# US 8,541,484 B2 · PVA-PAA hydrogels > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,541,484 B2 - Document ID: US8541484B2 - Status: Granted - Kind: B2 - Application number: 12/597,056 - Filed: 2008-04-24 - Published: 2010-04-29 - Granted: 2013-09-24 - Earliest claimed: 2007-04-24 - Assignees: The General Hospital Corporation - Applicants: Jeeyoung Choi; Orhun K. Muratoglu - Inventors: Jeeyoung Choi; Orhun K. Muratoglu - Web page: https://patentgrep.com/patent/US8541484B2 ## CPC - A61L 27/26: Mixtures of macromolecular compounds - A61L 27/16: obtained by reactions only involving carbon-to-carbon unsaturated bonds - A61L 27/52: Hydrogels or hydrocolloids - C08J 3/075: Macromolecular gels - C08L 29/04: Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids - C08J 2329/04: Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids - C08L 33/02: Homopolymers or copolymers of acids; Metal or ammonium salts thereof - C08L 71/02: Polyalkylene oxides - 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 (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29) - C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06) ## Abstract The invention provides fabricated PVA-hydrogels, PVA-hydrogel-containing compositions, and methods of making the same. The invention also provides methods of implanting or administering the PVA-hydrogels, or the PVA-hydrogel-containing compositions to treat a subject in need. Methods of cross-linking pre-solidified or pre-gelled hydrogel particles and making cross-linked PVA-hydrogels, and cross-linked PVA-hydrogel-containing compositions also are disclosed herein. ## Claims ### Claim 1 A method of making a PVA-hydrogel comprising: a) contacting an aqueous solution of poly(vinyl alcohol) (PVA) with an aqueous solution of poly(acrylic acid) (PAA) at a temperature above the room temperature, thereby forming a homogenous PVA-PAA solution wherein the PVA-PAA solution includes no polyethylene glycol (PEG); b) pouring the PVA-PAA solution onto a mold followed by cooling down to room temperature, thereby allowing formation of the PVA-hydrogel; c) cooling the PVA-hydrogel by freezing at a temperature below 0° C.; d) thawing the PVA-hydrogel to a temperature above 0° C.; and e) immersing PVA-hydrogel in a PEG solution, thereby allowing diffusion of the PEG into the PVA-hydrogel. ### Claim 2 (depends on 1) The method according to claim 1, wherein the PVA:PAA ratio is about 99.9:0.1 to 5:5. ### Claim 3 (depends on 1) The method according to claim 1, wherein the total polymer content in PVA-PAA solution is about 10% to about 50%. ### Claim 4 (depends on 1) The method according to claim 1, wherein the PVA-PAA solution is poured into a pre-heated mold followed by cooling down to room temperature, thereby allowing formation of the PVA-hydrogel. ### Claim 5 (depends on 1) The method according to claim 1, wherein the PVA-PAA solution is heated to a temperature above room temperature to about 90° C. ### Claim 6 (depends on 1) The method according to claim 1, wherein the PVA-PAA solution is poured into a pre-heated mold followed by freezing below 0° C. and thawing to a temperature above 0° C., thereby allowing formation of the PVA-hydrogel. ### Claim 7 (depends on 1) The method according to claim 1, wherein the PVA-PAA solution is poured into a pre-heated mold followed by freezing below 0° C. and thawing to a temperature above 0° C., thereby allowing formation of the PVA-hydrogel. ### Claim 8 (depends on 1) The method according to claim 1, wherein the PVA-hydrogel is re-hydrated in water or saline. ### Claim 9 (depends on 1) The method according to claim 1, wherein the freeze-thaw step is repeated for at least 2 to 100 cycles. ### Claim 10 (depends on 1) The method according to claim 1, wherein the freeze-thaw step is repeated for at least 2, 3, 4, 5, 6, 7, 8, 9, 10, or more cycles. ### Claim 11 (depends on 1) The method according to claim 1, wherein the PVA-hydrogel is dehydrated to remove part or all of the water content. ### Claim 12 (depends on 1) The method according to claim 1, wherein the PVA-hydrogel is dehydrated by a method comprising the steps of: a) contacting the PVA-hydrogel with an organic solvent, wherein the hydrogel comprises a polymer which is not soluble in the solvent, and wherein the solvent is at least partially miscible in water; and b) air-drying the hydrogel at room temperature or heat drying the hydrogel. ### Claim 13 (depends on 1) The method according to claim 1, wherein the PVA-hydrogel is dehydrated by a method comprising the steps of: a) contacting the PVA-hydrogel with an organic solvent, wherein the hydrogel comprises a polymer which is not soluble in the solvent, and wherein the solvent is at least partially miscible in water; and b) subjecting the hydrogel to at least one freeze-thaw cycle and allowing the hydrogel to warm-up room to temperature. ### Claim 14 (depends on 11) The method according to claim 11, wherein the dehydration is carried out by placing the hydrogel in: a) a non-solvent, wherein i) the non-solvent is PEG, alcohols, acetones, saturated salinated water, vitamin, or carboxylic acid, aqueous solution of a salt of an alkali metal, and ii) the non-solvent contains more than one ingredient including water, PEG, vitamin, polymer, ester, proteoglycan, and carboxylic acid, or b) in a supercritical fluid. ### Claim 15 (depends on 11) The method according to claim 11, wherein the dehydration is carried out at about 40° C. to above 200° C. ### Claim 16 (depends on 11) The method according to claim 11, wherein the dehydration is carried out in an atmosphere containing 100% air, 100% inert gas, a mixture of one or more inert gases mixed with 0.1% to 99.9% air, or a mixture of one or more inert gases containing 0.1% to 99.9% oxygen. ### Claim 17 (depends on 11) The method according to claim 11, wherein the dehydrated hydrogel is re-hydrated by placing the dehydrated hydrogel: i) in water, saline solution, Ringer's solution, salinated water, buffer solution, and the like, ii) in a humid chamber, and/or iii) at room temperature or at an elevated temperature. ### Claim 18 (depends on 1) The method according to claim 1, wherein the PVA-hydrogel is re-hydrated to reach an equilibrium. ### Claim 19 (depends on 1) The method according to claim 1, wherein the pHmt of a PVA-PAA solution containing 1.654 w/w % aqueous PAA solution and 25% total polymer having a PVA:PAA ratio of 19:1 is between about 3.0 and about 5.5. ### Claim 20 (depends on 1) The method according to claim 1, wherein the PVA-hydrogel comprises one or more hydrophilic polymers selected from the group consisting of: PVA-PAA copolymer, poly(ethylene oxide) (PEO)-PAA copolymer, Poly(methacrylic acid) (PMAA), polyvinylpyrrolidone (PVP), hyaluronic acid (HA), and poly(allylamine hydrochloride) (PAH). ### Claim 21 (depends on 1) The method according to claim 1, wherein the hydrogel comprises water and/or one or more other ingredients, wherein the ingredient is PEG of different molecular weights or a blend of PEGs of different molecular weights. ### Claim 22 (depends on 1) The method of claim 1 further comprising dehydrating the hydrogel. ### Claim 23 (depends on 1) The method of claim 1 further comprising forming a medical implant from the PVA-hydrogel.