WO1988007870A1 - Procede de piegeage de substances biologiquement actives et son utilisation - Google Patents

Procede de piegeage de substances biologiquement actives et son utilisation Download PDF

Info

Publication number
WO1988007870A1
WO1988007870A1 PCT/SE1988/000183 SE8800183W WO8807870A1 WO 1988007870 A1 WO1988007870 A1 WO 1988007870A1 SE 8800183 W SE8800183 W SE 8800183W WO 8807870 A1 WO8807870 A1 WO 8807870A1
Authority
WO
WIPO (PCT)
Prior art keywords
biologically active
formulation according
polymer
substances
characterizedby
Prior art date
Application number
PCT/SE1988/000183
Other languages
English (en)
Inventor
Ulf SCHRÖDER
Catharina Lager
Original Assignee
Carbomatrix Ab
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 Carbomatrix Ab filed Critical Carbomatrix Ab
Publication of WO1988007870A1 publication Critical patent/WO1988007870A1/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
    • A61K9/48—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)

Definitions

  • This invention relates to a way of produce, use and/ or utilize a pharmaceutical formulation for biologically active substances.
  • Such formulations may be used within human and veterinary verbn and in the agricultural areas.
  • Examples of this kind of formulations are slow release systems for drugs, targeting of drugs or the use as contrast agents.
  • this invention relates however, to a method for fabrication and use of slow release systems for a biologically active substances using a process which allows entrappment of biologically active substances within polymers which are biodegradable and biocompatible.
  • a drug within the scope of the present invention, is defined in its broadest sense, such as a biologically active substance having effects and/ or is used within human and/ or veterinary verbn as well as wihin agricultural areas. Within the medical areas one can divide the biologically active substances after there area of use.
  • Substances for the use within the respiratory tract cough reducing (e.g. noscapine) or opiates (e.g. ethylmorphine).
  • Mucusmembrane affectors e.g. ephedrin, terbutalin and theophylline.
  • Heart and bloodvessel agents glycosides, such as digoxin, kinidin, lidocain, procainamide.
  • Beta-blocking agents such as alprenolol or metoproloL
  • alfa-blocking agents e.g. phentolamine
  • beta- stimulaters e.g. bamethan
  • alkylnitrates calciumantagonists (e.g. nifedipin), nicotinic acid derivatives, adrenergics (e.g. adrenalin) sympaticus moderaters (e.g. guanetidin) gangiie blockers (e.g.
  • trimetafan hydrazine derivatives, tiazide derivatives, bensen- sulfonamide derivatives, bumetamide, furoseamide, etacrynic acid, spironolacton Varix treatment (e.g. polidokanol), cholesterol synthesis blockers (e.g. clofibrate).
  • Antihistamins e.g. prometazin, terbutalin at allergic disorders. - Spasmolytic substances; papeverinderivatives, anticholinergic (e.g. atropin), cholinergic substances (e.g. karbacol). Drugs for tumour diseases; vitamines (e.g. B-12 or folic acid), alkylating cytostatic drugs (e.g. cyclofosfamid), antibiotics (e.g. daunomycin, bleo- mycin), mitos blockers (e.g. vinblastin), cisplatinum, nitrosurea derivatives, estramustin, steroidderivatives, cimetidin, ranitidin.
  • papeverinderivatives e.g. atropin
  • cholinergic substances e.g. karbacol.
  • Drugs for tumour diseases e.g. B-12 or folic acid
  • alkylating cytostatic drugs e.
  • Chemotherapeutic and antibiotic substances sulfonamides, peni- cillines, cephalosporins, tetracyclines, aminoglycosides, macrolides, aminosalicylicacid derivatives, iso-nicotinic acid derivatives, iodine.
  • Malaria drugs e.g. clorokin
  • Substances against fungus infections e.g. griseofulvin.
  • Immunstimulating substances e.g. interferons, interleukins).
  • Anticholinergic and anestetic drugs morfin derivatives, fenylpiperidin derivatives, diphenylpropylamine derivatives, salicylic acid derivatives, bensotriazin derivatives, anilides, indol-acetic acid derivatives, fenyl- acetic acid derivatives, naftyl-acetic acid derivatives, ergotamine derivatives, serotonin antagonists, clonidin, lidocain derivatives.
  • these substances are not by any means limited to the use within the areas mentioned above, the substances can be, and are used for other purposes or indications than the ones described above.
  • hydrophobic substances In agricultural areas substances that are used as herbicides or stimulators on crop maybe used Also substances that have an affect on various parasites are included (e.g. pesticides).
  • a hydrophobic substance is characterized by beeing preferentially solvable in a hydrophobic solvent This means that the solvent has a capability of dissolving various fatty substances, such as fatty acids, oils or the like.
  • Hydrophilic refers to similar solvation capability but for . water soluble substances.
  • polymers that has attracted large interest during the last years are the use of polymerized hydroxicarboxylic acids.
  • An example of a monomer, which can be used for this type of polymisationer is lactic acid: polymerized into poly-lactic acid (PLA), often polymerized together with glycolic acid This co-polymer is namned as PLGA (poly- o lactic-glycolic acid).
  • Microspheres prepared of PLGA are relativly stable in a physiological enviroment due to the hydrophobic interactions between the hydrophobic PLGA polymer.
  • poly-capronic acid Another polymer showing the same characteristics is poly-capronic acid
  • the use and the interest for polymers made of PLGA is partly based upon the fact that the monomer is an endogenous substance and partly 0 that the monomers are bonded to each other by ester bonds. These esterbonds are slowly hydrolized in contact with water whereby the original monomer is reformed
  • hydrophobic interactions within the polymer are utilized when the polymer is used as matrix. Since PLGA is a hydrophobic polymer it will adsorb hydrophobic substances.
  • hydrophobic interactions are only slowly broken up, preferentially this is seen in connection with hydrolysis of the esterbonds in the polymers, appearing in a hydrophilic enviroment such as a human body.
  • Another type of monomers that can be used for the purpose of this invention due to their biocompatability, are polymers of oxaloacetate, citrate, isocitrate, oxalosuccinate, ketoglutarate, succinate, fumarate, malate or a derivative of these.
  • Another type of acceptable polymer that can be used within the scope of this invention is a graft polymer between PLA PLGA and carbohydrates. This type of polymers are described in Swedish patent application 8601563-3.
  • polymers which already have found use within this area and could be used in connection with this invention are the poly- anhydrides (e.g. poly-bis(p-carb ⁇ xyphenoxy)alkane anhydride), poly- ethylenevinyl acetate, poly-orthoesters, poly-vinyl alcohol, poly-vinyl acetate, poly-vinyl chloride, acrylic polymers, poly-amino acids, poly- urethane, poly-silanes. Furthermore, there are a number of combinations and derivatives of these that can be used As mentioned above, the main use of PLGA is for hydrophobic low molecular weight biologically active substances.
  • poly- anhydrides e.g. poly-bis(p-carb ⁇ xyphenoxy)alkane anhydride
  • poly-ethylenevinyl acetate poly-orthoesters
  • poly-vinyl alcohol poly-vinyl acetate
  • poly-vinyl chloride poly-vinyl chloride
  • acrylic polymers poly-a
  • microspheres to be used for entrappment of X- ray contrast agents.
  • the main interest is in preparing a microsphere having a diameter of 2 ⁇ m which can be injected into the bloodstream.
  • Such a microsphere should thus be useable as a specific contrast agent for the reticuloendothelial system (RES).
  • RES reticuloendothelial system
  • Another great interest for the type of formulations, as described in this invention, is if one could prepare a microsphere with entrapped biologically active substances having a size allowing inhalation, e.g. as a spray.
  • the use of such a preparation containing e.g. terbutalin or theofylline is primarely in the treatment of asthma
  • Another substance awoking a new and special interest is nicotinic acid, since it has been shown it has effects at tumour treatment
  • Proteins are also incorporated into this group of particularly interesting substances since this group of substances have high demands on the preparation methodology in order to protect the three dimensionell structure.
  • Methods for preparation of known formulations, as discussed in this invention is mainly based on the following principles: phase eva ⁇ poration, precipitation or spraydrying.
  • phase evaporation may be mentioned that PLGA microspheres are primarely prepared according to this technology (US 4,389,330).
  • polymers used for the preparation of microspheres are carbohydrate polymers, e.g. starch, which also are considered to have fulfilled all the necessary demands in order to be used as a carrier of biologically active substances.
  • Precipitation systems (crystallization) is described in PCT/SE83/- 00268 where the polymer beeing described is starch. Polymerization systems is also described for the preparation of starch microspheres (SE 7407461-8). Also complexes and solutions are described (Swedish appL 8501094.0) as useful formulations within this area.
  • starch is to hydrophilic to be used for hydrophilic low molecular weight substances.
  • the invention is not restricted to the use within the methodologies mentioned above for slow release, the expert in the field may easily adopt the methodology for the use in other areas where there is a need for a matrix system according to the present invention.
  • the invention shows that by using this technology, which involves covering a hydrophilic matrix with a hydrophobic polymer in a process
  • the methodology involves in the first step production of a aphere/particle of a biologically active substance according to the basic technology described in PCT/SE83/00268. There is also the possibility to use a microsphere of crossslinked starch as described in Swedish
  • the formulation my be obtained as a suspension in physiological enviroment without having the microspheres aggregated. This may be accomplished using known technology, such as adsorbation of detergents on the surface of the microspheres before these are dried
  • the invention in based upon the unexpected result that the hydro ⁇ phobic polymer was shown to cover the surface of the hydrophilic microsphere, resulting in a sphere, to the extent that a high retardation of the release of the biologically active substance was obtained after suspension of the formulation in water.
  • the hydrophobic polymer was shown to cover the surface of the hydrophilic microsphere, resulting in a sphere, to the extent that a high retardation of the release of the biologically active substance was obtained after suspension of the formulation in water.
  • the hydrophobic polymer at the process of covering of the hydrophilic microsphere there is also the possibility to adsorb the hydrophobic polymer using successiveivly higher molecular weight of the polymer.
  • the low molecular weight polymers will be able to penetrate further into the hydrophilic structure, whereby is given the possibility to prepare the formulation with various release rates of the biologically active substance.
  • this methodology has shown to be useful by adsorption of the hydrophobic polymer using sonication.

Landscapes

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

Abstract

Formulation pharmaceutique réalisée à partir d'une microsphère/particule préfabriquée, combinée avec un polymère pharmaceutiquement acceptable retardant la libération de la substance biologiquement active. L'utilisation de la formulation se rapportant à la substance biologiquement active est également divulguée.
PCT/SE1988/000183 1987-04-09 1988-04-11 Procede de piegeage de substances biologiquement actives et son utilisation WO1988007870A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE8701479A SE8701479L (sv) 1987-04-09 1987-04-09 Metod foer inneslutning av biologiskt verksamma preparat samt anvaendning daerav
SE8701479-1 1987-04-09

Publications (1)

Publication Number Publication Date
WO1988007870A1 true WO1988007870A1 (fr) 1988-10-20

Family

ID=20368147

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE1988/000183 WO1988007870A1 (fr) 1987-04-09 1988-04-11 Procede de piegeage de substances biologiquement actives et son utilisation

Country Status (2)

Country Link
SE (1) SE8701479L (fr)
WO (1) WO1988007870A1 (fr)

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995022318A1 (fr) * 1994-02-17 1995-08-24 Pankaj Modi Medicaments, vaccins et hormones incorpores dans des microspheres recouvertes de polylactides
EP0737472A1 (fr) * 1995-03-16 1996-10-16 LG Chemical Limited Formulation de vaccin pour une administration unique
EP0535937B1 (fr) * 1991-10-01 1997-06-11 Takeda Chemical Industries, Ltd. Préparation à base de microparticules à libération prolongée et production de celle-ci
US5976574A (en) * 1996-12-31 1999-11-02 Inhale Therapeutic Systems Processes for spray drying hydrophobic drugs in organic solvent suspensions
FR2778336A1 (fr) * 1998-05-11 1999-11-12 Jean Pierre Perraud Implant injectable en sous-cutane et en sous-gingival resorbable a base de maltodextrine micro-encapsulee et resorbable en un temps determine
US6120787A (en) * 1995-10-19 2000-09-19 Biogram Ab Sustained release particles
EP0535387B2 (fr) † 1991-09-03 2001-10-04 Hoechst Aktiengesellschaft Particule échographique, préparation et application
WO2004094595A2 (fr) 2003-04-17 2004-11-04 Alnylam Pharmaceuticals Inc. Agents modifiés d'arni
WO2004094345A2 (fr) 2003-04-17 2004-11-04 Alnylam Pharmaceuticals Inc. Monomeres proteges
EP2216407A2 (fr) 2003-03-07 2010-08-11 Alnylam Pharmaceuticals, Inc. Compositions Therapeutiques
WO2011109427A2 (fr) 2010-03-01 2011-09-09 Alnylam Pharmaceuticals, Inc. Amélioration de l'activité biologique de parni par modulation de son profil thermodynamique
US8936813B2 (en) 2001-11-01 2015-01-20 Novartis Ag Spray drying methods and related compositions
US9120031B2 (en) 2000-11-09 2015-09-01 Nektar Therapeutics Compositions of particulate coformulation
WO2016057693A1 (fr) 2014-10-10 2016-04-14 Alnylam Pharmaceuticals, Inc. Procédés et compositions pour administration par inhalation d'oligonucléotide conjugué
EP3141265A1 (fr) 2007-12-04 2017-03-15 Alnylam Pharmaceuticals, Inc. Conjugués glucidiques utilisés comme agents d'administration pour des oligonucléotides
US9700529B2 (en) 2002-05-03 2017-07-11 Nektar Therapeutics Particulate materials
US9808030B2 (en) 2011-02-11 2017-11-07 Grain Processing Corporation Salt composition
EP3604533A1 (fr) 2008-04-11 2020-02-05 Arbutus Biopharma Corporation Délivrance spécifique à un site d'acides nucléiques en combinant des ligands de ciblage avec des composants endosomolytiques

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE328670B (fr) * 1962-12-19 1970-09-21 Smith Kline French Lab
SE413578B (sv) * 1973-03-28 1980-06-09 Benzon As Alfred Forfarande for framstellning av orala lekemedelspreparat med forlengda verkningstider
EP0026599A1 (fr) * 1979-09-12 1981-04-08 Eli Lilly And Company Copolymère de l'acide lactique et de l'acide glycolique et procédé pour sa préparation
WO1984000294A1 (fr) * 1982-07-09 1984-02-02 Ulf Schroeder Matrice d'hydrate de carbone cristallise pour des substances biologiquement actives, procede de preparation d'une telle matrice et son utilisation
EP0102265A2 (fr) * 1982-07-29 1984-03-07 The Stolle Research And Development Corporation Formulation injectable de microparticules à effet prolongé pour l'administration d'agents anti-inflammatoires
US4479911A (en) * 1982-01-28 1984-10-30 Sandoz, Inc. Process for preparation of microspheres and modification of release rate of core material
EP0147335A2 (fr) * 1984-01-02 1985-07-03 LABORATOIRES D'HYGIENE ET DE DIETETIQUE L.H.D. Société Anonyme dite: Matrice pharmaceutique inerte à base de polycaprolactone et procédé de préparation d'une forme galénique orale

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE328670B (fr) * 1962-12-19 1970-09-21 Smith Kline French Lab
SE413578B (sv) * 1973-03-28 1980-06-09 Benzon As Alfred Forfarande for framstellning av orala lekemedelspreparat med forlengda verkningstider
EP0026599A1 (fr) * 1979-09-12 1981-04-08 Eli Lilly And Company Copolymère de l'acide lactique et de l'acide glycolique et procédé pour sa préparation
US4479911A (en) * 1982-01-28 1984-10-30 Sandoz, Inc. Process for preparation of microspheres and modification of release rate of core material
WO1984000294A1 (fr) * 1982-07-09 1984-02-02 Ulf Schroeder Matrice d'hydrate de carbone cristallise pour des substances biologiquement actives, procede de preparation d'une telle matrice et son utilisation
EP0102265A2 (fr) * 1982-07-29 1984-03-07 The Stolle Research And Development Corporation Formulation injectable de microparticules à effet prolongé pour l'administration d'agents anti-inflammatoires
EP0147335A2 (fr) * 1984-01-02 1985-07-03 LABORATOIRES D'HYGIENE ET DE DIETETIQUE L.H.D. Société Anonyme dite: Matrice pharmaceutique inerte à base de polycaprolactone et procédé de préparation d'une forme galénique orale

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PATENT ABSTRACTS OF JAPAN, Vol. 9, No. 180 (C-293); & JP,A,60 048 923, published 16 March 1985. *

Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0535387B2 (fr) † 1991-09-03 2001-10-04 Hoechst Aktiengesellschaft Particule échographique, préparation et application
EP0535937B1 (fr) * 1991-10-01 1997-06-11 Takeda Chemical Industries, Ltd. Préparation à base de microparticules à libération prolongée et production de celle-ci
WO1995022318A1 (fr) * 1994-02-17 1995-08-24 Pankaj Modi Medicaments, vaccins et hormones incorpores dans des microspheres recouvertes de polylactides
EP0737472A1 (fr) * 1995-03-16 1996-10-16 LG Chemical Limited Formulation de vaccin pour une administration unique
US5753234A (en) * 1995-03-16 1998-05-19 Lg Chemical Ltd. Single-shot vaccine formulation
US6120787A (en) * 1995-10-19 2000-09-19 Biogram Ab Sustained release particles
US6572893B2 (en) 1996-12-31 2003-06-03 Inhale Therapeutic Systems, Inc. Systems and processes for spray drying hydrophobic drugs with hydrophilic excipients
US5976574A (en) * 1996-12-31 1999-11-02 Inhale Therapeutic Systems Processes for spray drying hydrophobic drugs in organic solvent suspensions
US5985248A (en) * 1996-12-31 1999-11-16 Inhale Therapeutic Systems Processes for spray drying solutions of hydrophobic drugs and compositions thereof
US6001336A (en) * 1996-12-31 1999-12-14 Inhale Therapeutic Systems Processes for spray drying aqueous suspensions of hydrophobic drugs and compositions thereof
US6077543A (en) * 1996-12-31 2000-06-20 Inhale Therapeutic Systems Systems and processes for spray drying hydrophobic drugs with hydrophilic excipients
US6365190B1 (en) 1996-12-31 2002-04-02 Inhale Therapeutic Systems, Inc. Systems and processes for spray drying hydrophobic drugs with hydrophilic excipients
FR2778336A1 (fr) * 1998-05-11 1999-11-12 Jean Pierre Perraud Implant injectable en sous-cutane et en sous-gingival resorbable a base de maltodextrine micro-encapsulee et resorbable en un temps determine
US10798955B2 (en) 2000-11-09 2020-10-13 Nektar Therapeutics Compositions of particulate coformulation
US9120031B2 (en) 2000-11-09 2015-09-01 Nektar Therapeutics Compositions of particulate coformulation
US8936813B2 (en) 2001-11-01 2015-01-20 Novartis Ag Spray drying methods and related compositions
US10945972B2 (en) 2002-05-03 2021-03-16 Nektar Therapeutics Particulate materials
US10188614B2 (en) 2002-05-03 2019-01-29 Nektar Therapeutics Particulate materials
US9700529B2 (en) 2002-05-03 2017-07-11 Nektar Therapeutics Particulate materials
EP2216407A2 (fr) 2003-03-07 2010-08-11 Alnylam Pharmaceuticals, Inc. Compositions Therapeutiques
EP2239329A1 (fr) 2003-03-07 2010-10-13 Alnylam Pharmaceuticals, Inc. Compositions thérapeutiques
EP3450559A1 (fr) 2003-03-07 2019-03-06 Alnylam Pharmaceuticals, Inc. Compositions thérapeutiques
EP2660322A2 (fr) 2003-04-17 2013-11-06 Alnylam Pharmaceuticals Inc. Agents iARN modifiés
WO2004094345A2 (fr) 2003-04-17 2004-11-04 Alnylam Pharmaceuticals Inc. Monomeres proteges
WO2004094595A2 (fr) 2003-04-17 2004-11-04 Alnylam Pharmaceuticals Inc. Agents modifiés d'arni
EP2669377A2 (fr) 2003-04-17 2013-12-04 Alnylam Pharmaceuticals Inc. Agents iARN modifiés
EP2666858A1 (fr) 2003-04-17 2013-11-27 Alnylam Pharmaceuticals Inc. Agents iARN modifiés
EP2664672A1 (fr) 2003-04-17 2013-11-20 Alnylam Pharmaceuticals Inc. Agents iARN modifiés
EP3705125A1 (fr) 2007-12-04 2020-09-09 Alnylam Pharmaceuticals, Inc. Conjugués glucidiques utilisés en tant qu'agents d'administration pour des oligonucléotides
EP3141265A1 (fr) 2007-12-04 2017-03-15 Alnylam Pharmaceuticals, Inc. Conjugués glucidiques utilisés comme agents d'administration pour des oligonucléotides
EP4223299A2 (fr) 2007-12-04 2023-08-09 Alnylam Pharmaceuticals, Inc. Conjugués glucidiques utilisés comme agents d'administration pour des oligonucléotides
EP4321177A2 (fr) 2007-12-04 2024-02-14 Alnylam Pharmaceuticals, Inc. Conjugués glucidiques utilisés comme agents d'administration pour des oligonucléotides
EP3604533A1 (fr) 2008-04-11 2020-02-05 Arbutus Biopharma Corporation Délivrance spécifique à un site d'acides nucléiques en combinant des ligands de ciblage avec des composants endosomolytiques
WO2011109427A2 (fr) 2010-03-01 2011-09-09 Alnylam Pharmaceuticals, Inc. Amélioration de l'activité biologique de parni par modulation de son profil thermodynamique
US9808030B2 (en) 2011-02-11 2017-11-07 Grain Processing Corporation Salt composition
WO2016057693A1 (fr) 2014-10-10 2016-04-14 Alnylam Pharmaceuticals, Inc. Procédés et compositions pour administration par inhalation d'oligonucléotide conjugué

Also Published As

Publication number Publication date
SE8701479L (sv) 1988-10-10
SE8701479D0 (sv) 1987-04-09

Similar Documents

Publication Publication Date Title
WO1988007870A1 (fr) Procede de piegeage de substances biologiquement actives et son utilisation
US5384124A (en) Solid porous unitary form comprising micro-particles and/or nano-particles, and its preparation
Kas Chitosan: properties, preparations and application to microparticulate systems
US4794001A (en) Formulations providing three distinct releases
US4904476A (en) Formulations providing three distinct releases
US4728512A (en) Formulations providing three distinct releases
EP0148811B1 (fr) Composition pharmaceutique
EP0239361B1 (fr) Préparation pharmaceutique à libération prolongée
US4263273A (en) Pharmaceutical preparation comprising a cardiac glycoside with a polymer coating
JP5175017B2 (ja) 有効成分の経口吸収を改善するための粒子状担体
FI77573C (fi) Ny konsistens.
US9839617B2 (en) Nanoencapsulation of hydrophilic active compounds
US20060115525A1 (en) Pharmaceutical compositions
KR20050005438A (ko) 활성 성분 마이크로캡슐의 경구 현탁액
JPH07145045A (ja) 経口投与用薬物の微細カプセル化方法
CN106421800A (zh) 丝素蛋白改性凹坑结构乳酸基聚合物载药微球及制备方法
JP2006527265A (ja) レクチン含有天然物の腸溶性コーティング用組成物
WO1989003674A1 (fr) Microspheres, procede de production des microspheres et leur utilisation
CS396391A3 (en) Theophyline-containing retarded preparation
US20050079222A1 (en) Production of nanoparticles from methyl vinyl ether and maleic anhydride for the administration of hydrophilic pharmaceuticals, more particularly of puric and pyrimidinic bases
US20020076444A1 (en) Novel method for obtaining microspheres and resulting products
WO1992001443A1 (fr) Compositions contenant des matrices de microparticules
WO1987006241A1 (fr) Materiau matriciel, procede pour sa preparation, et son utilisation
EP0843559A2 (fr) Systeme d'administration de medicaments a base de chitosan
CN102406610B (zh) 一种具有长循环性能的微粒给药系统及其制备方法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LU NL SE