US2014256617A1PendingUtilityA1

In Situ Forming Hydrogel and Method Using Same

Assignee: UNIV ARIZONA STATEPriority: Oct 12, 2011Filed: Oct 12, 2012Published: Sep 11, 2014
Est. expiryOct 12, 2031(~5.2 yrs left)· nominal 20-yr term from priority
A61L 27/52A61L 2300/404A61K 47/32A61L 2430/24A61K 9/0024A61K 38/14A61K 9/06A61P 19/00A61L 27/54A61L 27/50A61L 2400/06
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Claims

Abstract

A hydrogel (I), comprising a polymer backbone wherein an aqueous solution of the hydrogel comprises a first lower critical solution temperature, and wherein the hydrogel is configured to be converted in vivo into a modified hydrogel, and wherein an aqueous solution of the modified hydrogel comprises a second lower critical solution temperature, and wherein the second lower critical solution temperature is greater than the first lower critical solution temperature.

Claims

exact text as granted — not AI-modified
1 . A hydrogel, comprising:
 a polymer backbone comprising a plurality of repeat units, wherein one or more of the plurality of repeat units comprises a pendent water soluble polymer attached thereto;   wherein:   an aqueous solution of a polymer comprises a first lower critical solution temperature (“LCST”);   said solution forms said hydrogel when heated above that first LCST;   said hydrogel is configured to be converted in vivo into a modified hydrogel;   an aqueous solution of said modified hydrogel comprises a second lower critical solution temperature (“LCST”);   said second LCST is greater than said first LCST.   
     
     
         2 . (canceled) 
     
     
         3 . The hydrogel of  claim 1 , wherein said polymer backbone comprises a terpolymer. 
     
     
         4 . The hydrogel of  claim 3 , wherein said terpolymer comprises a second plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
         wherein R3 and R4 are each independently selected from the group consisting of H and alkyl. 
       
     
     
         5 . The hydrogel of  claim 4 , wherein said terpolymer comprises a third plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
         wherein linkage R8 is selected from the group consisting of ester, amide, thioamide, thiourea, anhydride, thioester, thiourea, and alkyl; 
         wherein R6 is selected from the group consisting of alkyl, phenyl, polyesters, and lactones; and 
         wherein either R8 or R6 comprises at least one ester or anhydride. 
       
     
     
         6 . The hydrogel of  claim 5 , wherein said first plurality of repeat units comprise a structure: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The hydrogel of  claim 5 , wherein said first plurality of repeat units comprise a structure: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The hydrogel of  claim 5 , wherein said first plurality of repeat units comprise a structure: 
       
         
           
           
               
               
           
         
       
     
     
         9 . The hydrogel of  claim 5 , wherein said terpolymer further comprises a first plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
       
     
     
         10 . The hydrogel of  claim 5 , wherein said terpolymer further comprises a first plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The hydrogel of  claim 5 , wherein said terpolymer further comprises a first plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The hydrogel of  claim 5 , wherein the water soluble polymer comprises a polyether. 
     
     
         13 . The hydrogel of  claim 12 , wherein the polyether comprises a fourth plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
       
     
     
         14 . The hydrogel of  claim 12 , wherein the polyether comprises a fourth plurality of repeat units having a structure 
       
         
           
           
               
               
           
         
       
     
     
         15 . A method to deliver a medicament in vivo, comprising:
 providing a medicament and a hydrogel, wherein said hydrogel comprises a polymer with a first lower critical solution temperature (“LCST”); wherein one or more of the plurality of repeat units of said polymer comprises a pendent water soluble polymer attached thereto by a linkage selected from the group consisting of amide, thioamide, urea, thiourea, ester, and anhydride;   administering at an administration site said medicament and said hydrogel into an animal, wherein said animal comprises a body temperature   wherein said body temperature is greater than said LCST;   releasing in vivo said medicament from said hydrogel;   converting in vivo said hydrogel into a modified polymer, wherein an aqueous solution of said modified polymer comprises a second lower critical solution temperature (“LCST”), and wherein said second LCST is greater than said body temperature;   excreting said modified polymer by said animal.   
     
     
         16 . The method of  claim 15 , wherein said polymer comprises a first plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
         wherein R7 is selected from the group consisting of an amide linkage, a thioamide linkage, a urea linkage, a thiourea linkage, an anhydride linkage, and an ester linkage. 
       
     
     
         17 . The method of  claim 16 , wherein said polymer backbone comprises a terpolymer. 
     
     
         18 . The method of  claim 17 , wherein said terpolymer comprises a second plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
         wherein R3 and R4 are each independently selected from the group consisting of H, methyl, ethyl, and phenyl. 
       
     
     
         19 . The method of  claim 18 , wherein said terpolymer comprises a third plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
         wherein linkage R8 is selected from the group consisting of ester, amide, thioamide, thiourea, anhydride, thioester, thiourea, and alkyl; 
         wherein R6 is selected from the group consisting of alkyl, phenyl, polyesters, and lactones; and 
         wherein either R8 or R6 comprises at least one ester or anhydride. 
       
     
     
         20 . The method of  claim 19 , wherein said first plurality of repeat units comprise a structure: 
       
         
           
           
               
               
           
         
       
     
     
         21 . The method of  claim 19 , wherein said first plurality of repeat units comprise a structure: 
       
         
           
           
               
               
           
         
       
     
     
         22 . The method of  claim 19 , wherein said first plurality of repeat units comprise a structure: 
       
         
           
           
               
               
           
         
       
     
     
         23 . The method of  claim 19 , wherein said first plurality of repeat units comprise a structure: 
       
         
           
           
               
               
           
         
       
     
     
         24 . The method of  claim 19 , wherein said terpolymer further comprises a first plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
       
     
     
         25 . The method of  claim 19 , wherein said terpolymer further comprises a first plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
       
     
     
         26 . The method of  claim 16 , wherein the water soluble polymer comprises a polyether. 
     
     
         27 . The hydrogel of  claim 26 , wherein the polyether comprises a fourth plurality of repeat units having a structure: 
       
         
           
           
               
               
           
         
       
     
     
         28 . The hydrogel of  claim 26 , wherein the polyether comprises a fourth plurality of repeat units having a structure 
       
         
           
           
               
               
           
         
       
     
     
         29 . A method to administer a hydrogel in vivo to an animal to an administration site, including a human, wherein:
 said hydrogel comprises a polymer;   said hydrogel contains over 50% by weight of an aqueous solvent;   said polymer forms physical crosslinks during the use of said hydrogel in response to an environmental condition.   
     
     
         30 - 41 . (canceled) 
     
     
         42 . The method of  claim 29 , wherein said polymer forms physical crosslinks in response to a change in temperature. 
     
     
         43 . The method of  claim 29 , wherein said administration site comprises a joint space. 
     
     
         44 . The method of  claim 29 , wherein said administration site comprises a knee joint. 
     
     
         45 . The method of  claim 29 , wherein said administration site comprises a hip joint. 
     
     
         46 . The method of  claim 29 , wherein said administration site comprises a surface of an implanted medical device. 
     
     
         47 . The method of claim  34 , wherein said implanted medical device comprises a prosthetic joint. 
     
     
         48 . The method of  claim 46 , wherein said implanted medical device is used in orthopaedic surgery. 
     
     
         49 . The method of  claim 46 , wherein said hydrogel is administered to said implanted medical device after implantation of said implanted medical device 
     
     
         50 . The method of  claim 29 , wherein said hydrogel comprises one or more medicaments. 
     
     
         51 . The method of  claim 29 , wherein said hydrogel contains no medicament. 
     
     
         52 . The method of  claim 29 , wherein said hydrogel comprises an antimicrobial.

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