Absorbable in situ gel-forming system, method of making and use thereof

Abstract

An in situ gel-forming composition is disclosed. The in situ gel-forming composition comprises one or more absorbable polymers, solvents such as N-methyl-2-pyrrolidone, polyethylene glycol or DMSO, and optionally one or more bioactive agent. The composition forms a hydrogel or semi-solid mass on contact with an aqueous environment. The method of using in situ gel-forming composition for various applications is also disclosed.

1 - 32 . (canceled) 
     
     
         33 . An in situ gel-forming composition, comprising: one or more absorbable polymers; and
 a solvent selected from the group consisting of N-methyl-2-pyrrolidone (NMP), polyethylene glycol (PEG), dimethyl sulfoxide (DMSO) and mixtures thereof, wherein said composition is an injectable liquid at a temperature in the range of about 18° C. to about 37° C. and forms a hydrogel or semi-solid mass on contact with an aqueous environment; wherein   the one or more absorbable polymers comprise a molecular chain having a X-Y-X or (X-Y)n structure, wherein X represents a relatively hydrophobic polyester block and Y represents a relatively hydrophilic block; and wherein   the X-Y-X or (X-Y)n structure is formed by grafting hydrophobic X blocks from monomers selected from the group consisting of glycolide, lactide, ε-caprolactone, p-dioxanone, trimethylene carbonate or combinations thereof, to hydrophilic Y blocks selected from the group consisting of polyoxyethylene, poly(oxyethylene-b-oxypropylene), polypeptide polyalkylene oxamate, polysaccharide, derivatives thereof, and liquid, high molecular weight polyether glycols interlinked with an oxalate or succinate functionalities in linear or branched form.   
     
     
         34 . The in situ gel-forming composition of  claim 33 , further comprising one or more bioactive agent. 
     
     
         35 . The in situ gel-forming composition of  claim 34 , wherein said one or more bioactive agents comprise a sclerosant. 
     
     
         36 . The in situ gel-forming composition of  claim 33 , wherein said one or more absorbable polymers comprise a segmented aliphatic polyurethane. 
     
     
         37 . The in situ gel-forming composition of  claim 36 , wherein said segmented aliphatic polyurethane is a lactide/glycolide based polyurethane. 
     
     
         38 . The in situ gel-forming composition of  claim 37 , wherein said lactide/glycolide based polyurethane has a lactide:glycolide mole ratio of 70:30 to 85:15. 
     
     
         39 . The in situ gel-forming composition of  claim 36 , wherein said segmented aliphatic polyurethane comprises polyoxyalkylene glycol chains covalently linked to polyester or polyester-carbonate chain segments, interlinked with aliphatic urethane segments. 
     
     
         40 . The in situ gel-forming composition of  claim 39 , wherein said polyoxyalkylene glycol chain has an average molecular weight of 200-1200 Dalton. 
     
     
         41 . The in situ gel-forming composition of  claim 39 , wherein said polyester or polyester-carbonate chain segments are derived from at least one cyclic monomer selected from the group represented by ε-caprolactone, trimethylene carbonate, p-dioxanone, 1,5-dioxepan-2-one, l-lactide, dl-lactide, glycolide, morpholinedione, and combinations thereof 
     
     
         42 . The in situ gel-forming composition of  claim 39 , wherein said aliphatic urethane segments are derived from at least one diisocyanate selected from the group consisting of hexamethylene diisocyanate, lysine-derived diisocyanate, and cyclohexane bis (methylene isocyanate) at a prepolymer:diisocyanate ratio (w/w) of 1:0.6 to 1:1.4. 
     
     
         43 . The in situ gel-forming composition of  claim 36 , wherein said one or more absorbable polymers comprise a mixture of a copolymer of caprolactone/glycolide and a copolymer of lactide/glycolide. 
     
     
         44 . The in situ gel-forming composition of  claim 36 , wherein said one or more absorbable polymers comprise a mixture of a copolymer of lactide/trimethylene carbonate and a copolymer of lactide/glycolide. 
     
     
         45 . The in situ gel-forming composition of  claim 36 , wherein said one or more absorbable polymers comprise a terpolymer of lactide/carprolactone/trimethylene carbonate/glycolide. 
     
     
         46 . The in situ gel-forming composition of  claim 33 , wherein said one or more absorbable polymers comprise a molecular chain having a X-Y-X structure. 
     
     
         47 . The in situ gel-forming composition of  claim 46 , wherein said one or more absorbable polymers comprise a segmented aliphatic polyurethane. 
     
     
         48 . The in situ gel-forming composition of  claim 33 , wherein said one or more absorbable polymers comprise a molecular chain having a (X-Y)n structure 
     
     
         49 . The in situ gel-forming composition of  claim 48 , wherein said one or more absorbable polymers comprise a segmented aliphatic polyurethane. 
     
     
         50 . Use of an in situ gel-forming composition of  claim 33  for treating a vascular disease or condition in a subject. 
     
     
         51 . Use of an in situ gel-forming composition of  claim 33  for treating a cancer or tumor in a subject. 
     
     
         52 . Use of an in situ gel-forming composition of  claim 33  for minimizing restenosis following angioplasty.