EP2809368A1 - Implant matriciel constitué d'un mélange de polymères - Google Patents

Implant matriciel constitué d'un mélange de polymères

Info

Publication number
EP2809368A1
EP2809368A1 EP13704352.7A EP13704352A EP2809368A1 EP 2809368 A1 EP2809368 A1 EP 2809368A1 EP 13704352 A EP13704352 A EP 13704352A EP 2809368 A1 EP2809368 A1 EP 2809368A1
Authority
EP
European Patent Office
Prior art keywords
mixture
matrix
porous implant
implant matrix
polymers
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Withdrawn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
EP13704352.7A
Other languages
German (de)
English (en)
Inventor
Martin GÖRNE
Thomas Kordick
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.)
Bioenergy Capital AG
Original Assignee
Bioenergy Capital 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 Bioenergy Capital AG filed Critical Bioenergy Capital AG
Priority to EP13704352.7A priority Critical patent/EP2809368A1/fr
Publication of EP2809368A1 publication Critical patent/EP2809368A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61L27/26—Mixtures of macromolecular compounds
    • 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
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • 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
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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
    • 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
    • A61L27/58—Materials at least partially resorbable by the body
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/249921—Web or sheet containing structurally defined element or component
    • Y10T428/249953—Composite having voids in a component [e.g., porous, cellular, etc.]
    • Y10T428/249987—With nonvoid component of specified composition
    • Y10T428/249991—Synthetic resin or natural rubbers
    • Y10T428/249992—Linear or thermoplastic

Definitions

  • the present application relates to porous matrices for surgical purposes.
  • Cell implants based on porous matrices of biocompatible polymers are known from WO 2004/108810 AI.
  • the pores are cross-linked and serve as a template for the location of cells in vivo (eg, therapeutically) or in vitro (eg, diagnostically).
  • a bioresorbable matrix can serve for the temporary localization of the graft and as a placeholder for progressively forming tissue.
  • the known templates are not yet fully satisfactory in some applications, in particular with regard to the clinical results.
  • the invention therefore sets itself the goal of achieving an improvement in the clinical performance of the template.
  • the invention proposes a porous template of a mixture of different rapidly degradable polymers, wherein nominal absorption times of two of the mixture components, each of which accounts for at least 10% of the mixture differ by a factor of at least 5.
  • nominal absorption times of two of the mixture components each of which accounts for at least 10% of the mixture differ by a factor of at least 5.
  • the inventors believe that the polymer which is absorbed more rapidly gradually creates space for the vessels forming, while the cohesion of the overall structure is ensured by the slower absorption of the polymer, without individual structural elements as foreign bodies Act.
  • the progressive degradation of the polymer which is absorbed more rapidly alters the physiological milieu in a manner favorable for therapeutic success.
  • the invention proposes methods of making porous bioresorbable matrices, followed by a mixture of at least two polymers with different rates of resorption and a water-soluble pore-forming agent and a solvent prepared for one of the polymers - Evaporation of the solvent and watering for pore formation.
  • the mixture is compacted after evaporation of the solvent. Both methods result in highly porous polymer matrix discs whose clinical performance is outstanding. The degradation times of the polymers differ by a factor of 5 or more.
  • the porous matrix is hydrophilic, e.g. B. coated with (meth) acrylic acid polymer. This is followed by a plasma coating step followed by a plasma-free coating step, whereby the required layer thicknesses of more than one micrometer are achieved.
  • the coating leads to a further improvement in cell adhesion.
  • matrices are provided for defect coverage, such as hernia dehiscence. It is envisaged that a first portion of the polymer mixture used is degraded faster and erodes another part of the polymer mixture more slowly (ratio of degradation times at least 5) and the structural cohesion longer time, z. B. 2.5-3 years (or at least 2 and / or less than 5 years) guaranteed. By gradually dissolving the faster degradable portion of the matrix within 3-4 months, or at least 2 and / or less than 7 months, the physiological milieu is influenced in a manner conducive to therapeutic success.
  • Such polymers are useful based on ⁇ -hydroxycarboxylic acids such as lactic acid and / or glycolic acid, eg. PLA or PLGA. Manufacturers of such polymers approved for use in the human body indicate the nominal degradation times that are relevant here.
  • the polymers used here are z. Available from Evonik and bear the designations L210s, L210, L09s, L207s, - -
  • L206s slower degradable PLGA polymers
  • RG502, RG502H, RG505 faster degradable PLGA polymers
  • the matrices according to the invention are produced mechanically sufficiently stable that they are, for. B. withstand the stresses of surgical sewing. At its periphery, the matrices can thereby be connected to body tissue. Their porosity ensures that the matrices are infiltrated with connective tissue cells. Particularly good adhesion is achieved by coating with PAA in a combined PECVD / CVD process in which an initial plasma-generated layer serves as a bonding agent for a subsequent crystalline PAA layer.
  • the matrix has a pore-poor or free side that provides the proper cover, and a pore-rich that is favorable for infiltration.
  • the smoother, low-pore side can be arranged facing the interior of the body in order not to provide a point of attack when pressure is exerted by the body organs on the defect site.
  • the matrix is first infiltrated, for example, with hepatocytes and / or with Langerhans's islet cells.
  • biochemical function cells adhere to the inner walls of the pores of the foamy matrix (attachment rates above 80% or, suitably coated, above 95%) and can be transplanted with the matrix into mesothelial pockets, ideally the cell donor itself. that in this case no rejection reaction takes place, but only a comparatively mild, for the therapeutic process favorable foreign body stimulus is exercised.
  • the matrix becomes vascularized and the implanted cells no longer rely on diffusive supply.
  • the matrices are arranged so that the pore-poor (or -free) side is on the inside and the pore-rich side on the outside to keep the loss rate low due to the migration of the cells.
  • coated matrices namely those which in a combined PECVD / CVD process are first plasma-coated with a thin (eg 20-30 nm) PAA layer and then closing with a thicker PAA layer (eg., 20-30 ⁇ ) are coated without plasma interference.
  • This upper layer forms a crystalline, hydrophilic layer.
  • a solution of one of the polymers used in chloroform approved for medical purposes is poured into a mold and the solvent is evaporated off at 45 ° -65 °.
  • a polymer mixture of defined particle size distribution is mixed with a saline granules also defined particle size distribution, mixed with a solution of one of the polymers in chloroform and then added to the already prepared polymer layer.
  • the solvent evaporates at a slightly elevated temperature (45-65 ° C) from; if desired, it can then be compacted by applying pressure.
  • the compact is watered to provide the desired porosity by removing the salt.
  • an initially produced polymer layer remains pore-free.
  • the thickness of the low-pore layer can be adjusted by the amount and concentration of the initial solution. For example, to obtain a stable membrane, if at a concentration of the solution of z. B.
  • the filling height is about 5-50 mm, typically 20-25 mm.
  • the evaporation of the chloroform then takes about 1.5 h and results in a layer thickness of about 0.5-2 mm.
  • the evaporation of the chloroform is completed faster (about 20-30 min), and the resulting membrane has a thickness of only about 10-20 m has.
  • the saline particles of the pore-forming mixture are slightly coarser (median at 400-420 ⁇ ) than the polymer particles (median of slower degradable polymer between 210 ⁇ and 230 ⁇ , that of the faster degradable polymer between 150 ⁇ and 170 ⁇ ).
  • the distribution widths (5% / 95%) are similar, namely about ⁇ 85-95 ⁇ for salt or polymer in total.
  • the distribution form can be bi- or trimodal.
  • the composition of the layer mixture is about 96% salt, 1-1.5% solid polymer and another about 3-5% dissolved polymer, wherein the volume fractions of solids and liquid are about the same. Overall, The proportion of the rapidly degradable polymer contributes only about 5-20% of the polymer.
  • the total thickness of the pore-forming layer is 4-5 mm.
  • the salt can be chosen a bit finer (median about 350-370 pm). In this case, the total thickness of the pore-forming layer is 5-6 mm.
  • the water lasts about 24 h and is followed by drying at 45-50 ° C. When a coating is made, the matrix is on the low-pore side (if any) and therefore, it is predominantly coated on the open-pore side.
  • a matrix as described above may serve to fix cells exposed to agents in a bioreactor.
  • defined cell types may be screened for whether or not they respond to candidate drugs, and the therapy may be scheduled in response to assay results obtained in this manner.
  • drug development can be simplified because toxicity is detected early.

Landscapes

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

Abstract

Implant matriciel poreux constitué principalement d'un mélange de polymères à durée de dégradation différente, les durées de résorption nominales de deux des constituants du mélange, représentant chacun au moins 10% du mélange, se différenciant à raison d'un facteur d'au moins 5. Ledit implant matriciel poreux est produit à partir d'un mélange des au moins deux polymères à durée de dégradation différente, des particules des deux polymères étant mélangées avec des particules d'une matière solide hydrosoluble et avec un solvant pour l'un des polymères, et étant compactées si nécessaire après évaporation du solvant, la matière solide étant alors éliminée par lavage à l'eau.
EP13704352.7A 2012-02-01 2013-02-01 Implant matriciel constitué d'un mélange de polymères Withdrawn EP2809368A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP13704352.7A EP2809368A1 (fr) 2012-02-01 2013-02-01 Implant matriciel constitué d'un mélange de polymères

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP20120000651 EP2623133B1 (fr) 2012-02-01 2012-02-01 Matrice d'implant à base d'un mélange polymère
PCT/EP2013/000325 WO2013113515A1 (fr) 2012-02-01 2013-02-01 Implant matriciel constitué d'un mélange de polymères
EP13704352.7A EP2809368A1 (fr) 2012-02-01 2013-02-01 Implant matriciel constitué d'un mélange de polymères

Publications (1)

Publication Number Publication Date
EP2809368A1 true EP2809368A1 (fr) 2014-12-10

Family

ID=47715967

Family Applications (2)

Application Number Title Priority Date Filing Date
EP20120000651 Not-in-force EP2623133B1 (fr) 2012-02-01 2012-02-01 Matrice d'implant à base d'un mélange polymère
EP13704352.7A Withdrawn EP2809368A1 (fr) 2012-02-01 2013-02-01 Implant matriciel constitué d'un mélange de polymères

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP20120000651 Not-in-force EP2623133B1 (fr) 2012-02-01 2012-02-01 Matrice d'implant à base d'un mélange polymère

Country Status (7)

Country Link
US (1) US9314550B2 (fr)
EP (2) EP2623133B1 (fr)
JP (2) JP5819544B2 (fr)
ES (1) ES2475166T3 (fr)
FI (1) FI20145749L (fr)
PL (1) PL2623133T3 (fr)
WO (1) WO2013113515A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015096875A1 (fr) * 2013-12-27 2015-07-02 Lenswista Ag Procédé de revêtement de surfaces de lentilles
WO2016130559A1 (fr) * 2015-02-10 2016-08-18 Lifenet Health Échafaudages biologiquement fonctionnels pour tissus mous et implants

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5522895A (en) * 1993-07-23 1996-06-04 Rice University Biodegradable bone templates
GB9914616D0 (en) 1999-06-23 1999-08-25 Univ Sheffield Attachment surface
US20020183858A1 (en) 2001-06-05 2002-12-05 Contiliano Joseph H. Attachment of absorbable tissue scaffolds to scaffold fixation devices
JP4975432B2 (ja) 2003-06-06 2012-07-11 ヒューマンオートセル ゲーエムベーハー マトリクス、細胞インプラント並びにそれらの調製方法及び使用方法
US8529625B2 (en) 2003-08-22 2013-09-10 Smith & Nephew, Inc. Tissue repair and replacement
DE102004059169A1 (de) * 2004-12-08 2006-06-22 Humanautocell Gmbh Verfahren zum Testen von Substanzen an Biomatrices
US7964210B2 (en) * 2006-03-31 2011-06-21 Abbott Cardiovascular Systems Inc. Degradable polymeric implantable medical devices with a continuous phase and discrete phase
WO2008031596A1 (fr) 2006-09-13 2008-03-20 Dsm Ip Assets B.V. Preparation pour revetement medical
JP5334081B2 (ja) * 2007-02-15 2013-11-06 独立行政法人物質・材料研究機構 多孔質体とその製造方法
BRPI0909064A2 (pt) * 2008-03-12 2019-02-26 Dsm Ip Assets Bv revestimento hidrofílico

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2013113515A1 *

Also Published As

Publication number Publication date
EP2623133B1 (fr) 2014-04-02
PL2623133T3 (pl) 2014-09-30
ES2475166T3 (es) 2014-07-10
JP5819544B2 (ja) 2015-11-24
EP2623133A1 (fr) 2013-08-07
US9314550B2 (en) 2016-04-19
JP2015505492A (ja) 2015-02-23
US20150004638A1 (en) 2015-01-01
FI20145749L (fi) 2014-08-29
JP2015198951A (ja) 2015-11-12
WO2013113515A1 (fr) 2013-08-08

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