EP2991694A1 - Materiaux composites a base de polymeres bioresorbables et de verre biocompatible - Google Patents
Materiaux composites a base de polymeres bioresorbables et de verre biocompatibleInfo
- Publication number
- EP2991694A1 EP2991694A1 EP14720148.7A EP14720148A EP2991694A1 EP 2991694 A1 EP2991694 A1 EP 2991694A1 EP 14720148 A EP14720148 A EP 14720148A EP 2991694 A1 EP2991694 A1 EP 2991694A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- glass particles
- biocompatible glass
- mixture
- composite material
- biocompatible
- 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- Withdrawn
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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
-
- 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
Definitions
- the present invention relates to composite materials based on bioabsorbable polymers and biocompatible glass. These composite materials are particularly suitable for producing implantable medical devices, particularly bone repair devices. BACKGROUND OF THE INVENTION
- biocomposites consist of a polymer matrix in which inorganic particles are dispersed.
- Biocomposites can thus be prepared by the solvent method according to the methods described Manson et al.
- B Copper blends for bioresorbable composites (Mathieu Mathieu, P.E. Bourban, J.-AE Manson - Composites Science and Technology 66 (2006) 1606-1614): hydroxyapatite or ⁇ -tricalcium ceramics phosphate are dispersed in a solution of PLLA in chloroform. The solvent is then evaporated to obtain ceramic / polymer biocomposites.
- the work of Manson et al. show that solvent shaping leads to partially homogeneous dispersions of ceramics in the polymer matrix.
- Solvent shaping has many disadvantages. NMR analyzes revealed the presence of residual solvent in PLA, which is unacceptable for medical applications. In addition, the biocomposites obtained have poor and poorly controlled properties, with, inter alia, a decrease in the glass transition temperature Tg, in the melting temperature Tf (in the case of semi-crystalline PLA) and in the traction module. (Processing of Homogeneous Ceramics / Polymer Blends for Bioresorbable Composites - LM Mathieu, P.E. Bourban, J.-AE Manson - Composites Science and Technology 66 (2006) 1606-1614).
- the melted route nevertheless has advantages (development of implants of complex shape, no use of solvent), a need exists for the development of a composite material that can be shaped by the molten route, typically by extrusion, and which overcomes the disadvantages described above.
- the present invention relates to a process for preparing a composite material comprising a bioabsorbable polymer matrix and modified biocompatible glass particles comprising the steps of:
- modified biocompatible glass particles are biocompatible glass particles having surface biocompatible bioabsorbable polymers (for example, biocompatible glass particles onto which bioabsorbable polymers or biocompatible glass particles coated with a bioabsorbable polymer are grafted),
- step b) heating the mixture obtained in step a) under an inert atmosphere so as to obtain a fluid mixture
- the present invention also relates to a composite material obtainable by a method as hereinbefore described, as well as implantable medical devices comprising said composite materials and methods of making them.
- the present invention also relates to a process for the preparation of biocompatible glass particles modified by grafting bioresorbable polymers comprising the steps of:
- step b) adding to the mixture obtained in step a) a polymerization initiator; (c) stirring and heating the mixture under an inert atmosphere;
- step a) preparing a solution, preferably at 10g / L, of chitosan from the solution obtained in step a);
- step b adding the biocompatible glass particles to the solution obtained in step b); (d) stirring the mixture;
- the present invention relates to modified biocompatible glass particles comprising biocompatible glass particles onto which are grafted bioresorbable polymers chosen from polyvinyl alcohols and aliphatic polyesters or comprising biocompatible glass particles coated with a bioabsorbable polymer chosen from alcohols. polyvinyls and aliphatic polyesters.
- FIG. 1 represents the evolutions of the storage modulus as a function of frequency pulsation, at 150 ° C., for a residence time of 30 seconds in the extruder.
- FIG. 2 represents the evolution of the loss modulus as a function of frequency pulsation, at 150 ° C., for a residence time of 30 seconds in the extruder.
- FIG. 3 represents the evolution of the complex dynamic viscosity as a function of the frequency pulse at 150 ° C. for a residence time of 30 seconds in the extruder.
- Figure 4 shows FTIR analysis results.
- FIG. 5 represents the follow-up of the evolution of the axial force over time during the extrusion operation of the composite materials
- bioabsorbable qualifies materials that, after implantation in the body, can be degraded into simple products that are eliminated through metabolic pathways.
- biocompatible glass particles refers to glass particles compatible with biological tissues. Glass particles compatible with biological tissues do not induce rejection or toxicity and do not cause damage to biological tissues upon contact.
- the biocompatible glass particles may be bioabsorbable. They are able to promote osteoconduction and / or osseointegration. Such particles are well known to those skilled in the art.
- modified biocompatible glass particles refers to biocompatible glass particles having bioresorbable polymers on their surface.
- the present invention relates to a composite material comprising a bioabsorbable polymer matrix and modified biocompatible glass particles.
- the bioabsorbable polymer matrix typically comprises at least one polymer selected from aliphatic polyesters.
- aliphatic polyesters include poly lactic acid (PLA), poly (L-lactide) (PLLA), poly (DL-lactide (PDLLA), polyhydric glycolide (PGA), polycaprolactone (PCL), poly lactic acid -co-glycolic acid (PLGA) and mixtures thereof.
- the molar mass of the polymers generally ranges from 2.10 to 5 g / mol to 10 e g / mol.
- the polymers generally used as polymer matrix in composite materials according to the invention are well Those skilled in the art, in particular, the bioabsorbable polymer matrix may be as described by Cao et al (W.Cao, L.L.Hench, Bioactive materials, Ceramics International, 1996, vol 22, pp.493- 507) or Bonfield et al (W. Bonfield, M. Wang, KE Tanner, Interface in analog Bone materials, Acta Mater Vol 46, 1998, pp. 2509-2518)
- Polymer matrix is a composite HAPEX® (composite of hydroxyapatite and polyethylene).
- the modified biocompatible glass particles are biocompatible glass particles having bioresorbable polymers on their surface.
- Biocompatible glass particles having bioabsorbable polymers on the surface can be biocompatible glass particles onto which are grafted bioabsorbable polymers or biocompatible glass particles coated with a bioabsorbable polymer.
- Bioresorbable polymers are typically selected from polyvinyl alcohols, aliphatic polyesters or natural polymers.
- aliphatic polyesters examples include poly lactic acid (PLA), poly (L-lactide) (PLLA), poly (DL-lactide (PDLLA), polyhydric glycolide (PGA), polycaprolactone (PCL), poly lactic acid -CO-glycolic (PLGA) and their mixture PLA is particularly advantageous since it has antimicrobial properties.
- the aliphatic polyesters used for this application generally have a mass mass by weight ranging from 2.10 5 g / mol to 10 e g / mol.
- aliphatic polyesters examples include products from the Resomer® range supplied by Boehringer Ingelheim, Germany, particularly medical grade PDLLAs, such as Resomer®LR 706 S and Resomer® LR 708.
- Bioresorbable polymers may also be as described by Mathieu et al. (Processing of homogeneous ceramic / polymer blends for bioabsorbable composites - L.M. Mathieu, P.E. Bourban, J.-A.E. Manson - Composites Science and Technology 66 (2006) 1606-1614), Blaker et al. (Premature degradation of poly (ct-hydroxyesters) during thermal processing of Bioglass®-containing composites - Jonny J. Blaker, Alexander Bismarck, Aldo R. Boccaccini, Anne M. Young, Showan N. Nazhat - Acta Biomaterialia 6 (2010) 756 -762), Niemela et al.
- bioabsorbable polymers can be as described in US 5,716,413, US 5,977,204, US 6,344,496 B1 or WO 200601853.
- the biocompatible glass particles consist mainly of silicon oxide (SiO 2 ), sodium oxide (Na 2 O), calcium oxide (CaO) and phosphorus oxide (P 2 O 5 ).
- the biocompatible glass particles comprise from 30 to 60% or 35 to 55%, more particularly 45% by weight of SiO 2 , from 10 to 50%, or from 20 to 30%, more particularly 24.5% by weight.
- the biocompatible glass particles may comprise 45% by weight of Si0 2 , 24.5% by weight of CaO, 24.5% by weight of Na 2 0 and 6% by weight of P 2 0 5 .
- Such biocompatible glass is known as Bioverre 45S5 (Bioglass®).
- the biocompatible glass particles may be as described in US 5,716,413, US 5,977,204, US 6,344,496 B1 and WO 200601853.
- the biocompatible glass particles typically have a size ranging from 3.5 ⁇ to 0.5 mm.
- the biocompatible glass particles may be spherical or nonspherical.
- the modified biocompatible glass particles may be prepared by grafting bioabsorbable polymers to their surface.
- the graft-modified biocompatible glass particles are prepared by a process comprising the following steps:
- the polymerization initiator may be chosen from catalytic systems commonly used in the academic and industrial fields, such as Sn (Oct) 2 tin octoate or Ti (OBu) 4 titanium tetrabutoxide.
- the polymerization initiator may be tin octoate.
- the concentration of polymerization initiator typically ranges from 0.5% to 2% molar relative to the molar concentration of monomers.
- the mixture is typically heated at a temperature ranging from 80 ° C to 150 ° C, preferably at 120 ° C.
- the heating time generally varies from 20 hours to 50 hours, it is preferably 48 hours. Stirring and heating are carried out under an inert atmosphere, preferably under a nitrogen atmosphere.
- the mixture is dissolved in a suitable solvent, typically chloroform.
- a suitable solvent typically chloroform.
- the modified biocompatible glass particles are then precipitated cold, typically in methanol.
- biocompatible glass particles are dried. Drying is preferably carried out under vacuum at 40 ° C for 24 hours.
- the graft-modified biocompatible glass particles may be prepared by a process comprising the following steps:
- the grafted biocompatible glass particles of the present invention have a grafting rate of up to 40%.
- the average grafting rate generally ranges from 30% to 40%.
- the degree of grafting is determined by thermogravimetric analysis (ATG) and Fourier transform infrared spectrometry (FTIR). The grafting is qualitatively confirmed by dissolution of the biocompatible glass coated / grafted in chloroform and characterization by FTIR and ATG.
- Graft-modified biocompatible glass particles particularly include biocompatible glass particles onto which poly (L-lactide) (PLLA) or poly (DL-lactide) (PDLLA) is grafted.
- the modified biocompatible glass particles may be prepared by coating the surface of the biocompatible glass particles with a bioabsorbable polymer.
- the biocompatible glass particles are preferably coated with chitosan.
- the coating is carried out by a process comprising the following steps:
- step a) preparing a solution, preferably at 10g / L, of chitosan from the solution obtained in step a);
- step b) adding the biocompatible glass particles to the solution obtained in step b);
- Drying is preferably carried out under vacuum at 40 ° C for 24 hours.
- the coating can be characterized by electron microscopy MEB and / or MET. Biocompatible glass particles surrounded by a micrometric layer of chitosan are thus obtained.
- the modified biocompatible glass particles of the present invention are used to prepare the composite material of the present invention.
- the composite material of the present invention typically comprises 10% to 60%, or 20% to 50% by weight of modified biocompatible glass particles and 40 to 90%, or 50 to 80% by weight of a matrix. polymer with respect to the mass of the biocomposite material.
- the composite material of the present invention can be obtained by a method comprising the following steps:
- the constituent polymer (s) of the polymer matrix are typically in the form of granules.
- the mixture is typically heated at a temperature ranging from 150 to 180 ° C, preferably at 150 ° C, to obtain a fluid and stable mixture.
- the heating is maintained for a period of 30 s to 5 min.
- the cooling can be achieved by means of a coolant circuit, followed by cooling in air.
- the composite material obtained after casting and cooling can be ground to form granules.
- the composite material of the present invention is distinguished by a distinctive dynamic rheology.
- FIGS. 1, 2 and 3 respectively show the evolutions of the conservation modulus, the loss module and the complex dynamic viscosity as a function of the frequency pulse, at 150 ° C., for a residence time of 30 seconds in the extruder.
- melt processing makes it possible to obtain composite materials having properties superior to those of composite materials obtained by the solvent route: higher G 'and G "modules, higher complex viscosity.
- biocompatible glass particles makes it possible to obtain composite materials whose viscoelastic properties (modules, viscosities, etc.) are similar to those of the bioabsorbable polymer matrix, unlike composite materials. based on non-grafted or uncoated biocompatible glass particles.
- the composite material of the present invention has the advantage of not degrading.
- the interferogram of PLA-based composite materials and 10% ungrafted or uncoated biocompatible glass particles has a peak at 1600 cm -1 This peak is indicative of a degradation reaction of the matrix according to the mechanism:
- the interferograms of the composite materials of the present invention have no peak at 1600 cm -1, which means that the grafting or coating of the biocompatible glass particles makes it possible to counteract this degradation reaction which takes place at the interface between the biocompatible glass and the matrix.
- the dispersions obtained by molten route are more homogeneous than those obtained by the solvent route.
- the composites of the present invention have higher compression moduli than the bioabsorbable polymer matrix.
- the composite material of the present invention can be melted and cast into a suitable mold to form implantable medical devices.
- Implantable medical devices comprising a composite material of the present invention are useful in the field of orthopedics.
- the present invention also relates to a method of manufacturing an implantable medical device comprising the steps of:
- the molding is typically carried out by extrusion.
- the extrusion temperature typically varies from 150 to 180 ° C, preferably the extrusion temperature is 150 ° C.
- the residence time is optimized and the shaping is carried out in an inert medium.
- the method of manufacturing an implantable medical device may include the steps of:
- Cooling and demoulding to provide an implantable medical device Cooling and demoulding to provide an implantable medical device.
- the molding is typically carried out by extrusion.
- the extrusion temperature typically varies from 150 to 180 ° C, preferably the extrusion temperature is 150 ° C.
- FIG. 5 shows that the introduction of biocompatible glass particles modified by grafting or coating according to the present invention into the bioabsorbable polymer matrix increases the axial force developed during the extrusion. Without coating or grafting, the forces are much lower than that of the matrix.
- implantable medical devices of the present invention can take complex forms.
- implantable medical devices according to the present invention include screws, plates, multilayers. These implantable medical devices are useful for bone repair applications.
- the implantable medical devices of the present invention have good mechanical strength and do not have the disadvantages of implantable medical devices conventionally prepared by the molten route.
- the preparation of this mixture is done directly in the extruder. After choosing the appropriate twin-screw profile, the native 45S5® biocompatible glass particles (10% by weight) are mixed with the PDLLA granules so as to obtain a homogeneous mixture. The biocompatible glass particles are added using a gravimetric metering device. The temperature of the material is controlled at 150 ° C. The rotational speed of the extruder is 50 rpm and the residence time of the material is 30 seconds. The mixture is produced under an inert atmosphere. Finally, the mixture is cooled once injected in situ in the mold. at. PDLLA + 10% BVNT - Solvent route
- Step 1 Preparation of the PDLLA Blend Granules + 10% Biocompatible Glass (BV) Particles in the Solvent
- Step 2 Hot granules injection into a mold
- the granules prepared in step 1 are introduced into a transfer jar heated to 150 ° C and then injected into a cold mold after 2 minutes of residence time.
- Step 1 Grafting PDLLA or PLLA onto Biocompatible Glass Particles (BV / PDLLA or BV / PLLA)
- a sample of BV / PDLLA or BV / PLLA as obtained in step 1 is mixed with PDLLA granules so that the grafted biocompatible glass particles represent 10% by weight of the composite.
- the mixture is made by means of a gravimetric doser. The temperature of the mixture is maintained at 150 ° C. The rotational speed of the extruder is 50 rpm and the residence time of the material is 30 seconds. The mixture is produced under an inert atmosphere. Finally, the mixture is cooled after injection in situ in a mold. vs. PDLLA + 10% BV / CTN
- Step 1 Coating Biocompatible Glass Particles with Chitosan (BV / CTN)
- a demineralised water solution containing 1% acetic acid is prepared. From this solution is immediately prepared a 10g / L solution of chitosan (to avoid evaporation of the solvent and percolation of chitosan). 45S5 ® biocompatible glass particles (10% by weight) are then added to the latter solution. The whole is stirred mechanically for 15 minutes and then filtered under vacuum. Glass particles biocompatible coated with chitosan are collected and dried under vacuum at 40 ° C for 24 hours.
- Step 2 Biocomposites shaping by extrusion and injection molding
- a BV / CTN sample as obtained in the previous step 1 is mixed with PDLLA granules so that the coated biocompatible glass particles represent 10% by weight of the composite.
- the mixture is made by means of a gravimetric doser.
- the temperature of the mixture is maintained at 150 ° C.
- the rotational speed of the extruder is 50 rpm and the residence time of the material is 30 seconds.
- the mixture is produced under an inert atmosphere. Finally, the mixture is cooled after injection in situ in a mold.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Transplantation (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Inorganic Chemistry (AREA)
- Composite Materials (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Materials For Medical Uses (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR1353899A FR3004986B1 (fr) | 2013-04-29 | 2013-04-29 | Materiaux composites a base de polymeres bioresorbables et de verre biocompatible |
PCT/EP2014/058744 WO2014177575A1 (fr) | 2013-04-29 | 2014-04-29 | Materiaux composites a base de polymeres bioresorbables et de verre biocompatible |
Publications (1)
Publication Number | Publication Date |
---|---|
EP2991694A1 true EP2991694A1 (fr) | 2016-03-09 |
Family
ID=48795742
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP14720148.7A Withdrawn EP2991694A1 (fr) | 2013-04-29 | 2014-04-29 | Materiaux composites a base de polymeres bioresorbables et de verre biocompatible |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP2991694A1 (fr) |
FR (1) | FR3004986B1 (fr) |
WO (1) | WO2014177575A1 (fr) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116173314B (zh) * | 2023-01-17 | 2024-04-16 | 成都美益博雅材料科技有限公司 | 复合材料及其制备方法和用途 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5716413A (en) | 1995-10-11 | 1998-02-10 | Osteobiologics, Inc. | Moldable, hand-shapable biodegradable implant material |
US5977204A (en) | 1997-04-11 | 1999-11-02 | Osteobiologics, Inc. | Biodegradable implant material comprising bioactive ceramic |
US20050277860A1 (en) | 2004-06-14 | 2005-12-15 | Jentec, Inc. | Extended stay-on wound dressing |
DE102005042078B4 (de) * | 2005-09-01 | 2008-09-04 | Friedrich-Baur-Gmbh | Werkstoff für den überwiegend medizinischen, langfristigen in-vivo Einsatz und Verfahren zu seiner Herstellung |
US20100168798A1 (en) * | 2008-12-30 | 2010-07-01 | Clineff Theodore D | Bioactive composites of polymer and glass and method for making same |
-
2013
- 2013-04-29 FR FR1353899A patent/FR3004986B1/fr not_active Expired - Fee Related
-
2014
- 2014-04-29 WO PCT/EP2014/058744 patent/WO2014177575A1/fr active Application Filing
- 2014-04-29 EP EP14720148.7A patent/EP2991694A1/fr not_active Withdrawn
Non-Patent Citations (2)
Title |
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None * |
See also references of WO2014177575A1 * |
Also Published As
Publication number | Publication date |
---|---|
FR3004986A1 (fr) | 2014-10-31 |
WO2014177575A1 (fr) | 2014-11-06 |
FR3004986B1 (fr) | 2015-09-04 |
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