Method of treating ocular allergy by topical application of a 2-substituted-1,2-benzisoselenazol-3(2H)-one

A method of treating an ocular allergy in a mammal comprising the topical application of an effective anaphylactic inhibiting amount of a compound of the formula: ##STR1## wherein R is phenyl or phenyl substituted lower alkyl, the phenyl group of each being unsubstituted or substituted by halo, lower alkyl, lower alkoxy, trifluoromethyl, nitro, di-loweralkylamino, cyano, carboxy, methylenedioxy, loweralkoxycarbonyl, carboxyloweralky, or loweralkoxycarbonyl-lower alkyl, or R is cycloalkyl of 5 to 10 carbon atoms; and PA1 R.sub.1 and R.sub.2 are independently hydrogen, halo, lower alkyl, lower alkoxy, hydroxy, trifluoromethyl, or nitro or R.sub.1 and R.sub.2 taken together are methylenedioxy; to the eye of said mammal in need of the same.

BACKGROUND OF THE INVENTION 
The instant invention relates to a method of treating an ocular allergy in 
a warm blooded mammal, including man, by topically applying an effective 
anaphylactic inhibiting amount of a 2-aryl, aralkyl or 
cycloalkyl-1,2-benzisoselenazol-3(2H)-one to the eye of said mammal in 
need of the same. 
The compounds useful in the practice of the present invention are known and 
are described as possessing anti-inflammatory properties, as see U.S. Pat. 
Nos. 4,352,799; 4,397,858; 4,418,069; and 4,454,068 the disclosures of 
which are incorporated by reference herein. 
It is now surprisingly been discovered that, in addition to the 
aforementioned anti-inflammatory properties, such 
2-substituted-1,2-benzoisoselenazol-3(2H)-one compounds surprisingly and 
unexpectedly possesses the property of inhibiting an allergic ocular 
condition upon topical application to the eye of the host. 
It is accordingly an object of the present invention to provide a method 
for treating ocular allergies. 
It is further object of the present invention to provide a method for 
inhibiting ocular anaphylactic reactions to environmental dusts, pollens, 
industrial irritants, and the like by topically administering to a 
mammalian host susceptible to such reactions an effective inhibiting 
amount of an ocular compatable composition containing a 
2-substituted-1,2-benzisoselenazol-3(2H)-one. 
It is yet a further object of the present invention to provide ocular 
compositions for use in such methods. 
These and other objects of the present invention are apparent from the 
following detailed description.

DETAILED DESCRIPTION OF THE INVENTION 
One embodiment of the present invention relates to a method of treating an 
ocular allergy in a mammal comprising the topical application to the eye 
of said mammal in need of the same an effective anaphylactic inhibiting 
amount of a compound of the formula 
##STR2## 
wherein R is phenyl or phenyl substituted lower alkyl, the phenyl group of 
each being unsubstituted or substituted by halo, lower alkyl, lower 
alkoxy, trifluoromethyl, nitro, di-loweralkylamino, cyano, carboxy, 
methylenedioxy, lower alkoxycarbonyl, carboxy-loweralkyl or lower 
alkoxycarbonyl substituted lower alkyl, or R is cycloalkyl of 5 to 10 
carbon atoms; and 
R.sub.1 and R.sub.2 are independently hydrogen, halo, lower alkyl, lower 
alkoxy, hydroxy, trifluoromethyl or nitro, or R.sub.1 and R.sub.2 are 
adjacent and taken together are methylenedioxy. 
The term, anaphylactic, as used herein is used in its broadest sense to 
include all forms of allergic hypersensitivity. 
Preferred are those compounds of formula I wherein R is said phenyl or 
substituted phenyl and R.sub.1 and R.sub.2 are hydrogen. Most preferred R 
is phenyl and R.sub.1 and R.sub.2 are hydrogen. 
By "lower" as in lower alkyl, or lower alkoxy, etc. is meant alkyl of 1 to 
4 carbon atoms, preferably 1 to 2 carbon atoms. 
By "halo" is meant preferably chloro, bromo or fluoro, most preferably 
chloro. 
The compounds can be prepared by methods known, per se. Thus, the compounds 
of formula I can be prepared by reacting a compound of the formula 
##STR3## 
with an amine of the formula 
EQU R--NH.sub.2 III 
under conventional ring closure conditions, e.g. at a temperature between 
about -20.degree. C. to about 20.degree. C., optionallyin the presence of 
an organic tertiary amine, such as a tri-lower alkyl amine such as 
triethylamine, or pyridine, in an inert diluent, such as tetrahydrofuran 
or carbon tetrachloride, and recovering the product. 
The compounds of formula I and their preparation are more fully described 
in U.S. Pat. Nos. 4,352,799; 4,397,858; 4,418,069 and 4,454,068, the 
disclosures of which are incorporated herein. 
Advantageously the compound of formula is topically administered to the eye 
in the form of an aqueous solution, suspension, ointment or cream or in 
the form of a controlled release lozenge or within a rate controlled 
membrane containing device for placement within the conjunctival sac. 
Preferably, the compound is administered in the form of an aqueous 
solution or suspension containing between about 0.002 to about 5 percent 
by weight, most preferably between about 0.004 and about 2% by weight, of 
a compound of formula I. 
In order to enhance the solubility of the active agent of formula I in the 
ocular composition, pharmaceutically acceptable eye compatable adjuvants, 
such as ethoxylated castor oil, propylene glycol, glycerine, low molecular 
weight polyethylene glycol, poloxamers and the like, in amounts between 
about 0.01 and about 30 weight percent, based upon the total weight of the 
composition, may be employed. Also, conventional pharmaceutical 
excipients, such as sodium borate, boric acid, tromethamine, potassium 
chloride, sodium phosphate, sodium citrate and the like may be present in 
amounts between about 0.01 and 3 weight percent, based upon the total 
weight of the composition. In addition, opthamologically acceptable 
preservatives, such as sodium edetate, benzalkonium chloride, sorbic acid 
and the like may be present in amounts between about 0.005 and about 0.1 
weight percent, based upon the total weight of composition. If desired, 
the resulting composition osmolality may be adjusted, e.g. with sodium 
chloride or the like, such that the composition is substantially isotonic. 
Preferably, the pH of the aqueous composition is between about 5 and about 
7. 
While not being bound by any specific mode of ocular anaphylactic 
inhibition, it is believed that the instant compounds operate to inhibit 
mass cell degranulation in the ocular region, thereby inhibiting the 
release of histamine. Moreover, it is believed that the compounds also 
inhibit leucocyte cell infiltration. 
The following Example is merely for illustrative purposes and is not 
intended to limit the invention. All parts are parts by weight unless 
otherwise indicated. 
EXAMPLE 1 
0.055 Mg of micronized 2-phenyl-1,2-benzisoselenazol-3(2H)-one, 50 grams of 
polyethoxylated high purity castor oil (Cremophor.RTM. EL, BASF Wyandotte 
Corp.), 19 grams of boric acid and 0.75 grams of tromethamine are combined 
with sufficient water to provide one liter of solution. The solution has a 
pH of between 5.2 and 5.5 and contains the 
2-phenyl-1,2-benzisoselenazol-3(2H)-one in a concentration of 0.2 
micromolar. One to two drops of the solution (about 50 to about 100 
microliters) can be placed into each eye of the mammalian host.