Ophthalmic Solutions

• US 20080050335A1
• Filed: 07/24/2007
• Published: 02/28/2008
• Est. Priority Date: 07/25/2006
• Status: Abandoned Application

• Current Assignee: Osmotica Kereskedelmi Es Szolgaltato Kft (Osmotica Pharmaceuticals Plc)
• Original Assignee: Osmotica Corp.
• Inventors: FAOUR, Joaquina, PASTINI, Ana
• Application Number:
  US11/782,135
• Publication Number:
  US 20080050335A1
• Time in Patent Office: Days
• US Class Current: 424/78.04
• CPC Class Codes: A61K 31/382 having six-membered rings, e.g. thioxanthenes thiothixene A61K31/496
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 27/04 Artificial tears; Irrigation solutions

Abstract

Aqueous ophthalmic solutions containing a combination of hyaluronic acid or a pharmaceutically acceptable salt thereof, e.g. sodium hyaluronate, and polyvinyl alcohol are disclosed. These solutions have a synergistic effect on viscosity and provide a statistically significant improvement over the prior art formulations. The solutions are used as artificial tear for the treatment of dry eye syndrome and ocular discomfort and may be administered whenever the use of artificial tears is advisable. The solutions are also suitable for use as vehicle for ophthalmic drugs.

Claims

1. An aqueous ophthalmic solution comprising a viscosity enhancing amount of the combination of 0.05 to 0.4% w/v hyaluronic acid or a pharmaceutically acceptable salt thereof, and 0.25 to 4.0% w/v polyvinyl alcohol, wherein the solution has a viscosity of 20 to 150 centistoke and is buffered to a pH 5.0 to 8.5.

2. The solution of claim 1, all the limitations of which are hereby incorporated by reference, wherein the solution has less than 0.6% w/v the one or more ionic-tonicity agents.

3. The solution of claim 2, all the limitations of which are hereby incorporated by reference, wherein the pharmaceutically acceptable salt of hyaluronic acid is sodium hyaluronate.

4. The solution of claim 3, all the limitations of which are hereby incorporated by reference, wherein the content of sodium hyaluronate ranges from 0.05 to 0.3% w/v.

8. The solution of claim 4, all the limitations of which are hereby incorporated by reference, wherein the content of polyvinyl alcohol ranges from 0.25 to 3% w/v.

10. The solution of claim 8, all the limitations of which are hereby incorporated by reference, further comprising one or more pharmaceutically acceptable agents selected from the group consisting of buffering agents, preservative agents, preservative adjuncts, surfactants, solubilizing agents, stabilizing agents, comfort-enhancing agents, emollients, pH-adjusting agents, demulcents, lubricants, and mixtures thereof.

11. The solution of claim 10, all the limitations of which are hereby incorporated by reference, wherein

the buffering agent is selected from the group consisting of boric acid, dibasic sodium phosphate, monobasic sodium phosphate, hydrochloric acid, sodium hydroxide, tris(hydroxymethyl)aminomethane, bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane, sodium hydrogen carbonate, and mixtures thereof;

the preservative agent is selected from the group consisting of benzalkonium chloride, per-salts, alcohols, peroxides, preservative agents containing quaternary ammonium salts, biguanide-containing preservatives, chlorine dioxide precursors, metal chlorites, sorbic acid and ophthalmically acceptable salts thereof, and mixtures thereof;

the demulcent is selected from the group consisting of glycerin, propylene glycol, hydroxypropyl methyl cellulose, carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, polyvinyl pyrrolidone, polyethylene oxide polyethylene glycol, polyacrylic acid, and mixtures thereof; and

the lubricant is selected from the group consisting of polyethylene glycol, cellulose derivatives, dextran 70, gelatin, glycerin, polysorbate 80, propylene glycol, povidone, and mixtures thereof.

12. The solution of claim 11, all the limitations of which are hereby incorporated by reference, wherein the content of monobasic sodium phosphate is about 0.05% w/v.

14. The solution of claim 11, all the limitations of which are hereby incorporated by reference, wherein the biguanide-containing preservative is polyhexamethylene biguanide or benzalkonium chloride.

15. The solution of claim 14, all the limitations of which are hereby incorporated by reference, wherein the content of polyhexamethylene biguanide is about 0.001% w/v or the content of benzalkonium chloride ranges from about 0.01 to about 0.10% w/v.

19. The solution of claim 11, all the limitations of which are hereby incorporated by reference, wherein the ophthalmically acceptable salt of sorbic acid is potassium sorbate.

20. The solution of claim 19, all the limitations of which are hereby incorporated by reference, wherein the content of potassium sorbate ranges from about 0.10 to about 0.20% w/v.

22. The solution of claim 1, all the limitations of which are hereby incorporated by reference, further comprising a tonicity agent.

23. The solution of claim 22, all the limitations of which are hereby incorporated by reference, wherein the tonicity agent is selected from the group consisting of inorganic salts, electrolytes, sodium chloride, potassium chloride, sodium phosphate, potassium phosphate, sodium, potassium sulfates, sodium and potassium bicarbonates, alkaline earth metal salts, mannitol, dextrose, glycerin, propylene glycol, and mixtures thereof.

24. The solution of claim 2, all the limitations of which are hereby incorporated by reference, wherein the ionic-tonicity agent is sodium chloride.

25. The solution of claim 24, all the limitations of which are hereby incorporated by reference, wherein the content of sodium chloride is about 0.1% to about 0.38% w/v.

29. The solution of claim 11, all the limitations of which are hereby incorporated by reference, wherein the content of propylene glycol is about 1.0% w/v.

32. The solution of claim 11, all the limitations of which are hereby incorporated by reference, wherein the content of polyethylene glycol is about 0.4% w/v.

33. The solution of claim 1, all the limitations of which are hereby incorporated by reference, further comprising one or more active agents.

34. The solution of claim 33, all the limitations of which are hereby incorporated by reference, wherein the active agent is selected from the group consisting of anti-glaucoma agent, anti-infective agent, anti-inflammatory agent, antihistamine, anti-allergic agent, decongestant, hormone, vitamin, growth factor, cytokine, mucin, surface stimulating drug, immunomodulator, immune response modifier, cytokine modifying agent, immunosuppressive agent, antineoplastic agent, anti-angiogenesis agent, eyelash growth stimulators, and combinations thereof.

35. The solution of claim 34, all the limitations of which are hereby incorporated by reference, wherein the anti-glaucoma agent is selected from the group consisting of beta-blocker, miotic agent, carbonic anhydrase inhibitor, prostaglandin serotonergic, muscarinic, dopaminergic agonist, adrenergic agonist, and a combination thereof.

36. The solution of claim 35, all the limitations of which are hereby incorporated by reference, wherein the anti-glaucoma agent is selected from the group consisting of timolol, betaxolol, levobetaxolol, carteolol, metipranolol, levobunolol, pilocarpine, dorzolamide, brinzolamide, dorzolamide hydrochloride, travoprost, latanoprost, bimatoprost, apraclonidine, brimonidine, dipivefrin, and mixtures thereof.

49. The solution of claim 34, all the limitations of which are hereby incorporated by reference, wherein the anti-infective agent is selected from the group consisting of antibiotic, antimicrobial peptide, antiviral, antiparasitic, antifungal, and a combination thereof.

50. The solution of claim 49, all the limitations of which are hereby incorporated by reference, wherein the anti-infective agent is selected from the group consisting of ciprofloxacin, ofloxacin, moxifloxacin, tobramycin, gentamicin, sulfacetamide, trimethoprim, polymyxin B, trifluridine, and mixtures thereof.

56. The solution of claim 34, all the limitations of which are hereby incorporated by reference, wherein the anti-inflammatory agent is selected from the group consisting of non-steroidal anti-inflammatory agent, steroidal anti-inflammatory agent, and a combination thereof.

57. The solution of claim 56, all the limitations of which are hereby incorporated by reference, wherein the anti-inflammatory agent is selected from the group consisting of suprofen, flurbiprofen, diclofenac, ketorolac, rimexolone, tetrahydrocortisol, prednisolone, dexamethasone, and mixtures thereof.

60. The solution of claim 34, all the limitations of which are hereby incorporated by reference, wherein the anti-allergic agent is selected from the group consisting of olopatadine, cromolyn, lodoxamide, emedastine, epinastine, and mixtures thereof.

61. The solution of claim 34, all the limitations of which are hereby incorporated by reference, wherein the decongestant is selected from the group consisting of naphazoline, phenylephrine, and mixtures thereof.

62. The solution of claim 34, all the limitations of which are hereby incorporated by reference, wherein the hormone is an androgen.

63. The solution of claim 34, all the limitations of which are hereby incorporated by reference, wherein the growth factor is epidermal growth factor.

65. A method for treating conditions selected from the group consisting of dry eye syndrome, keratitis sicca, xerophthalmia, keratoconjunctivitis sicca, ocular discomfort, rhinological allergic complications, Sjogren'"'"'s syndrome, and Stevens Johnson syndrome comprising the step of administering a solution of claim 1, all the limitations of which are hereby incorporated by reference.

66. A method of lubricating an eye comprising the step of administering a solution of claim 1, all the limitations of which are hereby incorporated by reference.

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64. An ophthalmic solution comprising the following ingredients in the amounts indicated:

67. An aqueous ophthalmic solution comprising a viscosity enhancing amount of the combination of 0.05 to 0.3% w/v sodium hyaluronate, 0.25 to 3.0% w/v polyvinyl alcohol, about 0.05% w/v monobasic sodium phosphate, preservative, tonicity agent, demulcent, lubricant, one or more active agents, wherein the solution has a viscosity of 20 to 150 centistoke and is buffered to a pH 5.0 to 8.5, and the solution has less than 0.6% w/v the one or more ionic-tonicity agents.