Stable ophthalmic oil-in-water emulsions with sodium hyaluronate for alleviating dry eye

• US 20050196370A1
• Filed: 04/04/2005
• Published: 09/08/2005
• Est. Priority Date: 03/18/2003
• Status: Abandoned Application

• Current Assignee: Advanced Medical Optics Incorporated (Johnson & Johnson)
• Original Assignee: Advanced Medical Optics Incorporated (Johnson & Johnson)
• Inventors: Crawford, Lauren L., Cook, James N., Yu, Zhi-Jian, Huth, Stanley W.
• Application Number:
  US11/098,827
• Publication Number:
  US 20050196370A1
• Time in Patent Office: Days
• US Class Current: 424/70.13
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 36/535 Perilla (beefsteak plant)
• CPC Class Codes: A61K 36/55 Linaceae (Flax family), e.g. Linum
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/08 containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61L 12/141 Biguanides, e.g. chlorhexidine
• CPC Class Codes: A61L 12/142 Polymeric biguanides
• CPC Class Codes: A61L 12/143 Quaternary ammonium compounds
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions

Abstract

Stable oil-in-water emulsions are described which contain a demulcent for the treatment of dry eye such as sodium hyaluronate. The oil-in-water emulsions are stable and have anti-microbial activity sufficient for use as contact lens disinfecting solutions.

Claims

1. A self-emulsifying composition comprising:

oil globules having an average size of less than 1 micron dispersed in an aqueous phase, said globules comprising;

(a) a surfactant component;

(b) a polar oil component, said surfactant component and said oil component selected to self-emulsify when mixed without mechanical homogenization; and

(c) a first therapeutic component comprising a water-soluble polymer.

2. The self-emulsifying composition of claim 1, wherein the surfactant component consists essentially of one or two surfactants.

3. The self-emulsifying composition of claim 1, wherein the water soluble polymer is selected from the group consisting of hyaluronic acid and salts thereof, polyvinylpyrrolidone (PVP), cellulose polymers, dextran 70, gelatin, polyethylene glycols and polyvinyl alcohol.

4. The self-emulsifying composition of claim 3, wherein the cellulose polymer is carboxymethylcellulose or hydroxypropyl methylcellulose.

5. The self-emulsifying composition of claim 3, wherein the polyethylene glycol is PEG 300 or PEG 400.

6. The self-emulsifying composition of claim 1, wherein the oil component comprises castor oil or a natural oil.

7. The self-emulsifying composition of claim 1, further comprising a chlorite preservative component.

8. The self-emulsifying composition of claim 7, wherein the chlorite preservative component is selected from the group consisting of stabilized chlorine dioxide (SCD), metal chlorites, and mixtures thereof.

9. The self-emulsifying composition of claim 1, which further comprises a cationic antimicrobial selected from the group consisting of poly[dimethylimino-w-butene-1,4-diyl]chloride, alpha-[4-tris(2-hydroxyethyl)ammonium]-dichloride (Polyquaternium 1®

), poly (oxyethyl(dimethyliminio)ethylene dmethyliminio)ethylene dichloride (WSCP®

), polyhexamethylene biguanide (PHMB), polyaminopropyl biguanide (PAPB), benzalkonium halides, salts of alexidine, alexidine-free base, salts of chlorhexidine, hexetidine, alkylamines, alkyl di- and tri-amine, tromethamine(2-amino-2-hydroxymethyl-1,3 propanediol), Octenidine (N,N′

-(1,10-Decanediyldi-1-(4H)-pyridinyl-4-ylidenebis-[1-octanamine]dihydrochloride, hexamethylene biguanides and their polymers, cetylpyridinium chloride, cetylpyridinium salts, antimicrobial polypeptides, and mixtures thereof.

10. The self-emulsifying composition of claim 1, wherein the surfactant component has a hydrophobic portion which comprises a first part oriented proximal to the aqueous phase that is larger than a second part of the hydrophobic portion of the surfactant component oriented towards the interior of the oil globule.

11. The self-emulsifying composition of claim 10 wherein the surfactant component consists essentially of one surfactant with the first part of the hydrophobic portion of the surfactant that contains more atoms than the second part of the hydrophobic portion of the surfactant.

12. The self-emulsifying composition of claim 10, wherein the surfactant component consists essentially of two surfactants, a first of said surfactants comprising a first hydrophobic portion and a second of said surfactants comprising a second hydrophobic portion, said first hydrophobic portion having a longer chain length than the second hydrophobic portion.

13. A self-emulsifying composition according to claim 1, further comprising an additional surfactant that does not interfere with self-emulsification.

14. The self-emulsifying composition of claim 1, wherein the surfactant component is selected from the group consisting of (a) a compound having at least one ether formed from at least about 1 to 100 ethylene oxide units and at least one fatty alcohol chain having from at least about 12 to 22 carbon atoms;

(b) a compound having at least one ester formed from at least about 1 to 100 ethylene oxide units and at least one fatty acid chain having from at least about 12 to 22 carbon atoms;

(c) a compound having at least one ether, ester or amide formed from at least about 1 to 100 ethylene oxide units and at least one vitamin or vitamin derivative; and

(d) combinations thereof consisting of no more than two surfactants.

15. The self-emulsifying composition of claim 1, wherein the surfactant component is selected from the group consisting of Lumulse GRH-40 and TPGS.

16. The self-emulsifying composition of claim 1, wherein the oil globules have an average size of less than about 0.25 micron.

17. The self-emulsifying composition of claim 1, wherein the oil globules have an average size of less than about 0.15 micron.

18. The self-emulsifying composition of claim 1, further comprising a cationic antimicrobial component having an HLB value significantly higher than an HLB value of the polar oil component.

19. A therapeutic composition comprising the self-emulsifying composition of claim 1 and a second therapeutic component.

20. The therapeutic composition of claim 19, wherein the second therapeutic component is selected from the group consisting of cyclosporin, prostaglandins, Brimonidine, and Brimonidine salts.

21. A therapeutic composition comprising the self-emulsifying composition of claim 14, further comprising a second therapeutic component.

22. The therapeutic composition of claim 21, wherein the second therapeutic component is selected from the group consisting of cyclosporin, prostaglandins, Brimonidine, and Brimonidine salts.

23. The self-emulsifying composition of claim 1, wherein the self-emulsifying compposition is a multipurpose solution for contact lenses.

24. A method of treating an eye comprising administering the self-emulsifying composition of claim 1 to an individual in need thereof.

25. The method of claim 24, wherein the treatment is for dry eye.

26. The method of claim 24, wherein the individual is a mammal.

27. A method of preparing a self-emulsifying composition comprising:

preparing an oil phase comprising a polar oil and a surfactant component, wherein the polar oil and the surfactant component in the oil phase are in the liquid state;

preparing an aqueous phase at a temperature that permits self-emulsification;

wherein the aqueous phase comprises a water soluble polymer; and

mixing the oil phase and the aqueous phase to form an emulsion, without mechanical homogenization.

28. A method of preparing a self-emulsifying composition according to claim 27, further comprising forming a paste between the oil phase and a part of the aqueous phase and mixing the paste with the rest of the aqueous phase to form an emulsion.

29. The method of preparing a self-emulsifying composition according to claim 27, wherein the water soluble polymer is selected from the group consisting of hyaluronic acid and salts thereof, polyvinylpyrrolidone (PVP), cellulose polymers, dextran 70, gelatin, polyethylene glycol and polyvinyl alcohol.

30. The method of claim 29, wherein the cellulose polymer is carboxymethylcellulose or hydroxypropyl methylcellulose.

31. The method of claim 29, wherein the polyethylene glycol is PEG 300 or PEG 400.

32. The method of preparing a self-emulsifying composition according to claim 27, wherein the surfactant component consists essentially of one or two surfactants.