Abstract:
An ophthalmic composition comprising Prazosin or a pharmaceutically acceptable salt thereof and a topically administrable ophthalmic pharmaceutical carrier. The foregoing composition is useful in lowering intraocular pressure in the eye. Reduction of intraocular pressure is of particular importance in the treatment of glaucoma, a disease characterized by elevated intraocular pressure.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a topical ophthalmic composition and method for the therapeutic use thereof. More particularly, the present invention relates to a topical, ophthalmic composition containing Prazosin useful in temporarily reducing intraocular pressure and alleviating the symptoms of glaucoma. 
     2. Background of the Prior Art 
     The active compound described herein is known in the art, e.g., U.S. Pat. No. 3,511,836. Prazosin is the designated name for a compound with the chemical name 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanyl carbonyl)piperazine. Its method of manufacture is disclosed in U.S. Pat. No. 3,511,836, the relevant portions of which are hereby incorporated by this reference. Prazosin has been used heretofore in the treatment of systemic hypertension. 
     Glaucoma is a condition of the eye characterized by increased intraocular pressure. Untreated, the condition eventually leads to irreversible retinal damage and blindness. Conventional therapy for glaucoma is with pilocarpine and/or epinephrine administered topically to the eye several times daily. 
     SUMMARY OF THE INVENTION 
     The present invention relates to a therapeutic composition comprising a topically administrable ophthalmic formulation containing an effective amount of Prazosin or a pharmaceutically acceptable salt thereof. 
     The present invention also relates to a method for temporarily reducing intraocular pressure in humans comprising topically administering to the eyes of a human an effective amount of the foregoing composition. 
     The present invention also relates to a method for temporarily alleviating the symptoms of glaucoma in humans comprising topically administering to the eyes of a human having glaucoma an effective amount of the foregoing composition. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Many physiologically and pharmaceutically acceptable salts of the compound discussed above are known to those skilled in the art and all such salts may be employed in the present invention. Examples of suitable acids to form salts with Prazosin include fumaric, hydrochloric, nitric, sulfuric and tartaric acids. 
     The concentration of the active compound which is an effective amount and which may be used in the present invention ranges from about 0.0005 to about 5 percent and preferably from about 0.01 to about 1 percent by weight. 
     Suitable ophthalmic carriers are known to those skilled in the art and all such conventional carriers may be employed in the present invention. Thus, a particular carrier may take the form of a sterile ophthalmic ointment, cream, gel, solution or dispersion. Also including as suitable ophthalmic carriers are slow release polymers, e.g., &#34;Ocusert&#34; polymers, &#34;Hydron&#34; polymers, etc. Stabilizers may also be used such as, for example, chelating agents, e.g., EDTA. Antioxidants may also be used, e.g., sodium bisulfite, sodium thiosulfite, 8-hydroxy quinoline or ascorbic acid. Sterility typically will be maintained by conventional ophthalmic preservatives, e.g., chlorbutanol, benzalkonium chloride, cetalpyridium chloride, phenyl mercuric salts, thimerosal, etc., for aqueous formulations, and used in amounts which are non-toxic and which generally vary from about 0.001 to about 0.1% by weight of the aqueous solution. Conventional preservatives for ointments include methyl and propyl parabens. Typical ointment bases include white petrolatum and mineral oil or liquid petrolatum. However, preserved aqueous carriers are preferred. Solutions may be manually delivered to the eye in suitable dosage form, e.g., eye drops, or delivered by suitable microdrop or spray apparatus typically affording a metered dose of medicament. Examples of suitable ophthalmic carriers include sterile, substantially isotonic, aqueous solutions containing minor amounts, i.e., less than about 5% by weight hydroxypropyl-methylcellulose, polyvinyl alcohol, carboxymethylcellulose, hydroxyethylcellulose, glycerine and EDTA. The solutions are preferably maintained at substantially neutral pH and isotonic with appropriate amounts of conventional buffers, e.g., phosphate, borate, acetate, tris, etc. 
     A preferred ophthalmic composition is a preserved aqueous solution containing the following ingredients at the indicated concentration. 
     
         ______________________________________Prazosin         Wt. percent  0.5Stabilizer       &#34;            0.01Preservative     &#34;            0.005Buffer           M            0.05NaCl q.s. ad isotonic.Water q.s. ad 100 percent.______________________________________ 
    
     The amount of the foregoing composition to be used in the therapeutic treatment of glaucoma will vary with the age of the patient and the severity of the glaucoma. Generally a dose level of one or two drops of the foregoing aqueous solution 1-4 times daily would be a suitable dosage amount. 
     EXAMPLE 
     The intraocular pressure of six albino rabbits was measured tonometrically to obtain a baseline. Concentrations of 0.001 to 1 percent physiologic saline solutions of Prazosin were prepared and 0.05 ml administered to the right eye of each rabbit. A similar volume of physiologic saline was placed in the left eye. At hourly intervals (from 0-6 hours after treatment) the intraocular pressure of both eyes of each rabbit was measured tonometrically. The results are shown in the Table below. 
     
                       Table______________________________________Effect of Prazosin on IOP.sup.1 in Rabbits.sup.2        HoursEye   0      0.5    1    2    3    4    5    6    8______________________________________Con-trol  20.5   20.0   19.5 18.0 18.0 19.0 19.0 20.0 --Treat-ed.sup.3 20.5   19.0   18.0 17.0 17.5 18.5 19.0 19.5 --Con-trol  16.5   14.0   16.0 14.0 15.0 14.5 --   15.0 --Treat-ed.sup.4 17.0   12.5   12.0 12.0 12.5 13.0 --   15.0 --Con-trol  17.0   14.5   15.0 14.5 16.5 17.0 15.5 18.0 17.5Treat-ed.sup.5 17.5   12.5   11.5 11.0 13.0 14.0 14.5 15.5 17.5Con-trol  15.0   13.0   11.0 11.0 12.5 12.5 14.0 13.5 15.0Treat-ed.sup.6 14.5   12.0   10.5 10.5 11.0 11.5 11.5 12.5 12.5______________________________________ .sup.1 Pressure measured in mm Hg .sup.2 Results reported as average of six rabbits .sup.3 0.001% Prazosin .sup.4 0.01% Prazosin .sup.5 0.1% Prazosin .sup.6 1% Prazosin