Formulations and Kits for Forming Bioadhesive Matrices

Abstract

A bioadhesive formulation, comprising gelatin, alginate and a coupling agent, capable of forming a bioadhesive matrix, which is characterized by rapid curing, optimal viscosity, high bonding strength, flexibility, biocompatibility and biodegradability, is disclosed. Further disclosed is such a bioadhesive formulation which further comprises a bioactive agent, and a drug-eluting bioadhesive matrix formed therefrom, the bioadhesive matrix being capable of delivering the bioactive agent to a bodily site. Methods utilizing the bioadhesive formulations and matrices in various biological and medical procedures are also disclosed.

What is claimed is: 
     
         1 . A kit for preparing a bioadhesive formulation, comprising sub-formulation A and sub-formulation B, said sub-formulation A comprises gelatin and alginate dissolved in water and said sub-formulation B comprises a carbodiimide, whereas combining said sub-formulation A with said sub-formulation B affords the bioadhesive formulation, the bioadhesive formulation being for forming a bioadhesive matrix upon allowing a curing time to elapse, and wherein upon said combining:
 a concentration of said gelatin in the bioadhesive formulation ranges from 50 mg/ml to 400 mg/ml,   a concentration of said alginate in the bioadhesive formulation ranges from 10 mg/ml to 60 mg/ml, and   a concentration of said carbodiimide in the bioadhesive formulation ranges from 5 mg/ml to 50 mg/ml,   such that prior to curing, the bioadhesive formulation is characterized by a room temperature viscosity that ranges from 1 Pa-sec to 50 Pa-sec, and such that said curing time ranges from 5 seconds to 30 minutes.   
     
     
         2 . The kit of  claim 1 , wherein said carbodiimide in said sub-formulation B is dissolved in water. 
     
     
         3 . The kit of  claim 1 , wherein said matrix is characterized by at least one of:
 a bonding strength of viable biological objects that ranges from 2,000 pascal to 60,000 pascal;   a flexural strength at physiological conditions that ranges from 0.5 MPa to 200 MPa; and   a biodegradability rate that ranges from 7 days to 6 months.   
     
     
         4 . The kit of  claim 1 , wherein the concentration of said gelatin in the formulation ranges from 200 mg/ml to 300 mg/ml, the concentration of said alginate in the formulation ranges from 20 mg/ml to 40 mg/ml and the concentration of said carbodiimide in the formulation ranges from 10 mg/ml to 30 mg/ml. 
     
     
         5 . The kit of  claim 1 , wherein said sub-formulation A and/or said sub-formulation B further comprises a crosslinking promoting agent. 
     
     
         6 . The kit of  claim 5 , wherein a concentration of said crosslinking promoting agent in said formulation ranges from 1% to 50% relative to the amount of said carbodiimide in said formulation. 
     
     
         7 . The kit of  claim 1 , wherein said sub-formulation A and/or said sub-formulation B further comprises a filler. 
     
     
         8 . The kit of  claim 7 , wherein a concentration of said filler in said formulation ranges from 0.1% w/v to 1% w/v of the formulation. 
     
     
         9 . The kit of  claim 1 , wherein said sub-formulation A and/or said sub-formulation B further comprises a bioactive agent. 
     
     
         10 . The kit of  claim 9 , wherein a concentration of said bioactive agent in said formulation ranges from 0.1 percent weight per volume to 10 percent weight per volume of the total volume of said formulation. 
     
     
         11 . The kit of  claim 1 , being in a form of a dual chamber dispenser, wherein said dispenser comprises at least a chamber A for containing and dispensing said sub-formulation A, and a chamber B for containing and dispensing said sub-formulation B. 
     
     
         12 . A dual chamber dispenser for use in applying the bioadhesive formulation of  claim 1 , comprising a dual barrel cartridge assembly having a joint delivery port, a mount for coupling with a mixing tube and a mixing tube, wherein a barrel cartridge A of said dual barrel cartridge assembly is configured for dispensing said sub-formulation A, and a barrel cartridge B of said dual barrel cartridge assembly is configured for dispensing said sub-formulation B, such that upon said dispensing, said sub-formulation A and said sub-formulation B are combined to thereby form the bioadhesive formulation.