WO2005016328A1 - Compositions topiques d'uree - Google Patents

Compositions topiques d'uree Download PDF

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Publication number
WO2005016328A1
WO2005016328A1 PCT/IL2004/000542 IL2004000542W WO2005016328A1 WO 2005016328 A1 WO2005016328 A1 WO 2005016328A1 IL 2004000542 W IL2004000542 W IL 2004000542W WO 2005016328 A1 WO2005016328 A1 WO 2005016328A1
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WO
WIPO (PCT)
Prior art keywords
agent
composition
cosmetic
weight percentages
urea
Prior art date
Application number
PCT/IL2004/000542
Other languages
English (en)
Inventor
Moshe Arkin
Nir Avram
Olga Buriakovsky
Amira Zeevi
Benjamin Schneider
Stephen Cherkez
Original Assignee
Agis Industries(1983) Ltd.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from US10/850,462 external-priority patent/US20050036953A1/en
Priority claimed from US10/850,461 external-priority patent/US20050037040A1/en
Priority claimed from US10/850,435 external-priority patent/US20050042182A1/en
Application filed by Agis Industries(1983) Ltd. filed Critical Agis Industries(1983) Ltd.
Publication of WO2005016328A1 publication Critical patent/WO2005016328A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/006—Antidandruff preparations
    • 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
    • A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
    • 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
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A61K9/122—Foams; Dry foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/007—Preparations for dry skin

Definitions

  • the present invention relates to pharmaceutical, cosmetic and cosmeceutical compositions for topical application, and their use in the treatment of medical, cosmetic and cosmeceutical conditions such as dry skin and/or scalp.
  • Dry skin is a common condition associated with a plurality of disorders and frequently requires therapeutic intervention.
  • Dermatologists often call dry skin in later life "xerosis" or "ichthyosis".
  • Xerosis is a term used to describe abnormal skin dryness.
  • Ichthyosis is a term used to describe a group of cutaneous disorders characterized by increased or aberrant keratinisation, and resulting in non-inflammatory scaling of the skin.
  • ichthyosis There are at least twenty varieties of ichthyosis, including inherited and acquired forms. Further details regarding xerosis and ichthyosis can be found in "Atlas of Clinical Dermatology” by Anthony du Nivier, 3rd edition (July 17, 2002) Publisher: Churchill Livingstone, which is incorporated herein by reference. Dry skin often leads to dermatitis, a condition in which the skin becomes red and itchy, and which is typically characterized by a crazy-paving appearance on the lower legs (eczema craquele) or round patches scattered over the trunk and limbs (a dry form of nummular dermatitis).
  • dermatitis a condition in which the skin becomes red and itchy, and which is typically characterized by a crazy-paving appearance on the lower legs (eczema craquele) or round patches scattered over the trunk and limbs (a dry form of nummular dermatitis).
  • the dry skin is just itchy, without much of a rash. Dry skin results from, or is aggravated by, low humidity, sunlight, abrasive clothing and/or a repeated use of soaps, detergents or other lipid solvents, and is further strongly influenced by factors such as age, race, genetics, climate and lifestyle.
  • moisturizer to soften
  • humectants which are introduced into the stratum corneum to increase its water holding capacity
  • occlusives which provide a layer of oil on the surface of the skin to slow water loss and thus increase the moisture content of the stratum corneum.
  • Some moisturizers contain both occlusives and humectants.
  • “Emollients” is a general term used to describe substances that cover the surface of the stratum corneum so as to prevent moisture loss, thus resulting in the closure of microcracks and fissures and restoration of the natural epidermal barrier. (Marie Loden, Clinics in Dermatology, 21, 145-157, 2003).
  • hydrating agent are used interchangeably.
  • the final form of a topical composition plays an important role in its efficacy and its usage convenience, particularly in cases where the composition is used to treat a skin condition associated with dry skin and/or scalp.
  • the challenge in topically applying a composition is to achieve percutaneous penetration of the active agent to the site of treatment, in many cases the epidermis.
  • it is important that the composition should have desirable characteristics.
  • application should be easy, smooth and should result in no irritation, discomfort or inconvenience.
  • the composition should not leave a residue on the surface of the skin.
  • Topical compositions in forms such as gels, ointments, lotions, creams, pads and pastes are often very viscous, requiring substantial rubbing to achieve penetration of the active agent to the affected skin layer, an act which often results in discomfort and further irritation.
  • Non-viscous creams and lotions require quick and dexterous application as they are inclined to flow off the site of treatment before penetration of the active ingredient is achieved.
  • foams are well suited for the topical application of compositions.
  • Foam compositions are typically formulated in a single or multiple phase liquid form and housed in a suitable container, optionally together with a propellant which facilitates the expulsion of the composition from the container, thus transforming it into a foam upon application.
  • foam forming techniques include, for example the "Bag-in-a-can" formulation technique.
  • Compositions thus formulated typically contain a low-boiling hydrocarbon, e.g., isopropane. Application and agitation of such a composition at the body temperature cause the isopropane to vaporize and generate the foam, in a manner similar to a pressurized aerosol foaming system.
  • a foam composition has physical characteristics which are dependent, at least in part, upon the choice and relative amounts of components such as solvents, propellants and surfactants, which may be present in the composition.
  • the combination of these components determines the stability of the foam, which may retain its foam-like structure upon application or, alternatively, may be "a slow- breaking foam” or "a quick-breaking foam", whereby this terminology relates to the behavior of the foam towards shearing action as is sustained when the foam is rubbed into or spread over a surface onto which it has been dispensed.
  • Many of the physical characteristics of foam compositions render it highly beneficial and advantageous over other forms.
  • One such exemplary characteristic is the semi-solid to solid nature of the foam matrix, which allows the composition to be applied with the hand in any orientation without the risk of run off.
  • Another beneficial characteristic of foams is their convenient application to large areas of the body surface.
  • foams can be water-based or hydroalcoholic, typically they are formulated with high alcohol content which, upon application to the skin of a user, quickly evaporates, driving the active ingredient through the upper skin layers to the site of treatment.
  • Urea is one of the most well-known and widely used humectants. Urea is used in various biological systems, serving, inter alia, as a modifier of protein solubility. Urea is known to exert antibacterial activity as well as protein complexes denaturation activity. In topical applications, urea in known to act as a penetrating moisturizer with high osmotic activity, attributed to its capability to break hydrogen bonds in the outer layers of the stratum corneum, thus dispersing epidermal keratin and exposing water-binding sites.
  • Urea also has a stabilizing effect on the stratum corneum barrier, which can be demonstrated by reduction of trans-epidermal water loss (TEWL) and of irritative hyperemia produced by the application of an irritant (John Ademola et al., Am. J. Clin. Dermatol 3(3), 217-222, 2002).
  • TEWL trans-epidermal water loss
  • irritative hyperemia produced by the application of an irritant
  • a representative example of a commercially available family of 40 % urea-containing preparations is the Carmol (R) 40 cream, gel and lotion (marketed by Doak Dermatologies, a subsidiary of Bradley Pharmaceuticals Inc.), which is known as a tissue softener.
  • Carmol (R) 40 cream, gel and lotion marketed by Doak Dermatologies, a subsidiary of Bradley Pharmaceuticals Inc.
  • tissue softener As early as the 1960s, topical compositions containing urea were used in the treatment of various dermatological conditions.
  • Swanbeck in Acta derm-vener., 48, 123, 1968
  • soaking of pieces of horny layer from normal, ichthyotic and psoriatic skin in a 30 % urea solution resulted in a considerable increase in the water binding capacity of the skin, and suggested that a cream containing urea in a concentration of 10 % may be used for the treatment of ichthyosis and other hyperkeratotic conditions.
  • Swanbeck and Rajka (Acta derm-vener 50, 225, 1970) presented a study in which solutions containing 20 % urea were used in the treatment of pruritus.
  • topical preparations that contain high concentrations of urea suffer many disadvantages.
  • commercially available formulations such as the above-mentioned Carmol (R) 40 are characterized by an alkaline pH, namely a pH value higher than 8.0. Such a pH value is much higher than that of the natural skin (about 5.5), and may therefore cause irritations when applied.
  • European Patent Application No. 0101887 A2 discloses cosmetic compositions that comprise an aqueous solution of urea or derivatives thereof, in a concentration of between 0.5 M and 12 M, and an ammonium salt of an unreactive acid, which is added to adjust the pH of the solution to between 6.0 and 8.0.
  • the ammonium salt is aimed at retarding the production of titratable alkali from the aqueous urea solution, to thereby prolong the shelf-life of the composition.
  • Preferred ammonium salts include ammonium salts of strong acids such as carboxylic acids having up to four carbon atoms.
  • the instability of urea in aqueous solutions is widely taught by this reference.
  • JP 59020217 (to Kawaken Fine Chemical KK) describes an aqueous, jelly-like composition containing between 1 and 48 weight percentages urea, an ammonium compound and a carboxyvinyl polymer.
  • the pH of the composition is adjusted to 5.5-7.5, by adding a base made up of hydroxides of alkali metals, alkanolamines, basic amino acids and aqueous ammonia.
  • JP 59020217 further teaches that the combination of all the components present in the disclosed composition synergistically provides for inhibition of the decomposition of urea. It is therefore implied in this patent that the stability of the composition would be reduced if any of the constitutional components would be missing.
  • a topical composition formulated as a foam, which comprises urea as an active ingredient, would be a highly potent composition for treating a variety of de ⁇ natological conditions, and particularly dry skin and scalp conditions and associated disorders.
  • WO 86/00014 discloses a method for the prevention and/or reduction of skin damage caused by ultraviolet radiation, which is effected by topically applying a composition comprising urea and a pharmaceutically acceptable carrier.
  • the urea is used in this composition as an agent that moderates the effect of nitrate reduction products, which are formed as a result of exposure to ultraviolet radiation.
  • the preferred concentration of urea is from about 0.1 to about 40 weight percentages, more preferably between about
  • compositions are applied to the skin in the form of conventional alcoholic lotions, liquid emulsions, creams, transparent gels, or aerosol sprays.
  • This reference therefore fails to teach a composition that is directed to treat a dry skin and/or scalp condition and is further not directed to such compositions that are foamable.
  • U.S. Patent No. 5,919,470 discloses a dermatological composition that comprises from about 21 to about 40 weight percentages urea and a method of treating xerosis, which is effected by applying the composition.
  • the de ⁇ natological composition further comprises skin protectants of an oleaginous nature, derived from petroleum, emulsifiers and thickeners, and is in a semi-solid form at room temperature.
  • the composition is preferably formulated as a cream.
  • this patent fails to teach compositions that comprises less than 21 weight percentages urea and is not directed to foamable compositions.
  • 2003064969 disclose various compositions, all containing urea in concentrations of up to 40 weight percentages, in combination with other active ingredients such as, for example, anti-fungals (U.S. Patent No. 6,281,239), sulfacetamide and sulfur (U.S. Patent No. 6,429,231), astringents such as calcium acetate and aluminum sulfate (U.S. Patent No. 6,495,602) and antimicrobials (U.S. Patent Application No. 2003064969), for the treatment of various dermatological conditions.
  • active ingredients such as, for example, anti-fungals (U.S. Patent No. 6,281,239), sulfacetamide and sulfur (U.S. Patent No. 6,429,231), astringents such as calcium acetate and aluminum sulfate (U.S. Patent No. 6,495,602) and antimicrobials (U.S. Patent Application No. 2003064969), for the treatment of various dermatological conditions.
  • compositions disclosed in these patents and patent application are not limited to a particular form, some of these references teach that the composition is preferably applied in the form of a cream and or a lotion. These references are therefore not directed to foamable compositions for treating dry skin and or scalp conditions.
  • U.S. Patent No. 6,423,323 discloses a foam skin cream composition that is prepared by a specific process, which can optionally contain urea, as a hydratizing agent. As urea is used as an optional adjuvant, according to the teachings of this patent, it is used in a relatively low concentration of up to 20 %.
  • the process taught by this reference includes adjusting the pH of the composition to between 7.6 and 8.2.
  • JP Patent Application No. 2002-275454 discloses a water- containing aerosol composition containing a stock solution and a propellant; the stock solution being an aqueous solution containing 10-50 % of a nitrogen-containing water-soluble component, whereby the nitrogen-containing component is preferably urea.
  • the nitrogen-containing component according to the teachings of this reference, is aimed at stabilizing the aqueous stock solution by preventing its freezing, to thereby enable a perfect dispersion state of the composition while being used at a low temperature.
  • JP Patent Application No. 2003-12511 discloses an aerosol composition that comprises an aqueous stock solution of urea in a concentration of between 2 and 35 weight percentages, and between 30 and 90 weight percentages water. According to the teachings of this patent application, the compositions are aimed at stabilizing an effective amount of urea, by mixing the propellant and the stock solution at certain volumes ratio, in a liquid state.
  • Preferred propellants are a dimethylether or liquefied petroleum gas, which are commonly used in aerosol compositions.
  • this patent teaches compositions of urea and a propellant, it fails to teach such compositions which are formulated as a foam.
  • U.S. Patent No. 5,679,324 discloses quick-breaking foamable fragrance compositions, which comprise a surfactant, a propellant, a fragrance and a thickener. These compositions, according to the teachings of this patent, may optionally further include skin moisturizers such as urea. According to the teachings of this patent, urea, in a concentration of between 0.1 % and about 10 %, may further be added to the compositions as an optional medicament that may be included in the composition. As this patent is directed to fragrance compositions, it fails to teach compositions for treating dry skin conditions, in which urea is present in an effective amount for treating these conditions. U.S. Patent No.
  • urea may optionally be added to the composition as a moisturizer, in a concentration of, as arbitrarily stated, between 0.1
  • % and 20 % preferably, as stated, in a low concentration of between 2 % and 5 %.
  • urea is an optional adjuvant and fails to teach compositions for treating dry skin conditions, in which urea is present in an effective amount for treating these conditions.
  • U.S. Patent Application No. 20020151446 discloses a foaming cleanser composition that comprises a mild surfactant system, a moisturizer system and a solvent system.
  • urea may also be included in the disclosed composition, as a humectant, in an amount that ranges between about 1 weight percentages and about 5 weight percentages.
  • the composition disclosed in this patent application comprises low concentrations of urea and is aimed at cleansing and conditioning of hair and skin.
  • foamable compositions that comprise urea and/or a derivative thereof, in a relatively high concentration, can serve as efficient pharmaceutical, cosmetic and cosmeceutical compositions for the treatment of various dermatological disorders (e.g., dry skin and/or scalp).
  • various dermatological disorders e.g., dry skin and/or scalp.
  • a foamable pharmaceutical, cosmetic or cosmeceutical composition for topical application which is identified for use in the treatment of a medical, cosmetic and/or cosmeceutical condition associated with dry skin and/or scalp.
  • the composition of the present invention comprises urea and/or a derivative thereof, one or more propellant(s) and a pharmaceutically, cosmetically or cosmeceutically acceptable carrier.
  • the foamable pharmaceutical, cosmetic or cosmeceutical compositions of the present invention is packaged in a packaging material and identified in print, in or on the packaging material, for use in the treatment of a medical, cosmetic and/or cosmeceutical condition associated with dry skin and/or scalp, such as, but not limited to, xerosis, ichthyosis, keratosis, keratoderma, pruritus, acne, dermatitis, neuro-dermatitis, dermatitis herpetiformis, actinic keratosis, hyper keratosis, inflamed keratosis, eczema, atopic eczema, melanoma, psoriasis, rosacea, urticaria, seborrheic dermatitis, skin cancer, and xeroderma pigmentosum.
  • a medical, cosmetic and/or cosmeceutical condition associated with dry skin and/or scalp such as, but not
  • the concentration of the urea and/or the derivative thereof is greater than 5 weight percentages of the total weight of the composition. More preferably it is greater than 10 weight percentages . According to still further features in the described preferred embodiments the concentration of the urea and/or the derivative thereof ranges between about 5.1 weight percentages and about 48 weight percentages of the composition. More preferably, it ranges between about 20 weight percentages and about 48 weight percentages of the composition.
  • the concentration of the propellant(s) preferably ranges between about 0.5 weight percentage and about 60 weight percentages, more preferably between about 10 weight percentages and about 20 weight percentages.
  • the propellant(s) preferably include propane, iso-butane, n-butane, isopentane, n-pentane, and mixtures thereof.
  • the composition of the present invention further comprises one or more additional active ingredient(s) such as, but not limited to, an antibiotic agent, an antimicrobial agent, an anti-acne agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammato-ry agent, an anesthetic agent, an antipruriginous agent, an antiprotozoal agent, an anti-oxidant, a chemotherapeutic agent, an antidepressant, an antihistamine, a vitamin, a hormone and an antidandruff agent.
  • an antibiotic agent such as, but not limited to, an antibiotic agent, an antimicrobial agent, an anti-acne agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal anti
  • composition of the present invention further comprises one or more ingredient(s) selected from the group consisting of a humectant, a deodorant agent, an antiperspirant, a sun screening agent, a sunless tanning agent, a hair conditioning agent, a pH adjusting agent, a chelating agent, a preservative, an emulsifier, an occlusive agent, an emollient, a thickener, a solubilizing agent, a penetration enhancer, an anti-irritant, a colorant and a surfactant.
  • ingredient(s) selected from the group consisting of a humectant, a deodorant agent, an antiperspirant, a sun screening agent, a sunless tanning agent, a hair conditioning agent, a pH adjusting agent, a chelating agent, a preservative, an emulsifier, an occlusive agent, an emollient, a thickener, a solubilizing agent, a penetration
  • the pharmaceutical, cosmetic or cosmeceutical compositions of the present invention have a pH value that preferably ranges between about 4.0 and about 7.0, more preferably between about 5.0 and about 6.0.
  • the pharmaceutical, cosmetic or cosmeceutical compositions of the present invention are preferably devoid of an enduring perfume composition.
  • processes of preparing the pharmaceutical, cosmetic or cosmeceutical compositions of the present invention comprises admixing the urea and/or the derivative thereof, the propellant(s) and a pharmaceutically, cosmetically or cosmeceutically acceptable carrier.
  • the processes further comprise admixing the active ingredient or any other ingredient with the urea and/or the derivative thereof, the propellant(s) and the carrier.
  • the methods comprise topically applying onto one or more biological surface(s) of a subject in need thereof, a pharmaceutically, cosmetically or cosmeceutically effective amount of the composition described hereinabove.
  • the biological surface(s) is selected from the group consisting of a lateral aspect of a forearm, a lateral aspect of a leg, an elbow, a palm, a foot, a backhand, a back and a scalp.
  • the present invention successfully addresses the shortcomings of the presently known configurations by providing foamable compositions containing urea and/or a derivative thereof and methods of treating various dermatological conditions such as conditions associated with dry skin and/or scalp utilizing same, which are highly efficient and convenient, and are thus superior to the presently available urea preparations.
  • all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
  • compositions for topical application which can be efficiently used in the treatment of various medical, cosmetic and/or cosmeceutical conditions.
  • the present invention is of (i) compositions for topical application, which contain, as an active ingredient urea and/or a derivative thereof; (ii) processes of preparing these compositions; and (iii) their use in treating medical, cosmetic and/or cosmeceutical conditions associated with dry skin and/or scalp such as, but not limited to, xerosis, ichthyosis, keratosis, keratoderma, pruritus, acne, dermatitis, neuro-dermatitis, dermatitis herpetiformis, actinic keratosis, hyper keratosis, inflamed keratosis, eczema, atopic eczema, melanoma, psoriasis, rosace
  • hydrating efficacy and hence, the therapeutic or cosmetic performance, as well as the usage convenience of hydrating agents and any other agents for topical application depend, inter alia, on the final form of the composition in which these agents are formulated.
  • foam formulations are well suited for the topical application of compositions.
  • the presently known preparations that include urea as the active ingredient are typically formulated as creams, lotions, gels, ointment and the like, and therefore their efficacy and usage convenience are limited.
  • foam compositions which include urea as an optional ingredient are known, these compositions are not aimed at treating dry skin or scalp conditions and therefore do not include urea in a substantial concentration (e.g., higher than 5 weight percentages), such that it may serve as the main active hydrating agent.
  • a composition that comprises urea, preferably in a relatively high concentration, which is formulated as a foam is highly efficient in the treatment of dry skin and/or scalp and is further characterized by improved absorption, after feel and comfort, as compared with the presently known formulations, and is devoid of stickiness and other adverse effects that accompany the use of the presently known formulations.
  • urea preferably in a relatively high concentration
  • the topical application of such a foamable composition is highly efficient and convenient, as compared with the presently known urea formulations.
  • a foamable pharmaceutical, cosmetic or cosmeceutical composition for topical application which is identified for use in the treatment of a medical, cosmetic and/or cosmeceutical condition associated with dry skin and/or scalp.
  • the composition comprises urea, one or more propellant(s) and a pharmaceutically, cosmetically or cosmeceutically acceptable carrier.
  • topical application describes application onto a biological surface, e.g., skin or scalp.
  • a composition for topical application describes a composition that is applied to a subject by direct laying or spreading on the skin, scalp or any other biological surface of the subject.
  • the topical application is preferably performed onto a dry skin area.
  • the dry skin area can be one or more of, for example, the lateral aspect of a forearm, the lateral aspect of a leg, an elbow, a palm, a foot, a backhand, a back and/or a scalp.
  • comprising means that other steps and ingredients which do not affect the end results can be added. This term encompasses the terms “consisting of and “consisting essentially of.
  • Consisting essentially of means that the composition may include additional ingredients, but only if the additional ingredients do not materially alter the basic and novel characteristics of the claimed compositions or methods.
  • active ingredient as used herein means an ingredient that exerts a pharmaceutical, cosmetic or cosmeceutical activity.
  • the phrase "active ingredient" whenever used herein in the context of urea and/or a related substance refers to an ingredient that exerts hydration activity, namely, a hydrating agent.
  • urea is a well known and widely used hydrating agent
  • derivatives of urea are also known to exert hydration properties, as is described, for example, in EP Application No. 0101887 A2.
  • Such urea derivatives can therefore be beneficially used in the composition of the present invention, in addition to or instead of urea.
  • the pharmaceutical, cosmetic or cosmeceutical composition for topical application comprises urea and/or a derivative thereof.
  • An urea derivative, according to the present invention can be described by the general formula:
  • alkyl refers to a saturated aliphatic hydrocarbon including straight chain and branched chain groups.
  • the alkyl group has 1 to 20 carbon atoms.
  • the alkyl group may contain 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc., up to and including 20 carbon atoms. More preferably, it is a medium size alkyl having 1 to 10 carbon atoms. Most preferably, it is a lower alkyl having 1 to 4 carbon atoms.
  • the alkyl group may be substituted or unsubstituted.
  • the substituent group can be, for example, hydroxy, halo, amino, nitro, cyano, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonamide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, thiocarboxy, C-amido, N-amido, C-carboxy, O-carboxy, and sulfonamido.
  • a "cycloalkyl” group refers to an all-carbon monocyclic or fused ring (i.e., rings which share an adjacent pair of carbon atoms) group wherein one of more of the rings does not have a completely conjugated pi-electron system.
  • examples, without limitation, of cycloalkyl groups are cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane, cyclohexadiene, cycloheptane, cycloheptatriene, and adamantane.
  • a cycloalkyl group may be substituted or unsubstituted.
  • the substituent group can be, for example, hydroxy, halo, amino, nitro, cyano, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonamide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, thiocarboxy, C-amido, N-amido, C-carboxy, O-carboxy, and sulfonamido.
  • An "alkenyl” group refers to an alkyl group, as is defined hereinabove, which consists of at least two carbon atoms and at least one carbon-carbon double bond.
  • aryl group refers to an all-carbon monocyclic or fused-ring polycyclic (i.e., rings which share adjacent pairs of carbon atoms) groups having a completely conjugated pi-electron system. Examples, without limitation, of aryl groups are phenyl, naphthalenyl and anthracenyl. The aryl group may be substituted or unsubstituted.
  • the substituent group can be, for example, hydroxy, halo, amino, nitro, cyano, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonamide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, thiocarboxy, C-amido, N-amido, C-carboxy, O-carboxy, and sulfonamido.
  • a "hydroxy" group refers to an -OH group.
  • alkoxy refers to both an -O-alkyl and an -O-cycloalkyl group, as defined herein.
  • An "aryloxy” group refers to both an -O-aryl and an -O-heteroaryl group, as defined herein.
  • a "thiohydroxy” group refers to a -SH group.
  • a “thioalkoxy” group refers to both an -S-alkyl group, and an -S-cycloalkyl group, as defined herein.
  • a “thioaryloxy” group refers to both an -S-aryl and an -S-heteroaryl group, as defined herein.
  • a “halo” group refers to fluorine, chlorine, bromine or iodine.
  • a “trihalomethyl” group refers to a -CX 3 group wherein X is a halo group as defined herein.
  • R are as defined herein.
  • An “Amino” group refers to an -NR'R” group where R' and R" are as defined herein.
  • a "nitro” group refers to a -NO 2 group.
  • a “cyano” group refers to a -G ⁇ N group.
  • phosphinyl describes a -PR'R" group, with R' and R" as defined hereinabove.
  • urea and/or a derivative thereof, serves as the main active ingredient in the composition of the present invention, its concentration is relatively high, so as to efficiently exert a hydrating effect.
  • the concentration of the urea and/or the derivative thereof in the composition of the present invention is preferably greater than 5 weight percentages, more preferably greater than 6 weight percentages, more preferably greater than 7 weight percentages, more preferably greater than 8 weight percentages, more preferably greater than 9 weight percentages, more preferably greater than 10 weight percentages, more preferably greater than 11 weight percentages, more preferably greater than 12 weight percentages, more preferably greater than 13 weight percentages, more preferably greater than 14 weight percentages, more preferably greater than 15 weight percentages, more preferably greater than 16 weight percentages, more preferably greater than 17 weight percentages, more preferably greater than 18 weight percentages, more preferably greater than 19 weight percentages and, according to one of the presently most preferred embodiments of the present invention, it is about 20 weight percentages.
  • the concentration of the urea and/or the derivative thereof in the composition of the present invention can further preferably be greater than 20 weight percentages, more preferably greater than 21 weight percentages, more preferably greater than 22 weight percentages, more preferably greater than 23 weight percentages, more preferably greater than 24 weight percentages, more preferably greater than 25 weight percentages, more preferably greater than 26 weight percentages, more preferably greater than 27 weight percentages, more preferably greater than 28 weight percentages, more preferably greater than 29 weight percentages, more preferably greater than 30 weight percentages, more preferably greater than 31 weight percentages, more preferably greater than 32 weight percentages, more preferably greater than 33 weight percentages, more preferably greater than 34 weight percentages, more preferably greater than 35 weight percentages, more preferably greater than 36 weight percentages, more preferably greater than 37 weight percentages, more preferably greater than 38 weight percentages, more preferably greater than 39 weight percentages, and according to one of the presently most preferred embodiments of the present invention, it is about 40 weight percentages.
  • the concentration of the urea and/or the derivative thereof in the composition of the present invention can further preferably be greater than 40 weight percentages and up to about 48 weight percentages.
  • the phrase "greater than” as used herein with respect to a numerical indication encompasses any number (integral or fractional) that is greater than the indicated number.
  • the concentration of the urea and/or the derivative thereof in the composition preferably ranges between, for example, about 5.1 weight percentages and about 48 weight percentages, more preferably between about 10 and about 40 weight percentages, and even more preferably between about 20 and about 40 weight percentages.
  • weight percentages describes the weight percentages (of an ingredient) of the total weight of a composition containing same.
  • composition of the present invention further includes a pharmaceutically, cosmetically or cosmeceutically acceptable carrier.
  • pharmaceutically, cosmetically or cosmeceutically acceptable carrier describes a carrier or a diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the applied active ingredient.
  • acceptable carriers include carrier materials that are well-known for use in the cosmetic and medical arts as bases for foams and the like.
  • the composition of the present invention is formulated in the form of a foam.
  • the foam is formed by the passage of a pressurized mixture of a concentrate and a propellant through a nozzle.
  • the propellant is in the form of a compressed gas, typically a liquefiable gas.
  • the mixture is preferably contained in a dispenser equipped with a dispensing head and valve, and pressurized with the propellant.
  • the volatilization of the dispersed liquid droplets of propellant causes the dispensed concentrate to foam.
  • the dispensed product may range from a dense creamy foam to a light foam, dependent on desired aesthetics in the hand and when spread onto the substrate.
  • the concentration of the propellant in the composition preferably ranges between about 0.5 and about 60 weight percentages, more preferably between about 1 and about 20 weight percentages of the total composition.
  • Any propellant suitable for use in pharmaceutical, cosmetic or cosmeceutical compositions can be used herein, alone or in combination with other propellant.
  • suitable propellants include nitrous oxide, carbon dioxide, nitrogen, and hydrocarbon propellants such as propane, iso-butane, n-butane, isopentane, n-pentane, and dimethyl ether.
  • Preferred propellants are selected from, for example, propane, iso-butane, n-butane, isopentane, n-pentane, and mixtures thereof.
  • Chlorinated fluorocarbons such as 1,1-difluoro- or 1,1,1,2-tetrafluoroethane are also suitable but their use is being limited for environmental reasons.
  • the propellants listed above typically have a low boiling point and are in a gaseous form at room temperature in standard conditions.
  • the composition of the present invention can optionally further comprise a variety of components that are suitable for rendering the composition more cosmetically or aesthetically acceptable or to provide the composition with additional usage benefits.
  • Such conventional optional components or ingredients are well known to those skilled in the art and are referred to herein as "ingredients”.
  • these include any cosmetically acceptable ingredients such as those found in the CTFA International Cosmetic Ingredient Dictionary and Handbook, 8th edition, edited by Wenninger and Canterbery, (The Cosmetic, Toiletry, and Fragrance Association, Inc., Washington, D.C., 2000).
  • Some non-limiting representative examples of these ingredients include humectants, deodorants, antiperspirants, sun screening agents, sunless tanning agents, hair conditioning agents, pH adjusting agents, chelating agents, preservatives, emulsifiers, occlusive agents, emollients, thickeners, solubilizing agents, penetration enhancers, anti-irritants, colorants and surfactants.
  • composition of the present invention can comprise, in combination with urea and/or a derivative thereof, one or more additional humectants or moisturizing agents.
  • additional humectants or moisturizing agents include, without limitation, guanidine, glycolic acid and glycolate salts (e.g.
  • aloe vera in any of its variety of forms (e.g., aloe vera gel), allantoin, urazole, polyhydroxy alcohols such as sorbitol, glycerol, hexanetriol, propylene glycol, butylene glycol, hexylene glycol and the like, polyethylene glycols, sugars and starches, sugar and starch derivatives (e.g., alkoxylated glucose), hyaluronic acid, lactamide monoethanolamine, acetamide monoethanolamine and any combination thereof.
  • the composition of the present invention can further comprise a pH-adjusting agent.
  • Suitable pH adjusting agents include, for example, one or more adipic acids, glycines, citric acids, calcium hydroxides, magnesium aluminometasilicates, buffers or any combinations thereof.
  • compositions for topical application should preferably have a pH value of between 4.0 and 7.0, preferably between 5.0 and 6.0, most preferably about 5.5 or substantially 5.5, so as to avoid irritation.
  • a pH adjusting agent is typically added so as to bring the pH of the composition to the desired value.
  • the composition of the present invention is therefore preferably formulated so as to have a pH value that ranges between about
  • deodorant agents that are usable in the context of the present invention include, without limitation, quaternary ammonium compounds such as cetyl-trimethyla monium bromide, cetyl pyridinium chloride, benzethonium chloride, diisobutyl phenoxy ethoxy ethyl dimethyl benzyl ammonium chloride, sodium N-lauryl sarcosine, sodium N-palmlthyl sarcosine, lauroyl sarcosine, N- myristoyl glycine, potassium N-lauryl sarcosine, stearyl, trimethyl ammonium chloride, sodium aluminum chlorohydroxy lactate, tricetylmethyl ammonium chloride, 2,4,4 , -trichloro-2'-hydroxy diphenyl ether, diaminoalkyl amides such as L- lysine he
  • deodorant agents include, without limitation, odor absorbing materials such as carbonate and bicarbonate salts, e.g. as the alkali metal carbonates and bicarbonates, ammonium and tetiaalkylammonium carbonates and bicarbonates, especially the sodium and potassium salts, or any combination of the above.
  • Antiperspirant agents can be incorporated in the composition of the present invention either in a solubilized or a particulate form and include, for example, aluminum or zirconium astringent salts or complexes.
  • sun screening agents include, without limitation, p-aminobenzoic acid, salts and derivatives thereof (ethyl, isobutyl, glyceryl esters; p-dimethylaminobenzoic acid); anthranilates (i.e., o-amino-benzoates; methyl, menthyl, phenyl, benzyl, phenylethyl, linalyl, terpinyl, and cyclohexenyl esters); salicylates (amyl, phenyl, octyl, benzyl, menthyl, glyceryl, and di-pro-pyleneglycol esters); cinnamic acid derivatives (menthyl and benzyl esters, a-phenyl cinnamonitrile; butyl cinnamoyl pyruvate); dihydroxycinnamic acid derivatives (umbelliferone
  • sunless tanning agents usable in context of the present invention include, without limitation, dihydroxyacetone, glyceraldehyde, indoles and their derivatives.
  • the sunless tanning agents can be used in combination with the sunscreen agents.
  • Suitable hair conditioning agents that can be used in the context of the present invention include, for example, one or more collagens, cationic surfactants, modified silicones, proteins, keratins, dimethicone polyols, quaternary ammonium compounds, halogenated quaternary ammonium compounds, alkoxylated carboxylic acids, alkoxylated alcohols, alkoxylated amides, sorbitan derivatives, esters, polymeric ethers, glyceryl esters, or any combinations thereof.
  • the chelating agents are optionally added to the composition of the present invention so as to enhance the preservative or preservative system.
  • Preferred chelating agents are mild agents, such as, for example, ethylenediatninetetraacetic acid (EDTA), EDTA derivatives, or any combination thereof.
  • Suitable preservatives for use in the composition of the present composition include, without limitation, one or more alkanols, disodium EDTA (et-hylenediamine tetraacetate), EDTA salts, EDTA fatty acid conjugates, isothiazolinone, parabens such as methylparaben and propylparaben, propylene glycols, sorbates, urea derivatives such as diazolindinyl urea, or any combinations thereof.
  • Suitable emulsifiers that can be used in the context of the present invention include, for example, one or more sorbitans, alkoxylated fatty alcohols, alkylpolyglycosides, soaps, alkyl sulfates, monoalkyl and dialkyl phosphates, alkyl sulphonates, acyl isothionates, or any combinations thereof.
  • Suitable occlusive agents that can be used in the context of the present invention include, for example, petrolatum, mineral oil, beeswax, silicone oil, lanolin and oil-soluble lanolin derivatives, saturated and unsaturated fatty alcohols such as behenyl alcohol, hydrocarbons such as squalane, and various animal and vegetable oils such as almond oil, peanut oil, wheat germ oil, linseed oil, jojoba oil, oil of apricot pits, walnuts, palm nuts, pistachio nuts, sesame seeds, rapeseed, cade oil, corn oil, peach pit oil, poppyseed oil, pine oil, castor oil, soybean oil, avocado oil, safflower oil, coconut oil, hazelnut oil, olive oil, grape seed oil and sunflower seed oil.
  • petrolatum mineral oil
  • beeswax silicone oil
  • lanolin and oil-soluble lanolin derivatives saturated and unsaturated fatty alcohols such as behenyl alcohol
  • hydrocarbons such
  • Suitable emollients other than urea and a derivative thereof, that can be used in the context of the present invention include, for example, dodecane, squalane, cholesterol, isohexadecane, isononyl isononanoate, PPG Ethers, petrolatum, lanolin, safflower oil, castor oil, coconut oil, cottonseed oil, palm kernel oil, palm oil, peanut oil, soybean oil, polyol carboxylic acid esters, derivatives thereof and mixtures thereof.
  • Suitable thickeners that can be used in the context of the present invention include, for example, non-ionic water-soluble polymers such as hydroxyethylcellulose (commercially available under the Trademark Natrosol R TM 250 or 350), cationic water-soluble polymers such as Polyquat 37 (commercially available under the Trademark Synthalen R TM CN), fatty alcohols, fatty acids and their alkali salts and mixtures thereof.
  • non-ionic water-soluble polymers such as hydroxyethylcellulose (commercially available under the Trademark Natrosol R TM 250 or 350), cationic water-soluble polymers such as Polyquat 37 (commercially available under the Trademark Synthalen R TM CN), fatty alcohols, fatty acids and their alkali salts and mixtures thereof.
  • solubilizing agents that are usable in this context of the present invention include, without limitation, complex-forming solubilizers such as citric acid, ethylenediamine-tetraacetate, sodium meta-phosphate, succinic acid, urea, cyclodextrin, polyvinylpyrrolidone, diethyla--nmonium-ortho-benzoate, and nticelle-fo-rming solubilizers such as TWEENS and spans, e.g., TWEEN 80.
  • complex-forming solubilizers such as citric acid, ethylenediamine-tetraacetate, sodium meta-phosphate, succinic acid, urea, cyclodextrin, polyvinylpyrrolidone, diethyla--nmonium-ortho-benzoate, and nticelle-fo-rming solubilizers such as TWEENS and spans, e.g., TWEEN 80.
  • solubilizers that are usable for the composition of the present invention are, for example, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene n-alkyl ethers, n- alkyl amine n-oxides, poloxamers, organic solvents, phospholipids and cyclodextrines.
  • Suitable penetration enhancers usable in context of the present invention include, but are not limited to, dimethylsulfoxide (DMSO), dimethyl formamide
  • the permeation enhancer may also be a vegetable oil.
  • oils include, for example, safflower oil, cottonseed oil and corn oil.
  • Suitable anti-irritants that can be used in the context of the present invention include, for example, steroidal and non steroidal anti-inflammatory agents or other materials such as aloe vera, chamomile, alpha-bisabolol, cola nitida extract, green tea extract, tea tree oil, licoric extract, allantoin, caffeine or other xanthines, glycyrrhizic acid and its derivatives.
  • steroidal and non steroidal anti-inflammatory agents or other materials such as aloe vera, chamomile, alpha-bisabolol, cola nitida extract, green tea extract, tea tree oil, licoric extract, allantoin, caffeine or other xanthines, glycyrrhizic acid and its derivatives.
  • the composition is preferably devoid of an enduring perfume composition.
  • an enduring perfume composition describes a composition that comprises one or more perfumes that provide a long lasting aesthetic benefit with a minimum amount of material. Enduring perfume compositions are substantially deposited and remain on the body throughout any rinse and/or drying steps. Representative examples of such compositions are described, for example, in U.S. Patent No. 6,086,903. However, it should be noted that fragrances other than enduring perfume compositions, perfumes or perfume compositions, which are fast removable from the surface they are deposited on, can be included in the composition of the present invention.
  • composition of the present invention can comprise one or more additional active ingredients, which are. aimed at providing the composition with an additional therapeutic, cosmeceutical or cosmetic effect.
  • active ingredient refers to an ingredient which exerts a pharmacological, dermatological or any other beneficial activity.
  • additional active ingredient refers herein to any active ingredient other than urea or derivatives thereof, as is described hereinabove.
  • Compositions according to the present invention, which further comprises one or more additional active ingredients can therefore be further efficiently used, in addition to treatment of a condition associated with dry skin and or scalp, in the treatment of any medical, cosmetic and/or cosmeceutical condition in which applying the additional active ingredient is beneficial.
  • Preferred additional active ingredients according to the present invention include, without limitation, one or more, or any combination of an antibiotic agent, an antimicrobial agent, an anti-acne agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, an anesthetic agent, an antipruriginous agent, an antiprotozoal agent, an anti- oxidant, a chemotherapeutic agent, an antidepressant, an anti histamine, a vitamin, a hormone and an anti-dandruff agent.
  • an antibiotic agent an antimicrobial agent, an anti-acne agent, an antibacterial agent, an antifungal agent, an antiviral agent, a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, an anesthetic agent, an antipruriginous agent, an antiprotozoal agent, an anti- oxidant, a chemotherapeutic agent, an antidepressant, an anti his
  • Suitable anti-acne agents for use in this context of the present invention include, without limitation, keratolytics such as salicylic acid, sulfur, glycolic, pyruvic acid, resorcinol, and N-acetylcysteine and retinoids such as retinoic acid and its derivatives (e.g., cis and trans, esters).
  • keratolytics such as salicylic acid, sulfur, glycolic, pyruvic acid, resorcinol, and N-acetylcysteine
  • retinoids such as retinoic acid and its derivatives (e.g., cis and trans, esters).
  • Suitable antibiotics for use in this context of the present invention include, without limitation, benzoyl peroxide, octopirox, erythromycin, zinc, tetracyclin, triclosan, azelaic acid and its derivatives, phenoxy ethanol and phenoxy proponol, ethylacetate, clindamycin and meclocycline; sebostats such as flavinoids; alpha and beta hydroxy acids; and bile salts such as scymnol sulfate and its derivatives, deoxycholate and cholate.
  • non-steroidal anti-inflammatory agents include, without limitation, oxicams, such as piroxicam, isoxicam, tenoxicam, sudoxicam, and CP- 14,304; salicylates, such as aspirin, disalcid, benorylate, trilisate, safapryn, solprin, diflunisal, and fendosal; acetic acid derivatives, such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac, zomepirac, clindanac, oxepinac, felbinac, and ketorolac; fenamates, such as mefenamic, meclofenamic, flufenamic, mflumic, and tol
  • salicylates such as aspirin, dis
  • steroidal anti-inflammatory drugs include, without limitation, corticosteroids such as hydrocortisone, hydroxyltriamcinolone, alpha- methyl dexamethasone, dexamethasone-phosphate, beclomethasone dipropionates, clobetasol valerate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butyles
  • Suitable antipruritic agents for use in this context of the present invention include, without limitation, pharmaceutically acceptable salts of methdilazine and trimeprazine.
  • anesthetic drugs that are suitable for use in the context of the present invention include pharmaceutically acceptable salts of lidocaine, bupivacaine, chlorprocaine, dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine, hexylcaine, procaine, cocaine, ketamine, pramoxine and phenol.
  • Suitable antimicrobial agents including antibacterial, antifungal, antiprotozoal and antiviral agents, for use in the context of the present invention include, without limitation, beta-lactam drugs, quinolone drugs, ciprofloxacin, norfloxacin, tetracycline, e-tythromycin, amikacin, triclosan, doxycycline, capreomycin, chlorhexidine, chlortetracycline, oxytetracycline, clindamycin, ethambutol, metronidazole, pentamidine, gentamicin, kanamycin, 1-ineomycin, methacycline, methenamine, minocycline, neomycin, netilmicin, streptomycin, tobramycin, and miconazole.
  • tetracycline hydrochloride famesol, erythromycin estolate, erythromycin stearate (salt), amikacin sulfate, doxycycline hydrochloride, chlorhexidine gluconate, chlorhexidine hydrochloride, chlortetracycline hydrochloride, oxytetracycline hydrochloride, clindamycin hydrochloride, ethambutol hydrochloride, metronidazole hydrochloride, pent-amidine hydrochloride, gentamicin sulfate, kanamycin sulfate, lineomycin hydrochloride, methacycline hydrochloride, methenamine hippurate, methenamine mandelate, minocycline hydrochloride, neomycin sulfate, netilmicin sulfate, paromomycin sulfate, streptomycin sulfate, tobramycin sulfate, micon
  • Non-limiting examples of suitable anti-oxidants for use in the context of the present invention include ascorbic acid (vitamin C) and its salts, ascorbyl esters of fatty acids, ascorbic acid derivatives (e.g., magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbyl sorbate), tocopherol (vitamin E), tocopherol sorbate, tocopherol acetate, other esters of tocopherol, butylated hydroxy benzoic acids and their salts, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (commercially available under the trade name Trolox R ), gallic acid and its alkyl esters, especially propyl gallate, uric acid and its salts and alkyl esters, sorbic acid and its salts, lipoic acid, amines (e.g., N,N-diethylhydroxylamine, amino-guanidine), sulfhydryl compounds (e.g.
  • Non-limiting examples of suitable chemotherapeutic agents for use in the context of the present invention include daunorubicin, doxorubicin, idarubicin, amrubicin, pirarubicin, epirubicin, mitoxantrone, etoposide, teniposide, vinblastine, vincristine, mitomycin C, 5-FU, paclitaxel, docetaxel, actinomycin D, colchicine, topotecan, irinotecan, gemcitabine cyclosporin, verapamil, valspodor, probenecid, MK571, GF120918, LY335979, biricodar, terfenadine, quinidine, pervilleine A and XR9576.
  • Non-limiting examples of suitable antidepressants for use in the context of the present invention include norepinephrine-reuptake inhibitors ("NRIs”), selective- serotonin-reuptake inhibitors (SSRIs), monoamine-oxidase inhibitors (MAOIs), serotonin-and-noradrenaline-reuptake inhibitors ("SNFIs), corticotropin-releasing factor (CRF) antagonists, ⁇ -adrenoreceptor antagonists, NK1 -receptor antagonists, 5- HT 1A -receptor agonist, antagonists, and partial agonists and atypical antidepressants, as well as norepinephrine-reuptake inhibitors such as, but are not limited to amitriptyline, desmethylamitriptyline, clomipramine, doxepin, imipramine, imipramine-oxide, t--rimipr-amine; adinazolam, amiltriptylinoxide, amo
  • anti-dandruff ingredients usable in the context of the present invention include, without limitation, zinc pyrithione, shale oil and derivatives thereof such as sulfonated shale oil, selenium sulfide, sulfur; salicylic acid, coal tar, povidone-iodine, imidazoles such as ketoconazole, dichlorophenyl imidazolodioxalan, clotrimazole, itraconazole, miconazole, climbazole, tioconazole, sulconazole, butoconazole, fluconazole, miconazolenitrite and any possible stereo isomers and derivatives thereof such as anthralin, piroctone olamine (Octopirox), selenium sulfide, and ciclopirox olamine, and mixtures thereof.
  • zinc pyrithione shale oil and derivatives thereof such as sulfonated shale oil, selenium
  • Non-limiting examples of vitamins usable in context of the present invention include vitamin A and its analogs and derivatives: retinol, retinal, retinyl palmitate, retinoic acid, tretinoin, iso-tretinoin (known collectively as ret oids), vitamin E (tocopherol and its derivatives), vitamin C (L-ascorbic acid and its esters and other derivatives), vitamin B 3 (niacinamide and its derivatives), alpha hydroxy acids (such as glycolic acid, lactic acid, tartaric acid, malic acid, citric acid, etc.) and beta hydroxy acids (such as salicylic acid and the like).
  • vitamin A and its analogs and derivatives include vitamin A and its analogs and derivatives: retinol, retinal, retinyl palmitate, retinoic acid, tretinoin, iso-tretinoin (known collectively as ret oids), vitamin E (tocopherol and its derivatives), vitamin C (L-ascor
  • Non-limiting examples of dermatological active ingredients usable in context of the present invention include jojoba oil and aromatic oils such as methyl salicylate, wintergreen, peppermint oil, bay oil, eucalyptus oil and citrus oils, as well as ammonium phenolsulfonate, bismuth subgallate, zinc phenolsulfonate and zinc salicylate.
  • Non-limiting examples of antifungal agents include miconazole, clotrimazole, butoconazole, fenticonasole, tioconazole, terconazole, sulconazole, fluconazole, haloprogin, ketonazole, ketoconazole, oxinazole, econazole, itraconazole, terbinafine, nystatin and griseofulvin.
  • Non-limiting examples of antiMst-amines usable in context of the present invention include cMo ⁇ hen amine, brompher ⁇ rami-ne, dexchlorpheniramine, tripolidine, clemastine, diphenhydramine, promethazine, piperazines, piperidines, astemizole, loratadine and terfenadine.
  • Suitable hormones for use in the context of the present invention include, for example, androgenic compounds and progestin compounds.
  • Representative examples of androgenic compounds include, without limitation, methyltestosterone, androsterone, androsterone acetate, androsterone propionate, androsterone benzoate, androsteronediol, androsteronediol-3 -acetate, androsteronediol-17-acetate, androsteronediol 3-17-diacetate, androsteronediol- 17- benzoate, androsteronedione, androstenedione, androstenediol, dehydroepiandrosterone, sodium dehydroepiandrosterone sulfate, dromostanolone, dromostanolone propionate, ethylestrenol, fluoxymesterone, nandrolone phenpropionate, nandrolone decanoate, nandrolone furylpropionate, nandrolone cyclohexane-propionate, nandrol
  • progestin compounds include, without limitation, desogestrel, dydrogesterone, ethynodiol diacetate, medroxyprogesterone, levonorgestrel, medroxyprogesterone acetate, hydroxyprogesterone caproate, norethindrone, norethindrone acetate, norethynodrel, allylestrenol, 19-nortestosterone, lynoestrenol, quingestanol acetate, medrogestone, norgestrienone, dimethisterone, ethisterone, cyproterone acetate, chlormadinone acetate, megestrol acetate, norgestimate, norgestrel, desogrestrel, trimegestone, gestodene, nomegestrol acetate, progesterone, 5 ⁇ -pregnan-3 ⁇ ,20 ⁇ -diol sulf
  • composition of the present invention may be packed or presented in any convenient way.
  • they may be packed in a tube, a bottle, or a pressurized container, using techniques well known to those skilled in the art and as set forth in reference works such as Remington's Pharmaceutical Science 15 th Ed. It is preferred that the packaging is done in such a way so as to minimize contact of the unused compositions with the environment, in order to minimize contamination of the composition before and after the container is opened.
  • composition of the present invention includes urea and/or a derivative thereof, preferably in a substantial concentration, it is highly beneficial in preventing or treating medical, cosmetic and/or cosmeceutical conditions associated with dry skin and/or scalp such as, for example, xerosis, ichthyosis, keratosis, keratoderma, pruritus, acne, dermatitis, neuro-dermatitis, dermatitis herpetiformis, actinic keratosis, hyper keratosis, inflamed keratosis, eczema, atopic eczema, melanoma, psoriasis, rosacea, urticaria, seborrheic dermatitis, skin cancer, warts, dandruffs and xeroderma pigmentosum.
  • medical, cosmetic and/or cosmeceutical conditions associated with dry skin and/or scalp such as, for example, xerosis,
  • the composition described hereinabove is packaged in a packaging material and is identified in print, in or on the package, for use in the treatment or prevention of dry skin and/or scalp and/or any one or more of the conditions described or listed herein.
  • a method of treating a medical, cosmetic and/or cosmeceutical condition is effected by topically applying onto one or more affected biological surface(s) of a subject in need thereof, e.g. dry skin and/or scalp, a pharmaceutically, cosmetically or cosmeceutically effective amount of the composition of the present invention as described herein.
  • the term “treating” includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.
  • topically applying describes application onto one or more biological surface(s), e.g., skin or scalp, by direct laying or spreading a composition on the surface.
  • biological surfaces onto which the composition of the present invention can be topically applied include the lateral aspect of forearms, the lateral aspect of legs, elbows, palms, feet, backhands, back, scalp and any other dry skin surface.
  • a representative, non-limiting example of an application regime of the composition of the present invention includes topical application of the composition between one and four times a day, more preferably twice a day (e.g., once in the morning and once in the evening).
  • the topical application of the composition of the present invention is preferably carried out for a time period that ranges between 1 and 30 days, more preferably for a time period of about fourteen days.
  • pharmaceutically, cosmetically or cosmeceutically effective amount describes an amount of a composition that is sufficient to significantly induce a positive modification in the condition being treated, but low enough to avoid significant side effects, within the scope of sound judgment of the skilled artisan.
  • the effective amount of the composition may vary with the particular skin being treated, the age and physical condition of the biological subject being treated, the severity of the condition, the duration of the treatment, the nature of concurrent therapy, the specific compound, composition or other material employed, the particular pharmaceutically, cosmetically or cosmeceutically acceptable topical carrier utilized, and like factors within the knowledge and expertise of the skilled artisan. While the method according to this aspect of the present invention is preferably beneficial in treating conditions associated with dry skin and/or scalp, in cases where the compositions of the present invention further comprises additional active ingredient(s), the method can be further used for treating other conditions in which applying the additional active ingredient(s) is beneficial. Such conditions include, for example, infections, fungi, allergies, aging and more.
  • a process of preparing the novel composition described hereinabove generally comprises admixing the urea and/or the derivative thereof, as described hereinabove, the propellant(s) and the pharmaceutically, cosmetically or cosmeceutically acceptable carrier.
  • the process includes admixing these ingredients together with the urea and/or the derivative thereof, the propellant(s) and the carrier.
  • the mixing technique utilized in the process of the present invention can be any one of the known techniques for formulating foamable compositions.
  • EXAMPLE 1 A representative example of a foam skin and scalp topical composition according to the present invention, containing urea in a 40 weight percentages concentration, was prepared using conventional methods (see, for example, Harry's Cosmeticology, Seventh Edition, Edited by JB Wilkinson and RJ Moore, Longmann Scientific & Technical, 1982, Chapter 13 "The Manufacture of Cosmetics" pages 757- 799).
  • the composition comprises about 10 weight percentages of a propellant, as described hereinabove.
  • Other components of the composition are listed in Table 1 hereinbelow. Table 1
  • EXAMPLE 2 Another representative example of a foam skin and scalp topical composition according to the present invention, containing urea in a 20 weight percentages concentration, was prepared using conventional methods (see, for example, Harry's Cosmeticology, Seventh Edition, Edited by JB Wilkinson and RJ Moore, Longmann Scientific & Technical, 1982, Chapter 13 "The Manufacture of Cosmetics" pages 757- 799).
  • the composition comprises about 10 weight percentages of a propellant, as described hereinabove.
  • Other components of the composition are listed in Table 2 hereinbelow. Table 2

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Abstract

La présente invention concerne des compositions moussantes pharmaceutiques, cosmétiques et cosméceutiques destinées à une application topique, qui contiennent comme principe actif de l'urée et/ou un dérivé de celle-ci, des processus de fabrication de ces compositions et d'utilisation de ces compositions dans le traitement de divers états dermatologiques tels que par exemple des états associés à la peau sèche et/ou au cuir chevelu sec.
PCT/IL2004/000542 2003-08-13 2004-06-17 Compositions topiques d'uree WO2005016328A1 (fr)

Applications Claiming Priority (14)

Application Number Priority Date Filing Date Title
US49457903P 2003-08-13 2003-08-13
US49458103P 2003-08-13 2003-08-13
US60/494,579 2003-08-13
US60/494,581 2003-08-13
US51055403P 2003-10-14 2003-10-14
US60/510,554 2003-10-14
US52727903P 2003-12-08 2003-12-08
US60/527,279 2003-12-08
US10/850,462 US20050036953A1 (en) 2003-08-13 2004-05-21 Topical compositions of ammonium lactate
US10/850,435 2004-05-21
US10/850,461 US20050037040A1 (en) 2003-08-13 2004-05-21 Topical compositions of urea and ammonium lactate
US10/850,435 US20050042182A1 (en) 2003-08-13 2004-05-21 Topical compositions of urea
US10/850,461 2004-05-21
US10/850,462 2004-05-21

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PCT/IL2004/000541 WO2005016360A1 (fr) 2003-08-13 2004-06-17 Preparations topiques au lactate d'ammonium
PCT/IL2004/000542 WO2005016328A1 (fr) 2003-08-13 2004-06-17 Compositions topiques d'uree

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PCT/IL2004/000541 WO2005016360A1 (fr) 2003-08-13 2004-06-17 Preparations topiques au lactate d'ammonium

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PL2371350T3 (pl) 2010-03-04 2013-09-30 Neubourg Skin Care Gmbh & Co Kg Preparaty piankowe do leczenia chorób skóry u zwierząt
US9962361B2 (en) 2011-01-03 2018-05-08 The William M. Yarbrough Foundation Isothiocyanate functional surfactants, formulations incorporating the same, and associated methods of use
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US10273205B2 (en) 2011-01-03 2019-04-30 The William M. Yarbrough Foundation Isothiocyanate functional surfactants, formulations incorporating isothiocyanate functional surfactants and associated methods for treating biofilms
US11407713B2 (en) 2011-01-03 2022-08-09 The William M. Yarbrough Foundation Isothiocyanate functional surfactants, formulations incorporating the same, and associated methods of use
US10640464B2 (en) 2011-01-03 2020-05-05 The William M. Yarbrough Foundation Use of isothiocyanate functional surfactants as Nrf2 inducers to treat epidermolysis bullosa simplex and related diseases
US11279674B2 (en) 2011-01-03 2022-03-22 The William M. Yarbrough Foundation Isothiocyanate functional surfactant and associated method of use
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US9839621B2 (en) 2012-07-26 2017-12-12 The William M. Yarbrough Foundation Method for treating bladder cancer
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US10434082B2 (en) 2012-07-26 2019-10-08 The William M. Yarbrough Foundation Isothiocyanate functional compounds augmented with secondary antineoplastic medicaments and associated methods for treating neoplasms
US10335387B2 (en) 2012-07-26 2019-07-02 The William M. Yarbrough Foundation Method for treating infectious diseases with isothiocyanate functional compounds
US10434081B2 (en) 2012-07-26 2019-10-08 The William M. Yarbrough Foundation Inhibitors of macrophage migration inhibitory factor
US8865772B2 (en) 2012-07-26 2014-10-21 The William M. Yarbrough Foundation Method for treating skin cancer
US10441561B2 (en) 2012-07-26 2019-10-15 The William M. Yanbrough Foundation Method for treating benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer
DE102013110608A1 (de) * 2013-09-26 2015-03-26 Florian Lang Substanz zur Hemmung von Gewebskalzifizierung, Gewebsfibrosierung und altersassoziierten Erkrankungen
CN105232357B (zh) * 2014-07-11 2020-06-26 杭州泽芙雪化妆品有限公司 一种用于治疗皮肤干燥症的保湿霜及其制备方法
CN111973478A (zh) * 2020-08-20 2020-11-24 广州博氏化妆品有限公司 一种足部护理液及其制备方法和使用方法

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IL162608A0 (en) 2005-11-20
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IL162606A0 (en) 2005-11-20
WO2005016329A1 (fr) 2005-02-24

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