WO1989000045A1 - Comprimes a liberation de medicaments regulee de maniere enzymatique - Google Patents

Comprimes a liberation de medicaments regulee de maniere enzymatique Download PDF

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Publication number
WO1989000045A1
WO1989000045A1 PCT/US1988/002131 US8802131W WO8900045A1 WO 1989000045 A1 WO1989000045 A1 WO 1989000045A1 US 8802131 W US8802131 W US 8802131W WO 8900045 A1 WO8900045 A1 WO 8900045A1
Authority
WO
WIPO (PCT)
Prior art keywords
enzyme
pharmaceutical
pharmaceutical composition
substrate
substance
Prior art date
Application number
PCT/US1988/002131
Other languages
English (en)
Inventor
Horst-Georg Zerbe
Jorn Ullrich Becker
Original Assignee
Riker Laboratories, Incorporated
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 Riker Laboratories, Incorporated filed Critical Riker Laboratories, Incorporated
Priority to AU21245/88A priority Critical patent/AU618748B2/en
Priority to JP88506264A priority patent/JPH02504145A/ja
Publication of WO1989000045A1 publication Critical patent/WO1989000045A1/fr

Links

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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1664—Compounds of unknown constitution, e.g. material from plants or animals
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; 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
    • A61K9/48—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
    • A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
    • 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
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates to a pharmaceutical composition in pellet form with enzymatically controlled release of the pharmaceutical substance.
  • pharmaceutical substances are administered to patients as pharmaceutical compositions with so-called sustained release. After the patient has taken the pharmaceutical composition, the pharmaceutical 0 substance is released in the gastro-intestinal tract slowly over several hours. In this way, the frequency of administration of the pharmaceutical composition, which in many cases the patient considers annoying, can be reduced. At the same time, the sustained release of the c; pharmaceutical substance prevents plasma level peaks and undesired side effects may result from fast resorption.
  • the sustained release of the pharmaceutical substance can be achieved for instance by mixing the pharmaceutical substance with a water-insoluble carrier and Q compressing it into tablets.
  • Suitable carrier materials are cellulose derivatives, waxes, synthetic materials, such as polyvinylchloride, polyvinylacetate , polyethylene or differently substituted polymethacrylic acid derivatives.
  • Other water-insoluble polymers are known to the expert.
  • the release of the pharmaceutical substance can also be retarded by mixing the pharmaceutical substance with hydropnilic macromolecules and compressing the mixture into tablets.
  • Such substances are also known to the expert. Examples are gum arabic, cellulose derivatives, water-soluble polyacrylic acid derivatives, polyvinyl pyrrolidone, tragacanth or guar.
  • so called matrix systems are produced, from which the pharmaceutical substance, after having been administered to the patient, is released under controlled diffusion.
  • the degree to which the release of the pharmaceutical substance is retarded essentially Q depends on the quantitative ratio of the pharmaceutical substance and the polymer forming the matrix.
  • the tablets, pellets or granules containing the pharmaceutical substance are coated with a lacquer layer of a film-forming
  • film formers are known to the expert.
  • preferred film formers are ethyl cellulose, polyvinylacetate, anionic polymers of methacrylic acid and methacrylic acid esters, acrylic and methacrylic acid ester
  • 2o copolymers such as 1:1 methacrylic acid/methacrylate copolymers and 2rl ethylacrylate/methylmethacrylate copolymers, shellac or mixtures of these substances.
  • the film may additionally contain pore-forming substances which are likewise known to the expert. Polyethylene glycols, 5 polyvinyl pyrrolidone, hydroxypropylmethyl cellulose, hydroxypropyl cellulose or mixtures of these substances are preferred. The type and amount of these additives depends on the rate at which the pharmaceutical substance is to be released.
  • US Patent 3,916,899 for instance, describes a • j o preparation (Osmogit R ) consisting of two compartments separated by a semipermeable membrane, one of these compartments being filled with an osmotically active agent such as potassium chloride and the other compartment containing the pharmaceutical substance. After the 5 preparation has been administered to the patient, gastro-intestinal fluid diffuses into the compartment containing the osmotically active agent, whereby the solution of the pharmaceutical substance is pressed into the gastro-intestinal tract by a specific opening provided 0 for this purpose.
  • Other embodiments of this preparation are described in US Patents 4,612,008, 4,503,030, 4,210,139 and DE-OS 33 10 096.
  • a further disadvantage of this preparation is 0 that it is in the "single-unit" form. As such its duration of stay in the portions of the gastro-intestinal tract which are capable of absorption depends to a large degree on the individual variations in the passage times of the gastrointestinal tract. In the case of a reduced passage 5 time, the duration of the pharmaceutical compositions in those portions of the intestine which are capable of absorption is shortened so that a considerable part of the pharmaceutical substance is discharged unused.
  • US Patent 3,493,652 describes the use in pharmaceutical compositions of a substrate and an enzyme disintegrating the substrate. The pharmaceutical substance is closely surrounded by the substrate which is a carbohydrate, lipid or protein whereby the release of the pharmaceutical substance is prevented.
  • the enzyme causes the matrix to disintegrate and thus allows the pharmaceutical substance to dissolve in the gastro-intestinal juice.
  • the structure and the principle of operation of the invention disclosed in US Patent 3,493,652 have the consequence that the rate of release of the incorporated pharmaceutical substance continues to depend on physiological influences, such as viscosity of the intestinal content and intestinal peristalsis, and thus may be subject to considerable individual variations.
  • the technical problem underlying the present invention is to provide a pharmaceutical composition in pellet form comprising a core, which core contains the pharmaceutical substance, and an envelope layer surrounding the core, which minimizes the influence of the physiological factors, such as intestinal peristalsis and the viscosity of the intestinal content, on the release of the active ingredient and at the same time balances individual variations of the gastro-intestinal passage times.
  • the core contains the pharmaceutical substance OL a mixture of pharmaceutical substances, a pharmacologically acceptable enzyme or enzyme mixture and a pharmacologically acceptable polymer as a filler and substrate for the enzyme or enzyme mixture
  • the envelope layer contains a pharmacologically acceptable, water-insoluble, film-forming macromolecular substance and a water-soluble pore-former.
  • the core contains in simple mixture a pharmaceutically acceptable polymer as a filler and substrate, and an enzyme or enzyme mixture for disintegrating said polymer.
  • the envelope layer contains a pharmacologically acceptable water-insoluble, film-forming macromolecular substance and a water-soluble pore-former.
  • the pellets are preferably filled into hard gelatin capsules of a suitable size.
  • the purpose behind this pharmaceutical composition is that after the composition has been taken by the patient and come into contact with the gastro-intestinal fluid, the polymer is enzymatically decomposed into pharmaceutically acceptable degradation products (water-soluble subunits) which are dissolved by the gastro-intestinal juice.
  • the increase in the osmotic pressure thus produced in the interior of the pellets results in a continuous flow of the solution of the pharmaceutical substance from the interior of the pellet through the envelope layer surrounding the core.
  • the formation of the osmotic pressure in the interior of the pharmaceutical composition of the present invention occurs independently from physiological influences such as pH, viscosity and peristalsis and depends solely on the enzyme activity; the release rate being finally controlled by the outer layer surrounding the pellet of the invention.
  • the drawing is an illustration of a pellet of the invention.
  • the core of the pellet contains the active ingredient 1, the enzyme or enzyme mixture 2, the substrate 3 and, optionally, further granulation auxiliaries.
  • the 0 cote is surrounded by the envelope layer 4.
  • Suitable substrate polymers in accordance with g the invention are substances whose enzymatic degradation leads to pharmacologically acceptable degradation products which are soluble in the gastro-intestinal juice .
  • Examples are polyglucosides, glycogen, ⁇ -amylose, amylopectin, pullulan, laminarin, paramylum, callose, cellulose, inulin, o phlean, mannans, xylans, arabinans, galactomannans, chitin, chi.tosan, gelatin, casein or ribonucleic acid.
  • Suitable corresponding enzymes are ⁇ -amylase, amyloglucosidase, ⁇ -glucosidase, pullulanase, ⁇ -glucosidase, cellulase, ⁇ -fructosidase, mannosidase, pectinase, chitinase, 5" proteases or ribonucleases.
  • the combination of enzyme or enzyme mixture and substrates is chosen in such a way that the substrate is degraded to water-soluble subunits.
  • a preferred enzyme-substrate combination is ⁇ -amylase/pregelatinized corn starch or amylose.
  • the quantitative ratio of polymer to the corresponding enzyme depends on the desired duration of release and usually ranges from 100 : 1 and 100,000 : 1. By a suitable selection of the quantitative ratio of polymer and corresponding enzyme, the duration of release 5 of the pharmaceutical substance can be controlled to range from 8 to 24 hours.
  • the core may additionally contain granulation auxiliaries, such as soluble dextrins, polyvinyl pyrrolidone or hydroxypropyl cellulose, which are known to the person skilled in the art.
  • the envelope layer surrounding the core and retarding the release of the pharmaceutical substance comprises a film-forming macromolecular substance(s) which - is essentially insoluble in the gastro-intestinal juices. These are known to the expert.
  • Ethyl cellulose with an ethoxy content of 47.5 to 49% is preferably used.
  • Other suitable substances are hydroxypropylmethyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, acrylic acid ester, methacrylic acid ester, shellac, cellulose acetate phthalate or copolymers of neutral methacrylic acid esters.
  • the envelope layer additionally contains pore-forming substances which are likewise known to the expert. Polyethylene glycol with a molecular weight in the range from 200 to 6,000 is particularly preferred for this purpose.
  • Suitable pore formers are propylene glycol, diethylphthalate, dibutylphtalate, triacetin, citric acid ester, glycerin, sorbitol or ethylene glycol.
  • the type and quantity of these additives depend on the rate at which the pharmaceutical substance is to be released.
  • compositions in accordance with the invention are for instance antibiotics, hormones, antipyretics, antidiabetics, coronary dilators, cardiac glycosides, spasmolytics, antihypertensive agents, psychotropic agents, agents for treating migraine, corticoids, analgesics, antirheumatics, anticholinergics, sympatholytics, sympathomimetics, vasodilators, anticoagulants, or antiarrhyth ics.
  • the drawing shows the structure of a pellet of the invention.
  • the core contains the active ingredient 1, the enzyme or enzyme mixture 2, the substrate 3, and optionally further granulation auxiliaries.
  • the core is surrounded by the envelope layer 4 comprising a water-insoluble polymer(s).
  • the envelope layer 4 additionally contains water-soluble pore-forming substances, the quantitative portion of which is from 5 to 50% of weight of the envelope layer, and which result upon ingestion in pores 5 being formed in the envelope layer.
  • the pharmaceutical composition of the invention shows the following advantages:
  • the pharmaceutical substance is released from the individual pellets irrespective of the mentioned physiological influences, i.e., the pH value, gastro-intestinal motility and viscosity.
  • the substances resulting from the enzymatic degration 5 of the polymers are physiologically acceptable; in addition, they are not released punctiformly as in the case of the Osmogit R preparations, but are released into the gastro-intestinal tract from the entire surface of the pharmaceutical, composition. Thus a "cutting torch" effect o is avoided.
  • a pharmaceutical composition is prepared as follows: The corresponding amounts of polymer, pharmaceutical substance and enzyme are thoroughly mixed in a dry state. The mixture is then thoroughly moistened by a 5 small amount of isopropanol. The mixture is granulated with a 5% aqueous solution of hydroxypropyl cellulose
  • the extrudate is transferred into a suitable spheronizer and rendered round at maximum rotation.
  • the crude pellets are transferred to a fluidized bed dryer and dried in the air stream.
  • the dried pellets are sprayed in the fluidized bed dryer with a suspension of ethyl cellulose (7 weight %), polyethylene glycol (PEG) 6000 and talcum in ethanol.
  • Example 1 was repeated except for using a higher amylase t - portion.
  • the resulting product had the following composition:
  • the amount of the pharmaceutical substance released in vitro was measured in the paddle apparatus of USP XXI, incorporated herein by reference. For this 5 purpose, 100 mg each of the products prepared according to Examples 1 and 2 were incubated in 900 ml of water at 37°C. The stirring rate was 50 rpm. The amounts of pharmaceutical substance released at the time of removing them were determined spectrophotometrically. 0 The results are shown in Table I. The increase in the enzyme concentration caused an increase in the release of the pharmaceutical substance per time unit.
  • a pharmaceutical composition containing theophyllin as a pharmaceutical substance was prepared in accordance with example 1. Its composition is shown in Table II.
  • composition was prepared in accordance with Example 3, however without adding an enzyme.
  • the composition is also shown in Table II.
  • composition of the theophyllin-containing products is Composition of the theophyllin-containing products.
  • a pharmaceutical composition containing flunarizin as a pharmaceutical substance was prepared in accordance with Example 3. Its composition is shown in Table IV.
  • pregelatinized starch 26.16 corn starch (native) 26.16 ⁇ -amylase 0.026 hydroxypropyl cellulose 1.16 flunarizin (model substance) 5.81 ethyl cellulose 25.42
  • a pharmaceutical composition containing salbutamol sulfate as a pharmaceutical substance was prepared in accordance with Example 4. Its composition is shown in Table V. Table V
  • Aerosil R (highly dispersed silicic acid) 1.086- salbutamol sulfate 6.88

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  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Zoology (AREA)
  • Botany (AREA)
  • Medicinal Preparation (AREA)

Abstract

Sont décrites des compositions pharmaceutiques sous forme de comprimés à libération régulée de manière enzymatique de la substance pharmaceutique, comprenant un noyau et un couche enveloppant ledit noyau. Le noyau contient la substance pharmaceutique, une enzyme et un substrat destiné à l'enzyme. La couche d'enveloppe contient une substance macromoléculaire formant une couche mince insoluble dans l'eau ainsi qu'un élément formant des pores solubles dans l'eau.
PCT/US1988/002131 1987-06-30 1988-06-23 Comprimes a liberation de medicaments regulee de maniere enzymatique WO1989000045A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU21245/88A AU618748B2 (en) 1987-06-30 1988-06-23 Pellets with enzymatically controlled drug release
JP88506264A JPH02504145A (ja) 1987-06-30 1988-06-23 酵素制御薬物放出性ペレット

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19873721574 DE3721574A1 (de) 1987-06-30 1987-06-30 Arzneimittel in form von pellets mit enzymatisch kontrollierter arzneistoff-freisetzung
DEP3721574.4 1987-06-30

Publications (1)

Publication Number Publication Date
WO1989000045A1 true WO1989000045A1 (fr) 1989-01-12

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ID=6330589

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1988/002131 WO1989000045A1 (fr) 1987-06-30 1988-06-23 Comprimes a liberation de medicaments regulee de maniere enzymatique

Country Status (7)

Country Link
EP (1) EP0370049A1 (fr)
JP (1) JPH02504145A (fr)
AU (1) AU618748B2 (fr)
DE (1) DE3721574A1 (fr)
NZ (1) NZ225158A (fr)
WO (1) WO1989000045A1 (fr)
ZA (1) ZA884622B (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990011786A1 (fr) * 1989-04-10 1990-10-18 Pharmacia Ab Composition contenant une enzyme pour le nettoyage de verres de contact et methode pour un tel nettoyage
EP0527946A1 (fr) * 1990-05-09 1993-02-24 Micro Vesicular Systems Vehicule a liberation regulee.
US5252318A (en) * 1990-06-15 1993-10-12 Allergan, Inc. Reversible gelation compositions and methods of use
WO1994001091A1 (fr) * 1992-07-03 1994-01-20 Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno Composition a liberation regulee d'une substance active, et son procede de preparation
WO1994001092A1 (fr) * 1992-07-03 1994-01-20 Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno Composition a liberation regulee d'une substance active et son procede de preparation
WO1994002121A1 (fr) * 1992-07-24 1994-02-03 Labopharm Inc. Materiau polyhydroxylique reticule pour liberation de medicaments regulee enzymatiquement
WO1994014479A1 (fr) * 1992-12-28 1994-07-07 Bausch & Lomb Incorporated Composition pour la liberation regulee de substances actives dans un milieu aqueux
US5603956A (en) * 1990-11-27 1997-02-18 Labopharm Inc. Cross-linked enzymatically controlled drug release
WO2001010467A1 (fr) * 1999-08-09 2001-02-15 Dainippon Pharmaceutical Co., Ltd. Preparations solides contenant de la poudre de chitosane et procede de production associe
WO2001037811A1 (fr) * 1999-11-22 2001-05-31 Akzo Nobel N.V. Compositions permettant de liberer un ingredient actif de façon predefinie et regulee, preparation et utilisation de ces compositions
FR2938433A1 (fr) * 2008-11-19 2010-05-21 Francois Fauran Compositions pharmaceutiques utilisant l'inuline comme excipient de granulation
CN113172887A (zh) * 2021-03-15 2021-07-27 中国科学院上海硅酸盐研究所 一种仿生同轴3d打印喷头及具有缓释功能的同轴支架材料

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3918801A1 (de) * 1989-06-06 1991-05-08 Schmidt Walter Praeparat zur geregelten wirkstoffabgabe und verfahren zu dessen herstellung
JP6069782B2 (ja) * 2012-11-09 2017-02-01 国立大学法人佐賀大学 基質応答性自律振動型マイクロカプセル

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3493652A (en) * 1962-09-14 1970-02-03 Charles W Hartman Controlled release medicament
US4261969A (en) * 1979-05-03 1981-04-14 World Health Organization Controlled drug release composition
WO1983003061A1 (fr) * 1982-03-04 1983-09-15 Battelle Development Corp Microcapsules doubles

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US3977404A (en) * 1975-09-08 1976-08-31 Alza Corporation Osmotic device having microporous reservoir
DE2923279C2 (de) * 1979-06-08 1987-07-09 Kali-Chemie Pharma Gmbh, 3000 Hannover Verfahren zur Herstellung von Pankreatin-Pellets und diese enthaltende Arzneimittel
JPS5640151A (en) * 1979-09-06 1981-04-16 Daiichi Seiyaku Co Coating device for tablet
US4609374A (en) * 1985-04-22 1986-09-02 Alza Corporation Osmotic device comprising means for governing initial time of agent release therefrom

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3493652A (en) * 1962-09-14 1970-02-03 Charles W Hartman Controlled release medicament
US4261969A (en) * 1979-05-03 1981-04-14 World Health Organization Controlled drug release composition
WO1983003061A1 (fr) * 1982-03-04 1983-09-15 Battelle Development Corp Microcapsules doubles

Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990011786A1 (fr) * 1989-04-10 1990-10-18 Pharmacia Ab Composition contenant une enzyme pour le nettoyage de verres de contact et methode pour un tel nettoyage
EP0527946A1 (fr) * 1990-05-09 1993-02-24 Micro Vesicular Systems Vehicule a liberation regulee.
EP0527946A4 (en) * 1990-05-09 1993-04-28 Micro Vesicular Systems, Inc. Controlled release vehicle
US5252318A (en) * 1990-06-15 1993-10-12 Allergan, Inc. Reversible gelation compositions and methods of use
US5441732A (en) * 1990-06-15 1995-08-15 Allergan, Inc. Reversible gelation emulsion compositions and methods of use
US5603956A (en) * 1990-11-27 1997-02-18 Labopharm Inc. Cross-linked enzymatically controlled drug release
WO1994001091A1 (fr) * 1992-07-03 1994-01-20 Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno Composition a liberation regulee d'une substance active, et son procede de preparation
WO1994001092A1 (fr) * 1992-07-03 1994-01-20 Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno Composition a liberation regulee d'une substance active et son procede de preparation
US5629018A (en) * 1992-07-03 1997-05-13 Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno Composition for controlled release of an active substance and method for the preparation of such a composition
AU678166B2 (en) * 1992-07-03 1997-05-22 Nederlandse Organisatie Voor Toegepast- Natuurwetenschappelijk Onderzoek Tno Composition for controlled release of an active substance and method for the preparation of such a composition
AU677591B2 (en) * 1992-07-03 1997-05-01 Nederlandse Organisatie Voor Toegepast- Natuurwetenschappelijk Onderzoek Tno Composition for controlled release of an active substance and method for the preparation of such a composition
US5585114A (en) * 1992-07-03 1996-12-17 Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno Composition for controlled release of an active substance and method for the preparation of such a composition
WO1994002121A1 (fr) * 1992-07-24 1994-02-03 Labopharm Inc. Materiau polyhydroxylique reticule pour liberation de medicaments regulee enzymatiquement
AU668198B2 (en) * 1992-07-24 1996-04-26 Labopharm (Barbados) Limited Cross-linked polyhydroxylic material for enzymatically controlled drug release
AU676268B2 (en) * 1992-12-28 1997-03-06 Bausch & Lomb Incorporated Controlled release composition for active substances into anaqueous medium
WO1994014479A1 (fr) * 1992-12-28 1994-07-07 Bausch & Lomb Incorporated Composition pour la liberation regulee de substances actives dans un milieu aqueux
US5645848A (en) * 1992-12-28 1997-07-08 Bausch & Lomb Incorporated Controlled release composition for active substances into an aqueous medium
WO2001010467A1 (fr) * 1999-08-09 2001-02-15 Dainippon Pharmaceutical Co., Ltd. Preparations solides contenant de la poudre de chitosane et procede de production associe
US7604820B1 (en) 1999-08-09 2009-10-20 Dainippon Sumitomo Pharma Co., Ltd. Solid preparation containing chitosan powder and process for producing the same
WO2001037811A1 (fr) * 1999-11-22 2001-05-31 Akzo Nobel N.V. Compositions permettant de liberer un ingredient actif de façon predefinie et regulee, preparation et utilisation de ces compositions
FR2938433A1 (fr) * 2008-11-19 2010-05-21 Francois Fauran Compositions pharmaceutiques utilisant l'inuline comme excipient de granulation
WO2010058104A2 (fr) * 2008-11-19 2010-05-27 Fauran Francois Compositions pharmaceutiques utilisant l'inuline comme excipient de granulation
WO2010058104A3 (fr) * 2008-11-19 2010-10-07 Fauran Francois Compositions pharmaceutiques utilisant l'inuline comme excipient de granulation
CN113172887A (zh) * 2021-03-15 2021-07-27 中国科学院上海硅酸盐研究所 一种仿生同轴3d打印喷头及具有缓释功能的同轴支架材料

Also Published As

Publication number Publication date
ZA884622B (en) 1990-02-28
EP0370049A1 (fr) 1990-05-30
AU2124588A (en) 1989-01-30
JPH02504145A (ja) 1990-11-29
AU618748B2 (en) 1992-01-09
NZ225158A (en) 1990-12-21
DE3721574A1 (de) 1989-01-12

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