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).

Claims

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.sub.6H.sub.5CH.sub.2N(CH.sub.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.sub.6H.sub.5CH.sub.2N(CH.sub.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.

Description

EXAMPLE 1

Sodium Hyaluronate, BAK, CMC Composition Prepared in Two Parts

[0029] 1. Dissolve a quantity of sodium hyaluronate in 100 mL of water to a concentration of 0.4%.
2. Dissolve a quantity of BAK in 200 mL of water to a concentration of 0.005%.
3. To the dissolved BAK, add and dissolve a quantity of CMC to a concentration of 0.5%.
4. Add the dissolved sodium hyaluronate solution to the dissolved BAK-CMC solution.

[0030] The method of Example 1 yielded 300 mL of an aqueous composition comprising: 0.133% sodium hyaluronate, 0.0033% BAK, and 0.33% CMC.

EXAMPLE 2

Sodium Hyaluronate, BAK, CMC Composition Prepared in Three Parts

[0031] 1. Dissolve a quantity of sodium hyaluronate in 100 mL of water to a concentration of 0.6%.
2. Dissolve a quantity of CMC in 100 mL of water to a concentration of 1.5%.
3. Dissolve a quantity of BAK in 100 mL of water to a concentration of 0.015%.
4. Add the dissolved sodium hyaluronate solution to the dissolved BAK solution.
5. Add the dissolved CMC solution to the combined sodium hyaluronate-BAK solution.
6. Filter the combined sodium hyaluronate-BAK-CMC solution.

[0032] The method of Example 2 yielded 300 mL of an aqueous composition comprising: 0.2% sodium hyaluronate, 0.005% BAK, and 0.5% CMC. The filtered solution had a transmittance of about 100%.

[0033] The foregoing description of various aspects of the invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and obviously, many modifications and variations are possible. Such modifications and variations that may be apparent to a person skilled in the art are intended to be included within the scope of the invention as defined by the accompanying claims.