ES2812048A1 - BIODEGRADABLE BIOMATERIAL (Machine-translation by Google Translate, not legally binding) - Google Patents
BIODEGRADABLE BIOMATERIAL (Machine-translation by Google Translate, not legally binding) Download PDFInfo
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- ES2812048A1 ES2812048A1 ES202030999A ES202030999A ES2812048A1 ES 2812048 A1 ES2812048 A1 ES 2812048A1 ES 202030999 A ES202030999 A ES 202030999A ES 202030999 A ES202030999 A ES 202030999A ES 2812048 A1 ES2812048 A1 ES 2812048A1
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- Prior art keywords
- pva
- poly
- phbv
- pha
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- 239000012965 benzophenone Substances 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
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- 229920001222 biopolymer Polymers 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
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- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
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- ANSXAPJVJOKRDJ-UHFFFAOYSA-N furo[3,4-f][2]benzofuran-1,3,5,7-tetrone Chemical compound C1=C2C(=O)OC(=O)C2=CC2=C1C(=O)OC2=O ANSXAPJVJOKRDJ-UHFFFAOYSA-N 0.000 description 1
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- 229920002521 macromolecule Polymers 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- AMWRITDGCCNYAT-UHFFFAOYSA-L manganese oxide Inorganic materials [Mn].O[Mn]=O.O[Mn]=O AMWRITDGCCNYAT-UHFFFAOYSA-L 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
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- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229940100595 phenylacetaldehyde Drugs 0.000 description 1
- 239000005015 poly(hydroxybutyrate) Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
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- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L29/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers
- C08L29/02—Homopolymers or copolymers of unsaturated alcohols
- C08L29/04—Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
-
- A61F13/01017—
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L45/00—Compositions of homopolymers or copolymers of compounds having no unsaturated aliphatic radicals in side chain, and having one or more carbon-to-carbon double bonds in a carbocyclic or in a heterocyclic ring system; Compositions of derivatives of such polymers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L67/00—Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers
Abstract
Description
DESCRIPCIÓNDESCRIPTION
Biom aterial biodegradableBiodegradable biom aterial
La presente invención se refiere a un biomaterial biodegradable hidrófilo que comprende una red semiinterpenetrada (semi-IPN) constituida por un polímero de la familia del polihidroxialcanoato (PHA), y otro polímero de polivinil alcohol (PVA). Asimismo, la invención se refiere a su procedimiento de obtención y a una composición que comprende dicho material y partículas con propiedades conductoras y antimicrobianas útiles para la prevención y tratamiento de infecciones microbianas y de enfermedades que requieren electroestimulación.The present invention refers to a hydrophilic biodegradable biomaterial comprising a semi-interpenetrated network (semi-IPN) made up of a polymer of the polyhydroxyalkanoate (PHA) family, and another polyvinyl alcohol (PVA) polymer. Likewise, the invention relates to its method for obtaining and to a composition comprising said material and particles with conductive and antimicrobial properties useful for the prevention and treatment of microbial infections and diseases that require electrostimulation.
ANTECEDENTES DE LA INVENCIÓNBACKGROUND OF THE INVENTION
En el estado de la técnica se han descrito materiales compuestos por polihidroxibutiratoco-valerato (PHBV) y polivinil alcohol (PVA).Materials composed of polyhydroxybutyrate valerate (PHBV) and polyvinyl alcohol (PVA) have been described in the state of the art.
El documento WO2015/059709A1 divulga láminas biodegradables formadas por al menos una capa que comprende un polímero hidrofóbico seleccionado entre un grupo que incluye los polihidroxialcanoatos tales como el copolímero PHBV. El material puede comprender otros componentes como, por ejemplo, el poli(vinil alcohol) (PVA).WO2015 / 059709A1 discloses biodegradable sheets formed by at least one layer comprising a hydrophobic polymer selected from a group that includes polyhydroxyalkanoates such as PHBV copolymer. The material can comprise other components such as polyvinyl alcohol (PVA).
El documento CN103341327A (citado por el cliente) se refiere a un material compuesto basado en poli(hidroxibutirato-co-hidroxivalerato) (PHBV) y un polímero hidrofílico, como es el poli(alcohol vinílico) (PVA), así como un procedimiento para su preparación y su uso como membranas. Así, una solución de PHBV en cloroformo/etanol se somete a electrospinning para dar lugar a las fibras que forman la capa base de la membrana, sobre la que se genera un recubrimiento a partir de una solución de PVA.Document CN103341327A (cited by the customer) refers to a composite material based on poly (hydroxybutyrate-co-hydroxyvalerate) (PHBV) and a hydrophilic polymer, such as poly (vinyl alcohol) (PVA), as well as a process for their preparation and their use as membranes. Thus, a solution of PHBV in chloroform / ethanol is subjected to electrospinning to give rise to the fibers that form the base layer of the membrane, on which a coating is generated from a PVA solution.
El documento International Journal of Biological Macromolecules 2018, Vol. 109, pp. 85 98 se refiere a estructuras tricapa fibrosas que incorporan factor de crecimiento endotelial vascular (VEGF) y concentrado de factor plaquetario (PFC) diseñadas para mimetizar arterias. Estas estructuras, que se obtienen mediante técnicas de electrospinning, comprenden nanofibras de poli(hidroxibutirato-co-hicroxivalerato) (PHBV) y poli(alcohol vinílico) (PVA) alineadas longitudinalmente en la capa interna y fibras PHBV/PVA multiescala en la capa periférica.The document International Journal of Biological Macromolecules 2018, Vol. 109, pp. 85 98 refers to fibrous trilayer structures incorporating vascular endothelial growth factor (VEGF) and platelet factor concentrate (PFC) designed to mimic arteries. These structures, which are obtained by electrospinning techniques, comprise nanofibers of poly (hydroxybutyrate-co-hydroxyvalerate) (PHBV) and polyvinyl alcohol (PVA) aligned longitudinally in the inner layer and multiscale PHBV / PVA fibers in the peripheral layer.
El documento WO2000/043579A1 divulga materiales compuestos, películas o composiciones para su uso en la fabricación de diversos artículos y que son degradables en condiciones básicas. Estos materiales comprenden polímeros fácilmente hidrolizables, como el copolímero PHBV, junto a polímeros solubles en agua, como poli(vinil alcohol) (PVA), que pueden disponerse en películas de una sola capa, películas multi-capa, o diversos tipos de fibras o microfibras (ver página 5, líneas 13-28). En concreto, el documento describe microfibras multi-capa que comprenden PH BV/PVA/PH BV.WO2000 / 043579A1 discloses composites, films or compositions for use in the manufacture of various articles and which are degradable under basic conditions. These materials comprise easily hydrolyzable polymers, such as PHBV copolymer, together with water-soluble polymers, such as poly (vinyl alcohol) (PVA), which can be arranged in single-layer films, multi-layer films, or various types of fibers or microfibers (see page 5, lines 13-28). In particular, the document describes multi-layer microfibers comprising PH BV / PVA / PH BV.
En el estado de la técnica también se ha descrito la incorporación de otros materiales para mejorar sus propiedades.In the state of the art, the incorporation of other materials to improve their properties has also been described.
Así, por ejemplo, el documento Nanomaterials 2015, Vol. 5, pp. 2054-2130 recoge una revisión sobre la incorporación de nanopartículas a hidrogeles, que da lugar a materiales con propiedades mecánicas, biológicas y fisicoquímicas mejoradas. Los hidrogeles nanocompuestos obtenidos a partir de hidrogeles y nanopartículas poliméricas tienen especial interés en el sector biomédico. Entre los materiales divulgados se encuentran un sistema de liberación de fármacos basado en un hidrogel de alginato sódico con nanopartículas de polipirrol inmovilizadas y un material compuesto sensible a la luz láser formado por un hidrogel entrecruzado que posee una doble red agarosa/alginato y nanopartículas de polipirrol.Thus, for example, the document Nanomaterials 2015, Vol. 5, pp. 2054-2130 includes a review on the incorporation of nanoparticles to hydrogels, which gives rise to materials with improved mechanical, biological and physicochemical properties. Nanocomposite hydrogels obtained from hydrogels and polymeric nanoparticles are of special interest in the biomedical sector. Among the materials disclosed are a drug delivery system based on a sodium alginate hydrogel with immobilized polypyrrole nanoparticles and a composite material sensitive to laser light formed by a cross-linked hydrogel that has a double agarose / alginate network and polypyrrole nanoparticles. .
Del mismo modo, el documento International Journal of Polymeric Materials 2020, Vol.Similarly, the document International Journal of Polymeric Materials 2020, Vol.
69, N° 11, pp. 709-727 es una revisión sobre materiales bionanocompuestos basados en polímeros conductores que exhiben propiedades de conductividad, biocompatibilidad y biodegradabilidad que los hace útiles en aplicaciones biomédicas, agrícolas y analíticas. Entre los materiales descritos se hallan los composites derivados de polipirrol y diversos polímeros biodegradables, como citosán, polilactida, policaprolactona, poli(lactida-glicolida), poli(lactida-co-policaprolactona), gelatina o colágeno.69, No. 11, pp. 709-727 is a review on conductive polymer-based bionanocomposites that exhibit conductivity, biocompatibility, and biodegradability properties that make them useful in biomedical, agricultural, and analytical applications. Among the materials described are composites derived from polypyrrole and various biodegradable polymers, such as cytosan, polylactide, polycaprolactone, poly (lactide-glycolide), poly (lactide-co-polycaprolactone), gelatin or collagen.
Por tanto, sería deseable disponer de materiales que combinen las propiedades de absorción de agua del PVA con las propiedades de resistencia mecánica de un polímero de la familia de los polihidroxialcanoatos (PHA), preferentemente el PHBV y que, por tanto, confiera propiedades hidrófilas al PHBV que, además, sean biodegradables y, por tanto, resulten útiles en el campo de la biotecnología y, en particular, en el campo de la ingeniería tisular.Therefore, it would be desirable to have materials that combine the water absorption properties of PVA with the mechanical strength properties of a polymer. of the family of polyhydroxyalkanoates (PHA), preferably PHBV and that, therefore, confers hydrophilic properties to PHBV that, in addition, are biodegradable and, therefore, are useful in the field of biotechnology and, in particular, in the field of tissue engineering.
Asimismo, sería deseable que dichos materiales puedan incorporar otros compuestos que le confieran propiedades antimicrobianas para prevenir infecciones y propiedades conductoras para aplicaciones biomédicas que requieran estimulación eléctrica.Likewise, it would be desirable for said materials to be able to incorporate other compounds that confer antimicrobial properties to prevent infections and conductive properties for biomedical applications that require electrical stimulation.
DESCRIPCIÓN DE LA INVENCIÓNDESCRIPTION OF THE INVENTION
En un primer aspecto, la presente invención se refiere a un material que comprende:In a first aspect, the present invention refers to a material comprising:
- polihidroxialcanoato (PHA), preferiblemente donde el polihidroxialcanoato (PHA) se selecciona de poli(3-hidroxibutirato-co-3-hidroxivalerato) (PHBV), poli(3-hidroxipropionato), poly(3-hidroxibutirato), poli(3-hidroxivalerato), poli(3-hidroxihexanoato), poli(3-hidroxioctoato), poli(3-hidroxioctadecanoato), poli(4-hidroxibutirato), poli(4-hidroxivalerato), poli(5-hidroxivalerato) y sus respectivos copolímeros, y más preferiblemente donde el polihidroxialcanoato (PHA) es poli(3-hidroxibutirato-co-3-hidroxivalerato) (PHBV), y- polyhydroxyalkanoate (PHA), preferably where the polyhydroxyalkanoate (PHA) is selected from poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly (3-hydroxypropionate), poly (3-hydroxybutyrate), poly (3- hydroxyvalerate), poly (3-hydroxyhexanoate), poly (3-hydroxyoctoate), poly (3-hydroxyoctadecanoate), poly (4-hydroxybutyrate), poly (4-hydroxyvalerate), poly (5-hydroxyvalerate) and their respective copolymers, and more preferably where the polyhydroxyalkanoate (PHA) is poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and
- poli(alcohol vinílico) (PVA).- poly (vinyl alcohol) (PVA).
Estos materiales presentan propiedades hidrófilas que forman películas compuestas por una red semiinterpenetrada constituida por un polímero de la familia de los polihidroxialcanoatos (PHA), preferiblemente de polihidroxibutirato-co-valerato (PHBV), y por el polivinil alcohol (PVA).These materials have hydrophilic properties that form films composed of a semi-interpenetrated network made up of a polymer of the polyhydroxyalkanoate (PHA) family, preferably of polyhydroxybutyrate-co-valerate (PHBV), and of polyvinyl alcohol (PVA).
A lo largo de la presente invención el término "películas basadas en semi-IPNs PHA/PVA” se refieren al material de la invención.Throughout the present invention the term "films based on PHA / PVA semi-IPNs" refers to the material of the invention.
En otra realización la invención se refiere al material definido anteriormente, donde la relación en peso de PHA y PVA es de entre 0/100 y 100/0 p/p respectivamente.In another embodiment the invention refers to the material defined above, where the weight ratio of PHA and PVA is between 0/100 and 100/0 w / w respectively.
En otra realización la invención se refiere al material definido anteriormente donde: el polihidroxialcanoato (PHA) es poli(3-hidroxibutirato-co-3-hidroxivalerato) (PHBV), y la proporción en peso de PHBV y PVA es de 30/70 p/p. In another embodiment the invention refers to the material defined above where: the polyhydroxyalkanoate (PHA) is poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and the weight ratio of PHBV and PVA is 30/70 p / p.
Otro aspecto de la invención se refiere a un procedimiento de obtención del material definido anteriormente, que comprende las etapas de:Another aspect of the invention refers to a process for obtaining the material defined above, which comprises the steps of:
i. preparación de una disolución de PHA, preferiblemente PHBV, en un disolvente seleccionado de cloroformo, trifluoroetanol, diclorometano, hexafluor-2-propanol, acetona, etanol, metanol, carbonato de propileno, dimetilsulfóxido, cloruro de metileno, tolueno, N, N-dimetilformamida y dioxano, preferiblemente en cloroformo,i. preparation of a solution of PHA, preferably PHBV, in a solvent selected from chloroform, trifluoroethanol, dichloromethane, hexafluoro-2-propanol, acetone, ethanol, methanol, propylene carbonate, dimethylsulfoxide, methylene chloride, toluene, N, N-dimethylformamide and dioxane, preferably in chloroform,
ii. preparación de una disolución de PVA en un disolvente seleccionado de 1-metil-2-pirrolidona, agua, mezcla de agua y alcohol, dimetilsulfóxido, etilen glicolhexileno, etilenglicol y suero, y preferiblemente en 1-metil-2-pirrolidona;ii. preparation of a solution of PVA in a solvent selected from 1-methyl-2-pyrrolidone, water, a mixture of water and alcohol, dimethylsulfoxide, ethylene glycolhexylene, ethylene glycol and serum, and preferably in 1-methyl-2-pyrrolidone;
iii. mezcla de la disolución de PHA de la etapa (i) y de la disolución de PVA de la etapa (ii); yiii. mixing the PHA solution from step (i) and the PVA solution from step (ii); Y
iv. entrecruzamiento de la mezcla de las disoluciones de la etapa (iii) con un agente de entrecruzamiento químico o un agente de entrecruzamiento físico.iv. crosslinking the mixture of the solutions of step (iii) with a chemical crosslinking agent or a physical crosslinking agent.
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente, donde:In another embodiment, the invention refers to the procedure for obtaining the material defined above, where:
en la etapa (ii) el disolvente es una mezcla de agua y alcohol; yin stage (ii) the solvent is a mixture of water and alcohol; Y
el alcohol se selecciona de etanol, metanol, glicerol y propanol.the alcohol is selected from ethanol, methanol, glycerol, and propanol.
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente, donde en el agente de entrecruzamiento de la etapa (iv) es un agente de entrecruzamiento químico, preferiblemente donde el agente de entrecruzamiento químico de la etapa (iv) se selecciona de aldehídos, ácido bórico, nitrato sódico, ácido ferúlico, dianhídrido, ácido maleico, ácido succínico, ácido fumárico, ácido cítrico, ácido tartárico, glioxal, ácido sulfosuccínico epiclorhidrina, diisocianato, tetraetoxisilano, nanomaterial de carbono, nanocompuesto con nanomateriales de carbono y un ión, y más preferiblemente donde el agente de entrecruzamiento químico de la etapa (iv) es glutaraldehído (GA).In another embodiment, the invention refers to the process for obtaining the material defined above, where the crosslinking agent of step (iv) is a chemical crosslinking agent, preferably where the chemical crosslinking agent of step (iv) is selected of aldehydes, boric acid, sodium nitrate, ferulic acid, dianhydride, maleic acid, succinic acid, fumaric acid, citric acid, tartaric acid, glyoxal, sulfosuccinic acid epichlorohydrin, diisocyanate, tetraethoxysilane, carbon nanomaterial, carbon nanocomposite and a carbon nanocomposite ion, and more preferably where the chemical crosslinking agent of step (iv) is glutaraldehyde (GA).
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente, donde el agente de entrecruzamiento de la etapa (iv) químico es un aldehído seleccionado de glutaraldehído (GA), glioxal, formaldehído, benzaldehído, sialicilaldehído, propanal y fenilacetaldehído, y preferiblemente donde el agente de entrecruzamiento de la etapa (iv) químico es glutaraldehído (GA). In another embodiment, the invention refers to the process for obtaining the material defined above, where the crosslinking agent of chemical step (iv) is an aldehyde selected from glutaraldehyde (GA), glyoxal, formaldehyde, benzaldehyde, sialicylaldehyde, propanal and phenylacetaldehyde, and preferably where the crosslinking agent of chemical step (iv) is glutaraldehyde (GA).
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente, donde el agente de entrecruzamiento de la etapa (iv) químico es un dianhídrido seleccionado de benzofenona tetracarboxílico (BTDA), ácido carboxílico pirometílico (PMDA), ácido butano tetracarboxílico (BTCA), etilen diaminotetraacético (EDTA) y oxidiftálico (ODPA).In another embodiment, the invention refers to the process for obtaining the material defined above, where the crosslinking agent of chemical step (iv) is a dianhydride selected from benzophenone tetracarboxylic (BTDA), pyromethyl carboxylic acid (PMDA), butane tetracarboxylic acid ( BTCA), ethylene diamine tetraacetic (EDTA) and oxydiphthalic (ODPA).
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente, donde el agente de entrecruzamiento de la etapa (iv) químico es un nanomaterial de carbono seleccionado de grafito, grafeno, óxido de grafeno, óxido de grafeno reducido, grafeno reducido, nanotubos de carbono de pared simple o múltiple, nanofibras de carbono, fullereno, óxido de grafeno funcionalizado con alquilamina o con amoniaco, grafeno dopado con boro, grafeno dopado con nitrógeno, grafeno dopado con fósforo, grafeno dopado con azufre, grafeno dopado con boro y nitrógeno, grafeno dopado con fósforo y nitrógeno, grafeno dopado con azufre y nitrógeno y óxido de grafeno reducido sulfonado.In another embodiment, the invention refers to the process for obtaining the material defined above, where the crosslinking agent of chemical step (iv) is a carbon nanomaterial selected from graphite, graphene, graphene oxide, reduced graphene oxide, reduced graphene , single or multiple walled carbon nanotubes, carbon nanofibers, fullerene, ammonia or alkylamine functionalized graphene oxide, boron doped graphene, nitrogen doped graphene, phosphorus doped graphene, sulfur doped graphene, boron doped graphene and nitrogen, phosphorus and nitrogen doped graphene, sulfur and nitrogen doped graphene, and sulfonated reduced graphene oxide.
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente, donde el agente de entrecruzamiento de la etapa (iv) químico es un nanocompuesto con nanomateriales de carbono seleccionado de grafeno/TiO 2 , grafeno/Fe 3 O 4 , grafeno/Mn 3 O 4 , grafeno/Pd, grafeno/Pt, grafeno/PtCo, grafeno/PtPd, grafeno reducido/TiO 2 , grafeno reducido/Fe3O4, grafeno reducido/Mn3O4, grafeno reducido/Pd, grafeno reducido/Pt, grafeno reducido/PtCo y grafeno reducido/PtPd.In another embodiment, the invention refers to the process for obtaining the material defined above, where the crosslinking agent of chemical step (iv) is a nanocomposite with carbon nanomaterials selected from graphene / TiO 2 , graphene / Fe 3 O 4 , graphene / Mn 3 O 4 , graphene / Pd, graphene / Pt, graphene / PtCo, graphene / PtPd, reduced graphene / TiO 2 , reduced graphene / Fe3O4, reduced graphene / Mn3O4, reduced graphene / Pd, reduced graphene / Pt, reduced graphene / PtCo and reduced graphene / PtPd.
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente, donde el agente de entrecruzamiento de la etapa (iv) químico es un ion seleccionado de Fe3+, Ca2+, Zn2+, Ba2+, Al3+ y Cd2+.In another embodiment, the invention refers to the process for obtaining the material defined above, where the crosslinking agent of chemical step (iv) is an ion selected from Fe3 +, Ca2 +, Zn2 +, Ba2 +, Al3 + and Cd2 +.
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente, donde el agente de entrecruzamiento de la etapa (iv) es un agente de entrecruzamiento físico, preferiblemente donde el agente de entrecruzamiento físico de la etapa (iv) se selecciona de ciclos de congelado/descongelado, calor y radiación.In another embodiment the invention refers to the process for obtaining the material defined above, where the crosslinking agent of step (iv) is a physical crosslinking agent, preferably where the physical crosslinking agent of step (iv) is selected from freeze / thaw cycles, heat and radiation.
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente, que además comprende la etapa (v) de evaporación del disolvente de la disolución obtenida en la etapa de entrecruzamiento (iv) sobre moldes, preferiblemente placas Petri, cristalizadores de vidrio o cristalizadores de politetrafluoroetileno (PTFE), y más preferiblemente placas Petri, para obtener películas reticuladas.In another embodiment, the invention refers to the procedure for obtaining the material defined above, which also comprises step (v) of evaporation of the solvent of the solution obtained in the crosslinking step (iv) on molds, preferably Petri dishes, glass crystallizers or polytetrafluoroethylene (PTFE) crystallizers, and more preferably Petri dishes, to obtain crosslinked films.
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente, que además comprende la etapa (vi) de inmersión en agua de las películas reticuladas obtenidas en la etapa (v) de eliminación de disolventes para eliminar el agente entrecruzador residual.In another embodiment, the invention refers to the process for obtaining the material defined above, which further comprises step (vi) of immersion in water of the crosslinked films obtained in step (v) of removing solvents to remove the residual crosslinking agent.
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente que comprende las etapas de:In another embodiment, the invention refers to the procedure for obtaining the material defined above, which comprises the steps of:
i. preparación de una disolución de PHA, preferiblemente PHBV, en un disolvente seleccionado de cloroformo, trifluoroetanol, diclorometano, hexafluor-2-propanol, acetona, etanol, metanol, carbonato de propileno, dimetilsulfóxido, cloruro de metileno, tolueno, N,N-dimetilformamida y dioxano, y preferiblemente en cloroformo;i. preparation of a solution of PHA, preferably PHBV, in a solvent selected from chloroform, trifluoroethanol, dichloromethane, hexafluoro-2-propanol, acetone, ethanol, methanol, propylene carbonate, dimethylsulfoxide, methylene chloride, toluene, N, N-dimethylformamide and dioxane, and preferably in chloroform;
ii. preparación de una disolución de PVA en un disolvente seleccionado de 1-metil-2-pirrolidona, agua, mezcla de agua y alcohol, dimetilsulfóxido, etilen glicolhexileno, etilenglicol y suero, y preferiblemente en 1-metil-2-pirrolidona;ii. preparation of a solution of PVA in a solvent selected from 1-methyl-2-pyrrolidone, water, a mixture of water and alcohol, dimethylsulfoxide, ethylene glycolhexylene, ethylene glycol and serum, and preferably in 1-methyl-2-pyrrolidone;
iii. mezcla de la disolución de PHA de la etapa (i) y de la disolución de PVA de la etapa (ii);iii. mixing the PHA solution from step (i) and the PVA solution from step (ii);
iv. entrecruzamiento de la mezcla de las disoluciones de la etapa (iii) con un agente de entrecruzamiento químico o un agente de entrecruzamiento físico.iv. crosslinking the mixture of the solutions of step (iii) with a chemical crosslinking agent or a physical crosslinking agent.
v. evaporación del disolvente de la disolución obtenida en la etapa de entrecruzamiento (iv) sobre moldes, preferiblemente placas Petri, cristalizadores de vidrio o cristalizadores de politetrafluoroetileno (PTFE), y más preferiblemente placas Petri, para obtener películas reticuladas; yv. evaporation of the solvent from the solution obtained in the crosslinking step (iv) on molds, preferably Petri dishes, glass crystallizers or polytetrafluoroethylene (PTFE) crystallizers, and more preferably Petri dishes, to obtain cross-linked films; Y
vi. inmersión en agua de las películas reticuladas obtenidas en la etapa (v) de eliminación de disolventes para eliminar el agente entrecruzador residual.saw. immersion in water of the crosslinked films obtained in the solvent elimination step (v) to eliminate the residual crosslinking agent.
El material descrito combina las propiedades de absorción de agua del PVA y la resistencia mecánica de un polímero de la familia de los polihidroxialconoatos (PHA), particularmente PHBV, por lo que sus películas presentan unas características de degradación térmica, comportamiento térmico y mojabilidad que las hace adecuadas para las aplicaciones biomédicas e industriales.The material described combines the water absorption properties of PVA and the mechanical resistance of a polymer of the polyhydroxyalconeoate (PHA) family, particularly PHBV, which is why its films have characteristics of thermal degradation, thermal behavior and wettability that makes adequate for biomedical and industrial applications.
El material de la invención presenta propiedades que lo hacen útil para el tratamiento y prevención de infecciones causadas por heridas y úlceras.The material of the invention has properties that make it useful for the treatment and prevention of infections caused by wounds and ulcers.
Así, otro aspecto de la invención se refiere al material de la invención definido anteriormente para la fabricación de apósitos para el tratamiento y prevención de infecciones causadas por heridas o úlceras.Thus, another aspect of the invention refers to the material of the invention defined above for the manufacture of dressings for the treatment and prevention of infections caused by wounds or ulcers.
Otro aspecto de la invención se refiere al uso del material definido anteriormente, como apósito tópico, material absorbente para prevención de sangrado, tapones postoperatorios y tampones auditivos post-otoplastia.Another aspect of the invention refers to the use of the material defined above, as a topical dressing, absorbent material for the prevention of bleeding, postoperative plugs and post-otoplasty ear plugs.
Otro aspecto de la invención se refiere al uso del material de la invención definido anteriormente, como andamio celular (scaffold) en ingeniería tisular.Another aspect of the invention relates to the use of the material of the invention defined above, as a cellular scaffold (scaffold) in tissue engineering.
Otro aspecto de la invención se refiere al uso del material de la invención definido anteriormente, como sutura biodegradable, como medio de suministro controlado de fármacos o agentes biológicos y como material biodegradable.Another aspect of the invention relates to the use of the material of the invention defined above, as a biodegradable suture, as a means of controlled delivery of drugs or biological agents and as a biodegradable material.
Otro aspecto de la invención se refiere a una composición que comprende el material definido anteriormente y partículas con propiedades conductoras y antimicrobianas.Another aspect of the invention refers to a composition comprising the material defined above and particles with conductive and antimicrobial properties.
En otra realización la invención se refiere a la composición que comprende el material definido anteriormente, donde las partículas conductoras y antimicrobianas se seleccionan de nanomateriales de carbono, nanopartículas de polímeros conductores de un tamaño de entre 1 nm y 500 nm, micropartículas de polímeros conductores de un tamaño de entre 0,5 y 1000 pm, cerámicas y biometales.In another embodiment, the invention refers to the composition comprising the material defined above, where the conductive and antimicrobial particles are selected from carbon nanomaterials, nanoparticles of conductive polymers with a size between 1 nm and 500 nm, microparticles of conductive polymers of a size between 0.5 and 1000 pm, ceramics and biometals.
En otra realización la invención se refiere a la composición que comprende el material definido anteriormente, donde los nanomateriales de carbono se seleccionan de grafito, grafeno, óxido de grafeno, óxido de grafeno reducido, nanotubos de carbono de pared simple o múltiple, nanofibras de carbono, fullereno, óxido de grafeno funcionalizado con alquilamina o con amoniaco, grafeno dopado con boro, grafeno dopado con nitrógeno, grafeno dopado con fósforo, grafeno dopado con azufre, grafeno dopado con boro y nitrógeno, grafeno dopado con fósforo y nitrógeno, grafeno dopado con azufre y nitrógeno y óxido de grafeno reducido sulfonado, y nanocompuestos con nanomateriales de carbono como el grafeno/TiO 2 , grafeno/Fe 3 O 4 , grafeno/Mn 3 O 4 , grafeno/Pd, grafeno/Pt, grafeno/PtCo, grafeno/PtPd, grafeno reducido/TiO 2 , grafeno reducido/Fe 3 O 4 , grafeno reducido/Mn 3 O 4 , grafeno reducido/Pd, grafeno reducido/Pt, grafeno reducido/PtCo y grafeno reducido/PtPd.In another embodiment the invention refers to the composition comprising the material defined above, where the carbon nanomaterials are selected from graphite, graphene, graphene oxide, reduced graphene oxide, single or multiple walled carbon nanotubes, carbon nanofibers , fullerene, ammonia or alkylamine functionalized graphene oxide, boron doped graphene, nitrogen doped graphene, phosphorus doped graphene, sulfur doped graphene, boron doped graphene and nitrogen, nitrogen phosphorus doped graphene, nitrogen sulfur doped graphene and sulfonated reduced graphene oxide, and nanocomposites with carbon nanomaterials such as graphene / TiO 2 , graphene / Fe 3 O 4 , graphene / Mn 3 O 4 , graphene / Pd, graphene / Pt, graphene / PtCo, graphene / PtPd, reduced graphene / TiO 2 , reduced graphene / Fe 3 O 4 , reduced graphene / Mn 3 O 4 , reduced graphene / Pd, reduced graphene / Pt, reduced graphene / PtCo and reduced graphene / PtPd.
En otra realización la invención se refiere a la composición que comprende el material de la invención definido anteriormente, donde los polímeros conductores se seleccionan de polipirrol (PPy), polianilina y polímeros de politiofeno, preferiblemente donde los polímeros conductores se seleccionan de polipirrol (PPy), polianilina, politiofeno, poli(3,4-etilen-dioxitiofeno, poli(3,4-etilen-dioxitiofeno, poli(3,4-etilendioxitiofeno)-poli(estireno sulfonato), politiofeno-vinilideno), poly(2,5-tietileno-vinilideno), poli(3-alquiltiofeno, poli (p-fenileno), poli-p-fenileno-sulfuro, poli (p-fenilenvinileno), poli (pfenileno-tereftalamida), poli (3-octiltiofeno-3-metiltiofeno) y poli (p-fenilenotereftalamida), y más preferiblemente donde los polímeros conductores se seleccionan de polipirrol (PPy).In another embodiment the invention refers to the composition comprising the material of the invention defined above, where the conductive polymers are selected from polypyrrole (PPy), polyaniline and polythiophene polymers, preferably where the conductive polymers are selected from polypyrrole (PPy) , polyaniline, polythiophene, poly (3,4-ethylene-dioxythiophene, poly (3,4-ethylene-dioxythiophene, poly (3,4-ethylenedioxythiophene) -poly (styrene sulfonate), polythiophene-vinylidene), poly (2,5 -thyethylene-vinylidene), poly (3-alkylthiophene, poly (p-phenylene), poly-p-phenylene-sulfide, poly (p-phenylenevinylene), poly (p-phenylene-terephthalamide), poly (3-octylthiophene-3-methylthiophene) ) and poly (p-phenylene terephthalamide), and more preferably where the conductive polymers are selected from polypyrrole (PPy).
En otra realización la invención se refiere a la composición que comprende el material de la invención definido anteriormente, donde las cerámicas son hidroxiapatita, óxido de zinc, nitruro de boro y óxido de aluminio.In another embodiment the invention refers to the composition comprising the material of the invention defined above, where the ceramics are hydroxyapatite, zinc oxide, boron nitride and aluminum oxide.
En otra realización la invención se refiere a la composición que comprende el material de la invención definido anteriormente, donde los biometales se seleccionan de plata, zinc, magnesio, cobre, hierro, titanio, plomo, cobalto, cromo calcio, oro y estroncio.In another embodiment the invention refers to the composition comprising the material of the invention defined above, where the biometals are selected from silver, zinc, magnesium, copper, iron, titanium, lead, cobalt, chromium, calcium, gold and strontium.
En otra realización la invención se refiere a la composición que comprende el material definido anteriormente, donde las partículas conductoras y antimicrobianas son polímeros conductores de polipirrol (PPy).In another embodiment the invention refers to the composition comprising the material defined above, where the conductive and antimicrobial particles are conductive polypyrrole polymers (PPy).
En otra realización la invención se refiere a la composición que comprende el material de la invención tal y como se ha definido anteriormente donde el PHA es PHBVA y las partículas conductoras y antimicrobianas son de polipirrol (PPy).In another embodiment the invention refers to the composition comprising the material of the invention as defined above where the PHA is PHBVA and the conductive and antimicrobial particles are polypyrrole (PPy).
Otro aspecto de la invención se refiere al procedimiento de obtención de la composición que comprende el material definido anteriormente que comprende las etapas de: i. preparación de una disolución de PHA, preferiblemente PHBV, en un disolvente seleccionado de cloroformo, trifluoroetanol, diclorometano, hexafluor-2-propanol, acetona, etanol, metanol, carbonato de propileno, dimetilsulfóxido, cloruro de metileno, tolueno, N,N-dimetilformamida y dioxano, preferiblemente en cloroformo,Another aspect of the invention relates to the procedure for obtaining the composition comprising the material defined above comprising the steps of: i. preparation of a solution of PHA, preferably PHBV, in a solvent selected from chloroform, trifluoroethanol, dichloromethane, hexafluoro-2-propanol, acetone, ethanol, methanol, propylene carbonate, dimethylsulfoxide, methylene chloride, toluene, N, N-dimethylformamide and dioxane, preferably in chloroform,
ii. dispersión de partículas conductoras y antimicrobianas, preferiblemente nanomateriales de carbono, nanopartículas de polímeros conductores de un tamaño de entre 1 nm y 500 nm, micropartículas de polímeros conductores de un tamaño de entre 0,5 y 1000 pm, cerámicas y biometales, y más preferiblemente de polipirrol (PPy), sobre la disolución de PVA, preferiblemente de PHBV, obtenida en la etapa (i);ii. dispersion of conductive and antimicrobial particles, preferably carbon nanomaterials, nanoparticles of conductive polymers with a size between 1 nm and 500 nm, microparticles of conductive polymers with a size between 0.5 and 1000 pm, ceramics and biometals, and more preferably polypyrrole (PPy), on the PVA solution, preferably PHBV, obtained in step (i);
iii. preparación de una disolución de PVA en un disolvente seleccionado de 1-metil-2-pirrolidona, agua, mezcla de agua y alcohol, dimetilsulfóxido, etilen glicolhexileno, etilenglicol y suero, preferiblemente en 1-metil-2-pirrolidona;iii. preparation of a solution of PVA in a solvent selected from 1-methyl-2-pyrrolidone, water, a mixture of water and alcohol, dimethylsulfoxide, ethylene glycolhexylene, ethylene glycol and serum, preferably in 1-methyl-2-pyrrolidone;
iv. mezcla de la disolución de PHA con partículas dispersas de la etapa (ii) y de la disolución de PVA de la etapa (iii); yiv. mixing the PHA solution with dispersed particles from step (ii) and the PVA solution from step (iii); Y
v. entrecruzamiento de la mezcla de las disoluciones de la etapa (iv) con un agente de entrecruzamiento químico o un agente de entrecruzamiento físico.v. crosslinking of the mixture of the solutions of step (iv) with a chemical crosslinking agent or a physical crosslinking agent.
En otra realización la invención se refiere al procedimiento de obtención de la composición que comprende el material de la invención definido anteriormente, que además comprende la etapa (vi) de evaporación del disolvente de la disolución obtenida en la etapa de entrecruzamiento (v) sobre moldes, preferiblemente placas Petri, cristalizadores de vidrio o cristalizadores de politetrafluoroetileno (PTFE), y más preferiblemente placas Petri, para obtener películas reticuladas.In another embodiment, the invention refers to the process for obtaining the composition comprising the material of the invention defined above, which also comprises the stage (vi) of evaporation of the solvent from the solution obtained in the crosslinking stage (v) on molds , preferably Petri dishes, glass crystallizers or polytetrafluoroethylene (PTFE) crystallizers, and more preferably Petri dishes, to obtain cross-linked films.
En otra realización la invención se refiere al procedimiento de obtención del material definido anteriormente, que además comprende la etapa (vii) de inmersión en agua de las películas reticuladas obtenidas en la etapa (vi) de eliminación de disolventes para eliminar el agente entrecruzador residual.In another embodiment, the invention refers to the process for obtaining the material defined above, which further comprises the step (vii) of immersing the crosslinked films obtained in step (vi) of removing solvents in water to remove the residual crosslinking agent.
Estas composiciones de polímeros de la familia PHA, preferiblemente PHBV y PVA que comprende nanopartículas conductoras presentan propiedades eléctricas y antimicrobianas, preferiblemente cuando las nanopartículas conductoras son de PPy. These polymer compositions of the PHA family, preferably PHBV and PVA comprising conductive nanoparticles, exhibit electrical and antimicrobial properties, preferably when the conductive nanoparticles are PPy.
Así, las nanopartículas, micropartículas u otros nanomateriales (como nanomateriales de carbono, polímeros conductores, cerámicas o biometales) de la composición definida anteriormente, y en particular las nanopartículas conductoras de PPy le confieren propiedades antimicrobianas muy deseables para prevenir infecciones y por otra parte la capacidad conductora, que amplía su uso biomédico en aplicaciones de ingeniaría tisular que requieren estimulación eléctrica.Thus, the nanoparticles, microparticles or other nanomaterials (such as carbon nanomaterials, conductive polymers, ceramics or biometals) of the composition defined above, and in particular the conductive PPy nanoparticles, confer highly desirable antimicrobial properties to prevent infections and, on the other hand, the conductive capacity, which broadens its biomedical use in tissue engineering applications that require electrical stimulation.
Por tanto, otro aspecto de la invención se refiere al uso de la composición que comprende el material definido anteriormente, como apósito tópico, material absorbente para prevención de sangrado, tapones postoperatorios, tampones auditivos postotoplastia, andamio celular (scaffold) en ingeniería tisular, sutura biodegradable, como medio de suministro controlado de fármacos o agentes biológicos y como material biodegradable.Therefore, another aspect of the invention refers to the use of the composition comprising the material defined above, such as topical dressing, absorbent material for the prevention of bleeding, postoperative plugs, postotoplasty ear plugs, cellular scaffold (scaffold) in tissue engineering, suture biodegradable, as a means of controlled delivery of drugs or biological agents and as a biodegradable material.
Otro aspecto de la invención se refiere a la composición que comprende el material definido anteriormente, para el tratamiento y prevención de infecciones microbianas y estimulación celular mediante electroestimulación en regeneración tisular, y preferiblemente donde la regeneración tisular es a nivel neuronal, musculoesquelética, ósea o cardíaca.Another aspect of the invention refers to the composition comprising the material defined above, for the treatment and prevention of microbial infections and cell stimulation by electrostimulation in tissue regeneration, and preferably where tissue regeneration is at the neuronal, musculoskeletal, bone or cardiac level. .
Así pues, los materiales de la invención, es decir, las redes semiinterpenetradas (semi-INP), combinan las propiedades de absorción de agua del PVA y la resistencia mecánica del polímero de la familia de los PHA, particularmente del PHBV. Por tanto, tienen la ventaja de reforzar un material como el PVA, que es un hidrogel con propiedades mecánicas pobres, y proporcionar propiedades hidrófilas al polímero hidrófobo PHBV.Thus, the materials of the invention, that is, the semi-interpenetrated networks (semi-INP), combine the water absorption properties of PVA and the mechanical resistance of the polymer of the PHA family, particularly of PHBV. Thus, they have the advantage of reinforcing a material such as PVA, which is a hydrogel with poor mechanical properties, and providing hydrophilic properties to the hydrophobic polymer PHBV.
Además, como ambos biomateriales son biodegradables, se consigue crear un material compuesto que mantiene su capacidad de biodegradación.In addition, as both biomaterials are biodegradable, it is possible to create a composite material that maintains its ability to biodegrade.
Las películas hidrófilas de la invención poseen propiedades adecuadas de degradación térmica, comportamiento térmico, absorción de agua y mojabilidad adecuadas para aplicaciones biomédicas e industriales entre un amplio rango de áreas donde se requieran materiales no tóxicos biodegradables.The hydrophilic films of the invention possess adequate properties of thermal degradation, thermal behavior, water absorption and wettability suitable for biomedical and industrial applications among a wide range of areas where non-toxic biodegradable materials are required.
Se ha demostrado que las películas basadas en redes semi-IPN PHBV/PVA, particularmente en proporción 30:70 respectivamente (redes semi-IPN PHBV/PVA), no presentan citotoxicidad a nivel celular.Films based on semi-IPN PHBV / PVA networks have been shown to particularly in the 30:70 ratio respectively (semi-IPN PHBV / PVA networks), they do not show cytotoxicity at the cellular level.
Estos resultados indican que estos materiales biodegradables no presentarán problemas de biocompatibilidad celular, convirtiéndose en materiales de gran interés y potencial en el campo de la biotecnología, en particular en aplicaciones como apósitos tópicos, material absorbente para prevención de sangrado, tapones postoperatorios, tampones auditivos post-otoplastia, andamios celulares (scaffolds) para aplicaciones de ingeniería tisular y suministro controlado de fármacos u otros agentes biológicos (incluidos microorganismos).These results indicate that these biodegradable materials will not present cellular biocompatibility problems, becoming materials of great interest and potential in the field of biotechnology, particularly in applications such as topical dressings, absorbent material for bleeding prevention, postoperative plugs, post-operative ear tampons. -otoplasty, cell scaffolds for tissue engineering applications and controlled delivery of drugs or other biological agents (including microorganisms).
A lo largo de la descripción y las reivindicaciones la palabra "comprende” y sus variantes no pretenden excluir otras características técnicas, aditivos, componentes o pasos. Para los expertos en la materia, otros objetos, ventajas y características de la invención se desprenderán en parte de la descripción y en parte de la práctica de la invención. Los siguientes ejemplos y figuras se proporcionan a modo de ilustración, y no se pretende que sean limitativos de la presente invención.Throughout the description and the claims, the word "comprises" and its variants are not intended to exclude other technical characteristics, additives, components or steps. For those skilled in the art, other objects, advantages and characteristics of the invention will be partly understood of the description and in part of the practice of the invention The following examples and figures are provided by way of illustration, and are not intended to be limiting of the present invention.
BREVE DESCRIPCIÓN DE LAS FIGURASBRIEF DESCRIPTION OF THE FIGURES
Fig. 1 Muestra una representación esquemática del proceso de síntesis y la estructura de las películas poliméricas biodegradables de la invención: polímero de la familia de los PHA, particularmente del PHBV y poli (alcohol vinílico) (PVA) en proporción 30/70. Además, se representa la incorporación de nanopartículas conductoras antimicrobianas de polipirrol.Fig. 1 Shows a schematic representation of the synthesis process and the structure of the biodegradable polymeric films of the invention: polymer of the PHA family, particularly of PHBV and poly (vinyl alcohol) (PVA) in a 30/70 ratio. In addition, the incorporation of conductive antimicrobial polypyrrole nanoparticles is depicted.
Fig. 2 Muestra imágenes de microscopía electrónica de las películas basadas en semi-IPN de PHBV/PVA (superficie (a) y corte transversal (b)). Nanopartículas de polipirrol (c) .Fig. 2 shows electron microscopy images of PHBV / PVA semi-IPN-based films (surface (a) and cross-section (b)). Polypyrrole nanoparticles (c).
Fig. 3 Muestra imágenes de microscopía electrónica de las semi-IPN de PHBV/PVA con 2% p/p (superficie (a) y corte transversal (b)), 10% p/p (superficie (c) y corte transversal (d) y 15 % p/p de nanopartículas de polipirrol (corte transversal (e) y zona ampliada (f)). La imagen g) muestra una amplificación de la imagen f), haciendo visible la incrustación de las nanopartículas dentro de la matriz polimérica. Fig. 3 Shows electron microscopy images of PHBV / PVA semi-IPNs with 2% w / w (surface (a) and cross section (b)), 10% w / w (surface (c) and cross section ( d) and 15% w / w of polypyrrole nanoparticles (cross section (e) and enlarged area (f)). Image g) shows an amplification of image f), making visible the embedding of the nanoparticles within the matrix polymeric.
Fig. 4 Muestra el espectro FTIR en la región de 4000-300 cm-1. PHBV, PVA, PHBV/PVA, PVA entrecruzado (PVA E) y PHBV/PVA entrecruzado (PHBV/PVA E).Fig. 4 shows the FTIR spectrum in the 4000-300 cm-1 region. PHBV, PVA, PHBV / PVA, Cross-linked PVA (PVA E) and Cross-linked PHBV / PVA (PHBV / PVA E).
Fig. 5 Muestra el espectro FTIR en la región de 4000-300 cm-1. PHBV/PVA E con diferentes porcentajes de nanopartículas de PPy (2, 5, 10 y 15% referido a la masa de muestra).Fig. 5 shows the FTIR spectrum in the 4000-300 cm-1 region. PHBV / PVA E with different percentages of PPy nanoparticles (2, 5, 10 and 15% based on the sample mass).
Fig. 6 Muestra el grado de hinchamiento en equilibrio para el PHBV/PVA E con diferentes porcentajes de nanopartículas de PPy desde 0 a 15 p/p %. La muestra PVA E está incluida como referencia. Las diferencias estadísticas significativas (p < 0,05) se representan mediante ‘* ’.Fig. 6 shows the degree of swelling at equilibrium for PHBV / PVA E with different percentages of PPy nanoparticles from 0 to 15 w / w%. Sample PVA E is included for reference. Statistical significant differences (p <0.05) are represented by '*'.
EJEMPLOSEXAMPLES
MaterialesMaterials
Los materiales utilizados para la presente invención son los siguientes: poli (3-hidroxibutirato-co-3-hidroxivalerato) con una relación molar de copolímero de hidroxilavarato de 2% de biopolímero (PHBV), poli (alcohol vinílico) con Mw 13,000 23,000 y 87-89% hidrolizado (PVA), disolvente 1-metil-2 -pirrolidona (NMP) y nanopartículas de polipirrol (PPy) dopadas con un ácido sulfónico orgánico como dopante (conductividad 10-50 S / cm y estable hasta 290 °C). Se utiliza cloroformo, glutaraldehído (GA) (solución al 25% p/p), metanol y ácido sulfúrico (95-98% extra puro).The materials used for the present invention are the following: poly (3-hydroxybutyrate-co-3-hydroxyvalerate) with a molar ratio of hydroxylavarate copolymer of 2% biopolymer (PHBV), poly (vinyl alcohol) with Mw 13,000 23,000 and 87-89% hydrolyzate (PVA), 1-methyl-2-pyrrolidone (NMP) solvent and polypyrrole (PPy) nanoparticles doped with an organic sulfonic acid as dopant (conductivity 10-50 S / cm and stable up to 290 ° C) . Chloroform, glutaraldehyde (GA) (25% w / w solution), methanol and sulfuric acid (95-98% extra pure) are used.
Preparación de películas basadas en una red sem iinterpenetrada de PHBV/PVA Las películas basadas en semi-IPNs PHBV/PVA se preparan utilizando la técnica basada en evaporación de solvente. En primer lugar, se preparan las disoluciones de los componentes PHBV y PVA y a continuación se prepara la mezcla de ambas disoluciones y el entrecruzado de la fase de PVA.Preparation of films based on a semi-interpenetrated network of PHBV / PVA Films based on semi-IPNs PHBV / PVA are prepared using the technique based on solvent evaporation. First, the solutions of the PHBV and PVA components are prepared and then the mixture of both solutions and the crosslinking of the PVA phase are prepared.
El PHBV se disuelve en cloroformo (3% p/p) a 50°C con agitación constante durante 120 minutos y el PVA se disuelve en NMP (5% p/p), también con agitación constante durante 120 minutos, aumentando la temperatura de la placa calefactora de la base gradualmente hasta 150°C.PHBV is dissolved in chloroform (3% w / w) at 50 ° C with constant stirring for 120 minutes and PVA is dissolved in NMP (5% w / w), also with constant stirring for 120 minutes, increasing the temperature of the base heating plate gradually up to 150 ° C.
Una vez preparadas las disoluciones, se preparan mezclas de PHBV/PVA a partir de las disoluciones de PHBV/cloroformo y PVA/NMP (relación 30/70 p/p) con agitación magnética durante 24 h a 50°C.Once the solutions have been prepared, PHBV / PVA mixtures are prepared from the PHBV / chloroform and PVA / NMP solutions (30/70 w / w ratio) with magnetic stirring for 24 h at 50 ° C.
La fase de PVA se entrecruza para lograr un material estable en agua como semi-IPN con PHBV (no reticulado) en forma de hidrogel. El entrecruzamiento o reticulado de la fase de PVA en el semi-IPN se realiza de acuerdo con el procedimiento de Rudraa et al., utilizando GA como entrecruzador (4% p/p de GA con respecto al contenido total de PVA) (Rudraa, R.; et al.. J. Name 2013, 0, 1-20). En primer lugar, se preparan 4 disoluciones acuosas: 1) disolución GA al 25% (entrecruzador), 2) disolución al 10% de ácido sulfúrico, el cual actua como catalizador, 3) disolución al 10% de ácido acético como un controlador de pH y 4) disolución al 50% de metanol como activador de la reacción de entrecruzamiento. A partir de estas disoluciones se realiza una mezcla en una relación volumétrica 2: 1: 3: 2 y luego se transfiere a la disolución mixta PHBV/cloroformo y PVA/NMP preparada anteriormente. La disolución final se agita vigorosamente durante 30 minutos a 50 °C hasta conseguir la total homogeneización de los reactivos.The PVA phase is cross-linked to achieve a water stable material such as semi-IPN with PHBV (not cross-linked) in the form of a hydrogel. The crosslinking or crosslinking of the PVA phase in the semi-IPN is carried out according to the procedure of Rudraa et al., Using GA as a crosslinker (4% w / w of GA with respect to the total content of PVA) (Rudraa, R .; et al .. J. Name 2013, 0, 1-20). First, 4 aqueous solutions are prepared: 1) 25% GA solution (crosslinker), 2) 10% sulfuric acid solution, which acts as a catalyst, 3) 10% acetic acid solution as a control of pH and 4) 50% solution of methanol as activator of the crosslinking reaction. From these solutions, a mixture is made in a volumetric ratio 2: 1: 3: 2 and then transferred to the mixed PHBV / chloroform and PVA / NMP solution prepared above. The final solution is vigorously stirred for 30 minutes at 50 ° C until the reagents are fully homogenized.
Seguidamente, la disolución se vierte sobre placas Petri y se deja 12 h a temperatura ambiente para evaporar el cloroformo. A continuación, las muestras se introducen en un horno a una temperatura superior a la temperatura ambiente pero inferior a la temperatura de degradación de los polímeros (temperatura máxima 100 °C) hasta peso contante, preferiblemente 60 °C durante 96 h para evaporar el NMP. Tras este proceso se obtienen las películas reticuladas en forma de semi-IPN. Finalmente, las películas reticuladas se sumergen 2 veces en agua a 37°C (24 horas) para eliminar cualquier residuo de GA, se dejan a temperatura ambiente durante 48h para evaporar el agua. Para eliminar restos de humedad de las películas, éstas se colocan en una estufa de vacío a 60 °C hasta conseguir un peso constante.The solution is then poured onto Petri dishes and left for 12 h at room temperature to evaporate the chloroform. The samples are then placed in an oven at a temperature higher than room temperature but lower than the degradation temperature of the polymers (maximum temperature 100 ° C) up to constant weight, preferably 60 ° C for 96 h to evaporate the NMP . After this process, the crosslinked films are obtained in the form of semi-IPN. Finally, the cross-linked films are immersed 2 times in water at 37 ° C (24 hours) to eliminate any residue of GA, they are left at room temperature for 48 hours to evaporate the water. To remove traces of moisture from the films, they are placed in a vacuum oven at 60 ° C until a constant weight is achieved.
Como películas (muestras control) se han preparado muestras de PHBV, PVA, PVA entrecruzado (PVA E) y mezclas PHVA/PVA (sin entrecruzar). Las muestras control de PHBV se obtienen a partir de la disolución del PHBV en cloroformo (3% p/p), la cual después de verterse en una placa Petri se deja a temperatura ambiente hasta la completa evaporación del disolvente. Las muestras control de PVA se obtienen a partir de la disolución del PVA en NMP (5% p/p), la cual, después de verterla sobre una placa Petri, se coloca en un horno de aire a 60 °C durante 96 h para la evaporación del solvente. Por último, las muestras control de PHBV/PVA 30/70 (sin entrecruzamiento) se obtienen a partir de la disolución mixta PHBV/cloroformo y PVA/NMP. Tras verter la disolución mixta en una placa Petri, se deja evaporar 12h a temperatura ambiente y seguidamente se coloca en un horno de aire a 60°C durante 92 h para finalizar la evaporación del solvente.As films (control samples) samples of PHBV, PVA, cross-linked PVA (PVA E) and PHVA / PVA mixtures (no cross-linked) have been prepared. The PHBV control samples are obtained from the PHBV solution in chloroform (3% w / w), which after being poured into a Petri dish is left at room temperature until complete evaporation of the solvent. Control PVA samples are obtained from the dissolution of PVA in NMP (5% w / w), which, after pouring it onto a Petri dish, is placed in an air oven at 60 ° C for 96 h to evaporation of solvent. Finally, the control samples of PHBV / PVA 30/70 (without crosslinking) are obtained from the mixed solution PHBV / chloroform and PVA / NMP. After pouring the mixed solution into a Petri dish, it is allowed to evaporate for 12 hours at room temperature and then it is placed in an air oven at 60 ° C for 92 hours to finish the evaporation of the solvent.
incorporación de nanopartículas antim icrob ianas conductoras de po lip irro l incorporation of antimicrobial nanoparticles conductive of po lip irro l
Para la preparación de las películas basadas en semi-IPN de PHBV/PVA 30/70 con nanopartículas de polipirrol con concentración 2, 5, 10 y 15% el procedimiento empleado se describe a continuación.For the preparation of the films based on semi-IPN of PHBV / PVA 30/70 with polypyrrole nanoparticles with concentration 2, 5, 10 and 15%, the procedure used is described below.
En primer lugar, las nanopartículas de PPy se dispersan en disolvente NMP mediante sonicación durante 30 minutos. A continuación, el PVA se disuelve el en la suspensión de NMP-PPy. Finalmente, las películas semi-IPN de PHBV/PVA/PPy se preparan siguiendo el protocolo descrito para la síntesis de las películas de PHBV/PVA entrecruzadas con GA.First, the PPy nanoparticles are dispersed in NMP solvent by sonication for 30 minutes. The PVA is then dissolved in the NMP-PPy suspension. Finally, the PHBV / PVA / PPy semi-IPN films are prepared following the protocol described for the synthesis of the GA cross-linked PHBV / PVA films.
M icroestructura de los materiales desarrolladosMicrostructure of the developed materials
Se incluyen imágenes de la morfología de los materiales (Figura 2 y 3)Images of the morphology of the materials are included (Figure 2 and 3)
En la Tabla 1 se indica la notación utilizada para los nuevos materiales desarrollados, así como las películas utilizadas como control para el análisis de los materiales.Table 1 indicates the notation used for the new materials developed, as well as the films used as control for the analysis of the materials.
identificación Descripción de la muestraidentification Description of the sample
PHBV (control) 100% PHBVPHBV (control) 100% PHBV
PVA (control) 100% PVAPVA (control) 100% PVA
PVA E (control) 100% PVA entrecruzadoPVA E (control) 100% cross-linked PVA
PHBV/PVA (control) 30% PHBV / 70% PVA mezclasPHBV / PVA (control) 30% PHBV / 70% PVA mixtures
PHBV/PVA E 30% PHBV / 70% PVA semi-IPNPHBV / PVA E 30% PHBV / 70% PVA semi-IPN
PPy (control) PPy nanopartículasPPy (control) PPy nanoparticles
PHBV/PVA E2 30% PHBV / 70% PVA semi-IPN con 2% PPyPHBV / PVA E2 30% PHBV / 70% PVA semi-IPN with 2% PPy
PHBV/PVA E5 30% PHBV / 70% PVA semi-IPN con 5% PPy PHBV / PVA E5 30% PHBV / 70% PVA semi-IPN with 5% PPy
PHBV/PVA E10 30% PHBV / 70% PVA semi-IPN con 10% PPyPHBV / PVA E10 30% PHBV / 70% PVA semi-IPN with 10% PPy
PHBV/PVA E15 30% PHBV / 70% PVA semi-IPN con 15% PPyPHBV / PVA E15 30% PHBV / 70% PVA semi-IPN with 15% PPy
Tabla 1Table 1
Propiedades fís ico-quím icas de los nuevos materiales.Phys ico-chemical properties of the new materials.
Las propiedades físico-químicas de los nuevos materiales se indican a continuación. Se han incluido los resultados de las películas control como referencia.The physicochemical properties of the new materials are indicated below. The results of the control films have been included for reference.
• Hidrofilicidad de los materiales sintetizados • Hydrophilicity of synthesized materials
Para mostrar las propiedades de hidrofilicidad de los materiales desarrollados, en la tabla 2 se muestra el ángulo de contacto en agua medido en las semi-IPN PHBV/PVA compuestas con diferentes contenidos de nanopartículas de PPy y PHBV.To show the hydrophilicity properties of the developed materials, table 2 shows the contact angle in water measured in the semi-IPN PHBV / PVA composed with different contents of PPy and PHBV nanoparticles.
Muestra Sample Ángulo deAngle of
contacto (°) contact (°)
PHBV 105.9±6.9PHBV 105.9 ± 6.9
PHBV/PVA E 93.7±5.7(*)PHBV / PVA E 93.7 ± 5.7 (*)
PHBV/PVA E2 89.8±4.2(*)PHBV / PVA E2 89.8 ± 4.2 (*)
PHBV/PVA E5 87.4±6.8(*)PHBV / PVA E5 87.4 ± 6.8 (*)
PHBV/PVA E10 90.4±7.4(*)PHBV / PVA E10 90.4 ± 7.4 (*)
PHBV/PVA E15 94.4±2.0(*)PHBV / PVA E15 94.4 ± 2.0 (*)
(*) diferencia significativa (p<0.05) con(*) significant difference (p <0.05) with
PHBVPHBV
Tabla 2Table 2
• Propiedades de comportamiento y degradación térmica de los materiales sintetizados • Behavioral properties and thermal degradation of synthesized materials
La tabla 3 y la tabla 4 muestran las propiedades térmicas de los materiales desarrollados en comparación con las películas control.Table 3 and table 4 show the thermal properties of the developed materials in comparison with the control films.
En la tabla 3 se recoge la temperatura de transición vítrea (Tg), anchura de la transición vítrea (ATg), incremento de capacidad calorífica en la transición vítrea (ACp), cristalización (Tc) y temperatura de fusión (Tm), entalpía de fusión (AH), grado de cristalinidad (Xc) y temperatura de descomposición a la cual hay una pérdida de peso del 50% (Td- 50 %) para PHBV and PVA puros, PVA entrecruzado, mezcla de PHBV/PVA y semi-IPN de PHBV/PVA.Table 3 shows the glass transition temperature (Tg), width of the glass transition (ATg), increase in heat capacity in the glass transition (ACp), crystallization ( Tc) and melting temperature (Tm), enthalpy of melting (AH), degree of crystallinity ( Xc) and decomposition temperature at which there is a 50% weight loss (Td- 50 %) for pure PHBV and PVA, cross-linked PVA, PHBV / PVA mixture and semi-IPN from PHBV / PVA.
Tg ATg ACp Tc Tm AHf Td-50% Muestra Xc Tg ATg ACp Tc Tm AHf Td-50% Sample Xc
(°C) (°C) (J/g °C) (°C) (°C) (J/g) (°C) PHBV (control) 0.77 3.67 0.5 46.7(*) 160.5 73.5 0.56 276.1 PVA (control) 69.2 13.2 0.55 183.5 217.5 64.4 0.44 286.8 PVA E (control) 74 36 2.05 - - 386.9(° C) (° C) (J / g ° C) (° C) (° C) (J / g) (° C) PHBV (control) 0.77 3.67 0.5 46.7 (*) 160.5 73.5 0.56 276.1 PVA (control ) 69.2 13.2 0.55 183.5 217.5 64.4 0.44 286.8 PVA E (control) 74 36 2.05 - - 386.9
PHBV/PVA 32.8 33.3 0.54 154 192.4 17.32 - 315.8PHBV / PVA 32.8 33.3 0.54 154 192.4 17.32 - 315.8
PHBV/PVA E 49.2(**) - - 151.5 188.2 11.2 0.28 359.2PHBV / PVA E 49.2 (**) - - 151.5 188.2 11.2 0.28 359.2
(*) Cristalización en frío exotérmica (escaneo de calentamiento)(*) Exothermic cold crystallization (heating scan)
(**) Obtenida de la curva derivada (dop/dT vs. T) (**) Obtained from the derived curve ( dop / dT vs. T)
Tabla 3Table 3
La tabla 4 recoge la temperatura de cristalización (To ) y fusión (Tm ), entalpía de fusión (AHí)), grado de cristalinidad (Xo) y temperatura de descomposición a la cual hay una pérdida de peso del 50% (Td- 50 %) para las semi-IPN PHBV/PVA con diferentes porcentajes de nanopartículas de PPyTable 4 shows the crystallization ( To ) and melting temperature (Tm), enthalpy of fusion ( AHí)), degree of crystallinity ( Xo) and decomposition temperature at which there is a 50% weight loss (Td- 50 %) for semi-IPN PHBV / PVA with different percentages of PPy nanoparticles
Tc Tm AHf Td-50% Muestra Xc Tc Tm AHf Td-50% Sample Xc
(°C) (°C) (J/g) (°C)(° C) (° C) (J / g) (° C)
PHBV/PVA E2 137.5/53.5(*) 160.4 21.9 0.57 366.3PHBV / PVA E2 137.5 / 53.5 (*) 160.4 21.9 0.57 366.3
PHBV/PVA E5 141.7/51.2(*) 161.2 22.9 0.61 368.3PHBV / PVA E5 141.7 / 51.2 (*) 161.2 22.9 0.61 368.3
PHBV/PVA E10 58.4(*) 164.8 16.4 0.45 368.5PHBV / PVA E10 58.4 (*) 164.8 16.4 0.45 368.5
PHBV/PVA E15 59.9(*) 162.7 14.0 0.42 356.8PHBV / PVA E15 59.9 (*) 162.7 14.0 0.42 356.8
(*) Cristalización en frío exotérmica (escaneo de calentamiento)(*) Exothermic cold crystallization (heating scan)
Tabla 4Table 4
• Propiedades eléctricas de los materiales sintetizados • Electrical properties of synthesized materials
En la tabla 5 se muestran las propiedades eléctricas de los materiales sintetizados, con las películas de PHBV y PVA como control.Table 5 shows the electrical properties of the synthesized materials, with the PHBV and PVA films as controls.
Así, la tabla 5 recoge los valores de conductividad eléctrica superficial de PHVA puro y, redes de PHBV/PVA 30/70 y materiales compuestos con contenidos de nanopartículas de polipirrol desde 2 hasta 15%. Thus, table 5 lists the surface electrical conductivity values of pure PHVA and 30/70 PHBV / PVA networks and composite materials with contents of polypyrrole nanoparticles from 2 to 15%.
OsYou
MuestraSample
(mSm-1)(mSm-1)
PHBV (control) 2.38±0.05PHBV (control) 2.38 ± 0.05
PVA (control) 3.55±0.14PVA (control) 3.55 ± 0.14
PHBV/PVA E 2.79±0.03PHBV / PVA E 2.79 ± 0.03
PHBV/PVA E2 3.48±0.06(*)PHBV / PVA E2 3.48 ± 0.06 (*)
PHBV/PVA E5 3.76±0.04(*)PHBV / PVA E5 3.76 ± 0.04 (*)
PHBV/PVA E10 4.93±0.12(*)PHBV / PVA E10 4.93 ± 0.12 (*)
PHBV/PVA E15 6.35±0.15(*)PHBV / PVA E15 6.35 ± 0.15 (*)
(*) Diferencias significativas (p<0.05) respecto a(*) Significant differences (p <0.05) with respect to
PHBV/PVA EPHBV / PVA E
Tabla 5Table 5
• Propiedades químicas de los materiales desarrollados por espectroscopia FTIR • Chemical properties of materials developed by FTIR spectroscopy
En la figura 4 y en la figura 5 se muestran las propiedades químicas de los materiales desarrollados, con las películas de PHBV, PVA, PVA entrecruzado, PHBV/PVA mezcla y partículas de polipirrol como control.In figure 4 and in figure 5 the chemical properties of the developed materials are shown, with the films of PHBV, PVA, cross-linked PVA, mixed PHBV / PVA and polypyrrole particles as control.
• Propiedades de absorción de agua • Water absorption properties
En la figura 6 se muestra las propiedades de absorción de agua de los materiales desarrollados, incluyendo la película de PVA entrecruzado como control. Figure 6 shows the water absorption properties of the developed materials, including the cross-linked PVA film as a control.
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CN113398325A (en) * | 2021-06-11 | 2021-09-17 | 叶川 | Fibrous membrane for enhancing screw stability and inducing bone regeneration and preparation method thereof |
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