Rapid-gelling biocompatible polymer composition and associated methods of preparation and use

A method for preparing a biocompatible gel, comprising:

• (a) admixing a biocompatible crosslinking component A having m sulfhydryl groups with a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein m≧2, n≧2 and m+n≧4, and further wherein the sulfhydryl-reactive groups are capable of undergoing a free radical reaction with the m sulfhydryl groups to form a gel in less than one minute;
• (b) initiating the free radical reaction
• (i) by incorporation of a free radical initiator into the admixture prepared in (a),
• (ii) by irradiating the admixture prepared in (a),
• (iii) both (i) and (ii), or
• (iv) with heat;
• and
• (c) allowing the components to react and thereby form a gel.

A method for preparing a biocompatible gel, comprising:

• (a) providing, in an aqueous medium having a pH in the range of about 3 to 6, a biocompatible crosslinking component A having m sulfhydryl groups and a biocompatible crosslinking component B having n sulfhydryl-reactive groups, wherein m≧2, n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of covalent reaction with the m sulfhydryl groups upon admixture of components A and B in a basic aqueous medium to form a gel in less than one minute;
• (b) increasing the pH of the aqueous medium to a pH in the range of about 7.5 to about 11, by adding at least one basic reagent to the aqueous medium;
• and
• (c) allowing the components to react and thereby form a gel.

A biocompatible gel-forming system for in vivo administration, comprising:

• (a) a biocompatible crosslinking component A having m sulfhydryl groups wherein m≧2, in a liquid medium having an alkaline pH;
• and
• (b) a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein n≧2 and m+n>4,
• wherein the sulfhydryl-reactive groups of component A are capable of covalent reaction with the m sulfhydryl groups of component B upon admixture of components A and B without any added solvent.

A biocompatible gel-forming system, comprising:

• (a) a biocompatible crosslinking component A having m sulfhydryl groups wherein m≧2;
• and
• (b) a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein n≧2 and m+n>4,
• wherein the sulhydryl-reactive groups are capable of undergoing a free radical reaction with the m sulfhydryl groups to form a gel in less than one minute.

A method for effecting the nonsurgical attachment of a first surface to a second surface, comprising:

• (a) forming a reactive composition by admixing a biocompatible crosslinking component A having m sulhydryl groups with a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein m≧2, n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of covalent reaction with the m sulfhydryl groups upon admixture of components A and B under effective crosslinking conditions to form a gel in less than one minute;
• and
• (b) either during or immediately subsequent to step (a), applying the reactive composition to a first surface;
• and
• (c) contacting the first surface with a second surface to effect adhesion therebetween.

A method for effecting the nonsurgical attachment of a first surface to a second surface, comprising:

• (a) admixing a biocompatible crosslinking component A having m sulfhydryl groups and a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein m≧2, n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of undergoing a free radical reaction with the m sulhydryl groups to form a gel in less than one minute;
• (b) either during or subsequent to step (a), applying the admixture to a first surface;
• (c) contacting the first surface with a second surface;
• (d) immediately prior to, during or subsequent to step (c), initiating the free radical reaction;
• and
• (e) allowing the components to react and thereby effect adhesion between the first and second surfaces.

A method for introducing a biocompatible gel into a tissue within a body of a mammalian subject, comprising:

• (a) forming a reactive composition by admixing a biocompatible crosslinking component A having m sulfhydryl groups with a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein m≧2, n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of covalent reaction with the m sulfhydryl groups upon admixture of components A and B under effective crosslinking conditions to form a gel in less than one minute;
• and
• (b) either during or immediately subsequent to step (a), applying the reactive composition to the tissue;
• and
• (c) allowing the reactive composition to gel in situ.

A method for introducing a biocompatible gel into a tissue within a body of a mammalian subject, comprising:

• (a) admixing a biocompatible crosslinking component A having m sulfhydryl groups with a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein m≧2, n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of undergoing a free radical reaction with the m sulfhydryl groups to form a gel in less than one minute;
• (b) either during or subsequent to step (a), applying the admixture to the tissue;
• (c) immediately prior to, during, or subsequent to step (b), initiating the free radical reaction;
• and
• (d) allowing the components to react and thereby form a gel in situ.

A method for preventing the formation of adhesions following surgery or injury, comprising:

• (a) forming a reactive composition by admixing a biocompatible crosslinking component A having m sulfhydryl groups with a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein m≧2, n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of covalent reaction with the m sulfhydryl groups upon admixture of components A and B under effective crosslinking conditions to form a gel in less than one minute;
• (b) either during or immediately subsequent to step (a), applying the reactive composition to the tissues comprising, surrounding, and/or adjacent to a wound resulting from surgery or injury;
• and
• (c) allowing the reactive composition to gel in situ.

A method for preventing the formation of adhesions following surgery or injury, comprising:

• (a) admixing a biocompatible crosslinking component A having m sulfhydryl groups with a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein m≧2, n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of undergoing a free radical reaction with the m sulfhydryl groups to form a gel in less than one minute;
• (b) either during or subsequent to step (a), applying the admixture to the tissues comprising, surrounding, and/or adjacent to a wound resulting from surgery or injury;
• (c) immediately prior to, during, or subsequent to step (b), initiating the free radical reaction;
• and
• (d) allowing the components to react and thereby form a gel in situ.

A method for effecting the augmentation of tissue within the body of a mammalian subject, comprising:

• (a) forming a reactive composition by admixing a biocompatible crosslinking component A having m sulfhydryl groups with a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein m≧2, n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of covalent reaction with the m sulfhydryl groups upon admixture of components A and B under effective crosslinking conditions to form a gel in less than one minute;
• (b) either during or immediately subsequent to step (a), applying the reactive composition to the tissues comprising, surrounding, and/or adjacent to a tissue site in need of augmentation;
• and
• (c) allowing the reactive composition to gel in situ.

A method for effecting the augmentation of tissue within the body of a mammalian subject, comprising:

• (a) admixing a biocompatible crosslinking component A having m sulfhydryl groups with a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein m≧2, n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of undergoing a free radical reaction with the m sulfhydryl groups to form a gel in less than one minute;
• (b) either during or subsequent to step (a), applying the reactive mixture to the tissues comprising, surrounding, and/or adjacent to a tissue site in need of augmentation;
• (c) immediately prior to, during, or subsequent to step (b), initiating the free radical reaction;
• and
• (d) allowing the components to react and thereby form a gel in situ.

A method for providing a biocompatible coating on the surface of a synthetic implant, comprising:

• (a) forming a reactive composition by admixing a biocompatible crosslinking component A having m sulfhydryl groups with a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein m≧2, n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of covalent reaction with the m sulfhydryl groups upon admixture of components A and B under effective crosslinking conditions to form a gel in less than one minute;
• (b) either during or immediately subsequent to step (a), applying the reactive composition to a surface of a synthetic implant to provide a coating thereon;
• and
• (c) allowing the coating to gel in situ.

A method for providing a biocompatible coating on the surface of a synthetic implant, comprising:

• (a) admixing a biocompatible crosslinking component A having m sulfhydryl groups with a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein m≧2, n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of undergoing a free radical reaction with the m sulfhydryl groups to form a gel in less than one minute;
• (b) either during or subsequent to step (a), applying the reactive admixture to a surface of a synthetic implant to provide a coating thereon;
• (c) immediately prior to, during, or subsequent to step (b), initiating the free radical reaction;
• and
• (d) allowing the components of the coating to gel in situ.

A method for locally administering a biologically active agent to a selected site within a patient's body, comprising:

• (a) preparing a reactive composition by admixing (i) a biologically active agent with (ii) a biocompatible crosslinking component A having m sulfhydryl groups wherein m≧2, and (iii) a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of covalent reaction with the m sulfhydryl groups upon admixture of components A and B under effective crosslinking conditions to form a gel in less than one minute;
• (b) either during or immediately subsequent to step (a), introducing the composition into the patient's body at the selected site;
• and
• (c) allowing the composition to gel in situ, thereby forming a gelled implant that provides for controlled release of the biologically active agent.

A method for locally administering a biologically active agent to a selected site within a patient's body, comprising:

• (a) preparing a reactive composition by admixing (i) a biologically active agent with (ii) a biocompatible crosslinking component A having m sulfhydryl groups wherein m≧2, and (iii) a biocompatible crosslinking component B having n sulfhydryl-reactive groups wherein n≧2 and m+n>4, and further wherein the sulfhydryl-reactive groups are capable of undergoing a free radical reaction with the m sulfhydryl groups to form a gel in less than one minute;
• (b) either during or subsequent to step (a), introducing the admixture into the patient's body at the selected site;
• (c) immediately prior to, during, or subsequent to step (b), initiating the free radical reaction;
• and
• (d) allowing the components to react in situ, thereby forming a gelled implant that provides for controlled release of the biologically active agent.