PRESERVED COMPOSITIONS CONTAINING HYALURONIC ACID OR A PHARMACEUTICALLY-ACCEPTABLE SALT THEREOF AND RELATED METHODS
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).
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.