Abstract:
The present invention is directed to a topical composition for the treatment of psoriasis. The composition comprises a film forming agent, a plasticizer, an aqueous alcoholic solution and an amount of alkali effective to prevent the gellation of the film forming agent. Vinyl acetate crotonic acid copolymer and poly(vinyl)acetate are especially preferred film-forming agents.

Description:
This application is a continuation-in-part of Ser. Nos. 08/098,497 and 08/444,180, both now abandoned; the latter is a divisional of the former. 
    
    
     BACKGROUND OF THE INVENTION 
     The present invention is directed to a topical composition for the treatment of psoriasis. 
     Psoriasis is a skin disease marked by the presence of small elevations of the skin as well as silvery scales. In the area where scales have been shed, tiny bleeding points called &#34;Auspitz sign&#34; appear. The major pathophysiological events involved in the disease process are accelerated epidermal proliferation and metabolic activity, proliferation of capillaries in the dermal region, and invasion of the dermis and epidermis by inflammatory cells. 
     Coal Tar and Salicylic Acid are the only two Category I drugs mentioned in the Final Monograph for dandruff, seborrheic and psoriatic drugs. There are a number of prescription products (different drug entities) that are also useful, e.g. Theophylline which arrests the proliferation of cells during the metaphase stage of cell division. 
     It is also known that psoriatic zones lose water 8-10 times faster than normal skin. This leads to increased metabolic rates at the expense of tissue catabolism and muscle wasting. 
     U.S. Pat. No. 4,210,633 issued Jul. 1, 1980 refers to treatment of psoriasis by application of a film forming composition containing flurandrenolide. The film forming components are polyvinyl alcohol and polyvinylpyrrolidone. 
     French Patent Number 2539 refers to a psoriasis treatment comprising a thin plastic film, for example, vinyl polymers, polyamides or polyesters, impregnated with a corticoid. 
     Australian Patent Number 6218907 refers to a pharmaceutical composition for the treatment of psoriasis comprising coal tar and a flexible carrier material. 
     West German Offenleguschrift Number 297329 refers to a pharmaceutical composition for the treatment of localized psoriasis which comprises a copolymer of acrylic acid esters and/or methacrylic acid esters as the active agent. The composition is applied as a fine spray which forms an elastic film. 
     PCT Application Number 92/04019 refers to the use of 6-methoxy-2-naphthylacetic acid as a topical treatment for psoriasis. 
     PCT Application Number 91/02538 refers to a composition for treating keratinous tissue, e.g. psoriasis, in mammals comprising a film forming protein, a compatible reducing agent, a reactive zinc salt and at least one film-forming polymer. 
     U.S. Pat. No. 4,826,677 issued May 2, 1989 refers to a liquid formulation for the treatment of psoriasis containing dithranol dispersed in a film forming polymer. 
     European Patent Application Number 223671 refers to an antipsoriatic composition containing a corticosteroid and a beta-agonist. The composition may be applied as a film. 
     U.S. Pat. No. 4,652,557 issued Mar. 24, 1987 and U.S. Pat. No. 4,575,515 issued Mar. 11, 1986 refer to a topical solution for psoriasis treatment. The solution contains dimethyl sulfoxide, a polyalcohol, a dispersant, triethanolamine salicylate and water. 
     United Kingdom Patent Number 2165453 refers to a topical composition for the treatment of psoriasis which comprises dithranol distributed in the adhesive layer of a non-permeable self-adhesive film. 
     Japanese Patent Number 56061312 refers to an adhesive sheet for curing skin diseases which contains beta-methazone valerate in the adhesive base. 
     SUMMARY OF THE INVENTION 
     In one embodiment, the present invention is directed to a composition comprising: 
     (a) a film-forming agent, 
     (b) a plasticizer, 
     (c) an aqueous alcoholic solution, 
     (d) an amount of alkali effective to prevent the gellation of said film-forming agent, said composition, when applied to a psoriatic zone of the skin of a human, forming an occlusive area suppressing greater than 70 percent of water transmission from the psoriatic zone. 
     Preferred is the composition wherein said film-forming agent is vinyl acetate crotonic acid copolymer. 
     Also preferred is the composition wherein said plasticizer is dibutyl sebacate. 
     In a preferred embodiment, the present invention is directed to a composition comprising: 
     (a) from about 50 to about 90 weight percent alcohol in an aqueous solution, 
     (b) from about 0.01 to about 0.5 weight percent alkali, 
     (c) from about 5 to about 25 weight percent film-forming agent, and 
     (d) from about 0.01 to about 0.2 weight percent plasticizer, said composition, when applied to a psoriatic zone of the skin of a human, forming an occlusive area suppressing greater than 70 percent of water transmission from the psoriatic zone. 
     Preferred is the composition wherein said alkali is potassium hydroxide. 
     Also preferred is the composition wherein said film-forming agent is vinyl acetate crotonic acid copolymer. 
     Especially preferred is the composition wherein said plasticizer is dibutyl sebacate. 
     In another embodiment, the present invention is directed to a method for the treatment of psoriasis in a human in need of such treatment comprising the application to the psoriatic zone of a composition of the present invention. 
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention is directed to a spray-on patch for psoriasis. The solution which forms the patch is formulated so that when sprayed onto the psoriatic zone by, for example, a pump spray, it sets in a short period of time and forms a flexible skin, thereby preventing water transmission from the psoriatic zone. 
     One component of the formulation is a film-forming agent. An especially preferred film-forming agent is vinylacetate crotonic acid copolymer or poly(vinylacetate phthlate). When used in the formulation, it is present at a concentration of from about 5 to about 25 weight percent, preferably from about 5 to 15 weight percent, more preferably about 13 weight percent. 
     Another component of the formulation is a plasticizer. An especially preferred plasticizer is dibutyl sebacate. When used in the formulation, dibutyl sebacate is present at a concentration of from about 0.01 to about 0.2 weight percent, preferably at about 0.05 weight percent. 
     Since the film-forming agent of the present formulation has a tendency towards gellation, the present formulation also contains a small amount of alkali to prevent gelling thus promoting the occlusive properties of the patch. A preferred alkali is potassium hydroxide. The alkali is present at a concentration of from about 0.01 to about 0.5 weight percent, preferably at about 0.20 weight percent. 
     Another component of the formulation of the present invention is a solvent system consisting essentially of an aqueous cosmetically acceptable alcoholic solution. Examples of cosmetically acceptable alcohols include ethanol and isopropyl alcohol, preferably ethanol. It has been found that if less than 200 proof (100%) alcohol is used, the small amount of water present adds to the occlusive properties of the spray or patch. In the formulation of the present invention, the aqueous alcoholic solution is present at a concentration of from about 50 to about 90 weight percent, preferably at about 87 weight percent. Alternatively, a 200 proof alcohol can be diluted to a 180-190 proof (90-95%) alcohol by the addition of water. Such diluted aqueous alcoholic solutions, either with or without a denaturant, preferably with a denaturant, can also be used in the formulations of the present invention. 
     The formulation of the present invention may be packaged in any container. A preferred package is one containing a suitable spraying device. A simple pump spray may be used. A moderate pressure aerosolized spraying device may also be used. The formulation may also be packaged in a container with a brush or sponge-type applicator or a roll-on container. 
     Having described the invention in general terms, reference is now made to specific examples. It is to be understood that these examples are not meant to limit the invention, the scope of which is determined by the appended claims. 
    
    
     EXAMPLE 1 
     A formulation was prepared with the following ingredients. 
     
         ______________________________________Ingredient             % w/w______________________________________Alcohol, USP.sup.1     86.75Potassium Hydroxide NF 0.20Vinyl Acetate Crotonic Acid Copolymer.sup.2                  13.00Dibutyl Sebacate.sup.3 0.05                  100.00______________________________________ .sup.1 190 Proof Ethyl Alcohol .sup.2 Vinac ® ASB516 .sup.3 Uniflex ® DBS 
    
     The formulation was prepared in the following manner. 
     Into a 500 ml stainless steel beaker was charged 260.25 grams of alcohol (USP Ethanol 190 proof). The alcohol was mixed with a Lightnin mixer at 500 RPM to generate a vortex. 
     0.60 grams of potassium hydroxide were added and dissolved by mixing at 500 RPM for three minutes. 
     39.00 grams of vinylacetate crotonic acid copolymer (Vinac® ASB-516) was then added and the resultant solution was mixed at 500 RPM for one hour. To insure that all the Vinac® had dissolved, mixing was continued for an additional 30 minutes. 
     After all the Vinac® had dissolved, 0.15 grams of dibutyl sebacate was added and the solution was mixed for five minutes. The final solution was discharged into an 8 ounce clear glass bottle. 
     The solution had the following physical characteristics. 
     
         ______________________________________1.       Drying Time      3-4 minutes    Sprayability     Satisfactory2.       pH               7.333.       Viscosity        23.07 CPS4.       Specific Gravity 0.8505______________________________________ 
    
     When sprayed onto a psoriatic zone, the solution set into a flexible skin which showed greater than 70% suppression of water transmission.