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ES2525553T3 - Dispositivos y aplicaciones médicas de polímeros polihidroxialcanoato - Google Patents

Dispositivos y aplicaciones médicas de polímeros polihidroxialcanoato Download PDF

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Publication number
ES2525553T3
ES2525553T3 ES10075553.7T ES10075553T ES2525553T3 ES 2525553 T3 ES2525553 T3 ES 2525553T3 ES 10075553 T ES10075553 T ES 10075553T ES 2525553 T3 ES2525553 T3 ES 2525553T3
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repair
devices
grafts
hydroxyalkanoate
hydroxybutyrate
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Simon F Williams
David P Martin
Frank Skraly
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Yield10 Bioscience Inc
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Metabolix Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • A61F2/07—Stent-grafts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • 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
    • A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
    • A61L17/06—At least partially resorbable materials
    • A61L17/10—At least partially resorbable materials containing macromolecular materials
    • A61L17/12—Homopolymers or copolymers of glycolic acid or lactic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
    • C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
    • C08J9/26—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/0008—Organic ingredients according to more than one of the "one dot" groups of C08K5/01 - C08K5/59
    • C08K5/0033—Additives activating the degradation of the macromolecular compound
    • 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
    • C08L67/04—Polyesters derived from hydroxycarboxylic acids, e.g. lactones
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/62—Carboxylic acid esters
    • C12P7/625—Polyesters of hydroxy carboxylic acids
    • 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
    • A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2201/00—Foams characterised by the foaming process
    • C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
    • C08J2201/044—Elimination of an inorganic solid phase
    • C08J2201/0444—Salts
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2201/00—Foams characterised by the foaming process
    • C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
    • C08J2201/048—Elimination of a frozen liquid phase
    • C08J2201/0482—Elimination of a frozen liquid phase the liquid phase being organic
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
    • C08J2367/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S606/00—Surgery
    • Y10S606/907—Composed of particular material or coated
    • Y10S606/911—Memory material

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Vascular Medicine (AREA)
  • Surgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Polymers & Plastics (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • Materials Engineering (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pulmonology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Cardiology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Materials For Medical Uses (AREA)
  • Polyesters Or Polycarbonates (AREA)
  • Surgical Instruments (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Prostheses (AREA)

Abstract

Un implante médico biocompatible para la sujeción, la fijación, el apoyo, la reparación o el refuerzo de tejido blando, comprendiendo el implante una composición del copolímero de poli(4-hidroxibutirato-co-hidroxialcanoato) depirogenado, en el que la composición del copolímero de poli(4- hidroxibutirato-co-hidroxialcanoato), comprende opcionalmente aditivos que alteran la estabilidad química del polímero, en el que el copolímero de poli(4- hidroxibutirato-co-hidroxialcanoato) tiene un peso molecular medio ponderal en el intervalo entre 10.000 y 10.000.000 Dalton, en el que el implante se selecciona entre el grupo consistente en agentes de relleno y de carga adecuados en la cirugía plástica para rellenar defectos o como un material aumentador de volumen del esfínter para el tratamiento de la incontinencia de adultos, válvulas para venas, estructuras de soporte de médula ósea, dispositivos de aumento del ligamento, injertos de ligamentos y tendones, sustitutos de injerto de hueso, placas óseas, sistemas de recubrimiento óseo, sustitutos de la piel, sustitutos durales, hemostatos, implantes de células oculares, jaulas de fusión espinal, dispositivos de regeneración de menisco, injertos vasculares, válvulas cardíacas, grapas de sutura; dispositivos de reparación meniscal; remaches; tachuelas; tornillos interferenciales; mallas quirúrgicas, incluyendo mallas quirúrgicas en forma de un tapón de malla o para implantes de tejido blando para el refuerzo de tejido blando, para la reducción de defectos fasciales, para un parche de tráquea u otro órgano, para la restauración de órganos, para material de injerto dural, para vendajes de heridas o quemaduras, o para un tampón hemostático; tirantes; clavos ortopédicos; dispositivos de reparación de cartílagos articulares; guías nerviosas, dispositivos de reparación de tendones, dispositivos de reparación de defectos septales auriculares, parches cardiovasculares para injertos de parches vasculares, parches intracardiacos o para el cierre de parches tras la endarterectomía; y parches de reparación para la reparación de defectos de la pared abdominal y torácica, inguinales, paracolostómicos, hernias ventrales, paraumbilicales, escrotales o femorales, para reforzar el colgajo muscular, para reforzar líneas de grapas e incisiones largas, para la reconstrucción del suelo pélvico, para la reparación del prolapso rectal o vaginal, para refuerzos de sutura y grapas, o para reparación urinaria o de la vejiga.

Description

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E10075553
05-12-2014
Tabla 1: Propiedades térmicas y mecánicas de polímeros médicos seleccionados
Polímero
Tm(°C) Tg(°C) Res. Tracción (psi) Módulo (psi) Elongación ( %) Degradación
'P4HB
60 -51 7.500 9.400 1000 Depende de conf.
'pP4HB50a
60 -51 895 2.155 164 Depende de conf.
'pP4HB80b
60 -51 180 257 100 Depende de conf.
6P4HB-3HB 10 %
50 -42 9.000 14.500 1080 No informado
'PHB
175 0 4.000 110.000 4 >52 semanas
2PGA
230 35 10.000 1.000.000 17 8 semanas
3PDLLA
Am 53 5.000 300.000 5 <8 semanas
3PLLA
175 55 10.000 500.000 8 >8 semanas
2DLGLG 50/50
Am 48 7.000 300.000 5 3-8 semanas
5LDPE
2.000 400-700 No degradable
5HDPE
4.000 100-1000 No degradable
5UHMWPE
7.250 450 No degradable
PP
4.000 20.000 200-700 No degradable
PET
8.500 50 No degradable
PTFE
3.000 al Rendimiento 50.000 300 No degradable
a pP4HB50, P4HB 50 % poroso, véase ejemplo 7. b pP4HB80, P4HB 80 % poroso, véase ejemplo 7. Referencias de la tabla: 1. De este trabajo medido según la ASTMD638 a temperatura ambiente y a una velocidad de cepa de 1,27 o 0,25 cm/min (0,05 o 0,1 in./min). 2. Hutmatcher et.al. Int. Oral Max. Imp. 1996, H 667-78. 3. Nobes et. Al.. enviada. 4. Mark, Physical Properties of Polymers Handbook, American Inst. Of Physics, Woodbury, New York, 1996. 5. Schwartz S.S. and Goodman, S.H. Plastic Materials and Processes, Van Nostrand Reinhold Company, New York, 1982. 6. Saito Y. and Doi, Y. Intl. J. Biol. Macromol. (1994) 16:99-104.
Ejemplo comparativo 3: Moldeado por compresión de P4HB poroso
5 Cristales clasificados de cloruro de sodio (80-180 mm) se mezclaron con el P4HB fundido descrito en los Ejemplos 4 y
5. (La proporción de la sal del polímero puede ajustarse para producir la porosidad deseada, mientras que el tamaño de partículas puede ajustarse para producir poros de diverso tamaño). La mezcla de sal del polímero se comprimió hasta lograr una película fina utilizando las condiciones descritas en el Ejemplo 3. Después de permitir que el material solidificara, la película se retiró del apoyo del mylar. La película se extrajo exhaustivamente con agua para retirar la sal,
10 dejando una película porosa de P4HB. La remoción de la sal se monitoreó mediante análisis de cloruros en el material flotante y se confirmó mediante análisis elemental de la película lixiviada (menos de 0,5 % de cloruro). Los datos mecánicos para P4HB con 50 % y 80 % de porosidad (pP4HB50 y pP4HB80, respectivamente) se muestran en la Tabla 1.
15 Ejemplo comparativo 4: Siembra de células en estructuras de soporte de P4HB
El P4HB poroso, tal como lo describe el Ejemplo 6, se esterilizó mediante tratamiento en frío con óxido de etileno. Se sembró con células vasculares bovinas y se cultivó in vitro. Los datos preliminares indicaron buena sujeción de estas células al material. Esto es una demostración más de la biocompatibilidad de este material. El número de células que
20 se fijaron al material se puede cuantificar utilizando un ensayo de ADN comparándolo con los estándares para los bastidores de apoyo de ingeniería de tejidos, malla PGA.
Ejemplo comparativo 5: Orientación de la fibra de P4HB
25 Las tiras de P4HB moldeadas mediante compresión se estiraron uniaxialmente. La muestra se volvió más estrecha y se aclaró, mostrando señales de adoptar forma de collarín. Después de este procesamiento de estiramiento, el polímero parecía más resistente y algo más flexible, demostrando una orientación uniaxial de la muestra. Ejemplo comparativo 6: Producción de espuma de P4HB
30 Se utilizó un método térmico de separación por fases para lograr espuma de P4HB. Primeramente, se disolvió el P4HB en dioxano de 1 a 5 % p/v. Esta solución de polímero se fundió como una película fina y se solidificó por enfriamiento en hielo por debajo del punto de fusión del dioxano. El disolvente se evaporó a partir de este material sólido a baja presión para aportar una espuma porosa con las dimensiones aproximadas de la película gruesa inicial. El análisis ESEM de este material mostró una estructura altamente porosa de tipo esponjoso. La concentración de polímero y el
35 proceso de enfriamiento pueden variarse para alterar la porosidad de la espuma. Antes de la congelación, la solución del polímero puede conformarse en varias formas, desmenuzarse en material particulado o utilizarse como
23
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Claims (1)

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ES10075553.7T 1999-03-25 2000-03-24 Dispositivos y aplicaciones médicas de polímeros polihidroxialcanoato Expired - Lifetime ES2525553T3 (es)

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ES00919621T Expired - Lifetime ES2295021T3 (es) 1999-03-25 2000-03-24 Utilizacion y aplicaciones medicas de polimeros de poli(hidroxialcanoatos).
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