WO1999048532A1 - Compositions medicinales adherant a l'estomac/au duodenum - Google Patents

Compositions medicinales adherant a l'estomac/au duodenum Download PDF

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Publication number
WO1999048532A1
WO1999048532A1 PCT/JP1999/001311 JP9901311W WO9948532A1 WO 1999048532 A1 WO1999048532 A1 WO 1999048532A1 JP 9901311 W JP9901311 W JP 9901311W WO 9948532 A1 WO9948532 A1 WO 9948532A1
Authority
WO
WIPO (PCT)
Prior art keywords
stomach
drug
polymer
duodenum
water
Prior art date
Application number
PCT/JP1999/001311
Other languages
English (en)
Japanese (ja)
Inventor
Toshio Inagi
Hiroyuki Shirai
Norikazu Yamaguchi
Takeshi Nishino
Original Assignee
Kowa Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kowa Co., Ltd. filed Critical Kowa Co., Ltd.
Priority to CA002320387A priority Critical patent/CA2320387A1/fr
Priority to AU28524/99A priority patent/AU748299B2/en
Priority to NZ506280A priority patent/NZ506280A/en
Priority to EA200000973A priority patent/EA003512B1/ru
Priority to EP99909193A priority patent/EP1062955A1/fr
Priority to HU0101248A priority patent/HUP0101248A2/hu
Priority to BR9908616-6A priority patent/BR9908616A/pt
Priority to US09/600,885 priority patent/US6582720B1/en
Priority to KR1020007009050A priority patent/KR20010041019A/ko
Publication of WO1999048532A1 publication Critical patent/WO1999048532A1/fr
Priority to NO20004049A priority patent/NO20004049L/no

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Classifications

    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus

Definitions

  • the present invention relates to a pharmaceutical composition that adheres only to gastric mucosa and duodenal mucosa and that has a controlled drug release.
  • preparations with controlled release of the drug from the preparation can release the drug for a long time, reducing the number of doses and maintaining the blood concentration for a certain period of time
  • There are great advantages such as being able to. Therefore, long-lasting preparations are being studied from various aspects.
  • Drugs intended to allow the drug to act in the stomach include those with enhanced gastroretentivity by making the drug floatable (Da viss SS eta 1. Ph arm. R e s. 19 8 6: 2 0 8-2 13 3) Formulation with increased contact ratio to mucosal surface by increasing specific gravity (De Ver ereu XJE eta 1. Pharma col 199 0 0; 4 2: 5 0-5 0 1) has been reported. However, these formulations did not have sufficient retention.
  • an object of the present invention is to provide a preparation which adheres only to the mucous membrane of the stomach and duodenum, controls the release of the drug, and has selectively excellent pharmacological action on the stomach and duodenum. Disclosure of the invention
  • the present inventors have conducted intensive studies and have found that the release of a drug is controlled by a component selected from a water-insoluble polymer, a polyglycerin fatty acid ester, a lipid and a wax. If a polymer that adheres to the stomach and does not adhere under neutral or alkaline conditions imparts selective adhesion only to the mucosa of the stomach or duodenum, the drug will act on the gastric and duodenal membranes for a long time. The present inventor has found that a drug having a higher concentration and a higher pharmacological action can be obtained with a lower concentration of a drug because the drug is rapidly excreted from the intestinal tract, thereby completing the present invention.
  • a component selected from a water-insoluble polymer, a polyglycerin fatty acid ester, a lipid and a wax.
  • the present invention provides a composition containing a drug that acts on the stomach and Z or the duodenum and a component selected from a water-insoluble polymer, a polyglycerin fatty acid ester, a lipid and a wax on the surface of the gastrointestinal mucosa under acidic conditions.
  • An object of the present invention is to provide a gastro-duodenal adhesive pharmaceutical composition characterized in that it is coated with a polymer having an adhesive ability and detachable from the gastrointestinal mucosa in neutral or alkaline conditions.
  • FIG. 1 is a diagram showing the relationship between the particle size and the adhesion rate of the preparation to cells.
  • FIG. 2 is a diagram showing the relationship between PH and adhesiveness.
  • FIG. 3 is a graph showing the transferability of a drug to gelatin.
  • FIG. 4 is a diagram showing the eradication effect.
  • FIG. 5 is a graph showing the bactericidal effect of formulations having different release times.
  • pH-dependent adhesive polymer is not particularly limited, but is preferably one having a dissolution pH of 4 or more and having an anionic group.
  • the following are examples of such a pH-dependent adhesive polymer.
  • Natural polymer purified shellac, white shellac. ,
  • Hydroxypropyl methylcellulose phthalate hydroxypropylmethyl.
  • Cellulose acetate succinate carboxymethyl ethyl cellulose, cellulose acetate trimellitate, cellulose acetate phthalate, etc.
  • a polymer obtained from acrylic acid and / or methacrylic acid A polymer obtained from acrylic acid and / or methacrylic acid
  • the pH-dependent adhesive polymer used in the present invention is particularly preferably a polymer having a carboxyl group, particularly preferably a polymer obtained from acrylic acid and / or methacrylic acid, and further, acrylic acid and Z or methacrylic acid, and a carboxylic acid ester.
  • the polymers obtained from and are preferred.
  • carboxylate used herein examples include acrylic esters and methacrylic esters such as methyl acrylate, ethyl acrylate, n-propyl acrylate, isopropyl acrylate, n-butyl acrylate, isobutyl acrylate, T-butyl acrylate, 2-hydroquinethyl acrylate, 2-hydroquinpropyl acrylate, methyl methacrylate, methyl methacrylate, n-propyl methacrylate, isopropyl methacrylate, methyl methacrylate
  • Examples include 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, and t-butyl methacrylate.
  • a copolymer of methacrylic acid and methyl methacrylate is particularly preferred, especially those having a methacrylic acid content of 20 to 60%, such as Eudragit L100 or S100. Particularly preferred.
  • pH-dependent adhesive polymers may be used alone or in combination of two or more.
  • the component (water-insoluble component) selected from the water-insoluble polymer, polyglycerin fatty acid ester, lipid and wax used in the present invention (hereinafter sometimes referred to as “water-insoluble component”) is a component for controlling the release of the medicinal component.
  • the water-insoluble polymer used in the present invention is not particularly limited as long as it is generally used in pharmaceutical preparations as a sustained-release base. These polymers may be used alone or in combination of two or more. Examples of such polymers include the following.
  • Cellulosic polymers crystalline cellulose, ethylcellulose, hydroxymethylcellulose phthalate, hydroxymethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate fluorate, etc.
  • ethyl cellulose is particularly preferred.
  • the polyglycerin fatty acid ester used in the present invention is not particularly limited, and may be di-, tri- or higher polyglycerin fatty acid ester.
  • the fatty acid portion of the polyglycerin fatty acid ester is preferably a fatty acid having 8 to 30 carbon atoms, and the polyglycerin portion is preferably from diglycerin to eicosaglycerin.
  • polyglycerin fatty acid esters include diglyceryl monostearate, tetraglyceryl monostearate, hexaglyceryl monostearate, deglyceryl monostearate, tetraglyceryl tristearate, decaglyceryl tristearate, and pentane Tetraglyceryl stearate, pentaste Hexaglyceryl acrylate, hexaglyceryl monooleate, decaglyceryl monooleate, triglyceryl dioleate, tetraglyceryl dioleate, tetraglyceryl pentaoleate, hexaglyceryl penoleate, triglyceryl dilinoleate, dilinoleate Tetraglyceryl monophosphate, hexylglyceryl dilinoleate, tetraglyceryl monopalmitate, monono, hexaglyceryl he
  • Examples of the lipid used in the present invention include higher fatty acids or salts thereof, higher alcohols and fatty acid glycerin esters, and examples of the wax include waxes, hydrocarbons, and the like.
  • Examples of higher saturated fatty acids or salts thereof include fatty acids having 8 to 30 carbon atoms or salts thereof, for example, stearic acid, magnesium stearate, and aluminum stearate.
  • Examples of the higher alcohol include aliphatic alcohols having 10 to 24 carbon atoms, such as stearyl alcohol and cetyl alcohol.
  • the fatty acid glycerin ester may be not only triglyceride with fatty acid but also monoglyceride or diglyceride.
  • Examples of the waxes include carnapalow and beeswax.
  • Examples of the hydrocarbon include microcrystalline wax, paraffin and the like.
  • water-insoluble components that is, the water-insoluble polymer, polyglycerol fatty acid ester, lipid and wax may be used alone or in combination of two or more. Further, in order to arbitrarily control the release of the drug from the preparation, a water-soluble polymer may be added to the water-insoluble component in any ratio. Examples of such a polymer include polyethylene glycol, hydroquinethyl cellulose, hydroxypropyl cellulose, aminoalkyl methacrylate copolymer, and polyvinyl acetate acetyl amino acetate.
  • the ratio of the water-soluble polymer to the water-insoluble component is preferably in the range of 0.1 to 60% by weight.
  • the drug used in the present invention the c
  • Such drugs drugs acting in the stomach and duodenum are preferred, antacids, gastric mucosa protective agents, H 2 blockers, Purotonpo Npuinhibi evening one (PPI), antibacterial Substances, protease inhibitors and the like.
  • Examples of the antacid used in the present invention include magnesium hydroxide, magnesium aluminate and the like.
  • the gastric mucosa protective agent used in the present invention includes, for example, methylmethionine sulfonyl chloride (MMSC), vietnam sodium, sucralfate, and setraxate hydrochloride.
  • H 2 blockers used in the present invention e.g., famotidine, cimetidine, mouth Kisachijinase evening one preparative and ranitidine, and the like.
  • PPI used in the present invention examples include Omebrabule and Lansobrasol.
  • protease inhibitor used in the present invention examples include cetohydroxamic acid and caprihydroxamic acid.
  • Examples of the antibacterial substance used in the present invention include an anti-Helicobacter pylori active substance, a bismuth salt, and a quinolone compound. Among them, an anti-Helicobacter pylori active substance is preferable.
  • Examples of anti-Helicobacter pylori active substances include penicillin antibiotics (such as moxicillin and ampicillin), macrolide antibiotics (such as erythromycin and clarithromycin), and tetracycline antibiotics (such as tetracycline). , Minocycline, streptomycin, etc.).
  • the antibacterial substance used in the present invention is preferably a penicillin antibiotic, and particularly preferably is moxicillin (hereinafter referred to as “AMOX”) having high antibacterial properties against Helicobacter pylori.
  • the content of the drug may be appropriately determined depending on the type and preparation of the drug, but is generally preferably about 0.1 to 95% by weight, particularly preferably 0.1 to 90% by weight. Is preferable.
  • the type of the water-insoluble component, the release time of the drug, etc. may be determined according to the formula, but generally it is preferably contained in the composition in an amount of 0.1 to 95% by weight, particularly preferably 1 to 60% by weight.
  • the pH-dependent adhesive polymer is preferably 0.1 to 95% by weight, more preferably 1 to 50% by weight in the composition.
  • composition of the present invention conventional additives used in the production of solid pharmaceuticals may be used.
  • additives used in the production of solid pharmaceuticals.
  • Excipients lactose, corn starch, talc, powdered sugar, light caffeic anhydride, carbonated magnesium, magnesium carbonate, etc.
  • Binder starch, sucrose, gelatin, gum arabic, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, hydroxydipropylmethylcellulose, polyvinylpyrrolidone, pullulan, dextrin, etc.
  • Plasticizer polyethylene glycol, triethyl citrate, etc.
  • additives include a coloring agent; a flavoring agent; an adsorbent; a preservative; a wetting agent;
  • the amounts of these additives are appropriately selected within a range that does not impair the pH-dependent adhesion to the gastric mucosa and does not affect the release of the drug.
  • the composition of the present invention is obtained by coating a composition containing a drug, an additive, if necessary, and the water-insoluble component with a pH-dependent adhesive polymer.
  • the drug, the necessary additive and the composition containing the water-insoluble component may be a drug or a mixture of this and an additive coated with the water-insoluble component, or may be a drug, a necessary additive and A matrix in which the water-insoluble components are mixed may be used, but the former is preferred.
  • coating includes not only the case where the entire particle surface is uniformly coated with a coating agent but also the case where the particle surface is partially coated.
  • the release time of the drug from the preparation of the present invention may be arbitrarily set in consideration of the properties of the selected drug, etc. In order to fully demonstrate the quality, continuous and long time is desirable. In addition, considering the effects of gastrointestinal fluid and metabolism of gastric epithelial cells and the effects of diet, it is desirable that the release of the drug be completed within the time of adhering and staying on gastric mucosa. In consideration of the above points, the release time of the drug from the preparation is desirably 2 to 8 hours. The release time may be controlled by adjusting the ratio of the water-insoluble component to the water-soluble polymer, the amount of the water-insoluble component, and the like.
  • the particle size of the pharmaceutical composition of the present invention is preferably in the range of 30 to 300 ⁇ m, particularly 75 to 300 ⁇ m, from the viewpoint of adhesion to the stomach and Z or duodenal membrane. It is more preferably in the range of 100 to 250 m.
  • the pharmaceutical composition of the present invention comprises, for example, in the case of a preparation coated with the water-insoluble component, after preparing particles containing a drug using a conventional granulator or the like, the water-insoluble component and the pH-dependent adhesive polymer are mixed. It can be manufactured by sequentially performing coating. For the granulation, a fluidized bed granulation method, a stirring granulation method, an extrusion granulation method and the like can be adopted. Conventional coating methods such as a pan coating method and a fluidized bed coating method can be used for coating. When the coating agent is a solution or dispersion containing water or an organic solvent, a spray coating method can also be employed.
  • the water-insoluble component is dissolved in an appropriate organic solvent, and then kneaded with the drug, dried, and pulverized. Is dissolved in a suitable solvent, dispersed in a solution that is immiscible with the solvent, and the solvent is evaporated by heating to prepare particles. May be performed.
  • the type of the organic solvent is not particularly limited, and examples thereof include alcohols such as methanol, ethanol, and isopropanol; ketones such as acetone; and halogenated hydrocarbons such as chloroform and dichloromethane.
  • the coating agent and the matrix may contain the above-mentioned additives and the like.
  • a stomach and z or duodenal narrowing membrane adhesive preparation was prepared using a fluid bed coating machine.
  • a solution prepared by dissolving 75 g of riboflavin phosphate in 3 L of water was sprayed on 300 g of anhydrous calcium hydrogen phosphate (average particle size: 150 urn) and dried.
  • a solution obtained by dissolving 00 g in 4 L of ethanol was sprayed to perform coating.
  • 500 g of methacrylic acid-methyl methacrylate copolymer (trade name: Eudragit L100) and 50 g of triethyl citrate dissolved in 5 L of ethanol are sprayed and coated.
  • a yellow stomach and Z or duodenal mucosa adhesive preparation 1 was obtained.
  • preparations for gastric and / or duodenal mucosa-adhesive preparations were prepared. After dissolving 20 g of methacrylic acid-methyl methacrylate copolymer (trade name: Eudragit L100) and 2 g of triethyl citrate in 5 OmL of ethanol, 25 g of drug and 75 g of excipient were added. The mixture was mixed well while heating to 60 ° C, and then dried. After drying, pulverization and classification are carried out to give products with an average particle size of about 30, 70, 100, 150, 200, 270, 325, 350 and 400 m. I got
  • Preparation I spherical fine particles
  • 80/15 Omesh spherical fine particles
  • a preparation that adheres to the gastrointestinal mucosa was prepared using a polymer that gels with water, described in Japanese Patent Application Laid-Open No. 5-13234. That is, 85 g of stearic acid was dissolved in 70, and then 15 g of an atalylic acid-based polymer (trade name: Hibis @ KO 104) was added, mixed well for 10 minutes, and then cooled and solidified. After solidification, a preparation having a particle size of about 150; m was obtained by pulverization and classification.
  • Example 1 and Comparative Example 1 were suspended in 10% (W / V) of 1 solution in Japan Pharmacopoeia and suspended in a 24-hour fasted rat (SD system, 8 weeks old).
  • W / V 10%
  • the stomach was removed and a formulation that remained in the stomach was examined.
  • the yellow preparation was retained in the stomach of the preparation of Example 1 for 1 and 3 hours, but the preparation of Comparative Example 1 was confirmed to be a yellow preparation in the stomach after 1 hour could not. From the results, it was confirmed that the retention of the drug in the gastric mucosa required the inclusion of methacrylic acid-methyl methacrylate copolymer.
  • Particle size r, Specific gravity of preparation: d, Amount of coating: W
  • the pH is different between the preparation containing methacrylic acid-methyl methacrylate copolymer prepared in Reference Example 1 and having a particle size of 150 ⁇ m, and the comparison preparation containing an acrylic acid polymer prepared in Comparative Example 2 Adhesion to human fibroblasts in solution was examined. The results are shown in FIG.
  • the preparation containing methacrylic acid-methyl methacrylate copolymer shows good adhesion in JP 1 (pH 1.2), but no adhesion in saline adjusted to pH 6. Was.
  • the comparative preparation containing the acrylic acid-based polymer no difference was observed in the adhesiveness depending on the pH. From this, it was confirmed that the adhesiveness of the methacrylic acid-methyl methacrylate copolymer was pH-dependent and had high local selectivity.
  • a 20% gelatin solidified as a gastric mucosa model is placed in a solution, on which the gastric and / or duodenal mucoadhesive preparation prepared in Example 1 5 Omg (1 mg as lipoflavin phosphate) and riboflavin phosphate drug substance lmg each, and stirred at 25 rm to eliminate the concentration gradient. The physical quantity was measured. The results are shown in FIG.
  • the AMO X-containing stomach and Z or duodenal mucosa-adherent preparations [1, 2 and ⁇ in Table 3] produced in Example 2 were suspended in a 0.1% tragacanth solution to prepare a preparation administration solution.
  • AMOX bulk powder was suspended in the same solution to prepare a drug substance administration solution.
  • HP Helicobacter one pylori the ATC C 43504 were infected in orogastric (1 0 9 bacteria count X 3 / mouse) formulations and drug substance administered after 27 days
  • the solutions were prepared so that AMOX was 0.1 mgZkg (using formulation I) and lmgZkg (using formulation I and II), respectively, and orally administered for 5 consecutive days.
  • the stomach was removed, and the stomach crushed solution was inoculated on an HP selection medium, cultured under microaerobic conditions for 8 days, and the number of viable bacteria was measured.
  • Figure 4 shows the measured HP numbers. From the results, it was confirmed that the group to which the AMOX-containing stomach and Z or duodenal mucosa-adhesive preparations had a higher eradication effect than the group to which the drug was administered.
  • the gastric / duodenal mucosa-adhesive pharmaceutical composition of the present invention has pH-dependent adhesive properties, and directly adheres to the gastrointestinal mucosa under acidic conditions, and has a high retention in the gastrointestinal tract. Therefore, the drug can be directly released from the drug product to the stomach and the Z or duodenal mucosa, and it also has controlled release, so that a sustained release can be obtained. It can be efficiently transferred into the intestinal mucosa. Therefore, a sufficient effect can be obtained with a low dose, so that the safety is high and the medicinal ingredient can be used effectively.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne des compositions médicinales adhérant à l'estomac/au duodénum, qui se caractérisent en qu'elles sont produites par l'enrobage d'une composition contenant un médicament agissant dans l'estomac et/ou le duodénum et un composant choisi parmi des polymères insolubles dans l'eau, des esters d'acides gras de polyglycérol, des lipides et des cires, d'un polymère adhérant à la surface de la muqueuse du tube digestif dans des conditions acides, mais pelable dans des conditions neutres ou alcalines. L'utilisation de ces compositions adhérant exclusivement aux muqueuses gastro-duodénale permet la libération de médicaments sur une longue période et une efficacité suffisante du médicament à faible dose.
PCT/JP1999/001311 1998-03-20 1999-03-17 Compositions medicinales adherant a l'estomac/au duodenum WO1999048532A1 (fr)

Priority Applications (10)

Application Number Priority Date Filing Date Title
CA002320387A CA2320387A1 (fr) 1998-03-20 1999-03-17 Compositions medicinales adherant a l'estomac/au duodenum
AU28524/99A AU748299B2 (en) 1998-03-20 1999-03-17 Medicinal compositions adhering to stomach/duodenum
NZ506280A NZ506280A (en) 1998-03-20 1999-03-17 Medicinal compositions adhering to stomach/duodenum
EA200000973A EA003512B1 (ru) 1998-03-20 1999-03-17 Желудочная и/или дуоденальная клейкая лекарственная форма
EP99909193A EP1062955A1 (fr) 1998-03-20 1999-03-17 Compositions medicinales adherant a l'estomac/au duodenum
HU0101248A HUP0101248A2 (hu) 1998-03-20 1999-03-17 Gyomor- és/vagy nyombél-adhezív gyógyászati készítmények
BR9908616-6A BR9908616A (pt) 1998-03-20 1999-03-17 Composição farmacêutica adesiva gástrica e/ou duodenal.
US09/600,885 US6582720B1 (en) 1998-03-20 1999-03-17 Medicinal compositions adhering to stomach/duodenum
KR1020007009050A KR20010041019A (ko) 1998-03-20 1999-03-17 위 및/또는 십이지장 부착성 의약 조성물
NO20004049A NO20004049L (no) 1998-03-20 2000-08-11 Medisinske blandinger adhererende til mage/duodenum

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP10/72098 1998-03-20
JP10072099A JPH11269064A (ja) 1998-03-20 1998-03-20 胃・十二指腸付着性医薬組成物
JP10/72099 1998-03-20

Publications (1)

Publication Number Publication Date
WO1999048532A1 true WO1999048532A1 (fr) 1999-09-30

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Application Number Title Priority Date Filing Date
PCT/JP1999/001311 WO1999048532A1 (fr) 1998-03-20 1999-03-17 Compositions medicinales adherant a l'estomac/au duodenum

Country Status (3)

Country Link
JP (1) JPH11269064A (fr)
BG (1) BG64499B1 (fr)
WO (1) WO1999048532A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE407674T1 (de) * 2002-04-09 2008-09-15 Flamel Tech Sa Orale pharmazeutische formulierung in form einer wässrigen suspension von mikrokapseln zur modifizierten freisetzung von amoxicillin

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5962521A (ja) * 1982-08-13 1984-04-10 エイ／エス・アルフレツド・ベンツオン 医薬用の経口放出調整複合単位製剤とその製法
JPH04290816A (ja) * 1990-11-17 1992-10-15 Bayer Ag 延長された胃の滞留時間を有する制酸調製物
JPH05331074A (ja) * 1992-05-27 1993-12-14 Nippon Oil & Fats Co Ltd 薬物運搬体
JPH07215843A (ja) * 1991-05-30 1995-08-15 Recordati Sa 生物学的付着性を有する徐放性薬理組成物

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5962521A (ja) * 1982-08-13 1984-04-10 エイ／エス・アルフレツド・ベンツオン 医薬用の経口放出調整複合単位製剤とその製法
JPH04290816A (ja) * 1990-11-17 1992-10-15 Bayer Ag 延長された胃の滞留時間を有する制酸調製物
JPH07215843A (ja) * 1991-05-30 1995-08-15 Recordati Sa 生物学的付着性を有する徐放性薬理組成物
JPH05331074A (ja) * 1992-05-27 1993-12-14 Nippon Oil & Fats Co Ltd 薬物運搬体

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BG104733A (en) 2001-07-31
JPH11269064A (ja) 1999-10-05
BG64499B1 (bg) 2005-05-31

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