Ophthalmic composition containing a carbonic anhydrase inhibitor and xanthan gum

• US 6,264,935 B1
• Filed: 06/14/1999
• Issued: 07/24/2001
• Est. Priority Date: 10/17/1996
• Status: Expired due to Fees

• Current Assignee: Laboratories MSD - Chibret
• Original Assignee: Laboratories MSD - Chibret
• Inventors: Chastaing, Gilles, Plazonnet, Bernard, Rozier, Annouk
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US09/284,718
• Time in Patent Office: 771 Days
• Field of Search: 424/78.04, 424/427, 424/428, 514/782, 514/913
• US Class Current: 424/78.04
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/38 having sulfur as a ring hetero atom
• CPC Class Codes: A61K 31/382 having six-membered rings, e.g. thioxanthenes thiothixene A61K31/496
• CPC Class Codes: A61K 31/535 having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics

Abstract

The present invention relates to ophthalmic compositions for the treatment of ocular hypertension and glaucoma, comprising a hypotonic solution of 0.1 to 0.2% (w/w) of xanthan gum and 0.5 to 5% (w/w) of a topical carbonic anhydrase inhibitor or an ophthalmologically acceptable salt thereof.

Claims

1. An ophthalmic composition for the treatment of ocular hypertension and glaucoma in a subject in need thereof, comprising a hypotonic solution of 0.1 to 2% (w/w) of xanthan gum and 0.5 to 5% (w/w) of a topical carbonic anhydrase inhibitor of the structural formula:

an individual diastereomer, an individual enantiomer or mixture thereof, or an ophthalmologically acceptable salt thereof, wherein;

A is carbon or nitrogen;

Z is —

NHR or —

OR;

R is C_1-6alkyl, either straight or branched chain;

R¹ is

(a) hydrogen,

(b) C_1-3alkyl, or

(c) C_1-4alkoxy-C_1-4alkyl; and

X is —

SO₂—

or —

C(O)—

.

2. The composition of claim 1 wherein A is carbon, Z is —

NHR, and X is —

SO₂—

.

3. The composition of claim 1 or 2 wherein:

R is

a) —

CH₂CH₃,

b) —

CH₂CH₂CH₃, or

c) —

CH₂CH(CH₃)₂; and

R¹ is

a) hydrogen,

b) —

CH₃,

c)—

CH₂CH₃,

d) —

CH₂CH₂CH₃,

e) —

CH₂CH₂CH₂OCH₃, or

f) —

CH₂0CH₂CH₃.

4. The composition of any one of claims 1 to 3 wherein A is carbon;

and wherein;

R is —

CH₂CH₃ and R¹ is —

CH₃;

or R is —

CH₂CH₂CH₃ and R¹ is —

CH₂CH₂CH₂OCH₃;

or R is —

CH₂CH₃ and R¹ is —

CH₂CH₂CH₃;

or R is —

CH₂CH₂(CH₃)₂ and R¹ is hydrogen;

or R is —

CH₂CH₃ and R¹ is —

CH₂OCH₂CH₃; and

carbons 4 and 6 of the topical carbonic anhydrase inhibitor both have S absolute stereochemical configuration.

5. The composition of claim 1 wherein the topical carbonic anhydrase inhibitor is (S,S)-(−

)-5,6-dihydro4-ethylamino-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide-7,7-dioxide hydrochloride.

6. The composition of any one of claims 1 to 5 wherein the concentration of carbonic anhydrase inhibitor is 2.0% (w/w).

7. The composition of any one of claims 1 to 6 wherein the concentration of xanthan gum is 0.4 to 0.7% (w/w).

8. The composition of any one of claims 1 to 7 wherein the freezing point depression of the hypotonic solution is between −

0.28°

C. and −

0.4°

C.

9. The composition of any one of claims 1 to 7 wherein the hypotonicity of the solution is between 150 and 215 mOs/kg.

10. The composition of any one of claims 1 to 9 which additionally comprises about 0.01 to 1% (w/w) of a β

-adrenergic receptor blocking agent, or an ophthalmologically acceptable salt thereof.

11. A composition of claim 10 wherein the concentratoion of β

-adrenergic receptor blocking agent is about 0.1 to 0.5% (w/w).

12. A composition of claim 10 or claim 11 in which the β

-adrenergic receptor blocking agent is timolol maleate.

13. A method of treating ocular hypertension or glaucoma which comprises the topical ocular administration to a patient in need of such treatment of a unit dose of the composition of any one of claims 1 to 12.