Ophthalmic solution comprising diquafosol

Patent metadata

Field	Value
Publication number	US-9486529-B2
Application number	US-201314386169-A
Country	US
Kind code	B2
Filing date	Mar 25, 2013
Priority date	Mar 26, 2012
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

Regarding Diquafosol ophthalmic solution comprising a chelating agent at a concentration of 0.0001 to 1% (w/v), formation of insoluble precipitates found in Diquafosol ophthalmic solution during storage of the solution, as well as deterioration of the filtration performance in the course of production (course of filtration sterilization), have been inhibited. Further, in Diquafosol ophthalmic solution comprising a chelating agent, reduction of eye irritation and enhancement of the preservative effectiveness have been confirmed, in comparison to Diquafosol ophthalmic solution comprising no chelating agent. Accordingly, the present invention has been confirmed to provide physicochemical properties that are stable during the courses of production and distribution as well as the course of storage by a patient, and also reduce eye irritation and enhance preservative effectiveness.

First claim

The invention claimed is:

1. An aqueous ophthalmic solution consisting of diquafosol or a salt thereof at a concentration of 0.1 to 10% (w/v) and a chelating agent at a concentration of 0.0001 to 1% (w/v) and optionally containing at least one of a preservative, buffer agent, isotonizing agent, surfactant or pH adjuster, wherein the surfactant is selected from the group consisting of polyoxyl 40 stearate and polyoxyethylene hydrogenated castor oil.

2. The ophthalmic solution according to claim 1 , wherein the chelating agent is at least one type selected from the group consisting of edetic acid, citric acid, metaphosphoric acid, pyrophosphoric acid, polyphosphoric acid, malic acid, tartaric acid, phytic acid, and salts thereof.

3. The ophthalmic solution according to claim 1 , wherein the chelating agent is at least one type selected from the group consisting of edetic acid, citric acid, metaphosphoric acid, polyphosphoric acid, and salts thereof.

4. The ophthalmic solution according to claim 1 , wherein the chelating agent is a salt of edetic acid.

5. The ophthalmic solution according to claim 1 , wherein the chelating agent is at a concentration of 0.0005 to 0.5% (w/v) in the ophthalmic solution.

6. The ophthalmic solution according to claim 1 , wherein the chelating agent is at a concentration of 0.001 to 0.1% (w/v) in the ophthalmic solution.

7. The ophthalmic solution according to claim 1 , wherein diquafosol or a salt thereof is at a concentration of 1 to 10% (w/v) in the ophthalmic solution.

8. The ophthalmic solution according to claim 1 , wherein diquafosol or a salt thereof is at a concentration of 3% (w/v) in the ophthalmic solution.

9. The ophthalmic solution according to claim 1 , wherein the chelating agent is a salt of edetic acid, the chelating agent is at a concentration of 0.001 to 0.1% (w/v) in the ophthalmic solution, and diquafosol or a salt thereof is at a concentration of 3% (w/v) in the ophthalmic solution.

10. The ophthalmic solution according to claim 1 , wherein the ophthalmic solution contains the preservative.

11. A method for producing the aqueous ophthalmic solution of claim 1 , comprising the step of mixing diquafosol or a salt thereof and a chelating agent in an amount that causes a final concentration of the chelating agent in the aqueous ophthalmic solution to be 0.0001 to 1% (w/v), to obtain an aqueous solution in which formation of insoluble precipitates is inhibited.

12. The method according to claim 11 , further comprising the step of filtering the obtained aqueous solution through a filtration sterilization filter having a pore size of 0.1 to 0.5 μm.

13. A method for inhibiting formation of insoluble precipitates in the aqueous ophthalmic solution of claim 1 , the method comprising adding a chelating agent at a concentration of 0.0001 to 1% (w/v) to the aqueous ophthalmic solution.

14. A method for preparing the aqueous ophthalmic solution of claim 1 , the method comprising adding a chelating agent at a concentration of 0.0001 to 1% (w/v) to the aqueous ophthalmic solution.

15. A method for enhancing preservative effectiveness of the aqueous ophthalmic solution of claim 1 , the method comprising adding a chelating agent at a concentration of 0.0001 to 1% (w/v) to the aqueous ophthalmic solution.

16. The ophthalmic solution according to claim 1 , wherein the buffer agent is at least one type selected from the group consisting of sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium acetate, and epsilon aminocaproic acid.

17. The ophthalmic solution according to claim 1 , wherein the isotonizing agent is at least one type selected from the group consisting of sodium chloride, potassium chloride, and concentrated glycerin.

Assignees

• Santen Pharmaceutical Co Ltd
• Santen Pharmceutical Co Ltd

Inventors

• Sakatani Akiko
• Ikei Tatsuo
• Inagaki Koji
• Nakamura Masatsugu
• Hosoi Kazuhiro
• Saito Mikiko
• Sonoda Masaki
• Fukui Yoko
• Kuwano Mitsuaki

Classifications

• A61P27/02

  Ophthalmic agents · CPC title

• A61P27/04

  Artificial tears; Irrigation solutions · CPC title

• A61K47/12

  Carboxylic acids; Salts or anhydrides thereof · CPC title

• A61K9/0048

  Eye, e.g. artificial tears · CPC title

• A61K31/7084 Primary

  Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide · CPC title