Compositions and methods for treating presbyopia, mild hyperopia, and irregular astigmatism

Abstract

The present invention is directed to compositions and methods for treating ocular conditions, including presbyopia, mild hyperopia, irregular astigmatism, hyperopic accommodative esotropia, and glaucoma. The compositions can also be used to potentiate or enhance interventions that retard, reverse, or modify the aging process of the crystalline lens and its surrounding tissues. The compositions include a cholinergic agent, such as a muscarinic acetylcholine receptor M3 agonist, and an alpha agonist having an imidazoline group or a non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity. It has been found that an alpha agonist having an imidazoline group or non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity in combination with a cholinergic agent, such as pilocarpine, act synergistically to improve the accommodative and focusing ability of the eye while minimizing the side effects from each compound.

1 . A composition for treatment of an ocular condition, comprising a muscarinic acetylcholine receptor M 3  agonist and at least one of the following:
 an alpha-stimulant agonist having an imidazoline group; or   a non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity;   wherein the ocular condition comprises presbyopia, mild hyperopia, irregular astigmatism, hyperopic accommodative esotropia, or glaucoma.   
     
     
         2 . The composition of  claim 1 , wherein the composition comprises:
 from about 0.01% to about 4% w/w muscarinic acetylcholine receptor M 3  agonist; and   from about 0.01% to about 0.5% w/w alpha-stimulant agonist having an imidazoline group or about 0.01% to about 2% NSAID having COX-2 selectivity, or both.   
     
     
         3 . The composition of  claim 1 , wherein the composition comprises:
 from about 0.01% to about 2% w/w muscarinic acetylcholine receptor M 3  agonist; and   from about 0.01% to about 0.2% w/w alpha-stimulant agonist having an imidazoline group or about 0.01% to about 1% NSAID having COX-2 selectivity, or both.   
     
     
         4 . The composition of  claim 1 , wherein the composition comprises:
 from about 0.5% to about 1.5% w/w muscarinic acetylcholine receptor M 3  agonist; and   from about 0.02% to about 0.1% w/w alpha-stimulant agonist having an imidazoline group or NSAID having COX-2 selectivity.   
     
     
         5 . The composition of  claim 1 , wherein the muscarinic acetylcholine receptor M 3  agonist comprises acetylcholine, bethanechol, carbachol, oxotremorine, pilocarpidine, or pilocarpine. 
     
     
         6 . The composition of  claim 1 , wherein the muscarinic acetylcholine receptor M 3  agonist is pilocarpine. 
     
     
         7 . The composition of  claim 1 , wherein the muscarinic acetylcholine receptor M 3  agonist is carbachol. 
     
     
         8 . The composition of  claim 1 , wherein the alpha-stimulant agonist comprises oxymetazoline, naphazoline, tetrahydrozoline, tramazoline, or xylometazoline. 
     
     
         9 . The composition of  claim 1 , wherein the alpha-stimulant agonist is oxymetazoline. 
     
     
         10 . The composition of  claim 1 , wherein the alpha-stimulant agonist is naphazoline. 
     
     
         11 . The composition of  claim 1 , wherein the alpha-stimulant agonist is tetrahydrozoline. 
     
     
         12 . The composition of  claim 1 , wherein the NSAID having COX-2 selectivity comprises meloxicam, celecoxib, rofecoxib, valdecoxib, parecoxib, etoricoxib, nimesulide, etodolac or nabumetone. 
     
     
         13 . The composition of  claim 1 , wherein the NSAID having COX-2 selectivity is meloxicam. 
     
     
         14 . The composition of  claim 1 , wherein the composition further comprises an ophthalmically acceptable carrier. 
     
     
         15 . The composition of  claim 1 , wherein the composition further comprises a cyclodextrin or derivative thereof to enhance ocular penetration of the composition. 
     
     
         16 . The composition of  claim 1 , wherein the composition is in the form of an eye drop, suspension, gel, ointment, injectable solution, or spray. 
     
     
         17 . A method of treating presbyopia in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a therapeutically effective amount of a muscarinic acetylcholine rececptor M 3  agonist and at least one of the following:
 an alpha-stimulant agonist having an imidazoline group; or   a non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity.   
     
     
         18 . A method of treating mild hyperopia in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a therapeutically effective amount of a muscarinic acetylcholine receptor M 3  agonist and at least one of the following:
 an alpha-stimulant agonist having an imidazoline group; or   a non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity.   
     
     
         19 . A method of treating irregular astigmatism in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a therapeutically effective amount of a muscarinic acetylcholine receptor M 3  agonist and at least one of the following:
 an alpha-stimulant agonist having an imidazoline group; or   a non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity.   
     
     
         20 . A method of treating hyperopic accommodative esotropia in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a therapeutically effective amount of a muscarinic acetylcholine receptor M 3  agonist and at least one of the following:
 an alpha-stimulant agonist having an imidazoline group; or   a non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity.   
     
     
         21 . A method of treating glaucoma in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a therapeutically effective amount of a muscarinic acetylcholine receptor M 3  agonist and at least one of the following:
 an alpha-stimulant agonist having an imidazoline group; or   a non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity.   
     
     
         22 . A method of potentiating or enhancing interventions that retard, reverse, or modify the aging process of the crystalline lens and its surrounding tissues, in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a therapeutically effective amount of a muscarinic acetylcholine receptor M 3  agonist and at least one of the following:
 an alpha-stimulant agonist having an imidazoline group; or   a non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity.   
     
     
         23 . The method of  claim 27 , wherein administering comprises administering the composition to an eye of the subject. 
     
     
         24 . The method of  claim 23 , wherein the composition is administered to only one eye of the subject. 
     
     
         25 . The method of  claim 27 , wherein the composition increases refractive power of an eye of the subject by up to about 4.0 diopters. 
     
     
         26 . The method of  claim 27 , wherein the subject is human. 
     
     
         27 . A method of treating an ocular condition in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a therapeutically effective amount of pilocarpine and at least one of the following:
 an alpha-stimulant agonist having an imidazoline group; or   a non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity.   
     
     
         28 . The method of  claim 27  wherein the ocular condition comprises presbyopia, mild hyperopia, irregular astigmatism, hyperopic accommodative esotropia, or glaucoma. 
     
     
         29 . The method of  claim 27  wherein the ocular condition could alternatively be corrected with eye glasses having about +0.5D to about +1.0D lenses and wherein the therapeutically effective amount comprises from about 0.3% to about 1.0% pilocarpine. 
     
     
         30 . The method of  claim 27  wherein the ocular condition could alternatively be corrected with eye glasses having about +1.0D to about +1.5D lenses and wherein the therapeutically effective amount comprises from about 0.8% to about 1.6% pilocarpine. 
     
     
         31 . The method of  claim 27  wherein the ocular condition could alternatively be corrected with eye glasses having about +1.5D to about +2.0D lenses and wherein the therapeutically effective amount comprises from about 1.4% to about 2.2% pilocarpine.