CN102813637B - Kallidinogenase enteric coated tablet and preparation method thereof - Google Patents
Kallidinogenase enteric coated tablet and preparation method thereof Download PDFInfo
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- CN102813637B CN102813637B CN 201210320063 CN201210320063A CN102813637B CN 102813637 B CN102813637 B CN 102813637B CN 201210320063 CN201210320063 CN 201210320063 CN 201210320063 A CN201210320063 A CN 201210320063A CN 102813637 B CN102813637 B CN 102813637B
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- kallidinogenase
- enteric
- granule
- blank granule
- mix homogeneously
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- 102000001399 Kallikrein Human genes 0.000 title claims abstract description 125
- 108060005987 Kallikrein Proteins 0.000 title claims abstract description 125
- 229960003709 kallidinogenase Drugs 0.000 title claims abstract description 117
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 239000002662 enteric coated tablet Substances 0.000 title abstract description 9
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 35
- 239000007888 film coating Substances 0.000 claims abstract description 27
- 238000009501 film coating Methods 0.000 claims abstract description 27
- 239000002671 adjuvant Substances 0.000 claims abstract description 24
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 18
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- 238000007689 inspection Methods 0.000 claims abstract description 4
- 239000008187 granular material Substances 0.000 claims description 101
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 74
- 239000000203 mixture Substances 0.000 claims description 63
- 235000019359 magnesium stearate Nutrition 0.000 claims description 37
- 238000012856 packing Methods 0.000 claims description 35
- 239000011248 coating agent Substances 0.000 claims description 26
- 238000000576 coating method Methods 0.000 claims description 26
- UHZZMRAGKVHANO-UHFFFAOYSA-M chlormequat chloride Chemical compound [Cl-].C[N+](C)(C)CCCl UHZZMRAGKVHANO-UHFFFAOYSA-M 0.000 claims description 25
- 238000002156 mixing Methods 0.000 claims description 25
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 23
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 23
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 23
- 229960003943 hypromellose Drugs 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 22
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 17
- 239000008101 lactose Substances 0.000 claims description 17
- 229920002472 Starch Polymers 0.000 claims description 14
- 239000008107 starch Substances 0.000 claims description 14
- 235000019698 starch Nutrition 0.000 claims description 14
- 230000001476 alcoholic effect Effects 0.000 claims description 12
- 230000004087 circulation Effects 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 12
- 238000001125 extrusion Methods 0.000 claims description 12
- 238000007602 hot air drying Methods 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 12
- 239000008213 purified water Substances 0.000 claims description 12
- 239000007779 soft material Substances 0.000 claims description 12
- 229910001220 stainless steel Inorganic materials 0.000 claims description 12
- 239000010935 stainless steel Substances 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 11
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 11
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 11
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 11
- 239000004033 plastic Substances 0.000 claims description 11
- 239000007921 spray Substances 0.000 claims description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 6
- 235000015424 sodium Nutrition 0.000 claims description 6
- 239000000661 sodium alginate Substances 0.000 claims description 6
- 235000010413 sodium alginate Nutrition 0.000 claims description 6
- 229940005550 sodium alginate Drugs 0.000 claims description 6
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 5
- 239000001110 calcium chloride Substances 0.000 claims description 5
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 5
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- 229940057948 magnesium stearate Drugs 0.000 claims description 4
- 235000002639 sodium chloride Nutrition 0.000 claims description 4
- 235000011148 calcium chloride Nutrition 0.000 claims description 2
- 229960001375 lactose Drugs 0.000 claims description 2
- 229940001593 sodium carbonate Drugs 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 229940032147 starch Drugs 0.000 claims description 2
- 239000003826 tablet Substances 0.000 abstract description 42
- 230000000694 effects Effects 0.000 abstract description 9
- 239000003381 stabilizer Substances 0.000 abstract description 9
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 102000004190 Enzymes Human genes 0.000 abstract description 4
- 108090000790 Enzymes Proteins 0.000 abstract description 4
- 229940088598 enzyme Drugs 0.000 abstract description 4
- 229910017053 inorganic salt Inorganic materials 0.000 abstract description 4
- 238000007796 conventional method Methods 0.000 abstract description 2
- 239000004480 active ingredient Substances 0.000 abstract 3
- 239000000853 adhesive Substances 0.000 abstract 3
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- 229940039088 kininogenase Drugs 0.000 description 7
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- 108010025252 Kassinin Proteins 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention discloses a kallidinogenase enteric coated tablet which contains kallidinogenase which is used as an active ingredient, and a tablet core contains sodium alga acid or inorganic salt which is taken as a stabilizer. The invention further discloses a preparation method of the kallidinogenase enteric coated tablet, wherein adjuvants are taken as blank particles at first, kallidinogenase serving as the main active ingredient is then added and is uniformly mixed, the tablet is produced according to a conventional method, and finally, enteric coating is used to coat a premixing agent into enteric film coating. The added stabilizer has the activity of being combined with the kallidinogenase into activating enzyme, so the kallidinogenase is prevented from titer loss during the production process, and the active ingredient input is in accordance with finished product yield. An adhesive has strong adhesive force, large particle adhesive power, and is easily mixed with the kallidinogenase uniformly. The formula has the characteristics of little unit titer loss during the production process and high finished product titer recovery rate; all adjuvants have no interference with the finished product inspection, the finished product is high in quality, safe and effective.
Description
Technical field
The present invention relates to a kind of kallidinogenase enteric coated tablet and preparation method thereof.
Background technology
Kallidinogenase is a kind of peripheral vasodilators with the effect of blood vessel dilating microcirculation improvement, kallidinogenase acts on kininogen in vivo and discharges kassinin kinin, directly act on little blood vessel and blood capillary, thereby produce a series of pharmacodynamics effect, as diastole blood capillary, expansion small artery etc., in blood vessel dilating, improve permeability and the blood flow of blood vessel; The effect of the blood pressure of adjusting is arranged, reduce myocardial oxygen consumption; Also can promote prostatic secretion, improve each organ blood flow.Kallidinogenase is a kind of determined curative effect, the slight enzyme drug of untoward reaction as a kind of internationally recognized microcirculation improving agent, is suitable for taking for a long time, is applicable to the treatment of various microcirculation dysfunctions.Kallidinogenase is remarkable to the therapeutic effect of early nephropathy, the microcirculation of kidney can be improved effectively, with the other medicines partner treatment, glomerule goal arterial pressure can be reduced, have effects such as the glomerular basement membrane of impelling earlier damage reparation, the market prospect of this product is very wide.
Kallidinogenase can be prepared into various dosage form for clinical use according to the conventional formulation method.Pertinent literature and publication show, existing kallidinogen enzyme preparation, particularly tablet, owing to adopt wet granulation easily to make the loss of tiring bigger in the production process, adopt blank granule method easily to make the uniformity of dosage units of finished product against regulation, tire and easily reduce, encapsulation process adopts water-soluble film coating pre-mix dose easier loss etc. the defective of tiring that makes at high temperature, causes the quality instability of medicine.
Publication number is that the Chinese invention patent of CN101069742 discloses a kind of pancreatic kininogenase tablet and preparation method thereof, the tablet release of its preparation can reach more than 85%, purity reaches 77%, but it exists technological design unreasonable, easily causes the reduction of tiring, the undesirable defective of uniformity of dosage units in preparation process and storage process.
Summary of the invention
The objective of the invention is provides a kind of kallidinogenase enteric coated tablet and preparation method thereof for overcoming above-mentioned the deficiencies in the prior art.
For achieving the above object, the present invention adopts following technical proposals:
A kind of kallidinogenase enteric coated tablet, described enteric coated tablet contains kallidinogenase as active component, contains inorganic salt or sodium alginate as stabilizing agent in label.
Described inorganic salt is sodium carbonate, calcium chloride, magnesium sulfate or sodium chloride.
Described tablet also comprises filler, binding agent, disintegrating agent, lubricant; Described filler is starch or lactose; Described binding agent is hypromellose; Described disintegrating agent is carboxymethylstach sodium or microcrystalline Cellulose; Described lubricant is magnesium stearate.
The weight ratio of each component of label consists of: kallidinogenase: filler: disintegrating agent: stabilizing agent: binding agent: lubricant=9-14 ten thousand units: 120-140 gram: the 15-20 gram: the 17-33 gram: the 6-9 gram: the 2-3 gram.
The percentage composition of the gross weight of described stabilizer comprises label is 8-17%.
The coating material of described enteric film coated tablet is A Hua, Ying Mao, Ka Lekang.
The purity of described raw material kallidinogenase is more than 80%.
The described unit that contains kallidinogenase is 50～280u/ sheet, and the weight ratio that contains pharmaceutic adjuvant is 80～90%, and the weight ratio that contains enteric film coating material is 10～14%.
The present invention also provides the preparation method of kallidinogenase enteric coated tablet, according to earlier adjuvant being made blank granule, the back adds main active kallidinogenase mix homogeneously, makes tablet more according to a conventional method, is bundled into the enteric film clothing with enteric coating coating pre-mixing agent at last.
Concrete steps are as follows:
1, prepares: kallidinogenase, filler, disintegrating agent, binding agent, stabilizing agent, lubricant were pulverized 80 mesh sieves;
2, make blank granule: with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing; Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby;
3, principal agent mixes: kallidinogenase is doubly measured incremental method with blank granule employing mix, at first the blank granule with equivalent mixes with kallidinogenase, behind the mix homogeneously, add the doubly blank granule remix of amount and then, behind the mix homogeneously, doubly amount increases progressively successively, finishes until whole mixing, adds the magnesium stearate mix homogeneously at last;
4, tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness;
5, enteric coated: get the enteric film coating pre-mix dose, consumption is 10 ~ 14% of label weight, and it is that making the coating solution compound concentration is 15 ~ 20% in 70 ~ 90% the alcoholic solution that the enteric film coating pre-mix dose is dissolved in volumetric concentration; 30 ℃ of design temperatures are opened coating pan, evenly are sprayed onto enteric coating liquid on the label;
6, packing namely gets the kallidinogenase enteric coatel tablets.
Described kallidinogenase, filler starch and lactose, disintegrator carboxymethylstarch sodium and microcrystalline Cellulose, binding agent hypromellose, stabilizing agent inorganic salt and adjuvants such as sodium alginate, magnesium stearate lubricant were pulverized 80 mesh sieves, that pulverizes is thinner, more be conducive to the performance of effective ingredient, instant effect.
Described kallidinogenase is doubly measured incremental method with blank granule employing and is mixed, and it is more even that kallidinogenase and blank granule can be mixed, and the uniformity of dosage units of finished product is lower.
Operations such as this preparation technology comprises product prescription, makes blank granule, principal agent mixing, tabletting, enteric coated, packing.The present invention has carried out preferably the prescription of kallidinogenase enteric coatel tablets, and principal agent composition kallidinogenase purity is preferably 85～90%.Adopt and at first make blank granule, principal agent is doubly measured the incremental method mixing then, the kallidinogenase enteric coatel tablets that make of tabletting again, its optimum finished product release can reach tire more than 93%, purity reaches more than 92.36%, uniformity of dosage units 3.2% indicates content and reaches 124.9%, and other every quality index are up to specification.
Innovative point of the present invention has:
1, prescription advantage: this product prescription science, safety is good, it is a unique prescription with unique proportioning, this prescription comprises conventional filler, disintegrating agent, binding agent, lubricant, also increased stabilizing agent at kallidinogenase enzyme preparation and tablet manufacturing technology, binding agent preferably adopts the stronger hypromellose of viscosity.Stabilizing agent has the vigor of kinase of being combined with kallidinogenase, prevents the kallidinogenase loss of tiring in process of production, raw material is dropped into conform to finished product output ratio.The bonding force of binding agent is strong, and it is big to have particle adhesion power, easy and kallidinogenase mix homogeneously.It is few that this prescription has a production process potency unit loss, the finished product response rate height of tiring, and each adjuvant is noiseless in product inspection, finished product superior in quality, characteristics such as safe and effective.
2, process innovation: process using is doubly measured incremental method, and it is more even that kallidinogenase is mixed with granule, and the uniformity of dosage units of finished product is good.This product adopts the enteric film-coated technique, has avoided the tire loss of product in gastric juice, has improved content and the stability of enteric coatel tablets, has effectively guaranteed the clinical efficacy of product.
3, the novelty of quality standard control: the purity of having set up gel chromatography check kallidinogenase enteric coatel tablets, the potency unit of enzyme activity specificity check kallidinogenase, make product have controlled quality standard comprehensively, each step intermediate in producing from the crude drug to the solid preparation is to finished product, all control of carrying out purity and tiring guarantees the product curative effect effectively.
The specific embodiment
The present invention will be further elaborated below by instantiation, should be noted that following explanation only is in order to explain the present invention, its content not to be limited.
Embodiment 1 preparation pancreatic kininogenase tablet
A kind of kallidinogenase enteric coatel tablets, per 1000 comprise following component:
Kallidinogenase: 140,000 units
Starch: 130g
Microcrystalline Cellulose: 20g
Sodium carbonate 17g:
Hypromellose: 8g
Magnesium stearate 3g
Enteric film coat pre-mixing agent (A Hua) 24g
Preparation method:
1, prepares: adjuvants such as kallidinogenase, starch, microcrystalline Cellulose, sodium carbonate, hypromellose, magnesium stearate were pulverized 80 mesh sieves.
2, make blank granule: press recipe quantity with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing.Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby.
3, principal agent mixes: kallidinogenase is doubly measured incremental method with blank granule employing mix, at first the blank granule with equivalent mixes with kallidinogenase, behind the mix homogeneously, add the doubly blank granule remix of amount and then, behind the mix homogeneously, doubly amount increases progressively successively, finishes until whole mixing, adds the magnesium stearate mix homogeneously at last.
4, tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness.
5, enteric coated: get the enteric film coating pre-mix dose, consumption is 12% of label weight, and it is that making the coating solution compound concentration is 20% in 75% the alcoholic solution that the enteric film coating pre-mix dose is dissolved in volumetric concentration.30 ℃ of design temperatures are opened " hot blast ", " air draft ", rotate coating pan, open " spray gun " enteric coating liquid evenly is sprayed onto on the label.
6, packing: adopt aluminium-plastic bubble plate packing, the complex pocket of packing at last namely gets the kallidinogenase enteric coatel tablets.
7, product inspection.
Embodiment 2 preparation pancreatic kininogenase tablets
A kind of kallidinogenase enteric coatel tablets, per 1000 comprise following component:
Kallidinogenase: 90,000 units
Lactose: 140g
Microcrystalline Cellulose: 15g
Sodium alginate 25g
Hypromellose: 6g
Magnesium stearate 3g
Enteric film coat pre-mixing agent (Ying Mao) 28
1, prepares: adjuvants such as kallidinogenase, lactose, microcrystalline Cellulose, sodium alginate, hypromellose, magnesium stearate were pulverized 80 mesh sieves.
2, make blank granule: press recipe quantity with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing.Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby.
3, principal agent mixes: kallidinogenase is doubly measured incremental method with blank granule employing mix, at first the blank granule with equivalent mixes with kallidinogenase, behind the mix homogeneously, add the doubly blank granule remix of amount and then, behind the mix homogeneously, doubly amount increases progressively successively, finishes until whole mixing, adds the magnesium stearate mix homogeneously at last.
4, tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness.
5, enteric coated: get the enteric film coating pre-mix dose, consumption is 14% of label weight, and it is that making the coating solution compound concentration is 15% in 80% the alcoholic solution that the enteric film coating pre-mix dose is dissolved in volumetric concentration.30 ℃ of design temperatures are opened " hot blast ", " air draft ", rotate coating pan, open " spray gun " enteric coating liquid evenly is sprayed onto on the label.
6, packing: adopt aluminium-plastic bubble plate packing, the complex pocket of packing at last namely gets the kallidinogenase enteric coatel tablets.
Embodiment 3 preparation pancreatic kininogenase tablets
A kind of kallidinogenase enteric coatel tablets, per 1000 comprise following component:
Kallidinogenase: 120,000 units
Lactose: 120g
Carboxymethylstach sodium: 18g
Calcium chloride 27g
Hypromellose: 7g
Magnesium stearate 2g
Enteric film coat pre-mixing agent (A Hua) 20g
1, prepares: adjuvants such as kallidinogenase, lactose, carboxymethylstach sodium, calcium chloride, hypromellose, magnesium stearate were pulverized 80 mesh sieves.
2, make blank granule: press recipe quantity with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing.Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby.
3, principal agent mixes: kallidinogenase is doubly measured incremental method with blank granule employing mix, at first the blank granule with equivalent mixes with kallidinogenase, behind the mix homogeneously, add the doubly blank granule remix of amount and then, behind the mix homogeneously, doubly amount increases progressively successively, finishes until whole mixing, adds the magnesium stearate mix homogeneously at last.
4, tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness.
5, enteric coated: get the enteric film coating pre-mix dose, consumption is 10% of label weight, the enteric film coating pre-mix dose is dissolved in the alcoholic solution of volumetric concentration 90%, and making the coating solution compound concentration is 18%.30 ℃ of design temperatures are opened " hot blast ", " air draft ", rotate coating pan, open " spray gun " enteric coating liquid evenly is sprayed onto on the label.
6, packing: adopt aluminium-plastic bubble plate packing, the complex pocket of packing at last namely gets the kallidinogenase enteric coatel tablets.
Embodiment 4 preparation pancreatic kininogenase tablets
A kind of kallidinogenase enteric coatel tablets, per 1000 comprise following component:
Kallidinogenase: 130,000 units
Starch: 130g
Carboxymethylstach sodium: 17g
Magnesium sulfate 30g
Hypromellose: 7g
Magnesium stearate 3g
Enteric film coat pre-mixing agent (Ka Lekang) 26g
1, prepares: adjuvants such as kallidinogenase, starch, carboxymethylstach sodium, magnesium sulfate, hypromellose, magnesium stearate were pulverized 80 mesh sieves.
2, make blank granule: press recipe quantity with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing.Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby.
3, principal agent mixes: kallidinogenase is doubly measured incremental method with blank granule employing mix, at first the blank granule with equivalent mixes with kallidinogenase, behind the mix homogeneously, add the doubly blank granule remix of amount and then, behind the mix homogeneously, doubly amount increases progressively successively, finishes until whole mixing, adds the magnesium stearate mix homogeneously at last.
4, tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness.
5, enteric coated: get the enteric film coating pre-mix dose, consumption is 13% of label weight, the enteric film coating pre-mix dose is dissolved in the alcoholic solution of volumetric concentration 80%, and making the coating solution compound concentration is 17%.30 ℃ of design temperatures are opened " hot blast ", " air draft ", rotate coating pan, open " spray gun " enteric coating liquid evenly is sprayed onto on the label.
6, packing: adopt aluminium-plastic bubble plate packing, the complex pocket of packing at last namely gets the kallidinogenase enteric coatel tablets.
Embodiment 5 preparation pancreatic kininogenase tablets
A kind of kallidinogenase enteric coatel tablets, per 1000 comprise following component:
Kallidinogenase: 110,000 units
Lactose: 120g
Carboxymethylstach sodium: 16g
Sodium chloride: 33g
Hypromellose: 9g
Magnesium stearate 3g
Enteric film coat pre-mixing agent (Ying Mao) 25g
1, prepares: adjuvants such as kallidinogenase, lactose, carboxymethylstach sodium, sodium chloride, hypromellose, magnesium stearate were pulverized 80 mesh sieves.
2, make blank granule: press recipe quantity with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing.Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby.
3, principal agent mixes: kallidinogenase is doubly measured incremental method with blank granule employing mix, at first the blank granule with equivalent mixes with kallidinogenase, behind the mix homogeneously, add the doubly blank granule remix of amount and then, behind the mix homogeneously, doubly amount increases progressively successively, finishes until whole mixing, adds the magnesium stearate mix homogeneously at last.
4, tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness.
5, enteric coated: get the enteric film coating pre-mix dose, consumption is 12.5% of label weight, and it is that making the coating solution compound concentration is 16% in 85% the alcoholic solution that the enteric film coating pre-mix dose is dissolved in volumetric concentration.30 ℃ of design temperatures are opened " hot blast ", " air draft ", rotate coating pan, open " spray gun " enteric coating liquid evenly is sprayed onto on the label.
6, packing: adopt aluminium-plastic bubble plate packing, the complex pocket of packing at last namely gets the kallidinogenase enteric coatel tablets.
Table 1, the embodiment of the invention and publication comparing result
The conclusion that is obtained by table 1 is: every quality index such as the uniformity of dosage units of five embodiment, release, purity, content all are better than publication (CN101069742A).
Experimental example 1, preparation pancreatic kininogenase tablet (the former technology of enteric coatel tablets)
A kind of kallidinogenase enteric coatel tablets, per 1000 comprise following component:
Kallidinogenase: 110,000 units
Lactose: 120g
Carboxymethylstach sodium: 16g
The about 18g of 8% starch slurry
Magnesium stearate: 3g
Enteric film coat pre-mixing agent (Ying Mao) 25g
1, prepares: adjuvants such as kallidinogenase, lactose, carboxymethylstach sodium, 8% starch slurry, magnesium stearate were pulverized 80 mesh sieves.
2, make blank granule: press recipe quantity with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing.Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby.
3, principal agent mixes: adopt full dose to mix kallidinogenase and blank granule, behind the mix homogeneously, add the magnesium stearate mix homogeneously.
4, tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness.
5, enteric coated: get the enteric film coating pre-mix dose, consumption is 12.5% of label weight, and it is that making the coating solution compound concentration is 16% in 85% the alcoholic solution that the enteric film coating pre-mix dose is dissolved in volumetric concentration.30 ℃ of design temperatures are opened " hot blast ", " air draft ", rotate coating pan, open " spray gun " enteric coating liquid evenly is sprayed onto on the label.
6, packing: adopt aluminium-plastic bubble plate packing, the complex pocket of packing at last namely gets the kallidinogenase enteric coatel tablets.
Table 2, the embodiment of the invention and experimental example-original enteric coatel tablets production technology comparing result
The conclusion that is obtained by table 2 is: the former technology filler of kallidinogenase enteric coatel tablets is that starch or lactose, disintegrating agent are that carboxymethylstach sodium or microcrystalline Cellulose, binding agent are that 8% starch slurry, lubricant are adjuvants such as magnesium stearate, and the every quality index of the enteric coatel tablets that adopt above-mentioned technology to make all is lower than five embodiment of the present invention.
Claims (5)
1. kallidinogenase enteric coatel tablets is characterized in that, per 1000 comprise following component:
Kallidinogenase: 140,000 units
Starch: 130g
Microcrystalline Cellulose: 20g
Sodium carbonate: 17g
Hypromellose: 8g
Magnesium stearate: 3g
Enteric film coat pre-mixing agent: 24g, its preparation method:
1) prepares: kallidinogenase, starch, microcrystalline Cellulose, sodium carbonate, hypromellose, magnesium stearate were pulverized 80 mesh sieves;
2) make blank granule: press recipe quantity with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing; Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby;
3) principal agent mixes: kallidinogenase is doubly measured incremental method with blank granule employing mix, at first the blank granule with equivalent mixes with kallidinogenase, behind the mix homogeneously, add the doubly blank granule remix of amount and then, behind the mix homogeneously, doubly amount increases progressively successively, finishes until whole mixing, adds the magnesium stearate mix homogeneously at last;
4) tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness;
5) enteric coated: get the enteric film coating pre-mix dose, consumption is 12% of label weight, and it is that making the coating solution compound concentration is 20% in 75% the alcoholic solution that the enteric film coating pre-mix dose is dissolved in volumetric concentration; 30 ℃ of design temperatures are opened " hot blast ", " air draft ", rotate coating pan, open " spray gun " and evenly are sprayed onto enteric coating liquid on the label;
6) packing: adopt aluminium-plastic bubble plate packing, the complex pocket of packing at last namely gets the kallidinogenase enteric coatel tablets;
7) product inspection.
2. kallidinogenase enteric coatel tablets is characterized in that, per 1000 comprise following component:
Kallidinogenase: 90,000 units
Lactose: 140g
Microcrystalline Cellulose: 15g
Sodium alginate: 25g
Hypromellose: 6g
Magnesium stearate: 3g
Enteric film coat pre-mixing agent: 28g, its preparation method:
1) prepares: kallidinogenase, lactose, microcrystalline Cellulose, sodium alginate, hypromellose, magnesium stearate were pulverized 80 mesh sieves;
2) make blank granule: press recipe quantity with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing; Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby;
3) principal agent mixes: kallidinogenase is doubly measured incremental method with blank granule employing mix, at first the blank granule with equivalent mixes with kallidinogenase, behind the mix homogeneously, add the doubly blank granule remix of amount and then, behind the mix homogeneously, doubly amount increases progressively successively, finishes until whole mixing, adds the magnesium stearate mix homogeneously at last;
4) tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness;
5) enteric coated: get the enteric film coating pre-mix dose, consumption is 14% of label weight, and it is that making the coating solution compound concentration is 15% in 80% the alcoholic solution that the enteric film coating pre-mix dose is dissolved in volumetric concentration; 30 ℃ of design temperatures are opened " hot blast ", " air draft ", rotate coating pan, open " spray gun " and evenly are sprayed onto enteric coating liquid on the label;
6) packing: adopt aluminium-plastic bubble plate packing, the complex pocket of packing at last namely gets the kallidinogenase enteric coatel tablets.
3. kallidinogenase enteric coatel tablets is characterized in that, per 1000 comprise following component:
Kallidinogenase: 120,000 units
Lactose: 120g
Carboxymethylstach sodium: 18g
Calcium chloride: 27g
Hypromellose: 7g
Magnesium stearate: 2g
Enteric film coat pre-mixing agent: 20g, its preparation method:
1) prepares: kallidinogenase, lactose, carboxymethylstach sodium, calcium chloride, hypromellose, magnesium stearate were pulverized 80 mesh sieves;
2) make blank granule: press recipe quantity with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing; Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby;
3) principal agent mixes: kallidinogenase is doubly measured incremental method with blank granule employing mix, at first the blank granule with equivalent mixes with kallidinogenase, behind the mix homogeneously, add the doubly blank granule remix of amount and then, behind the mix homogeneously, doubly amount increases progressively successively, finishes until whole mixing, adds the magnesium stearate mix homogeneously at last;
4) tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness;
5) enteric coated: get the enteric film coating pre-mix dose, consumption is 10% of label weight, the enteric film coating pre-mix dose is dissolved in the alcoholic solution of volumetric concentration 90%, and making the coating solution compound concentration is 18%; 30 ℃ of design temperatures are opened " hot blast ", " air draft ", rotate coating pan, open " spray gun " and evenly are sprayed onto enteric coating liquid on the label;
6) packing: adopt aluminium-plastic bubble plate packing, the complex pocket of packing at last namely gets the kallidinogenase enteric coatel tablets.
4. kallidinogenase enteric coatel tablets is characterized in that, per 1000 comprise following component:
Kallidinogenase: 130,000 units
Starch: 130g
Carboxymethylstach sodium: 17g
Magnesium sulfate: 30g
Hypromellose: 7g
Magnesium stearate: 3g
Enteric film coat pre-mixing agent: 26g, its preparation method:
1) prepares: kallidinogenase, starch, carboxymethylstach sodium, magnesium sulfate, hypromellose, magnesium stearate were pulverized 80 mesh sieves;
2) make blank granule: press recipe quantity with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing; Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby;
3) principal agent mixes: kallidinogenase is doubly measured incremental method with blank granule employing mix, at first the blank granule with equivalent mixes with kallidinogenase, behind the mix homogeneously, add the doubly blank granule remix of amount and then, behind the mix homogeneously, doubly amount increases progressively successively, finishes until whole mixing, adds the magnesium stearate mix homogeneously at last;
4) tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness;
5) enteric coated: get the enteric film coating pre-mix dose, consumption is 13% of label weight, the enteric film coating pre-mix dose is dissolved in the alcoholic solution of volumetric concentration 80%, and making the coating solution compound concentration is 17%; 30 ℃ of design temperatures are opened " hot blast ", " air draft ", rotate coating pan, open " spray gun " and evenly are sprayed onto enteric coating liquid on the label;
6) packing: adopt aluminium-plastic bubble plate packing, the complex pocket of packing at last namely gets the kallidinogenase enteric coatel tablets.
5. kallidinogenase enteric coatel tablets is characterized in that, per 1000 comprise following component:
Kallidinogenase: 110,000 units
Lactose: 120g
Carboxymethylstach sodium: 16g
Sodium chloride: 33g
Hypromellose: 9g
Magnesium stearate: 3g
Enteric film coat pre-mixing agent: 25g, its preparation method:
1) prepares: kallidinogenase, lactose, carboxymethylstach sodium, sodium chloride, hypromellose, magnesium stearate were pulverized 80 mesh sieves;
2) make blank granule: press recipe quantity with load weighted adjuvant mix homogeneously, add purified water and stir, make soft material, the blank granule of the 20 mesh sieve systems of crossing; Granule is placed heated-air circulation oven, hot air drying below 50 ℃, dried blank granule is with 20 order stainless steel sift granulate, and is standby;
3) principal agent mixes: kallidinogenase is doubly measured incremental method with blank granule employing mix, at first the blank granule with equivalent mixes with kallidinogenase, behind the mix homogeneously, add the doubly blank granule remix of amount and then, behind the mix homogeneously, doubly amount increases progressively successively, finishes until whole mixing, adds the magnesium stearate mix homogeneously at last;
4) tabletting: add the kallidinogenase hybrid particles in hopper, blanking is strengthened gradually by minimum, and tab is thick and sheet heavy, carries out tabletting, checks that the tablet of extrusion is answered weight, consistency of thickness;
5) enteric coated: get the enteric film coating pre-mix dose, consumption is 12.5% of label weight, and it is that making the coating solution compound concentration is 16% in 85% the alcoholic solution that the enteric film coating pre-mix dose is dissolved in volumetric concentration; 30 ℃ of design temperatures are opened " hot blast ", " air draft ", rotate coating pan, open " spray gun " and evenly are sprayed onto enteric coating liquid on the label;
6) packing: adopt aluminium-plastic bubble plate packing, the complex pocket of packing at last namely gets the kallidinogenase enteric coatel tablets.
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| 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 |
| CN106668131B (en) * | 2016-11-01 | 2020-03-31 | 南京恒生制药有限公司 | Earthworm composition and preparation method thereof |
| CN108853045A (en) * | 2018-08-06 | 2018-11-23 | 成都通德药业有限公司 | A kind of art for coating of kallidinogenase enteric coatel tablets |
| CN108904786A (en) * | 2018-09-30 | 2018-11-30 | 重庆天致药业股份有限公司 | Pancreatic enzymes enteric coated preparation method |
| CN112220916A (en) * | 2020-10-26 | 2021-01-15 | 西南药业股份有限公司 | Preparation process of biological enzyme tablet and product thereof |
| CN113694034B (en) * | 2021-09-23 | 2023-03-21 | 常州千红生化制药股份有限公司 | Preparation method of enzyme tablet and enzyme tablet |
| CN117180215B (en) * | 2023-11-07 | 2024-02-02 | 成都通德药业有限公司 | Pancreatic kininogenase enteric-coated tablet and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1733913A (en) * | 2004-08-11 | 2006-02-15 | 北京赛生药业有限公司 | High purity venom kininogenase prepartion method and its pharmaceutical formulation |
| CN1737134A (en) * | 2004-08-20 | 2006-02-22 | 北京赛生药业有限公司 | High purity kallidinogenase prepartion method and its pharmaceutical formulation |
| CN101069742A (en) * | 2007-06-06 | 2007-11-14 | 上海丽珠制药有限公司 | Pancreatic kininogenase tablet and preparing method |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1733913A (en) * | 2004-08-11 | 2006-02-15 | 北京赛生药业有限公司 | High purity venom kininogenase prepartion method and its pharmaceutical formulation |
| CN1737134A (en) * | 2004-08-20 | 2006-02-22 | 北京赛生药业有限公司 | High purity kallidinogenase prepartion method and its pharmaceutical formulation |
| CN101069742A (en) * | 2007-06-06 | 2007-11-14 | 上海丽珠制药有限公司 | Pancreatic kininogenase tablet and preparing method |
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