Use of carrageenans in topical ophthalmic compositions

• US 5,403,841 A
• Filed: 08/18/1993
• Issued: 04/04/1995
• Est. Priority Date: 01/15/1991
• Status: Expired due to Term

• Current Assignee: Alcon Research Limited (Nestle SA)
• Original Assignee: Alcon Laboratories Incorporated (Alcon Incorporated)
• Inventors: Keister, Jamieson C., Missel, Paul J. T., Stancioff, Dimitri J., Lang, John C.
• Primary Examiner(s): FAY, ZOHREH A
• Application Number:
  US08/108,824
• Time in Patent Office: 594 Days
• Field of Search: 514/392, 514/54, 514/226.8, 514/912
• US Class Current: 514/226.8
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears

Abstract

Topical ophthalmic compositions of carrageenans which are administrable as a drop but which become more viscous or gel upon instillation in the eye are disclosed. Methods for use of the compositions as topical ophthalmic vehicles for pharmaceutically active agents, and alone as lubricants or tear supplements, are also disclosed.

Claims

1. A method of delivering a drug to the eye which comprises topically administering a composition comprising a drug and a carrageenan capable of gelation upon exposure to sodium ions at concentrations found in lachrymal fluid, wherein the carrageenan is present at a concentration which allows the composition to be administrable as a drop which gels upon instillation to the eye, wherein the carrageenan has not more than about 1.0 sulfate moieties per disaccharide repeating unit.

2. The method of claim 1 wherein the carrageenan concentration is between about 0.1% to about 3.0% by weight/volume.

3. The method of claim 1 wherein the carrageenan has an average of less than about 0.5 sulfate moieties per disaccharide repeating unit.

4. The method of claim 1 wherein said carrageenan is extracted from Eucheuma gelatinae.

5. The method of claim 1 wherein said carrageenan is extracted from Furcellaria fastigiata.

6. The method of claim 1 wherein the drug is para-amino clonidine.

7. The method of claim 1 wherein the drug is a carbonic anhydrase inhibitor.

8. The method of claim 7 wherein the carbonic anhydrase inhibitor is (+)-4-ethylamino-2,3-dihydro-4H-2-methylthieno[3,2-e ]-1,2-thiazine-6-sulfonamide-1,1-dioxide or a pharmaceutically acceptable salt thereof.

9. The method of claim 1, wherein said carrageenan is extracted from an algae selected from the group consisting of:

Eucheuma gelatinae, Eucheuma speciosum, Endocladia muricata, Furcellaria fastigiata and Eucheuma cottonii.

10. The method of claim 1 wherein the pre-dosed viscosity is in the range of about 1 to about 500 cps and the post-dosed viscosity is greater than about 50 cps.

11. The method of claim 1 wherein the pre-dosed viscosity is in the range of about 1 to about 500 cps and the post-dosed gel has a modulus of elasticity in the range of 1×

10⁴ to about 5×

10⁵ dynes/cm³.

12. The method of claim 1 wherein the pre-dosed modulus of elasticity is in the range of about 1×

10⁴ to about 3×

10⁵ dynes/cm² and the post-dosed modulus of elasticity is in the range of about 1×

10⁴ to about 2×

10⁶ dynes/cm².

13. The method of claim 1 wherein the composition is thixotropic, having a pre-dosed modulus of elasticity in the range of about 1×

10⁴ to about 2×

10⁵ dynes/cm² and, when shaken, a pre-dosed viscosity in the range of about 1 to about 5000 cps and having a post-dosed modulus of elasticity in the range of about 1×

10⁴ to about 2×

10⁶ dynes/cm².