THREADS OF CROSS-LINKED HYALURONIC ACID AND METHODS OF USES THEREOF
This invention relates generally to threads of hyaluronic acid, methods of making such threads and uses thereof, for example, in aesthetic applications (e.g., facial contouring, dermal fillers), surgery (e.g., sutures), drug delivery, negative pressure wound therapy, moist wound dressing, and the like.
1 . A method of making a dermal filler thread comprising hyaluronic acid wherein at least a portion of the hyaluronic acid is interlocked and further wherein at least a portion of the hyaluronic acid is cross-linked, said method comprising drying under ambient conditions, for a period between about 30 minutes to about 72 hours, an aqueous gel composition comprising hyaluronic acid and a cross-linking agent, to provide a dried thread.
2 . The method of claim 1 , wherein the aqueous gel composition is buffered.
3 . The method of claim 2 , wherein the aqueous gel composition has a pH of about 7.
4 . The method of claim 2 , wherein the aqueous gel composition has a pH of about 9.
5 . The method of claim 2 , wherein the aqueous gel composition has a pH of about 10.
6 . The method of claim 3 , further comprising the step of adjusting the pH of the solution with a base.
7 . The method of claim 6 , wherein the base is sodium carbonate or sodium hydroxide.
8 . The method of claim 1 , wherein the composition is provided by adding the cross-linking agent to an aqueous solution comprising hyaluronic acid.
9 . The method of claim 8 , wherein the aqueous solution comprises from about 1% to about 30% by weight hyaluronic acid.
10 . The method of claim 8 , wherein the hyaluronic acid has a molecular weight of from about 0.6 MDa to about 2.6 MDa.
11 . The method of claim 8 , wherein the hyaluronic acid has a molecular weight of from about 1.4 MDa to about 1.6 MDa.
12 . The method of claim 8 , wherein from about 0.1 to about 5.0% by volume of cross-linking agent is added to the solution.
13 . The method of claim 8 , wherein from about 0.2 to about 0.8% by volume of cross-linking agent is added to the solution.
14 . The method of claim 1 , wherein the aqueous gel composition has a viscosity of from about 150 Pascal-seconds (Pa·s) to about 2,000 Pascal-seconds (Pa·s).
15 . The method of claim 1 , wherein prior to drying the gel is degassed.
16 . The method of claim 1 , wherein the composition is dried for from about 12 hours to about 24 hours.
17 . The method of claim 11 , further comprising rehydrating the dried thread with an aqueous solvent to form a hydrated thread.
18 . The method of claim 17 , further comprising stretching the hydrated thread.
19 . The method of claim 17 , further comprising re-drying the hydrated thread.
20 . The method of claim 19 , further comprising stretching the rehydrated thread during the re-drying.