Preserved compositions containing hyaluronic acid or a pharmaceutically-acceptable salt thereof and related methods

Abstract

The invention provides a composition containing hyaluronic acid (HA) or a pharmaceutically-acceptable salt thereof preserved with a cationic preservative and related methods. In one embodiment, the pharmaceutically-acceptable salt is sodium hyaluronate. In another embodiment, the cationic preservative includes benzalkonium chloride (BAK).

What is claimed is: 
     
         1 . A method for preparing a preserved hyaluronic acid composition, the method comprising:
 dissolving a cationic preservative in a first quantity of a solvent;   dissolving a quantity of hyaluronic acid (HA) or physiologically-acceptable salt thereof in a second quantity of the solvent; and   adding the dissolved HA or physiologically-acceptable salt thereof to the dissolved cationic preservative,   wherein precipitation of the cationic preservative and the HA or physiologically-acceptable salt thereof is substantially prevented by dissolving each in the first and second quantities of solvent before they are combined.   
     
     
         2 . The method of  claim 1 , wherein the cationic preservative includes benzalkonium chloride (BAK). 
     
     
         3 . The method of  claim 2 , wherein the BAK has the formula:
 [C 6 H 5 CH 2 N(CH 3 )R]Cl, wherein R is an alkyl group having between eight and 18 carbon atoms.   
     
     
         4 . The method of  claim 2 , wherein the BAK is in solution form. 
     
     
         5 . The method of  claim 4 , wherein the solution includes BAK at a concentration between about 5% and about 50%. 
     
     
         6 . The method of  claim 5 , wherein the concentration of BAK is between about 10% and about 30%. 
     
     
         7 . The method of  claim 1 , wherein the physiologically-acceptable salt includes sodium hyaluronate. 
     
     
         8 . The method of  claim 1 , wherein the HA has a molecular weight between about 500,000 daltons and about 4,000,000 daltons. 
     
     
         9 . The method of  claim 8 , wherein the molecular weight is between about 1,000,000 daltons and about 2,000,000 daltons. 
     
     
         10 . The method of  claim 1 , wherein the solvent includes water. 
     
     
         11 . The method of  claim 10 , wherein the solvent further includes at least one of the following: glycerin, polyethylene glycol (PEG), and propylene glycol. 
     
     
         12 . The method of  claim 1 , wherein a ratio of the first quantity of the solvent to the second quantity of the solvent is between about 1.8:1 and about 2.2:1. 
     
     
         13 . The method of  claim 12 , wherein the ratio is about 2:1. 
     
     
         14 . The method of  claim 1 , further comprising:
 filtering the combined HA or physiologically-acceptable salt thereof and cationic preservative solution.   
     
     
         15 . The method of  claim 14 , wherein the HA or physiologically-acceptable salt thereof and cationic preservative solution has a transmittance between about 93% and about 98% at 440 nm before filtration. 
     
     
         16 . The method of  claim 14 , wherein the combined HA or physiologically-acceptable salt thereof and cationic preservative solution has a transmittance between about 95% and about 100% at 440 nm after filtration. 
     
     
         17 . The method of  claim 1 , wherein the composition has a concentration of unprecipitated HA between about 0.1% and about 0.5%. 
     
     
         18 . A composition prepared according to the method of  claim 1 . 
     
     
         19 . A method for preparing a preserved hyaluronic acid composition, the method comprising:
 dissolving a cationic preservative in a first quantity of a solvent;   dissolving a quantity of hyaluronic acid (HA) or physiologically-acceptable salt thereof in a second quantity of the solvent;   dissolving a quantity of an anionic cellulose derivative in a third quantity of the solvent;   adding the dissolved HA or physiologically-acceptable salt thereof to the dissolved cationic preservative; and   adding the dissolved anionic cellulose derivative to at least one of the following: the dissolved HA or physiologically-acceptable salt thereof, the dissolved cationic preservative, and the combined dissolved HA or physiologically-acceptable salt thereof and cationic preservative,   wherein precipitation of the cationic preservative and the HA or physiologically-acceptable salt thereof is substantially prevented by dissolving each in the first and second quantities of solvent before they are combined.   
     
     
         20 . A preserved aqueous composition comprising:
 a solvent;   hyaluronic acid (HA) or a physiologically-acceptable salt thereof; and   an effective amount of a cationic preservative including benzalkonium chloride (BAK) having the formula [C 6 H 5 CH 2 N(CH 3 )R]Cl, wherein R is an alkyl group having at least one of: between eight and 10 and between 14 and 18 carbon atoms,   wherein the composition is substantially free of precipitants of the cationic preservative and the HA or physiologically-acceptable salt thereof.