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WO2003033580A2 - Materiaux poreux non degradables ou degradables presentant des surfaces tres actives - Google Patents

Materiaux poreux non degradables ou degradables presentant des surfaces tres actives Download PDF

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Publication number
WO2003033580A2
WO2003033580A2 PCT/US2002/033000 US0233000W WO03033580A2 WO 2003033580 A2 WO2003033580 A2 WO 2003033580A2 US 0233000 W US0233000 W US 0233000W WO 03033580 A2 WO03033580 A2 WO 03033580A2
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solvent
polymer
degradable
porous material
mixture
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PCT/US2002/033000
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English (en)
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WO2003033580A3 (fr
Inventor
Peter X. Ma
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The Regents Of The University Of Michigan
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Publication of WO2003033580A2 publication Critical patent/WO2003033580A2/fr
Publication of WO2003033580A3 publication Critical patent/WO2003033580A3/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
    • B01J20/28078—Pore diameter
    • B01J20/28085—Pore diameter being more than 50 nm, i.e. macropores
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
    • B01J20/26—Synthetic macromolecular compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • B01J20/28002—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their physical properties
    • B01J20/28004—Sorbent size or size distribution, e.g. particle size
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • B01J20/28002—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their physical properties
    • B01J20/28004—Sorbent size or size distribution, e.g. particle size
    • B01J20/28007—Sorbent size or size distribution, e.g. particle size with size in the range 1-100 nanometers, e.g. nanosized particles, nanofibers, nanotubes, nanowires or the like
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
    • B01J20/28023—Fibres or filaments
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
    • B01J20/28047—Gels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
    • B01J20/28057—Surface area, e.g. B.E.T specific surface area
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
    • B01J20/28069—Pore volume, e.g. total pore volume, mesopore volume, micropore volume
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C67/00—Shaping techniques not covered by groups B29C39/00 - B29C65/00, B29C70/00 or B29C73/00
    • B29C67/20—Shaping techniques not covered by groups B29C39/00 - B29C65/00, B29C70/00 or B29C73/00 for porous or cellular articles, e.g. of foam plastics, coarse-pored
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C67/00—Shaping techniques not covered by groups B29C39/00 - B29C65/00, B29C70/00 or B29C73/00
    • B29C67/20—Shaping techniques not covered by groups B29C39/00 - B29C65/00, B29C70/00 or B29C73/00 for porous or cellular articles, e.g. of foam plastics, coarse-pored
    • B29C67/202—Shaping techniques not covered by groups B29C39/00 - B29C65/00, B29C70/00 or B29C73/00 for porous or cellular articles, e.g. of foam plastics, coarse-pored comprising elimination of a solid or a liquid ingredient
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • 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
    • C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
    • 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
    • C12P21/00—Preparation of peptides or proteins
    • C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
    • 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
    • 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
    • C08J2201/054—Precipitating the polymer by adding a non-solvent or a different solvent

Definitions

  • the present invention relates generally to porous materials having high surface areas, and more particularly to such materials which are non-degradable, degradable or partially degradable, and methods for fabricating the same.
  • Membranes have been typically used for filtration (microfiltration, ultrafiltration, nanofiltration), reverse osmosis (hyperfiltration), dialysis, pervaporation, and gas separation applications. See Scott, K. and R. Hughes, Industrial Membrane Separation Technology, 1996, London: Blackie Academic & Professional; Baker, R.W., Membrane technology and applications, McGraw-Hill professional engineering, 2000, New York: McGraw-Hill; and Cardew, P.T., M.S. Le, and Royal Society of Chemistry, Process Technology Group, Membrane processes : a technology guide, 1998, Cambridge: Royal Society of Chemistry.
  • a solid membrane can be made of synthetic polymers, natural macromolecules, inorganic compounds, ceramic, or metallic materials. These membrane materials are generally fabricated through sintering, stretching, extrusion, phase inversion and etching, or casting. See Scott, K. and R. Hughes, Industrial Membrane Separation Technology, 1996, London: Blackie Academic & Professional; and Pinnau, I. and B.D. Freeman, Membrane formation and modification, ACS symposium series, 744, 2000, Washington, DC [New York]: American Chemical Society, Distributed by Oxford University Press.
  • Porous membranes are advantageous in their low resistance to mass transfer of solutes in solution due to the increased permeation rate resulting from the pores. Therefore, porous membranes have been employed for separation of mixtures of proteins and macromolecules, salt concentration, sterilization, etc. They can also serve as 3-D matrices for chemical and biochemical mass exchange or reactions to take place, or for cells or other living organisms (e.g., bacteria, viruses, fungi) to grow. Therefore, they can be used as matrices in diagnostic systems, catalysis systems, culture systems, drug delivery systems, wound dressings, etc.
  • 6,146,892 discloses a method for producing nanofibrillar matrices utilizing degradable polymers, such as for example, poly(L- lactic acid) (PLLA), poly(D,L-lactic acid-co-glycolic acid) (PLGA), and the like.
  • the disclosed nanofibrillar matrices are highly porous and work well for various applications. However, the pores sizes are very small (on the order of 2 ⁇ m to 3 ⁇ m), which may in some instances render it more difficult for cells to enter. Further, small pore sizes may render it more difficult for material transport, especially materials which are particulate or contain particles. Yet further, the disclosed non-fibrillar structure (a platelet structure) was not as mechanically strong as may be desirable in some instances.
  • the present invention comprises a method for preparing a highly porous, high surface area material, comprising the steps of mixing a non-degradable polymer with a solvent or mixture of solvents; gelling the mixture; and treating the gel under conditions whereby a substantially solvent free porous structure is created having a porosity greater than about 80%; wherein the material is mechanically strong and has an architecture comprising at least one of nano fibrous, micro fibrous, non fibrous, complex porous structure with nano fibrous architecture, and mixtures thereof.
  • the present invention further comprises a method for preparing a highly porous, high surface area material, comprising the steps of mixing a degradable or partially degradable polymer with a mixed solvent comprising a first solvent and a second solvent, wherein the mixed solvent comprises a ratio higher than 1:1, first solvent to second solvent; gelling the mixture; and treating the gel under conditions whereby a substantially solvent free porous structure is created having a porosity greater than about 80%; wherein the material is mechanically strong and has a complex porous structure with nano fibrous architecture.
  • Figure la is a SEM micrograph of PA-6,6 foam prepared from a 10% PA-6,6 solution in a mixed solvent of acetic acid/water (80/20) at the following gelation temperature: room temperature;
  • Figure lb is a SEM micrograph of PA-6,6 foam prepared from a 10% PA-6,6 solution in a mixed solvent of acetic acid/water (80/20) at the following gelation temperature: -20 °C;
  • Figure lc is a SEM micrograph of PA-6,6 foam prepared from a 10% PA-6,6 solution in a mixed solvent of acetic acid/water (80/20) at the following gelation temperature: -70 °C;
  • Figure Id is a SEM micrograph of PA-6,6 foam prepared from a 10%
  • Figure 2a is a SEM micrograph of PA-6,6 foam prepared from a 10% PA-6,6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature: room temperature;
  • Figure 2b is a SEM micrograph of PA-6,6 foam prepared from a 10% PA-6,6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature: -20 °C;
  • Figure 2c is a SEM micrograph of PA-6,6 foam prepared from a 10% PA-6,6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature: -70°C, at x500 magnification;
  • Figure 2d is a SEM micrograph of PA-6,6 foam prepared from a 10% PA-6,6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature: -70 °C, at x4000 magnification;
  • Figure 3 a is a SEM micrograph of PA-6,6 foam prepared from 10%
  • Figure 3b is a SEM micrograph of PA-6,6 foam prepared from 10% PA-6,6 solutions in a mixed solvent of formic acid/water (70/30) quenched in liquid nitrogen, at x2000 magnification
  • Figure 3c is a SEM micrograph of PA-6,6 foam prepared from 10% PA-6,6 solutions in a mixed solvent of formic acid/water (80/20) quenched in liquid nitrogen, at x500 magnification;
  • Figure 3d is a SEM micrograph of PA-6,6 foam prepared from 10% PA-6,6 solutions in a mixed solvent of formic acid/water (80/20) quenched in liquid nitrogen, at x4000 magnification;
  • Figure 4a is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature: room temperature;
  • Figure 4b is a SEM micrograph of PA-6,6 foam prepared from a 5%
  • Figure 4c is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature: -70°C;
  • Figure 4d is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature: in liquid nitrogen;
  • Figure 5a is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature (dioxane instead of water was used for solvent exchange): room temperature;
  • Figure 5b is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature (dioxane instead of water was used for solvent exchange): - 20°C;
  • Figure 5c is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature (dioxane instead of water was used for solvent exchange): - 70°C;
  • Figure 5d is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature (dioxane instead of water was used for solvent exchange): in liquid nitrogen;
  • Figure 6a is a SEM micrograph of PA-6,6 foam prepared from a 5%
  • Figure 6b is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/THF (40/60) at the following gelation temperature: -20 °C;
  • Figure 6c is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/THF (40/60) at the following gelation temperature: -70 °C;
  • Figure 6d is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/THF (40/60) at the following gelation temperature: in liquid nitrogen;
  • Figure 7a is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/acetic acid/water (64/16/20) at the following gelation temperature: -20°C;
  • Figure 7b is a SEM micrograph of PA-6,6 foam prepared from a 5%
  • Figure 7c is a SEM micrograph of PA-6,6 foam prepared from a 5% PA-6,6 solution in a mixed solvent of formic acid/acetic acid/water (64/16/20) at the following gelation temperature: in liquid nitrogen;
  • Figure 8a is a SEM micrograph of PA-6,6 PA-6 (50/50) polymer blend foam prepared from a 5% PA-6,6/PA-6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature: -20 °C;
  • Figure 8b is a SEM micrograph of PA-6,6/PA-6 (50/50) polymer blend foam prepared from a 5% PA-6,6/PA-6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature: -70 °C;
  • Figure 8c is a SEM micrograph of PA-6,6/PA-6 (50/50) polymer blend foam prepared from a 5% PA-6,6/PA-6 solution in a mixed solvent of formic acid/water (70/30) at the following gelation temperature: in liquid nitrogen;
  • Figure 9a is a SEM micrograph of PA-6 foam prepared from a 5% PA-6 solution in a mixed solvent of acetic acid/water (60/40) at the following gelation temperature: -20°C;
  • Figure 9b is a SEM micrograph of PA-6 foam prepared from a 5% PA-6 solution in a mixed solvent of acetic acid/water (60/40) at the following gelation temperature: in liquid nitrogen, at x500 magnification;
  • Figure 9c is a SEM micrograph of PA-6 foam prepared from a 5%
  • PA-6 solution in a mixed solvent of acetic acid/water (60/40) at the following gelation temperature: in liquid nitrogen, at x2000 magnification;
  • Figure 9d is a SEM micrograph of PA-6 foam prepared from a 5% PA-6 solution in a mixed solvent of acetic acid/water (60/40) at the following gelation temperature: in liquid nitrogen, at x2000 magnification;
  • Figure 10a is a SEM micrograph of porous PVDF material prepared with PVDF solution in DMSO, phase-separation temperature of -18°C, low magnification;
  • Figure 10b is a SEM micrograph of porous PVDF material prepared with PVDF solution in DMSO, phase-separation temperature of - 18 ° C, intermediate magnification;
  • Figure 10c is a SEM micrograph of porous PVDF material prepared with PVDF solution in DMSO, phase-separation temperature of -18°C, high magnification
  • Figure lOd is a SEM micrograph of porous PVDF material prepared with PVDF solution in DMSO, phase-separation temperature of -70°C, low magnification;
  • Figure lOe is a SEM micrograph of porous PVDF material prepared with PVDF solution in DMSO, phase-separation in liquid nitrogen, low magnification
  • Figure 1 la is a SEM micrograph of porous PLLA material generated with PLLA solution in dioxane/pyridine mixed solvent with a ratio higher than 1:1, specifically, 7.5% PLLA in 2:1 dioxane/pyridine, at lOOx magnification;
  • Figure 1 lb is a SEM micrograph of porous PLLA material generated with PLLA solution in dioxane/pyridine mixed solvent with a ratio higher than 1:1, specifically, 7.5% PLLA in 2:1 dioxane/pyridine, at lOOOx magnification;
  • Figure 1 lc is a SEM micrograph of porous PLLA material generated with PLLA solution in dioxane/pyridine mixed solvent with a ratio higher than 1:1, specifically, 7.5% PLLA in 3:1 dioxane/pyridine, at 400x magnification; and
  • Figure 1 Id is a SEM micrograph of porous PLLA material generated with PLLA solution in dioxane/pyridine mixed solvent with a ratio higher than 1:1, specifically, 7.5% PLLA in 3:1 dioxane/pyridine, at 7000x magnification.
  • DETAILED DESCRIPTION OF THE EMBODIMENTS It would be desirable to provide highly porous structures having large pore sizes and high specific surface areas. It would further be desirable to provide such structures which are mechanically strong.
  • the present invention is predicated upon the unexpected and fortuitous discovery that a recently discovered phase separation technique may be utilized to render highly porous, mechanically strong, high surface areas materials having varied architectures (eg. nano fibrous, micro fibrous, non fibrous, complex porous structure with nano fibrous architecture) by using non-degradable polymers.
  • the novel materials of the present invention may have pore sizes ranging between about 30 ⁇ m and about 300 ⁇ m, with similarly sized connections, hi contrast, it had been expected that, whatever polymer were used, if the process as disclosed in U.S. Patent No. 6,146,892 were followed, it would render primarily nanofibrous structures. Further, it had been expected that if a non-nanofibrous structure were created, it may not be as mechanically strong as desirable for certain applications.
  • High surface areas are very desirable in that, if a material has a very high surface area, less of the material (compared to a low surface area material) may be used in order to render the same result; ie. the reaction is more efficient.
  • Some exemplary polymers suitable for the present invention comprise at least one of natural or synthetic hydrophilic polymers, natural or synthetic hydrophobic polymers, natural or synthetic amphiphilic polymers, degradable polymers, partially degradable polymers, and mixtures thereof.
  • non-limitative non-degradable water soluble (hydrophilic) polymers include polyvinyl alcohol, polyethylene oxide, polymethacrylic acid (PMAA), polyacrylic acid, polyethylene glycol, alginate, collagen, gelatin, hyaluronic acid, and mixtures thereof. It is to be understood that the natural macromolecules such as alginate, collagen, gelatin and hyaluronic acid are generally not degradable unless treated with appropriate enzymes.
  • non-limitative non-degradable water insoluble (hydrophobic) polymers include polytetrafluoroethylene (PTFE), polyvinylchloride (PVC), polyamides (PA, Nylons), polyethylenes (PE), polysulfones, polyethersulphone, polypropylenes (PP), silicon rubbers, polystyrenes, polycarbonates, polyesters, polyacrylonitrile (PAN), polyimides, polyetheretherketone (PEEK), polymethylmethacrylate (PMMA), polyvinylacetate (PVAc), polyphenylene oxide, cellulose and its derivatives, polypropylene oxide (PPO), polyvinylidene fluoride (PVDF), polybutylene, and mixtures thereof.
  • PTFE polytetrafluoroethylene
  • PVC polyvinylchloride
  • PA polyamides
  • PE polyethylenes
  • PE polysulfones
  • PP polypropylenes
  • silicon rubbers silicon rubbers
  • Some degradable polymers of choice comprise at least one of poly(lactide-co-glycolide) (PLGA), poly(lactide) (PLA), poly(L-lactic acid) (PLLA), poly(D,L-lactic acid) (PDLLA), polyglycolic acid (PGA), polyanhydrides, poly(ortho ethers), and mixtures thereof.
  • PLGA poly(lactide-co-glycolide)
  • PLA poly(lactide)
  • PLA poly(L-lactic acid)
  • PLLA poly(D,L-lactic acid)
  • PGA polyglycolic acid
  • polyanhydrides poly(ortho ethers), and mixtures thereof.
  • non-limitative degradable polymers include polyamino acids, engineered artificial proteins, natural proteins, biopolymers, and mixtures thereof.
  • Partially degradable polymers may be formed through the block copolymerization of a degradable polymer with a non-degradable polymer.
  • non-degradable polymers are disclosed hereinabove.
  • partially degradable polymers include a block copolymer of PMMA PLA; and a block copolymer of polyethylene oxide/PLA.
  • the solvent comprises at least one of water, acetic acid, formic acid, tetrahydiOfuran (THF), dimethylsulfoxide
  • DMSO dioxane
  • benzene and mixtures thereof.
  • a mixed solvent is used at a ratio of higher than 1:1, first solvent to second solvent.
  • the first solvent comprises dioxane, benzene, and mixtures thereof; and the second solvent comprises pyridine, tetrahydrofuran (THF), and mixtures thereof.
  • dioxane may be mixed with pyridine and/or THF; and that benzene may be mixed with pyridine and/or THF.
  • the ratio of first solvent to second solvent is 2:1; and in an alternate embodiment, the ratio of first solvent to second solvent is 3:1.
  • the dissolution/precipitation process is one of the most frequently used techniques to manufacture membrane materials. See, Young, T.H., L.P. Cheng, D.J. Lin, L. Fane, and W.Y. Chuang, Mechanisms of PVDF membrane formation by immersion-precipitation in soft (1-octanol) and harsh (water) nonsolvents, Polymer, 1999, 40(19): p. 5315-5323.
  • a polymer is first dissolved in a good solvent and cast on a substrate. The cast material is then immersed in a non-solvent' or poor solvent for the polymer to induce polymer precipitation from the solution.
  • Zhang Fibrillar Matrices, in United States Patent 6,146,892, 2000, which Patent is incorporated by reference herein in its entirety; Zhang, R. and P.X. Ma, Synthetic nanofibrillar extracellular matrices with predesigned macroporous architectures, J Biomed Mater Res, 2000, 52(2): p. 430-438; and Zhang, R. and P.X. Ma, Fabrication of polymer scaffolds: Phase separation, in Methods of Tissue Engineering, A. Atala and R. Lanza, Editors, 2001, Academic Press: San Diego, CA (in press). With the new techniques, dissolution/gelation (phase- separation)/solvent exchange (may be optional) /freezing/freeze-drying are some illustrative sequences to create the porous nano fibrous structure.
  • the present invention has unexpectedly and fortuitously discovered new porous polymeric materials with a variety of porous architectures (e.g., nano fibrous, micro fibrous, or non fibrous, or complex porous structure with nano fibrous architecture) and very high surface areas, which are fabricated with the new techniques.
  • Their structures and properties generally depend on either the polymer/solvent systems and/or the phase-separation conditions; such as type of polymer(s), type of solvent(s), mixture ratio of two or more types of polymer(s) and/or solvent(s), polymer concentration, phase-separation temperature and so forth.
  • This invention discloses polymeric (or substantially polymeric) materials with very high surface areas, such as >5 m 2 /g, >10 m 2 /g, >20 m 2 /g, >50 m 2 /g, or much higher, and having high porosity such as 70%, 80%, 90% or even higher, using the new fabrication techniques.
  • the novel materials of the present invention have a specific surface area ranging between about 5 m 2 /g and about 1000 m 2 /g.
  • the materials have a specific surface area ranging between about 10 m 2 /g and about 500 m 2 /g.
  • the materials have a specific surface area ranging between about 20 m 2 /g and about 200 m 2 /g.
  • novel materials of the present invention may have pore sizes ranging between about 30 ⁇ m and about 300 ⁇ m, with similarly sized connections. In an alternate embodiment, the novel materials of the present invention may have pore sizes ranging between about 50 ⁇ m and about 100 ⁇ m, with similarly sized connections.
  • the polymers may be synthetic or natural. They may be homopolymers (with one structural unit) or copolymers (with two or more structural units).
  • the copolymers maybe random copolymers, block copolymers, graft copolymers, and/or mixtures thereof. They may be one single polymer type or polymer blends.
  • the materials may also be a composite of polymeric and non- polymeric materials. Further, it is to be understood that chemically or biologically active or inert materials may be involved as additives or as major components. These polymers may be physically, chemically, and/or biologically modified to improve certain properties or function. It is to be yet further understood that such modification may be carried out before fabrication (raw materials) or after fabrication of the porous materials. Fabrication Techniques 1. Polymer solution preparation
  • the polymer solution contains between about 1% and about 20% polymer.
  • the polymers were dissolved for two hours or longer to ensure a homogeneous solution when stirred with a magnetic stirrer at either room temperature or an elevated temperature (at or higher than room temperature, for example, 20°C, 40°C, 50°C, 60°C, 70°C and so forth).
  • a porous polymer material from a polymer solution:
  • (A) Polymer solution (typically pre- warmed to a temperature at or higher than room temperature, for example, 20 °C, 40°C, 50°C, 60°C, 70°C, 100°C and so forth) was added into a mold or container (e.g., Teflon vial).
  • the mold containing the polymer solution was then rapidly transferred into a cooling device (e.g. a refrigerator or freezer) at a preset temperature to induce gelation.
  • the cooling device is maintained at a predetermined temperature between about room temperature and about liquid nitrogen.
  • the gelation time depended on temperature, solvent(s) and the polymer concentration of the solution.
  • the gel was kept at the gelling temperature for typically 2 hours or longer.
  • the mold containing the gel was immersed in a liquid (poor or non- solvent for the polymer) such as distilled water for solvent exchange. The water (or other liquid) was changed three times a day for two days.
  • C The gel was removed from the water (or other liquid) and blotted by a piece of filter paper, and then was placed in a device set at a desired freezing temperature, the freezing temperature ranging between about room temperature and about liquid nitrogen. In an embodiment, the freezing temperature ranges between about room temperature and about -20 °C. h an alternate embodiment, the freezing temperature ranges between about room temperature and about -70 °C. The gel was frozen for typically 2 hours or longer.
  • the frozen gel was taken into a freeze-drying vessel, and was freeze- dried under a predetermined vacuum and at a predetermined temperature. It is to be understood that any suitable vacuum and temperature may be used; however, in an embodiment, a vacuum lower than 0.5 mmHg was used at a temperature ranging between about -5 °C and about -10°C.
  • the frozen gel was freeze dried in an ice/salt bath for one week.
  • the dried porous polymer material was then kept in a desiccator until characterization. Ch ar acterization
  • the morphologies of the porous materials were examined with scamiing electron microscopy (SEM) (S-3200N, Hitachi, Japan) at 15 kV.
  • SEM scamiing electron microscopy
  • the samples were coated with gold using a sputter coater (Desk-II, Denton Vacuum hie.) for 200 seconds with a gas pressure of lower than about 50 mtorr and a current of about 40 mA.
  • the compressive mechanical properties of the scaffolds were measured with an MTS mechanical tester (Model: Synergie 200, MTS Systems
  • PA-6,6 was completely dissolved in pure acetic acid or acetic acid/water mixture with water content ranging from 10 to 30%. The gelation of the solution was observed when water content was higher than 20%. The gelation occurred when the temperature was from room temperature to liquid nitrogen.
  • the typical morphologies of the resulting porous foams are shown in Figures la - Id. Figures la and lb are partially nano fibrous; and Figures lc and Id are non fibrous.
  • PA-6,6 was completely dissolved in pure formic acid or a mixture of formic acid and water with water content ranging from 0% to 35%.
  • concentration of the polymer was higher than 10%
  • gelation was observed when the water content of the solvent was higher than 20% and the temperature was lower than -20 °C.
  • polymer concentration lower than 5% gelation was observed when water content was higher than 30%.
  • the gelation was observed in a temperature range from -20°C to liquid nitrogen.
  • the liquid used for solvent exchange was either water or tetrahydrofuran (THF).
  • THF tetrahydrofuran
  • Figures 2a through 5d Figures 2a and 2b are partially nano fibrous. Figures 2c and 2d have morphologies including several different structures. Figures 3a and 3b are non fibrous. Figures 3c and 3d are partially nano fibrous. Figures 4a, 4b and 4c are complex porous structure with nano fibrous architecture. Figure 4d is a spherical structure. Figures 5a - 5d are non fibrous.
  • PA-6,6 was completely dissolved in formic acid/THF co-solvent with THF content ranging from 5% to 60%. Gelation was observed when THF content was 60%. The gelation temperature range was from room temperature to liquid nitrogen. The typical morphologies of the foams are shown in Figures 6a - 6d.
  • Figures 6a - 6d are partially nano fibrous with interconnect structure and high surface area.
  • PA-6,6 was completely dissolved in formic acid/acetic acid (80/20)/water co-solvent with water content ranging from 0% to 30%. Gelation of the solution was observed when the water content was higher than 20%. The gelation temperature was from room temperature to liquid nitrogen. The typical morphologies of the foams are shown in Figures 7a - 7c. Figure 7b is non fibrous. Figure 7c is partially nano fibrous. 5. PA-6,6 and PA-6 blends in formic acid and water:
  • PA-6 was completely dissolved in acetic acid/water co-solvent with water content ranging from 0 to 40%. Gelation of the solution was observed when water content was higher than 30%. The gelation temperature was from room temperature to liquid nitrogen. The typical morphologies of the foam are shown in Figure 9.
  • Figures 9a - 9d are complex porous structure with nano fibrous architecture.
  • PVDF was easily dissolved in DMSO, and gelation occurred at a wide range of temperatures. With the new phase-separation and freeze-drying techniques, porous materials with complex architectures were formed. They had fibrous architecture, and the fibers are further composed of smaller features at the micrometer scale. Typical mo ⁇ hologies are shown in Figures 10a - lOe. Figures 10a - lOe are micro fibrous. 8. PLLA in dioxane and pyridine:
  • PLLA was easily dissolved in a mixed solvent of dioxane and pyridine. We have previously found that PLLA solution could be used to fabricate nano fibrous PLLA foams with our fabrication techniques. See Ma, P.X. and R. Zhang, Fibrillar Matrices, in United States Patent 6,146,892, 2000; Ma, P.X. and R. Zhang, Synthetic nano-scale fibrous extracellular matrix, J Biomed Mater Res, 1999, 46(1): p. 60-72; and Zhu, S. and P.X. Ma, Development of phase structure during the processing ofpoly(l-lactic acid) scaffolds for tissue engineering, Polymer Preprints, 2000, 41(2): p. 1675-1676.
  • PLGA is dissolved in a mixed solvent of benzene and THF. Ratios of 2:1 and 3 : 1 benzene to THF are used.
  • the polymer/solvent mixture contains between about 1% and about 20% PLGA. However, it is to be understood that any ratio higher than 1 : 1 may be used to gain the advantages of the present invention.
  • the porous materials have complex mo ⁇ hologies, e.g. porous architecture at the micrometer scale (such as ladder-like) and fibrous architecture at the nanometer scale.
  • the generated highly porous materials have many interesting architectural features, which are novel.
  • the porous materials generated in the present invention are believed to have excellent mechanical properties and higher specific surface areas than previously known porous materials. They have high potential to be used in a variety of biomedical, industrial and household applications. For many of these applications, a high specific surface area and the mechanical integrity are important.
  • the specific surface area and mechanical properties are characterized.
  • the compressive moduli are 5.22 ⁇ 0.77 kPa and 7.36 ⁇ 4.11 kPa for a PA-6,6 foam generated from 10% PA- 6,6 solution in formic acid/water (70/30) and a PA-6,6 foam generated from 5% PA- 6,6 solution in formic acid/THF (40/60) respectively.
  • the mechanical properties for such highly porous materials are excellent.
  • the specific surface area of a PA-6,6 foam prepared from 5% PA-6,6 solution in formic acid/THF (40/60) is 55 m 2 /g (BTE method), which is substantially higher than those currently on the market (typically lower than 5 m 2 /g).
  • the present invention comprises non-degradable porous materials having very high surface areas, and methods for fabricating the same.
  • a variety of 3D architectures with features at the nanometer and or micrometer scales may advantageously be generated.
  • the materials may be synthetic polymers, natural macromolecules, or their derivatives. They may be hydrophilic, hydrophobic, or amphiphilic. Further, the materials may be homo-polymers, copolymers, blends, mixtures, or composites of polymers.
  • the novel porous materials may advantageously be used in a variety of applications including medical devices (eg.
  • porous materials may be desirable for use as tissue engineering scaffolds for a variety of applications, including implants. While preferred embodiments, forms and arrangements of parts of the invention have been described in detail, it will be apparent to those skilled in the art that the disclosed embodiments may be modified. Therefore, the description herein is to be considered exemplary rather than limiting, and the true scope of the invention is that defined in the following claims.

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Abstract

L'invention concerne un procédé de préparation d'un matériau très poreux, non dégradable et présentant une surface très active. Le procédé consiste à: mélanger un polymère non dégradable avec un solvant ou un mélange de solvants; gélifier le mélange; et traiter le gel dans des conditions propres à créer une structure poreuse sensiblement exempte de solvant présentant une porosité supérieure à environ 80 %. Le matériau résultant présente une résistance mécanique et une architecture comprenant au moins une structure poreuse nanofibreuse, ou microfibreuse, ou non fibreuse complexe à architecture nanofibreuse, ou un mélange desdits éléments. L'invention concerne en outre un procédé de préparation d'un matériau très poreux, dégradable ou partiellement dégradable et présentant une surface très active. Le procédé consiste à: mélanger un polymère dégradable ou partiellement dégradable avec un mélange de solvants comprenant un premier solvant et un second solvant, le mélange de solvants présentant un ratio du premier solvant au second solvant supérieur à 1:1; gélifier le mélange; et traiter le gel dans des conditions propres à créer une structure poreuse sensiblement exempte de solvant présentant une porosité supérieure à environ 80 %. Le matériau résultant présente une résistance mécanique et une structure poreuse complexe à architecture nanofibreuse.
PCT/US2002/033000 2001-10-17 2002-10-16 Materiaux poreux non degradables ou degradables presentant des surfaces tres actives WO2003033580A2 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8268344B2 (en) * 2005-04-27 2012-09-18 The Regents Of The University Of Michigan Particle-containing complex porous materials
US20200102670A1 (en) * 2010-03-18 2020-04-02 National Institute For Materials Science Networked polymeric nanofibers, process for producing same, gas adsorbent, and gas separation material

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ATE168040T1 (de) * 1991-12-20 1998-07-15 Allied Signal Inc Materialien mit niedriger dichte und hoher spezifischer oberflaeche und daraus geformte artikel zur verwendung in der metallrueckgewinnung
US6281257B1 (en) * 1998-04-27 2001-08-28 The Regents Of The University Of Michigan Porous composite materials
US6146892A (en) * 1998-09-28 2000-11-14 The Regents Of The University Of Michigan Fibrillar matrices
WO2001087575A2 (fr) * 2000-05-12 2001-11-22 The Regents Of The University Of Michigan Fabrication inversee de materiaux poreux

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8268344B2 (en) * 2005-04-27 2012-09-18 The Regents Of The University Of Michigan Particle-containing complex porous materials
US8568769B2 (en) 2005-04-27 2013-10-29 The Regents Of The University Of Michigan Particle-containing complex porous materials
US20200102670A1 (en) * 2010-03-18 2020-04-02 National Institute For Materials Science Networked polymeric nanofibers, process for producing same, gas adsorbent, and gas separation material
US12104283B2 (en) * 2010-03-18 2024-10-01 National Institute For Materials Science Networked polymeric nanofibers, process for producing same, gas adsorbent, and gas separation material

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