A TOPICAL ANTIVIRAL COMPOSITION Field of Invention

The present invention relates to a topical composition comprising an antiviral active ingredient or analogues or derivatives thereof which is enhanced with antiherpes oils in a combination with an acid active ingredient or analogues or derivatives thereof which is enhanced with oils.

Background of Invention

Herpes simplex Virus 1 and 2 are very large viruses with very similar characteristics. Almost any human cell type can be infected by HSV. In many cells, such as endothelial cells and fibroblasts, infection is lytic but neurones normally support a latent infection. The hallmark of herpes infection is the ability to infect epithelial mucosal cells or lymphocytes. A reddened area gives rise to a macule which crusts to form a papule. The fluid in this blister is full of virus. As long as the virus is kept moist it can remain infectious Herpes simplex 1 and 2 can infect both humans and other animals but only humans show symptoms of disease.

Oral herpesis usually caused by HSV-I, but rarely can be caused by HSV-2. In primary herpetic gingivostomatitis, the typical clear lesions first develop followed by ulcers that have a white appearance. The infection, often initially on the lips can spread to all parts of the mouth and pharynx. Reactivation from the trigeminal ganglia can result in what are known as cold sores. Herpes pharyngitis is often associated with other viral infections of the upper respiratory tract. The disease is more severe in immunosuppressed people such as AIDS patients. Herpes Labialis (HSV- 1 ), also known as cold sores, is characterized by a high rate of recurrences, most often at the site of initial infection (recurrent Herpes Labialis). The global sero-prevalence of HSV-I in adults is currently 70-80%, which results in 400 million or more cold sores annually. In the United States 40-50% of the adolescent population and 80- 90% of the adult population has been exposed to HSV-I. Approximately 40% of the infected population has had a cold sore at one time or another and most people who have had cold sores will have recurrent outbreaks. Over 50 million adults in the United States have 2 or more outbreaks per year. Episodes generally regress within 7-10 days with complete healing by 12 - 14 days, although a flat scar or erythema may persist. While recurrent Herpes Labialis is a benign disease that regresses spontaneously, it is highly contagious with high viral titers in blisters and effluent. Herpes Labialis causes physical pain and can also be disfiguring especially in those patients with frequent recurrences.

Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development. Antiviral drugs are one class of antimicrobials, a larger group which also includes antibiotic (also termed antibacterial), antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from viricides, which are not medication but deactivate or destroy virus particles, either inside or outside the body.

There are two topical antiviral medications prescribed for the treatment of oral HSV symptoms: acyclovir (shown as Formula I) ointment (brand name Zovirax®) and penciclovir (shown as Formula II) cream (brand name Denavir®). Both work to speed up the healing process and reduce the viral activity; however, the drugs only provide palliative relief or shorten outbreaks only by about 12 hours. These topical drugs are put directly on the lesions themselves, but can also be used at the onset of prodrome. Other topical treatments for oral herpes are available over-the-counter (OTC), but are not antiviral compounds like acyclovir and penciclovir.

Formula I. Acyclovir Formula II. Penciclovir In prior art, acyclovir derivatives first disclosed in US patent US patent 04199574. A topical pharmaceutical formulation for use in treating virus infections of the skin or mucosa containing acyclovir or a salt or ester is described in EP0044543 (B1 ).

In prior art, penciclovir derivatives disclosed in WO8705604. A topical pharmaceutical formulation for the treatment of virus infections is described in W091 1 1 187.

There are also several patents and applications which disclose topical formulations of acyclovir or penciclovir but none of them specified on acyclovir and allantoin or penciclovir and dexpanthenol or panthenol combinations which is enhanced with antiherpes oils.

On the other hand, acyclovir and penciclovir topical cream is commonly associated (>1 % of patients) with: dry or flaking skin or transient stinging/burning sensations. Infrequent adverse effects include erythema or itch. (Rossi, S, ed. (2013). Australian Medicines Handbook (2013). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0- 9805790-9-3) In addition, adverse effects or events associated with antiviral drugs include rash, pruritus, toxic epidermal necrolysis, urticarial. Acyclovir and penciclovir also suffers from the disadvantage that it has a low solubility in water and is almost totally insoluble in hydrophobic solvent systems. It is accordingly difficult to produce a topical formulation containing a sufficient dissolved concentration of active ingredient for it to exert its full effect and also to optimize the flux of the compound into the skin. It's hard to provide a particularly rapid cure because of poor penetration of the active ingredient into the skin. In addition to ease of release it is also important that any formulation of a pharmaceutically active compound should be stable for long periods of time, should not lose its potency, should not discolor or form insoluble substances or complexes, and should not be unduly irritating to the skin or mucosa.

A new antiviral topical formulation has now been discovered, having improved properties as compared with conventional formulations. In this present invention, topical formulation also satisfy the criteria of adequate stability, maintenance of potency and are not unduly irritating to the skin or mucosa and have the advantages over the prior art formulation of penetrating skin more effectively and in greater concentration with the result that a rapid, complete cure of the infection is achieved. Description of the invention

The present invention relates to a topical pharmaceutical composition comprising an antiviral active ingredient or analogues or derivatives thereof in a combination with an acid active ingredient or analogues or derivatives thereof.

The present invention relates to a topical composition comprising an antiviral active ingredient or analogues or derivatives thereof which is enhanced with antiherpes oils in a combination with an acid active ingredient or analogues or derivatives thereof which is enhanced with oils.

According to the embodiment, an antiviral active ingredient is selected from the group consisting of acyclovir, valacyclovir, famciclovir, ganciclovir, penciclovir, docosanol, edoxudine, ibacitabine, idoxuridine, imiquimod, inosine, muramidase, podophyllotoxin, sinecatechins or tromantadine or analogues or derivatives thereof..

According to one embodiment, an antiviral active ingredient is preferably guanosine analogue of antiviral active ingredient. Guanosine is a purine nucleoside. Nucleoside and nucleotide analogues can be used in therapeutic drugs, include a range of antiviral products used to prevent viral replication in infected cells.

According to the embodiment, an antiviral active ingredient is preferably acyclovir or penciclovir.

Acyclovir, is a guanosine analogue antiviral medication. It is primarily used for the treatment of herpes simplex virus infections. The chemical name is acycloguanosine (ACV). Penciclovir is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections. It is a nucleoside analogue which exhibits low toxicity and good selectivity. Because penciclovir is absorbed poorly when given orally (by mouth) it is used as a topical treatment. According to one embodiment, an acid active ingredient is selected from the group consisting of glyoxylic acid, uric acid or pantothenic acid or analogues or derivatives thereof.

Dexpanthenol is an alcoholic analogue of D-pantothenic acid and cholinergic agent. Allantoin is is a diureide of glyoxylic acid and it is a product of oxidation of uric acid by purine catabolism.

According to the embodiment, an acid active ingredient is preferably panthenol, dexpanthenol or allantoin.

The topical use of allantoin has several beneficial effects including: a moisturizing and keratolytic effect, increasing the water content of the extracellular matrix and enhancing the desquamation of upper layers of dead skin cells, increasing the smoothness of the skin; promoting cell proliferation and wound healing; and a soothing, anti-irritant, and skin protectant effect by forming complexes with irritant and sensitizing agents. Allantoin ameliorates the wound healing process, by modulating the inflammatory response. Allantoin also promotes fibroblast proliferation and synthesis of the extracellular matrix.

It has now been found that, in order to optimize the release of acyclovir from topical formulations, the maximum solubilised concentration of drug should be in the topical pharmaceutical composition. This is achieved by the use of allantoin.

According to one embodiment, the topical pharmaceutical composition comprising acyclovir in a combination with an acid active ingredient or analogues or derivatives thereof.

According to the embodiment, the topical pharmaceutical composition comprising acyclovir in a combination with an acid active ingredient or analogues or derivatives thereof wherein acyclovir is present in an amount of 1 .0 to 10.0% by weight of total formulation. According to another embodiment, the topical pharmaceutical composition comprising an antiviral active ingredient or analogues or derivatives thereof in a combination with allantoin.

According to the embodiment, the topical pharmaceutical composition comprising an antiviral active ingredient or analogues or derivatives thereof in a combination with allantoin, wherein allantoin is present in an amount of 0.1 to 5.0% by weight of total formulation. According to one embodiment, the topical pharmaceutical composition comprising acyclovir in a combination with allantoin.

According to the embodiment, the topical pharmaceutical composition comprising acyclovir is present in an amount of 1 .0 to 10.0% and allantoin is present in an amount of 0.1 to 5.0% by weight of total formulation.

It has been found that by using this specific concentration of allantoin, an increased concentration of solubilised acyclovir can be attained, leading to enhanced activity and efficacy of the formulation. It provides rapid penetration with minimized skin irritation.

The topical use of panthenol or dexpanthenol is based on good skin penetration and high local concentrations of dexpanthenol when administered in an adequate vehicle. Topical dexpanthenol acts like a moisturizer, improving stratum corneum hydration, reducing transepidermal water loss and maintaining skin softness and elasticity. It activates of fibroblast proliferation, which is of relevance in wound healing. The stimulation of epithelization, granulation and mitigation of itching were the most prominent effects of formulations containing dexpanthenol. Usually, the topical administration of dexpanthenol preparations is well tolerated, with minimal risk of skin irritancy or sensitization.

It has now been found that, in order to optimize the release of penciclovir from topical formulations, the maximum solubilised concentration of drug should be in the topical pharmaceutical composition. This is achieved by the use of dexpanthenol or panthenol.

According to one embodiment, the topical pharmaceutical composition comprising penciclovir in a combination with an acid active ingredient or analogues or derivatives thereof.

According to the embodiment, the topical pharmaceutical composition comprising penciclovir in a combination with an acid active ingredient or analogues or derivatives thereof wherein penciclovir is present in an amount of 0.1 to 5.0% by weight of total formulation.

According to another embodiment, the topical pharmaceutical composition comprising an antiviral active ingredient or analogues or derivatives thereof in a combination with dexpanthenol or panthenol. According to the embodiment, the topical pharmaceutical composition comprising an antiviral active ingredient or analogues or derivatives thereof in a combination with dexpanthenol or panthenol wherein dexpanthenol or panthenol is present in an amount of 1 .0 to 10.0% by weight of total formulation.

According to one embodiment, the topical pharmaceutical composition comprising penciclovir in a combination with dexpanthenol or panthenol.

According to the embodiment, the topical pharmaceutical composition penciclovir is present in an amount of 0.1 to 5.0% and dexpanthenol is present in an amount of 1 .0 to 10.0% by weight of total formulation.

It has been found that by using this specific concentration of panthenol or dexpanthenol, an increased concentration of solubilised penciclovir can be attained, leading to enhanced activity and efficacy of the formulation. It provides rapid penetration with minimized skin irritation.

According to one embodiment, said compositions further comprise at least one pharmaceutically acceptable excipient.

According to this embodiment, one or more pharmaceutically acceptable excipient is selected from the group consisting of oils, lipophilic substances, antimicrobial preservatives, water or the mixtures thereof. According to one embodiment, the oil is selected from the group consisting of almond oil, anise oil, avocado oil, babassu oil, basil oil, bay laurel oil, bergamot oil, black, pepper oil, bulgarian lavender oil, cajeput oil, calendula oil, camellia oil, canola oil, cardamom oil, carrot seed oil, caster oil, catnip oil, chamomile oil, cinnamon leaf oil, citronella oil, clary sage oil, clove bud oil, clove blossom oil, coconut oil, coriander seed oil, corn oil, eucalyptus oil, evening primrose oil, fir needle oil, frankincense oil, geranium oil, german blue chamomile oil, ginger oil, grapefruit oil, grapeseed oil, hazelnut oil, helichrysum oil, hemp seed oil, hyssop oil, jojoba oil, juniper berry oil, kukui nut oil, lavandin oil, lavender oil, lemon balm oil, lemon eucalyptus oil, lemon oil, lime oil, macadamia nut oil, may chang oil, melissa officinalis oil, mink oil, myrrh oil, myrtle oil, neroli oil, niaouli oil, olive oil, orange oil, oregano oil, palmarosa oil, patchouli oil, peanut oil, peppermint oil, petitgrain oil, ravensara oil, rose geranium oil, rose otto oil, rosehip oil, rosemary oil, rosewood oil, safflower oil, sage oil, st. john's wort oil, sandalwood oil, sesame oil, Spanish rosemary oil, spearmint oil, spike lavender oil, spruce oil, sunflower oil, sweet birch oil, sweet fennel oil, sweet marjoram oil, sweet orange oil, tangerine oil, tea tree oil, valerian root oil, vetiver oil, walnut oil, wheatgerm oil, white camphor oil, wintergreen oil, yarrow oil or mixtures thereof. According to one embodiment, the oils are preferably geranium oil, lavender oil, melissa officinalis oil, peppermint oil, rosemary oil or mixtures thereof.

The preferred composition comprises acyclovir, allantoin, geranium oil, lavender oil, melissa officinalis oil, peppermint oil, rosemary oil or mixtures thereof.

Another preferred composition comprises penciclovir, dexpanthenol or panthenol, geranium oil, lavender oil, melissa officinalis oil, peppermint oil, rosemary oil or mixtures thereof.

According to the embodiment, oil is present in an amount of 0.001 % to 0.5 by weight of total formulation.

It has been found that the combined use of acyclovir or penciclovir with oils, preferably melissa officinalis oil, peppermint oil, rosemary oil or mixtures can treat active herpes viral infections. This combination has several advantages over prior methods for treating herpes simplex lesions. In labialis and genitalis lesions, the novel formulation can decrease the time of healing, decrease the frequency of recurrent lesions, and can prevent lesion formation when prodromal symptoms are noted. It has further been found that this combination even effective in the treatment of lesions resistant to high dose antivirals.

According to one embodiment, melissa officinalis oil is present in an amount of 0.001 % to 0.1 % by weight of total formulation.

According to the embodiment, peppermint oil is present in an amount of 0.001 % to 0.1 % by weight of total formulation.

According to one embodiment, rosemary oil is present in an amount of 0.001 % to 0.1 % by weight of total formulation. On the other hand, geranium oil and lavender oil or mixtures are well-known for positive effects on various skin disorders like rashes, dermatitis, eczema, infections and scars, etc. It has been found that the combined use of acyclovir or penciclovir with oils, preferably geranium oil, lavender oil or mixtures can help sore fade away, make skin flawless and enhance moisturizer, improving stratum corneum hydration, reducing transepidermal water loss and maintaining skin softness and elasticity activities of allantoin and panthenol or dexpanthenol.

According to one embodiment, geranium oil is present in an amount of 0.001 % to 0.1 % by weight of total formulation.

According to one embodiment, lavender oil is present in an amount of 0.001 % to 0.1 % by weight of total formulation.

In one embodiment, it has been found that the ratio of oil to acyclovir is between 0.0001 - 0.5 (w/w).

In another embodiment, it has been found that the ratio of oil to penciclovir is between 0.0002 - 5 (w/w).

It has been found that this specific ratio improves the therapeutic effect of acyclovir and penciclovir because it accelerates lesion healing, decreases the frequency of recurrent lesions, prevents lesion formation when prodromal symptoms are noted.

It is important with a topical formulation of an antiherpes virus drug that the quantity of drug absorbed by the skin is sufficient to exert a significant antiviral effect and that the drug rapidly reaches its site of action within the skin. This novel ratio provide rapid penetration and a rapid cure.

According to the embodiment, the lipophilic substance is selected from the group consisting of beeswax, capric acid, caprylic acid, silicone oil, white soft paraffin, liquid paraffin, di- isopropyladipate, isocetyl stearate, macrogol cetostearyl ether, diester of coconut fatty acids, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, sorbitan stearate, 2- ethylhexyl palmitate, cetyl alcohol, stearyl alcohol or mixtures thereof.

According to one embodiment, the lipophilic substance are preferably white soft paraffin, liquid paraffin, macrogol cetostearyl ether, sorbitan stearate, cetyl alcohol, stearyl alcohol or mixtures thereof.

The selected lipophilic substances are important to achieve a rapid transdermal penetration of the active ingredient. According to one embodiment, macrogol cetostearyl ether is present in an amount of 1 .0% to 10.0% by weight of total formulation.

According to one embodiment, cetyl alcohol is present in an amount of 1 .0% to 10.0% by weight of total formulation. According to one embodiment, stearyl alcohol is present in an amount of 1 .0% to 10.0% by weight of total formulation.

According to one embodiment, liquid paraffin is present in an amount of 1 .0% to 10.0% by weight of total formulation.

According to one embodiment, white soft paraffin is present in an amount of 1 .0% to 10.0% by weight of total formulation.

According to one embodiment, sorbitan stearate is present in an amount of 1 .0% to 10.0% by weight of total formulation.

In this present invention, the desired ointment and emulsifying base has been achieved with these specific amounts of lipophilic substances. According to one embodiment, the antimicrobial preservative is selected from the group consisting of propylene glycol, phenoxyethanol, methyl paraben, propyl paraben and their salts (such as sodium, potassium), sodium benzoate, citric acid, benzoic acid, butylated hydroxytoluene, boric acid, sorbic acid, benzyl alcohol, benzalconium chloride, parahydroxybenzoic acids or butylated hydroxyanisole or mixtures thereof.

According to one embodiment, the antimicrobial preservatives are preferably propylene glycol, phenoxyethanol or mixtures thereof.

According to the embodiment, said topical pharmaceutical composition applied in the form of foam, cream, gel, paste, lotion, emulsion, balm or combinations thereof.

According to one embodiment, said topical pharmaceutical composition preferably applied in the form of cream. According to the embodiment, the topical pharmaceutical composition is for use in treating a herpes virus infection, preventing a herpes virus infection, preventing recurrent herpes virus infection, preventing reactivation of a herpes virus, minimizing reactivation of a herpes virus. According to one embodiment, said herpes viral infection is cold sore.

According to the embodiment, the herpes virus infection is caused by a herpes virus selected from the group consisting of Herpes Simplex Virus Type 1 (HSV-I), Herpes Simplex Virus Type 2 (HSV-2), Varicella Zoster Virus (VZV), Epstein-Bar Virus (EBV), Cytomegalovirus (CMV), Herpes Lymphotropic Virus, Human Herpes Virus Type 7 (HHV- 7), Human Herpes Virus Type 8 (HHV-8).

In one embodiment, the topical pharmaceutical composition comprising; a. 1 .0 to 10.0% acyclovir by weight of total formulation, preferably 4.0 to 6.0% acyclovir by weight of total formulation b. 0.1 to 5.0% allantoin by weight of total formulation, preferably 0.1 to 2.0% allantoin by weight of total formulation c. 0.001 % to 0.1 % peppermint oil by weight of total formulation, preferably 0.005 to 0.05% peppermint oil by weight of total formulation d. 0.001 % to 0.1 % melissa officinalis oil by weight of total formulation, preferably 0.01 to 0.05% melissa officinalis oil by weight of total formulation e. 0.001 % to 0.1 % rosemary oil by weight of total formulation, preferably 0.01 % to 0.1 % rosemary oil by weight of total formulation f. 0.001 % to 0.1 % geranium oil by weight of total formulation, preferably 0.005% to 0.05% geranium oil by weight of total formulation g. 0.001 % to 0.1 % lavender oil by weight of total formulation, preferably 0.01 % to 0.1 % lavender oil by weight of total formulation

In one embodiment, the topical pharmaceutical composition consisting of; a. 1 .0 to 10.0% acyclovir by weight of total formulation, preferably 4.0 to 6.0% acyclovir by weight of total formulation b. 0.1 to 5.0% allantoin by weight of total formulation, preferably 0.1 to 2.0% allantoin by weight of total formulation c. 0.001 % to 0.1 % peppermint oil by weight of total formulation, preferably 0.005 to 0.05% peppermint oil by weight of total formulation d. 0.001 % to 0.1 % melissa officinalis oil by weight of total formulation, preferably 0.01 to 0.05% melissa officinalis oil by weight of total formulation e. 0.001 % to 0.1 % rosemary oil by weight of total formulation, preferably 0.01 % to 0.1 % rosemary oil by weight of total formulation f. 0.001 % to 0.1 % geranium oil by weight of total formulation, preferably 0.005% to 0.05% geranium oil by weight of total formulation g. 0.001 % to 0.1 % lavender oil by weight of total formulation, preferably 0.01 % to 0.1 % lavender oil by weight of total formulation h. 1 .0% to 10.0% macrogol cetostearyl ether by weight of total formulation, preferably 4.0 to 6.0% macrogol cetostearyl ether by weight of total formulation i. 1 .0% to 10.0% cetyl alcohol by weight of total formulation, preferably 3.0% to 6.0% cetyl alcohol by weight of total formulation j. 1 .0% to 10.0% stearyl alcohol by weight of total formulation, preferably 3.0% to 6.0% stearyl alcohol by weight of total formulation k. 1 .0% to 10.0% liquid paraffin by weight of total formulation, preferably 5.0% to 8.0% liquid paraffin by weight of total formulation

I. 1 .0% to 10.0% white soft paraffin by weight of total formulation, preferably 5.0% to 9.0% white soft paraffin by weight of total formulation m. 1 .0% to 10.0% sorbitan stearate by weight of total formulation, preferably 2.0% to 5.0% sorbitan stearate by weight of total formulation n. 1 .0% to 10.0% propylene glycol by weight of total formulation, preferably 2.0% to 5.0% propylene glycol by weight of total formulation o. 0.1 % to 10.0% phenoxyethanol by weight of total formulation, preferably 0.5% to 3.0% phenoxyethanol by weight of total formulation p. q.s. water In one embodiment, the topical pharmaceutical composition comprising; a. 0.1 to 5.0% penciclovir by weight of total formulation, preferably 0.5 to 3.0% penciclovir by weight of total formulation b. 1 .0 to 10.0% dexpanthenol by weight of total formulation, preferably 2.0 to 5.0% dexpanthenol by weight of total formulation c. 0.001 % to 0.1 % peppermint oil by weight of total formulation, preferably 0.005 to 0.05% peppermint oil by weight of total formulation d. 0.001 % to 0.1 % melissa officinalis oil by weight of total formulation, preferably 0.01 to 0.05% melissa officinalis oil by weight of total formulation e. 0.001 % to 0.1 % rosemary oil by weight of total formulation, preferably 0.01 % to 0.1 % rosemary oil by weight of total formulation f. 0.001 % to 0.1 % geranium oil by weight of total formulation, preferably 0.005% to 0.05% geranium oil by weight of total formulation g. 0.001 % to 0.1 % lavender oil by weight of total formulation, preferably 0.01 % to 0.1 % lavender oil by weight of total formulation

In one embodiment, the topical pharmaceutical composition consisting of; a. 0.1 to 5.0% penciclovir by weight of total formulation, preferably 0.5 to 3.0% penciclovir by weight of total formulation b. 1 .0 to 10.0% dexpanthenol by weight of total formulation, preferably 2.0 to 5.0% dexpanthenol by weight of total formulation c. 0.001 % to 0.1 % peppermint oil by weight of total formulation, preferably 0.005 to 0.05% peppermint oil by weight of total formulation d. 0.001 % to 0.1 % melissa officinalis oil by weight of total formulation, preferably 0.01 to 0.05% melissa officinalis oil by weight of total formulation e. 0.001 % to 0.1 % rosemary oil by weight of total formulation, preferably 0.01 % to 0.1 % rosemary oil by weight of total formulation f. 0.001 % to 0.1 % geranium oil by weight of total formulation, preferably 0.005% to 0.05% geranium oil by weight of total formulation g. 0.001 % to 0.1 % lavender oil by weight of total formulation, preferably 0.01 % to 0.1 % lavender oil by weight of total formulation h. 1 .0% to 10.0% macrogol cetostearyl ether by weight of total formulation, preferably 4.0 to 6.0% macrogol cetostearyl ether by weight of total formulation i. 1 .0% to 10.0% cetyl alcohol by weight of total formulation, preferably 3.0% to 6.0% cetyl alcohol by weight of total formulation j. 1 .0% to 10.0% stearyl alcohol by weight of total formulation, preferably 3.0% to 6.0% stearyl alcohol by weight of total formulation k. 1 .0% to 10.0% liquid paraffin by weight of total formulation, preferably 5.0% to

8.0% liquid paraffin by weight of total formulation

I. 1 .0% to 10.0% white soft paraffin by weight of total formulation, preferably 5.0% to 9.0% white soft paraffin by weight of total formulation m. 1 .0% to 10.0% sorbitan stearate by weight of total formulation, preferably 2.0% to 5.0% sorbitan stearate by weight of total formulation n. 1 .0% to 10.0% propylene glycol by weight of total formulation, preferably 2.0% to 5.0% propylene glycol by weight of total formulation o. 0.1 % to 10.0% phenoxyethanol by weight of total formulation, preferably 0.5% to 3.0% phenoxyethanol by weight of total formulation p. q.s. water

The topical formulations of the present invention is used as an antiviral treatment especially for cold sore with the advantage of moisturizer to treat or prevent skin from irritation during the therapy. Acyclovir and penciclovir display antiviral activity and melissa officinalis oil, peppermint oil, rosemary oil or mixtures enhance antiviral activity. Panthenol dexpanthenol or allantoin soften and moisturize the skin and decrease itching and flaking and geranium oil and lavender oil or mixtures enhance this activity. These novel formulations provide rapid penetration and a rapid cure with a complete healing to the patient who suffers from herpes virus infection. Example 1 : Acyclovir and Allantoin topical cream

Production method:

• Acyclovir and allantoin, oils, propylene glycol, liquid paraffin, phenoxyethanol are mixed and heated to 75 ^Q C (mixture 1 ).

• Cetyl alcohol, stearyl alcohol, macragol cetostearyl ether, sorbitan stearate and white soft paraffin are mixed in 80 ^Q C. (mixture 2).

• Mixture 1 is homogenized with melted mixture 2. This mixture is transferred to a beaker with heated to 80 ^Q C water and homogenized in a homogeniser.

Example 2: Penciclovir and Dexpanthenol topical cream

Ingredients Amount (% w/w)

Penciclovir 1 .0

Dexpanthenol 3.0 Peppermint oil 0.01

Melissa officinalis oil 0.02

Rosemary oil 0.06

Geranium oil 0.01

Lavender oil 0.05

Macrogol cetostearyl ether 5.0

Cetyl alcohol 4.2

Stearyl alcohol 4.2

Liquid paraffin 7.0

White soft paraffin 8.0

Sorbitan stearate 3.0

Propylene glycol 3.0

Phenoxyethanol 1 .0

Water 60.45

Production method:

• Penciclovir and dexpanthenol, oils, propylene glycol, liquid paraffin, phenoxyethanol are mixed and heated to 75 ^Q C (mixture 1 ).

• Cetyl alcohol, stearyl alcohol, macragol cetostearyl ether, sorbitan stearate and white soft paraffin are mixed in 80 ^Q C. (mixture 2).

• Mixture 1 is homogenized with melted mixture 2. This mixture is transferred to a beaker with heated to 80 ^Q C water and homogenized in a homogeniser.