Urinary toxin removing capsule and preparation method thereof

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a uremia clearing capsule and a preparation method thereof. The uremia clearing dry paste powder comprises the following raw materials in parts by weight: 60-80 parts of uremia clearing dry paste powder, 20-40 parts of a filling agent and 0.005-0.02 part of a lubricating agent, the filling agent comprises corn starch, pregelatinized starch and mannitol. The preparation method of the capsule comprises the following steps: mixing the uremia clearing dry paste powder, the filling agent and part of the lubricating agent, performing dry granulation, mixing granules and the remaining lubricating agent, and filling to prepare the capsule. By selecting the filling agent, the hygroscopicity of the content can be effectively reduced, and the stability of the capsule is improved; moreover, the dry paste powder can be successfully tableted and granulated by adopting a dry granulation process, a roller is not adhered, the granule forming rate is high, and a complex wet granulation process is avoided. And the process conditions of the dry paste powder are optimized, and the dry paste powder is prepared into capsules, so that the compliance of patients is improved.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to a urea-clearing capsule and a preparation method thereof. Background Art

[0002] The basic formula of Urea Clearing Granules is made of rhubarb and astragalus as the main ingredients, with raw materials such as Morus alba, Sophora flavescens, Codonopsis pilosula, Atractylodes macrocephala, Poria cocos, Polygonum multiflorum, White peony root, Salvia miltiorrhiza, Chuanxiong, Chrysanthemum, Pinellia ternata, Plantago, Bupleurum and Licorice. It can clear the bowels and reduce turbidity, strengthen the spleen and eliminate dampness, and promote blood circulation and remove blood stasis. It is commonly used for chronic renal failure, azotemia stage and early stage of uremia, and patients with spleen deficiency and dampness turbidity and spleen deficiency and blood stasis according to TCM syndrome differentiation.

[0003] Capsules have the advantages of reducing the effect of irritating drugs on the stomach, covering up the unpleasant smell of drugs, increasing patient compliance, avoiding the deterioration of drug components that are prone to moisture absorption, and improving drug stability. In addition, the drug is directly filled into the capsule shell in the form of powder or granules, which can be quickly dispersed, dissolved and absorbed in the gastrointestinal tract. However, there are also certain disadvantages. For example, easily soluble drugs, easily weathered drugs, hygroscopic drugs, etc. can easily make the capsule wall soft or brittle, which is not conducive to the long-term storage of capsules.

[0004] Urea Clearing Granules contain more than a dozen Chinese medicinal materials, and their extracts contain a considerable amount of sugar substances. The dry powder is hygroscopic and sticky, which brings difficulties to the preparation and stability of the capsules.

[0005] At present, China's invention patent application CN1672711A discloses a Urea-clearing capsule and its preparation method. Specifically, the preparation method is as follows: by weight, 2-3% each of rhubarb, liquorice, and bupleurum, 6-8% each of astragalus, mulberry bark, codonopsis, white peony root, and ligusticum chuanxiong, 2-5% each of sophora flavescens, chrysanthemum, and ginger pinellia, and 8-11% each of atractylodes, poria, processed polygonum multiflorum, salvia miltiorrhiza, and plantain. The above-mentioned medicinal materials are decocted with water for 3 times, the first time for 3 hours, and the second and third times for 2 hours each time, and the decoction is combined and 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, sieved through a 120-mesh sieve, and used for standby use. The dry paste powder is mixed with an appropriate amount of auxiliary materials, granulated, and dried. The granules are filled into capsules to obtain.

[0006] The above method also does not improve the storage stability problem of capsules. In addition, the dosage of drugs in the prior art is large and the patient compliance is poor. Many problems need to be improved. Summary of the invention

[0007] In view of the deficiencies in the prior art, the present invention provides a urine drug removal composition and a preparation method thereof.

[0008] In order to achieve the purpose of the present invention, the technical solution adopted is as follows:

[0009] A urea-clearing composition, characterized in that, by weight, the raw materials of the composition include 60-80 parts of urea-clearing dry paste powder, 20-40 parts of filler and 0.005-0.02 parts of lubricant;

[0010] The fillers include corn starch, pregelatinized starch and mannitol.

[0011] Preferably, the mass ratio of the corn starch, pregelatinized starch and mannitol is 1-2:1:0.2-0.6.

[0012] Preferably, the lubricant is selected from at least one of polyethylene glycol, micropowder silica gel and magnesium lauryl sulfate.

[0013] Preferably, the lubricant comprises magnesium lauryl sulfate.

[0014] Preferably, the raw materials of the urea-clearing paste powder include the following components in parts by weight: rhubarb, astragalus, mulberry bark, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, poria, processed Polygonum multiflorum, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and licorice.

[0015] Preferably, the mass ratio of rhubarb, astragalus, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, tuckahoe, mulberry bark, white peony root, salvia miltiorrhiza, ligusticum chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and liquorice is 1:4:3:2:3:5:5:5:3:5:3:2.5:2:5:1.5:0.9;

[0016] Preferably, the preparation method of the urea-clearing paste powder comprises the following steps:

[0017] (1) Rhubarb, astragalus, mulberry bark, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, poria, prepared shouwu, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and liquorice are mixed, soaked in water, extracted, filtered and concentrated to obtain an extract;

[0018] (2) adding the extract to an ethanol solution for alcohol precipitation, filtering, and collecting the filtrate;

[0019] (3) Recover the ethanol in the alcohol precipitation filtrate, concentrate it, and dry it.

[0020] Preferably, the extraction temperature in step (1) is 75-85°C, the extraction time is 1-3h, the number of extractions is 1-3 times, and the relative density of the extract at 80°C is 1.2-1.4.

[0021] Preferably, the ethanol in step (2) is an ethanol aqueous solution with a volume concentration of 55-85%, and the alcohol precipitation time is 8-24h.

[0022] Preferably, the ethanol in step (2) is an ethanol aqueous solution with a volume concentration of 55-70%, and the extraction is a heating reflux extraction.

[0023] Preferably, acetone with a volume concentration of 5-10% is added to the ethanol solution in step (2). Adding acetone can better remove impurities and extract and purify the active components.

[0024] Preferably, the concentration in step (3) is to concentrate to a relative density of 1.2-1.4 (80° C.), and the drying method is vacuum drying, freeze drying, spray drying or vacuum belt drying.

[0025] Another object of the present invention is to provide a method for preparing the above-mentioned urea-clearing composition, comprising the following steps:

[0026] The urea-clearing paste powder, filler and part of lubricant are mixed, granulated by dry method, the granules are mixed with the remaining lubricant and filled into capsules.

[0027] Preferably, the process conditions of dry granulation include: the rotation speed of the tableting roller is 1.50 r / min, the feed speed is 23.8 r / min; and the partial lubricant is 30-60% lubricant by mass.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] (1) The present invention selects corn starch-pregelatinized starch-mannitol as a filler, which can effectively reduce the hygroscopicity of the content and improve the stability of the capsule; and after premixing and compounding of special raw materials, the dry paste powder can be successfully tableted and granulated using a dry granulation process, which does not stick to the roller and has a high particle forming rate, avoiding the complex process of wet granulation. When using ethanol wet granulation, special care should be taken when drying the particles.

[0030] (2) The present invention also screens lubricants and selects magnesium lauryl sulfate, which is more suitable for the dry granulation of the present invention and is mixed with fillers to achieve better tableting effect and prevent wheel sticking.

[0031] (3) The present invention optimizes the process conditions of dry paste powder, adopts a combination of water extraction and alcohol precipitation purification, extracts the maximum content of active ingredients, reduces the daily dosage, makes it into capsules, and improves patient compliance. DETAILED DESCRIPTION

[0032] The present invention will be further described below in conjunction with specific implementation modes.

[0033] Example 1

[0034] Urea Clearing Capsules, calculated by weight, contain the following raw materials:

[0035] 70 parts of urea-clearing paste powder; the raw materials of urea-clearing paste powder are: the mass ratio of rhubarb, astragalus, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, tuckahoe, mulberry bark, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and liquorice is 1:4:3:2:3:5:5:5:3:5:3:2.5:2:5:1.5:0.9;

[0036] Filler (corn starch, pregelatinized starch and mannitol in a mass ratio of 1:1:0.5) 30 parts;

[0037] Lubricant: 0.01 parts of magnesium lauryl sulfate.

[0038] The preparation method of Urea Clearing Capsule is as follows:

[0039] (1) Rhubarb, astragalus, mulberry bark, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, poria, prepared shouwu, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and liquorice are mixed, soaked in 5 times the amount of water for 30 min, extracted twice at 80° C., each extraction time for 0.5 h, filtered, concentrated to a relative density of 1.3 at 80° C., and an extract is obtained;

[0040] (2) Add 75% ethanol aqueous solution to the extract, stir, place in a -4°C refrigerator for 12 h, filter, and collect the filtrate;

[0041] (3) Recovering the ethanol from the alcohol precipitation filtrate, concentrating the filtrate to a relative density of 1.3 at 80° C., and vacuum drying to obtain the urea-clearing paste powder.

[0042] (4) The urea-clearing dry paste powder, filler, and 50% by mass of lubricant are mixed, dry granulated, passed through a No. 4 sieve, the granules are mixed with the remaining lubricant, and filled into capsules; the dry granulator is manufactured by FREUND Corporation, and the process conditions are: the rotation speed of the tableting roller is 1.20 r / min, and the feed speed is 24 r / min.

[0043] Example 2

[0044] Urea-clearing capsules, calculated by weight, are made from the following raw materials:

[0045] 60 parts of urea-clearing paste powder; the raw materials of urea-clearing paste powder are: the mass ratio of rhubarb, astragalus, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, tuckahoe, mulberry bark, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and liquorice is 1:4:3:2:3:5:5:5:3:5:3:2.5:2:5:1.5:0.9;

[0046] Filler (corn starch, pregelatinized starch and mannitol in a mass ratio of 2:1:0.2) 40 parts;

[0047] Lubricant: 0.005 parts of magnesium lauryl sulfate.

[0048] The preparation method of Urea Clearing Capsule is as follows:

[0049] (1) Rhubarb, astragalus, mulberry bark, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, poria, prepared shouwu, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and liquorice are mixed, soaked in 5 times the amount of water for 30 min, extracted 3 times at 75°C, each extraction time is 0.5 h, filtered, concentrated to a relative density of 1.2 at 80°C, and an extract is obtained;

[0050] (2) Add 85% ethanol aqueous solution to the extract, stir, place in a -4°C refrigerator for 8 h, filter, and collect the filtrate;

[0051] (3) Recovering the ethanol from the alcohol precipitation filtrate, concentrating the filtrate to a relative density of 1.2 at 80° C., and vacuum drying to obtain the urea-clearing paste powder.

[0052] (4) The urea-clearing dry paste powder, filler, and 50% by mass of lubricant are mixed, dry granulated, passed through a No. 4 sieve, the granules are mixed with the remaining lubricant, and filled into capsules; the dry granulator is manufactured by FREUND Corporation, and the process conditions are: the rotation speed of the tableting roller is 1.50 r / min, and the feed speed is 22 r / min.

[0053] Example 3

[0054] Urea-clearing capsules, calculated by weight, are made from the following raw materials:

[0055] 80 parts of urea-clearing paste powder; the raw materials of urea-clearing paste powder are: the mass ratio of rhubarb, astragalus, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, tuckahoe, mulberry bark, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and liquorice is 1:4:3:2:3:5:5:5:3:5:3:2.5:2:5:1.5:0.9;

[0056] Filler (corn starch, pregelatinized starch and mannitol in a mass ratio of 1.4:1:0.6) 20 parts;

[0057] Lubricant: 0.02 parts of magnesium lauryl sulfate.

[0058] The preparation method of Urea Clearing Capsule is as follows:

[0059] (1) Rhubarb, astragalus, mulberry bark, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, poria, prepared shouwu, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and liquorice are mixed, soaked in 5 times the amount of water for 30 minutes, extracted at 85°C for 1 hour, filtered, and concentrated to a relative density of 1.4 at 80°C to obtain an extract;

[0060] (2) Add 55% ethanol-5% acetone aqueous solution to the extract, stir, let stand for 24 hours, filter, and collect the filtrate;

[0061] (3) The filtrate is concentrated to an extract having a relative density of 1.4 at 80° C., and vacuum dried to obtain a urea-clearing paste powder;

[0062] (4) The urea-clearing dry paste powder, filler, and 50% by mass of lubricant are mixed, dry granulated, passed through a No. 4 sieve, the granules are mixed with the remaining lubricant, and filled into capsules; the dry granulator is manufactured by FREUND Corporation, and the process conditions are: the speed of the tableting roller is 1.00 r / min, and the feed speed is 25 r / min.

[0063] Comparative Example 1

[0064] The filler in this comparative example is 30 parts of a mixture of corn starch and pregelatinized starch in a mass ratio of 1:1.5, and the rest is the same as in Example 1.

[0065] Comparative Example 2

[0066] The fillers in this comparative example are corn starch and 30 parts of mannitol in a mass ratio of 1:1.5, and the rest are consistent with Example 1.

[0067] Comparative Example 3

[0068] The filler in this comparative example is 30 parts, which is a mixture of pregelatinized starch and lactose in a mass ratio of 2:0.5, and the rest is consistent with Example 1.

[0069] Comparative Example 4

[0070] The lubricant in this comparative example is magnesium stearate, and the rest is consistent with Example 1.

[0071] Comparative Example 5

[0072] The process conditions of dry granulation are as follows: the rotation speed of the tabletting roller is 0.8 r / min, and the feeding speed is 27 r / min. The rest are the same as those in Example 1.

[0073] Comparative Example 6

[0074] The process conditions of dry granulation are as follows: the rotation speed of the tabletting roller is 3 r / min, and the feeding speed is 18 r / min. The rest are the same as those in Example 1.

[0075] Experiment 1: Effects of different formulations and processes on capsule preparation

[0076] The present invention studies the auxiliary materials of Urea Clearing Capsules. The effects of different auxiliary materials on the dry granulation roller sticking condition and the granule forming rate are shown in Table 1.

[0077] The dry-pressed tablets are crushed into granules by shaking and passed through a No. 4 sieve. The mass of the granules is m1, the total mixture is recorded as m2, and the granule forming rate % = m1 / m2×100%, which is the calculated value of the first granulation.

[0078] Table 1

[0079] Grouping Roller sticking condition Particle forming rate Example 1 The tableting hardness is moderate, the tablets are pressed into strips, and the wheel is non-stick. 93.20％ Example 2 The tableting hardness is moderate, the tablets are pressed into strips, and the wheel is non-stick. 90.51％ Example 3 The tableting hardness is moderate, the tablets are pressed into strips, and the wheel is non-stick. 91.08％ Comparative Example 1 The color of the middle strip of the tablet is too dark 88.60％ Comparative Example 2 The tableting is discontinuous and more fine powder is produced during tableting 72.35％ Comparative Example 3 The tableting is not continuous and more fine powder is produced during tableting 78.19％ Comparative Example 4 The color of the middle strip of the tablet is too dark, and the tablet is too hard 89.95％ Comparative Example 5 The color of the middle strip of the tablet is too dark 87.40％ Comparative Example 6 The tableting is not continuous and more fine powder is produced during tableting 63.55％

[0080] Experiment 2: Stability Experiment

[0081] The quality of the Urea Clearing Capsules prepared by the present invention was tested by arranging an accelerated test at 40±2°C and 75±5%RH to examine the changes in each test item. The test results of each capsule at 0 month all met the quality requirements of the capsule. The results of the accelerated stability test at 3 months and 6 months are shown in Table 2 and Table 3. The content of the index component astragaloside IV was determined using the method of our invention patent application CN 115184500A.

[0082] Table 2 Three-month stability test report of each capsule

[0083]

[0084] Table 3 Six-month stability test report of each capsule

[0085]

[0086]

[0087] The above detailed description is a specific description of one feasible embodiment of the present invention. The embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or modification that does not deviate from the present invention should be included in the scope of the technical solution of the present invention.

Claims

1. A urea-clearing capsule, characterized in that: By weight, the raw materials of the capsules include 60-80 parts of urea-clearing paste powder, 20-40 parts of fillers and 0.005-0.02 parts of lubricants; the fillers include corn starch, pregelatinized starch and mannitol.

2. The Urea Clearing Capsule according to claim 1, characterized in that: The mass ratio of the corn starch, pregelatinized starch and mannitol is 1-2:1:0.2-0.

6.

3. The Urea Clearing Capsule according to claim 1, characterized in that: The lubricant is selected from at least one of polyethylene glycol, micro powder silica gel and lauryl magnesium sulfate.

4. The Urea-clearing capsule according to claim 3, characterized in that: The lubricant is magnesium lauryl sulfate.

5. The Urea-clearing capsule according to claim 1, characterized in that: The raw materials of the urea-clearing paste powder include the following components: rhubarb, astragalus, mulberry bark, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, tuckahoe, processed radix polygoni multiflori, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and liquorice.

6. The Urea-clearing capsule according to claim 5, characterized in that: The preparation method of the urea-clearing paste powder comprises the following steps: (1) Rhubarb, astragalus, mulberry bark, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, poria, prepared shouwu, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and liquorice are mixed, soaked in water, extracted, filtered and concentrated to obtain an extract; (2) adding the extract to an ethanol solution for alcohol precipitation, filtering, and collecting the filtrate; (3) Recover the ethanol in the alcohol precipitation filtrate, concentrate it, and dry it.

7. The uremic capsule according to claim 6, characterized in that: The extraction temperature in step (1) is 75-85°C, the extraction time is 1-3h, the extraction times are 1-3 times, and the relative density of the extract at 80°C is 1.2-1.

4.

8. The Urea-clearing capsule according to claim 6, characterized in that: The ethanol in step (2) is an ethanol aqueous solution with a volume concentration of 55-85%, and the alcohol precipitation time is 8-24h.

9. A method for preparing the Urea Clearing Capsule according to any one of claims 1 to 8, characterized in that: The method comprises the following steps: mixing urea-clearing dry paste powder, a filler and a part of a lubricant, dry granulating, mixing the granules and the remaining lubricant, and filling to form capsules.

10. The preparation method according to claim 9, characterized in that: The process conditions of dry granulation include: the rotation speed of the tabletting roller is 0.6-2.0 r / min, the feeding speed is 20-25 r / min, and the partial lubricant is a lubricant with a mass percentage of 30-60%.

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