EP3337512A1 - Composition antivirale topique - Google Patents

Composition antivirale topique

Info

Publication number
EP3337512A1
EP3337512A1 EP16759693.1A EP16759693A EP3337512A1 EP 3337512 A1 EP3337512 A1 EP 3337512A1 EP 16759693 A EP16759693 A EP 16759693A EP 3337512 A1 EP3337512 A1 EP 3337512A1
Authority
EP
European Patent Office
Prior art keywords
oil
weight
total formulation
pharmaceutical composition
topical pharmaceutical
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP16759693.1A
Other languages
German (de)
English (en)
Inventor
Ali TÜRKYILMAZ
Nur PEHLIVAN AKALIN
Sevda TUNA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanovel Ilac Sanayi ve Ticaret AS
Original Assignee
Sanovel Ilac Sanayi ve Ticaret AS
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Filing date
Publication date
Application filed by Sanovel Ilac Sanayi ve Ticaret AS filed Critical Sanovel Ilac Sanayi ve Ticaret AS
Publication of EP3337512A1 publication Critical patent/EP3337512A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A61K31/708—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals

Definitions

  • the present invention relates to a topical composition
  • 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.
  • 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.
  • 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 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.
  • 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.
  • 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.
  • acyclovir shown as Formula I
  • ointment brand name Zovirax®
  • penciclovir shown as Formula II cream
  • Denavir® brand name Denavir®
  • 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.
  • 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). Sydney: The Australian Medicines Handbook Unit Trust. ISBN 978-0- 9805790-9-3)
  • 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.
  • 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.
  • 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
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • an acid active ingredient is preferably panthenol, dexpanthenol or allantoin.
  • 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.
  • the topical pharmaceutical composition comprising acyclovir in a combination with an acid active ingredient or analogues or derivatives thereof.
  • 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.
  • the topical pharmaceutical composition comprising an antiviral active ingredient or analogues or derivatives thereof in a combination with allantoin.
  • 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.
  • the topical pharmaceutical composition comprising acyclovir in a combination with allantoin.
  • 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.
  • 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.
  • the topical administration of dexpanthenol preparations is well tolerated, with minimal risk of skin irritancy or sensitization.
  • the topical pharmaceutical composition comprising penciclovir in a combination with an acid active ingredient or analogues or derivatives thereof.
  • 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.
  • the topical pharmaceutical composition comprising an antiviral active ingredient or analogues or derivatives thereof in a combination with dexpanthenol or panthenol.
  • 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.
  • the topical pharmaceutical composition comprising penciclovir in a combination with dexpanthenol or panthenol.
  • 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.
  • panthenol or dexpanthenol 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.
  • compositions further comprise at least one pharmaceutically acceptable excipient.
  • one or more pharmaceutically acceptable excipient is selected from the group consisting of oils, lipophilic substances, antimicrobial preservatives, water or the mixtures thereof.
  • 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,
  • 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.
  • compositions comprises penciclovir, dexpanthenol or panthenol, geranium oil, lavender oil, melissa officinalis oil, peppermint oil, rosemary oil or mixtures thereof.
  • oil is present in an amount of 0.001 % to 0.5 by weight of total formulation.
  • acyclovir or penciclovir with oils, preferably melissa officinalis oil, peppermint oil, rosemary oil or mixtures can treat active herpes viral infections.
  • oils preferably melissa officinalis oil, peppermint oil, rosemary oil or mixtures.
  • 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.
  • melissa officinalis oil is present in an amount of 0.001 % to 0.1 % by weight of total formulation.
  • peppermint oil is present in an amount of 0.001 % to 0.1 % by weight of total formulation.
  • rosemary oil is present in an amount of 0.001 % to 0.1 % by weight of total formulation.
  • 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.
  • geranium oil is present in an amount of 0.001 % to 0.1 % by weight of total formulation.
  • lavender oil is present in an amount of 0.001 % to 0.1 % by weight of total formulation.
  • the ratio of oil to acyclovir is between 0.0001 - 0.5 (w/w).
  • the ratio of oil to penciclovir is between 0.0002 - 5 (w/w).
  • 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.
  • 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.
  • macrogol cetostearyl ether is present in an amount of 1 .0% to 10.0% by weight of total formulation.
  • cetyl alcohol is present in an amount of 1 .0% to 10.0% by weight of total formulation.
  • stearyl alcohol is present in an amount of 1 .0% to 10.0% by weight of total formulation.
  • liquid paraffin is present in an amount of 1 .0% to 10.0% by weight of total formulation.
  • white soft paraffin is present in an amount of 1 .0% to 10.0% by weight of total formulation.
  • sorbitan stearate is present in an amount of 1 .0% to 10.0% by weight of total formulation.
  • 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.
  • the antimicrobial preservatives are preferably propylene glycol, phenoxyethanol or mixtures thereof.
  • said topical pharmaceutical composition applied in the form of foam, cream, gel, paste, lotion, emulsion, balm or combinations thereof.
  • said topical pharmaceutical composition preferably applied in the form of cream.
  • 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.
  • said herpes viral infection is cold sore.
  • 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).
  • HSV-I Herpes Simplex Virus Type 1
  • HSV-2 Herpes Simplex Virus Type 2
  • VZV Varicella Zoster Virus
  • EBV Epstein-Bar Virus
  • CMV Cytomegalovirus
  • HHV- 7 Human Herpes Virus Type 7
  • HHV-8 Human Herpes Virus Type 8
  • 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
  • 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.
  • the topical pharmaceutical composition comprising; a.
  • 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
  • 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.
  • 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.
  • 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.
  • Penciclovir and dexpanthenol, oils, propylene glycol, liquid paraffin, phenoxyethanol are mixed and heated to 75 Q C (mixture 1 ).
  • 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.

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Abstract

La présente invention concerne une composition topique comprenant un principe actif antiviral ou des analogues ou dérivés de ce dernier, qui est enrichi en huiles contre l'herpès en combinaison avec un principe actif acide ou des analogues ou dérivés de ce dernier qui est enrichi en huiles.
EP16759693.1A 2015-08-17 2016-08-16 Composition antivirale topique Withdrawn EP3337512A1 (fr)

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TR201510146 2015-08-17
PCT/EP2016/069450 WO2017029298A1 (fr) 2015-08-17 2016-08-16 Composition antivirale topique

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CN112514926B (zh) * 2020-12-14 2021-10-01 杭州象外环保科技有限公司 一种灭活冠状病毒的天然植萃精油消毒剂及应用
CN112616861B (zh) * 2020-12-14 2021-10-01 杭州象外环保科技有限公司 一种天然植萃精油新型冠状病毒消毒剂及其应用
WO2023062348A1 (fr) 2021-10-13 2023-04-20 Reckitt Benckiser Health Limited Compositions antivirales et leurs procédés de production et d'utilisation

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US4199574A (en) 1974-09-02 1980-04-22 Burroughs Wellcome Co. Methods and compositions for treating viral infections and guanine acyclic nucleosides
GB2080106B (en) 1980-07-18 1984-03-07 Weelcome Foundation Ltd Acyclovin preparations
DE3582399D1 (de) 1984-09-20 1991-05-08 Beecham Group Plc Purin-derivate und ihre pharmazeutische verwendung.
GB9001886D0 (en) 1990-01-26 1990-03-28 Beecham Group Plc Pharmaceutical formulation
US5869529A (en) * 1994-07-20 1999-02-09 Agis Industries (1983) Ltd. Topical preparation for the prevention and treatment of lesions and sores associated with a herpes virus
WO1998017264A1 (fr) * 1996-10-24 1998-04-30 Nextech Enterprises International Composition et procede de traitement topique des infections a herpesvirus actives
JP4972062B2 (ja) * 2008-03-17 2012-07-11 メディヴィル・アクチエボラーグ 抗ウイルス製剤
ITMI20111747A1 (it) * 2011-09-28 2013-03-29 Fidia Farmaceutici Composizioni farmaceutiche topiche comprendenti aciclovir
WO2014131096A1 (fr) * 2013-02-27 2014-09-04 Advance Pharma Tecnologia E Inovação Ltda - Me Formulation obtenue par association de l'antiviral aciclovir avec la vitamine b6 et un anti-histaminique pour le traitement de l'herpès et moyen d'application

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