ES2629282T3 - Composiciones y dispositivos de poli-4-hidroxibutirato - Google Patents
Composiciones y dispositivos de poli-4-hidroxibutirato Download PDFInfo
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- ES2629282T3 ES2629282T3 ES14723154.2T ES14723154T ES2629282T3 ES 2629282 T3 ES2629282 T3 ES 2629282T3 ES 14723154 T ES14723154 T ES 14723154T ES 2629282 T3 ES2629282 T3 ES 2629282T3
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- polymer
- p4hb
- ethanol
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- biomass
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- 229920002791 poly-4-hydroxybutyrate Polymers 0.000 title abstract description 39
- 239000000203 mixture Substances 0.000 title abstract 3
- 229920000642 polymer Polymers 0.000 abstract description 36
- 238000004458 analytical method Methods 0.000 abstract description 2
- 238000004817 gas chromatography Methods 0.000 abstract description 2
- 150000002632 lipids Chemical class 0.000 abstract description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 abstract 2
- 235000021314 Palmitic acid Nutrition 0.000 abstract 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- 101001072202 Homo sapiens Protein disulfide-isomerase Proteins 0.000 description 37
- 102100036352 Protein disulfide-isomerase Human genes 0.000 description 37
- 239000002904 solvent Substances 0.000 description 27
- 239000002028 Biomass Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 10
- 238000005406 washing Methods 0.000 description 9
- 238000000605 extraction Methods 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
- 239000012535 impurity Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000013557 residual solvent Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229910001385 heavy metal Inorganic materials 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241001646716 Escherichia coli K-12 Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229950005228 bromoform Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002354 inductively-coupled plasma atomic emission spectroscopy Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052976 metal sulfide Inorganic materials 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
Classifications
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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
- 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
-
- 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
- A61L17/105—Polyesters not covered by A61L17/12
-
- 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/04—Macromolecular materials
- A61L29/06—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
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/085—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- 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
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- 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
- 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
- C08G63/88—Post-polymerisation treatment
- C08G63/90—Purification; Drying
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Surgery (AREA)
- Vascular Medicine (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Polyesters Or Polycarbonates (AREA)
- Materials For Medical Uses (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Extraction Or Liquid Replacement (AREA)
Abstract
Una composición que comprende polímero de poli-4-hidroxibutirato, teniendo la composición un contenido de lípidos de menos de 100 ppm de ácido palmítico medido mediante análisis por cromatografía de gases después de butanólisis.
Description
En una realización particularmente preferida, la biomasa de P4HB derivada de E. coli K12 recombinante se lava con etanol para retirar impurezas. Se ha descubierto que el uso de etanol para extraer las impurezas de la biomasa de P4HB de E. coli K12 es muy eficiente. Durante la etapa de lavado, el etanol normalmente se decolorará con un aspecto amarillento a medida que las impurezas se extraen en el etanol. Estas impurezas se han identificado
5 principalmente como ácidos grasos saturados e insaturados mediante análisis por CG, siendo los ácidos grasos C16:0 y C18:1 y el oleato los más prevalentes. Al final de la etapa de lavado, el extracto de etanol concentrado (que tiene el aspecto de un alquitrán de color negro) tiene un alto contenido de nitrógeno que normalmente podría ser aproximadamente del 0,65 % en peso. Como tal, se ha demostrado que el lavado con etanol retira los contaminantes que contienen nitrógeno, así como los lípidos y los contaminantes coloreados.
Después del lavado con etanol, la biomasa puede separarse del lavado de etanol mediante un método de separación sólido-líquido y puede recogerse mediante cualquier medio adecuado. En una realización preferida, la biomasa de P4HB se recoge por filtración o centrifugación. Si se desea, puede realizarse un lavado adicional de la biomasa de P4HB recogida o la biomasa de P4HB puede aclararse con etanol o etanol acuoso durante la recogida.
15 Aunque no es necesario secar completamente la biomasa de P4HB después de retirar el lavado de etanol, en una realización preferida, la biomasa de P4HB lavada con etanol se seca al aire. En una realización particularmente preferida, la biomasa de P4HB se seca a una concentración de etanol residual de entre el 1 y el 30 % en peso de etanol. Se ha descubierto que la presencia de mayores cantidades de etanol residual en la biomasa de P4HB lavada no afecta adversamente al rendimiento de recuperación del polímero o al peso molecular promedio en peso del producto.
En comparación con los procedimientos de extracción acuosa, se ha descubierto que el lavado de la biomasa con etanol produce una biomasa de P4HB que es más fácil de secar. Cuando se requiere una biomasa de P4HB seca, el lavado con etanol no solo retira las impurezas, sino que también desplaza el agua de la biomasa, lo que facilita
25 considerablemente el secado. Como resultado, el lavado con etanol puede suponer un ahorro en los costes de secado y acelerar y simplificar el proceso de recuperación.
Después de que la biomasa de P4HB se haya lavado con etanol, el polímero de P4HB puede extraerse con un disolvente. Idealmente, el polímero de P4HB tiene una alta solubilidad en disolventes utilizados para extraer el polímero. Los disolventes preferidos para la extracción del polímero de P4HB de la biomasa lavada con etanol incluyen cloruro de metileno, cloroformo, dicloroetano, tetracloroetano, tricloroetano, dibromometano, bromoformo, tetrahidrofurano, acetona, dimetilformamida y 1,4-dioxano. La relación de disolvente a biomasa depende del
35 contenido de polímero de la biomasa y de la naturaleza del disolvente. Si se usa demasiado poco disolvente, la viscosidad de la solución de polímero extraído puede volverse demasiado alta haciendo difícil el procesamiento adicional de la solución de polímero. En una realización particularmente preferida, la cantidad necesaria de disolvente se ajusta de manera que se forme una solución de disolvente de polímero que contenga el 2-5 % en peso de polímero de P4HB hacia el final de la extracción.
Se ha descubierto que la cantidad de disolvente requerida para extraer el polímero de P4HB con un buen rendimiento se reduce significativamente cuando se usa etanol para lavar la biomasa antes de la extracción del polímero. Además de ahorrar el coste de un disolvente adicional, el volumen de extracción reducido también disminuye la cantidad de no disolvente para el polímero de P4HB que posteriormente se necesita para precipitar el
45 polímero en la solución de disolvente. Aunque se prefiere precipitar el polímero en la solución para proporcionar un polímero con la mayor pureza posible, se produce una reducción de los costes de evaporación del disolvente si el polímero simplemente se concentra después de la extracción y no se precipita.
El polímero de P4HB puede recogerse a partir de soluciones de disolventes de P4HB, que se han extraído de biomasa de P4HB lavada con etanol, mediante la precipitación del polímero con un no disolvente. Esto es preferible a la cristalización del polímero en una solución de disolvente, que puede requerir cantidades muy grandes de disolvente con el fin de producir un producto altamente puro y, por tanto, puede ser muy costosa.
55 El no disolvente utilizado para precipitar el polímero de P4HB en una solución en disolvente de P4HB es preferentemente un alcohol o alcohol acuoso que sea un mal disolvente para el polímero de P4HB. Pueden usarse agua, etanol, etanol acuoso y el metanol para precipitar el P4HB, sin embargo, el metanol no es un no disolvente preferido debido a la potencial toxicidad de los residuos de metanol en el producto purificado. En una realización particularmente preferida, el mismo tipo de disolvente (o una solución acuosa del disolvente) que se usa para lavar la biomasa de P4HB también se usa como el no disolvente para precipitar el polímero de P4HB en la solución de polímero de P4HB. Esto es particularmente deseable, ya que limita el número de disolventes utilizados en el proceso de extracción y, por tanto, limita el número de residuos de disolvente es necesario retirar y someter a ensayo en el producto purificado final. En una realización particularmente preferida, se usa etanol para lavar la biomasa de P4HB
65 y se usa etanol o etanol acuoso como un no disolvente para precipitar el polímero en una solución en disolvente de P4HB. En una realización aún más preferida, la biomasa de P4HB se lava con etanol y el polímero se precipita en
7
Se analizó el polímero de P4HB purificado de acuerdo con el método descrito en el presente documento para
5 determinar el contenido de metales pesados, residuo de ignición, la presencia de disolvente residual y el contenido de azufre. El contenido de metales pesados del polímero se determinó mediante USP <231> (un procedimiento colorimétrico basado en la precipitación de sulfuros metálicos insolubles) y se descubrió que era de <20 ppm. El residuo tras la ignición del polímero purificado se determinó mediante USP <281> y se descubrió que era del <0,1 %. La cantidad de disolvente residual en el polímero se midió por CG de espacio de cabeza-EM usando un HP 5890 II
10 GC equipado con un detector 5972 MS y una columna capilar ZB-5 (60 m x 0,32 mm DI x 1 µm FC). Las muestras de polímero se calentaron en viales tapados a 130 ºC durante una hora antes del análisis. Se descubrió que el contenido de disolvente residual del polímero de P4HB era de <5 ppm. El contenido de azufre del polímero de P4HB purificado se determinó por espectroscopía de emisión óptica de plasma acoplado inductivamente y se descubrió que era de <50 ppm.
12
Claims (1)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/801,393 US9290612B2 (en) | 2013-03-13 | 2013-03-13 | Compositions and devices of poly-4-hydroxybutyrate |
| US201313801393 | 2013-03-13 | ||
| PCT/US2014/023373 WO2014164741A1 (en) | 2013-03-13 | 2014-03-11 | Compositions and devices of poly-4-hydroxybutyrate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2629282T3 true ES2629282T3 (es) | 2017-08-08 |
Family
ID=50687614
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14723154.2T Active ES2629282T3 (es) | 2013-03-13 | 2014-03-11 | Composiciones y dispositivos de poli-4-hidroxibutirato |
| ES17158763T Active ES2805785T3 (es) | 2013-03-13 | 2014-03-11 | Composiciones y dispositivos de poli-4-hidroxibutirato |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17158763T Active ES2805785T3 (es) | 2013-03-13 | 2014-03-11 | Composiciones y dispositivos de poli-4-hidroxibutirato |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US9290612B2 (es) |
| EP (2) | EP3205683B1 (es) |
| CA (1) | CA2905765C (es) |
| DK (2) | DK2970572T3 (es) |
| ES (2) | ES2629282T3 (es) |
| PL (1) | PL3205683T3 (es) |
| PT (2) | PT3205683T (es) |
| WO (1) | WO2014164741A1 (es) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9290612B2 (en) * | 2013-03-13 | 2016-03-22 | Tepha, Inc. | Compositions and devices of poly-4-hydroxybutyrate |
| US9480780B2 (en) * | 2013-11-05 | 2016-11-01 | Tepha, Inc. | Compositions and devices of poly-4-hydroxybutyrate |
| US10364319B2 (en) | 2015-04-10 | 2019-07-30 | Colorado State University Research Foundation | Ring-opening polymerization methods and recyclable biorenewable polyesters |
| US12402885B2 (en) | 2017-09-23 | 2025-09-02 | Universität Zürich | Medical occlusion device |
| EP3459469A1 (en) | 2017-09-23 | 2019-03-27 | Universität Zürich | Medical occluder device |
| CN107596456A (zh) * | 2017-10-11 | 2018-01-19 | 广州新诚生物科技有限公司 | 一种具有止血功能的生物医用膜及其制备方法 |
| GB2568526A (en) * | 2017-11-20 | 2019-05-22 | Rebio Tech Oy | Composition |
| EP3720514B1 (en) | 2017-12-04 | 2022-04-13 | Tepha, Inc. | Vacuum membrane thermoformed poly-4-hydroxybutyrate medical implants |
| CA3102277C (en) | 2018-06-11 | 2024-11-12 | Tepha, Inc. | PROCESSES FOR 3D PRINTING POLY-4-HYDROXYBUTYRATE AND COPOLYMERS |
| WO2021059273A2 (en) | 2019-09-26 | 2021-04-01 | Universitat Zurich | Left atrial appendage occlusion devices |
| WO2021191833A1 (en) | 2020-03-25 | 2021-09-30 | Universitat Zurich | Medical occluder delivery systems |
| EP4153654B1 (en) | 2020-05-18 | 2024-04-03 | Venvirotech Biotechnology SL. | Process for isolating pha from a pha-rich bacterial biomass |
| CA3213145A1 (en) | 2021-03-11 | 2022-09-15 | Tepha, Inc. | Breast reconstruction implant |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1334430C (en) | 1989-04-06 | 1995-02-14 | Claude Chavarie | Separation of poly-.beta.-hydroxyalkanoic acids from microbial biomass |
| DE3937649A1 (de) | 1989-11-11 | 1991-05-16 | Boehringer Ingelheim Kg | Polyester auf der basis von 4-hydroxyalkansaeuren und verfahren zu ihrer herstellung |
| US5942597A (en) | 1995-08-21 | 1999-08-24 | The Procter & Gamble Company | Solvent extraction of polyhydroxyalkanoates from biomass |
| US5811272A (en) | 1996-07-26 | 1998-09-22 | Massachusetts Institute Of Technology | Method for controlling molecular weight of polyhydroxyalkanoates |
| EP0975788A1 (en) | 1997-04-15 | 2000-02-02 | Monsanto Company | Methods of pha extraction and recovery using non-halogenated solvents |
| US6087471A (en) | 1997-04-15 | 2000-07-11 | Monsanto Company | High temperature PHA extraction using PHA-poor solvents |
| US6610764B1 (en) | 1997-05-12 | 2003-08-26 | Metabolix, Inc. | Polyhydroxyalkanoate compositions having controlled degradation rates |
| US6867248B1 (en) | 1997-05-12 | 2005-03-15 | Metabolix, Inc. | Polyhydroxyalkanoate compositions having controlled degradation rates |
| ATE354600T1 (de) * | 1997-05-12 | 2007-03-15 | Metabolix Inc | Polyhydroxyalkanoate für in vivo anwendungen |
| US6828357B1 (en) | 1997-07-31 | 2004-12-07 | Metabolix, Inc. | Polyhydroxyalkanoate compositions having controlled degradation rates |
| US6309659B1 (en) | 1997-09-02 | 2001-10-30 | Gensci Orthobiologics, Inc. | Reverse phase connective tissue repair composition |
| ES2281147T3 (es) | 1997-12-22 | 2007-09-16 | Metabolix, Inc. | Composiciones de polihidroxialcanoato con tasas controladas de degradacion. |
| AU778081B2 (en) | 1999-03-25 | 2004-11-11 | Tepha, Inc. | Medical devices and applications of polyhydroxyalkanoate polymers |
| US7025980B1 (en) | 1999-09-14 | 2006-04-11 | Tepha, Inc. | Polyhydroxyalkanoate compositions for soft tissue repair, augmentation, and viscosupplementation |
| DE10013514C2 (de) | 2000-03-14 | 2002-06-27 | Ufz Leipzighalle Gmbh | Verfahren zur Gewinnung von Polyhydroxyalkanoaten (PHA) oder deren Copolymeren |
| EP1529072B1 (en) | 2002-08-06 | 2012-09-12 | Metabolix, Inc. | Polymer extraction methods |
| TW200508393A (en) | 2003-01-20 | 2005-03-01 | Kaneka Corp | Method of collecting highly pure polyhydroxyalkanoate from microbial cells |
| PT1638615E (pt) | 2003-05-08 | 2015-02-04 | Tepha Inc | Fibras e tecidos médicos de polihidroxialcanoato |
| US7098298B2 (en) | 2003-11-21 | 2006-08-29 | Kaneka Corporation | Method for producing polyhydroxyalkanoate crystal |
| DE602004018971D1 (de) * | 2003-11-28 | 2009-02-26 | Phb Ind Sa | Verfahren zur gewinnung von polyhydroxyalkanolaten ( phas ) aus zellbiomasse |
| US7435567B2 (en) | 2004-03-04 | 2008-10-14 | Kaneka Corporation | Method for degradation of nucleic acids and use thereof |
| TW200613560A (en) | 2004-06-29 | 2006-05-01 | Procter & Gamble | Solvent extraction of polyhydroxyalkanoates from biomass |
| ES2395464T3 (es) | 2004-08-03 | 2013-02-12 | Tepha, Inc. | Suturas de polihidroxialcanoato no rizadas |
| WO2006031492A1 (en) | 2004-09-13 | 2006-03-23 | Metabolix, Inc. | Single solvent polymer extraction methods |
| US7118897B2 (en) | 2004-09-15 | 2006-10-10 | The Procter & Gamble Company | Process for the extraction of polyhydroxyalkanoates from biomass |
| BRPI0501844B1 (pt) | 2005-03-04 | 2019-12-24 | Phb Ind S/A | processo para extração e recuperação de polihidroxialcanoatos (phas) a partir de uma biomassa celular bacteriana |
| ES2624589T3 (es) | 2006-02-07 | 2017-07-17 | Tepha, Inc. | Métodos y dispositivos para la reparación del manguito de los rotadores |
| ES2395112T3 (es) | 2006-02-07 | 2013-02-08 | Tepha, Inc. | Polímeros y copolímeros de ácido poliláctico endurecidos |
| WO2009085823A1 (en) | 2007-12-19 | 2009-07-09 | Tepha, Inc. | Medical devices containing melt-blown non-wovens of poly-r-hydroxybutyrate and copolymers |
| CN102781901B (zh) | 2010-02-11 | 2016-08-03 | 梅塔玻利克斯公司 | 用于从经遗传修饰的聚羟基链烷酸酯生物质制备单体组分的方法 |
| EP2558133B1 (en) | 2010-03-26 | 2020-01-22 | Tepha, Inc. | Coatings for the manufacture and application of polyhydroxyalkanoate medical devices |
| EP2582866B1 (en) | 2010-06-15 | 2014-09-17 | Tepha, Inc. | Medical devices containing dry spun non-wovens of poly-4-hydroxybutyrate and copolymers |
| EP2637734B1 (en) | 2010-11-09 | 2017-09-13 | Tepha, Inc. | Drug eluting cochlear implants |
| BR112014002859A2 (pt) | 2011-08-10 | 2017-06-13 | Metabolix Inc | purificação pós-processamento para produção de gama-butiro lactona |
| US9290612B2 (en) * | 2013-03-13 | 2016-03-22 | Tepha, Inc. | Compositions and devices of poly-4-hydroxybutyrate |
| US9480780B2 (en) * | 2013-11-05 | 2016-11-01 | Tepha, Inc. | Compositions and devices of poly-4-hydroxybutyrate |
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| CA2905765A1 (en) | 2014-10-09 |
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| EP2970572B1 (en) | 2017-04-19 |
| US9290612B2 (en) | 2016-03-22 |
| US20160158402A1 (en) | 2016-06-09 |
| US20140275325A1 (en) | 2014-09-18 |
| PT3205683T (pt) | 2020-07-14 |
| EP2970572A1 (en) | 2016-01-20 |
| PT2970572T (pt) | 2017-07-04 |
| DK2970572T3 (en) | 2017-06-06 |
| EP3205683B1 (en) | 2020-04-22 |
| EP3205683A1 (en) | 2017-08-16 |
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