Title:  Method and composition for treating viral outbreaks

United States Patent:  6,803,056

Issued:  October 12, 2004

Inventors:  Dolak; Terence M. (27 Mountain View Dr., Andover, NJ 07821)

Appl. No.:  385099

Filed:  March 10, 2003

Abstract

The invention provides a method and composition for treatment of lesions associated with viral infections, such as human Herpes simplex, by applying to the lesions an effective amount of a topical composition comprising: propolis extract in from about 0.5 to 10%, preferably about 1 to 8%, by weight; a skin protectant in from about 0.5% to 50% by weight; a penetration enhancing agent in from about 5 to 30%, preferably 5 to 25%, by weight; and an emulsifier in from about 1 to 20% by weight. The subject compositions possess enhanced activity in the treatment of such lesions in that they stop the outbreak at the stage of progression when they are applied and promote full healing, generally within 36 to 48 hours.

Description of the Invention

FIELD OF THE INVENTION

This invention relates to a method and composition for the treatment of lesions associated with viral infections, such as Herpes simplex or Herpes zoster.

BACKGROUND OF THE INVENTION

Herpes viral infections are chronic. Once the virus enters the body, it lies dormant in the nerve cells and periodically reactivates. When the virus reactivates, it characteristically causes a sore at the site where it first entered the body. To date, there is neither a vaccine to prevent the Herpes infection, nor any way to eliminate the virus from the body. Once infected, the patient has the virus for life.

Recurrent outbreaks of the Herpes virus generally follow a staged progression. The stages are easily identifiable and include prodrome, vesicles, ulceration, crust and healing. Some of these stages can last less than 24 hours. Prodrome is generally a short period of tingling, itching, numbness or burning with no visible sign of an outbreak. Vesicles is the formation of one or more fluid-filled blisters, often in a cluster and usually surrounded by sore, red skin. The ulceration stage is when the blisters open to form painful ulcers or open sores. At the edge of the sore, a soft or hard yellow crust begins to appear. Ulcers and painful, sore, red skin persist through this stage. At the crust stage, weeping sores or ulcers become completely covered by a crust or scab. No ulcers or blisters are present. The healing process is manifested by disappearance of the crust, swelling, pain and itching. Skin eruptions due to viral infection, especially Herpes viruses, generally have a normal infective course that lasts from 10 to 60 days depending on the exact causative species and anatomical location of the infection.

Propolis has been used in both water-based and oil-based preparations to treat viral outbreaks. Propolis preparations are reported to reduce the healing process by up to 50% or from an average of 9 to 10 days to an average of 4 to 5 days. In a placebo-controlled study involving 50 patients with recurrent oral Herpes, a commercial petroleum-based propolis ointment (Herpestat or HelaStop) reduced healing time by 50%, Szmeja and Konopacki, Otolaryng. Pol., XLI(3): 183-188 (1987). The average healing time for the placebo patients was 8 days and the average healing time for patients using Herpestat, which is also called Herstat, was 4 days. The same results were reported for a placebo controlled study using a commercial aqueous propolis extract solution, Nivcrisol-D Giurcaneanu et al., Virologie, 39(1):21-24 (1988). This study involved 65 patients. Patients using placebo had an average healing time of 8 days and those using Nivcrisol-D, an average healing time of 4 days.

In a placebo controlled study involving 90 patients with recurrent genital Herpes, the efficacy of acyclovir ointment and a petrolatum based propolis ointment (HelaStop) were compared. The average healing time for both the placebo and acyclovir ointment was 12 days and an average healing time for the propolis ointment group was 8-9 days, Vynograd et al., Phytomedicine, 7(1):1-6 (2000). In Table 3 of Vynograd eta, it is reported that of 30 patients treated with a propolis preparation, none had healed Herpes lesions after three days, only 10 had healed after seven days and 24 had healed after ten days.

Busciglio, U.S. Pat. No. 4,748,022 discloses compositions comprising diphenhydramine HCl, lidocaine HCl, aloe vera gel and propolis in a formulation having a basic pH. In the comparative data, while the composition containing all ingredients was superior to a similar formulation without the aloe vera gel and propolis, a formulation omitting only propolis demonstrated about 40% better average healing time than the formulation containing all ingredients. It should be noted that one subject reported no healing with the formulation omitting propolis. Regardless, the results must be viewed as inconclusive in terms of the capacity of the formulation ingredients to enhance the efficacy of propolis.

It is evident from these results that there is still a need for an effective treatment. It has been found that by using propolis in the compositions of the present invention, the healing time of Herpes outbreak is dramatically reduced to 36-48 hours and material progression of the outbreak is prevented beyond the stage of progression at the time of the initial application.

SUMMARY OF THE INVENTION

The present invention relates to topical preparations and methods for treatment of skin and mucosal membrane lesions associated with viral infections, such as Herpes simplex or Herpes zoster. More specifically, the present invention provides a composition and method for the treatment of lesions associated with Herpes viruses that reduces the healing time of a Herpes outbreak and stops the outbreak on contact with full healing, generally in 36 to 48 hours.

In particular, the present invention provides a composition for the treatment of lesions associated with viral infections comprising: propolis extract, a skin protectant, a penetration enhancing agent and an emulsion base. The present invention also provides a method for the treatment of lesions associated with viral infections comprising applying to the lesion an effective amount of the subject compositions.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides topical compositions and method for the treatment of lesions associated with viral infections, such as Herpes viruses. In the foregoing discussion, the progression of a viral outbreak was given as: prodrome, vesicles, ulceration, crust and healing. For brevity, the term "lesion" as utilized herein shall refer to any and all of such stages. Those of ordinary skill in the art will recognize that a lesion in this context designates any occurrence in the progression other than normal skin. lntraorally, lesions will manifest themselves as ulcers on the hard palate and dorsal tongue only. Intraoral lesions are not to be confused with idiopathic aphthous ulcers that occur on the movable oral mucosal. Idiopathic aphthous ulcer lesions are sufficiently distinctive in appearance to differentiate them from primary or recurrent herpetic oral lesions. In accordance with the present invention, application of the subject compositions not only dramatically reduces the healing time of Herpes lesions, but also stops the normal progression of the Herpes outbreak from the stage at which the initial application occurred. On the average, the present compositions reduce healing time of a Herpes outbreak to 36 to 48 hours.

The compositions of the present invention are those recognized in the pharmaceutical arts as being suitable for topical application and include, without intended limitation, creams, lotions, liquid emulsions and the like. The present compositions comprise: propolis extract in from about 0.5 to 10%, preferably from about 1 to 8%, by weight; a skin protectant in from about 0.5 to 50% by weight; a penetration enhancing agent in from about 1 to 30%, preferably 5 to 25%, by weight; and an emulsifier in from about 1 to 20% by weight. The careful selection of each of the components of the present compositions has provided an optimal anti-viral effect that has produced unexpectedly enhanced results. In addition to the surprising enhanced therapeutic effect, the subject compositions are advantageous in that the skin protectant protects against the irritation and resultant bacterial infections that tend to exacerbate a viral outbreak.

The skin protectant forms a barrier over the skin surface to help protect against irritation due to touching, itching, topical care products, chafing, etc. In the treatment of Herpes lesions on mucosal membranes, e.g. the oral cavity, the skin protectant, in addition to forming a protective barrier, provides a hydrophobic environment at the site of application that aids in preventing loss of the active ingredient to the action of saliva. The skin protectant comprises at least one member selected from the group consisting of allantoin, aluminum hydroxide gel, dimethicone, glycerin, kaolin, pyridoxine hydrochloride, topical starch, petrolatum, and white petrolatum. Preferred skin protectants, with their preferred concentrations in percent by weight, include one or more members selected from the group consisting of dimethicone 0.5-5.0%, allantoin 0.5-5.0%, glycerin 1.0-8.0%, petrolatum 5-50%, and white petrolatum 5-50%. For treatment of lesions on the oral mucosal membranes, aluminum hydroxide gel 5-20%, kaolin 2-10% and topical starch 1-15% are preferred for forming a physical barrier and dimethicone 0.5-5.0%, petrolatum 5-50% and white petrolatum 5-50% are preferred for providing a hydrophobic environment at the site of application.

The compositions of the present invention contain a penetration enhancing agent that helps facilitate the delivery of the active principle of propolis through the cornified layer of the skin to the layers of the skin where the viral infection and replication processes are ongoing. The penetration enhancing agent comprises ethanol or a combination thereof with at least one member selected from the group consisting of glycerol esters, propylene glycol, butylene glycol, cyclic amides, 1-dodecyl-aza-cyclophetan-2-one, 2-pyrrolidone, diisopropyl sebacate, C_1-30 alkyl esters of pyroglutamic acid, 1-methyl-2-pyrrolidone, 2-hydroxyoctanoic acid, polyoxylene sorbitan mono-oleates, polysorbate 80, polysorbate 60, fatty alcohols, alkylene glycol esters, diethylene glycol, diethylene glycol monoethyl ether, diethylene glycol monomethyl ether, dipropylene glycol and art recognized derivatives thereof possessing a like activity. Wherein ethanol is present in the compositions of the invention in combination with one of the other agents listed above, it is preferred that the concentration of ethanol does not exceed about 10% by weight, based on the overall composition. Ethanol is present in the compositions of the invention in propolis extract which is typically a 50% tincture in ethanol. Preferred penetration agents in accordance with the present invention are ethanol in combination with propylene glycol or polysorbate 60.

The emulsifier of the present composition provides a means of achieving a molecular dispersion of the active principals in propolis extract, the majority of which have limited water solubility. The poor solubility impedes the penetration of the active principals, particularly the flavonoid components, into the skin and, therefore, their ability to reach the viral infection site. The emulsifier also aids in hydrating the surface of the skin at the site of application, thereby further improving propolis absorption.

The emulsifier comprises at least one member selected from the group consisting of sorbitan derivatives, particularly sorbitan esters with fatty acids such as oleic acid, alkoxylated alcohols, polymeric ethers, glycerol esters, poly(oxyethylene-oxypropylene)-methylpolysiloxane copolyiners and their derivatives and water soluble salts of fatty acids with ammonia, alkanolamines, low molecular weight amines and alkali metals, such as sodium and potassium. It is within the purview of the present invention that certain of the emulsifiers listed above can function as penetration enhancing agents as well. Preferred emulsifiers include one or more of polysorbate 60, polysorbate 80, a polyethylene glycol and a sorbitan ester.

In addition to the foregoing essential ingredients, the compositions of the present invention may contain other ingredients such as are recognized by those skilled in the pharmaceutical compounding arts as being typically present in such formulations. These include, without intended limitation, one or more preservatives, osmotic regulators, thickeners, flavors, fragrances, emollients, humectants, colorants, pigments and the like. It will be appreciated that the compounding of the compositions of the present invention will be carried out utilizing some or all of these ingredients depending of the intended use. For example, for a lotion, colorants or pigments as well as humectants may be present and for a preparation intended for application in or around the mouth, it will be necessary to add flavors to mask the taste of the essential ingredients, particularly the propolis extract.

In addition to the choice of these additional ingredients, the intended use of the composition will influence the choice of certain of the essential ingredients as well, e.g. ingredients that are liquid or semisolid will be utilized to prepare a lotion and those of a higher molecular weight will be used to prepare ointments and the like. The choice of such ingredients is considered to be within the purview of the person skilled in the art of pharmaceutical compounding for a given type of preparation. The present compositions are preferably formulated to be hypoallergenic and are packaged in an antiseptic condition to minimize the possibility of complicating infections.

It has been found in accordance with the present invention, that application of the subject compositions at the prodrome stage, of a Herpes outbreak before vesicle formation, will preclude the formation of a visible sore or inflammation. Therefore, the present invention provides a method for treatment of lesions associated with viral infections comprising applying to the lesion an effective amount of the subject compositions. The method of this invention is particularly effective, where the viral infection is Herpes simplex or Herpes zoster.

Claim 1 of 9 Claims

What is claimed is:

1. A composition for topical treatment of skin and mucosal membrane lesions associated with viral infections comprising:

(a) propolis extract in from about 1 to 8% by weight;

(b) a skin protectant comprising one or more members selected from the group comprising of dimethicone, glycerin, petrolatum, and white petrolatum in from about 0.5 to 50% by weight;

(c) a penetration enhancing agent selected from a combination of ethanol and propylene glycol or ethanol and polysorbate 60 in from 5 to 25% by weight; and

(d) an emulsifier comprising one or more members selected from the group consisting of polysorbate 80, polysorbate 60 or other sorbitan ester in from 1 to 20% by weight.

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