CN1813728A - Enteric controlled release film coated omeprazol zinc oral solid formulation, oral semi-solid formulation and its preparing method - Google Patents
Enteric controlled release film coated omeprazol zinc oral solid formulation, oral semi-solid formulation and its preparing method Download PDFInfo
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- CN1813728A CN1813728A CN 200610057502 CN200610057502A CN1813728A CN 1813728 A CN1813728 A CN 1813728A CN 200610057502 CN200610057502 CN 200610057502 CN 200610057502 A CN200610057502 A CN 200610057502A CN 1813728 A CN1813728 A CN 1813728A
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Abstract
The present invention relates to several kinds of omeprazole zinc oral solid preparation and oral semisolid preparation which are coated with enteric film and their preparation method. These preparations are made up by using omeprazole zinc as main medicine and adding proper quantity of auxiliary material through a certain preparation process. On the basis of said invention said invention also provides a medicine preparation containing omeprazole zinc, poloxamer and/or bianze and its preparation method.
Description
Technical field
The present invention belongs to field of pharmaceutical preparations, specifically, relates to the multiple omeprazole zinc oral solid formulation of enteric film coat, oral semi-solid preparation and preparation method thereof of being surrounded by.
Background technology
The omeprazole chemical name is 5-methoxyl group-2-{[(4-methoxyl group-3,5-dimethyl-2-pyridine radicals)-methyl]-sulfinyl }-the 1H-benzimidazole, it is a kind of proton pump inhibitor.Effectively gastric acid inhibitory secretion of omeprazole is used for prevention and treatment and gastric acid diseases associated.
Omeprazole, omeprazole sodium salt and the magnesium salt of employing arranged at present,, all exist curative effect not ideal, the shortcoming that side effect is bigger though it can prevent and treatment and gastric acid diseases associated.
CN200510053986.X (full content of the document is incorporated herein by reference) discloses noval chemical compound S-omeprazole zinc; chemical name is left-handed 5-methoxyl group-2-{[(4-methoxyl group-3; 5-dimethyl-2-pyridine radicals)-methyl]-sulfinyl }-1H-benzimidazole zinc salt; S-omeprazole zinc has overcome the deficiency of prior art; be the salt of the S-omeprazole that a kind of curative effect is fast, side effect is little, be used for the treatment of application with the medicine of gastric acid related disorder.S-omeprazole zinc synthetic method is simple, is convenient to operation and manufactureization.
Have pharmaceutical preparatioies such as omeprazole, Omeprazole Sodium, magnesium omeprazole to use at present clinically, but the pharmaceutical preparation of omeprazole zinc does not appear in the newspapers as yet.
Summary of the invention
The inventor's unexpected omeprazole zinc of finding in experimentation has the effect of the inhibition gastric ulcer better than magnesium omeprazole.
An object of the present invention is to provide omeprazole zinc oral solid formulation, oral semi-solid preparation and preparation method thereof.
The inventor explores through a large amount of research, screens various pharmaceutical preparation prescriptions and preparation method, in conjunction with novel unique technique, has developed the pharmaceutical preparation multiple safe, effective, stable, easy to use of omeprazole zinc.For prevention and treatment and gastric acid diseases associated provide how better medication to select.
Pharmaceutical preparation of the present invention, described omeprazole zinc are a kind of in omeprazole zinc or the single enantiomer of omeprazole zinc.
Pharmaceutical preparation of the present invention in the preparation of per unit dosage, contains omeprazole zinc 0.0002mg to 400mg.Preferred 0.0005mg to 250mg; More preferably 0.0025mg to 150mg; More preferably 0.0025mg to 44mg.Concrete is in the preparation of per unit dosage, contains omeprazole zinc 0.0027375mg, or 0.0027375mg to 0.876mg, or 5.475mg, or 10.95mg, or 16.425mg, or 21.9mg, or 27.375mg, or 32.85mg, or 43.8mg.Be equivalent in the preparation of per unit dosage, contain omeprazole 0.0025mg, or 0.0025mg to 0.8mg, or 5mg, or 10mg, or 15mg, or 20mg, or 25mg, or 30mg, or 40mg.
Omeprazole zinc taking dose every day is generally 1mg to 400mg, and every day, taking dose can make the secretion of gastric acid excessively be suppressed above 400mg, may bring intensive harmful effect to the user.The volume of the single preparation of preparations such as granule, fine granule, pellet, microcapsule, microspheres agent is little, for making things convenient for the patient to take, usually need take many, as once taking 50 to 2000, so the content of omeprazole zinc reduces accordingly in the preparation of per unit dosage at every turn.
Pharmaceutical preparation of the present invention exists with unit dosage form, and described unit dosage form is meant single-dose preparations, as every of injection, and every bottle, every of oral formulations, every etc.
Pharmaceutical preparation of the present invention can be any pharmaceutical dosage form that is fit to clinical use.Preferably oral formulations comprises the oral solid formulation of omeprazole zinc, oral semi-solid preparation.Described preparation can be surrounded by one deck to the multilamellar enteric film coat.Described preparation can be tablet, capsule, pill, drop pill, granule, fine granule, pellet, microcapsule, microspheres agent, solid dispersion, semi-solid preparation.
Pharmaceutical preparation of the present invention can add the medicine acceptable auxiliary in case of necessity, and described adjuvant is pharmaceutically acceptable preparation adjuvant.
The omeprazole zinc that preferably contains 0.3%-85% (percentage by weight) in the pharmaceutical preparation of the present invention, and the pharmaceutically available adjuvant of 99.7%-15% (percentage by weight).The content of omeprazole zinc more preferably 0.5%-80%, more preferably 0.5%-70%, more preferably 0.5%-65% in described preparation.
For the preferred oral solid formulation of the present invention, oral semi-solid preparation, described medicine acceptable auxiliary is selected from pharmaceutically acceptable diluent, wetting agent, binding agent, disintegrating agent, fluidizer, antiplastering aid, lubricant, color, fragrant, flavor and regulator thereof, the solid dispersion carrier material, the capsule material, antioxidant, surfactant, stabilizing agent, blocker, promoter, plasticizer, cross-linking agent, the material of one or more in PH regulator and other pharmaceutically acceptable preparation adjuvant, every kind of adjuvant can not select or select for use one or more the material in this kind adjuvant.
Described diluent is one or more the material that is selected from starch, amylum pregelatinisatum, Icing Sugar, dextrin, lactose, microcrystalline Cellulose, mannitol, sorbitol, calcium sulfate, calcium carbonate and other the pharmaceutically acceptable diluent.
Described wetting agent is one or more the material that is selected from ethanol, water and other the pharmaceutically acceptable wetting agent.
Described binding agent is one or more the material that is selected from hypromellose, ethyl cellulose, sodium carboxymethyl cellulose, methylcellulose, hyprolose, starch slurry, polyvidone, gelatin, Polyethylene Glycol, 50% to 70% sucrose solution, sodium alginate soln and other the pharmaceutically acceptable binding agent.
Described disintegrating agent is one or more the material that is selected from carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, dried starch, polyvinylpolypyrrolidone, gas-producing disintegrant and other the pharmaceutically acceptable disintegrating agent.
Described fluidizer, antiplastering aid, lubricant are one or more the materials that is selected from Pulvis Talci, micropowder silica gel, magnesium stearate, polyethylene glycols, sodium laurylsulfate, magnesium laurylsulfate, hydrogenated vegetable oil and other pharmaceutically acceptable fluidizer, antiplastering aid, the lubricant.
Described color and regulator thereof are one or more the materials that is selected from medicinal pigment, food coloring, essence and other pharmaceutically acceptable color and the regulator thereof.
Described solid dispersion carrier material is to be selected from polyethylene glycols, cellulose derivative, organic acid, surfactant-based, the polyvidone class, saccharide and alcohols, cellulose family, the polyacrylic resin class, cupreol, cholesterol, cholesterol ester stearic acid, tripalmitin, castor oil hydrogenated, Oleum Ricini wax, Cera Flava, the material of one or more in Brazil wax and other pharmaceutically acceptable solid dispersion carrier material, every class solid dispersion carrier material can not select or select for use one or more the material in such solid dispersion carrier material.Surfactant, cellulose derivative, cellulose family, polyethylene glycols etc. such as preferred poloxamer, Brij.
Described capsule material is to be selected from poloxamer, Brij, alginate, chitosan, gelatin, arabic gum, the cellulose acetate phthalate ester, carboxymethyl cellulose salt, methylcellulose, ethyl cellulose, hypromellose, polylactic acid, poly-carbon ester, polyamino acid, the lactide glycolide copolymer, 6-caprolactone and lactide block copolymer, the polylactic acid-polyglycol block copolymer, polyamide, the material of one or more in silicone rubber and other pharmaceutically acceptable capsule material.
Described pH regulator agent can be at least a pharmaceutically acceptable material that is used to regulate pH value, can be one or more material of the pharmaceutically acceptable material that is used for regulating pH value of alkali compounds, buffer system, acid and other, as: sodium hydroxide, phosphate, acetate, Tris etc.
Described enteric film coat comprises the enteric film coat coating material, and described enteric film coat coating material contains one or more the material that is selected from crylic acid resin, polyvinyl alcohol phthalate ester, cellulose acetate phthalate ester, methacrylic acid copolymer, cellulose acetate benzenetricarboxylic acid ester, hydroxypropyl cellulose phthalate ester and other the pharmaceutically acceptable enteric film coat coating material.
Can not add or add one or more the material in dispersant, plasticizer, lubricant, color and regulator thereof and other the pharmaceutically acceptable additive in the described enteric film coat layer outermost layer coating.
The oral solid formulation of omeprazole zinc of the present invention, the preparation method of oral semi-solid preparation can adopt the preparation of galenic pharmacy routine techniques.Comprise in its preparation method omeprazole zinc and the blended step of described medicine acceptable auxiliary.
Described omeprazole zinc is being 0.1nm to 425 μ m with the size of particle diameter before adjuvant mixes or in finished product.Adopt superfine grinding method the particle diameter of omeprazole zinc crude drug can be dropped to about 200nm, methods such as employing chemical emulsification dispersion can drop to 10nm to 500nm with the particle diameter of omeprazole zinc crude drug.Adopt ultra micro concussion breaking method omeprazole zinc to be carried out methods such as chemical emulsification dispersion, the particle diameter of omeprazole zinc crude drug in dispersion soln can be dropped to about 1nm.
The preparation method of wherein said tablet can adopt direct powder pressing method, also can be comprise pulverizing, sieve, mix, the method for operation such as granulation, tabletting.The preparation method of described capsule can be comprise pulverizing, sieve, mix, the method for operation such as filling.The preparation method of described solid dispersion, semi-solid preparation can be comprise pulverizing, sieve, be under the liquid condition at diluent/solid dispersion carrier material mix, the method for tabletting/filling/pill/operations such as drop pill.The preparation method of described fine granule/pellet can be with comprising that extruding is sieved under the apocarpy, and is round as a ball, the method for operations such as granulate.
The coating method of described enteric film coat is to comprise acceptable enteric film coat coating method on the method for operations such as spray coating solution, drying, curing, drying and/or dropping preparation method and/or pressing and/or the other medicines preparation.
Omeprazole zinc enteric coatel tablets among the present invention and enteric coated capsule production technology are simple, production cost is lower, taking convenience, bioavailability are good; Omeprazole zinc enteric coated particles, enteric microparticle, enteric coated pill, enteric coated micropill, enteric-coated microcapsule, enteric-coated microsphere, enteric coated drop pill absorb soon, bioavailability is high; Omeprazole zinc less stable, but preparation provided by the present invention all has good stable.Production technology safety and environmental protection of the present invention helps medicament compartment internal medium and personnel's production safety.
The very important purpose of another one of the present invention is exactly on the basis of aforementioned invention, provides in addition a kind of more separately and contains omeprazole zinc, poloxamer and/or Brij and do not added or added one or more the pharmaceutical preparation and preparation method thereof of material in other pharmaceutically acceptable adjuvant.Described preparation method comprises: omeprazole zinc, poloxamer and/or Brij and/or described other pharmaceutically acceptable adjuvant are in the step that mix homogeneously under the liquid condition is made mixture at poloxamer and/or Brij.
In experimentation, the inventor is unexpected to find that omeprazole zinc, poloxamer and/or Brij are in the mixture that mix homogeneously is made under the liquid condition at poloxamer and/or Brij has very good character.This mixture is waxy solid at normal temperatures, can dissolve to be liquid after temperature raises.And poloxamer, Brij itself promptly are better non-ionic surface active agents, and toxicity is very little.
As use poloxamer and/or Brij as main adjuvant, itself and omeprazole zinc are under the liquid condition mix homogeneously at poloxamer and/or Brij make mixture, this mixture can be made multiple peroral dosage form, the dosage form that can select is many, as mixture is cooled off while extruding, again the bar of extruding is cut into the lamellar thing, with tablet bag enteric film coat, make Formulation again; Or mixture directly is filled in the enteric hollow capsule shell, make capsule; Or mixture adopted dropping preparation method, and the bag enteric film coat is made drop pill; Or employing spraying coagulation, mixture sprayed into to condense in the cold airflow form microcapsule/microsphere, or adopt other pharmaceutically acceptable microcapsule/method for preparing microsphere, and mixture is made microcapsule/microsphere, again gained microcapsule/microsphere bag enteric film coat is made microcapsule/microspheres agent.
The coating method of described enteric film coat is to comprise acceptable enteric film coat coating method on the method for operations such as spray coating solution, drying, curing, drying and/or dropping preparation method and/or pressing and/or the other medicines preparation.
Prepare simultaneously in the production process of described mixture and can not produce waste water,waste gas and industrial residue, produce and finish the back and only need inner surface of container to be cleaned and get final product with hot water; Poloxamer, Brij itself promptly are better non-ionic surface active agents, can no longer need other to clean adjuvant during cleaning, clean and generally can not produce the residual of cleaning adjuvant after finishing, the health that helps workshop internal medium and producers, can prolong the life-span of medicament compartment inner air cleaning system, prolong maintenance period, reduce the operation and maintenance cost.
And the operation of said preparation before finally making preparation is identical, can be implemented on the general-purpose platform and operate, selectable process route is many in actual production, can make full use of the production equipment in the existing pharmaceutical factory, reduce cost, provide curative effect is better, the dosage form selection space is bigger, cost the is lower prevention and the medicine of treatment and gastric acid diseases associated to become possibility for being embodied as the patient.
From the pharmacological evaluation of preparation of the present invention, as can be seen, the generation that omeprazole zinc preparation of the present invention can dose-dependent inhibition rat peptic gastric ulcer, under the Isodose, the effect of omeprazole zinc preparation of the present invention is better than the effect of magnesium omeprazole.Omeprazole zinc preparation of the present invention suppresses the effect of rat experiment gastric ulcer, main and gastric acid inhibitory secretion, and the rising gastric juice pH is relevant, and is also relevant with pepsin activity with the inhibition gastric secretion.
The specific embodiment
Below will the invention will be further described by embodiment, these descriptions are not that content of the present invention is done further qualification.One skilled in the art will understand that the equal replacement that technical characterictic of the present invention is done, or corresponding the improvement, still belong within protection scope of the present invention.
Embodiment
Omeprazole zinc in following examples provides by Xuanhong Medicine Technology Co., Ltd., Tianjin, and adjuvant is commercially available product.All preparations all are to wrap sealing coat earlier, wrap enteric film coat again.The preferred nonacid material of the material of described sealing coat.
Embodiment 1
Prepare sheet/capsule in the preparation of the present invention according to following prescription and method.
Prescription
(1) sheet/capsule 's content prescription: make 1000 slices/
| Prescription 1 | Prescription 2 | Prescription 3 | |
| Omeprazole zinc/S-omeprazole zinc | 2.0g | 21.9g | 120.0g |
| Lactose | 80.0g | 80.0g | 80.0g |
| Microcrystalline Cellulose | 80.0g | 80.0g | 80.0g |
| Carboxymethyl starch sodium | 10.0g | 10.0g | 10.0g |
| Carboxymethyl starch sodium slurry (6%) | In right amount | In right amount | In right amount |
| Magnesium stearate | 2g | 2g | 2g |
| Sodium lauryl sulphate | 2g | 2g | 2g |
(2) tablet enteric film coat prescription:
1000 of plain sheets
| Prescription 4 | Prescription 5 | Prescription 6 | |
| 90% ethanol | 100ml | 100ml | 150ml |
| Acrylic resin II+III number (2: 1) | 5g | 5g | 7.5g |
| Polyoxyethylene sorbitan monoleate | 2ml | 2ml | 3ml |
| Diethyl phthalate | 2ml | 2ml | 3ml |
| PEG400 | 2ml | 2ml | 3ml |
| Pulvis Talci | 6g | 6g | 9g |
| Titanium dioxide | 6g | 6g | 9g |
Preparation technology
(1) sheet/capsule technology
A. be that 200nm to 10 μ m, micronizing to 95% grain diameter are that 200nm to 10 μ m/ ground 120 mesh sieves, ground 100 mesh sieves with omeprazole zinc/S-omeprazole zinc micronizing to 95% grain diameter,
B. take by weighing adjuvant (except that the magnesium stearate) mix homogeneously of recipe quantity, cross 80 mesh sieve mixings,
C. with adjuvant and omeprazole zinc/S-omeprazole zinc increasing progressively the abundant mixing of dilution method,
D. with 6% carboxymethyl starch sodium slurry said mixture is made soft material, pushed 24 mesh sieves,
E.40 ℃ to 50 ℃ of dry 1h to 4h, cross 20 mesh sieve granulate, add magnesium stearate, mixing,
F. with above-mentioned granule tabletting, get plain sheet; Plain sheet sieve is removed fine powder, wrap enteric film coat in accordance with the following methods, promptly get omeprazole zinc of the present invention/S-omeprazole zinc enteric coatel tablets.
G. use hollow enteric coated capsule No. 3, No. 3, No. 2, above-mentioned " e " gained granule with capsule filling machine tool filler particles, with the polishing of gained capsule, is promptly got omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule then.
(2) tablet enteric film coat technology
A. it is even acrylic resin II+III number (2: 1) to be added 90% ethanol (about 80ml, 80ml, 120ml) high-speed stirred,
B. polyoxyethylene sorbitan monoleate, diethyl phthalate, PEG400 are added remaining 90% ethanol (20ml, 20ml, 30ml) high speed and stir vibration 10 minutes,
C. stir (slowly stirring 30 minutes) in the mixed liquor with Pulvis Talci, titanium dioxide adding a and b,
D. will join coating solution filter through 80 eye mesh screens, in case coarse granule blocks spray gun,
E. continue to stir coating solution in the coating process, blow and remove dust, spray gun is aimed at the sheet bed top of upset and is adjusted atomizing pressure and the fast 10ml/min of spray, lead to 40 ℃ to the coating pan bottom--50 ℃ of hot blasts, keeping the material bed tempertaure is 35 ℃, and approximately the spray coating time is 80min--90min
F. last the ventilation dries up, and stops hot blast,
G. coated tablet is taken out, spread out in porcelain dish, to dry and spend the night.
It is good that prescription among the embodiment 1 is made the sheet/capsule stability, the release that obtain behind sheet/capsule, has better tablets/capsules agent performance.
Pharmacological evaluation shows that under Isodose it is than magnesium omeprazole (the pink enteric coated tablet of selling in the market; Specification: 10mg/ sheet; Lot number: EL2125, manufacturing enterprise: AstraZenecaAB divides packing enterprise: the effect that has stronger inhibition rat peptic gastric ulcer AstraZeneca pharmaceutical Co. Ltd).
Relatively tradition is reliable for preparation technology simultaneously, can make full use of existing medicament compartment and equipment, can build new medicament compartment, can significantly reduce the present invention and put into serial production required hardware investment.Making to prevention and treatment and gastric acid diseases associated provides better medication to be selected to possibility.
Embodiment 2
Prepare 1000 slices/of sheet/capsules in the preparation of the present invention according to following prescription and method.
Prescription
| Prescription 7 | Prescription 8 | Prescription 9 | |
| Omeprazole zinc/S-omeprazole zinc | 2.0g | 21.9g | 45.0g |
| Starch | 80.0g | 80.0g | 80.0g |
| Microcrystalline Cellulose | 80.0g | 80.0g | 80.0g |
| Carboxymethyl starch sodium | 8.0g | 8.0g | 8.0g |
| Hyprolose | 8.0g | 8.0g | 8.0g |
| Micropowder silica gel | 2.5g | 2.5g | 2.5g |
| Magnesium stearate | 2.5g | 2.5g | 2.5g |
| Sodium lauryl sulphate | 2g | 2g | 2g |
Preparation technology
A. take by weighing the omeprazole zinc/S-omeprazole zinc of recipe quantity, cross 80 mesh sieves,
B. take by weighing the adjuvant mix homogeneously of recipe quantity, cross 80 mesh sieve mixings,
C. with adjuvant and omeprazole zinc/S-omeprazole increasing progressively the abundant mixing of dilution method,
D. with " c " step gained mixture with direct powder pressing method tabletting, plain sheet, again with plain sheet bag enteric film coat, promptly get omeprazole zinc of the present invention/S-omeprazole zinc metal sheet;
E. " c " step gained mixture directly is filled in the hollow enteric coated capsule, promptly gets omeprazole zinc of the present invention/S-omeprazole zinc capsule.
It is good that prescription among the embodiment 2 is made the sheet/capsule stability, the release that obtain behind sheet/capsule.Do not need heating in the preparation process simultaneously, preparation method is simple, step is few, the time is short, can more effectively protect omeprazole zinc crude drug not to be destroyed.
Simultaneously required production process and equipment are few, can save a large amount of medicament compartment areas, reduce a large amount of air cleaning, conditioning equipment and facility, significantly reduce the operation and maintenance cost of producing used medicament compartment.
Embodiment 3
Prepare granule, ball, microparticle, micropill, capsule in the preparation of the present invention according to following prescription and method.
Prescription
| Prescription 10 | Prescription 11 | Prescription 12 | Prescription 13 | |
| Omeprazole zinc/S-omeprazole zinc | 1.0g | 21.9g | 120.0g | 240.0g |
| Lactose | 80.0g | 80.0g | 80.0g | 80.0g |
| Microcrystalline Cellulose | 80.0g | 80.0g | 80.0g | 80.0g |
| Carboxymethyl starch sodium | 10.0g | 10.0g | 10.0g | 10.0g |
| Hypromellose slurry (8%) | In right amount | In right amount | In right amount | In right amount |
| Sodium lauryl sulphate | 2.0g | 2.0g | 2.0g | 2.0g |
Preparation technology
A. be that 200nm to 10 μ m, micronizing to 95% grain diameter are that 200nm to 10 μ m/ ground 200 mesh sieves, ground 200 mesh sieves, ground 200 mesh sieves with omeprazole zinc/S-omeprazole zinc micronizing to 95% grain diameter,
B. take by weighing the adjuvant mix homogeneously of recipe quantity, cross 200 orders, 200 orders, 150 orders, 150 mesh sieve mixings,
C. with adjuvant and omeprazole zinc/S-omeprazole zinc increasing progressively the abundant mixing of dilution method,
D. with 8% hypromellose slurry said mixture is made soft material (mixed-powder about 10% is not made soft material), pushed 40 mesh sieves, with the residue mixed-powder that granule is round as a ball; 45 ℃ of dry 30min to 4h again, 30 mesh sieve granulate; Air blast bag enteric film coat promptly gets omeprazole zinc of the present invention/S-omeprazole zinc enteric coated particles/ball then.
E. use 8% hypromellose that above-mentioned " c " step gained mixture is made soft material (mixed-powder about 10% is not made soft material), under apocarpy, pushed 100 mesh sieves, with the residue mixed-powder that granule is round as a ball under logical mild wind state; 45 ℃ of dry 30min to 4h again, 80 mesh sieve granulate, microparticle/micropill; With gained microparticle/micropill air blast bag enteric film coat, promptly get omeprazole zinc of the present invention/S-omeprazole zinc enteric microparticle/micropill then.
F. above-mentioned " e " step gained microparticle/micropill is filled to and promptly gets omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule in the hollow enteric coated capsule.
G. above-mentioned " e " step gained enteric microparticle/micropill is filled to and promptly gets omeprazole zinc of the present invention/S-omeprazole zinc capsule in the Capsules.
H. promptly get omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule in the hollow enteric coated capsule with being filled to after above-mentioned " e " step gained microparticle/micropill and the mixed of enteric microparticle/micropill by 5%-95%: 95%-5%.
Embodiment 3 gained granules, ball, microparticle, micropill bioavailability are higher; Gained capsule/enteric coated capsule method for filling novelty, carry taking convenience; " h " gained omeprazole zinc/S-omeprazole zinc enteric coated capsule both can be brought into play drug effect faster, had certain slow controlled-release effect again, can prolong the action time of effective ingredient.
Embodiment 4
Prepare micropill, capsule in the preparation of the present invention according to following prescription and method.
Prescription
| Prescription 14 | Prescription 15 | Prescription 16 | |
| Omeprazole zinc/S-omeprazole zinc | 1.0g | 21.9g | 45.0g |
| Poloxamer | 0.5g | 3.0g | 6.0g |
| 75% ethanol/acetone | 40.0ml | 150.0ml | 300.0ml |
| Blank micropill (diameter 0.1mm to 3.0mm) | 100.0g | 100.0g | 100.0g |
Preparation technology
A. omeprazole zinc/S-omeprazole zinc micronizing to 95% grain diameter is 200nm to 10 μ m, ground 200 mesh sieves, ground 200 mesh sieves,
B. take by weighing the poloxamer of recipe quantity, cross 200 orders, 200 orders, 150 mesh sieves,
C. with " b " step gained poloxamer and " a " step gained omeprazole zinc/S-omeprazole zinc to increase progressively the abundant mixing of dilution method, then it is slowly poured in 75% ethanol, the limit edged stirs, and again the mixture middling speed is stirred 30min to 4h, make mix homogeneously
D. with " b " step gained poloxamer and " a " step gained omeprazole zinc/S-omeprazole zinc to increase progressively the abundant mixing of dilution method, then it is slowly poured in the acetone, the limit edged stirs, again with the ultrasonic concussion 10min to 4h of mixture elder generation, middling speed stirs 30min to 4h again, makes mix homogeneously
E. adopt the method for bag film-coat, " c " step gained mixed liquor is sprayed onto blank micropill surface under stirring, limit spray snare drum is air-dry dry, gets micropill,
F. adopt the method for bag film-coat, " d " step gained mixed liquor is sprayed onto blank micropill surface under stirring, limit spray snare drum is air-dry dry, gets micropill,
G. with " e " step gained micropill bag enteric film coat, promptly get omeprazole zinc/S-omeprazole zinc enteric coated micropill.
H. with " f " step gained micropill bag enteric film coat, promptly get omeprazole zinc/S-omeprazole zinc enteric coated micropill.
I. above-mentioned " e "/" f " step gained micropill is filled to and promptly gets omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule in the hollow enteric coated capsule.
J. above-mentioned " g "/" h " step gained enteric coated micropill is filled to and promptly gets omeprazole zinc of the present invention/S-omeprazole zinc capsule in the Capsules.
K. promptly get omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule in the hollow enteric coated capsule with being filled to after above-mentioned " e "/" f " step gained micropill and the mixed of " g "/" h " step enteric microparticle/micropill by 5%-95%: 95%-5%.
Omeprazole zinc among the embodiment 4/S-omeprazole zinc is distributed in the surface of blank micropill, is absorbed by the patient easilier after being taken by the patient; Gained capsule/enteric coated capsule method for filling novelty, carry taking convenience; " k " gained omeprazole zinc/S-omeprazole zinc enteric coated capsule both can be brought into play drug effect faster, had certain slow controlled-release effect again, can prolong the action time of effective ingredient.
Embodiment 5
Prepare Formulation, capsule, drop pill, microsphere in the preparation of the present invention according to following prescription and method.Prescription
| Prescription 17 | Prescription 18 | Prescription 19 | Prescription 20 | |
| Omeprazole zinc/S-omeprazole zinc | 2.0g | 21.9g | 70.0g | 140.0g |
| Poloxamer | 400.0g | 430.0g | 430.0g | 430.0g |
| Prescription 21 | Prescription 22 | Prescription 23 | Prescription 24 | |
| Omeprazole zinc/S-omeprazole zinc | 2.0g | 21.9g | 70.0g | 140.0g |
| Brij | 400.0g | 430.0g | 430.0g | 430.0g |
Preparation technology
Prescription 17 and prescription 21, prescription 18 and prescription 22, prescription 19 and prescription 23, prescription 20 is identical with the preparation technology of prescription 24.
A. will write out a prescription 17,21, prescription 18,22, prescription 19,23, micronizing to 95% grain diameter is 200nm to 10 μ m to the omeprazole zinc/S-omeprazole zinc of prescription in 20,24 respectively, to grind 100 mesh sieves/ground 200 mesh sieves/micronizing to 95% grain diameter be 200nm to 10 μ m, ground 100 mesh sieves/ground 200 mesh sieves, ground 100 mesh sieves/ground 200 mesh sieves
B. take by weighing the adjuvant of recipe quantity, 45 ℃ to 80 ℃ dissolve and are incubated,
C. omeprazole zinc/S-omeprazole zinc is slowly added in the adjuvant several times, the limit edged stirs,
D. mixture is stirred 30min to 12h under 45 ℃ to 80 ℃ conditions, be filled to then in No. 1, No. 1, No. 1, No. 0 hollow enteric coated capsule, promptly get omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule.
E. with above-mentioned " c " step gained mixture ultrasonic concussion 30min to 6h of elder generation under 45 ℃ to 80 ℃ conditions, or else stir or middling speed stirring 30min to 6h, be filled to then in No. 1, No. 1, No. 1, No. 0 hollow enteric coated capsule, promptly get omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule.
F. 5min to 2h is pulverized in the first ultra micro concussion under 45 ℃ to 80 ℃ conditions of above-mentioned " c " step gained mixture, or else stir or middling speed stirring 10min to 2h, be filled at last in No. 1, No. 1, No. 1, No. 0 hollow enteric coated capsule, promptly get omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule.
G. above-mentioned " c " gained mixture is stirred 30min to 24h under 45 ℃ to 80 ℃ conditions,
H. utilize suitable mechanical implement, above-mentioned " g " gained mixture is cooled off while extruding, again the bar of extruding is cut into the lamellar thing,, promptly get omeprazole zinc/S-omeprazole zinc metal sheet shape preparation again with tablet bag enteric film coat.
I. above-mentioned " g " step gained mixture is evenly splashed into certain flow rate and make drop pill in the dimethicone, drop pill low temperature to room temperature bag enteric film coat, is promptly got omeprazole zinc of the present invention/S-omeprazole zinc enteric coated drop pill.
J. adopt the spraying coagulation, above-mentioned " g " step gained mixture sprayed into that making in the cold airflow condenses and form microsphere,
K. above-mentioned " j " step thus obtained microsphere low temperature to room temperature bag enteric film coat is promptly got omeprazole zinc of the present invention/S-omeprazole zinc enteric-coated microsphere.
L. above-mentioned " j " step thus obtained microsphere is filled to and promptly gets omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule in the hollow enteric coated capsule.
M. above-mentioned " k " step gained enteric-coated microsphere is filled to and promptly gets omeprazole zinc of the present invention/S-omeprazole zinc capsule in the Capsules.
N. promptly get omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule in the hollow enteric coated capsule with being filled to after above-mentioned " j " step thus obtained microsphere and the mixed of " k " gained enteric-coated microsphere by 5%-95%: 95%-5%.
Omeprazole zinc among the embodiment 5/S-omeprazole zinc is evenly distributed in poloxamer/Brij, can slowly dissolve and be absorbed after being taken by the patient, has certain slow-releasing and controlled-releasing action and compares high bioavailability.
Gained method for preparing tablet thereof novelty, it is few to produce dirt, and the production efficiency height is worthy to be popularized; The gained drop pill, microsphere is easier is absorbed by the patient.
The operation of said preparation before finally making preparation is identical, can be implemented on the general-purpose platform to operate, and selectable process route is many in actual production, can make full use of the production equipment in the existing pharmaceutical factory, reduces cost.
Simultaneously " l ", " m ", " n " gained capsule/enteric coated capsule method for filling novelty, carry taking convenience; " n " gained omeprazole zinc/S-omeprazole zinc enteric coated capsule both can be brought into play drug effect faster, had better slow controlled-release effect again, can prolong the action time of effective ingredient.
Embodiment 6
Prepare microcapsule, capsule in the preparation of the present invention according to following prescription and method.
Prescription
| Prescription 25 | Prescription 26 | Prescription 27 | |
| Omeprazole zinc/S-omeprazole zinc | 1.0g | 21.9g | 100.0g |
| Poloxamer | 2.0g | 2.0g | 2.0g |
| PEG6000 | 180.0g | 180.0g | 180.0g |
| PEG20000 | 5.0g | 5.0g | 5.0g |
Preparation technology
A. be that 200nm to 5 μ m, micronizing to 95% grain diameter are that 200nm to 5 μ m/ ground 200 mesh sieves, ground 200 mesh sieves with omeprazole zinc/S-omeprazole zinc micronizing to 95% grain diameter,
B. take by weighing the adjuvant of recipe quantity, 45 ℃ to 80 ℃ dissolve and are incubated,
C. omeprazole zinc/S-omeprazole zinc is slowly added in the adjuvant several times, the limit edged stirs,
D. mixture is stirred 30min to 12h under 45 ℃ to 80 ℃ conditions,
E. adopt the spraying coagulation, " d " gained mixture is sprayed into to condense in the cold airflow form microcapsule,
F. microcapsule low temperature to room temperature bag enteric film coat is promptly got omeprazole zinc of the present invention/S-omeprazole zinc enteric-coated microcapsule.
G. above-mentioned " e " gained microcapsule is filled to and promptly gets omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule in the hollow enteric coated capsule.
H. above-mentioned " f " gained enteric-coated microcapsule is filled to and promptly gets omeprazole zinc of the present invention/S-omeprazole zinc capsule in the Capsules.
I. promptly get omeprazole zinc of the present invention/S-omeprazole zinc enteric coated capsule in the hollow enteric coated capsule with being filled to after above-mentioned " e " gained microcapsule and the mixed of " f " gained enteric-coated microcapsule by 5%-95%: 95%-5%.
Embodiment 6 gained microcapsule bioavailability are higher; " g, " h, " i " gained capsule/enteric coated capsule method for filling novelty, carry taking convenience simultaneously; " i " gained omeprazole zinc/S-omeprazole zinc enteric coated capsule both can be brought into play drug effect faster, had certain slow controlled-release effect again, can prolong the action time of effective ingredient.
Embodiment 7
It below is the pharmacological evaluation of preparation of the present invention.
Omeprazole zinc is summarized as follows the experiment of rat experiment gastric ulcer influence:
1. experiment material
1.1 omeprazole zinc: preparation of the present invention, white enteric coated tablet; Specification: 20mg/ sheet; Xuanhong Medicine Technology Co., Ltd., Tianjin provides.It is standby to be made into the suspension of variable concentrations with 0.5% sodium carboxymethyl cellulose (0.5%CMC) before the experiment.
1.2 magnesium omeprazole: pink enteric coated tablet; Specification: 10mg/ sheet; Lot number: EL2125, manufacturing enterprise: AstraZeneca AB, divide packing enterprise: AstraZeneca pharmaceutical Co. Ltd.It is standby to be made into the suspension of variable concentrations with 0.5% sodium carboxymethyl cellulose (0.5%CMC) before the experiment.
1.3 laboratory animal: the Wistar rat, the male and female dual-purpose, available from Beijing Vital River Experimental Animals Technology Co., Ltd., the animal quality certification number: SCXK (capital) 2002-0003.
2. experimental technique and result
2.1 omeprazole zinc is to the influence of digestibility ulcer index:
Get 70 of healthy rats, male and female half and half, body weight 200 ± 10g is divided into 5 groups at random.Each organizes equal gastric infusion, once a day, and continuous 5 days.Single cage is raised after the administration in the 5th day, fasting (can't help water) 48 hours, and after 48 hours, the ligation pylorus, the operation metaduodenum is administered once.Behind the ligation pylorus 12 hours, the etherization rat after getting stomach and removing gastric juice, is injected 1% formalin 10ml, behind the 10min, cuts off stomach along greater gastric curvature, and water washes gastric content gently, and stomach is in the plane open and flat, with microscope auxiliary examination mucosa.Record ulcer number and ulcer area.Ulcer area=π * major diameter/2 * minor axis/2.With every Mus ulcer surface integration is 7 grades, as ulcer index, when the ulcer area is 0,1-8,9-24,25-63,64-120,121-168,＞169 or during perforation, ulcer index is respectively 0,1,2,3,4,5,6,7.Each group ulcer index is carried out statistics relatively.And calculate ulcer according to ulcer index and suppress percentage rate.Ulcer suppresses percentage rate=(matched group ulcer index-administration group ulcer index)/matched group ulcer index * 100%.
Use pylorus ligature law to set up rat experiment gastric ulcer model, exponential influence sees Table 1 to rat ulcer to record omeprazole zinc.
Table 1 omeprazole zinc preparation of the present invention is to the exponential influence of rat ulcer (x ± SD)
| Group | Dosage (mg/Kg) | Number of animals (n) | Ulcer index | Suppression ratio (%) |
| Model control group | -- | 14 | 3.21 ± 1.53 | -- |
| Omeprazole zinc group | 3.0 | 14 | 2.50 ± 1.23 | 22.2 |
| Omeprazole zinc group | 6.0 | 14 | 1.79 ± 1.48* | 44.4 |
| Omeprazole zinc group | 12.0 | 14 | 0.79 ± 0.98** △ | 75.6 |
| The magnesium omeprazole group | 12.0 | 14 | 1.64 ± 0.93** | 48.9 |
| Remarks: model control group gives 0.5%CMC; Compare * P＜0.05, * * P＜0.01 with model group; Compare △ P＜0.05 with positive drug. | ||||
2.2 omeprazole zinc preparation of the present invention to the shadow of gastric secretion, gastric acid pH value and pepsin activity to:
Get 70 of healthy rats, male and female half and half, body weight 190 ± 10g is divided into 5 groups at random.Each organizes equal gastric infusion, once a day, and continuous 5 days.Single cage is raised after the administration in the 5th day, fasting (can't help water) 48 hours, and after 48 hours, the ligation pylorus, the operation metaduodenum is administered once.Behind the ligation pylorus 8 hours, the etherization rat is got stomach, inclines to gastric content and be collected in the graduated centrifuge tube.(1) gets supernatant behind the centrifugal 15min of 2000rpm/min and measure the gastric juice volume.(2) centrifugal back liquid is measured gastric juice pH.(3) measure pepsin with Mai Tefa.More than in three indexs, gastric secretion and pepsin activity calculate suppression ratio (%) behind the drug respectively, method is tested with ulcer index.Gastric juice pH is obtained the percentage rate that raises behind the medicine, rising percentage rate=(administration group pH value-matched group pH value)/matched group pH value * 100%.
According to last method record omeprazole zinc preparation of the present invention to the influence of gastric secretion, gastric acid pH value and pepsin activity see Table 2, table 3, table 4.
Table 2 omeprazole zinc preparation of the present invention is to the influence of rat gastric secretion (x ± SD)
| Group | Dosage (mg/Kg) | Number of animals (n) | Gastric secretion (ml) | Suppression ratio (%) |
| Model control group | -- | 14 | 11.15 ± 2.28 | -- |
| Omeprazole zinc group | 3.0 | 14 | 10.39 ± 3.38 | 6.85 |
| Omeprazole zinc group | 6.0 | 14 | 9.21 ± 2.63 | 17.42 |
| Omeprazole zinc group | 12.0 | 14 | 9.57 ± 3.31 | 14.16 |
| The magnesium omeprazole group | 12.0 | 14 | 10.24 ± 2.24 | 8.20 |
| Remarks: model control group gives 0.5%CMC distilled water; Each group compares P＞0.05 with model group. | ||||
Table 3 omeprazole zinc preparation of the present invention is to the influence of rat gastric juice pH (x ± SD)
| Group | Dosage (mg/Kg) | Number of animals (n) | Gastric juice pH | Rate of rise (%) |
| Model control group | -- | 14 | 3.23 ± 2.01 | -- |
| Omeprazole zinc group | 3.0 | 14 | 3.25 ± 1.61 | 4.90 |
| Omeprazole zinc group | 6.0 | 14 | 4.67 ± 2.33 | 44.52 |
| Omeprazole zinc group | 12.0 | 14 | 4.95 ± 1.86* | 53.21 |
| The magnesium omeprazole group | 12.0 | 14 | 4.86 ± 1.98* | 50.40 |
| Remarks: model control group gives 0.5%CMC distilled water; Compare * P＜0.05 with model group. | ||||
Table 4 omeprazole zinc preparation of the present invention is to the influence of rat stomach proteinase activity (x ± SD)
| Group | Dosage (mg/Kg) | Number of animals (n) | Pepsin activity (μ) | Suppression ratio (%) |
| Model control group | -- | 14 | 1173.4 ± 330.8 | -- |
| Omeprazole zinc group | 3.0 | 14 | 1077.5 ± 292.7 | 8.17 |
| Omeprazole zinc group | 6.0 | 14 | 1055.9 ± 248.7 | 10.01 |
| Omeprazole zinc group | 12.0 | 14 | 1038.5 ± 324.3 | 11.49 |
| The magnesium omeprazole group | 12.0 | 14 | 1050.9 ± 205.9 | 10.44 |
| Remarks: model control group gives 0.5%CMC distilled water; Each group compares P＞0.05 with model group. | ||||
As can be seen from the above results, the generation that omeprazole zinc preparation of the present invention can dose-dependent inhibition rat peptic gastric ulcer, under the Isodose, the effect of omeprazole zinc preparation of the present invention is better than the effect of magnesium omeprazole.Omeprazole zinc preparation of the present invention suppresses the effect of rat experiment gastric ulcer, main and gastric acid inhibitory secretion, and the rising gastric juice pH is relevant, and is also relevant with pepsin activity with the inhibition gastric secretion.
Claims (13)
1, a kind of pharmaceutical preparation that contains omeprazole zinc is characterized in that described preparation is selected from: oral solid formulation and oral semi-solid preparation; Described preparation is surrounded by one deck to the multilamellar enteric film coat.
2, pharmaceutical preparation according to claim 1 is characterized in that described omeprazole zinc is a kind of in omeprazole zinc or the single enantiomer of omeprazole zinc.
3, pharmaceutical preparation according to claim 1 is characterized in that in the preparation of per unit dosage, contains omeprazole zinc 0.0002mg to 400mg; Preferred 0.0005mg to 250mg; More preferably 0.0025mg to 150mg; More preferably 0.0025mg to 44mg.
4, pharmaceutical preparation according to claim 3, it is characterized in that in the preparation of per unit dosage, contain omeprazole zinc 0.0027375mg to 0.876mg, or to 5.475mg, or to 10.95mg, or to 16.425mg, or to 21.9mg, or to 27.375mg, or to 32.85mg, or to 43.8mg.
5,, it is characterized in that described oral solid formulation, oral semi-solid preparation are selected from tablet, capsule, pill, drop pill, granule, fine granule, pellet, microcapsule, microspheres agent, solid dispersion, and semi-solid preparation according to described pharmaceutical preparation one of in the claim 1 to 4.
6, pharmaceutical preparation according to claim 5 is characterized in that described pharmaceutical preparation also contains the medicine acceptable auxiliary, and described adjuvant is pharmaceutically acceptable preparation adjuvant; For oral solid formulation and oral semi-solid preparation, described adjuvant is selected from one or more the material in pharmaceutically acceptable diluent, wetting agent, binding agent, disintegrating agent, fluidizer, antiplastering aid, lubricant, color and regulator thereof, solid dispersion carrier material, capsule material, antioxidant, surfactant, stabilizing agent, blocker, promoter, plasticizer, cross-linking agent, PH regulator and other the pharmaceutically acceptable preparation adjuvant, and every kind of adjuvant can not select or select for use one or more the material in this kind adjuvant.
7, pharmaceutical preparation according to claim 6 is characterized in that:
Described diluent is one or more the material that is selected from starch, amylum pregelatinisatum, Icing Sugar, dextrin, lactose, microcrystalline Cellulose, mannitol, sorbitol, calcium sulfate, calcium carbonate and other the pharmaceutically acceptable diluent;
Described wetting agent is one or more the material that is selected from ethanol, water and other the pharmaceutically acceptable wetting agent;
Described binding agent is one or more the material that is selected from hypromellose, ethyl cellulose, sodium carboxymethyl cellulose, methylcellulose, hyprolose, starch slurry, polyvidone, gelatin, Polyethylene Glycol, 50% to 70% sucrose solution, sodium alginate soln and other the pharmaceutically acceptable binding agent;
Described disintegrating agent is one or more the material that is selected from carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, dried starch, polyvinylpolypyrrolidone, gas-producing disintegrant and other the pharmaceutically acceptable disintegrating agent;
Described fluidizer, antiplastering aid, lubricant are one or more the materials that is selected from Pulvis Talci, micropowder silica gel, magnesium stearate, polyethylene glycols, sodium laurylsulfate, magnesium laurylsulfate, hydrogenated vegetable oil and other pharmaceutically acceptable fluidizer, antiplastering aid, the lubricant;
Described color and regulator thereof are one or more the materials that is selected from medicinal pigment, food coloring, essence and other pharmaceutically acceptable color and the regulator thereof;
Described solid dispersion carrier material is to be selected from polyethylene glycols, cellulose derivative, organic acid, surfactant-based, the polyvidone class, saccharide and alcohols, cellulose family, the polyacrylic resin class, cupreol, cholesterol, cholesterol ester stearic acid, tripalmitin, castor oil hydrogenated, Oleum Ricini wax, Cera Flava, the material of one or more in Brazil wax and other pharmaceutically acceptable solid dispersion carrier material, every class solid dispersion carrier material can not select or select for use one or more the material in such solid dispersion carrier material;
Described capsule material is to be selected from poloxamer, Brij, alginate, chitosan, gelatin, arabic gum, the cellulose acetate phthalate ester, carboxymethyl cellulose salt, methylcellulose, ethyl cellulose, hypromellose, polylactic acid, poly-carbon ester, polyamino acid, the lactide glycolide copolymer, 6-caprolactone and lactide block copolymer, the polylactic acid-polyglycol block copolymer, polyamide, the material of one or more in silicone rubber and other pharmaceutically acceptable capsule material;
Described pH regulator agent can be at least a pharmaceutically acceptable material that is used to regulate pH value, and the material of described adjusting pH value is one or more the material that is selected from the pharmaceutically acceptable material that is used for regulating pH value of alkali compounds, buffer system, acid and other;
Described enteric film coat comprises the enteric film coat coating material, and described enteric film coat coating material contains one or more the material that is selected from crylic acid resin, polyvinyl alcohol phthalate ester, cellulose acetate phthalate ester, methacrylic acid copolymer, cellulose acetate benzenetricarboxylic acid ester, hydroxypropyl cellulose phthalate ester and other the pharmaceutically acceptable enteric film coat coating material;
Can not add or add one or more the material in dispersant, plasticizer, lubricant, color and regulator thereof and other the pharmaceutically acceptable additive in the described enteric film coat outermost layer coating.
8, the pharmaceutical preparation described according to one of claim 1 to 4, wherein said enteric film coat comprises the enteric film coat coating material, and described enteric film coat coating material contains one or more the material that is selected from crylic acid resin, polyvinyl alcohol phthalate ester, cellulose acetate phthalate ester, methacrylic acid copolymer, cellulose acetate benzenetricarboxylic acid ester, hydroxypropyl cellulose phthalate ester and other the pharmaceutically acceptable enteric film coat coating material;
Can not add or add one or more the material in dispersant, plasticizer, lubricant, color and regulator thereof and other the pharmaceutically acceptable additive in the described enteric film coat outermost layer coating.
9, a kind of preparation contains the method for the pharmaceutical preparation of omeprazole zinc, it is characterized in that described preparation method comprises omeprazole zinc and the blended step of medicine acceptable auxiliary; Wherein when the described pharmaceutical preparation of preparation was tablet, described preparation method comprised direct powder pressing method.
10, method according to claim 9, when described pharmaceutical preparation employing was surrounded by one deck to the multilamellar enteric film coat, described preparation method also comprised the step of coating; Described coating steps comprises spray coating solution, drying, curing, exsiccant step and/or drips acceptable enteric film coat coating steps on system step and/or pressing step and/or the other medicines preparation.
11, a kind ofly contain omeprazole zinc, poloxamer and/or Brij and do not add or add one or more the pharmaceutical preparation of material in other pharmaceutically acceptable adjuvant.
12, a kind of method for preparing pharmaceutical preparation according to claim 11 is characterized in that described method comprises: omeprazole zinc, poloxamer and/or Brij and/or described other pharmaceutically acceptable adjuvant are in the step that mix homogeneously under the liquid condition is made mixture at poloxamer and/or Brij.
13, method according to claim 12 is characterized in that also comprising:
Described mixture is cooled off while extruding, again the bar of extruding is cut into the lamellar thing, with tablet bag enteric film coat, make Formulation again; Or
Described mixture directly is filled in the enteric hollow capsule shell, makes capsule; Or
Described mixture is adopted dropping preparation method, and the bag enteric film coat is made drop pill; Or
Adopt the spraying coagulation, described mixture is sprayed into to condense in the cold airflow form microcapsule/microsphere; Or
Adopt other pharmaceutically acceptable microcapsule/method for preparing microsphere, described mixture is made microcapsule/microsphere, again gained microcapsule/microsphere bag enteric film coat is made microcapsule/microspheres agent.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102406628A (en) * | 2010-09-26 | 2012-04-11 | 上海复星普适医药科技有限公司 | Method for preparing stable esomeprazole enteric-coated pills |
| CN104337788A (en) * | 2013-12-30 | 2015-02-11 | 四川迪康科技药业股份有限公司 | Enteric-coated preparation of esomeprazole sodium and preparation method thereof |
| CN104337789A (en) * | 2013-12-30 | 2015-02-11 | 四川迪康科技药业股份有限公司 | Enteric-coated preparation of rabeprazole sodium and preparation method thereof |
| CN107375230A (en) * | 2017-07-23 | 2017-11-24 | 南京正宽医药科技有限公司 | A kind of omeprazole enteric-coated capsules and preparation method thereof |
| CN110237041A (en) * | 2019-06-20 | 2019-09-17 | 南京知和医药科技有限公司 | A kind of Omeprazole Enteric-coated Tablets and preparation method thereof |
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2006
- 2006-03-09 CN CN 200610057502 patent/CN1813728A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102406628A (en) * | 2010-09-26 | 2012-04-11 | 上海复星普适医药科技有限公司 | Method for preparing stable esomeprazole enteric-coated pills |
| CN104337788A (en) * | 2013-12-30 | 2015-02-11 | 四川迪康科技药业股份有限公司 | Enteric-coated preparation of esomeprazole sodium and preparation method thereof |
| CN104337789A (en) * | 2013-12-30 | 2015-02-11 | 四川迪康科技药业股份有限公司 | Enteric-coated preparation of rabeprazole sodium and preparation method thereof |
| CN104337789B (en) * | 2013-12-30 | 2016-05-11 | 成都迪康药业有限公司 | Sodium rabeprazole enteric-coated preparation and preparation method thereof |
| CN104337788B (en) * | 2013-12-30 | 2016-05-11 | 成都迪康药业有限公司 | Esomeprazole sodium enteric coated preparations and preparation method thereof |
| CN107375230A (en) * | 2017-07-23 | 2017-11-24 | 南京正宽医药科技有限公司 | A kind of omeprazole enteric-coated capsules and preparation method thereof |
| CN110237041A (en) * | 2019-06-20 | 2019-09-17 | 南京知和医药科技有限公司 | A kind of Omeprazole Enteric-coated Tablets and preparation method thereof |
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