, measured by weight: 40 parts of rhubarb, 36 parts of liquorice, 160 parts of astragalus, 120 parts of mulberry bark, 80 parts of sophora flavescens, 120 parts of codonopsis pilosula, 200 parts of atractylodes macrocephala, 200 parts of tuckahoe, 120 parts of white peony root, 1000 parts of chrysanthemum, 200 parts of processed radix polygoni multiflori, 120 parts of ligusticum chuanxiong, 200 parts of salvia miltiorrhiza, 80 parts of ginger pinellia, 200 parts of plantain, 60 parts of bupleurum, 400 parts of pregelatinized starch, 100 parts of hydroxypropyl-β-cyclodextrin, 80 parts of co-processed product, 70 parts of low-substituted hydroxypropyl cellulose, 10 parts of anhydrous calcium hydrogen phosphate, 5 parts of fumaric acid and 22 parts of magnesium stearate.

[0039] The co-processed product is a mixture of a microcrystalline cellulose colloidal silicon dioxide co-processed product and a microcrystalline cellulose lactose co-processed product, and the mass ratio of the two is 1:4.

[0040] The low-substituted hydroxypropyl cellulose has a hydroxypropoxy content of 10-12.9% and an average particle size of 40 μm.

[0041] The preparation method of the above-mentioned urea-clearing tablets is specifically as follows:

[0042] S1. Add water to rhubarb, licorice, astragalus, mulberry bark, sophora flavescens, codonopsis, atractylodes, poria, white peony root, chrysanthemum, processed Polygonum multiflorum, ligusticum chuanxiong, salvia miltiorrhiza, ginger pinellia, plantain, and bupleurum, and decoct three times. The first and second decoction times are 2 hours, and the third decoction time is 1 hour. Combine the filtrate, filter, and concentrate the filtrate to a clear paste with a relative density of 1.25 (80°C). Mix the clear paste and the co-processed product evenly, dry, and grind to obtain a dry powder;

[0043] S2. Evenly mix the dry powder, pregelatinized starch, hydroxypropyl-β-cyclodextrin, low-substituted hydroxypropyl cellulose, anhydrous calcium hydrogen phosphate, fumaric acid and lubricant, and press into tablets.

[0044] Example 2

[0045] A urea-clearing tablet, comprising the following raw materials, measured by weight: 40 parts of rhubarb, 36 parts of liquorice, 160 parts of astragalus, 120 parts of mulberry bark, 80 parts of sophora flavescens, 120 parts of codonopsis pilosula, 200 parts of atractylodes macrocephala, 200 parts of tuckahoe, 120 parts of white peony root, 1000 parts of chrysanthemum, 200 parts of processed radix polygoni multiflori, 120 parts of ligusticum chuanxiong, 200 parts of salvia miltiorrhiza, 80 parts of ginger pinellia, 200 parts of plantain, 60 parts of bupleurum, 600 parts of pregelatinized starch, 200 parts of hydroxypropyl-β-cyclodextrin, 150 parts of co-processed product, 100 parts of low-substituted hydroxypropyl cellulose, 15 parts of anhydrous calcium hydrogen phosphate, 8 parts of fumaric acid and 32 parts of magnesium stearate.

[0046] The co-processed product is a mixture of a microcrystalline cellulose colloidal silicon dioxide co-processed product and a microcrystalline cellulose lactose co-processed product, and the mass ratio of the two is 3:8.

[0047] The low-substituted hydroxypropyl cellulose has a hydroxypropoxy content of 10-12.9% and an average particle size of 40 μm.

[0048] The preparation method of the above-mentioned Urea Clearing Tablets is the same as that of Example 1.

[0049] Example 3

[0050] A urea-clearing tablet, comprising the following raw materials, measured by weight: 40 parts of rhubarb, 36 parts of liquorice, 160 parts of astragalus, 120 parts of mulberry bark, 80 parts of sophora flavescens, 120 parts of codonopsis pilosula, 200 parts of atractylodes macrocephala, 200 parts of tuckahoe, 120 parts of white peony root, 1000 parts of chrysanthemum, 200 parts of processed radix polygoni multiflori, 120 parts of ligusticum chuanxiong, 200 parts of salvia miltiorrhiza, 80 parts of ginger pinellia, 200 parts of plantain, 60 parts of bupleurum, 500 parts of pregelatinized starch, 160 parts of hydroxypropyl-β-cyclodextrin, 120 parts of co-processed product, 90 parts of low-substituted hydroxypropyl cellulose, 13 parts of anhydrous calcium hydrogen phosphate, 6.5 parts of fumaric acid and 28 parts of magnesium stearate.

[0051] The co-processed product is a mixture of a microcrystalline cellulose colloidal silicon dioxide co-processed product and a microcrystalline cellulose lactose co-processed product, and the mass ratio of the two is 2:6.

[0052] The low-substituted hydroxypropyl cellulose has a hydroxypropoxy content of 10-12.9% and an average particle size of 40 μm.

[0053] The preparation method of the above-mentioned Urea Clearing Tablets is the same as that of Example 1.

[0054] Comparative Example 1

[0055] The difference from Example 3 is that the microcrystalline cellulose colloidal silicon dioxide co-processed product is replaced with microcrystalline cellulose lactose co-processed product of the same mass, and the rest are the same.

[0056] Comparative Example 2

[0057] The only difference from Example 3 is that the microcrystalline cellulose lactose co-processed product is replaced with microcrystalline cellulose mannitol co-processed product of equal mass, and the rest is the same.

[0058] Comparative Example 3

[0059] The only difference from Example 3 is that the pregelatinized starch is replaced with microcrystalline cellulose of the same mass, and the rest is the same.

[0060] Comparative Example 4

[0061] The only difference from Example 3 is that the hydroxypropoxy content of the low-substituted hydroxypropyl cellulose is 10-12.9%, and the average particle size is 50 μm, and the rest are the same.

[0062] Comparative Example 5

[0063] The only difference from Example 3 is that the mass ratio of the pregelatinized starch, hydroxypropyl-β-cyclodextrin, co-processed product and low-substituted hydroxypropyl cellulose is 30:5:8:3;

[0064] That is, the raw materials of the Urea Clearing Tablets are as follows, by mass: 40 parts of rhubarb, 36 parts of liquorice, 160 parts of astragalus, 120 parts of mulberry bark, 80 parts of sophora flavescens, 120 parts of codonopsis pilosula, 200 parts of atractylodes, 200 parts of tuckahoe, 120 parts of white peony root, 1000 parts of chrysanthemum, 200 parts of processed Polygonum multiflorum, 120 parts of ligusticum chuanxiong, 200 parts of salvia miltiorrhiza, 80 parts of ginger pinellia, 200 parts of plantain, 60 parts of bupleurum, 600 parts of pregelatinized starch, 100 parts of hydroxypropyl-β-cyclodextrin, 160 parts of co-processed product, 60 parts of low-substituted hydroxypropyl cellulose, 13 parts of anhydrous calcium hydrogen phosphate, 6.5 parts of fumaric acid, and 28 parts of magnesium stearate.

[0065] Comparative Example 6

[0066] The only difference from Example 3 is that anhydrous calcium hydrogen phosphate is replaced with calcium phosphate of equal mass, and the rest is the same.

[0067] Comparative Example 7

[0068] The only difference from Example 3 is that fumaric acid is replaced by tartaric acid of equal mass, and the rest are the same.

[0069] Comparative Example 8

[0070] The only difference from Example 3 is that the mass ratio of anhydrous calcium hydrogen phosphate to fumaric acid is 10:10;

[0071] That is, the raw materials of the Urea Clearing Tablets are as follows, by mass: 40 parts of rhubarb, 36 parts of liquorice, 160 parts of astragalus, 120 parts of mulberry bark, 80 parts of sophora flavescens, 120 parts of codonopsis pilosula, 200 parts of atractylodes, 200 parts of tuckahoe, 120 parts of white peony root, 1000 parts of chrysanthemum, 200 parts of processed Polygonum multiflorum, 120 parts of ligusticum chuanxiong, 200 parts of salvia miltiorrhiza, 80 parts of ginger pinellia, 200 parts of plantain, 60 parts of bupleurum, 500 parts of pregelatinized starch, 160 parts of hydroxypropyl-β-cyclodextrin, 120 parts of co-processed product, 90 parts of low-substituted hydroxypropyl cellulose, 10 parts of anhydrous calcium hydrogen phosphate, 10 parts of fumaric acid, and 28 parts of magnesium stearate.

[0072] Experimental Example 1 Quality Inspection of Uridine Tablets:

[0073] Appearance: Observe with naked eyes;

[0074] Hardness: Use a tablet hardness tester to test. Place the tablet in the fixture of the hardness tester and gradually apply pressure until the tablet breaks.

[0075] Friability: Tested according to the 2020 edition of the Chinese Pharmacopoeia, Part III (General Rule 0923);

[0076] Tablet weight difference detection method: Take 20 Urea Clearing Tablets, accurately weigh the total weight, calculate the average tablet weight, then accurately weigh each tablet, and compare the weight of each tablet with the average tablet weight. The results are shown in Table 2.

[0077] Table 2

[0078] Appearance Hardness / N Friability / % Tablet weight difference / % Example 1 Smooth, no cracks 98 0.3 ±1.2 Example 2 Smooth, no cracks 97 0.4 ±1.1 Example 3 Smooth, no cracks 98 0.2 ±0.9 Comparative Example 1 Basically smooth, with cracks 75 1.1 ±2.6 Comparative Example 2 Basically smooth, with cracks 72 1.3 ±4.1 Comparative Example 3 There are pockmarks and cracks 60 2.8 ±8.5 Comparative Example 4 Basically smooth, with cracks 70 1.5 ±5.2 Comparative Example 5 Occasionally pockmarked or with cracks 66 2.0 ±6.8 Comparative Example 6 Occasionally pockmarked or with cracks 68 1.8 ±6.5 Comparative Example 7 Smooth, no cracks 96 0.4 ±1.0 Comparative Example 8 Smooth, no cracks 90 1.0 ±2.2

[0079] As can be seen from Table 2, the Urea Clearing Tablets obtained in Examples 1-3 of the present invention have good tableting effect, smooth appearance, no cracks, high hardness, and low friability and tablet weight differences;

[0080] The compression effect of the obtained Urea Clearing Tablets decreased, the tablet splitting phenomenon occurred, the hardness decreased, and the friability and tablet weight differences increased in Comparative Examples 1 and 2 due to the changes in the composition of the co-processed product, Comparative Example 3 due to the replacement of pregelatinized starch with an equal mass of microcrystalline cellulose, Comparative Example 4 due to the change in the average particle size of low-substituted hydroxypropyl cellulose, Comparative Example 5 due to the mass ratio of pregelatinized starch, hydroxypropyl-β-cyclodextrin, co-processed product and low-substituted hydroxypropyl cellulose not being in the range of 23-27:6-9:5-7:4-5, and Comparative Example 6 due to the replacement of anhydrous calcium hydrogen phosphate with an equal mass of calcium phosphate.

[0081] Experimental Example 2: Disintegration time limit test of Urea Clear Tablets, test method: test according to Part III (General Rule 0921) of the 2020 edition of the Chinese Pharmacopoeia. The results are shown in Table 3.

[0082] Table 3

[0083]

[0084]

[0085] Experimental Example 3: Disintegration time of Urea Clear Tablets after storage at 25°C for 12 months, test method: test according to Part III (General Rule 0921) of the 2020 edition of the Chinese Pharmacopoeia. The results are shown in Table 4.

[0086] Table 4

[0087] Disintegration time / min Example 1 30 Example 2 29 Example 3 26 Comparative Example 1 48 Comparative Example 2 55 Comparative Example 3 38 Comparative Example 4 32 Comparative Example 5 35 Comparative Example 6 31 Comparative Example 7 28 Comparative Example 8 30

[0088] It can be seen from Table 3 and Table 4 that the Urea Clear Tablets obtained in Examples 1-3 of the present invention have good disintegration effect, and still have a fast disintegration speed even after long-term storage; the disintegration performance of the obtained Urea Clear Tablets in Comparative Examples 1 and 2 is significantly reduced due to the change in the composition of the co-processed product; the disintegration performance of the obtained Urea Clear Tablets in Comparative Example 3 is also reduced due to the replacement of pregelatinized starch with microcrystalline cellulose of the same mass, and the mass ratio of pregelatinized starch, hydroxypropyl-β-cyclodextrin, co-processed product and low-substituted hydroxypropyl cellulose in Comparative Example 5 is not within the range of 23-27:6-9:5-7:4-5.

[0089] Experimental Example 4 Long-term stability of urea-clearing tablets (25±2°C, 60±10%RH):

[0090] Moisture content: The moisture content of Urea Clearing Tablets after long-term storage was tested according to Part III of the 2020 edition of the Chinese Pharmacopoeia (General Rule 0832);

[0091] Microbial limit: The number of microorganisms in Urea Clearing Tablets after long-term storage is tested according to Part III of the 2020 edition of the Chinese Pharmacopoeia (General Rule 1105).

[0092] Rhubarb content: The rhubarb content of Urea Clearance Tablets after long-term storage was tested according to the HPLC method (General Rule 0512) in the 2020 edition of the Chinese Pharmacopoeia; the rhubarb content was calculated based on the total anthraquinone content of rhubarb;

[0093] Astragalus content: The Astragalus content of Urea Clearing Tablets after long-term storage was tested according to the HPLC method (General Rule 0512) in the 2020 edition of the Chinese Pharmacopoeia; the Astragalus content was calculated as the total amount of Astragaloside IV;

[0094] The results are shown in Tables 5 and 6.

[0095] Table 5

[0096]

[0097]

[0098] Table 6

[0099]

[0100]

[0101] It can be seen from Table 5 and Table 6 that the Urea Clearing Tablets obtained in Examples 1-3 of the present invention have good long-term stability without coating (low hygroscopicity, microbial content meets the standard, rhubarb content reduction rate is 1.21-1.64%; astragalus content reduction rate is 0.77-1%).

[0102] In Comparative Example 2, since the microcrystalline cellulose lactose co-processed product was replaced with an equal mass of microcrystalline cellulose mannitol co-processed product, in Comparative Example 3, since the pregelatinized starch was replaced with an equal mass of microcrystalline cellulose, and in Comparative Example 5, since the mass ratio of pregelatinized starch, hydroxypropyl-β-cyclodextrin, co-processed product and low-substituted hydroxypropyl cellulose was not in the range of 23-27:6-9:5-7:4-5, the stability of the obtained urea-clearing tablets decreased, but the change was not particularly large; in Comparative Example 6, since anhydrous calcium hydrogen phosphate was replaced with an equal mass of calcium phosphate; in Comparative Example 7, since fumaric acid was replaced with an equal mass of tartaric acid; in Comparative Example 8, since the mass ratio of anhydrous calcium hydrogen phosphate and fumaric acid was not in the range of 1-3:4-8, the stability of the obtained urea-clearing tablets decreased significantly (the water content after 12 months increased significantly, the total number of aerobic bacteria, molds and yeasts also increased significantly, and the reduction rate of rhubarb content and the reduction rate of astragalus content also increased).

[0103] 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 urea-clearing tablet, characterized in that: The raw materials include, by mass, 40 parts of rhubarb, 36 parts of licorice, 160 parts of astragalus, 120 parts of mulberry bark, 80 parts of sophora flavescens, 120 parts of codonopsis pilosula, 200 parts of atractylodes, 200 parts of tuckahoe, 120 parts of white peony root, 1000 parts of chrysanthemum, 200 parts of processed Polygonum multiflorum, 120 parts of ligusticum chuanxiong, 200 parts of salvia miltiorrhiza, 80 parts of ginger pinellia, 200 parts of plantain, 60 parts of bupleurum, 400-600 parts of pregelatinized starch, 100-200 parts of hydroxypropyl-β-cyclodextrin, 80-150 parts of co-processed product, 70-100 parts of low-substituted hydroxypropyl cellulose, 10-15 parts of anhydrous calcium hydrogen phosphate, 5-8 parts of fumaric acid, and 22-32 parts of lubricant.

2. The urea-clearing tablet according to claim 1, characterized in that The co-processed product is a mixture of a co-processed microcrystalline cellulose colloidal silicon dioxide product and a co-processed microcrystalline cellulose lactose product, and the mass ratio of the co-processed microcrystalline cellulose and lactose is 1-3:4-8.

3. The urea-clearing tablet according to claim 2, characterized in that: The mass ratio of the microcrystalline cellulose colloidal silicon dioxide co-processed product to the microcrystalline cellulose lactose co-processed product is 2:

6.

4. The urea-clearing tablet according to claim 1, characterized in that: The mass ratio of the pregelatinized starch, hydroxypropyl-β-cyclodextrin, the co-processed product and the low-substituted hydroxypropyl cellulose is 23-27:6-9:5-7:4-5.

5. The urea-clearing tablet according to claim 4, characterized in that: The mass ratio of the pregelatinized starch, hydroxypropyl-β-cyclodextrin, the co-processed product and the low-substituted hydroxypropyl cellulose is 25:8:6:4.

5.

6. The urea-clearing tablet according to claim 1, characterized in that: The mass ratio of the anhydrous calcium hydrogen phosphate to fumaric acid is 12-14:6-7.

7. The urea-clearing tablet according to claim 6, characterized in that: The mass ratio of the anhydrous calcium hydrogen phosphate to fumaric acid is 13:6.

5.

8. The urea-clearing tablet according to claim 1, characterized in that: The low-substituted hydroxypropyl cellulose has a hydroxypropoxy content of 10-12.9% and an average particle size of 40 μm.

9. The urea-clearing tablet according to claim 1, characterized in that: The raw materials include, by mass: 40 parts of rhubarb, 36 parts of licorice, 160 parts of astragalus, 120 parts of mulberry bark, 80 parts of sophora flavescens, 120 parts of codonopsis pilosula, 200 parts of atractylodes, 200 parts of tuckahoe, 120 parts of white peony root, 1000 parts of chrysanthemum, 200 parts of processed Polygonum multiflorum, 120 parts of ligusticum chuanxiong, 200 parts of salvia miltiorrhiza, 80 parts of ginger pinellia, 200 parts of plantain, 60 parts of bupleurum, 500 parts of pregelatinized starch, 160 parts of hydroxypropyl-β-cyclodextrin, 120 parts of co-processed product, 90 parts of low-substituted hydroxypropyl cellulose, 13 parts of anhydrous calcium hydrogen phosphate, 6.5 parts of fumaric acid, and 28 parts of lubricant.

10. The method for preparing the urine drug-clearing tablet according to any one of claims 1 to 9, characterized in that: The following steps are involved: S1. Add water to rhubarb, licorice, astragalus, mulberry bark, sophora flavescens, codonopsis, atractylodes, poria, white peony root, chrysanthemum, processed Polygonum multiflorum, ligusticum chuanxiong, salvia miltiorrhiza, ginger pinellia, plantain, and bupleurum, and boil three times, combine the filtrate, filter, and concentrate the filtrate into a clear paste, mix the clear paste with the co-processed product, dry, and crush to obtain a dry powder; S2. Evenly mix the dry powder, pregelatinized starch, hydroxypropyl-β-cyclodextrin, low-substituted hydroxypropyl cellulose, anhydrous calcium hydrogen phosphate, fumaric acid and lubricant, and press into tablets.

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