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WO2011058208A1 - Polymères hydrophiles utilisés en tant que systèmes de libération de composés bioactifs en mailles d'application chirurgicale - Google Patents

Polymères hydrophiles utilisés en tant que systèmes de libération de composés bioactifs en mailles d'application chirurgicale Download PDF

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Publication number
WO2011058208A1
WO2011058208A1 PCT/ES2010/070725 ES2010070725W WO2011058208A1 WO 2011058208 A1 WO2011058208 A1 WO 2011058208A1 ES 2010070725 W ES2010070725 W ES 2010070725W WO 2011058208 A1 WO2011058208 A1 WO 2011058208A1
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WIPO (PCT)
Prior art keywords
bioactive
acrylic copolymer
mesh
mesh prosthesis
monomers
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Ceased
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PCT/ES2010/070725
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English (en)
Spanish (es)
Inventor
Julio SAN ROMÁN DEL BARRIO
María del Mar FERNÁNDEZ GUTIÉRREZ
Juan M. BELLÓN CANEIRO
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Consejo Superior de Investigaciones Cientificas CSIC
Universidad Complutense de Madrid
Universidad de Alcala de Henares UAH
Original Assignee
Consejo Superior de Investigaciones Cientificas CSIC
Universidad Complutense de Madrid
Universidad de Alcala de Henares UAH
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Publication of WO2011058208A1 publication Critical patent/WO2011058208A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/0063—Implantable repair or support meshes, e.g. hernia meshes
    • 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
    • A61L27/40—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
    • 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
    • A61L27/58—Materials at least partially resorbable by the body

Definitions

  • HYDROPHILE POLYMERS AS BIOACTIVE COMPOUND RELEASE SYSTEMS IN SURGICAL APPLICATION BADS.
  • the present invention relates to the development of bioactive agent release systems, preferably antibiotics, based on hydrophilic polymers to be used as prosthetic coatings in the form of polymer mesh with special interest in abdominal surgical applications. Therefore the present application falls within the field of medicine.
  • the infection can alter the integration of the biomaterial in the tissue and therefore the healing process of the patient who may suffer another hernia and therefore another operation.
  • the adhesion of a bacterium to the surface of a biomaterial is the determining step in the pathogenesis of the infection.
  • Some microorganisms are capable of forming a biofilm or biofilm on the mesh that protects them from the immune system and the action of antibiotics.
  • the bacterium is wrapped and protected, thereby achieving strong and irreversible adhesion to the surface of the implant surviving on it.
  • AMPS is an anionic monomer, carrier of an ionized sulfonic group (strong acid) in virtually the entire pH range [Tong Z., LX, Swelling equilibria and volume phase transition in hydrogels with strongly dissociating electrolytes. Macromolecules, 1994. 27].
  • HEMA polymers and copolymers have wide applications in surgery and medicine, among which are: contact lenses [Rostoke M.V., L.L., Hema copolymers having high oxygen permeability., N.P.D. Corp, Editor. 1977: USA.], Healing, hemocompatible coatings, drug delivery systems, surgical prostheses, dialysis membranes, artificial corneas ... etc. [López G.P., R.B.D., Rapoza R.J., Horbett T.A., Plasma deposition of ultrathin films of poly (hydroxyethylmethacrylate): Sur ⁇ ace Analysis and protein adsorption measurements. Macromolecules, 1993. 26 (13): p. 3247-3253].
  • a first object or aspect of the present invention is to provide a mesh prosthesis comprising a medical mesh impregnated with a bioactive acrylic copolymer, characterized in that the amount of bioactive acrylic copolymer is between and 40% w / w (weight / weight) with respect to the total and the bioactive acrylic copolymer comprises: between 30 and 95% w / w of one or more monomers with hydroxyl groups; between 5 and 55% w / w of one or more monomers with sulfonic groups; Y between 0.01% and 50% w / w of a bioactive agent.
  • a second aspect of the present invention is a process for the manufacture of these mesh prostheses of the first aspect comprising at least the following steps: i) the bioactive acrylic copolymer is dissolved in ethanol;
  • the solvent is evaporated, preferably at room temperature.
  • stage (ii) is as homogeneous as possible, so that it can be carried out by deposition of the solution dropwise to the total coating or by simple immersion in the ethanolic solution.
  • Ethanol is important for its practically Zero toxicity, and its characteristics that reduce the formation of lumps during drying compared to other solvents.
  • a third aspect is the use of a bioactive acrylic copolymer comprising between 30 and 95% w / w of one or more monomers with hydroxyl groups; between 5 and 55% w / w of one or more monomers with sulfonic groups; and between 0.01% and 50% w / w of a bioactive agent for impregnating medical meshes, preferably abdominal mesh.
  • a preferred embodiment of the invention are mesh prostheses characterized in that the monomer with hydroxyl groups comprises at least one hydroxyalkyl acrylate or a hydroxyalkyl methacrylate of the general formula (I):
  • n is from 0 to 4.
  • n is from 0 to 1;
  • Ri is a hydrogen or a methyl radical.
  • 2-hydroxyethyl methacrylate is the preferred hydroxyl group monomer.
  • monomers with preferred sulfonic groups are those of the general formula (II):
  • Ri is a hydrogen or methyl radical
  • R2 and R3 are the same or different from each other and represent a hydrogen or a (C1-C3) alkyl radical
  • n is a value from 1 to 6.
  • the most preferred sulfonic group monomer is 2-acrylamido-2-methylpropane sulfonic.
  • the bioactive acrylic copolymer comprises 2-hydroxyethyl monomers and 2-acrylamido-2-methylpropane sulfonic monomers.
  • Bioactive agents may be of a different nature, but for biomedical applications the most important are antibiotics, antithrombogens, antiangiogenic, proangiogenic and any of their mixtures. Antibiotics are the most preferred to avoid post implantation operations. Different antibiotics are known that can be useful for the present invention such as quinolones, glycopeptides, tetracyclines, oxazolidinones, macrolides, lycosamides, streptogramins, sulfonamides, polypeptides, penicillins, ansamycins or any of their mixtures. Glycopeptides are the preferred antibiotics.
  • Glycopeptides they include vancomycin, erythromycin, neomicin streptomycin, daptomycin, rifamycin, puromycin, lincomycin or any combination thereof, preferably it is vancomycin.
  • the amount of bioactive acrylic copolymer is between 15 and 30% w / w. These percentages allow the incorporation of an adequate amount of bioactive agent, correctly coating the device, without exposed areas and without blocked pores.
  • the bioactive acrylic copolymer shows good release profiles of the bioactive agent when this copolymer comprises between 45 and 75% w / w of one or more monomers with hydroxyl groups.
  • the bioactive agent may preferably be between 5 and 30% w / w relative to the total bioactive acrylic copolymer.
  • the bioactive acrylic copolymer may additionally comprise polyethylene glycol, preferably between 10 and 30% w / w, which is a suitable range to achieve a homogeneous coating without lumping.
  • the medical mesh may have different natures, but preferably it is selected from the following types: Low molecular weight polypropylene monofilament; High molecular weight polypropylene monofilament; High molecular weight double filament polypropylene; Polypropylene large pore multifilament; High molecular weight multifilament polyester; Polytetrafuoroethylene (Gore-Tex®).
  • step (i) preferably in step (i) the bioactive acrylic copolymer is dissolved in a proportion between 1 and 5% w / v in ethanol, obtaining suitable viscosities for the coating of the medical mesh .
  • Viscosity is a critical parameter because if low viscosity solutions were obtained the coating could be low and, on the other hand, very high viscosities would encourage lump formation.
  • step (iii) The evaporation of step (iii) must be carried out in a way that the product obtained is homogeneous. This can be achieved simply by evaporating the solvent at room temperature.
  • the process for obtaining the bioactive acrylic copolymer comprises: i ') the bioactive agent is dissolved, preferably together with polyethylene glycol, in distilled water;
  • the mixture is frozen and lyophilized.
  • step (i ') the concentration of preferably bioactive agent in the aqueous solution is between 5 mg / mL and 40 mg / mL.
  • step (i ') the concentration of preferably polyethylene glycol in the aqueous solution is between 5 mg / mL and 40 mg / mL.
  • the process for obtaining the Acrylic copolymer comprises the following steps: i ") dissolve the monomers with a radical polymerization initiator in a mixture of water: isopropanol;
  • the radical polymerization initiator may be any of those known to those skilled in the art, preferably being azobis-isobutyronitrile (AIBN), and preferably being in a proportion between 0.25 and 2% w / w.
  • AIBN azobis-isobutyronitrile
  • the mixture is deoxygenated and this can be carried out with a stream of nitrogen.
  • step (iii ) the heat treatment can be carried out at a temperature between 60 and 80 ° C.
  • mesh in the context of the present invention refers to a woven or interwoven polymer network of biocompatible and biostable polymers: polyolefins, polyesters, polyethers, polyurethanes or biodegradable polymers: polyhydroxyalkanoates, polylactic, polybutyrates, polyglycolics used in various surgical procedures such as abdominal, dental or orthopedic for the purpose of insulating tissues or organs.
  • the mesh is abdominal, among other things because of the great relevance of infections to patients.
  • FIG. 1 - Standardized ATR-FTIR spectra of HA80, HA80rec and HA80recV copolymers. Transmittance vs. wavelength is represented.
  • Figure 3 Vancomycin release curve from HA70recV, HA80recV systems.
  • Figure 5. Death curve for a) S.aureus and b) S.epidermidis.
  • Figure 7 Macroscopic photos of rabbits treated with the different systems and infected with a) S. aureus and b) S. epidermidis.
  • Figure 8. Microscopic photos of rabbits treated with the different systems and infected with a) nothing, b) S. aureus and c) S. epidermidis.
  • Example 1 Preparation of systems based on copolymers of 2-hydroxyethyl methacrylate-2-acrylamido-2-methylpropanesulfonic acid and vancomycin.
  • HEMA / AMPS copolymers were prepared from 80/20 and 70/30% -p feed compositions (named HA80 and HA70 respectively. The reaction was carried out in solution, using water: isopropanol (50 : 50) as solvent, at 50 ° C and AIBN as initiator in concentration 1.5x10-2 M.
  • Isopropanol was used as solvent in order to obtain copolymers of controlled molecular weight due to its low toxicity (classified by Food and Drugs Administration (FDA) as class 3)
  • Guidance for the Industry Q3C Impurities Residual Solvents International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) 62 FR67377 (1997) and high transfer constant [Brandrup J., IEH, Grulke EA, Polymer Handbook, ed. IEH Brandrup J., Grulke EA (ed.).
  • the antibiotic was incorporated into the corresponding copolymer for which vancomycin (20% -p) was dissolved together with polyethylene glycol (20% -p) in distilled water and then the corresponding copolymer (HA80) was added. This mixture was left under magnetic stirring for 24 h and subsequently frozen and lyophilized. The system was named as HA80recV.
  • the control polymer was prepared in the absence of vancomycin (HA80rec).
  • the structural characterization of the copolymers was carried out by infrared spectroscopy with Fourier transform by Attenuated Total Reflectance, ATR-FTIR, in a Perkin-Elmer Spectrum One device. To this end, a sample of the corresponding copolymer was deposited on the window of the equipment exerting a pressure controlled on it in order to ensure a good window-copolymer contact (figure 1). The thermal stability of the copolymers was evaluated using a thermobalance (TA Instruments TGAQ500). For this, the weight loss of the sample subjected to a constant heating rate of 10 ° C / min between 50 and 500 ° C, in an atmosphere of N 2, was recorded. Each trial was performed in duplicate (figure 2).
  • Example 2 Study of the in vitro release of vancomycin from prostheses coated with polymer plus antibiotic.
  • prostheses coated with polymer-antibiotic of 1 cm 2 in size were used, which were immersed in 10 ml of phosphate buffer (composition detailed in the previous section) and incubated at 37 ° C. During certain periods of time (Table I) samples of the release medium (0.5 ml) were taken and replaced by fresh medium (0.5 ml).
  • Example 3 Bactericidal activity of the prostheses coated in liquid medium.
  • the experimental phase in vitro in liquid medium consists in the realization of a death curve.
  • the death curve is a microbiological method to know the concentrations in which an antibiotic kills a known bacterial strain. It is a protocol described by the NCCLS (National Committee for Clinical Laboratory Standards), so that the results are reproducible and comparable.
  • a known concentration of antibiotic is tested in death curve studies and viable colony forming units (CFU / ml) are quantified at each time. These studies consider that a decrease of 3logioUFC / ml compared to the control group (without antibiotic) indicates an adequate bactericidal response. The dose that achieves this decrease in CFU is considered bactericidal.
  • bare polypropylene mesh (PP), which was the control group, polymer coated polypropylene mesh without antibiotic (POL) and polymer coated mesh with vancomycin (VC). Each group had three meshes. A sterility control was also used. All meshes were sterilized by ethylene oxide.
  • the mesh that was used in the different examples herein was the low molecular weight monofilament polypropylene (Parietene®, K991400 Sofradim, Trevoux (France))
  • MIC 1 mg / L.
  • a bacterial suspension equivalent to a standard of 0.5 McFarland 1.5 x 108 CFU / ml was previously prepared by nephelometry. For each 10-ce tube, 100 microliters of the 0.5 McFarland bacterial suspension was inoculated.
  • the tubes were incubated at 37 0 C and samples were collected at 0, 3, 6, and 24 hours for S. aureus and 0, 2, 4, 6, and 24 hours for S. epidermidis. For each time the microbiological count, previously vortexing, with the serial dilution method in Mueller Hinton Agar, with a sample of 100 microliters, the detection limit being 10 CFU / mi.
  • Vancomycin levels were measured using an automated fluorescent polarization immunoassay technique (Tdx / Flx®, from Abbott laboratories), with a minimum detection threshold of 2 ⁇ g / ml.
  • Example 4 Bactericidal activity of coated prostheses. Agar test
  • the bactericidal activity of the coated prosthesis is determined by the diffusion method on agar plate commercial blood agar plates were used and cultured at 37 0 C for twenty four hours and fourteen days.
  • the Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermides strains of a sample from a patient's vascular catheter are used as model cultures. Both cultures are preserved by storing them at -80 ° C in glycerin / water mixtures (20% v / v).
  • the inoculum was done by planting a colony, twenty-four hours old, for each quadrant. Each plate was divided into 4 quadrants, of which one was free and in each of the other 3 a 1 cm 2 fragment of each mesh was studied: Polypropylene monofilament reticular prosthesis (PP), polypropylene with polymeric coating (Pol) and Polypropylene with polymer and vancomycin (Vaneo). In each group, 5 plates were used for each of the study times, which were established at 24 hours and 14 days.
  • PP Polypropylene monofilament reticular prosthesis
  • Polypropylene with polymeric coating Polypropylene with polymer and vancomycin
  • the halo area is measured by the ImageJ morphometric program, in photos of the blood agar plates, and statistically processed with the U-Mann Whitney statistical test for the average of paired data independent of the halo of the plates with Staphylococcus aureus and Staphylococcus epidermididis
  • bactericidal activity of the polymer is measured by evaluating the inhibition or retardation of the development of colonies just in the areas of direct contact with the surface of the prosthesis.
  • halo of inhibition can be seen in the polypropylene mesh covered with polymer with vancomycin, compared to the bare mesh or with polymer without vancomycin, in which its quadrant in the plate is Germ cover.
  • the mean halo for Staphylococcus aureus was 1.75 square centimeters (0.59 standard deviation) and for Staphylococcus epidermidis it was 1.84 square centimeters (0.12 standard deviation). There were no statistically significant differences in halo size for epidermidis or aureus. (Figure 4).
  • Example 5 In vivo experimental model: Rabbit abdominal wall defects.
  • the white New Zealand male rabbit was used as an experimental animal.
  • the weight of the animals was between 3,200 and 3,500 kg at the beginning of the study.
  • the animals were divided into 3 study groups, in total 84 rabbits were used, 12 from the control group, 36 rabbits at 14 days and 36 rabbits at 30 days.
  • the study groups are the following: - Control Group, without bacterial inoculum: The same rabbit was used for the control subgroups of PP and POL, implanting each mesh on one side of the alba line.
  • the animals Prior to surgery, the animals were anesthetized with a mixture of ketamine hydrochloride, 70 mg / kg, diazepam, 1.5 mg / kg and chlorpromazine, administered intramuscularly. In some of the animals it was necessary to administer an additional dose intraperitoneally during the intervention.
  • the skin and subcutaneous cellular tissue were sectioned. Defects were created in the anterior muscular wall of the abdomen (right and left lateral flank in the control group and right flank in the infected groups), which included the external and internal oblique, retaining the transverse muscle, the transversalis fascia and the parietal peritoneum to avoid contact of microorganisms with the visceral peritoneum.
  • the final surface of the defect was 15 cm 2 , corresponding to a rectangular defect of 5 cm of longitudinal axis and 3 cm of transverse axis. This defect was repaired by one of the meshes under study (PP, Pol, or Vaneo).
  • the biomaterial was fixed to the edges of the defect (prosthetic interface - anchor fabric) by means of a continuous 4/0 polypropylene suture interrupted only at the corners.
  • the skin incision was closed with a 3/0 silk. The technique can be seen in the surgical technique photos.
  • the defect bed was inoculated with 0.5 ml of 108 CFU / ml suspension of Staphylococcus aureus (Sa) or Staphylococcus epidermidis (Se), before placing the biomaterial.
  • the concentration of microorganisms was obtained by nephelometry (0.5 McFarland).
  • the animals were sacrificed at 14 and 30 days and the abdominal wall pieces were divided into three and processed for histological study with scanning and scanning electron microscopy, and for immunohistochemical study.
  • the pieces were fixed in solution F13, included in paraffin, cut into sections of 5 ⁇ and stained with hematoxylin-eosin or Masson's trichrome (Goldner-Gabe variety). Finally, they were observed under a Zeiss Axiophot microscope (Cari Zeiss, Oberkochen, Germany).
  • the immunohistochemical study was carried out using a monoclonal antibody specific for Staphylococcus aureus (Abcam, ab8067, Cambridge, UK) and Staphylococcus epidermidis (Abcam, ab20942, Cambridge, UK). After rehydration of the samples in saline phosphate buffer solution (PBS) pH 7.4 and specific blocking with 3% bovine serum albumin (BSA), the samples were incubated with the primary antibody for 12 h at 4 o C. Then the preparations were washed with PBS-BSA, and incubated with a biotinylated anti-mouse antibody (IgG, Sigma, St.
  • PBS saline phosphate buffer solution
  • BSA bovine serum albumin
  • the statistical analysis of the data was performed using the Graph Pad Prism 4 program. The results were expressed as mean values ⁇ the standard deviation. The Mann Withney U test was used to compare data from different study groups. The level of statistical significance was considered with p ⁇ 0.05. There were no signs of infection or other alterations in the animals of the control group. The animals of the PP group and the POL group infected with S. aureus in the first days after the intervention presented clinical signs of infection with loss of appetite and weight loss and a mortality rate of 16.67% in the PP group. , and 8.33% in the Pol group. In the VC group there was no clinical impact of weight loss and mortality was 0%.
  • the neoformed tissue was arranged concentrically around the prosthetic filaments. It was made up of collagen fibers and inflammatory cells. In the biomaterials with polymer (Pol and Vaneo) this coating also appeared surrounded by macrophage cells and giant foreign body cells, being evident in some of the samples studied, signs of degradation (Figure 8)

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Composite Materials (AREA)
  • Materials Engineering (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne une prothèse en mailles qui comprend une maille médicale imprégnée d'un copolymère acrylique bioactif, caractérisée en ce que la quantité copolymère acrylique bioactif se situe entre 5 et 40% en poids par rapport au poids total de la prothèse et le copolymère acrylique bioactif comprend: entre 30 et 95% en poids d'un ou plusieurs monomères avec des groupes hydroxyle, entre 5 et 55% en poids d'un ou plusieurs monomères avec des groupes sulfoniques; et entre 0,01 et 50% en poids d'un agent bioactif, et l'utilisation de cette prothèse en mailles dans des interventions chirurgicales pour la réparation des hernies.
PCT/ES2010/070725 2009-11-10 2010-11-10 Polymères hydrophiles utilisés en tant que systèmes de libération de composés bioactifs en mailles d'application chirurgicale Ceased WO2011058208A1 (fr)

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ESP200930975 2009-11-10
ES200930975A ES2359321B1 (es) 2009-11-10 2009-11-10 Pol�?meros hidrófilos como sistemas de liberación de compuestos bioactivos en mallas de aplicación quirúrgica.

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0596615A1 (fr) * 1992-10-30 1994-05-11 Medtronic, Inc. Article muni d'une surface bioactive
WO2002013871A2 (fr) * 2000-08-15 2002-02-21 Surmodics, Inc. Matrice renfermant un medicament
WO2008024510A2 (fr) * 2006-08-25 2008-02-28 Boston Scientific Scimed, Inc. Dispositifs médicaux ayant une performance mécanique améliorée
WO2008109098A2 (fr) * 2007-03-05 2008-09-12 Boston Scientific Scimed, Inc. Dispositifs médicaux présentant une performance améliorée

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0596615A1 (fr) * 1992-10-30 1994-05-11 Medtronic, Inc. Article muni d'une surface bioactive
WO2002013871A2 (fr) * 2000-08-15 2002-02-21 Surmodics, Inc. Matrice renfermant un medicament
WO2008024510A2 (fr) * 2006-08-25 2008-02-28 Boston Scientific Scimed, Inc. Dispositifs médicaux ayant une performance mécanique améliorée
WO2008109098A2 (fr) * 2007-03-05 2008-09-12 Boston Scientific Scimed, Inc. Dispositifs médicaux présentant une performance améliorée

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ES2359321B1 (es) 2012-03-26

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