TW201605444A - Topical pharmaceutical or cosmetic compositions comprising octenidine dihydrochloride - Google Patents

Abstract

Topical pharmaceutical or cosmetic compositions are described comprising octenidine dihydrochloride. Said compositions are stable and can be safely and easily applied over large surface areas of the skin in an acceptable way by the general patient population for the treatment or prevention of some skin disorders or diseases.

Description

a topical pharmaceutical composition or cosmetic composition comprising octenidine dihydrochloride

The present invention relates to a topical pharmaceutical composition or cosmetic composition comprising octenidine dihydrochloride. The invention further relates to methods of treating some skin diseases or conditions by administering such compositions.

"Atopic" is a term used to develop the propensity for eczema, asthma, and/or hay fever. An individual may be referred to as atopic when it has one of these conditions.

The terms "eczema" and "dermatitis" are interchangeable and mean the same thing. Atopic eczema (or atopic dermatitis) is dry, itchy and inflamed skin. Atopic eczema can affect any part of the skin, including the face; but most of the often affected areas are the elbows, around the knees, and around the wrists and neck. These parts are called "flexing" areas. The condition is usually very itchy and in some people, the condition interferes with their sleep. It also affects both sexes and usually begins weeks or months before life. This condition is most common in children, although it can persist to adult life or relapse in adolescence or early adulthood.

People with atopic eczema also have a tendency to dry skin, making them susceptible to the drying effect of soap (Williams et al., Atopic eczema, In: Evidence-based dermatology, BMJ Publishing Group, 2003, pp. 144-218).

Bacterial or fungal infections such as those infected by Staphylococcus aureus , which are common in all types of eczema, are a definite aggravating factor for atopic eczema.

When the atopic eczema is expanded, topical corticosteroid creams, lotions, and ointments can be applied to the affected area. Creams are often the best choice for treating wet or oozing areas of the skin. Ointments are preferably used to treat areas of the skin that are dry or thick. Lotions can be used to treat areas of the hair such as the scalp.

Treatment of eczema infected with S. aureus can include two different strategies: treatment of infected skin, and prevention of immunization/infection in patients at risk. Management of patients with atopic eczema often involves the use of antibacterial agents to prevent colonization or reduce bacterial counts.

An antibacterial agent is a disinfectant (a chemical agent that destroys or inhibits a pathogenic microorganism in a non-sporing or proliferative state) that is applied to the skin and other living tissues to limit or prevent infection (Martindale-The Complete drug reference, 32nd edition, 1999, Disinfectants and Preservatives).

The main advantage of antibacterial agents is that they induce the potential to resist Staphylococcus aureus even when repeated and widely used; the different preparations can be adapted to individual diseases depending on disease activity and associated treatment. Need; and, in contrast to some topical antibiotics, it rarely causes delayed type of allergies. The antibacterial agent is usually in the form of a bath (sodium hypochlorite), in the form of an antibacterial ointment (such as 1-2% triclosan added to the softener or 0.5-1% roceceptine gluconate) or in an aqueous solution (such as with 2%). Use of phenoxyethanol in combination with 0.1% octenidine dihydrochloride or 4% locefixidine gluconate (Schnopp C, Ring J, Mempel M., The role of antibacterial therapy in atopic eczema) ;Expert Opin.Pharmacother. April 2010; 11(6): 929-36).

However, due to the chemical nature of some antimicrobial agents such as lohexidine gluconate or octenidine dihydrochloride (cationic species), surfactants in the formulation can interfere with the activity of the antimicrobial agent (Sedlock et al, Microbicidal activity of octenidine hydrochloride, a new alkanediylbis [pyridine] germicidal agent, Antimicrob. Agents Chemother. 1985 December; 28(6): 786-790).

In the field of topical therapies for the treatment of skin diseases or conditions, in particular for the treatment of infectious eczema, skin bacterial infections or dermatophyte infections, the local composition of the antibacterial agent, in particular octenidine dihydrochloride The need for the presence of such compositions is effective (providing disinfectant properties), chemically stable, free of side effects, cosmetically acceptable (in terms of texture, dispersion, penetration, etc.) and can be provided to the skin Other benefits, such as improving the skin barrier and increasing skin moisture. In addition, it is desirable that the composition not only treats the skin once it has been infected, but also prevents patients at risk (i.e., patients suffering from atopic dermatitis and/or dry skin). Skin transfer/infection.

Pharmaceutical compositions and cosmetic compositions comprising octenidine dihydrochloride are known in the art. For example, WO 2007/031520 describes a pharmaceutical semi-solid preparation comprising octenidine dihydrochloride. In addition, none of the formulations described in WO 2007/031520 contain 1-20 wt.% of at least one petroleum hydrocarbon and simultaneously contain 30-70 wt.% water.

WO 2007/031519 describes an antimicrobial preparation comprising octenidine dihydrochloride encapsulated in liposomes, in particular phospholipid liposomes, which are used to reduce the risk of local side effects and improve user acceptance . However, the formulation described in WO 2007/031519 contains greater than 70 wt.% water and does not contain any petroleum hydrocarbons.

DE 10 2010 044 785 describes cosmetic or dermatological preparations which are formulated as microemulsions comprising octenidine dihydrochloride as a co-emulsifier. However, the formulation described in DE 10 2010 044 785 contains more than 70 wt.% water.

DE 10 2010 044 787 describes cosmetic or dermatological preparations which are formulated as macromolecules comprising octenidine dihydrochloride as a deodorant active ingredient. However, the formulation described in DE 10 2010 044 787 contains more than 70 wt.% water and does not contain any petroleum hydrocarbons.

None of these documents, however, describe topical compositions comprising octenidine dihydrochloride that provide antimicrobial properties while providing other benefits to the skin, such as improving skin barriers and increasing skin moisture.

The present application relates to a topical pharmaceutical composition or cosmetic composition comprising: (a) 0.01-3.0 wt.% of octenidine dihydrochloride; (b) 1-20 wt.% of at least one petroleum hydrocarbon; (c) 0.5 to 10 wt.% of at least one C ₆ -C ₂₄ fatty acid triglyceride; (d) 1 to 20 wt.% of at least one C ₆ -C ₂₄ fatty alcohol; (e) at least one of 1 to 15% by weight a nonionic surfactant; (f) from 1 to 20% by weight of at least one polyol; and (g) from 30 to 70% by weight of water.

The compositions are chemically stable, free of side effects and cosmetically acceptable. Accordingly, the compositions are suitable for treating a skin disease or condition selected from the group consisting of infectious eczema (infectious dermatitis or infectious skin disease), skin bacterial infection or skin fungal infection.

Additionally, the compositions of the present invention may be used by patients suffering from atopic dermatitis and/or dry skin to prevent microbial proliferation and restore skin barrier function.

The invention further relates to the use of a composition as defined above for the manufacture of a medicament for the treatment or prevention of a skin condition selected from the group consisting of infectious eczema (infectious dermatitis), skin bacterial infection or dermatophyte infection Or disease.

The invention further relates to the use of a composition as defined above for preventing microbial proliferation and restoring skin barrier function in a patient suffering from atopic dermatitis and/or dry skin.

The invention further relates to a method for treating a subject suffering from a skin condition or disease as defined above, the method comprising applying to the affected area of the subject a effective amount of a portion as defined above Pharmaceutical composition.

Alternidine dihydrochloride

Alternidine dihydrochloride (N,N'-(1,10-decanediyldi-1[4H]-pyridyl-4-ylidene)bis-(1-octylamine) dihydrochloride ; CAS RN 70775-75-6) is a bipyridine bactericidal antibacterial agent with some antiviral and antifungal activity with an empirical formula of C ₃₆ H ₆₂ N ₄ .2H ₂ O and a molecular weight of 623.8 g/mol (see Martindale) - The complete drug reference, 32nd edition, 1999, Disinfectants and Preservatives).

Topical pharmaceutical composition or cosmetic composition

Typically, the present invention provides a topical pharmaceutical composition or cosmetic composition comprising: (a) 0.01 to 3.0 wt.% of octenidine dihydrochloride; (b) 1 to 20 wt.% of at least one petroleum hydrocarbon (c) 0.5 to 10 wt.% of at least one C ₆ -C ₂₄ fatty acid triglyceride; (d) 1 to 20 wt.% of at least one C ₆ -C ₂₄ fatty alcohol; (e) at least 1 to 15% by weight A nonionic surfactant; (f) from 1 to 20% by weight of at least one polyol; and (g) from 30 to 70% by weight of water.

In accordance with the present invention, the term "topical composition" (or topical formulation) means any cosmetic product or formulation that is applied or spread over the surface of the skin.

Preferably, in the topical pharmaceutical composition or cosmetic composition according to the present invention, the total amount of (a) octenidine dihydrochloride is in the range of 0.03-1.5 wt.%, based on the total weight of the composition. More preferably, it is 0.05-1.0 wt.%. Particularly preferred amounts of (a) octenidine dihydrochloride are 0.05 wt.%, 0.1 wt.% and 0.25 wt.%, based on the total weight of the composition.

Preferably, in the topical pharmaceutical composition or cosmetic composition according to the present invention, (b) the total amount of petroleum is in the range of 3 to 15 wt.%, based on the total weight of the composition.

Preferably, in the topical pharmaceutical composition or cosmetic composition according to the present invention, the total amount of (c) C ₆ -C ₂₄ fatty acid triglyceride is in the range of 1-5 wt.% based on the total weight of the composition. .

Preferably, in the topical pharmaceutical composition or cosmetic composition according to the present invention, the total amount of (d) C ₆ -C ₂₄ fatty alcohol is in the range of 7 to 18 wt.%, based on the total weight of the composition.

Preferably, in the topical pharmaceutical composition or cosmetic composition according to the present invention, the total amount of (e) nonionic surfactant is in the range of 2 to 10 wt.%, based on the total weight of the composition.

Preferably, in the topical pharmaceutical composition or cosmetic composition according to the present invention, the total amount of (f) polyol is in the range of 5 to 15 wt.%, based on the total weight of the composition.

Preferably, in the topical pharmaceutical composition or cosmetic composition according to the present invention, the total amount of (g) water is in the range of 50 to 65 wt.%, based on the total weight of the composition.

Suitable petroleum hydrocarbons according to the invention, that is, mineral oils, paraffin waxes and waxes derived from petroleum are: hard paraffin, liquid paraffin (liquid paraffin or liquid paraffin), light liquid paraffin (light liquid paraffin or light liquid) Paraffinum Perliquidium, white soft paraffin (white paraffin), yellow soft paraffin (yellow paraffin), coarse crystalline paraffin (which is mainly composed of saturated C ₁₈ -C ₃₀ hydrocarbons and smaller amounts of isoalkanes and rings) a mixture of alkane compositions having a molecular weight between 250 g/mol and 450 g/mol, although it is solid at room temperature, having a low melting point typically between 40 ° C and 60 ° C), microcrystalline Paraffin wax (which consists of C ₄₀ -C ₅₅ compounds containing, in addition to linear hydrocarbons, a large number of isoalkanes and N-cycloalkanes having long alkyl side chains, which form crystallites, The microcrystalline paraffins have an average molecular weight of between 500 g/mol and 800 g/mol, a solid at room temperature, and a melting point between 60 ° C and 90 ° C or a mixture thereof.

Preferred petroleum hydrocarbons are hard paraffin, liquid paraffin, light liquid paraffin, white soft paraffin or mixtures thereof, particularly preferably liquid paraffin, white soft paraffin or mixtures thereof.

According to the invention, the C ₆ -C ₂₄ fatty acid triglyceride is especially a triglyceride of linear and/or branched, saturated and/or unsaturated alkanoic acids having a chain length of from 6 to 24 carbon atoms, preferably The ground is 8 up to 18 carbon atoms. The fatty acids at different positions of the esterified glycerol can be different in order to produce a large number of possible combinations, including positional combinations. The location of the different fatty acids in the natural triglyceride is not random, but depends on the source of the fat. Triglycerides are simpler as their triglycerides composed of individual fatty acids.

Preferred C ₆ -C ₂₄ fatty acid triglycerides according to the invention are, for example, selected from the group consisting of synthetic, semi-synthetic and natural oils, such as animal fats and oils, such as tallow, lard, bone oil, aquatic animals. Fats and oils (fish, such as salmon, mackerel or sardines; cetaceans; etc.); and vegetable fats and oils such as avocado oil, almond oil, hazelnut oil, carnauba oil, borage oil, Peanut oil, rapeseed oil, hemp oil, milk thistle oil, safflower oil, eucalyptus oil, coconut oil, rapeseed oil, black cumin oil, wheat germ oil, sunflower oil, linseed oil, Australian walnut oil, corn oil, walnut oil , olive oil and its by-products (such as olive residue), palm oil and its fractions (such as palm oil and palm stearin), evening primrose oil, rosehip oil, castor oil, rice bran oil, apricot kernel oil , cottonseed oil, pumpkin seed oil, palm kernel oil and fractions thereof (such as palm kernel oil and palm kernel stearin), grape seed oil, sesame oil, soybean oil, cocoa butter, shea butter and the like. Caproic acid, citric acid, octanoic acid, lauric acid, myristal, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, 2-ethylhexanoic acid, oleic acid, ricinoleic acid, behenic acid type or a mixture of aliphatic C ₆ -C ₂₄ fatty acid triglyceride is preferred, especially those derived from their plant sources. Specific preferred C ₆ -C ₂₄ fatty acid triglycerides of caproic acid, capric acid, caprylic acid and mixtures of lauric acid type and C ₆ -C ₂₄ fatty acid triglycerides.

Suitable fatty alcohols according to the invention are C ₆ -C ₂₄ fatty alcohols from the group consisting of vegetable and animal fats and oils, such as the oils previously described, cotton oil, safflower oil, coconut oil, rapeseed oil, linseed Oil, palm oil, palm kernel oil, sunflower oil, oil, olive oil, olive residue, castor oil, tallow, soybean oil, pine oil, etc., which may be wholly or partially hydrogenated; and, purified or synthesized fatty alcohol , such as hexitol, sterol, sterol, lauryl alcohol, myristyl alcohol, palmitol (cetyl alcohol), palmitol, stearol, isostearyl alcohol, 2-octyldodecanol (isohexadecanol), 2-ethylhexyl alcohol, oleyl alcohol, ricinoleol, oleyl alcohol, apigenic acid alcohol, flax alcohol, linolenic alcohol, eicosyl alcohol, eucalyptol, twenty A diol and a docadienyl alcohol, or a technical grade mixture thereof, such as cetearyl alcohol. Lauryl, myristyl, palmitate, palm oil, stearyl, isostearyl, 2-octyldodecan, 2-ethylhexyl, oil, castor oil and Dibasic types of fatty alcohols or technically graded mixtures thereof, such as cetearyl alcohol, are preferred, especially those from plant sources.

Suitable nonionic surfactants according to the invention are acetyl glycerides; diethylated monoglycerides; mono- and di-acetylated monoglycerides; mono- and diglycerides (such as mono-docosyl glycerides) , bis(docic acid) glyceride, glycerol monooleate, glyceryl dioleate, glyceryl monostearate, glyceryl distearate, glyceryl monopalmitate or dipalmitole Glyceryl stearate; an ester of ethylene glycol or propylene glycol with a C ₆ -C ₂₂ fatty acid (such as ethylene glycol monopalmitardate, ethylene glycol monostearate, propylene glycol monocaprylate, propylene glycol) Dioctanoate, propylene glycol dicaprylocaprate, propylene glycol monopalmitate, propylene glycol monostearate or propylene glycol alginate; polyoxyethylene alkyl ether [ Polyoxyethylene glycol ethers of n-alcohols such as lauryl alcohol, oleyl alcohol, myristyl alcohol, cetyl alcohol and stearol; such as polyethylene glycol cetearyl ether (polyoxy 6 cetyl hard) Aliphatic ether, polyoxy 20 cetyl stearyl ether or polyoxyl 25 cetyl stearyl ether), polyethylene glycol cetyl ether (such as polyoxy 2 cetyl) , polyoxy 10 cetyl ether or polyoxy 20 cetyl ether), polyethylene glycol lauryl ether (such as polyoxy 2 lauryl ether, polyoxy 4 lauryl ether, polyoxy 9 lauryl ether or polyoxyl) 23 lauryl ether), polyethylene glycol stearyl ether (such as polyoxy 2 stearyl ether, polyoxy 10 stearyl ether, polyoxy 21 stearyl ether or polyoxyl 100 stearyl ether) , or polyethylene glycol oleyl ether (such as polyoxy 2 oleyl ether, polyoxyl 10 oleyl ether or polyoxy 20 oleyl ether)]; polyethylene glycol monomethyl ether (having from 300 to 10,000, preferably a polyethylene glycol monomethyl ether having a nominal average molecular weight in the range of from 320 to 4,000, more preferably in the range of from 350 to 1,000, such as polyoxyethylene glycol 1000 cetyl ether; menthastanc ether; nonoxynol Ether (such as nonoxynol ether 9, nonoxynol ether 10 or nonoxynol ether 11); octoxynol (such as octoxynol 9); poloxamer (polyoxyethylene and polyoxypropylene copolymer) , such as poloxamer 188); polyoxy castor oil (such as polyoxy 35 castor oil); polyoxy hydrogenated castor oil (such as polyoxy 40 hydrogenated castor oil); polyoxystearate (hard a polyethoxylated derivative of a fatty acid, such as a polyoxy 2 hard Fatty acid, polyoxy 4 stearic acid, polyoxy 6 stearic acid, polyoxy 8 stearic acid, polyoxy 12 stearic acid, polyoxy 20 stearic acid, polyoxy 40 stearic acid , polyoxyl 50 stearic acid, polyoxyl 100 stearic acid, polyoxyl 150 stearic acid, polyoxy 4 distearate, polyoxy 8 distearate, polyoxy 12 Stearate, polyoxy 32 distearate or polyoxyl 150 distearate; polyoxyethylene sorbitan fatty acid ester (such as polysorbate 20, polysorbate 40, Polysorbate 60, polysorbate 65, polysorbate 80 or polysorbate 85); propylene glycol diacetate (PGDA, which is the reaction product of propylene oxide and acetic acid); sorbitan ester ( Such as sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, dehydrated Sorbitol trioleate or sorbitan tristearate) and sucrose esters.

Preferred nonionic surfactants according to the invention are mono- and diglycerides (such as mono-docosyl glyceride, bis(docosuccinate) glycerides, glycerol monooleate, glyceryl dioleate, Monostearate glyceride, glyceryl distearate, glyceryl monopalmitate or glyceryl dipalmitate; esters of ethylene glycol or propylene glycol with C ₆ -C ₂₂ fatty acids (such as Ethylene glycol monopalmitate stearate, ethylene glycol monostearate, propylene glycol monocaprylate, propylene glycol dicaprylate, propylene glycol dicaprylate / dicaprate, propylene glycol monopalmitose stearic acid Ester, propylene glycol monostearate or propylene glycol alginate); polyoxyethylene alkyl ether [polyoxyethylene B such as lauryl alcohol, oleyl alcohol, myristyl alcohol, cetyl alcohol and n-ol of stearyl alcohol Glycol ether; such as polyethylene glycol cetearyl ether (polyoxy 6 cetearyl ether, polyoxy 20 cetearyl ether or polyoxy 25 cetyl stearyl ether), polyethylene glycol Cetyl ether (such as polyoxy 2 cetyl ether, polyoxy 10 cetyl ether or polyoxy 20 cetyl ether), polyethylene glycol lauryl ether (such as polyoxy 2 lauryl ether, polyoxy 4 Ethyl ether, polyoxy 9 lauryl ether or polyoxy 23 lauryl ether), polyethylene glycol stearyl decyl ether (such as polyoxy 2 stearyl ether, polyoxy 10 stearyl ether, polyoxyl 21 stearic acid ether or polyoxyl 100 stearin ether), or polyethylene glycol oleyl ether (such as polyoxy 2 oleyl ether, polyoxyl 10 oleyl ether or polyoxy 20 oleyl ether)]; polyoxygen Ethylene sorbitan fatty acid ester (such as polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80 or polysorbate 85); propylene glycol diethyl Acid ester (PGDA, which is the reaction product of propylene oxide and acetic acid); and sorbitan ester (such as sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate) , sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate or sorbitan tristearate).

Particularly preferred nonionic surfactants according to the invention are mono- and diglycerides (such as mono-docosyl glyceride, bis(docosuccinate) glycerides, glycerol monooleate, glyceryl dioleate , glyceryl monostearate, glyceryl distearate, glyceryl monopalmitate or glyceryl dipalmitate); esters of ethylene glycol or propylene glycol with C ₆ -C ₂₂ fatty acids ( Such as ethylene glycol monopalmitate stearate, ethylene glycol monostearate, propylene glycol monocaprylate, propylene glycol dicaprylate, propylene glycol dicaprylate / dicaprate, propylene glycol monopalmitoside stearin Acid ester, propylene glycol monostearate or propylene glycol alginate); and polyoxyethylene sorbitan fatty acid ester (such as polysorbate 20, polysorbate 40, polysorbate 60, polysorbate) Ester 65, polysorbate 80 or polysorbate 85).

Suitable polyols according to the invention are preferably water-soluble polyols, such as polyols having two or more hydroxyl groups in their molecule. Specific examples may include ethylene glycol, propylene glycol, 1,3-butanediol, 1,4-butanediol, hexanediol, dipropylene glycol, polyethylene having an average molecular weight ranging from 100 to 1000 by weight. Alcohol, glucose, fructose, galactose, mannose, ribose, erythroglucose, maltose, maltobiose, maltotriose, sucrose, xylitol, sorbitol, threitol, erythritol, glycerol, Polyglycerol and starch alcohol. Preferred polyols according to the invention are ethylene glycol, propylene glycol, 1,3-butanediol, 1,4-butanediol, hexanediol, dipropylene glycol, and the average molecular weight ranges between 100 and 1000 by weight. Varying polyethylene glycol, glycerin, Polyglycerol and mixtures thereof.

Particularly preferred polyols in accordance with the present invention are 1,3-butanediol, 1,4-butanediol, hexanediol, dipropylene glycol, glycerin, and mixtures thereof.

In a particularly preferred embodiment, the topical pharmaceutical composition or cosmetic composition of the present invention comprises (a) 0.03-1.5 wt.% of octenidine dihydrochloride; (b) based on the total weight of the composition; 3-15 wt.% of at least one petroleum hydrocarbon; (c) 1-5 wt.% of at least one C ₆ -C ₂₄ fatty acid triglyceride; (d) 7-18 wt.% of at least one C ₆ -C ₂₄ fat (e) 2-10 wt.% of at least one nonionic surfactant; (f) 5-15 wt.% of at least one polyol; and (g) 50-65 wt.% of water.

In another particularly preferred embodiment, the topical pharmaceutical composition or cosmetic composition of the present invention comprises, based on the total weight of the composition: (a) 0.01 to 3.0 wt.%, preferably 0.03 to 1.5 wt.% (b) 1-20 wt.%, preferably 3-15 wt.% of at least one petroleum hydrocarbon selected from the group consisting of hard paraffin, liquid paraffin, light liquid paraffin, white soft paraffin, and mixtures thereof; (c) 0.5 to 10 wt.%, preferably 1 to 5 wt.% of at least one C ₆ -C ₂₄ fatty acid triglyceride; (d) 1 to 20 wt.%, preferably 7 to 18 wt.% of at least one C ₆ -C ₂₄ fatty alcohol; (e) 1 to 15% by weight, preferably 2 to 10% by weight, of at least one nonionic surfactant selected from the group consisting of mono- and diglycerides, ethylene glycol or propylene glycol and C ₆ -C ₂₂ the fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene sorbitan fatty acid esters, propylene glycol diacetate, sorbitan esters and mixtures thereof; (f) 1 to 20wt%, preferably 5- 15 wt.% of at least one polyol selected from the group consisting of ethylene glycol, propylene glycol, 1,3-butanediol, 1,4-butanediol, hexanediol, dipropylene glycol, and an average molecular weight of 100 and 1000 by weight Polyethylene glycol, glycerin, polyglycerol and Mixture;., And (g) 30-70wt%, preferably 50-65wt% water.

The topical pharmaceutical composition or cosmetic composition according to the present invention may further comprise other well-known pharmaceutically and/or cosmetically acceptable additives, such as, for example, anti-irritants, antioxidants, buffers (pH adjusters), and chelates, as needed. Mixtures, softeners, natural waxes, penetration enhancers, preservatives, polyoxyxides, solubilizers, thickeners, wetting agents or mixtures thereof.

Examples of suitable anti-irritants are aloe vera, chamomile, alpha-mycohol, cola extract, green tea extract, tea tree oil, licorice extract, shark liver alcohol (alpha-octadecyl glyceryl ether), squalene alcohol (α-9-octadecenyl glyceryl ether), stilbenol (α-hexadecyl glyceryl ether), ubiquinol, allantoin, caffeine or other xanthine, glycyrrhizic acid and its derivatives, and mixture.

The antioxidants used may be any antioxidant suitable or customary for cosmetic and/or dermatological applications. Suitable antioxidants are advantageously selected from the group consisting of amino acids (eg glycine, histidine, tyrosine, tryptophan) and derivatives thereof; imidazoles (eg 4-imidazole acrylic acid) and Derivatives; peptides such as D, L-carnosine, D-carnosine, L-carnosine and its derivatives (eg, carnosine); carotenoids; carotene (eg, alpha-carotene, beta-carotene, tomato red) And its derivatives; fatty acids and their derivatives (such as dihydrolipidic acid); thiogold-substituted glucose; propylthiouracil and other thiols (such as thioredoxin, glutathione, half Cystamine, cystine, cystamine and its glycosides, N-acetyl ester, methyl ester, ethyl ester, propyl ester, pentyl ester, butyl ester and lauryl ester, palm palmate, oil ester, γ-linseed oil Esters, cholesterol esters and glycerides) and their salts; dilauryl thiodipropionate, stearyl thiodipropionate; thiodipropionic acid and its derivatives (esters, ethers, peptides, lipids, Nucleotides, nucleosides and salts); and imipenem compounds (eg, pmol to μmol/kg) (eg, imipenem butyrate, homocysteine) Imine, butyl thiocyanate, imipenem pentoxide, imipenem hexamide, yttrium thiosinate; and (metal) chelating agents (eg alpha-hydroxy fatty acids) , palmitic acid, vegetable acid, lactoferrin); α-hydroxy acid (eg citric acid, lactic acid, malic acid); humic acid; cholic acid; bile extract; bilirubin; biliverdin; EDTA; EGTA and Its derivatives; unsaturated fatty acids and their derivatives (such as γ-linolenic acid, linoleic acid, oleic acid); folic acid and its derivatives; ubiquinone and panthenol and its derivatives; vitamin C and derivatives ( For example, ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate; tocopherols and derivatives (such as vitamin E acetate); and benzoin terpineol benzoate; ruthenium acid and its derivatives; Ferulic acid and its derivatives; butylated hydroxytoluene; butylated hydroxymethoxybenzene; dehydrogenation guaiac resin acid; dehydrogenated guaiac acid; trihydroxybutyric acid; uric acid and its derivatives Mannose and its derivatives; zinc and its derivatives (such as ZnO, ZnSO ₄ ); selenium and its derivatives (such as A Selenium thioate); stilbene and its derivatives (for example, stilbene oxide, cis-stilbene oxide); and derivatives of such active ingredients (salts, esters, ethers) suitable according to the invention , sugars, nucleotides, nucleosides, peptides and lipids).

Any pharmaceutically acceptable buffer may be used to adjust the pH of the aqueous liquid pharmaceutical composition according to the present invention to an acceptable range for topical administration, preferably in the range of 3.0 to 6.0, more preferably Within the range of 3.5 to 5. For example, a pharmaceutically acceptable acid such as acetic acid, citric acid, fumaric acid, phosphoric acid, hydrochloric acid, lactic acid or nitric acid or the like, or a mixture thereof is included in the composition. It will also be appreciated that certain compositions of the present invention may have a pH within the desired range without the need to specifically incorporate a pH adjusting agent to achieve this. Typically, however, an acidic buffer system is present in the composition to achieve the desired pH. The acid buffer system contains an acidulant and a buffer. Suitable acidifying agents are known to those skilled in the art and, illustratively, include acetic acid, citric acid, fumaric acid, hydrochloric acid, phosphoric acid, lactic acid, and nitric acid and the like, as well as mixtures thereof. Suitable buffering agents will likewise be known to those skilled in the art and, illustratively, include potassium metaphosphate, potassium phosphate, sodium phosphate, sodium acetate, sodium citrate, and the like, as well as mixtures thereof. Other buffer systems which are also suitable according to the invention are gluconic acid and sodium gluconate, glucono-delta-lactone (GDL) and sodium gluconate, mannoic acid and sodium mannate, 3-deoxy-d-mannonic acid. Esters and sodium mannose, L-gulonic acid and sodium L-gulote, L-idonic acid and sodium L-idonic acid, or mixtures thereof.

Suitable softening agents which can be used in the compositions of the present invention include, for example, dodecane, squalane, cholesterol, isohexadecane, isodecyl isononanoate, PPG ether, paraffin, lanolin, safflower oil, castor oil, Coconut oil, cotton Seed oil, palm kernel oil, palm oil, peanut oil, soybean oil, polyol carboxylic acid esters, derivatives thereof, and the like, and combinations thereof.

Suitable natural waxes according to the present invention are canary wax, canabar wax, japanese wax, esparto wax, softwood wax, guaruma wax, rice bran wax, sugar cane wax, small crown coconut wax, brown wax , beeswax, shellac wax, espermaceti, lanolin (wax), tail fat wax, ozokerite, peat wax, ground paraffin wax, and chemically modified wax (hard wax) such as brown wax ester, obtained by Fischer-Tropsch method Wax, hydrogenated jojoba wax and synthetic wax.

Examples of suitable penetration enhancers may include, for example, dimethyl hydrazine (DMSO), N-methylpyrrolidine, dimethylformamide (DMF), allantoin, uracil, N,N-dimethyl B. Indoleamine (DMA), mercaptomethyl hydrazine, polyethylene glycol monolaurate, propylene glycol, propylene glycol monolaurate, glycerol monolaurate, lecithin, 1-substituted azepan-2- Ketones, especially 1-n-dodecylcycloheterocycloheptan-2-one, alcohols, glycerol, hyaluronic acid, ethylene glycol monoethyl ether, and the like, and combinations thereof. Certain oil components, such as certain vegetable oils such as, for example, safflower oil, cottonseed oil, and corn oil, may also exhibit permeation enhancing properties.

Examples of suitable preservatives for the prevention of microbial contamination are alkyl parabens, especially methyl paraben, propyl paraben and butyl paraben; benzalkonium chloride; Sonin; benzoic acid; benzyl alcohol; sodium benzoate; bronopol; butylated hydroxytoluene; butylated hydroxymethoxybenzene; hexadecyltrimethylammonium bromide; chlorobutanol; chloromethylphenol; Herceptin; dehydroacetic acid; ethylenediaminetetraacetic acid; parabens; phenylethanol; phenol; phenoxyethanol; sorbic acid; potassium sorbate; mixture. The amount of preservative commonly used will vary depending on the preservative selected.

Suitable polyfluorenes according to the invention are cyclic and/or linear polyfluorenes which may be present as monomers which are typically characterized by structural elements such as: Wherein the ruthenium atom may be substituted by an equal or different alkyl or aryl group, usually represented by the R ₁ -R ₄ group.

Suitable linear polyfluorenes according to the invention are generally characterized by structural elements such as: Wherein the ruthenium atom may be substituted by an equal or different alkyl or aryl group represented generally by an R ₁ -R ₄ group (meaning that the number of different radicals is not necessarily limited to 4), and m may be from 2 to 200.000. .

Suitable cyclic polyfluorenes in accordance with the present invention are typically characterized by structural elements such as: Wherein the ruthenium atom may be substituted by an equal or different alkyl or aryl group, usually represented by an R ₁ -R ₄ group (meaning that the number of different radicals is not necessarily limited to 4), and n may have a value of 3/2 to 20. A fractional value of n indicates that an odd number of oxoalkyl groups may be present in the ring.

Specific examples include a cyclic methyl oxane having the formula [(CH ₃ ) ₂ SiO] _x wherein x is 3-6; or having the formula ((CH ₃ ) ₂ SiO[(CH ₃ ) ₂ SiO] _y Si ( Short chain linear methyl oxane of CH ₃ ) ₃ wherein y is 0-5.

Some suitable cyclic methyl oxanes are hexamethylcyclotrioxane (D3) which is a solid having a boiling point of 134 ° C and a formula of [(Me ₂ )SiO] ₃ ; octamethylcyclotetrazepine An alkane (D4) having a boiling point of 176 ° C, a viscosity of 2.3 mm ² /s, and a formula [(Me ₂ )SiO] ₄ ; decamethylcyclopentaoxane (D5) (cyclomethanthene), It has a boiling point of 210 ° C, a viscosity of 3.87 mm ² /s and a formula of [(Me ₂ )SiO] ₅ ; and, dodecamethylcyclohexaoxane (D6), which has a boiling point of 245 ° C, 6.62 mm ² / The viscosity of s and the formula [(Me ₂ )SiO] ₆ .

Some suitable short linear methyl oxiranes are hexamethyldioxane (MM) having a boiling point of 100 ° C, a viscosity of 0-65 mm ² /s, and a formula of Me ₃ SiOMe ₃ ; octamethyltriazine Oxytomane (MDM) having a boiling point of 152 ° C, a viscosity of 1.04 mm ² /s, and a formula of Me ₃ SiOMe ₂ SiOSiMe ₃ ; decamethyltetraoxane (MD 2 M) having a boiling point of 194 ° C, 1.53 mm ² /s viscosity and formula Me ₃ SiO(MeSiO) ₂ SiMe ₃ ; dodecamethylpentaoxane (MD3M), which has a boiling point of 229 ° C, a viscosity of 2.06 mm ² /s and a formula of Me ₃ SiO (Me ₂ SiO) ₃ SiMe _3; tetradecamethyl six silicon siloxane (MD4M), which has a boiling point of 245 deg.] C, 2.63mm ² / s, and the viscosity of the formula _{Me 3 SiO (Me 2 SiO)} 4 SiMe 3; and sixteen A Hexahydroxane (MD5M) having a boiling point of 270 ° C, a viscosity of 3.24 mm ² /s, and a formula of Me ₃ SiO(Me ₂ SiO) ₅ SiMe ₃ .

In addition, long-chain linear helioxane is also included, such as phenyl trimethicone, bis(phenylpropyl)dimethylphosphonium oxide, dimethicone, dimethicone, cyclomethine. Oxygen (octamethylcyclotetraoxane), hexamethylcyclotrioxane, poly(dimethyloxane), cetyl dimethicone, and dione.

Further, a mixture of cyclomethicone and isotridecyl isononanoate and a mixture of cyclomethicone and 2-ethylhexyl isostearate are also suitable polyoxyxides according to the present invention.

Examples of the co-solvent are, for example, nonionic surfactants from at least one of the following groups: 1 to 30 moles of ethylene oxide and/or 0 to 5 moles of propylene oxide are added to the linear C ₈ -C ₂₂ fatty alcohols, C ₁₂ -C ₂₂ fatty acids and products containing 8-15 carbons on the alkyl phenol in the alkyl group; containing 8 to 22 alkyl carbons and / or alkenyl oligoglycosides in the alkyl radical and An ethoxylated analog thereof; an addition product of 1 to 15 moles of ethylene oxide with castor oil and/or hydrogenated castor oil; an addition of 15 to 60 moles of ethylene oxide with castor oil and/or hydrogenated castor oil a product; a partial ester of glycerol and/or sorbitan with an unsaturated or saturated, linear or branched fatty acid having from 12 to 22 carbons and/or a hydroxycarboxylic acid having from 3 to 18 carbon atoms, and Addition products of 1 to 30 moles of ethylene oxide; mixtures of the following: alkoxylated glycerides and alkoxylated glycerol, polyglycerols (average degree of self-condensation 2 to 8), polyethylene glycol (weight average) Molecular weight 400 to 5000), trimethylolpropane, neopentyl alcohol, sugar alcohol (such as sorbitol), alkyl glucoside (such as methyl glucose) , butyl glucoside, dodecyl glucoside) and polyglucoside (eg cellulose) with saturated or unsaturated, linear or branched fatty acids containing 12 to 22 carbons and/or containing 3 to 18 carbons a partial ester of a hydroxycarboxylic acid and a mixed ester of pentaerythritol, a fatty acid, a citric acid and a fatty alcohol with an addition product of 1 to 30 moles of ethylene oxide, and/or a fatty acid having 6 to 22 carbons, a mixed ester of a base glucose and a polyhydric alcohol (preferably glycerin or polyglycerol); mono-, di- and trialkyl phosphates and mono-, di- and/or tri-PEG-alkyl groups and salts thereof; block polymers, for example Polyethylene glycol-30 dipolyhydroxystearate; polymer emulsifier; polyalkylene glycol and alkyl glyceryl ether. Particularly preferred co-solvent is ethylene oxide of 1 to 30 mole and / or 0 to 5 mole propylene oxide adduct of straight-chain C ₈ -C ₂₂ fatty alcohols (such as lauryl alcohol, myristyl alcohol, cetyl alcohol The product on (palmitol), stearyl alcohol, oleyl alcohol and castor oil.

Thickeners or viscosity enhancers can be included to substantially thicken the liquid pharmaceutical composition. While any suitable thickening agent may be included in the compositions of the present invention, preferred thickening agents in use include one or more of the following: gum arabic, alginic acid bentonite, carbomer, carboxymethyl Cellulose calcium or sodium, cetearyl alcohol, methyl cellulose, ethyl cellulose, Glycerin, gelatin, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, maltodextrin, polyvinyl alcohol, polyvinylpyrrolidone, propylene carbonate, propylene glycol alginate , sodium alginate, sodium starch glycolate, starch tragacanth and trisin, and any combination thereof. More preferred thickeners are glycerin, hydroxypropyl methylcellulose and trisin, and any combination thereof.

Examples of humectants (chemical substances which improve their propagation and penetration properties by reducing the surface tension of the liquid) include one or more cationic surfactants such as benzalkonium chloride; nonionic surfactants such as polyoxygen Ethylene and polyoxypropylene block polymers; polyoxyethylene fatty acid glycerides and oils (such as polyoxyethylene (6) caprylic/capric acid mono- and diglycerides), polyoxyethylene (40) hydrogenated castor oil; polyoxyethylene Sorbitan esters such as polysorbate 20 and polysorbate 80; propylene glycol fatty acid esters such as propylene glycol laurate; glyceryl fatty acid esters such as glyceryl monostearate; sorbitan esters Such as sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate and sorbitan monostearate; glyceryl fatty acid esters such as monostearic acid Ester glycerides; anionic surfactants such as sodium lauryl sulfate, sodium lauryl ether sulfate; or fatty acids and salts thereof, such as oleic acid, sodium oleate and triethanolamine oleate.

The pH of the topical pharmaceutical composition or cosmetic composition according to the present invention is within an acceptable range for topical administration, and is preferably in the range of from 3.0 to 9.0, more preferably in the range of from 3.5 to 6.0.

Typically, the topical pharmaceutical compositions or cosmetic compositions according to the present invention are formulated in the form of a cream, gel, ointment, paste, suspension, lotion, foam, spray, aerosol or solution.

In a particular embodiment, the topical composition according to the invention is a cosmetic composition, ie according to Regulation (EC) 1223/2009 (November 30, 2009, European Parliament and Commission Regulations on Cosmetic Products (EC) No. 1223/2009) to classify.

"Cosmetic composition" is any substance or composition intended to be applied to various external parts of the human body (skin, hair system, nails, lips and external reproductive organs) or to the mucous membranes of teeth and mouth. It is cleaned, primarily aromatized, altered in appearance, and/or corrected in body odor and/or protected or maintained in good condition.

The viscosity of the topical pharmaceutical composition or cosmetic composition according to the invention will depend on the form of the composition. For example, in the case of a cream, the viscosity is typically in the range of 2,000 to 15,000 mPa.s, preferably in the range of 2,500 to 10,000 mPa.s, more preferably in the range of 3,000 to 7,000 mPa.s, which is at 20 °C. The measurement was carried out using a DIN-rotating rheometer (Paar Physica); the measuring system Z 3 DIN; D=57.1/s.

In the case of a gel, the viscosity is typically in the range of 300 to 1,500 mPa.s, preferably in the range of 500 to 1,200 mPa.s, more preferably in the range of 600 to 900 mPa.s, which is used at 20 ° C in DIN. - Rotating rheometer (Paar Physica) for measurement; measuring system Z 3 DIN; D = 57.2 / s.

In a preferred embodiment, the topical pharmaceutical composition according to the present invention is formulated in the form of a cream.

As used herein, a cream is a homogeneous, semi-solid formulation consisting of an opaque emulsion system. Consistency and rheological properties depend on the type of emulsion, ie on water-in-oil (w/o) or oil-in-water (o/w), and on the internal phase The nature of medium solids (International Pharmacopoeia, 4th edition).

The invention further relates to a topical pharmaceutical composition or cosmetic composition as defined above, which is suitable for the treatment or prevention of a skin condition selected from the group consisting of infectious eczema (infectious dermatitis), skin bacterial infection or dermatophyte infection or disease.

Typically, eczema (dermatitis) is usually classified by the following types: 1. Contact dermatitis: 1.1. Housewife hand eczema; 1.2. Progressive palmar keratosis (Keratodermia tylodes palamaris progressiva); 1.3. Diapers Dermatitis; 2. Atopic dermatitis: 2.1. Atopic dermatitis in infants; 2.2. Atopic dermatitis in children; and 2.3. Atopic dermatitis in adolescents and adults; 3. Seborrheic dermatitis ; 4. Coin-like eczema; 5. Chronic simple moss (or lichen Vidal); 6. Auto-sensitive dermatitis; 7. Stagnant dermatitis; and 8. Other eczema: 8.1. Khan Herpes, blistering eczema; 8.2. facial simple pityriasis; and 8.3. perioral dermatitis.

In a preferred embodiment, the infectious eczema according to the present invention is selected from the group consisting of infectious contact dermatitis, infectious atopic dermatitis, infectious seborrheic dermatitis, infectious coin-shaped eczema, infection. Sexual chronic simple moss, infectious auto-sensitive dermatitis and infectious stagnant dermatitis. Preferably, the infectious eczema according to the present invention is selected from the group consisting of infectious contact dermatitis, infectious atopic dermatitis, and infectious seborrheic dermatitis, and infectious atopic dermatitis is particularly preferred.

Typically, the infection is caused by Staphylococcus aureus, Staphylococcus epidermis , Streptococcus pyogenes , Serratia marcescens or Pseudomonas aeruginosa .

Bacterial infections of the skin are caused by resident or transient bacteria in the epidermis and mucosa. Typically, bacterial infections of the skin are divided into four major subtypes based on clinical characteristics: 1. Acute skin infections (acute pyoderma); 2. Chronic skin infections (chronic pyoderma); 3. Toxins produced by bacteria Systemic infections caused; and 4. Diseases with specific clinical features caused by specific bacteria.

In a preferred embodiment, the bacterial infection of the skin according to the present invention is selected from the group consisting of pustular (infectious impetigo), erysipelas, cellulitis, folliculitis (acne vulgaris), suppurative sweat gland inflammation, hair Area of papillary dermatitis, purulent dermatitis, chronic buttocks, echinococcosis and red mites.

Fungal skin infections are caused by fungi, which are eukaryotic microorganisms that have cell walls and do not undergo photosynthesis. Its parasitic organic Body or as a spore. In superficial mycosis, fungi invade keratinized tissues such as keratinocyte layers, hair and nails. In deep fungal infections, fungi tend to parasitize the dermis and deeper. Typically, cutaneous fungal infections are classified as: 1. dermatophytosis; 2. candidiasis; 3. plaque infection; and 4. other deep fungal infections.

In a preferred embodiment, the fungal skin infection according to the present invention is selected from the group consisting of athlete's foot, hyperthyroidism, handcuffs, femoral hernia, Qianqi, facial paralysis, head lice, camouflage, bald acne (alopecia), Sputum, Candida to rubella (Candida albicans), candidiasis of the toes, candidiasis around the nail, candida hyperthyroidism, vaginal vaginal candidiasis, chronic mucocutaneous candidiasis, discoloration of pityriasis Pityriasis versicolor), dermatophyll folliculitis, sporotrichosis, mycosis (chromogenic fungal disease), cryptococcosis, dermatophytosis, cutaneous zygomycosis (white mold disease) and skin sheath inflammation.

The invention further relates to the use of a topical pharmaceutical composition or a cosmetic composition as defined above for the manufacture of a medicament for the treatment or prevention of an eczema selected from infectious eczema (infectious dermatitis or infectious skin disease), skin A skin condition or disease caused by a bacterial infection or a fungal skin infection.

The invention further relates to the use of a composition as defined above for the manufacture of a medicament for the treatment or prevention of an infection selected from the group consisting of infectious eczema (infectious dermatitis), skin bacterial infection or dermatophyte infection. A skin condition or disease.

The invention further relates to the use of a composition as defined above for preventing microbial proliferation and restoring skin barrier function in a patient suffering from atopic dermatitis and/or dry skin.

The invention further relates to a method for treating a subject suffering from a skin condition or disease as defined above, the method comprising applying an effective amount of a topical pharmaceutical composition as defined above to an affected area of the skin of the subject Or cosmetic composition.

The method of using the topical pharmaceutical composition of the present invention is achieved by applying the topical pharmaceutical composition to completely cover the affected area to form an occlusion barrier. The usual frequency of application is once or twice a day, preferably twice a day. The amount required depends on the size of the lesion site.

Typically, the area of the skin affected by the disease or condition is selected from the group consisting of the face, ears, scalp, neck, forearm, back, legs, arms and hands.

The following examples are given to provide those skilled in the art with a sufficiently clear and complete explanation of the invention, but should not be construed as limiting the basic aspects of the subject, as set forth in the previous section of the specification.

Instance Example 1

1.1. The composition according to the invention was prepared as indicated in Table 1 (wt.% based on the total weight of the composition).

1.2. The composition according to the invention was prepared as indicated in Table 2 (wt.% based on the total weight of the composition).

The compositions described in Tables 1 and 2 were prepared as follows:

1) Oil phase: the article cetearyl alcohol, polysorbate 40, caprylic/capric triglyceride, liquid paraffin, white soft paraffin, monostearate glyceride, stearin Acid propylene glycol ester and octyldodecanol were added to a stainless steel container. The ingredients were heated to 70 ° C and melted while stirring.

2) Aqueous phase: Water and butanediol were mixed into a stainless steel vessel and heated to 70 °C. The buffer material was added and completely dissolved while stirring. The mixture was stirred at 70 ° C for 30 minutes.

3) Combination: Transfer the hot water phase to the oil phase (stage 2) while homogenizing and stirring.

4) The emulsion was cooled to 55 ° C while stirring. The octenidine hydrochloride was added while homogenizing and stirring.

5) The formulation was cooled to room temperature while stirring.

Example 2

Clinical controls were used to assess the efficacy of the compositions of Examples 1-2 in improving the skin barrier of subjects affected by skin barriers. Twenty male or female subjects aged 18 years or older with significant atopic dermatitis used the cream of Example 12 during 2 weeks. The composition was applied to a test area (preferably for the limbs) having a minimum area of 300 cm ² twice a day (morning and evening). Measurements were performed on Day 1 (baseline), Day 4, Day 8, and Day 15: Body Skin Parameters "Transepidermal Water Loss" (TEWL) - used to determine the integrity of the skin barrier function The method is carried out; and the skin moisture is carried out by corneometry.

A parallel, clinical evaluation of the dermal response (erythema and dryness) was performed by scoring.

2.1. Transepidermal water loss (TEWL)

TEWL is measured using Tewameter (TM 300, Courage & Khazaka, attached to the MPA9 central unit and PC with appropriate software, or as a standalone device). A sensor (temperature sensor and thermal resistor) mounted in an 11 mm diameter open chamber in the probe measures the water pressure gradient across the skin. This allows quantification of the diffusion of water through the skin (ie TEWL). The probe was placed under pressure on a previously determined test field on the coated area. The measurement is performed until the stable value of TEWL is reached. The mean baseline TEWL measured on day 1 was 19.8 ± 8.0 g/m ² h. The results of TEWL are indicated in Table 3, which is expressed as the average % change from baseline (g/m ² h)

2.2. Skin Moisture Method

The hydration of the stratum corneum was assessed by measuring the capacitance of the skin using a Corneometer (CM 825, Courage & Khazaka) attached to the MPA5 central unit and with appropriate software. PC. The principle of skin moisture test measurement is based on the large difference in the dielectric constant of water compared to other substances found in the stratum corneum.

During the measurement, some of the water contained in the stratum corneum reaches the sky-electric interference field of the probe capacitor, causing its capacitance to change. This capacitance is then processed into a digital measurement that is proportional to the moisture content of the skin. The probe head is covered with a thin layer of glass. Therefore, there is no electrical resistance contact between the measured object and the probe, thereby preventing ionic conductivity and polarization effects that can affect the measurement.

Three previously selected test fields in the coated area are measured and three measurements (arbitrary units [a.u.]) are acquired. The average of the three skin moisture test values was used for statistical analysis. The average baseline skin moisture value on day 1 was 12.9 ± 7.6 a.u. The results of the skin moisture method measurements are indicated in Table 4, which is expressed as the average % change from baseline (a.u.).

2.3. erythema

At baseline (Day 1), mild erythema (score 1) was observed in 45% of subjects, and 55% of subjects had no erythema (score 0).

At the end of the 2-week treatment period with the composition of Examples 1-2 (Day 15), most subjects did not have erythema (80%). Mild erythema was noted in 20% of subjects (score 1).

2.4. Drying

On day 1, mild dryness (score 1) was observed in 55% of subjects and moderate dryness (score 2) was observed in 45% of subjects.

At the end of the 2-week treatment period with the composition of Examples 1-2 (Day 15), 45% of the subjects did not have dryness. Slight dryness was observed in 20% of subjects and moderate dryness was observed in 35% of subjects.

The composition of Examples 1-2 was applied twice daily for two weeks to reveal a positive effect on skin barrier function. This was confirmed by TEWL and skin moisture test measurements and clinical evaluation (erythema and dryness).

Based on the experimental results, it can be concluded that the composition of the present invention is safe, cosmetically acceptable, and improved after repeated application. Skin condition (skin barrier is improved and skin moisture is increased).

Modifications that do not affect, alter, modify, or modify the basic aspects of the described compounds, combinations, or pharmaceutical compositions are included within the scope of the invention.

Claims (16)

A topical pharmaceutical composition or cosmetic composition comprising: (a) 0.01-3.0 wt.% of octenidine dihydrochloride; (b) 1-20 wt.% of at least one petroleum hydrocarbon; (c) 0.5 - 10 wt.% of at least one C ₆ -C ₂₄ fatty acid triglyceride; (d) 1-20 wt.% of at least one C ₆ -C ₂₄ fatty alcohol; (e) 1-15 wt% of at least one nonionic surface An active agent; (f) from 1 to 20% by weight of at least one polyol; and (g) from 30 to 70% by weight of water. The composition of claim 1, wherein the total amount of (a) octenidine dihydrochloride is in the range of 0.03-1.5 wt.%, more preferably 0.05-1.0 wt%, based on the total weight of the composition. Within .%. The composition of any one of the preceding claims, wherein the total amount of (b) petroleum hydrocarbons is in the range of from 3 to 15 wt.%, based on the total weight of the composition. The composition of any one of the preceding claims, wherein the total amount of (c) C ₆ -C ₂₄ fatty acid triglyceride is in the range of from 1 to 5 wt.%, based on the total weight of the composition. The composition of any one of the preceding claims, wherein the total amount of (d) C ₆ -C ₂₄ fatty alcohol is in the range of from 7 to 18 wt.%, based on the total weight of the composition. The composition of any one of the preceding claims, wherein the total amount of (e) nonionic surfactant is in the range of 2 to 10 wt.%, based on the total weight of the composition. The composition of any one of the preceding claims, wherein the composition The total amount of (f) polyol is in the range of 5-15 wt.%, based on the total weight. The composition of any one of the preceding claims, wherein the total amount of (g) water is in the range of 50 to 65 wt.%, based on the total weight of the composition. The composition of any of the preceding claims, comprising: (a) 0.03-1.5 wt.% of octenidine dihydrochloride; (b) 3-15 wt.%, based on the total weight of the composition At least one petroleum hydrocarbon; (c) 1-5 wt.% of at least one C ₆ -C ₂₄ fatty acid triglyceride; (d) 7-18 wt.% of at least one C ₆ -C ₂₄ fatty alcohol; (e) 2 - 10 wt.% of at least one nonionic surfactant; (f) 5 to 15 wt.% of at least one polyol; and (g) 50 to 65 wt.% of water. The composition of claim 1, which comprises, based on the total weight of the composition: (a) 0.01-3.0 wt.% of octenidine dihydrochloride; (b) 1-20 wt.% of at least one petroleum a hydrocarbon selected from the group consisting of hard paraffin, liquid paraffin, light liquid paraffin, white soft paraffin, and mixtures thereof; (c) 0.5 to 10 wt.% of at least one C ₆ -C ₂₄ fatty acid triglyceride; (d) 1-20 wt .% of at least one C ₆ -C ₂₄ fatty alcohol; (e) 1-15 wt.% of at least one nonionic surfactant selected from the group consisting of monoglycerides and diglycerides, ethylene glycol or propylene glycol and C _6- C ₂₂ fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester, propylene glycol diacetate, sorbitan ester and mixtures thereof; (f) 1 to 20 wt.% At least one polyol selected from the group consisting of ethylene glycol, propylene glycol, 1,3-butylene glycol, 1,4-butanediol, hexanediol, dipropylene glycol, and an average molecular weight ranging from 100 to 1000 by weight Varying polyethylene glycol, glycerin, polyglycerol, and mixtures thereof; and (g) 30-70 wt.% water. The composition of any one of the preceding claims, wherein the composition further comprises an anti-irritant, an antioxidant, a buffer, a chelating agent, a softening agent, a penetration enhancer, a preservative, a solubilizing agent, a thickening agent, and a moisturizing agent. Or a mixture thereof. The composition of any of the preceding claims, wherein the composition has a pH in the range of from 3.0 to 9.0. A composition according to any of the preceding claims, wherein the composition is formulated in the form of a cream, gel, ointment, paste, suspension, lotion, foam, spray, aerosol or solution. The composition according to any one of claims 1 to 13, which is suitable for the treatment or prevention of a skin condition or disease selected from the group consisting of infectious eczema (infectious dermatitis), skin bacterial infection or dermatophyte infection. A use of a composition according to any one of claims 1 to 13 for the manufacture of a medicament for the treatment or prevention of a skin condition or disease as claimed in claim 14. A method for treating a subject suffering from a skin condition or disease according to claim 14 comprising applying an effective amount to the affected area of the subject's skin as claimed in any of claims 1 to 13 The composition of the item.