METHOD AND COMPOSITION FOR TREATING OCULAR HYPERTENSION AND GLAUCOMA

• US 20110152264A1
• Filed: 05/28/2009
• Published: 06/23/2011
• Est. Priority Date: 05/30/2008
• Status: Active Grant

• Current Assignee: AGC, Inc., Santen Pharmaceutical Company Limited
• Original Assignee: Asahi Glass Company, Limited (AGC, Inc.), Santen Pharmaceutical Company Limited
• Inventors: Lehmussaari, Kari, Oksala, Olli, Reunamaki, Timo, Pellinen, Pertti
• Granted Patent: US 9,999,593 B2
• Time in Patent Office: Days
• US Class Current: 514/236.2
• CPC Class Codes: A61K 31/5575 having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• 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 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to an ophthalmic aqueous composition containing PGF2α analogues for treating ocular hypertension and glaucoma, to a method for treating ocular hypertension and glaucoma by administering said composition to a subject in need of such treatment, and to a method for increasing aqueous solubility and stability of PGF2α analogues in an aqueous composition.

Claims

1. An ophthalmic aqueous solution for treating ocular hypertension and glaucoma, comprising PGF2α

analogue as an active ingredient, wherein said ophthalmic aqueous solution contains nonionic surfactant, stabilizing agent and substantially no preservatives in a container consisting essentially of polyethylene.

2. The ophthalmic aqueous solution according to claim 1 wherein the PGF2α

analogue is selected from the group consisting of latanoprost, isopropyl unoprostone, travoprost, bimatoprost and tafluprost or a mixture of two or more thereof.

3. The ophthalmic aqueous solution according to claim 1 wherein the PGF2α

analogue is tafluprost.

4. The ophthalmic aqueous solution according to claim 1 in a container comprising minor amounts of polypropylene, polyethylene terephthalate, polyvinyl chloride, acrylic resins, polystyrene, polymethyl methacrylate or nylon 6.

5. The ophthalmic aqueous solution according to claim 1 wherein the nonionic surfactant is selected from the group consisting of polyoxyethylene fatty esters such as polysorbate 80 [poly(oxyethylene) sorbitan monooleate], polysorbate 60 [poly(oxyethylene)sorbitan monostearate], polysorbate 40 [poly(oxyethylene)sorbitan monopalmitate], poly(oxyethylene)sorbitan monolaurate, poly(oxyethylene)sorbitan trioleate and polysorbate 65 [poly(oxyethylene)sorbitan tristearate], polyoxyethylene hydrogenated castor oils such as polyoxyethylene hydrogenated castor oil 10, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50 and polyoxyethylene hydrogenated castor oil 60, polyoxyethylene polyoxypropylene glycols such as polyoxyethylene (160) polyoxypropylene (30) glycol [pluronic F68], polyoxyethylene (42) polyoxypropylene (67) glycol [Pluronic P123], polyoxyethylene (54) polyoxypropylene (39) glycol [Pluronic P85], polyoxyethylene (196) polyoxypropylene (67) glycol [Pluronic F127] and polyoxyethylene (20) polyoxypropylene (20) glycol [Pluronic L-44], polyoxyl 40 stearate and sucrose fatty esters.

6. The ophthalmic aqueous solution according to claim 5, wherein the nonionic surfactant is polysorbate 80 or castor oil.

7. The ophthalmic aqueous solution according to claim 1 wherein the amount of the non-ionic surfactant is 0.05 to 0.5% (w/v), preferably 0.05 to 0.1% (w/v), and even more preferably about 0.075% (w/v).

8. The ophthalmic aqueous solution according to claim 1 wherein the stabilizing agent is selected from the group consisting of ethylenediaminetetraacetic acid and salts thereof, sodium nitrite, ascorbic acid, L-ascorbic acid stearate, sodium hydrogensulfite, alphathioglycerin, erythorbic acid, cysteine hydrochloride, citric acid, tocopherol acetate, potassium dichloroisocyanurate, 2,6-di-t-butyl-4-methylphenol, soybean lecithin, sodium thioglycollate, sodium thiomalate, natural vitamin E, tocopherol, ascorbyl pasthyminate, sodium pyrosulfite, butylhydroxyanisole, 1,3-butylene glycol, pentaerythtyl tetrakis[3-(3,5-di-t-butyl-4-hydroxyphenyl)]propionate, propyl gallate, 2-mercaptobenzimidazole and oxyquinoline sulphate.

9. The ophthalmic aqueous solution according to claim 8 wherein the stabilizing agent is disodium edetate.

10. The ophthalmic aqueous solution according to claim 1 wherein the amount of the stabilizing agent is 0.005 to 0.2%, preferably 0.01 to 0.1%, even more preferably about 0.05% (w/v).

11. The ophthalmic aqueous solution according to claim 1 in a single dose form.

12. The ophthalmic aqueous solution according to claim 1 comprising at least one further pharmaceutically active substance, such as timolol.

13. An ophthalmic aqueous solution comprising

0.0001-0.01% w/v PGF2α

analogue;

0.05-0.5% w/v non-ionic surfactant,

0.005-0.2% w/v stabilizing agent, and

optionally buffering agents, pH adjusters and tonicity agents conventionally used in ophthalmic solutions, and substantially no preservatives, in a container consisting essentially of polyethylene or in contact with container material consisting essentially of polyethylene.

16. The ophthalmic aqueous solution according to claim 13 in a container comprising minor amounts of polypropylene, polyethylene terephthalate, polyvinyl chloride, acrylic resins, polystyrene, polymethyl methacrylate or nylon 6.

17. The ophthalmic aqueous solution according to claim 13 in a single dose or unit dose form.

18. The ophthalmic aqueous solution according to claim 13 in a fluid dispenser form.

14. An ophthalmic aqueous solution comprising

0.0010-0.0015% w/v tafluprost;

0.05-0.1% w/v polysorbate 80,

0.01-0.1% w/v disodium edetate, and

optionally buffering agents, pH adjusters and tonicity agents conventionally used in ophthalmic solutions, and substantially no preservatives, in a container consisting essentially of polyethylene or in contact with container material consisting essentially of polyethylene.

15. An ophthalmic aqueous solution, comprising

0.0015% w/v tafluprost

0.075% w/v polysorbate 80,

0.05% w/v disodium edetate,

2.25% w/v glycerol,

0.2% w/v sodium dihydrogen phosphate dihydrate,

pH adjusters, and substantially no preservatives, in a container consisting essentially of polyethylene or in contact with container material consisting essentially of polyethylene.

19. A method for increasing aqueous solubility and improving stability of PGF2α

analogues in an aqueous ophthalmic solution, comprising the steps of preparing an aqueous ophthalmic solution containing PGF2α

analogue, nonionic surfactant, stabilizing agent and substantially no preservatives, and packaging the preservative-free ophthalmic solution in a container consisting essentially of polyethylene or in contact with container material consisting essentially of polyethylene.

20. (canceled)

21. (canceled)

22. A method for treating ocular hypertension and glaucoma, which comprises administration of an ophthalmic aqueous solution comprising PGF2α

analogue as an active ingredient thereof to a subject in need of said treatment, wherein said ophthalmic solution comprises nonionic surfactant, stabilizing agent, and substantially no preservatives.