| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | February 9, 1999 |
| PATENT TITLE |
Topical preparation for the prevention and treatment of lesions and sores associated with a herpes virus |
| PATENT ABSTRACT |
The invention provides a topical pharmaceutical composition for the prevention and treatment of lesions and sores of the skin or mucosa associated with a herpes virus, comprising a salt of an unsaturated C.sub.14-18 fatty acid having 1-2 double bonds as active ingredient therein, in combination with a pharmaceutically or cosmetically acceptable carrier. |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | February 6, 1996 |
| PATENT FOREIGN APPLICATION PRIORITY DATA | This data is not available for free |
| PATENT REFERENCES CITED |
HCAPLUS abstract AN-1992: 201098 (EP 465423 A2) 1992. Embase abstract 90018210, Seki, T. et al., (1989). Embase abstract 85192137, Cooper, E. R. et al. (1985). |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. A method for the treatment of pre-existing lesions and sores of the skin or mucosa associated with a herpes virus and for prevention of future lesions and sores of the skin or mucosa associated with a herpes virus, comprising administering a topical pharmaceutical composition, consisting essentially of an alkali oleate as active ingredient therein, in an effective amount for the treatment of lesions and sores of the skin or mucosa, in combination with a pharmaceutically or cosmetically acceptable carrier |
| PATENT DESCRIPTION |
FIELD OF THE INVENTION The present invention relates to a topical pharmaceutical composition and to methods for the treatment of a herpes virus using the same. More particularly, the present invention relates to a topical pharmaceutical composition for the prevention and treatment of lesions and sores of the skin or mucosa associated with a herpes virus, comprising a salt of an unsaturated C.sub.14-18 fatty acid having 1-2 double bonds as active ingredient therein, in combination with a pharmaceutically or cosmetically acceptable carrier. BACKGROUND OF THE INVENTION As compared to other areas of infectious disease, antiviral therapy has rapidly advanced during the last decades. However, despite intense efforts by pharmaceutical companies, relatively few antiviral drugs are available, in contrast to the plethora of antibiotics in clinical use. There are two main reasons for the limited use of antiviral agents: (1) most drug candidates have proven too toxic in humans, and (2) the widespread use of some antiviral agents has led to emergence of drug-resistant virus strains, particularly in immunocompromised patients. Due to the above constraints in use of antiviral agents, and following surprising results obtained and presented herewith, the present invention is meant to provide novel compositions which prevent, and/or provide, symptomatic relief of lesions and sores associated with a herpes virus, and which compositions do not require the presence of a nucleoside analogue or any other antiviral agent now in use. More specifically, in Israel Specification 104,283 there is described and claimed an antiviral topical pharmaceutical composition for treating viral diseases of the skin or mucosa, comprising a poorly soluble antiviral nucleoside derivative dispersed in an aqueous gel carrier containing a gelling agent and a water-solubilized carboxylic or dicarboxylic acid salt. The teachings of said specification are incorporated herein by reference. The invention described in said specification was based on the discovery that said formulation achieved better anti-viral effect than the ZoviraxR ointment or cream available on the market today. After further research and development, however, it was surprisingly discovered that the composition described in said specification, in what was thought to be a placebo and in which the soluble anti-viral nucleoside derivative, i.e., acyclovir, was absent, also achieved better effect than the ZoviraxR ointment or cream available on the market today. It has been concluded from the research performed with the nucleoside drug and with its absence that the antiviral effect of the composition is due to the enhanced penetration of the fatty acids as salts rather than free acids. The penetration of any antiviral agent is critical for the effective treatment of herpes virus, since the replication of the virus and the vesicles eruption occur deep in the basal epidermis (Stratum Granulosum). Therefore, in light of this surprising discovery, the present invention relates to a topical pharmaceutical composition for the prevention and treatment of lesions and sores of the skin or mucosa associated with a herpes virus, comprising a salt of an unsaturated C.sub.14-18 fatty acid having 1-2 double bonds as active ingredient therein, in combination with a pharmaceutically or cosmetically acceptable carrier. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graphic illustration of the transdermal permeation of acyclovir in mice as a function of time following administration of three different acyclovir formulations. FIG. 2 is a graphic illustration of the transdermal permeation of acyclovir in nude mice as a function of time following administration of two different acyclovir formulations having different pHs. SUMMARY OF THE INVENTION The present invention encompasses topical pharmaceutical compositions for the treatment of pre-existing lesions and sores of the skin or mucosa associated with a herpes virus and for prevention of future lesions and sores of the skin or mucosa associated with a herpes virus. The compositions comprise a salt of an unsaturated C.sub.14-18 fatty acid having 1-2 double bonds as active ingredients therein, in combination with a pharmaceutically or cosmetically acceptable carrier. The invention also encompasses methods for the treatment of pre-existing lesions and sores of the skin or mucosa associated with a herpes virus and for prevention of future lesions and sores of the skin or mucosa associated with a herpes virus, which comprise administering the above-described compositions in effective amounts for the treatment and/or prevention of these lesions. DESCRIPTION OF THE PREFERRED EMBODIMENTS More specifically, the present invention provides a topical pharmaceutical composition, wherein said antiviral agent is selected from the group consisting of myristoleates, linoleates, elaidates, palmitoleates and oleates. Especially preferred for use in the present invention is an alkali oleate. Preferably, said topical composition will comprise a polyhydroxy compound selected from the group consisting of glycerine, propylene glycol, and polyethylene glycol. Thus, the present invention, in especially preferred embodiments, provides a composition containing between about 0.1% and about 30% of a combination of alkali oleate and oleic acid, about 0 to 70% propylene glycol, and a pharmaceutically acceptable carrier. The pH of said composition is preferably adjusted to between 7 and 8. The invention also provides a method for the prevention and treatment of lesions and sores of the skin or mucosa associated with a herpes virus, comprising administering a topical pharmaceutical composition, comprising a salt of an unsaturated C.sub.14-18 fatty acid having 1-2 double bonds as active ingredient therein, in an effective amount for the treatment of lesions and sores of the skin or mucosa, in combination with a pharmaceutically or cosmetically acceptable carrier. Said composition can be effective for a wide range of virus-associated and viral-like diseases. These include herpes simplex labialis, post-herpetic neuralgia, recurrent genital herpes, cancer sore, aphthous stomatitis, vulvar vestibulities, etc. While, as indicated, it has been discovered that the above composition is effective in itself, the carboxylic acid salt of the present invention can obviously also be combined in a pharmaceutical composition with an additional poorly soluble antiviral nucleoside derivative, such as acyclovir, vidarabine, azidothymidine and ganciclovir. The pharmaceutically or cosmetically acceptable vehicle utilizable in the compositions of the present invention can be selected from the group comprising an oil-in-water or water-in-oil emulsion, solution, cream, suspension, gel, aerosol, or powder. Oil-in-water or water-in-oil emulsions are formulated in ways that a stable topical ointment, lotion, cream, stick or foam is achieved. The stabilization of the topical emulsions may be established and optimized by using the preferred combinations of hydrophilic and lipophilic emulsifiers, properly aligned at the water/oil interface. The emulsifying agents and their concentrations and proportions may be chosen according to the principle of the well-established HLB method published by W. C. Griffen ›"H. L. B. - The Hydrophilic-Lipophilic Balance," J. Soc. Cos. Met. Chem., Vol. 5, p. 249 (1954)!. In the case where the composition according to the invention is an emulsion, the oil phase is selected from the group consisting of beeswax, spermaceti, 2-octyl dodecanol, lanolin, sodium C.sub.12-15 alcohols sulphate, esters of fatty acids and high molecular weight alcohols such as cetyl palmitate and cetearyl octanoate, esters of fatty acids and branched alcohols or polyols such as isopropyl palmitate or myristate, cocoglycerides, cosbiol, wool alcohols, cocoa butter, stearyl alcohol, cholesterol, liquid paraffin, soft paraffin, hard paraffin, or the like. The emulsifying agents used for the purpose of dispersion of the above-mentioned fats or oils and the like in the aqueous phase are advantageously selected from the group of non-ionic surfactants consisting of sorbitan sesquioleate, PEG-5 glyceryl stearate, poloxamers, cetostearyl alcohol, polysorbate 60, sorbitan monostearate, sorbitan monooleate, and glyceryl monostearate. In the case where the composition according to the invention is a gel or solution, the composition preferably comprises an oleic acid/oleate salt, and generally a lower alkanol having from one to four carbon atoms, water, a gelifying agent (if a gel), one or more polyhydric alcohols selected from the group consisting of a lower alkylene glycol having from two to four carbon atoms, glycerine, and polyethylene glycol, having an average molecular weight from 200 to 2000, and a base, e.g., sodium hydroxide, or an acid, e.g., citric acid, for pH adjustment. The gelifying agents are selected from the group consisting of polysaccharides such as cellulose derivatives, acrylic polymers, proteins, polyhydroxy compounds such as polyethylene glycol having an average molecular weight from 400 to 2000, and polyoxyethylene-3-cetylstearyl alcohol, known as Emulgin B3. All semi-solid topical preparations should preferably be stable and consistent, non-leaky, non-staining, and non-greasy. In the case where the composition according to the present invention is a powder, the composition preferably comprises an oleic acid and/or alkali oleate, and generally a diluting powder compound suitable as a lubricant. This lubricant is selected from the group consisting of talc, microcrystalline cellulose, polyvinyl pyrrolidone, metal stearates, lactose or starch known to have non-irritating, non-toxic and inert properties. In accordance with another aspect of the invention, the oleic acid and/or oleate salt could be topically applied in a slow-release manner using an adhesive sponge bandage, or, alternatively, a gauze or sponge sandwich containing a layer of the active principals of the invention situated between upper and lower absorbent layers. The carboxylic/dicarboxylic acids and/or their salts of the present invention can also be applied onto the mucosa, for example, as a buccal gel or vaginal preparation. For this purpose, several bioadhesive polymers are selected from the group consisting of polyethylene glycols, cellulose derivatives, starch, and polyacrylic acid such as polycarbophil and Carbopol 934. As described hereinbefore, the vehicles can be in the form of a cream, lotion, ointment, gel, stick, topical solution, gargle solution, foam, spray, liquid soap, or powder. From the point of view regarding the formulation characteristics, the pharmaceutical preparations could be processed as a water-in-oil or an oil-in-water emulsion, clear solution, gel solution, aerosol, powder mix, film- forming liquid, bioadhesive preparation, detergents- containing gel, suspension in gel, liquid, or emulsion, etc. While the invention will now be described in connection with certain preferred embodiments in the following examples so that aspects thereof may be more fully understood and appreciated, it is not intended to limit the invention to these particular embodiments. On the contrary, it is intended to cover all alternatives, modifications and equivalents as may be included within the scope of the invention as defined by the appended claims. Thus, the following examples which include preferred embodiments will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purposes of illustrative discussion of preferred embodiments of the present invention only and are presented in the cause of providing what is believed to be the most useful and readily understood description of formulation procedures as well as of the principles and conceptual aspects of the invention. |
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| PATENT PHOTOCOPY | Available on request |
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