Cross-linked hyaluronic acid and collagen and uses thereof

Abstract

The present invention discloses a cross-linked hyaluronic acid/collagen formulation which has improved composition for dermal filling and higher persistence than cross-linked collagen or HA alone. Also disclosed are methods for preparing cross-linked hyaluronic acid/collagen formulations and using such for augmenting soft tissues in mammals.

What is claimed is: 
     
         1 . A process for preparing an injectable composition useful for correcting mammary hypoplasia, the process comprising:
 (1) contacting hyaluronic acid (HA) with a cross-linker to allow cross-linking of the HA by the cross-linker, thereby forming a first composition comprising a crosslinked HA;   (2) contacting the crosslinked HA with collagen to form a second composition comprising a collagen layer crosslinked to and surrounding a crosslinked HA core;   (3) homogenizing the second composition to form an injectable composition, the composition being injectable under normal manual pressure though a 25 gauge needle, thereby preparing the injectable composition useful for correcting the mammary hypoplasia.   
     
     
         2 . The process of  claim 1 , wherein the cross-linker is 1,4-butanediol diglycidyl ether (BDDE). 
     
     
         3 . The process of  claim 1 , wherein the concentration of the HA for forming the first composition is about 30 mg/ml or higher. 
     
     
         4 . The process of  claim 1 , wherein the pH of the HA for forming the first composition is about 9-12. 
     
     
         5 . The process of  claim 1 , wherein the collagen for contacting the first composition is soluble. 
     
     
         6 . The process of  claim 1 , wherein the concentration of the collagen for contacting the first composition is about 10-50 mg/ml. 
     
     
         7 . The process of  claim 1 , wherein the concentration of the collagen for contacting the first composition is about 30 mg/ml. 
     
     
         8 . The process of  claim 1 , wherein the pH of the collagen for contacting the first composition is about 2-3. 
     
     
         9 . The process of  claim 1 , wherein the pH of the second composition is about 6-8. 
     
     
         10 . The process of  claim 1 , wherein the pH of the second composition is about 7. 
     
     
         11 . The process of  claim 1 , further comprising adding a local anesthetic agent to the second composition. 
     
     
         12 . The process of  claim 11 , wherein the local anesthetic agent is lidocaine. 
     
     
         13 . The process of  claim 1  further comprising the step of adding soluble HA to the second composition. 
     
     
         14 . An injectable composition useful for correcting mammary hypoplasia in a patient, the composition made by the process of:
 (1) contacting hyaluronic acid (HA) with a cross-linker to allow cross-linking of the HA by the cross-linker, thereby forming a first composition comprising a crosslinked HA;   (2) contacting the crosslinked HA with collagen to form a second composition comprising a collagen layer crosslinked to and surrounding a crosslinked HA core; and   (3) homogenizing the second composition to form an injectable composition, thereby preparing the injectable composition useful for correcting the mammary hypoplasia.   
     
     
         15 . The composition of  claim 14 , wherein the cross-linker is 1,4-butanediol diglycidyl ether (BDDE). 
     
     
         16 . The composition of  claim 14 , wherein the concentration of the HA for forming the first composition is about 30 mg/ml or higher. 
     
     
         17 . The composition of  claim 14 , wherein the pH of the HA for forming the first composition is about 9-12. 
     
     
         18 . The composition of  claim 14 , wherein the collagen for contacting the first composition is soluble. 
     
     
         19 . The composition of  claim 14 , wherein the concentration of the collagen for contacting the first composition is about 10-50 mg/ml. 
     
     
         20 . The composition of  claim 14 , wherein the concentration of the collagen for contacting the first composition is about 30 mg/ml. 
     
     
         21 . The composition of  claim 14 , wherein the process further comprises adding lidocaine to the second composition. 
     
     
         22 . A method for volumizing a hypoplastic breast in a patient comprising introducing the composition of  claim 14  into the breast of a patient.