CN101069742B - Pancreatic kininogenase tablet and preparing method - Google Patents
Pancreatic kininogenase tablet and preparing method Download PDFInfo
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- CN101069742B CN101069742B CN2007101104544A CN200710110454A CN101069742B CN 101069742 B CN101069742 B CN 101069742B CN 2007101104544 A CN2007101104544 A CN 2007101104544A CN 200710110454 A CN200710110454 A CN 200710110454A CN 101069742 B CN101069742 B CN 101069742B
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- kallidinogenase
- carboxymethylstach sodium
- pancreatic kininogenase
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Abstract
The present invention relates to a kallidinogenase tablet preparation and its preparation method. In the invented kallidinogenase tablet preparation the kallidinogenase is contained, and is used as active component, and in its tablet core the hydroxymethyl starch sodium is contained and can be used as disintegrant.
Description
Technical field
The present invention relates to a kind of pancreatic kininogenase tablet and preparation method thereof.
Background technology
Kallidinogenase is a vasodilator, effect with microcirculation improvement, be mainly used in the treatment diseases with microcirculatory disturbance,, also can be used for the auxiliary treatment of hypertension as nephropathy, peripheral neuropathy, retinopathy, retinopathy and the ischemic cerebrovascular that diabetes cause.
Kallidinogenase has blood vessel dilating, microcirculation improvement effect; Activate fibrinolysin, reduce blood viscosity; Inhibition of phospholipase A 2 prevents platelet aggregation, prevents effects such as thrombosis.
Kallidinogenase can be prepared into various dosage form for clinical use according to the conventional formulation method.But existing kallidinogen enzyme preparation, particularly tablet, because the problem of sealing usually causes the drug quality instability.
Goal of the invention
The purpose of this invention is to provide pancreatic kininogenase tablet of a kind of quality improvement and preparation method thereof.Pancreatic kininogenase tablet of the present invention compare with the known tablet of prior art have the release height, multiple advantage such as purity height, the height of tiring, weight differential are little, can provide more stable, effective, safe product for the patient.
Summary of the invention
The invention provides a kind of pancreatic kininogenase tablet, wherein contain kallidinogenase, it is characterized in that: in label, contain carboxymethylstach sodium as disintegrating agent as active component.
The present invention also provides a kind of preferred pancreatic kininogenase tablet, and wherein kallidinogenase is 1-5 ten thousand units with the content ratio of carboxymethylstach sodium: 1 gram.
The present invention also provides a kind of preferred pancreatic kininogenase tablet, and wherein kallidinogenase is 30,000 units with the content ratio of carboxymethylstach sodium: 1 gram.
In tablet of the present invention, the weight content of carboxymethylstach sodium is 1%-6%.
In tablet of the present invention, the weight content of carboxymethylstach sodium is preferably 4%.
Tablet of the present invention is preferably coated tablet, and especially preferred is the film coated tablet.
The adjuvant that can be used for preparing tablet of the present invention can also comprise other any conventional adjuvant, for example magnesium stearate, lactose, microcrystalline Cellulose, sucrose, dextrin etc. except as the carboxymethylstach sodium of disintegrating agent.
The present invention is kallidinogen enzyme membrane coated tablet preferably, although described film coated tablet can carry out coating with for example prompt coloured silk of film coating materials commonly used, Ka Lekang, 930 Opadries, new prompt coloured silk etc., preferred film coating materials is new prompt color.
The present invention also provides a kind of preparation method of pancreatic kininogenase tablet, it is characterized in that: as active component, as disintegrating agent, make tablet according to conventional method with carboxymethylstach sodium with kallidinogenase.
To make the present invention by specific embodiment below and further specify, but the described here specific embodiment is only used for illustrating the present invention, but not limitation of the scope of the invention.
Embodiment 1
Prescription
| The supplementary material title | Fineness | 100,000 consumptions |
| Kallidinogenase | 80 orders | 1,500 ten thousand units |
| Lactose | 80 orders | 8.0kg |
| Microcrystalline Cellulose | 80 orders | 2.7kg |
| 10% dextrin+20% sucrose mixed adhesive | 80 orders | About 7.6kg |
| Magnesium stearate | 80 orders | 0.10kg |
| Carboxymethylstach sodium | 80 orders | 0.5kg |
| Film coating pre-mix dose (930 Opadry) | - | 1.925kg |
Opadry is purchased the flat space Bioisystech Co., Ltd in Shaoxing
Preparation method
Sieve: dextrin, microcrystalline Cellulose, lactose, magnesium stearate, carboxymethyl starch sodium described in the above-mentioned prescription are crossed 80 mesh sieves.
Binding agent preparation (in preparation 40.0kg): accurately take by weighing 8.0kg sucrose to stainless steel cask, add hot purified water 8kg, stir and make it dissolving; Accurately take by weighing the 4.0kg dextrin to stainless steel cask, add that purified water 10kg fully stirs more than 90 ℃, make it to disperse fully gelatinizing; Above-mentioned two solution are mixed the back add purified water to 40.0kg, 80 mesh sieves are crossed in the back that stirs.
Ratio according to kallidinogenase and granule gross weight is the ratio of 150 units: 130mg, count particles gross weight and blank granule expense (blank granule consumption=granule gross weight-magnesium stearate consumption-carboxymethylstach sodium consumption-kallidinogen enzyme dosage).
To make grain earlier and cross 16 mesh sieves, after removing bulky grain (piece), getting blank granule that weight is equivalent to one times of material quantity and kallidinogenase carries out craft and crosses 40～60 mesh sieve mix homogeneously, get the blank granule that is equivalent to one times of amount of mixture again and carry out craft 40～60 mesh sieve mix homogeneously excessively, after so repeating four times mixture is added in the remaining blank granule, and add the magnesium stearate of recipe quantity and carboxymethylstach sodium and put total mixing in the machine and mix.Process conditions: putting the interior incorporation time of total mixed machine is 30 minutes; Rotating speed was 8 rev/mins, every commutation in 1 minute.
Sampling and measuring content and loss on drying.
Tabletting
Mould specification: Φ 7mm scrobicula is dashed; Unit type: GZPL fully automatic high-speed tablet machine.Machine speed: 9～130,000 slices/hour.Sheet heavily is 130mg, tablet weight variation≤± 5.0%, label hardness: 40～60N/cm
2
Coating is got film coating pre-mix dose (930 Opadry), and consumption is 14.0% of a label weight.Film coating pre-mix dose is dissolved in purified water, and adjusting coating solution concentration is 20%.Tab bed tempertaure to 30～35 ℃, coating pan rotating speed are 3.5～8.0 rev/mins, carry out coating.
Embodiment 2
Prescription
| The supplementary material title | Fineness | 100,000 consumptions |
| Kallidinogenase | 80 orders | 5,000,000 units |
| Lactose | 80 orders | 5kg |
| Microcrystalline Cellulose | 80 orders | 4kg |
| 10% dextrin+20% sucrose mixed adhesive | 80 orders | 10kg |
| Magnesium stearate | 80 orders | 0.1kg |
| Carboxymethylstach sodium | 80 orders | 0.1kg |
| Film coating pre-mix dose (new prompt color) | - | 0.5kg |
Preparation method
According to the foregoing description 1 described similar method, form by above-mentioned prescription and to make the film coated tablet.
Embodiment 3
Prescription
| The supplementary material title | Fineness | 100,000 consumptions |
| Kallidinogenase | 80 orders | 8,000,000 units |
| Lactose | 80 orders | 10kg |
| Microcrystalline Cellulose | 80 orders | 1kg |
| 10% dextrin+20% sucrose mixed adhesive | 80 orders | 3kg |
| Magnesium stearate | 80 orders | 0.5kg |
| Carboxymethylstach sodium | 80 orders | 0.5kg |
| Film coating pre-mix dose (prompt color) | - | 5kg |
Preparation method
According to the foregoing description 1 described similar method, form by above-mentioned prescription and to make the film coated tablet.
Embodiment 4
Prescription
| The supplementary material title | Fineness | 100,000 consumptions |
| Kallidinogenase | 80 orders | 6,000,000 units |
| Lactose | 80 orders | 3kg |
| Microcrystalline Cellulose | 80 orders | 3kg |
| 10% dextrin+20% sucrose mixed adhesive | 80 orders | 5kg |
| Magnesium stearate | 80 orders | 0.3kg |
| Carboxymethylstach sodium | 80 orders | 0.3kg |
| Film coating pre-mix dose (Ka Lekang) | - | 0.6kg |
Preparation method
According to the foregoing description 1 described similar method, form by above-mentioned prescription and to make the film coated tablet.
Embodiment 5
Prescription
| The supplementary material title | Fineness | 100,000 consumptions |
| Kallidinogenase | 80 orders | 6,000,000 units |
| Lactose | 80 orders | 7kg |
| Microcrystalline Cellulose | 80 orders | 2kg |
| 10% dextrin+20% sucrose mixed adhesive | 80 orders | 7kg |
| Magnesium stearate | 80 orders | 0.1kg |
| Carboxymethylstach sodium | 80 orders | 0.2kg |
| Film coating pre-mix dose (930 Opadry) | - | 3kg |
Preparation method
According to the foregoing description 1 described similar method, form by above-mentioned prescription and to make the film coated tablet.
Embodiment 6
Prescription
| The supplementary material title | Fineness | 100,000 consumptions |
| Kallidinogenase | 80 orders | 6,000,000 units |
| Lactose | 80 orders | 4kg |
| Microcrystalline Cellulose | 80 orders | 1kg |
| 10% dextrin+20% sucrose mixed adhesive | 80 orders | 5kg |
| Magnesium stearate | 80 orders | 0.1kg |
| Carboxymethylstach sodium | 80 orders | 0.1kg |
| Film coating pre-mix dose (new prompt color) | - | 4kg |
Preparation method
According to the foregoing description 1 described similar method, form by above-mentioned prescription and to make the film coated tablet.
Comparative examples 1
Prescription
| The supplementary material title | Fineness | 100,000 consumptions |
| Kallidinogenase | 80 orders | 1,500 ten thousand units |
| Lactose | 80 orders | 8.0kg |
| Microcrystalline Cellulose | 80 orders | 2.7kg |
| 10% dextrin+20% sucrose mixed adhesive | 80 orders | About 7.6kg |
| Magnesium stearate | 80 orders | 0.10kg |
| Polyvinylpolypyrrolidone XL (PVPP) | 80 orders | 0.5kg |
| Film coating pre-mix dose (930 Opadry) | - | 1.925kg |
Preparation method
Sieve: dextrin, microcrystalline Cellulose, lactose, magnesium stearate, carboxymethyl starch sodium described in the above-mentioned prescription are crossed 80 mesh sieves.
Binding agent preparation (in preparation 40.0kg): accurately take by weighing 8.0kg sucrose to stainless steel cask, add hot purified water 8kg, stir and make it dissolving; Accurately take by weighing the 4.0kg dextrin to stainless steel cask, add that purified water 10kg fully stirs more than 90 ℃, make it to disperse fully gelatinizing; Above-mentioned two solution are mixed the back add purified water to 40.0kg, 80 mesh sieves are crossed in the back that stirs.
Ratio according to kallidinogenase and granule gross weight is the ratio of 150 units: 130mg, count particles gross weight and blank granule expense (blank granule consumption=granule gross weight-magnesium stearate consumption-carboxymethylstach sodium consumption-kallidinogen enzyme dosage).
To make grain earlier and cross 16 mesh sieves, after removing bulky grain (piece), getting blank granule that weight is equivalent to one times of material quantity and kallidinogenase carries out craft and crosses 40～60 mesh sieve mix homogeneously, get the blank granule that is equivalent to one times of amount of mixture again and carry out craft 40～60 mesh sieve mix homogeneously excessively, after so repeating four times mixture is added in the remaining blank granule, and add the magnesium stearate of recipe quantity and carboxymethylstach sodium and put total mixing in the machine and mix.Process conditions: putting the interior incorporation time of total mixed machine is 30 minutes; Rotating speed was 8 rev/mins, every commutation in 1 minute.
Sampling and measuring content and loss on drying.
Tabletting
Mould specification: Φ 7mm scrobicula is dashed; Unit type: GZPL fully automatic high-speed tablet machine.Machine speed: 9～130,000 slices/hour.Sheet heavily is 130mg, tablet weight variation≤± 5.0%, label hardness: 40～60N/cm
2
With above-mentioned label coating according to a conventional method.
Experimental example 1
The film coated tablet and the prior art that make with the embodiment of the invention 1 described method---comparative examples 1 described method make the film coated tablet compare experiment, draw as drawing a conclusion.
1. comparing result
2. the internal control quality standard of preparation and statutory standards leading indicator contrast table
| Project | Embodiment 1 (product of the present invention) | Comparative examples 1 |
| Purity | 77％ | 68％ |
| Release | 75％ | 70％ |
| Uniformity of dosage units | 6.0％ | 5.5％ |
| Weight differential | ±7.0％ | ±7.5％ |
| Indicate content | 90％-120％ | 85％ |
3. form and method according to product of the present invention, the applicant produces 1063 batches of kallidinogenase enteric coatel tablets altogether, and excellent superfine product rate reaches 100%.
4, according to national standard, kallidinogenase enteric coatel tablets effect duration is defined as 1.5 years, the applicant's reserved sample observing to 2 year, and every quality index is not seen obvious change yet.
Experimental example 2 adopts the influence of different coating materials to product of the present invention
This experiment stresses a tablet release difficult problem solved by the invention, particularly by coating material is screened, makes tablet of the present invention obtain best releasing effect.Prompt coloured silk, new prompt coloured silk are purchased in Pu, Shanghai power film preparation adjuvant company limited.Ka Lekang purchases in Shanghai Colorcon Coating Technology Co., Ltd.
The write out a prescription different materials coated tablet release of label (is example with embodiment 1) of production the present invention is compared as follows:
| Lot number | Specification | Coating material | Release % (should greater than 70%) | Estimate |
| 060103 | 60u | Prompt color | 41.6 25.6 33.1 36.9 40.5 39.6 | Defective |
| 060201 | 120u | Ka Lekang | 50.2 51.7 48.7 55.7 59.2 75.8 | Defective |
| 060508 | 60u | New prompt color | 64 69 72 90 64 96 (coating laboratory lab scale equipment) | Improvement is arranged |
Analyze: by above-mentioned experimental result as can be seen, different coating materials is for the tablet release
Influence is followed successively by: prompt coloured silk＞Ka Lekang＞new prompt color, wherein new prompt coloured silk is most preferred.
Experimental example 3 adopts the influence of different disintegrating agents to product of the present invention
Increase disintegrating agent on the basis of above-mentioned experimental example 2 prescriptions, relatively (laboratory bench scale) result is as follows for the release of its coated tablet:
● the former prescription of R-1 adds 4% polyvinylpolypyrrolidone XL (PVPP)
● the former prescription of R-2 adds 4% carboxymethyl starch sodium (imported from Holland)
| The experiment number | Coating material | The release % of 6 batch products (should be greater than 70%) according to national standard | Conclusion |
| R-1 | Prompt color | 67 65 61 61 69 66 | Defective |
| R-1 | Ka Lekang 930 | 44 77 65 57 74 100 | Defective |
| R-2 | Prompt color | 105 103 90 102 85 107 | Qualified |
| R-2 | Ka Lekang 930 | 87 93 98 80 73 87 | Qualified |
Analyze: polyvinylpolypyrrolidone helps that to collapse performance strong excessively, cause principal agent seepage outside the clothing film in the label, and the selection of carboxymethyl starch sodium can compensate its defect just.
By above-mentioned experimental result as can be seen, pancreatic kininogenase tablet of the present invention compare with the known tablet of prior art have the release height, multiple advantage such as purity height, the height of tiring, weight differential are little, can provide more stable, effective, safe product for the patient.
Claims (7)
1. a pancreatic kininogenase tablet wherein contains kallidinogenase as active component, contains carboxymethylstach sodium in label, it is characterized in that: in described tablet, carboxymethylstach sodium is as disintegrating agent, and its weight content is 1%-6%.
2. the described pancreatic kininogenase tablet of claim 1, wherein in described tablet, the weight content of carboxymethylstach sodium is 4%.
3. the described pancreatic kininogenase tablet of claim 1, wherein kallidinogenase and the content of carboxymethylstach sodium are than being 1-5 ten thousand units: 1 gram.
4. the described pancreatic kininogenase tablet of claim 3, wherein kallidinogenase is 30,000 units with the content ratio of carboxymethylstach sodium: 1 gram.
5. the described pancreatic kininogenase tablet of claim 1, wherein said tablet is a coated tablet.
6. the described pancreatic kininogenase tablet of claim 5, wherein said coated tablet is the film coated tablet.
7. the preparation method of any one described pancreatic kininogenase tablet among the claim 1-6 is characterized in that: as active component, as disintegrating agent, make tablet according to conventional method with carboxymethylstach sodium with kallidinogenase.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101104544A CN101069742B (en) | 2007-06-06 | 2007-06-06 | Pancreatic kininogenase tablet and preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101104544A CN101069742B (en) | 2007-06-06 | 2007-06-06 | Pancreatic kininogenase tablet and preparing method |
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| Publication Number | Publication Date |
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| CN101069742A CN101069742A (en) | 2007-11-14 |
| CN101069742B true CN101069742B (en) | 2010-09-15 |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102813637B (en) * | 2012-08-31 | 2013-08-21 | 济南维尔康生化制药有限公司 | Kallidinogenase enteric coated tablet and preparation method thereof |
| CN105168168B (en) * | 2015-10-30 | 2017-12-05 | 成都通德药业有限公司 | A kind of preparation method of kallidinogenase enteric coatel tablets |
| CN105287423B (en) * | 2015-11-02 | 2018-02-23 | 河南灵佑药业股份有限公司 | A kind of kallidinogenase piece |
| CN106310241A (en) * | 2016-08-31 | 2017-01-11 | 安徽省润生医药股份有限公司 | Pancreatic kininogenase tablet |
| CN111012749B (en) * | 2019-12-26 | 2022-08-05 | 常州千红生化制药股份有限公司 | A preparation capable of improving heat stability of tablet and kallidinogenase, and heat stable kallidinogenase tablet and its preparation method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1391212A1 (en) * | 2001-04-24 | 2004-02-25 | Lintec Corporation | Oral preparations and supports for oral preparations |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1391212A1 (en) * | 2001-04-24 | 2004-02-25 | Lintec Corporation | Oral preparations and supports for oral preparations |
Non-Patent Citations (2)
| Title |
|---|
| 毕殿洲等.药剂学 四.人民卫生出版社,2003,321-322. |
| 毕殿洲等.药剂学 四.人民卫生出版社,2003,321-322. * |
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| CN101069742A (en) | 2007-11-14 |
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