CN115192537B - Nafamostat mesylate composition and preparation method thereof - Google Patents
Nafamostat mesylate composition and preparation method thereof Download PDFInfo
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- CN115192537B CN115192537B CN202210896107.3A CN202210896107A CN115192537B CN 115192537 B CN115192537 B CN 115192537B CN 202210896107 A CN202210896107 A CN 202210896107A CN 115192537 B CN115192537 B CN 115192537B
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- 229950009865 nafamostat Drugs 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 239000000203 mixture Substances 0.000 title claims abstract description 23
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- 238000009505 enteric coating Methods 0.000 claims abstract description 20
- 238000002955 isolation Methods 0.000 claims abstract description 20
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- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 claims description 6
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- SRXKIZXIRHMPFW-UHFFFAOYSA-N [4-[6-[amino(azaniumylidene)methyl]naphthalen-2-yl]oxycarbonylphenyl]-(diaminomethylidene)azanium;methanesulfonate Chemical compound CS([O-])(=O)=O.CS([O-])(=O)=O.C1=CC(N=C([NH3+])N)=CC=C1C(=O)OC1=CC=C(C=C(C=C2)C([NH3+])=N)C2=C1 SRXKIZXIRHMPFW-UHFFFAOYSA-N 0.000 description 27
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
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- FPLYNRPOIZEADP-UHFFFAOYSA-N octylsilane Chemical group CCCCCCCC[SiH3] FPLYNRPOIZEADP-UHFFFAOYSA-N 0.000 description 2
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- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010033649 Pancreatitis chronic Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
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- 102000004142 Trypsin Human genes 0.000 description 1
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- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
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- 229940069328 povidone Drugs 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
- A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
- A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of medicines, and particularly relates to a nafamostat mesylate composition and a preparation method thereof, wherein the nafamostat mesylate composition sequentially comprises a pill core, an isolation coating layer and an enteric coating layer from inside to outside, the pill core comprises nafamostat mesylate, a diluent and an adhesive, and the isolation coating layer comprises an isolation coating material and chitosan; the nafamostat mesylate composition disclosed by the invention is resistant to gastric acid, is not easy to degrade and is good in stability. The invention uses chitosan, which is natural active polysaccharide, has good biocompatibility, no antigenicity, no toxic side effect and biodegradability. According to the invention, the chitosan is added into the isolation layer, so that the stability can be improved, the drug release can be increased, the absorption of the drug can be facilitated, and the bioavailability can be improved.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a nafamostat mesylate composition and a preparation method thereof.
Background
Naphtolimus mesylate has an English name of NafamostatMesylate, CAS, 82956-11-4 and a molecular formula of C 19 H 17 N 5 O 2 ·(CH 4 O 3 S) 2 The structural formula is as follows:
nafamostat mesylate is a synthesized protease inhibitor, has strong selective inhibition effect on trypsin, fibrin proteinase, kallikrein (kallikrein), trypsin-like serine proteinase such as C1r, C1S and the like, and is used for improving symptoms such as acute pancreatitis, acute exacerbation of chronic pancreatitis, acute pancreatitis after pancreatic duct imaging, traumatic pancreatitis, postoperative acute pancreatitis and the like.
Nafamostat mesylate is a white loose cake, is easily dissolved in water, and is easily degraded in a water-containing state to produce degradation impurities. And because the catalyst is of an ester structure, the catalyst is unstable in hot water, alkaline medium and strong acid condition, and is easy to degrade to generate impurities. The existing nafamostat mesylate administration route is injection, has the defects of pain at an injection site, inconvenient administration and the like, and has no property of an oral preparation, so that the nafamostat mesylate administration route has limited wide application.
The Japanese bird medical Co-Ltd first developed its freeze-dried powder injection, and in 1986 in Japanese, patent (CN200610161308. X) discloses a preparation method of nafamostat mesylate freeze-dried powder injection, which selects citrate buffer as pH regulator, and citrate has certain deliquescence, which is unfavorable for stable storage of medicine.
Patent (CN: 201110404953.0) discloses a nafamostat mesylate composition containing metal salt ions, which has a certain risk for medication safety.
Patent (CN: 201210101793.7) discloses a nafamostat mesylate freeze-dried powder injection, but the invention does not verify the stability of the medicament.
At present, the existing nafamostat mesylate administration route is injection, and the oral preparation is not reported in the literature.
Disclosure of Invention
The invention aims to solve the technical problem of providing a nafamostat mesylate composition and a preparation method thereof, and solves the problem of insufficient stability of the nafamostat mesylate.
The nafamostat mesylate composition comprises a pellet core, an isolation coating layer and an enteric coating layer from inside to outside, wherein the raw materials of the pellet core comprise nafamostat mesylate, a diluent and an adhesive, and the raw materials of the isolation coating layer comprise an isolation coating material and chitosan.
The barrier coating material may be a conventional barrier coating material such as methylcellulose. Preferably, the isolating coating material is one or more of hypromellose, povidone and acrylic resin.
Preferably, the weight ratio of the isolation coating material to the chitosan is 1:1-2, preferably 1:1.
Preferably, the diluent is one or more of lactose, mannitol and microcrystalline cellulose; the adhesive is one or more of hydroxypropyl cellulose and starch.
Preferably, the weight ratio of the nafamostat mesylate, the diluent and the binder is 1:1:0.25.
Preferably, the raw materials of the enteric coating layer are one or more of acrylic resin, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate and methacrylic acid-ethyl acrylate copolymer water dispersion.
Preferably, the nafamostat mesylate composition is a capsule preparation, and in the capsule preparation, the weight ratio of the pill core to the isolation coating layer to the enteric coating layer is 100:1-5:3-10.
The invention provides a preparation method of a nafamostat mesylate composition, which comprises the steps of mixing and granulating nafamostat mesylate, a diluent and an adhesive to obtain a pill core; dissolving the isolation coating material and chitosan, and spraying the mixture on the surface of the pill core to obtain the pill core; spraying the enteric coating material on the surface of the pill core to obtain the nafamostat mesylate composition.
The specific preparation process of the pill core comprises the following steps: pouring the diluent and the adhesive with the prescribed amount into a wet mixing granulator, adding the nemorostat mesylate, stirring at 50-100 rpm, cutting at 100-600 rpm, mixing for 5-15 min, adding ethanol to prepare a soft material, extruding and rounding wet particles to prepare pill cores (controlling the extrusion speed to 10 rpm, the condensed water temperature to 6-10 ℃, and when rounding, the feeding speed is 100-400 rpm, the feeding time is about 20-60 s, the rounding speed is 200-500 rpm, the rounding time is 30-60 s, the discharging rotating speed is 200rpm, and the time is about 30 s), and then drying and granulating to obtain the finished product.
Preferably, in the preparation of the pill core, after the isolation coating material and chitosan are dissolved, the pill core is placed in a fluidized bed coating machine, the air inlet temperature is controlled to be 45-52 ℃, the air outlet temperature is controlled to be 40-50 ℃, and the spraying pressure is regulated to be 0.3-0.4 MPa.
In the preparation of the final product nafamostat mesylate composition, an enteric coating material is stirred, passes through a colloid mill, is placed in a fluidized bed coating machine, the air inlet temperature is controlled to be 40-50 ℃, the air outlet temperature is controlled to be 30-50 ℃, the spray speed is controlled to be 12-20 rpm, the spray pressure is regulated to be 0.3-0.4 MPa, and then the coating material is dried and granulated to obtain the nafamostat mesylate composition. The above operation may be repeated 1 time, if necessary.
The nafamostat mesylate composition has the beneficial effects that the nafamostat mesylate composition can resist gastric acid, is not easy to degrade and has good stability. The invention uses chitosan, which is natural active polysaccharide, has good biocompatibility, no antigenicity, no toxic side effect and biodegradability. According to the invention, the chitosan is added into the isolation layer, and the chitosan can be combined with gastric acid to form a protective film, so that the components in the medicine are stabilized, the stability is increased, the medicine absorption is increased, the medicine solubility is delayed or controlled, and the bioavailability is improved.
Detailed Description
Example 1
Prescription: 20% of temsirolimus mesylate, 20% of lactose diluent, 10% of chitosan, 5% of adhesive hydroxypropyl cellulose, 10% of isolation coating material hydroxypropyl methylcellulose, 15% of enteric coating layer material acrylic resin and 20% of methacrylic acid-ethyl acrylate copolymer water dispersion.
The preparation method comprises the following steps:
1) Preparing a pill core: pouring lactose and hydroxypropyl cellulose with the prescribed amounts into a wet mixing granulator, adding the nemorostat mesylate, stirring at 50rpm and a cutter at 300rpm, mixing for 10min, adding ethanol to prepare a soft material, extruding and rounding wet granules, preparing a pill core (controlling the extruding speed to 40rpm and the temperature of condensed water to 8 ℃, and when rounding, the feeding speed is 300rpm, the feeding time is about 50s, the rounding speed is 400rpm, the rounding time is 50s, the discharging rotating speed is 200rpm and the time is about 30 s), and then drying and granulating to obtain the finished product.
2) And (3) coating a release coating: dissolving hypromellose and chitosan, placing in a fluidized bed coating machine, controlling air inlet temperature at 50deg.C, air outlet temperature at 40deg.C, spraying liquid at 18rpm and spraying pressure at 0.3MPa, drying, and granulating. The weight gain of the pill core is controlled at 3 percent.
3) Enteric coating layer: stirring enteric coating material (acrylic resin, methacrylic acid-ethyl acrylate copolymer water dispersion), colloid milling, placing in fluidized bed coating machine, controlling air inlet temperature to 45deg.C, air outlet temperature to 40deg.C, spraying liquid at 15rpm and spray pressure to 0.3MPa, drying, and granulating. The above operation was repeated 1 time. The weight gain of the pill core is controlled to be 5 percent.
4) Encapsulating, and controlling average grain weight.
Example 2
Prescription: 20% of temsirolimus mesylate, 25% of lactose, 10% of chitosan, 5% of adhesive hydroxypropyl cellulose, 10% of isolation coating material hydroxypropyl methylcellulose, 15% of enteric coating layer material acrylic resin and 15% of methacrylic acid-ethyl acrylate copolymer water dispersion.
The preparation method comprises the following steps:
1) Preparing a pill core: pouring lactose and hydroxypropyl cellulose with the prescribed amounts into a wet mixing granulator, adding the nemorostat mesylate, stirring at 40rpm and a cutter at 400rpm, mixing for 12min, adding ethanol to prepare a soft material, extruding and rounding wet granules, preparing a pill core (controlling the extruding speed at 40rpm and the temperature of condensed water at 10 ℃, and when rounding, the feeding speed is 300rpm, the feeding time is about 50s, the rounding speed is 450rpm, the rounding time is 50s, the discharging rotating speed is 200rpm and the time is about 30 s), and then drying and granulating to obtain the finished product.
Otherwise, the same as in example 1 was conducted.
Example 3
Prescription: 20% of temsirolimus mesylate, 20% of lactose, 10% of chitosan, 5% of adhesive hydroxypropyl cellulose, 10% of isolation coating material hydroxypropyl methylcellulose, 15% of enteric coating layer material acrylic resin and 15% of methacrylic acid-ethyl acrylate copolymer water dispersion.
The preparation method comprises the following steps:
1) Preparing a pill core: pouring lactose and hydroxypropyl cellulose with the prescribed amounts into a wet mixing granulator, adding the nemorostat mesylate, stirring at 50rpm and a cutter at 500rpm, mixing for 15min, adding ethanol to prepare a soft material, extruding and rounding wet granules, preparing a pill core (controlling the extruding speed to 40rpm and the temperature of condensed water to 6 ℃, when the rounding is carried out, the feeding speed is 300rpm, the feeding time is about 50s, the rounding speed is 450rpm, the rounding time is 50s, the discharging rotating speed is 200rpm and the time is about 30 s), and then drying and granulating to obtain the finished product.
Otherwise, the same as in example 1 was conducted.
Comparative example 1
The preparation method of the isolation coating is the same as that of example 1 except that no chitosan is added in the prescription of the isolation coating, and the chitosan is 20% of hydroxypropyl methylcellulose.
Comparative example 2
In the prescription, the chitosan is replaced by mannitol, and the dosage and the preparation method are the same as those of the example 1.
Comparative example 3
In the prescription, the chitosan is replaced by the acacia, and the dosage and the preparation method are the same as those of the example 1.
Comparative example 4
In the prescription, the chitosan is replaced by D-sorbitol, and the dosage and the preparation method are the same as those of the example 1.
Comparative example 5
The coating material was removed from the formulation, only chitosan was added, and the other formulation methods were the same as in example 1.
Test example 1
The influence of different weights (8%, 10% and 12%) of chitosan on the quality of the product was examined by using the properties, the content, the related substances, the acid resistance and the dissolution rate as indexes, and other prescriptions and preparation methods were the same as in example 1.
Investigation conditions: high temperature 60 deg.C, and storing for 30 days.
The results show that: the stability is optimal and more stable when 10 percent of chitosan is added.
TABLE 1 influence of different chitosan contents on stability
Test example 2
Examples 1, 2 and 3 and comparative examples 1, 2, 3 and 4 were examined for quality by using the content, the related substances, acid resistance and dissolution rate as indicators.
Investigation conditions: high temperature 60 deg.C, and storing for 30 days.
The results show that the prescription process of the example 1 is optimal, the stability of the prescriptions of the comparative examples 1-5 is worse than that of the example 1, and the chitosan has the effects of increasing the stability and increasing the drug release compared with mannitol, acacia and D-sorbitol auxiliary materials, and the results are shown in the following table:
TABLE 2 influence of different examples and comparative examples on stability
Test example 3
The method for measuring the related substances comprises the following steps:
1. chromatographic conditions: the detection is carried out according to the four general rules 0512 of the Chinese pharmacopoeia 2020 edition. Using octyl silane bonded silica gel as a filler; taking 0.01mol/L disodium hydrogen phosphate solution (pH value is adjusted to 7.6 by phosphoric acid) as a mobile phase A and acetonitrile as a mobile phase B; the detection wavelength is 260nm, and the sample injection amount is 10ul.
Elution gradients are described in table 3 below.
TABLE 3 elution gradient Table
| Time (min) | Mobile phase a (%) | Mobile phase B (%) |
| 0.01 | 90 | 10 |
| 20.00 | 83 | 17 |
| 30.00 | 75 | 25 |
| 50.00 | 65 | 35 |
| 51.00 | 90 | 10 |
Examination of related substance detection methodology
The relevant material methodology was verified and the results are shown in table 4.
The verification result shows that the method has good specificity, high accuracy, stability and feasibility, and can be used for detecting substances related to the nafamostat mesylate preparation.
TABLE 4 methodological validation of related substances
Test example 4
Dissolution rate measurement method:
chromatographic conditions: the detection is carried out according to the four general rules 0512 of the Chinese pharmacopoeia 2020 edition. Using octyl silane bonded silica gel as a filler; 0.01mol/L disodium hydrogen phosphate solution (pH value is adjusted to 7.6 by phosphoric acid) -acetonitrile (75:25) is taken as a mobile phase; the detection wavelength is 241nm, and the sample injection amount is 20ul.
Dissolution conditions: a dissolution rate measurement method (second method) is adopted, wherein 500ml of hydrochloric acid solution of sodium chloride (1 g of sodium chloride is taken, 3.5ml of hydrochloric acid is added, water is added to 500 ml) is taken as a dissolution medium, the rotation speed is 100 revolutions per minute, the method is operated according to the law, 400ml of 0.235mol/L disodium hydrogen phosphate solution preheated to 37 ℃ is added into an operation container after 120 minutes, the rotation speed is unchanged, the method is continuously operated according to the law, the solution is taken and filtered after 45 minutes, 5ml of continuous filtrate is precisely measured, 1ml of 0.25mol/L sodium hydroxide solution is precisely added, and the mixture is uniformly shaken to be taken as a sample solution.
Dissolution methodology investigation
The dissolution methodology was verified and the results are shown in table 5.
The verification result shows that the method is good in specificity, high in accuracy, stable and feasible, and can be used for detecting the dissolution rate of the nafamostat mesylate preparation.
TABLE 5 dissolution methodology validation results
Those of ordinary skill in the art will appreciate that: the discussion of any of the embodiments above is merely exemplary and is not intended to imply that the scope of the present application is limited to such examples; combinations of features of the above embodiments or in different embodiments are also possible within the spirit of the application, steps may be implemented in any order, and there are many other variations of the different aspects of one or more embodiments described above which are not provided in detail for the sake of brevity.
One or more embodiments herein are intended to embrace all such alternatives, modifications and variations that fall within the broad scope of the present application. Any omissions, modifications, equivalents, improvements, and the like, which are within the spirit and principles of the one or more embodiments in the present application, are therefore intended to be included within the scope of the present application.
Claims (3)
1. The nafamostat mesylate composition is characterized by comprising the following components in part by weight: 20% of temsirolimus mesylate, 20% of diluent lactose, 10% of chitosan, 5% of adhesive hydroxypropyl cellulose, 10% of isolation coating material hydroxypropyl methylcellulose, 15% of enteric coating layer material acrylic resin and 20% of methacrylic acid-ethyl acrylate copolymer water dispersion;
the preparation method comprises the following steps:
1) Preparing a pill core: pouring lactose and hydroxypropyl cellulose with the prescribed amounts into a wet mixing granulator, adding the nemorostat mesylate, stirring at 50rpm, cutting at 300rpm, mixing for 10min, adding ethanol to prepare soft materials, extruding and rounding the wet granules, preparing pill cores, controlling the extrusion speed at 40rpm and the condensed water temperature at 8 ℃; when rounding, the following steps are carried out: the material feeding speed is 300rpm, the material feeding time is 50s, the rounding speed is 400rpm, the rounding time is 50s, the material discharging rotating speed is 200rpm, the material discharging rotating speed is 30s, and then drying and granulating are carried out, so that the material is obtained;
2) And (3) coating a release coating: dissolving hypromellose and chitosan, placing in a fluidized bed coating machine, controlling air inlet temperature at 50deg.C, air outlet temperature at 40deg.C, spraying liquid at 18rpm and spraying pressure at 0.3MPa, drying, and granulating; the weight gain of the pill core is controlled at 3 percent;
3) Enteric coating layer: stirring enteric coating material which is acrylic resin, methacrylic acid-ethyl acrylate copolymer water dispersion, passing through colloid mill, placing in fluidized bed coating machine, controlling air inlet temperature to 45 deg.C, air outlet temperature to 40 deg.C, spraying liquid rotating speed to 15rpm, spraying pressure to 0.3MPa, drying, and granulating; repeating the above operation for 1 time; the weight gain of the pill core is controlled at 5 percent;
4) Encapsulating, and controlling average grain weight.
2. The nafamostat mesylate composition is characterized by comprising the following components in part by weight: 20% of temsirolimus mesylate, 25% of lactose, 10% of chitosan, 5% of adhesive hydroxypropyl cellulose, 10% of isolation coating material hydroxypropyl methylcellulose, 15% of enteric coating layer material acrylic resin and 15% of methacrylic acid-ethyl acrylate copolymer water dispersion;
the preparation method comprises the following steps:
1) Preparing a pill core: pouring lactose and hydroxypropyl cellulose with the prescribed amounts into a wet mixing granulator, adding the nemorostat mesylate, stirring at 40rpm, cutting at 400rpm, mixing for 12min, adding ethanol to prepare soft materials, extruding and rounding the wet granules, preparing pill cores, controlling the extrusion speed at 40rpm and the condensed water temperature at 10 ℃; when rounding, the following steps are carried out: the material feeding speed is 300rpm, the material feeding time is 50s, the rounding speed is 450rpm, the rounding time is 50s, the material discharging rotating speed is 200rpm, the material discharging rotating speed is 30s, and then drying and granulating are carried out, so that the material is obtained;
2) And (3) coating a release coating: dissolving hypromellose and chitosan, placing in a fluidized bed coating machine, controlling air inlet temperature at 50deg.C, air outlet temperature at 40deg.C, spraying liquid at 18rpm and spraying pressure at 0.3MPa, drying, and granulating; the weight gain of the pill core is controlled at 3 percent;
3) Enteric coating layer: stirring enteric coating material which is acrylic resin, methacrylic acid-ethyl acrylate copolymer water dispersion, passing through colloid mill, placing in fluidized bed coating machine, controlling air inlet temperature to 45 deg.C, air outlet temperature to 40 deg.C, spraying liquid rotating speed to 15rpm, spraying pressure to 0.3MPa, drying, and granulating; repeating the above operation for 1 time; the weight gain of the pill core is controlled at 5 percent;
4) Encapsulating, and controlling average grain weight.
3. The nafamostat mesylate composition is characterized by comprising the following components in part by weight: 20% of temsirolimus mesylate, 20% of lactose, 10% of chitosan, 5% of adhesive hydroxypropyl cellulose, 10% of isolation coating material hydroxypropyl methylcellulose, 15% of enteric coating layer material acrylic resin and 15% of methacrylic acid-ethyl acrylate copolymer water dispersion;
the preparation method comprises the following steps:
1) Preparing a pill core: pouring lactose and hydroxypropyl cellulose with the prescribed amounts into a wet mixing granulator, adding the nemorostat mesylate, stirring at 50rpm, cutting at 500rpm, mixing for 15min, adding ethanol to prepare soft materials, extruding and rounding the wet granules, preparing pill cores, controlling the extrusion speed at 40rpm and the condensed water temperature at 6 ℃; when rounding, the following steps are carried out: the material feeding speed is 300rpm, the material feeding time is 50s, the rounding speed is 450rpm, the rounding time is 50s, the material discharging rotating speed is 200rpm, the material discharging rotating speed is 30s, and then drying and granulating are carried out, so that the material is obtained;
2) And (3) coating a release coating: dissolving hypromellose and chitosan, placing in a fluidized bed coating machine, controlling air inlet temperature at 50deg.C, air outlet temperature at 40deg.C, spraying liquid at 18rpm and spraying pressure at 0.3MPa, drying, and granulating; the weight gain of the pill core is controlled at 3 percent;
3) Enteric coating layer: stirring enteric coating material which is acrylic resin, methacrylic acid-ethyl acrylate copolymer water dispersion, passing through colloid mill, placing in fluidized bed coating machine, controlling air inlet temperature to 45 deg.C, air outlet temperature to 40 deg.C, spraying liquid rotating speed to 15rpm, spraying pressure to 0.3MPa, drying, and granulating; repeating the above operation for 1 time; the weight gain of the pill core is controlled at 5 percent;
4) Encapsulating, and controlling average grain weight.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0454383A1 (en) * | 1990-04-23 | 1991-10-30 | Aicello Chemical Co., Ltd. | Large intestinal dissociative polypeptide series oral formulation |
| US5217720A (en) * | 1990-07-10 | 1993-06-08 | Shin-Etsu Chemical Co., Ltd. | Coated solid medicament form having releasability in large intestine |
| CN1377281A (en) * | 1999-08-09 | 2002-10-30 | 大日本制药株式会社 | Solid preparations containing chitosan power and process for producing the same |
| WO2021261837A1 (en) * | 2020-06-24 | 2021-12-30 | 뉴지랩파마 주식회사 | Oral pharmaceutical composition comprising nafamostat mesylate as active ingredient |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0454383A1 (en) * | 1990-04-23 | 1991-10-30 | Aicello Chemical Co., Ltd. | Large intestinal dissociative polypeptide series oral formulation |
| US5217720A (en) * | 1990-07-10 | 1993-06-08 | Shin-Etsu Chemical Co., Ltd. | Coated solid medicament form having releasability in large intestine |
| CN1377281A (en) * | 1999-08-09 | 2002-10-30 | 大日本制药株式会社 | Solid preparations containing chitosan power and process for producing the same |
| WO2021261837A1 (en) * | 2020-06-24 | 2021-12-30 | 뉴지랩파마 주식회사 | Oral pharmaceutical composition comprising nafamostat mesylate as active ingredient |
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