EP1154760A1 - Materiaux composites biodegradables pour la fabrication de microcapsules - Google Patents

Materiaux composites biodegradables pour la fabrication de microcapsules

Info

Publication number
EP1154760A1
EP1154760A1 EP00925026A EP00925026A EP1154760A1 EP 1154760 A1 EP1154760 A1 EP 1154760A1 EP 00925026 A EP00925026 A EP 00925026A EP 00925026 A EP00925026 A EP 00925026A EP 1154760 A1 EP1154760 A1 EP 1154760A1
Authority
EP
European Patent Office
Prior art keywords
composites
composites according
composite
water
solution
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP00925026A
Other languages
German (de)
English (en)
Inventor
Marianne Teller
Hans-Werner Heinrich
Joachim Teller
Udo Meyer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bioserv AG
Original Assignee
Bioserv AG
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 Bioserv AG filed Critical Bioserv AG
Publication of EP1154760A1 publication Critical patent/EP1154760A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/66—Polyesters containing oxygen in the form of ether groups
    • C08G63/664—Polyesters containing oxygen in the form of ether groups derived from hydroxy carboxylic acids
    • 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
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • 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
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0084—Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
    • C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
    • C08G69/26—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from polyamines and polycarboxylic acids
    • 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
    • A61K9/14—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
    • A61K9/1658—Proteins, e.g. albumin, gelatin

Definitions

  • the invention relates to biodegradable polymer composites for the production of microcapsules of any ingredients, such as e.g. Food, pharmaceuticals and immunogens or materials of the art such as e.g. Oils, dyes, enzymes etc.
  • the matrix, shell / capsule materials used mono-, di- and polysaccharides, proteins, polyamino acids, polycarboxylic acids, poly (lactide-co-glycolide), acrylates, polyalcohols and their copolymers, liposomes, silicate, etc. in various combinations and mixing ratios ) and
  • Transport vehicle functions in the intended area of activity and only at the destination
  • US Pat. No. 5,700,486 discloses biodegradable polymers or copolymers in pharmaceutical compositions for the formation of particles which are used for the controlled release of pharmacologically active substances.
  • the compositions listed consistently represent physical mixtures of the uniform polymers and copolymers, the proportions of which are varied before the encapsulation process.
  • the disadvantage of such biodegradable polymers is that the substance release is neither targeted nor by defined enzyme action.
  • US-A 5,686,113 describes the microencapsulation in aqueous solutions.
  • the biodegradable capsule material used is a mixture of an anionic polymer or its salts and an amino-functionalized monomer, the formation of the Reaction product takes place during the microencapsulation.
  • Such mixtures have the disadvantage that the formation reaction of microcapsules cannot take place simultaneously in aqueous and also in non-aqueous systems.
  • the particles can bind selectively to certain ligands, but a specific dissolution of the capsule wall at the binding site is not possible.
  • the object of the invention is to find biodegradable components which allow a technically simple process for the production of microcapsules of any ingredients and both for the temporary separation of any materials, such as e.g. Oils, dyes, enzymes, drugs, immunogens, nucleic acids, etc. from the surrounding environment, as well as or for a targeted transport and controllable release of active pharmaceutical ingredients.
  • any materials such as e.g. Oils, dyes, enzymes, drugs, immunogens, nucleic acids, etc.
  • a polymer composite is suitable as the capsule wall material, which is a uniform reaction product and has covalent bonds between the substructures, at least one of the components used having hydrophilic properties.
  • This composite allows the formation of microcapsules from solid or dissolved substances or preparations in both aqueous and non-aqueous systems.
  • biodegradable polymers according to the invention only bind to defined ligands and are only broken down into subunits under the influence of known factors.
  • the new polymers can be used for different applications.
  • Capsule materials are produced which bind to target cells according to their intended use, can be absorbed by them or dissolve on the cell surface or inside the cell.
  • This basic concept of the chemical connection of non-degradable or poorly degradable substances with substances that are specifically split by certain enzymes (composites) is used for a wide variety of biological and technical fields of application
  • polyester polyamides or polysaccharides
  • R 1 and R 2 denote the same or different end groups or protective groups or receptor molecules or markers, i, n and m are from the range of natural numbers and can assume zero or one in individual cases,
  • Q is an at least bifunctional structure with hydrophilic properties, derived from the
  • Fields of polyols, polyamides and polyesters, means used as capsule wall material, which is used to split the bonds between the
  • Substructures R, P and / or as well as within Q an enzymatic recognition and / or
  • Polymers with structural elements of hydroxycarboxylic acids, their salts or esters are particularly preferred for P 1 and P ". They are preferably polyesters, such as polyglycolides, polylactides, poly (hydroxybutyric acids) or copolymers resulting therefrom, polysaccharides, such as polygalacturonic acid or alginic acid.
  • R 1 and / or R 2 are acyl, alkyl or alkoxycarbonyl groups
  • R 1 and / or R 2 are markers, receptors or other molecules which bind specifically to structures, preferably from the substance classes of the oligopeptides, proteins, glycoproteins and oligonucleotides
  • Receptor molecules are preferably lectins, receptor ligands or antibodies.
  • Compounds which are derived from mono-, oligo- or polysaccharides and which optionally have amino or carboxy groups or for compounds which are derived from di-, oligo- or polypeptides are particularly suitable as structural element Q.
  • the structural element Q preferably has enzyme recognition and cut parts, preferably it has a di- or polysaccharide. or an oligopeptide with a defined protease interface.
  • the composite material according to the invention is used to produce microcapsules of substances, for example pollutants, such as mineral oil, for temporary separation from the surrounding environment.
  • the use of the composites according to the invention with different marker or receptor molecules R 1 and / or R 2 has the advantage that they recognize extracellular and / or intracellular structures.
  • a targeted transport and a targeted release of active substances can take place at the site of action of immunologically and or pharmacologically / toxicically active substances.
  • microcapsules with any ingredients e.g. Solid or dissolved materials from the fields of food, pharmaceutical preparations or technical products or additives using the composites according to the invention are carried out according to processes known per se in organic solvents or aqueous emulsions, e.g. through core-shell processes.
  • Lectin Lectin UEA I (Ulex Europaeus)
  • MS-PLA 2000 O-maleoyl polylactide 2000
  • Example 2 Composite of O-acetyl polylactide 2000 and dihistidine
  • Example 3 Composite of O-chloroacetyl polylactide 17000 and a cysteine-rich peptide
  • Example 7 Composite of O-acetyl polylactide 2000 and lactose
  • Example 8 Composite of O-acetyl polylactide 17000 and lactose
  • Example 9 Composite of O-acetyl polylactide 2000 and dextran 6000
  • Example 10 Composite of O-Maleoyl-polylactide 2000 and the lectin UEA I
  • MS-PLA2000 (0.736 mg) and EDC (0.269 mg) are suspended in 0.1 M MES buffer solution (1 ml) and activated for 30 min at room temperature in an ultrasonic bath.
  • the lectin UEA I (10 mg) is added and the mixture is shaken at room temperature for 2 h. The solid is then centrifuged (3000 rpm, 10 min), washed twice with water and freeze-dried.
  • Example 11 Composite of O-Maleoyl-Polylactid 2000 and Albumin (BSA) MS-PLA2000 (0.736 mg) and EDC (0.269 mg) are suspended in 0.1 M MES buffer solution (1 ml) and activated for 30 min at room temperature in an ultrasonic bath. BSA (20 mg) is added and the mixture is shaken at room temperature for 2 hours. The solid is then centrifuged (3000 rpm, 10 min), washed twice with water and freeze-dried.
  • BSA O-Maleoyl-Polylactid 2000 and Albumin
  • Example 12 Microencapsulation of a Rabbit IgG preparation with a composite according to Example 8.
  • 1 g of a lyophilized Rabbit IgG preparation (grain size 1 to 5 ⁇ m) is suspended in 100 ml of petroleum ether (80 - 110 ° C) by stirring. A solution of 1 g of composite from Example 8 and 5 ml of acetone in 10 portions is added dropwise within 5 h. Allow to stir for another hour. After sedimentation, the suspension is filtered, washed with 20 ml of petroleum ether and air-dried.
  • polylactide 17000 and the corresponding composite material according to Example 8 were used as
  • the release studies are carried out in an incubation shaker at 37 ° C in PBS buffer at pH 7.3. 200 mg of particles are suspended in 10 ml of PBS buffer.
  • Example 13 Microencapsulation of albumin (BSA) with a composite according to Example 7
  • Example 14 Microencapsulation of albumin (BSA) with a composite according to Example 7 by means of spray drying
  • BSA 400 mg BSA are dissolved in 200 ml water.
  • a solution of 20 g composite according to Example 7 is dispersed in 100 ml methylene chloride in such a way that the methylene chloride almost completely evaporated and a stable emulsion is formed. This emulsion is then spray dried.
  • Example 15 Core-Shell Encapsulation of Rabbit IgG / PLA 17000 Cores with Composites According to Example 10
  • a solution of 0.05 g of composite according to Example 10 and 0.05 g of PLA 17000 in 2 ml of acetone is added dropwise. Allow to stir for another hour. After sedimentation, the suspension is filtered, washed with 20 ml of petroleum ether and air-dried.
  • Example 16 Microencapsulation of silicate particles (impregnated with amaranth) with a composite according to Example 7
  • the release studies are carried out in an incubation shaker at 37 ° C in PBS buffer at pH 7.3. 200 mg of particles are suspended in 10 ml of PBS buffer. To study the influence of the enzyme on the stability of the particle shell, ß-galactosidase (20 units) is added before the particle is added. 500 ⁇ l of solution are removed at intervals of 30 minutes and analyzed for the content of amaranth by spectrophotometry at a wavelength of 520 nm. The results are summarized in Fig. 3.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Materials Engineering (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Manufacturing Of Micro-Capsules (AREA)
  • General Preparation And Processing Of Foods (AREA)
  • Formation And Processing Of Food Products (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Polyamides (AREA)
  • Polyesters Or Polycarbonates (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne des matériaux composites biodégradables utilisés pour la fabrication de microcapsules contenant des substances quelconques, telles que des aliments, des médicaments et des immunogènes ou pour la fabrication de matériaux à utilité technologique, tels que les huiles, les colorants, les enzymes et matériaux analogues. Selon l'invention, ils sont d'une composition polymère de formule générale R<1>n-P<1>-(Q-P<2>)i-R<2>m, où: P<1> et P<2> représentent des structures macromoléculaires identiques ou différentes; R<1> et R<2> représentent des groupes terminaux ou des groupes de protection, ou des molécules réceptrices ou des marqueurs, identiques ou différents; i, n et m sont des nombres naturels pouvant avoir individuellement la valeur zéro ou un; et Q représente une structure au moins bifonctionnelle ayant des propriétés hydrophiles, dérivée des polyols, des polyamides et des polyesters. La composition présente un site enzymatique de reconnaissance et/ou d'interface permettant la rupture des liaisons entre les sous-structures R, P et/ou à l'intérieur de la structure Q.
EP00925026A 1999-02-19 2000-02-20 Materiaux composites biodegradables pour la fabrication de microcapsules Withdrawn EP1154760A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19907227 1999-02-19
DE19907227 1999-02-19
PCT/DE2000/000526 WO2000048573A1 (fr) 1999-02-19 2000-02-20 Materiaux composites biodegradables pour la fabrication de microcapsules

Publications (1)

Publication Number Publication Date
EP1154760A1 true EP1154760A1 (fr) 2001-11-21

Family

ID=7898210

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00925026A Withdrawn EP1154760A1 (fr) 1999-02-19 2000-02-20 Materiaux composites biodegradables pour la fabrication de microcapsules

Country Status (9)

Country Link
US (1) US20020147296A1 (fr)
EP (1) EP1154760A1 (fr)
JP (1) JP2002537415A (fr)
CN (1) CN1339964A (fr)
AU (1) AU4390200A (fr)
CA (1) CA2362263A1 (fr)
DE (1) DE10008880A1 (fr)
RU (1) RU2001125666A (fr)
WO (1) WO2000048573A1 (fr)

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US20060177416A1 (en) 2003-10-14 2006-08-10 Medivas, Llc Polymer particle delivery compositions and methods of use
DE10113108B4 (de) * 2001-03-15 2007-07-26 Dot Gmbh Wirkstoffhaltige Calciumphosphat-Materialien
ATE366270T1 (de) * 2001-05-07 2007-07-15 Cornell Res Foundation Inc Biologisch abbaubare copolymere, die an ein segment mit mehreren funktionellen gruppen gebunden sind
DE10135494A1 (de) 2001-07-20 2003-11-06 Jobst Krauskopf Verwendung eines Lactatsalzes zur Behandlung und Prophylaxe der Athereosklerose
KR100517072B1 (ko) * 2002-11-25 2005-09-26 주식회사 태평양 폴리올/고분자 마이크로캡슐 및 이를 이용한 효소 안정화방법
DE10331202A1 (de) 2003-07-10 2005-03-31 S.K. Enterprise Gmbh Verwendung von Molkenpermeat zur Behandlung des Metabolischen Syndroms
US8119154B2 (en) 2004-04-30 2012-02-21 Allergan, Inc. Sustained release intraocular implants and related methods
CA2596011C (fr) * 2005-02-17 2013-05-14 Medivas, Llc Compositions d'administration particulaires, polymeriques, et leurs methodes d'utilisation
EP1926780B1 (fr) 2005-09-22 2013-08-14 Medivas, LLC Formules de poly(ester amide) et de poly(ester uréthane) contenant des diesters de bis-( -amino)-diol et méthodes d'emploi
WO2007038246A2 (fr) 2005-09-22 2007-04-05 Medivas, Llc Compositions polymeres solides pour administration et methodes d'utilisation de celles-ci
DE102006036285A1 (de) 2006-08-03 2008-02-07 "S.U.K." Beteiligungs Gmbh Fraktionen aus Molkepermeat und deren Verwendung zur Prävention und Therapie des Typ-2 Diabetes und des Metabolischen Syndroms
FR2937974B1 (fr) * 2008-10-30 2013-01-11 Univ Bordeaux 1 Copolymeres a blocs a base de polysaccharide et de polypeptide, les vesicules constituees de ces copolymeres et leur utilisation
EP3159368A1 (fr) 2011-06-23 2017-04-26 DSM IP Assets B.V. Nouveaux copolymères de polyester-amide biodégradables pour l'administration de médicaments
US9873765B2 (en) 2011-06-23 2018-01-23 Dsm Ip Assets, B.V. Biodegradable polyesteramide copolymers for drug delivery
WO2014028537A1 (fr) * 2012-08-14 2014-02-20 10X Technologies, Inc. Compositions de microcapsule et procédés
CN107106509B (zh) 2014-12-18 2021-11-30 帝斯曼知识产权资产管理有限公司 用于递送酸敏感药物的药物递送系统
EA202091446A1 (ru) * 2018-01-12 2021-01-29 Метимеди Фармасьютикалз Ко., Лтд. Способы лечения хронических воспалительных заболеваний
CN110205103B (zh) * 2019-07-11 2021-03-30 武汉中科先进技术研究院有限公司 一种生物可降解微胶囊蓄冷剂及其制备方法

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Also Published As

Publication number Publication date
CN1339964A (zh) 2002-03-13
US20020147296A1 (en) 2002-10-10
DE10008880A1 (de) 2000-08-24
CA2362263A1 (fr) 2000-08-24
WO2000048573A1 (fr) 2000-08-24
JP2002537415A (ja) 2002-11-05
RU2001125666A (ru) 2004-02-20
AU4390200A (en) 2000-09-04

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