WO2005007071A2 - Skin formulation - Google Patents
Skin formulation Download PDFInfo
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- WO2005007071A2 WO2005007071A2 PCT/IL2004/000629 IL2004000629W WO2005007071A2 WO 2005007071 A2 WO2005007071 A2 WO 2005007071A2 IL 2004000629 W IL2004000629 W IL 2004000629W WO 2005007071 A2 WO2005007071 A2 WO 2005007071A2
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- Prior art keywords
- composition
- skin
- lotion
- compound
- dead sea
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Classifications
-
- 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
- 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
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/02—Medicinal preparations containing materials or reaction products thereof with undetermined constitution from inanimate materials
- A61K35/08—Mineral waters; Sea water
-
- 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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/965—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of inanimate origin
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/70—Biological properties of the composition as a whole
- A61K2800/72—Hypo-allergenic
Definitions
- the present invention relates to compositions and methods of use thereof for pharmaceutical and cosmetic treatment of skin.
- Inflammatory skin disorders can be divided two groups, differing in their etiology as a result of exogenous causes (allergic contact or primary irritant) or endogenous, which implies all forms of dermatitis not directly related to an external causative factor. Dermatitis results in degenerative changes of the skin including the formation of distinct inflamed lesions that are characterized by color changes, roughening of texture, thickening, reduced moisture content, increased hardness, or a combination thereof. Symptoms include irritation and itching, scaling of the skin, and denuding of the upper layers, often producing bleeding from underlying skin layers. Some inflammatory skin disorders include psoriasis, eczema, acne and lichen planus, with each disease typically manifesting as a spectrum, ranging in severity in patient populations.
- dermatitis are the following: inflammatory epidermal rash, acute or chronic, redness, weeping, scaling and itching.
- the epidermis may erupt with clear or discolored bumps that may be very itchy.
- Skin irritation may occur anywhere on the body surface, including the hands, arms legs, upper or lower back, neck, genitals, scalp and nails. Each of these sites, in turn may present with some or all symptoms characteristic of dermatitis.
- Urea is thought to dissolve the intercellular matrix which results in loosening the horny layer of skin and shedding scaly skin at regular intervals, and hence behaves as a micro-exfolient that improves the appearance and condition of the skin. It is hypothesized that removal of damaged cells by urea expedites emergence of new skin cells from underlying germination layers to the surface of the skin. The newer cells can then rebuild an adequate defense barrier against damaging external agents, and invading pathogens. The actual mechanism of action of topically applied Urea is, however, not yet known.
- the present invention successfully overcomes the shortcomings of previous attempts by providing compositions and methods of use thereof wherein combmed urea and Dead Sea salt therapy provide significant therapeutic effect for inflammatory skin disorders.
- the present invention provides compositions and methods of use thereof for reducing skin damage or irritation, wherein the composition comprises an effective amount of a urea compound and Dead Sea salts.
- the present invention provides a pharmaceutical or cosmetic composition comprising a urea compound and Dead Sea salts, wherein the urea compound is at a concentration ranging in percentage from 7 to 15 and the Dead Sea salts are at a concentration ranging in percentage from 7 to 15 of the total weight of the composition.
- the present invention provides a method of reducing skin damage, the method comprising contacting skin with a composition comprising an effective amount of a urea compound and " Dead Sea salts, thereby reducing skin damage.
- the skin damage is as a result of an inflammatory response.
- this invention provides a method of reducing skin irritation, the method comprising contacting skin with a composition comprising an effective amount of a urea compound and Dead Sea salts, thereby reducing skin damage
- the present invention provides compositions and methods for reducing skin damage or irritation, comprising urea compounds in combination with mineral salts obtained from the Dead Sea for topical administration.
- the compositions of the invention are intended for use as a pharmaceutical or cosmetic preparation in the topical treatment of skin, wherein it is desired to optimize the delivery of combined urea and Dead Sea mineral salt preparations upon topical application.
- Such a composition has excellent properties when used as a keratolytic or a skin softener, in combination with one or more dermatological agents including an emollient, a lubricant, a moisturizer, a protectant, an enhancer of skin penetration, a softener, a PH adjuster, a solubilizer, a preservative or perfume agent.
- dermatological agents including an emollient, a lubricant, a moisturizer, a protectant, an enhancer of skin penetration, a softener, a PH adjuster, a solubilizer, a preservative or perfume agent.
- compositions of the present invention provide additional application in terms of anti-inflammatory capability. It is thus another object of the present invention to provide methods and compositions for topical administration for application in any skin inflammatory disorder.
- inflammatory skin disorders and "dermatitis” as used herein refer to a condition of the skin that is a result of an inflammatory response.
- the term “inflammatory response” in turn, refers to the influx of inflammatory cells within the upper layers of the skin, resulting in an array of pathological phenomenon including swelling, discoloration, keratinization, lesion formation, denuding of the upper layers of the skin, the appearance of a rash, blistering, peeling, scaling and hardening, with or without the accompaniment of itching, irritation or dryness, as a result of the influx of the cells, and products released at the site of influx within the skin.
- An inciting agent or stimulus precedes the development of the inflammatory response culminating in dermatitis.
- dermatitis may be exogenous (with the stimulus being a result of allergic contact or contact with a primary irritant) or endogenous in origin (with the stimulus often unknown however with evidence of an underlying genetic tendency to present with dermatitis), which implies that all forms of dermatitis are not necessarily related to an external causative factor.
- compositions of the present invention serve to minimize inflammatory damage or irritation to skin as a result of dermatitis.
- inflammatory damage all forms of damage including cell and tissue death, degradation of extracellular matrix components and swelling are considered, as are any clinical manifestations as a result of an inflammatory process occurring within the skin.
- irrigation refers to clinical symptoms as a result of the inflammatory process within the slcin, including swelling, blistering, peeling, scaling and hardening, with or without the accompaniment of itching, irritation or dryness.
- reducing skin damage” or “reducing skin irritation” are therefore meant to include a diminution or abrogation in any one or more, or combinations thereof, of the clinical manifestations and symptoms listed herein.
- compositions of the invention facilitate healing of denuded, exposed skin.
- Denuded epidermal layers provide a source of entry for invading pathogens, and as such, the compositions of the present invention may also contain anti-fungal, anti-bacterial or anti-parasitic compounds or pesticides. Additional compounds incorporated within the compositions may include detergents, surfactants and disinfectants, serving an anti-pathogenic function, or alternatively, for facilitating/participating in removal of undesirable slcin layers.
- Known compounds that stimulate wound healing or contain extracellular matrix components may be additional components of the compositions of the present invention, as well.
- a method of reducing skin damage or irritation via contacting the skin with a pharmaceutical composition comprising an effective amount of a urea compound and Dead Sea salts, thereby reducing skin damage or irritation.
- the pharmaceutical compositions for contacting skin are topically applied to affected areas in the form of a gel, cream, milk, stick, foam, soap, oil, fatty composition, lotion, scalp treatment, shampoo, conditioner, paste, mask, peel, makeup, powder, blush, or may be pressurized in an aerosol device, for ease of application.
- the compositions may be formulated to be water- or oil-based compositions.
- composition may therefore additionally include skin softeners, with or without cosmetic colorants and may be applied to the skin on at least a daily basis when the initial or premonitory signs of skin damage or irritation first become apparent.
- Skin irritation or damage may occur anywhere on the body surface, including the hands, arms, legs, upper or lower back, neck, genitals, scalp and nails.
- Each of these sites may present with some or all symptoms characteristic of dermatitis, and are sites for therapeutic intervention using the compounds and compositions of the present invention. It is to be understood that different formulations may be produced for optimal delivery to specific body sites. Multiple applications may be necessary and desired for optimal therapeutic effect, and represent a further embodiment of the present invention.
- compositions of the invention are applied, in one embodiment of the invention, to the limbs, face, or feet, on the basis of 1 to 10 mg of composition per cm of skin, for a period which can range from one week to one year or longer.
- the composition is suitable for the topical treatment of skin, in particular for the treatment of inflamed slcin, whereupon it is desirable to obtain a softer texture, and reduced evidence of irritation or damage to one or more layers of the skin.
- the composition is suitable for the chronic treatment of inflamed skin, wherein the composition is administered over a period of months or years.
- the composition is suitable for the chronic treatment of inflamed slcin, wherein the composition is administered at least once per day.
- composition of the present invention may be applied alone, or in combination with mechanical exfolients including, but not limited to, sponges, abrasive surfaces, abrasive particles, clothing, combs, brushes, peels, soaps, or a combination thereof.
- mechanical exfolients including, but not limited to, sponges, abrasive surfaces, abrasive particles, clothing, combs, brushes, peels, soaps, or a combination thereof.
- Cosmetic devices comprising the compositions of the present invention represent an additional embodiment.
- compositions containing urea compounds in combination with mineral salts obtained from the Dead Sea are prepared, in one embodiment, via the methods outlined herein.
- the components of the compositions will depend upon the particular formulation desired. Formulations are disclosed in Tables 1-4, herein. It is to be understood, however, that acceptable chemically equivalent or accepted substitutes may be employed, as will be known to one skilled in the art.
- oil and aqueous phases may be, in one embodiment, heated separately, then mixed at 80 °C, with high homogenization and mixing, followed by cooling for 90 minutes, at which time the temperature of the mixture will be approximately 45 °C. Fragrance may then be added to the mixture.
- Other methods of preparation are well described, and indeed accepted practice in the pharmaceutical and cosmetic fields, and are to be considered as part of this invention, as well.
- the concentration of urea in any of the compositions of the present invention may be at a range of between 7 and 20 % of the weight of the composition. In one embodiment, the concentration of urea in any of the compositions of the present invention may be at a range of between 7 and 8 %, or in another embodiment, between 8 and 9 %, or in another embodiment between 9 and 10 %, or in another embodiment between 10 and 11 %, or in another embodiment between 11 and 13 %, or in another embodiment between 13 and 15 %, or in another embodiment between 15 and 16 %, or in another embodiment between 16 and 17 %, of the weight of the composition.
- the concentration of urea in any of the compositions of the present invention may be at a range of between 7 and 10 %, or in another- embodiment, between 10 and 15 %, or in another embodiment between 8 and 12 % of the weight of the composition.
- the concentration of Dead Sea salts in any of the compositions of the present invention may be at a range of between 7 and 20 % of the weight of the composition. In one embodiment, the concentration of Dead Sea salts in any of the compositions of the present invention may be at a range of between 7 and 8 %, or in another embodiment, between 8 a-nd 9 %, or in another embodiment between 9 and 10 %, or in another embodiment between 10 and 11 %, or in another embodiment between 11 and 13 %, or in another embodiment between 13 and 15 %, or in another embodiment between 15 and 16 %, or in another embodiment between 16 and 17 %, of the weight of the composition.
- the concentration of Dead Sea salts in any of the compositions of the present invention may be at a range of between 7 and 10 %, or in another embodiment, between 10 and 15 %, or in another embodiment between 8 and 12 % of the weight of the composition.
- Compositions comprising urea and Dead Sea salts may, in another embodiment, comprise additional ingredients, in particular organic solvents.
- organic solvents may include, but are not limited to, ethanol, methanol, propanol, isopropanol, cetearyl alcohol, cetyl alcohol or combinations thereof.
- the composition of the invention may be in the form of a cream, and may comprise urea and Dead sea salts in a composition additionally containing water, isopropylmyristate, glyceryl stearate, cetyl alcohol, propylene glycol, glycerin, decyl oleate, caprylic/capric triglyceride, PEG-40 stearate, lanoline, sorbitan tristearate, imidazohdinyl urea, potassium sorbate, citric acid, methyl paraben, propyl paraben, 2-bromo 2-nitropropane 1,3-diol, BHT, ascorbyl palmitate, ragrance and oils.
- a composition additionally containing water, isopropylmyristate, glyceryl stearate, cetyl alcohol, propylene glycol, glycerin, decyl oleate, caprylic/capric triglyceride, PEG-40
- the composition is in the form of a lotion, and may comprise Dead sea salts with or without unsubstituted urea in a composition additionally containing water, ethyl hexyl stearate, cetearyl alcohol and ceteareth-20, propylene glycol, glycerin, cyclopentasiloxane and cyclohexasiloxne, imidazohdinyl urea, potassium sorbate, citric acid, methyl paraben, propyl paraben, 2-bromo 2-nitropropane 1,3-diol, fragrance and oils.
- the composition may be in the form of a scalp treatment, comprising Dead sea salts and urea in a composition additionally containing water, cetearyl alcohol and ceteareth-20, cetyl alcohol, cocamidopropyl betain, sea silt, caprylic/capric triglyceride, decyl oleate, cetrimoniuum chloride, sorbitan tristearate, imidazohdinyl urea, potassium sorbate, citric acid, methyl paraben, propyl paraben, 2- bromo 2-nitropropane 1,3-diol, fragrance and oils.
- a scalp treatment comprising Dead sea salts and urea in a composition additionally containing water, cetearyl alcohol and ceteareth-20, cetyl alcohol, cocamidopropyl betain, sea silt, caprylic/capric triglyceride, decyl oleate, cetrimoniuum chloride, sorbitan tristearate, imidazo
- compositions and treatments listed herein may be formulated for administration to adults, or to children, by methods well known to one skilled in the art.
- compositions are meant to be exemplary, and are by no means exclusive. Numerous methods of formulation, including the addition of other stabilizers, preservatives, etceteras, may be included in the formulation for enhanced product shelf life.
- the pharmaceutical or cosmetic composition further comprises emollients, lubricants, moisturizers, protectants, skin penetration enhancers, softeners, pH adjusters, solubilizers or perfume agents.
- compositions of the present invention were found to be stable, (Example 2) and hypo-allergenic (Example 3).
- the compositions of the present invention possess anti-inflammatory activity, as well.
- EXAMPLE 1 COMPOSITIONS COMPRISING A HIGH CONCENTRATION OF DEAD SEA SALTS AND UREA Materials and Methods: [0047] Compounds combined for the preparation of cream, lipolotion, hydrolotion and scalp treatment compositions and concentrations represented as percent of total composition weight were as listed in tables 1-4, respectively. Oil and aqueous phases were heated separately, then mixed at 80 °C, with high homogenization and mixing, followed by cooling for 90 minutes, at which time the temperature of the mixture was approximately 45 °C. Fragrance was then added to the mixture.
- Dead Sea salts can be formulated with urea compounds to provide compositions that can be applied topically.
- the composition as outlined in Table 1 was prepared. " A smooth white cream was isolated that was fragrant and pleasant to the touch.
- physiologically active concentrations of urea and Dead Sea Salts were prepared in the form of a lipolotion (an oil soluble formulation), and hydrolotion (a water soluble formulation), with the compositions as outlined in Tables 2 and 3, respectively.
- Both the lipolotion and hydrolotion when prepared as above produced white, smooth lotions that rapidly incorporated within the skin, penetrating beyond superficial layers, and was pleasant to the touch.
- Topical application of physiologically active concentrations of urea and Dead Sea Salts may be desired in formulations specific for scalp application, for treatment of inflammatory skin diseases, for example.
- a formulation specific for scalp treatment was prepared, as outlined in Table 4. The composition thus obtained yielded a smooth, white, thin-textured emulsion that was fragrant, and pleasant to the touch.
- compositions comprising urea and Dead Sea salts are stable. Compositions are determined to be stable if the microbial count is less than 10 colony forming units per gram of sample tested, if there is no color change and if there is no evidence of phase separation of the samples evaluated. No colony forming units were detected in any of the formulations tested. Further, there was no evidence of color change or phase separation in any of the samples analyzed. Thus all 4 formulations were stable.
- EXAMPLE 3 COMPOSITIONS COMPRISING HIGH CONCENTRATIONS OF UREA AND DEAD SEA SALTS ARE HYPO-ALLERGENIC Materials and Methods
- compositions comprising urea and Dead Sea salts are hypo-allergenic. Of the fifty subjects evaluated, none had any reaction whatsoever to any of the four formulations tested (Table 5), indicating the hypo-allergenic status of each formulation.
- EXAMPLE 4 COMPOSITIONS COMPRISING HIGH CONCENTRATIONS OF UREA AND DEAD SEA SALTS ARE ANTI-INFLAMMATORY
- PMA phorbol myristate acetate
- compositions assessed as compared to control compositions, comprising like compounds, with the exception of Dead Sea Salts, or Urea, or both. Comparisons may also be conducted with other known anti-inflammatory compounds such as hydrocortisone, indomethacin, manoalide and topsentin.
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Abstract
The present invention provides pharmaceutical and cosmetic compositions comprising Urea and Dead Sea Salts and their use in reducing skin irritation and skin damage.
Description
SKIN FORMULATION
FIELD OF THE INVENTION
[001] The present invention relates to compositions and methods of use thereof for pharmaceutical and cosmetic treatment of skin.
BACKGROUND OF THE INVENTION
[002] Inflammatory skin disorders, or dermatitis can be divided two groups, differing in their etiology as a result of exogenous causes (allergic contact or primary irritant) or endogenous, which implies all forms of dermatitis not directly related to an external causative factor. Dermatitis results in degenerative changes of the skin including the formation of distinct inflamed lesions that are characterized by color changes, roughening of texture, thickening, reduced moisture content, increased hardness, or a combination thereof. Symptoms include irritation and itching, scaling of the skin, and denuding of the upper layers, often producing bleeding from underlying skin layers. Some inflammatory skin disorders include psoriasis, eczema, acne and lichen planus, with each disease typically manifesting as a spectrum, ranging in severity in patient populations.
[003] Effects of the disease range from mild to severe, in terms of the discomfort produced, as a result of the inflammatory nature of the disease, with no one ideal treatment available to date. Numerous products are available, with varying success, most commonly topically applied medicaments, possessing some type of anti- inflammatory capability, with or without the addition of skin emollients to reduce skin irritation.
[004] During inflammation, modification of skin structure and function is observed. Often the skin protective barrier is compromised, providing an additional complication as a result of the introduction of pathogenic organisms gaining access to underlying skin layers, and in some cases to the bloodstream.
[005] Predominant clinical symptoms of dermatitis are the following: inflammatory epidermal rash, acute or chronic, redness, weeping, scaling and itching. The epidermis may erupt with clear or discolored bumps that may be very itchy. Skin irritation may occur anywhere on the body surface, including the hands, arms legs, upper or lower back, neck, genitals, scalp and nails. Each of these sites, in turn may present with some or all symptoms characteristic of dermatitis.
[006] While the etiology of dermatitis per se, may differ, as a result of endogenous or exogenous factors, common symptomatology exists between the two, chiefly as a result of downstream effects of inflammatory responses resulting in a dysfunction of the main biological mechanisms operating in the skin.
[007] Thus, among the treatment goals are to diminish inflammatory damage to the skin, resulting in a thickening and hardening of the upper skin layers, as well as a release of immmie molecules resulting in further skin irritation, compounding the damage. Treatment regimens aimed at replenishing skin moisture; protecting against on-going loss of moisture; removing dead skin cells; decreasing irritation and minimizing irritant release are among the most sought after treatments. The provision of additional medicaments to reduce or prevent infection is clearly desirable.
[008] Among current favored topical treatment regimens is the inclusion of urea in topical skin ointments and creams. Urea is thought to dissolve the intercellular matrix which results in loosening the horny layer of skin and shedding scaly skin at regular intervals, and hence behaves as a micro-exfolient that improves the appearance and condition of the skin. It is hypothesized that removal of damaged cells by urea expedites emergence of new skin cells from underlying germination layers to the surface of the skin. The newer cells can then rebuild an adequate defense barrier against damaging external agents, and invading pathogens. The actual mechanism of action of topically applied Urea is, however, not yet known.
[009] The therapeutic effect of urea in the treatment of dermatitis is nonetheless equivocal, as contradictory reports of beneficial [Loden M. et al, Skin Res Technol
(2001) 7: 209-13] and no inherent beneficial [Loden M. et al, Acta Derm Nenereol
(2002) 82: 45-7] effects have been reported. Indeed reports of the aggravation of dermatitis exist [Ando M. et al, Contact Dermatitis (2000) 42: 109-10; Narma S. et al, Clin Exp Dermatol (1999) 24: 164-6; and Bohn J. et al, J Eur Acad Dermatol Nenereol (1998) 10: 187-9], as a result of topical administration of Urea compounds. Preliminary experiments with treatment regimens containing both Urea and sodium chloride are encouraging, yet inconclusive as to a significant beneficial effect [Hagstromer L. et al, Skin Pharmacol Appl Skin Physiol (2001) 14: 27-33]. Furthermore, studies indicate that Magnesium salts and not sodium salts are therapeutic for dermatitis, resulting in marked downmodulation of immune responses, via specific doworegulation of MHC class II and costimulatory molecule expression [Schempp CM. et al, J Invest Dermatol (2000) 115: 680-6].
[0010] Mineral salts derived from the dead sea have been suggested to possess great therapeutic promise, owing to their high concentration, as a result of the evaporation of Dead Sea waters concentrating, in particular, magnesium, sodium, potassium, calcium and bromine salts. Dead Sea salts have been proposed as an alternate therapy to urea- based treatments for dry skin [Fisher A. A., Cutis. (1976) 18: 761-767], and dermatitis [Halevy S. et al, Isr Med Assoc J. (2001) 3: 828-32], with combination therapy with UNB exposure producing superior results [Schiffner R. et al. Br J Dermatol (2000) 142: 740-747], nevertheless these protocols are not entirely effective [Shani J. et al. Int J Dermatol (1997) 36: 481-492].
[001 1] The present invention successfully overcomes the shortcomings of previous attempts by providing compositions and methods of use thereof wherein combmed urea and Dead Sea salt therapy provide significant therapeutic effect for inflammatory skin disorders.
SUMMARY OF THE INVENTION [0012] The present invention provides compositions and methods of use thereof for reducing skin damage or irritation, wherein the composition comprises an effective amount of a urea compound and Dead Sea salts.
[0013] In one embodiment, the present invention provides a pharmaceutical or cosmetic composition comprising a urea compound and Dead Sea salts, wherein the urea compound is at a concentration ranging in percentage from 7 to 15 and the Dead Sea salts are at a concentration ranging in percentage from 7 to 15 of the total weight of the composition.
[0014] In another embodiment, the present invention provides a method of reducing skin damage, the method comprising contacting skin with a composition comprising an effective amount of a urea compound and "Dead Sea salts, thereby reducing skin damage. In one embodiment, the skin damage is as a result of an inflammatory response.
[0015] In another embodiment, this invention provides a method of reducing skin irritation, the method comprising contacting skin with a composition comprising an effective amount of a urea compound and Dead Sea salts, thereby reducing skin damage
DETAILED DESCRIPTION OF THE INVENTION
[0016] The present invention provides compositions and methods for reducing skin damage or irritation, comprising urea compounds in combination with mineral salts obtained from the Dead Sea for topical administration. The compositions of the invention are intended for use as a pharmaceutical or cosmetic preparation in the topical treatment of skin, wherein it is desired to optimize the delivery of combined urea and Dead Sea mineral salt preparations upon topical application. Such a composition has excellent properties when used as a keratolytic or a skin softener, in combination with one or more dermatological agents including an emollient, a lubricant, a moisturizer, a protectant, an enhancer of skin penetration, a softener, a PH adjuster, a solubilizer, a preservative or perfume agent. The inclusion of any other ingredient customarily used in compositions intended for topical application is considered part of the present invention as well.
[0017] The compositions of the present invention provide additional application in terms of anti-inflammatory capability. It is thus another object of the present invention to
provide methods and compositions for topical administration for application in any skin inflammatory disorder.
[0018] The terms "inflammatory skin disorders" and "dermatitis" as used herein refer to a condition of the skin that is a result of an inflammatory response. The term "inflammatory response" in turn, refers to the influx of inflammatory cells within the upper layers of the skin, resulting in an array of pathological phenomenon including swelling, discoloration, keratinization, lesion formation, denuding of the upper layers of the skin, the appearance of a rash, blistering, peeling, scaling and hardening, with or without the accompaniment of itching, irritation or dryness, as a result of the influx of the cells, and products released at the site of influx within the skin. An inciting agent or stimulus precedes the development of the inflammatory response culminating in dermatitis. The nature of the dermatitis may be exogenous (with the stimulus being a result of allergic contact or contact with a primary irritant) or endogenous in origin (with the stimulus often unknown however with evidence of an underlying genetic tendency to present with dermatitis), which implies that all forms of dermatitis are not necessarily related to an external causative factor.
[0019] The compositions of the present invention serve to minimize inflammatory damage or irritation to skin as a result of dermatitis. By use of the term "inflammatory damage", all forms of damage including cell and tissue death, degradation of extracellular matrix components and swelling are considered, as are any clinical manifestations as a result of an inflammatory process occurring within the skin. The term "irritation" refers to clinical symptoms as a result of the inflammatory process within the slcin, including swelling, blistering, peeling, scaling and hardening, with or without the accompaniment of itching, irritation or dryness. The terms "reducing skin damage" or "reducing skin irritation" are therefore meant to include a diminution or abrogation in any one or more, or combinations thereof, of the clinical manifestations and symptoms listed herein.
[0020] In one embodiment the compositions of the invention facilitate healing of denuded, exposed skin. Denuded epidermal layers provide a source of entry for
invading pathogens, and as such, the compositions of the present invention may also contain anti-fungal, anti-bacterial or anti-parasitic compounds or pesticides. Additional compounds incorporated within the compositions may include detergents, surfactants and disinfectants, serving an anti-pathogenic function, or alternatively, for facilitating/participating in removal of undesirable slcin layers. Known compounds that stimulate wound healing or contain extracellular matrix components may be additional components of the compositions of the present invention, as well.
[0021] Despite an early indication that urea or salt therapy would be therapeutic for dermatitis, the data are not to date, entirely encouraging. Clearly a treatment regimen beneficial for dermatitis is currently lacking, and it is likely that a combination therapy approach is what is most necessary for successful treatment of the various forms of dermatitis.
[0022] The applicant discovered, surprisingly, that the use of urea in combination with Dead Sea Salts acted synergistically to reduce damage or irritation of inflamed skin, when high concentrations of urea and Dead Sea salts comprise the composition.
[0023] Although either Dead Sea salts or urea has been reported to be therapeutic when used in the topical treatment of dermatitis, the results were equivocal, and as such their combination would not be expected to provide more definitive results. Nevertheless, demonstrable synergisitic effects were readily apparent following their combination, for reduction of inflammatory damage or irritation, in a composition that was hypo- allergenic, smooth and pleasant to the touch.
[0024] Therefore, according to one aspect of the invention, there is provided a method of reducing skin damage or irritation via contacting the skin with a pharmaceutical composition comprising an effective amount of a urea compound and Dead Sea salts, thereby reducing skin damage or irritation.
[0025] In one embodiment, the pharmaceutical compositions for contacting skin are topically applied to affected areas in the form of a gel, cream, milk, stick, foam, soap,
oil, fatty composition, lotion, scalp treatment, shampoo, conditioner, paste, mask, peel, makeup, powder, blush, or may be pressurized in an aerosol device, for ease of application. The compositions may be formulated to be water- or oil-based compositions.
[0026] Skin hardening is one of the hallmarks of inflammatory skin diseases, with other symptoms including irritation, discoloration, itching, cracking and soreness. The composition may therefore additionally include skin softeners, with or without cosmetic colorants and may be applied to the skin on at least a daily basis when the initial or premonitory signs of skin damage or irritation first become apparent.
[0027] Skin irritation or damage may occur anywhere on the body surface, including the hands, arms, legs, upper or lower back, neck, genitals, scalp and nails. Each of these sites, in turn may present with some or all symptoms characteristic of dermatitis, and are sites for therapeutic intervention using the compounds and compositions of the present invention. It is to be understood that different formulations may be produced for optimal delivery to specific body sites. Multiple applications may be necessary and desired for optimal therapeutic effect, and represent a further embodiment of the present invention.
[0028] Since, in some instances, areas of the skin exposed to environmental stresses, including temperature extremes, solvents, light and pressure are particularly prone to inflammation, the compositions of the invention are applied, in one embodiment of the invention, to the limbs, face, or feet, on the basis of 1 to 10 mg of composition per cm of skin, for a period which can range from one week to one year or longer.
[0029] In one embodiment of the invention, the composition is suitable for the topical treatment of skin, in particular for the treatment of inflamed slcin, whereupon it is desirable to obtain a softer texture, and reduced evidence of irritation or damage to one or more layers of the skin.
[0030] In another embodiment of the invention, the composition is suitable for the chronic treatment of inflamed skin, wherein the composition is administered over a period of months or years.
[0031] In another embodiment of the invention, the composition is suitable for the chronic treatment of inflamed slcin, wherein the composition is administered at least once per day..
[0032] The composition of the present invention may be applied alone, or in combination with mechanical exfolients including, but not limited to, sponges, abrasive surfaces, abrasive particles, clothing, combs, brushes, peels, soaps, or a combination thereof. Cosmetic devices comprising the compositions of the present invention represent an additional embodiment.
[0033] Compositions containing urea compounds in combination with mineral salts obtained from the Dead Sea are prepared, in one embodiment, via the methods outlined herein. The components of the compositions will depend upon the particular formulation desired. Formulations are disclosed in Tables 1-4, herein. It is to be understood, however, that acceptable chemically equivalent or accepted substitutes may be employed, as will be known to one skilled in the art.
[0034] To prepare the formulations, oil and aqueous phases may be, in one embodiment, heated separately, then mixed at 80 °C, with high homogenization and mixing, followed by cooling for 90 minutes, at which time the temperature of the mixture will be approximately 45 °C. Fragrance may then be added to the mixture. Other methods of preparation are well described, and indeed accepted practice in the pharmaceutical and cosmetic fields, and are to be considered as part of this invention, as well.
[0035] In another embodiment, the concentration of urea in any of the compositions of the present invention may be at a range of between 7 and 20 % of the weight of the composition. In one embodiment, the concentration of urea in any of the compositions of the present invention may be at a range of between 7 and 8 %, or in another
embodiment, between 8 and 9 %, or in another embodiment between 9 and 10 %, or in another embodiment between 10 and 11 %, or in another embodiment between 11 and 13 %, or in another embodiment between 13 and 15 %, or in another embodiment between 15 and 16 %, or in another embodiment between 16 and 17 %, of the weight of the composition. In another embodiment, the concentration of urea in any of the compositions of the present invention may be at a range of between 7 and 10 %, or in another- embodiment, between 10 and 15 %, or in another embodiment between 8 and 12 % of the weight of the composition.
[0036] In another embodiment, the concentration of Dead Sea salts in any of the compositions of the present invention may be at a range of between 7 and 20 % of the weight of the composition. In one embodiment, the concentration of Dead Sea salts in any of the compositions of the present invention may be at a range of between 7 and 8 %, or in another embodiment, between 8 a-nd 9 %, or in another embodiment between 9 and 10 %, or in another embodiment between 10 and 11 %, or in another embodiment between 11 and 13 %, or in another embodiment between 13 and 15 %, or in another embodiment between 15 and 16 %, or in another embodiment between 16 and 17 %, of the weight of the composition. In another embodiment, the concentration of Dead Sea salts in any of the compositions of the present invention may be at a range of between 7 and 10 %, or in another embodiment, between 10 and 15 %, or in another embodiment between 8 and 12 % of the weight of the composition.
[0037] Compositions comprising urea and Dead Sea salts may, in another embodiment, comprise additional ingredients, in particular organic solvents. Examples of organic solvents may include, but are not limited to, ethanol, methanol, propanol, isopropanol, cetearyl alcohol, cetyl alcohol or combinations thereof.
[0038] In one embodiment, the composition of the invention may be in the form of a cream, and may comprise urea and Dead sea salts in a composition additionally containing water, isopropylmyristate, glyceryl stearate, cetyl alcohol, propylene glycol, glycerin, decyl oleate, caprylic/capric triglyceride, PEG-40 stearate, lanoline, sorbitan
tristearate, imidazohdinyl urea, potassium sorbate, citric acid, methyl paraben, propyl paraben, 2-bromo 2-nitropropane 1,3-diol, BHT, ascorbyl palmitate, ragrance and oils.
[0039] In another embodiment the composition is in the form of a lotion, and may comprise Dead sea salts with or without unsubstituted urea in a composition additionally containing water, ethyl hexyl stearate, cetearyl alcohol and ceteareth-20, propylene glycol, glycerin, cyclopentasiloxane and cyclohexasiloxne, imidazohdinyl urea, potassium sorbate, citric acid, methyl paraben, propyl paraben, 2-bromo 2-nitropropane 1,3-diol, fragrance and oils.
[0040] In another embodiment the composition may be in the form of a scalp treatment, comprising Dead sea salts and urea in a composition additionally containing water, cetearyl alcohol and ceteareth-20, cetyl alcohol, cocamidopropyl betain, sea silt, caprylic/capric triglyceride, decyl oleate, cetrimoniuum chloride, sorbitan tristearate, imidazohdinyl urea, potassium sorbate, citric acid, methyl paraben, propyl paraben, 2- bromo 2-nitropropane 1,3-diol, fragrance and oils.
[0041] The compositions and treatments listed herein may be formulated for administration to adults, or to children, by methods well known to one skilled in the art.
[0042] The above compositions are meant to be exemplary, and are by no means exclusive. Numerous methods of formulation, including the addition of other stabilizers, preservatives, etceteras, may be included in the formulation for enhanced product shelf life.
[0043] In one embodiment, the pharmaceutical or cosmetic composition further comprises emollients, lubricants, moisturizers, protectants, skin penetration enhancers, softeners, pH adjusters, solubilizers or perfume agents.
[0044] Care is taken to provide formulations that are stable, and cause minimal skin irritation. The compositions of the present invention were found to be stable, (Example
2) and hypo-allergenic (Example 3). The compositions of the present invention possess anti-inflammatory activity, as well.
[0045] Other formulations and applications of the present invention are evident through the examples below, and represent additional embodiments of the present invention.
[0046] The following examples are intended to illustrate but not limit the present invention. EXAMPLES EXAMPLE 1: COMPOSITIONS COMPRISING A HIGH CONCENTRATION OF DEAD SEA SALTS AND UREA Materials and Methods: [0047] Compounds combined for the preparation of cream, lipolotion, hydrolotion and scalp treatment compositions and concentrations represented as percent of total composition weight were as listed in tables 1-4, respectively. Oil and aqueous phases were heated separately, then mixed at 80 °C, with high homogenization and mixing, followed by cooling for 90 minutes, at which time the temperature of the mixture was approximately 45 °C. Fragrance was then added to the mixture.
Table 1: Cream Composition
Table 4: Scalp Treatment Composition
Experimental Results: [0048] Dead Sea salts can be formulated with urea compounds to provide compositions that can be applied topically. In order to produce a cream composition that contained a physiologically active concentration of both urea and Dead Sea salts, the composition as outlined in Table 1 was prepared." A smooth white cream was isolated that was fragrant and pleasant to the touch.
[0049] In addition to cream compositions, physiologically active concentrations of urea and Dead Sea Salts were prepared in the form of a lipolotion (an oil soluble formulation), and hydrolotion (a water soluble formulation), with the compositions as outlined in Tables 2 and 3, respectively.
[0050] Both the lipolotion and hydrolotion, when prepared as above produced white, smooth lotions that rapidly incorporated within the skin, penetrating beyond superficial layers, and was pleasant to the touch.
[0051] Topical application of physiologically active concentrations of urea and Dead Sea Salts may be desired in formulations specific for scalp application, for treatment of inflammatory skin diseases, for example. Toward this end, a formulation specific for scalp treatment was prepared, as outlined in Table 4. The composition thus obtained yielded a smooth, white, thin-textured emulsion that was fragrant, and pleasant to the touch.
[0052] Thus physiologically active concentrations of urea and Dead Sea salts were incorporated in an array of formulations and compositions for topical application. Each formulation produced a fragrant, smooth substance that was pleasant to the touch.
EXAMPLE 2: COMPOSITIONS COMPRISING HIGH CONCENTRATIONS OF UREA AND DEAD SEA SALTS ARE STABLE Materials and Methods [0053] A sample of each formulation was cultured for microbiologic determination of the presence of colony forming units. 5-10 gram samples were placed in sterile tubes, and incubated at 37 °C for 14 days, following which, each sample was examined for evidence of phase separation and/or color change. Ex erimental Reults
[0054] Compositions comprising urea and Dead Sea salts are stable. Compositions are determined to be stable if the microbial count is less than 10 colony forming units per gram of sample tested, if there is no color change and if there is no evidence of phase separation of the samples evaluated. No colony forming units were detected in any of the formulations tested. Further, there was no evidence of color change or phase separation in any of the samples analyzed. Thus all 4 formulations were stable.
EXAMPLE 3: COMPOSITIONS COMPRISING HIGH CONCENTRATIONS OF UREA AND DEAD SEA SALTS ARE HYPO-ALLERGENIC Materials and Methods
[0055] 50 healthy subjects were recruited for the tests. Each formulation was placed in a Finn-chamber and tested individually on the skin of the back of each subject. Subjects did not wash the test area until readings were taken. Every 48 hours, for a duration of 24 hours, chambers were applied to the skin of the subjects. The procedure was repeated 9 times. Test results were evaluated by a dermatologist, and presented on a graded scale of 0-5, where 0 indicates no skin reaction, whatsoever, and 5 indicates an acute eczematous reaction, including evidence of vesiculation.
Experimental Results [0056] Compositions comprising urea and Dead Sea salts are hypo-allergenic. Of the fifty subjects evaluated, none had any reaction whatsoever to any of the four formulations tested (Table 5), indicating the hypo-allergenic status of each formulation.
Table 5: Hypo-AUergenicity of High Concentration Urea and Dead Sea Salt Formulations
EXAMPLE 4: COMPOSITIONS COMPRISING HIGH CONCENTRATIONS OF UREA AND DEAD SEA SALTS ARE ANTI-INFLAMMATORY [0057] The compositions and a known inflammatory agent, phorbol myristate acetate (PMA), are topically applied simultaneously to the left ears of mice. Three hours and 20 minutes following application, the mice are sacrificed. Both left ears and right ears are removed and standard sized bores taken. Edema (inflammation) is measured as the difference in weight between left and right ears (See Van Arman, C. G. (1974) Clin. Pharmacol. Ther. 16:900-904). The ability of any of the compositions to reduce edema in mouse ears (caused by application of phorbol myristate acetate), is assessed as compared to control compositions, comprising like compounds, with the exception of Dead Sea Salts, or Urea, or both. Comparisons may also be conducted with other known anti-inflammatory compounds such as hydrocortisone, indomethacin, manoalide and topsentin.
Claims
1. Use of an effective amount of a urea compound and Dead Sea salts in the manufacture of a composition comprising the urea compound and Dead Sea salts in a vehicle suitable for topical application, for reducing skin damage.
2. The use of claim 1, wherein said skin damage is a result of an inflammatory response.
3. The use of claim 1, wherein said composition comprises a urea compound in a percentage ranging from 7 to 15 and Dead Sea salts in a percentage ranging from 7 to 15 of the weight of the total composition.
4. The use of claim 1, wherein said composition further comprises one or more of an emollient, a lubricant, a moisturizer, a protectant, an enhancer of skin penetration, a softener, a PH adjuster, a solubilizer, a preservative or perfume agent.
5. The use of claim 1, wherein said composition further comprises one or more of an anti-bacterial, anti-fungal or anti-parasitic compound or pesticide.
6. The use of claim 1, wherein said composition further comprises a compound that stimulates wound healing.
7. The use of claim 1, wherein said composition further comprises a detergent, a surfactant or an anti-septic compound.
8. The use of claim 1, wherein said composition is a cream, a lotion or a scalp treatment.
9. The use of claim 8, wherein said lotion is an oil- or water-based lotion.
10. The use of claim 8, wherein said scalp treatment is a lotion, a cream, an oil, a shampoo, a conditioner, a mousse, a gel or is pressurized in an aerosol device.
11. Use of an effective amount of a urea compound and Dead Sea salts in the manufacture of a composition comprising the urea compound and Dead Sea salts in a vehicle suitable for topical application, for reducing skin irritation.
12. The use of claim 11, wherein said skin irritation is a result of an inflammatory response.
13. The use of claim 11, wherein said composition comprises a urea compound in a percentage ranging from 7 to 15 and Dead Sea salts in a percentage ranging from 7 to 15 of the total weight of the composition.
14. The use of claim 11, wherein said composition further comprises one or more of an emollient, a lubricant, a moisturizer, a protectant, an enhancer of skin penetration, a softener, a PH adjuster, a solubilizer, a preservative or perfume agent.
15. The use of claim 11, wherein said composition further comprises one or more of an anti-bacterial, anti-fungal or anti-parasitic compound or pesticide.
16. The use of claim 11, wherein said composition further comprises a compound that stimulates wound healing.
17. The use of claim 11, wherein said composition further comprises a detergent, a surfactant or an anti-septic compound.
18. The use of claim 11, wherein said composition is a cream, a lotion or a scalp treatment.
19. The use of claim 11 , wherein said lotion is an oil- or water-based lotion.
20. The use of claim 11, wherein said scalp treatment is an oil, a lotion, a cream, a shampoo, a conditioner, a mousse, a gel or is pressurized in an aerosol device.
21. A pharmaceutical or cosmetic composition comprising a urea compound and Dead Sea salts, wherein said urea compound is at a concentration ranging in percentage from 7 to 15 and said Dead Sea salts is at a concentration ranging in percentage from 7 to 15 of the total weight of the composition.
22. The pharmaceutical or cosmetic composition of claim 21, further comprising one or more of an emollient, a lubricant, a moisturizer, a protectant, an enhancer of skin penetration, a softener, a PH adjuster, a solubilizer, a preservative or a perfume agent.
23. The pharmaceutical or cosmetic composition of claim 21, further comprising one or more of an anti-bacterial, anti-fungal or anti-parasitic compound or pesticide.
24. The pharmaceutical or cosmetic composition of claim 21, further comprising a compound that stimulates wound healing.
25. The pharmaceutical or cosmetic composition of claim 21, further comprising a detergent, a surfactant or an anti-septic compound.
26. The pharmaceutical or cosmetic composition of claim 21, wherein said composition is a cream, a lotion or a scalp treatment.
27. The pharmaceutical or cosmetic composition of claim 26, wherein said lotion is an oil- or water-based lotion.
28. The pharmaceutical or cosmetic composition of claim 26, wherein said scalp treatment is a lotion, a cream, an oil, a shampoo, a conditioner, a mousse, a gel or is pressurized in an aerosol device.
9. A cosmetic device comprising the composition of claim 21.
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US48690203P | 2003-07-15 | 2003-07-15 | |
US60/486,902 | 2003-07-15 |
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WO2005007071A3 WO2005007071A3 (en) | 2005-12-01 |
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PCT/IL2004/000629 WO2005007071A2 (en) | 2003-07-15 | 2004-07-13 | Skin formulation |
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Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1685824A1 (en) * | 2005-01-30 | 2006-08-02 | Or-Le-Or Ltd. | Cosmetic composition |
AT414096B (en) * | 2005-05-03 | 2006-09-15 | Franz Kemptner | Topical formulation, useful to treat nail fungus and foot fungus, comprises carboxylic acid, sea salt of dead sea, glycol, arabic gum, salicylic acid, and mixture of e.g. sodium sulfate, sodium bicarbonate and pentasodium triphosphate |
EP2310022A1 (en) * | 2007-07-12 | 2011-04-20 | Whipbird Pain Relief Pty Ltd | Topical medicament |
JP2013075848A (en) * | 2011-09-30 | 2013-04-25 | Nippon Menaade Keshohin Kk | Anti-inflammatory agent |
AU2008274908B2 (en) * | 2008-07-11 | 2014-08-14 | Whipbird Pain Relief Pty Ltd | Topical medicament |
WO2014015881A3 (en) * | 2012-07-25 | 2014-11-13 | Kimovi Aps | A cosmetic or medical composition with kigelia africana |
US9693936B2 (en) | 2012-03-07 | 2017-07-04 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Dispersions in oil of Dead Sea nano sized material preparation and uses therof |
GB2569682A (en) * | 2017-10-20 | 2019-06-26 | Water Jel Europe Llp | Composition |
US11040066B2 (en) | 2017-10-20 | 2021-06-22 | Safeguard Medical Holdco, Llc | Topical composition for use in the treatment of burns |
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US6248340B1 (en) * | 1997-07-10 | 2001-06-19 | Dead Sea Laboratories, Ltd. | Skin care and protection composition and a method for preparation thereof |
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2004
- 2004-07-13 WO PCT/IL2004/000629 patent/WO2005007071A2/en active Application Filing
Patent Citations (1)
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US6248340B1 (en) * | 1997-07-10 | 2001-06-19 | Dead Sea Laboratories, Ltd. | Skin care and protection composition and a method for preparation thereof |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1685824A1 (en) * | 2005-01-30 | 2006-08-02 | Or-Le-Or Ltd. | Cosmetic composition |
AT414096B (en) * | 2005-05-03 | 2006-09-15 | Franz Kemptner | Topical formulation, useful to treat nail fungus and foot fungus, comprises carboxylic acid, sea salt of dead sea, glycol, arabic gum, salicylic acid, and mixture of e.g. sodium sulfate, sodium bicarbonate and pentasodium triphosphate |
EP2310022A1 (en) * | 2007-07-12 | 2011-04-20 | Whipbird Pain Relief Pty Ltd | Topical medicament |
EP2310022A4 (en) * | 2007-07-12 | 2011-08-24 | Whipbird Pain Relief Pty Ltd | Topical medicament |
AU2008274908B2 (en) * | 2008-07-11 | 2014-08-14 | Whipbird Pain Relief Pty Ltd | Topical medicament |
JP2013075848A (en) * | 2011-09-30 | 2013-04-25 | Nippon Menaade Keshohin Kk | Anti-inflammatory agent |
US9693936B2 (en) | 2012-03-07 | 2017-07-04 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Dispersions in oil of Dead Sea nano sized material preparation and uses therof |
WO2014015881A3 (en) * | 2012-07-25 | 2014-11-13 | Kimovi Aps | A cosmetic or medical composition with kigelia africana |
GB2569682A (en) * | 2017-10-20 | 2019-06-26 | Water Jel Europe Llp | Composition |
GB2569682B (en) * | 2017-10-20 | 2020-06-17 | Water Jel Europe Llp | Topical composition for use in the treatment of burns |
US11040066B2 (en) | 2017-10-20 | 2021-06-22 | Safeguard Medical Holdco, Llc | Topical composition for use in the treatment of burns |
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