EP1265952A1 - Matrices polymeres microporeuses - Google Patents

Matrices polymeres microporeuses

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Publication number
EP1265952A1
EP1265952A1 EP00977714A EP00977714A EP1265952A1 EP 1265952 A1 EP1265952 A1 EP 1265952A1 EP 00977714 A EP00977714 A EP 00977714A EP 00977714 A EP00977714 A EP 00977714A EP 1265952 A1 EP1265952 A1 EP 1265952A1
Authority
EP
European Patent Office
Prior art keywords
polymer
solution
solvent
pcl
mould
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Withdrawn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
EP00977714A
Other languages
German (de)
English (en)
Inventor
Allan Gerald A c/o Aston Pharmacy School COOMBES
Sandra c/o Smith & Nephew GRC DOWNES
William A Orthopaedic & Accident Surgery WALLACE
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.)
University of Nottingham
Original Assignee
University of Nottingham
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 University of Nottingham filed Critical University of Nottingham
Publication of EP1265952A1 publication Critical patent/EP1265952A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
    • C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • 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
    • C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
    • C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
    • C08G63/08—Lactones or lactides
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2201/00—Foams characterised by the foaming process
    • C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
    • C08J2201/054—Precipitating the polymer by adding a non-solvent or a different solvent
    • C08J2201/0545—Precipitating the polymer by adding a non-solvent or a different solvent from an aqueous solvent-based polymer composition
    • C08J2201/0546—Precipitating the polymer by adding a non-solvent or a different solvent from an aqueous solvent-based polymer composition the non-solvent being organic
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
    • C08J2367/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones

Definitions

  • This invention relates to the manufacture and use of microporous polymer matrices. Such materials may be useful for formulating controlled release devices for bioactive molecules such as growth factors and hormones and for fabricating scaffolds to support cell growth and development in tissue engineering.
  • PCL Poly( ⁇ -caprolactone)
  • PLA poly(L.lactide)
  • PLA poly(lactide co-glycolide)
  • PLG poly(lactide co-glycolide)
  • the rubbery characteristics of the polyrrier results in high permeability which has been exploited for delivery of low molecular weight drugs such as steroids.
  • Copolymerisation of lactic acid and ⁇ -caprolactone has been investigated to increase degradation rates and improve processability. However the poor mechanical properties of the copolymers have limited the number of applications for these copolymers.
  • Tissue engineering combines the biological, physical and chemical sciences with engineering disciplines to design and manufacture implants for repair, support, augmentation or replacement of damaged or diseased tissues and organs such as bone and skin.
  • bioactive molecules such as growth factors (eg bone morphogenetic protein (BMP), vascular endothelial growth factor (VEGF)) are released in a controlled fashion from an implanted device to modulate processes of cell interaction and adhesion, cell proliferation and cytodifferentiation so as to effect tissue repair or regeneration.
  • growth factors eg bone morphogenetic protein (BMP), vascular endothelial growth factor (VEGF)
  • BMP bone morphogenetic protein
  • VEGF vascular endothelial growth factor
  • cells are first incorporated into 3-D scaffolds or matrices ex-vivo. The cell-scaffold construct is subsequently transplanted and cell development continues to bring about repair and regeneration of tissues such as cartilage.
  • the microstructure and architecture of the scaffold exerts profound effects on cell alignment through contact guidance effects and governs the extent of tissue ingrowth and overgrowth which subsequently determines the quality of integration of new and host tissue. Scaffold design has been found to influence cell distribution, orientation and viability. The void volume and pore size also influences extra cellular matrix formation (Zeltinger et al, Advances in Tissue Engineering and Biomaterials, 1st Smith and Nephew Symposium, York 1997). Designing the scaffold to mimic the cell environment in the host tissue could be advantageous for achieving an appropriate cell arrangement and density so as to induce correct cell differentiation and function. Macropores increase the surface area for cell attachment and permit tissue ingrowth. In addition, the scaffold material should be microporous to allow exchange of nutrients and metabolites and may also provide a favourable surface topography for cell attachment.
  • Implant porosity can influence tissue repair by allowing limited tissue ingrowth for stabilisation of permanent implants or by providing pathways for tissue regeneration within or over a biological scaffold or matrix.
  • the pore size and structure of interconnections will determine the extent of tissue ingrowth.
  • a minimum pore size of approximately 100 ⁇ m in bioceramics has been defined for effective bone ingrowth (Klawitter, J.J. and Hulbert, S.P., J. Biomed. Mater. Res. 2 (1971), 161).
  • the optimum pore size is sufficient to accommodate blood vessel formation with closely associated osteocytes.
  • the pore size in synthetic polymer implants is also known to be a critical factor in determining the prevalence of fibrous or bony tissue generation.
  • the scaffolds for seeded cells may be fabricated by a variety of techniques and from a wide range of materials, both natural (eg collagen, alginate) and synthetic (eg resorbable polyglycolic acid (PGA) and polydioxanone).
  • One of the main advantages of synthetic materials is that physicochemical characteristics such as strength, stiffness, degradation rate and microstructure can be controlled during manufacture. Natural polymers present advantages of biocompatibility and can promote cell adhesion to the supporting scaffold.
  • Micro/macroporous PU materials have been produced by a freeze drying/salt leaching process. Salt crystals were mixed with a pre-polymer/monomer solution and freeze dried at -15°C. Removal of the solvent by sublimation produced the microporous structure ( ⁇ 50 ⁇ m). After curing the prepolymer/monomer/salt mixture, the salt was removed by washing to leave 150-300 ⁇ m macropores.
  • Micro/macroporous PLA implants have also been produced by direct machining of 500 ⁇ m channels in a block of microporous, gel-cast material (US 5,290,494).
  • Porous tubular materials have been described which were produced by spray or dip coating PGA, non-woven mesh (12 ⁇ m diameter fibres) using solutions of PLA or PLG (Mooney et al, Biomaterials 17 (1996) 115-124).
  • Porous biodegradable PLG scaffolds for nerve regeneration have been produced by melt extrusion of a PLG/salt mixture (150-300 ⁇ m crystals) to form a tube, followed by salt leaching and vacuum drying (Brandt et al., 1st Smith & Nephew Conference, York, 1997).
  • Open porous PMMA materials 300-1500 ⁇ m mean pore diameter for use in spinal fusion were prepared by phase separation of a mixture of PMMA and aqueous polymer solution (Wintermantel et al, Biomaterials, 17 (1996) 83-91).
  • Scaffolds for tissue engineering are required to provide mechanical support of developing tissue and also structural and biochemical cues to guide and organise developing tissue.
  • Complex scaffold architectures for bone regeneration have been produced by solid free-form fabrication in which thin layers of the scaffold are built up sequentially by a 3-D printing technique. Control over the size, orientation and material composition of pores and channels is possible to modulate tissue ingrowth. Patterned surface modifications have also been considered for spatial control of cell adhesion and migration (Koegler et al, 1st Smith & Nephew Conference, York, 1997).
  • Porosity is inherently present in fibrous materials such as fabrics, felts and mesh and as such these materials have been investigated for a variety of tissue engineered constructs.
  • Knitted fabrics exhibit three types of porosity: 1) the open space within interlocked loops, 2) the inter-filament spaces, and 3) inter-layer spaces (Wintermantel et al, Biomaterials, 17 (1996) 83-91).
  • Non-woven PGA mesh produced from 12 ⁇ m diameter fibres and having an inherent porosity of 97% has been used extensively as a scaffolding material for seeding cells to produce tissue engineered constructs.
  • Mechanical stabilisation of the PGA mesh has been achieved by spray coating or dip coating with a second polymer and by using thermal bonding techniques (Mikos et al, J. Biomed. Mater. Res. 27, (1993) 183).
  • Blending of polymers to achieve a balance in material properties has been applied extensively in biomedical materials and drug delivery research.
  • microporous materials for replacing bone graft have been produced by blending fast resorbing PLG and slow resorbing PLA to match the resorption rate and dimensional stability of the resulting material with local requirements of tissue repair.
  • PCL is much more permeable than PLG for delivery of bioactive materials but degrades very slowly. Blending of PCL and PLG has been shown to result in retention of permeability and form stability while increasing the overall degradation rate of the blend.
  • microporous polymer matrices which offers significant advantages in the formulation of controlled release devices for bioactive molecules, in the fabrication of scaffolds for tissue engineering, or in other applications.
  • a method for the manufacture of a microporous polymer matrix which method comprises the steps of
  • Step a) may be carried out by forming the solution in the mould, ie by adding the polymer and solvent separately to the mould.
  • the solution may be made up externally and poured or otherwise introduced into the mould.
  • the solvent is preferably an organic solvent. Acetone is currently the most preferred solvent. Another suitable solvent is ethyl acetate.
  • the suitability of a particular solvent for use in the method of the invention may be readily determined. In general, a solvent will be suitable if the polymer dissolves in it and is precipitated upon addition of the precipitant in a form which retains the shape of the mould.
  • the precipitant is preferably a solvent in which the polymer is substantially insoluble.
  • Preferred precipitants are polar solvents such as alcohols, in particular methanol.
  • the suitability of a particular material as a precipitant for use in the method of the invention may be readily determined. For instance, visual inspection of the effect of addition of a particular material may indicate whether it is effective in precipitating the polymer in a form suitable for use in the invention.
  • the concentration of polymer in the solvent may be above a certain threshold or critical level. Again, optimisation of the polymer concentration may be readily carried out.
  • precipitation occurs initially at the solution/precipitant interface, thereby forming a semi-permeable polymer membrane across which the solvent is extracted. Solidification may then occur by gradual crystallisation along a front proceeding from the solution/precipitant interface. In such an embodiment the polymer solution and the precipitant form distinct layers when brought carefully into contact. This characteristic is potentially useful for producing directionally solidified materials which exhibit oriented textures or morphologies for improving cell contact guidance.
  • Precipitation of the polymer at the polymer solution/precipitant interface may be rapid, occurring on a timescale of the order of minutes. Complete solidification of the moulded matrix may be more protracted, taking hours or days to complete, depending on, for instance, the dimensions and geometry of the mould.
  • the solvent power should generally be such that polymer precipitation results from extraction of the solvent across the semi-permeable membrane formed at the solvent/precipitant interface.
  • mixtures of solvents may be used. Such mixtures might include mixtures of a preferred solvent such as acetone with another solvent which may be less suitable when used on its own, eg dichloromethane.
  • the microporous materials obtained may be resilient and may be readily compressible. This facility offers the potential for varying the density and subsequently altering the drug release characteristics from these materials by controlled compression of drug-loaded matrices.
  • PCL is the preferred polymer.
  • Useful polymers for carrying out the method of the invention are those which show a tendency to crystallise from solution on solvent extraction. These include poly(L.lactide) or copolymers of poly(L.lactide) and a poly ( ⁇ -hydroxy acid) which will dissolve in acetone and subsequently crystallise upon solvent extraction.
  • Suitable polymers may thus be members of the class of polyesters formed by ring- opening polymerisation. Precursors to such polymers may thus have the generic formula
  • R represents an optionally substituted alkylene chain, eg a chain (CH 2 ) n in which n is an integer of from about 4 to 10.
  • n is 5.
  • R 1 and R 2 which may be the same or different, represent optionally substituted lower alkyl groups, ie alkyl groups of 1 to 6 carbon atoms. In one preferred case, at least one, and preferably both, of R 1 and R 2 represents methyl.
  • the solvent eg acetone, the precipitant, eg methanol, and water
  • the invention provides a number of different routes by which such a bioactive material may be incorporated into the polymer matrix.
  • the bioactive material may be dissolved, for example, with the polymer in the solvent, or in the precipitant, or in water used for washing the precipitated matrix.
  • Mixtures of the above-defined polymers may be used, as may copolymers.
  • the method of the invention allows incorporation of a wide range of materials in the matrix including natural and synthetic polymers, particulates and powders of bioceramics for variation of material properties and for modulating the release of incorporated bioactive molecules.
  • step a) Other materials may be therefore added to the primary solution in step a) to vary certain properties of the finished material such as degradation rate, density, thermal, mechanical, morphological and chemical characteristics.
  • the method of the invention is potentially useful for blending one or more different polymers (synthetic or natural) with PCL to obtain different physico-chemical characteristics so as to control the pattern of drug release from the blended polymer matrix or to modulate cell interaction with the material.
  • the degradation rate of the poly ( ⁇ -hydroxy acids) such as PLA and PLG can be varied from several weeks to over a year by copolymerisation, control of molecular weight, crystallinity and morphology. Blending of such polymers with PCL using the method of the invention would allow control of the degradation characteristics of the blend.
  • Non-water soluble, synthetic polymers may be co-dissolved with PCL in step a) to produce a blended solution. Hardening of the material in step b) may subsequently produce a microporous polymer blend.
  • Useful polymers include the poly ⁇ -hydroxy acids (PLA, PLG, DL.PLA), polymers of lactones, copolymers produced from lactide and non-lactide monomers such as lactones (eg ⁇ -caprolactone) or ethylene glycol, PMMA, PU, copolymers containing a thermoplastic elastomer or hydrogel-forming copolymers such as poly(hydroxyethyl methacrylate).
  • PCL may be blended with polyethylene glycol (PEG), polyethylene oxide (PEO), copolymers of poly(ethyleneoxide)-poly(propylene oxide) (eg Poloxamer, Pluronic, Tetronic copolymers), or polyvinylpyrrolidone (PVP) in step a) to prepare microporous materials having a water soluble phase.
  • PEG polyethylene glycol
  • PEO polyethylene oxide
  • copolymers of poly(ethyleneoxide)-poly(propylene oxide) eg Poloxamer, Pluronic, Tetronic copolymers
  • PVP polyvinylpyrrolidone
  • the method of the invention is useful for incorporating various particulate fillers in the microporous PCL matrix to produce composite materials.
  • Particulates may be mixed or homogenised with the solution in step a) prior to moulding.
  • Adjustment of particle size and density along with the viscosity of the solution allows control over particle sedimentation rate and subsequently the dispersion of the filler material.
  • useful particulate materials include natural materials such as polysaccharides (inulin, starch, dextran, cellulose and derivatives), sugar spheres, spray dried therapeutic polypeptides such as growth factors, proteins such as vaccine antigens and decalcified freeze dried bone (DFDB).
  • natural materials such as polysaccharides (inulin, starch, dextran, cellulose and derivatives), sugar spheres, spray dried therapeutic polypeptides such as growth factors, proteins such as vaccine antigens and decalcified freeze dried bone (DFDB).
  • particulate fillers include bioceramics such as hydroxyapatite (HA) and tricalcium phosphate (TCP) which have been widely investigated for production of bone substitutes and implant coatings, carbon, calcium carbonate, bioactive ceramic materials such as that known as 'Bioglass', etc
  • particulate synthetic polymers include PMMA powders such as those used in bone cements for implant fixation, polyesters (such as polyethylene polybutylene terephthalate, polyamides, PUS), biodegradable polymers such as PLA and PLG, polyorthoesters, polyanhydrides, oligosaccharide ester derivatives (OEDs) etc.
  • Discontinuous 'chopped' fibre fillers could include alumina, carbon and synthetic polymers such as polyester 'Dacron', polyamides, PCU and its co-polymers POLA, PGA, polydioxanone (PDS), PU etc.
  • the invention provides block-form material which may be machined to the required form for implantation, eg bone graft substitutes.
  • the solution in step a) may be formed or poured into a shaped mould which replicates the shape of the tissue to be repaired (eg craniofacial bone segments). This reduces or avoids the need for final shaping of the implant.
  • the method also allows for inserts to be 'moulded in' to provide attachment means to the host tissue eg suture sewing sites.
  • a layer or coating of microporous PCL may be applied to a device or encapsulation may be obtained by placing the component to be coated in the mould in step b).
  • Composite materials may be produced by impregnation of fibre preforms by PCL solution followed by hardening.
  • precipitation of the polymer matrix (step b)) will generally be followed by extraction of the precipitant, eg by washing with water.
  • the matrix may also be dried after formation.
  • microporous PCL polymers The release of incorporated bioactive factors from microporous PCL polymers will be influenced by the porous character (pore structure and connectivity) and material density of the delivery vehicle. These characteristics are adjustable by varying material composition, processing parameters such as the drying technique and by controlled compression of the drug-loaded material.
  • the microporous nature of the material results in increased surface area which can result in increased rates of degradation by hydrolysis and consequently provides an additional means of influencing drug release.
  • microporous matrices of the invention are potentially useful in a wide range of tissue repair applications. They may be used as a binder for bioceramics, decalcified allogeneic bone and as a delivery system for growth factors in bone repair.
  • the resilient characteristics of the microporous PCL material, coupled with high permeability may also find application in soft tissue reconstruction, eg cartilage repair.
  • the microporous materials may also be useful for fabricating controlled release rate delivery systems for bioactive molecules such as pharmaceuticals. Controlled release of contraceptive hormones or therapeutic polypeptide growth factors such as bone morphogenetic protein (BMP) is possible. Growth factors such as BMP may be incorporated in microporous materials by simple admixing of spray-dried particulates. In the case of therapeutic polypeptides, controlled delivery can overcome problems of short half lives and rapid absorption in vivo which can limit the efficacy of injected soluble formulations.
  • BMP bone morphogenetic protein
  • the rubbery characteristics of PCL result in high permeability which has been exploited previously for delivery of low molecular weight drugs such as steroids.
  • the microporous materials produced in accordance with the invention may find application as 'depot-type' delivery systems for anti-cancer drugs such as leutenising hormone releasing hormone (LHRH) used to treat prostate cancer and for drugs such as Carmustine (BCNU) used in brain tumour therapy.
  • LHRH leutenising hormone releasing hormone
  • BCNU Carmustine
  • TDDS transdermal delivery systems
  • Controlled release of DNA, oligonucleotides or vaccine antigens such as tetanus toxoid from depot-type devices is a further possibility.
  • Routes of drug administration for depot-type delivery devices formulated from microporous materials of the invention could include occular delivery, subcutaneous, intramuscular, intra-brain implantation, transdermai, and transmucosal routes.
  • Controlled release of agrochemicals is another potential field of application.
  • poly( ⁇ -caprolactone) molecular weight (MW) 50,000 by reduced viscosity measurements, Solvay-lnterox was used unless otherwise stated.
  • the interfacial film serves to stabilise the interface and provides a semi-permeable membrane for exchange of solvent and non-solvent between each phase.
  • the density of PCL microporous material determined by weighing 2 mm thick discs cut from cylindrical mouldings was 0.29 ⁇ 0.002g/cm 3 .
  • the solution was poured into a 10 ml PP mould and allowed to stand at room temperature for 1 week.
  • the material was demoulded and immersed in water (40ml) for 0 and 1 day respectively, to extract the methanol non-solvent.
  • Samples dried immediately after precipitation with methanol (Stage 4) exhibited shrinkage values after 6 days air drying which were similar to samples immersed in water for 1 and 7 days respectively prior to drying (Tables 1 and 2).
  • the former samples tended, however, to exhibit a coarser microstructure or texture than water treated materials, illustrating the potential for controlling the material morphology by varying the drying process.
  • HA hydroxyapatite
  • the sample was air dried at room temperature to produce a hard, white material.
  • the density of HA/PCL composite material determined by weighing 2mm thick discs cut from a cylindrical mouldings was 0.49g/cm 3 .
  • Inulin powder (1gm, from Chicory Root, Sigma Chemicals) was mixed with 4ml 12.5% w/v PCL solution in acetone and the suspension was poured into a 10ml PP mould. 2. Methanol (5ml) was added and the sample was retained at room temperature for 4 days to allow precipitation and hardening of the PCL matrix.
  • the density of the inulin/PCL composite material determined by weighing 3mm thick discs cut from cylindrical mouldings was 0.89 ⁇ 0.002g/cm 3 .
  • PMMA bone cement powder 500mg, DePuy-CMW
  • 4ml 12.5% w/v PCL solution in acetone
  • the suspension was poured into a 10ml PP mould.
  • HOB Primary human osteoblast cells

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Dispersion Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Materials Engineering (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne un procédé de fabrication d'une matrice polymère microporeuse qui consiste à: a) introduire dans un moule une solution de polymère dans un solvant et b) ajouter un précipitant à cette solution afin de provoquer la précipitation du polymère de la solution de façon à conserver la forme du moule une fois ce dernier retiré. Pour effectuer ce procédé, les polymères utiles sont ceux qui ont tendance à se cristalliser à partir de la solution lors de l'extraction du solvant. Il s'agit notamment de poly(L.lactide) ou des copolymères de poly(L.lactide) et un poly (α-hydroxy acide) qui se dissoudront dans l'acétone et se cristalliseront lors de l'extraction du solvant. Le polymère préféré est le poly(ε-caprolactone). Le précipitant est, de préférence, un solvant dans lequel le polymère est sensiblement insoluble. Les précipitants préférés sont des solvants polaires, par exemple des alcools, notamment du méthanol.
EP00977714A 1999-11-26 2000-11-24 Matrices polymeres microporeuses Withdrawn EP1265952A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB9927850.9A GB9927850D0 (en) 1999-11-26 1999-11-26 Microporous polymer matrices
GB9927850 1999-11-26
PCT/GB2000/004472 WO2001038428A1 (fr) 1999-11-26 2000-11-24 Matrices polymeres microporeuses

Publications (1)

Publication Number Publication Date
EP1265952A1 true EP1265952A1 (fr) 2002-12-18

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EP00977714A Withdrawn EP1265952A1 (fr) 1999-11-26 2000-11-24 Matrices polymeres microporeuses

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EP (1) EP1265952A1 (fr)
AU (1) AU1535001A (fr)
GB (1) GB9927850D0 (fr)
WO (1) WO2001038428A1 (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0307011D0 (en) 2003-03-27 2003-04-30 Regentec Ltd Porous matrix
CA2556688A1 (fr) * 2004-02-27 2005-09-15 Tagawa Greenhouses, Inc. Systemes de cultures de tissus cellulaires pour un traitement a grands volumes
US7351423B2 (en) 2004-09-01 2008-04-01 Depuy Spine, Inc. Musculo-skeletal implant having a bioactive gradient
WO2008134807A1 (fr) * 2007-05-04 2008-11-13 The University Of Sydney Méthode de fabrication d'une matrice polymérique poreuse
US11331191B2 (en) 2015-08-12 2022-05-17 Howmedica Osteonics Corp. Bioactive soft tissue implant and methods of manufacture and use thereof
CA2938576A1 (fr) * 2015-08-12 2017-02-12 Howmedica Osteonics Corp. Methodes de formation de structures de soutien
EP3241571B1 (fr) 2016-05-02 2020-07-22 Howmedica Osteonics Corporation Implant de tissu mou bioactif et leurs procédés de fabrication et d'utilisation

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2144102A5 (en) * 1971-06-30 1973-02-09 Polaroid Corp Microporous polyvinylidene fluoride membrane - for water purification
US5290494A (en) * 1990-03-05 1994-03-01 Board Of Regents, The University Of Texas System Process of making a resorbable implantation device

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0138428A1 *

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WO2001038428A1 (fr) 2001-05-31
GB9927850D0 (en) 2000-01-26
AU1535001A (en) 2001-06-04

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