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WO1999036053A1 - Compositions de blanchiment stabilisees et leur procede de preparation - Google Patents

Compositions de blanchiment stabilisees et leur procede de preparation Download PDF

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Publication number
WO1999036053A1
WO1999036053A1 PCT/US1998/022685 US9822685W WO9936053A1 WO 1999036053 A1 WO1999036053 A1 WO 1999036053A1 US 9822685 W US9822685 W US 9822685W WO 9936053 A1 WO9936053 A1 WO 9936053A1
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WO
WIPO (PCT)
Prior art keywords
composition
hydroxyacid
hydroxyacids
acid
skin
Prior art date
Application number
PCT/US1998/022685
Other languages
English (en)
Inventor
Jeffrey Ehrenberg
Linda Najdek
Elena M. Ciriello
Original Assignee
Color Access, Inc.
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
Application filed by Color Access, Inc. filed Critical Color Access, Inc.
Priority to AU12010/99A priority Critical patent/AU1201099A/en
Priority to KR10-1999-7008377A priority patent/KR100483391B1/ko
Priority to CA002283574A priority patent/CA2283574A1/fr
Priority to JP53717599A priority patent/JP3563413B2/ja
Publication of WO1999036053A1 publication Critical patent/WO1999036053A1/fr

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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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • 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
    • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • 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
    • A61K8/67—Vitamins
    • 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
    • A61K8/67—Vitamins
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • 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
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present invention relates to useful pharmaceutical and cosmetic compositions capable of causing a whitening affect on the skin.
  • the invention relates to a stabilized composition of hydroxyacid and a whitening agent together in solution capable of maintaining the independent pH values of its contents as well as other properties of the whitening agent and hydroxyacid.
  • the color of the skin is determined by melanin which is a biopolymer pigment manufactured by special dendritic cells known as melanocytes. elanocytes are located primarily below or between basal cells of the epidermis or upper layer of the skin.
  • the basal layer is one of two main layers of the epidermis. The viable basal layer is at the bottom of the epidermis in contact with the dermis. And, the second layer is the dead corneal or horny layer located above the basal layer which extends upward to the surface of the skin.
  • melanocytes have long, thin, branching, streamer-like dendrites or arms that reach between the epidermal cells in their immediate vicinity. An arrangement of epidermal cells is thereby created around each melanocyte. The activity of melanocytes determines the production of melanin and therefore, the color or rather the light or dark complexion of the skin.
  • Melanin production is stimulated by both internal and external factors. Melanin once produced, travels from the melanosome region to the dendrites of the melanocyte. Epidermal cells in contact with the melanin-laden dendrites phagocytose the tips of the dendrites and transfer melanin to the surrounding epidermal cells. Melanin granules move above the cell nucleus inside the epidermal cells. Because melanin orients itself in this manner, it is believed that melanin functions to protect cells from damaging ultraviolet ("UV") rays. Production of melanin is stimulated by the external factor of UV radiation. Internally, biochemical stimulation of melanin is achieved by the enzyme tyrosinase.
  • Tyrosinase causes oxidation of substrates tyrosine and levodopa to dopaquinone followed by subsequent polymerization of numerous intermediates into melanin.
  • the mechanism of melanin biosynthesis is a complex process and it is well known that tyrosinase is an important driving force in the process. See M.M. Wick, V.J. Hearing and H. Rorsman, Biochemistry of Melanization, pp. 251 -
  • compositions useful for inducing a depigmentation effect on the human skin focus on bleaching the skin with sodium hypochlorite, hydroquinone, monoethyl ether, ammoniated mercury, zinc peroxide, mercurous chloride or bichloride of mercury.
  • sodium hypochlorite sodium hypochlorite
  • hydroquinone monoethyl ether
  • ammoniated mercury zinc peroxide
  • mercurous chloride or bichloride of mercury are disadvantageous because they sensitize the skin, irritate the skin and do not provide predictable results. Therefore, an effective treatment is still desired that will inhibit either the production of the enzyme tyrosinase or the production of the intermediates during melanogenesis.
  • Compounds which inhibit synthesis of melanin include a serotonin uptake antagonist and a histamine agonist.
  • the serotonin uptake antagonist 6-nitroquipazine, inhibits melanin activity without affecting tyrosinase activity.
  • the histamine agonists decrease and eventually halt melanin production by affecting tyrosinase activity.
  • ascorbic acid and its derivatives are known to be useful in decomposing melanin in the epidermis. Ascorbic acid has been widely employed in skin whitening products. However, there are many challenges to formulating ascorbic acid due to the fact that in typical formulations, it can be quite unstable and readily degrades. Ascorbic acid is an alpha keto lactone and is sensitive to light, oxygen and water due its low pH value.
  • compositions for the effect of whitening can present a serious problem to the formulator because substances have varying properties.
  • substances having varying pH values when combined can neutralize each other such that the desired effect of the individual substances cannot be obtained.
  • the individual substances lose their desired properties or can no longer provide the properties they were intended to have when added to the solution.
  • such compositions contain substances of similar pH values.
  • the pH of the solution when formulating ascorbic acid, the pH of the solution must be below a pH value of about 3.5.
  • the acidity of the solution does not render the solution suitable for use as a cosmetic or pharmaceutical because it can irritate the skin.
  • MAP magnesium ascorbyl phosphate
  • MAP magnesium ascorbyl phosphate
  • the pH of a solution containing MAP is basic and when used on the skin is also irritating to the skin.
  • ascorbic acid causes melanin to decompose in the epidermis rendering a "whitening" affect on the skin.
  • Standard formulations are usually creams or lotions from which ascorbic acid must diffuse from the base formula to the skin to "whiten" the skin.
  • ascorbic acid and its derivatives have been shown to be an effective skin whitener, their stability in combination with other actives and ingredients in solution is a need that remains to be addressed. Further, a vehicle is needed to enhance the delivery of ascorbic acid from the base formula to the skin. Therefore, in order to fully exploit its useful properties as a whitener, a means is sought by which ascorbic acid and its derivatives can be stabilized in a desired composition with other actives and ingredients, while retaining their independent useful properties, and by which ascorbic acid can be readily delivered from the formula to the skin.
  • the present invention provides such a means, and is substantially non-irritating to the skin. The demand for whiteners that are cosmetically appealing continues to grow and therefore, there is a need for a stable whitening composition that satisfies consumer needs.
  • the present invention provides stable cosmetic and pharmaceutical compositions comprising at least one hydroxyacid encapsulated in a lamellar vesicle and a whitening agent in a cosmetically or pharmaceutically acceptable carrier.
  • the whitening agent is optimally stable at non- acidic pH levels.
  • the encapsulated hydroxyacid provides for adequate stability of the whitening composition by allowing the hydroxyacid and the whitening agent to coexist in solution together. Therefore, the properties of the acid and the whitening agent do not degrade while they are in solution together.
  • composition of the present invention can also contain two hydroxyacids.
  • Each of the hydroxyacids are encapsulated within a lamellar vesicle.
  • the individual vesicles containing individual hydroxyacids are combined in solution with a metal salt of a phosphoric acid ester of ascorbic acid.
  • the metal salt can be formed by a univalent, divalent, or trivalent metal.
  • the invention also provides a method for preparing a stable cosmetic or pharmaceutical composition for causing a whitening affect on the skin, comprising encapsulating at least one hydroxyacid and adding the encapsulated hydroxyacid to a solution containing an effective amount of a whitening agent. Further, the invention relates to a method of whitening the skin which comprises applying to the skin an effective amount of the subject whitening composition.
  • hydroxyacids are frequently desirable because of their properties.
  • hydroxyacids can assist in bringing about a whitening affect, thereby enhancing the efficacy of the composition as a whole by complementing the action of the main whitening active.
  • hydroxyacid is encapsulated in a lamellar vesicle to provide a means for adding an acid component to the whitening composition containing whitening agents that otherwise may degrade the properties of the acid, the whitening agent, or both.
  • the acid and the whitening agent can exist in solution together without affecting their desired properties. Therefore, the solution can contain numerous actives and other ingredients having various properties that exist independently in the solution. As a result, the composition is multifunctional in its effect when applied to the skin.
  • a preferred composition of the present invention is a cosmetic or pharmaceutical composition, in which the total amount of hydroxyacid is preferably from about 0.01 to about 5 percent, more preferably from about 0.02 to about 1.0 percent.
  • hydroxyacid for purposes of the present invention includes both alpha-hydroxyacids and beta-hydroxyacids in their free acid form, as well as covalent derivatives thereof. Suitable hydroxyacids include, but are not limited to.
  • alpha-hydroxyacids such as lactic acid, glycolic acid, citric acid, alpha-hydroxyoctanoic acid, alpha-hydroxydecanoic acid, alpha-hydroxylauric acid, tartaric acid, glucouronic acid, galactouronic acid, alpha-hydroxybutyric acid, alpha-hydroxyisobutyric acid, malic acid, mandelic acid, pyruvic acid, and tartronic acid, preferably alpha-hydroxydecanoic and alpha-hydroxyoctanoic acids; and beta-hydroxyacids such as salicylic acid.
  • Suitable covalent derivatives include esters, amides and lactones, and mixtures thereof.
  • the lamellar vesicles containing hydroxyacids in the amount stated above may be present in the composition in an amount of about 0.04 to about 20 percent by weight.
  • the total amount of encapsulated hydroxyacid is preferably from about 2 to about 10 percent by weight.
  • vesicles contain multiple lipid layers, each of which surround a small aqueous volume separating the layer.
  • Vesicles of this kind and methods of making the same have been described in, for example, U.S. Patent No. 5,585,109. The contents are incorporated by reference in its entirety.
  • the lamellar vesicle encapsulating the hydroxyacids is a lipid vesicle having lipid components.
  • lipid vesicle for purposes of the present invention refers to any spherical, self-closed structure composed of one or more lipid components arranged in the form of curved lipid bilayers which entrap part of the solvent in which they freely float.
  • Lipid vesicles are also commonly referred to as "liposomes" and may consist of one or several concentric membranes. While the thickness of the membrane is about 4 nanometers, the size of the liposome can range from about 20 nanometers to several dozen micrometers.
  • Liposomes are essentially microscopic spherical membrane enclosed vesicles or sacs that are non-toxic to living cells and capable of delivering their contents.
  • the contents of a liposome are contained by the bilayers of the liposome.
  • Phospholipids are a common lipid source for the bilayers of the liposome.
  • the liposomes of the present invention may be made from natural and synthetic phospholipids, glycolipids and other lipids and lipid congeners; cholesterol, cholesterol derivatives and other cholesterol congeners; charged species which impart a net charge to the membrane; reactive species which can react after liposome formation to link additional molecules to the liposome membrane; and other lipid soluble compounds which have chemical or biological activities.
  • phospholipids include but are limited to natural sources such as egg yolk lecithin, soya lecithin, phosphatidylethanolamines, phosphatidylserines, cereamides, cerebrosides. and phosphatidylglycerides.
  • the present invention also includes alternatives to natural phospholipids for example, synthetic phospholipids such as dipalmitoylphosphatidylcholine, synthetic amphiphiles such as polyglycerol derivatives, non-ionic materials such as polyoxyethylene ethers and esters, and cation ic materials.
  • Liposomes are artificially made by a variety of methods. Most methods of making lipid vesicles are derived from the Bangham method, see Bangham et al., J. Mol. Biol., 13:238-252 (1965). A more detailed discussion on lipid vesicles is provided in the following reference, D.D. Lasc, "Liposomes, From Physics To Applications,” (Elsevier, New York. 1993), incorporated herein by reference.
  • the liposomes of the present invention may be of various size and may comprise either one or several membrane layers separating the internal and external compartments.
  • Whitening agents can include licorice extract, ascorbic acid (Vitamin C) or an isomer, homolog, analog or derivative thereof, salicylic acid, lactic acid, tyrosinase inhibitors (e.g. kojic acid), antioxidant free radical traps, compounds which inhibit cyclic AMP, histamine agonists, serotonin uptake inhibitors, pituitary-ovarian axis suppressors, Vitamin E.
  • composition of the present invention can contain any whitening agent, a particular benefit is obtained when the whitening agent is one which is active at a non-acidic pH.
  • a particular benefit is obtained when the whitening agent is one which is active at a non-acidic pH.
  • Particularly preferred of this type are ascorbic acid derivatives.
  • the derivatives of ascorbic acid which may be used are, for example, ascorbyl esters of fatty acids, such as ascorbyl palmitate, ascorbyl dipalmitate, ascorbyl dimethylsilanol palmitate, and ascorbyl stearate; univalent, divalent or trivalent metal or metal phosphate salts, such as magnesium, calcium, sodium, or potassium ascorbyl phosphate, or magnesium, calcium, sodium or potassium ascorbate.
  • ascorbic acid is a univalent, divalent or trivalent metal salt of a phosphoric acid ester of ascorbic acid.
  • ascorbic acid is a derivative thereof in the form of a divalent metal salt of a phosphoric acid ester of ascorbic acid selected from the group consisting of magnesium or calcium. These can be used singly or in combinations of two or more.
  • the whitening composition of the present invention is comprised of at least two hydroxyacids encapsulated in separate lamellar vesicles in combination with a metal salt of a phosphoric acid ester of ascorbic acid.
  • one of the two hydroxyacids is an alpha-hydroxyacid and the other is a beta-hydroxyacid.
  • the composition contains lactic acid and salicylic acid which enhance the properties of the composition. Specifically, lactic acid and salicylic acid enhance the ability of the composition to whiten the skin. Further, salicylic acid acts as a keratolytic agent increasing the rate of cell turnover and providing an exfoliating property to the composition.
  • hydroxyacids which are acidic, stably exist in solution with the whitening agent which has a higher pH. Encapsulating the hydroxyacids also serves to keep them in the most effective layer of the skin. If more than one hydroxyacid is used, they may be added to the composition in a single liposome, or in separate individual liposomes, which may be of any type. However, in a preferred embodiment, if salicylic acid is employed, it is incorporated into a liposome specifically adapted for delivery of salicylic acid.
  • the appropriate vesicle for encapsulating salicylic acid is one that is designed slightly different than a liposome containing lactic acid in order to accommodate some of the challenges of encapsulating salicylic acid.
  • the liposome containing salicylic acid also known as a SalisomeTM, includes a membrane forming a liposomal bilayer surrounding the salicylic acid, a polar, water-soluble organic base, and water.
  • Suitable SalisomesTM is described, for example, in U.S. Patent No. 5,585,109 the contents of which are incorporated herein by reference.
  • various methods can be used. There are numerous techniques for making liposomes containing lactic acid. In general, these techniques involve mixing the components that form the lipid bilayer of the liposome, as well as the component, in this case lactic acid, which is to be encapsulated within the liposome, under conditions that permit its formation. Further, the ingredients used to make the liposome can be processed in a microfluidizer to mass manufacture the liposomes in a stable lamellar phase.
  • Microfluidization permits the formation of liposomes that can maintain an ordered lipid bilayer during storage.
  • suitable microfluidizers for making lamellar vesicles is described in Mayhew et al., "Characterization of Liposomes Prepared Using a Microemulsifier.” Biochem. et Biophys. Ada., 775, pp. 169-74 (1984).
  • the whitening compositions can also be formulated with a variety of cosmetically and/or pharmaceutically acceptable carriers.
  • the compositions of the present invention will comprise a pharmaceutically or cosmetically acceptable carrier, in an amount appropriate to accommodate the other components of the formulation.
  • pharmaceutically and/or cosmetically acceptable carrier refers to a vehicle, for either pharmaceutical or cosmetic use, which vehicle delivers the active components to the intended target and which will not cause harm to humans or other recipient organisms.
  • pharmaceutical or “cosmetic” will be understood to encompass both human and animal pharmaceuticals or cosmetics.
  • the carrier may be in any form appropriate to the mode of delivery, for example, solutions, colloidal dispersions, emulsions, suspensions, creams, lotions, gels, foams, mousses and the like.
  • the whitening compositions can be prepared in any form convenient for topical application to the skin. Such forms include, but are not limited to gels, creams, dispersions, emulsions (water-in-oil or oil-in-water), suspensions, lotions, foams, mousses and the like.
  • the carrier is a suspension, dispersion or emulsion.
  • the emulsion may be an oil-in-water emulsion, or a water-in-oil emulsion. These emulsions contain one or more oil components, an aqueous component, and a specific emulsifier component chosen depending on the nature of the desired emulsion.
  • the oil component may be any pharmaceutically or cosmetically acceptable material which is substantially insoluble in water. These materials can be found for example in the CTFA International Dictionary of Cosmetic Ingredients as well as the U.S. Pharmacopoeia or other equivalent sources.
  • Suitable oil components include, but are not limited to, natural oils, such as coconut oil; hydrocarbons, such as mineral oil and hydrogenated polyisobutene; fatty alcohols, such as octyldodecanol; esters, such as Cl 2-15 alkyl benzoate; diesters, such as propylene glycol dipelargonate; triesters, such as glyceryl trioctanoate; sterol derivatives, such as lanolin; animal waxes, such as beeswax; plant waxes, such as carnauba; mineral waxes, such as ozokerite; petroleum waxes, such as paraffin wax; synthetic waxes, such as polyethylene; and mixtures thereof.
  • Suitable oil components may also be silicones including, but not limited to, volatile silicones such as cyclomethicone; polymeric silicones such as dimethicone; alkylated derivatives of polymeric silicones, such as cetyl dimethicone and lauryl trimethicone; hydroxylated derivatives of polymeric silicones, such as dimethiconol; and mixtures thereof.
  • volatile silicones such as cyclomethicone
  • polymeric silicones such as dimethicone
  • alkylated derivatives of polymeric silicones such as cetyl dimethicone and lauryl trimethicone
  • hydroxylated derivatives of polymeric silicones such as dimethiconol
  • mixtures thereof such as dimethiconol
  • the aqueous component refers to any pharmaceutically or cosmetically acceptable material consisting essentially or predominantly of water.
  • the oil-in-water emulsifier will be an emulsifier having a hydrophilic-lipophilic balance (HLB) of at least 8, or a mixture of such emulsifiers with one or more water-in-oil emulsifiers (i.e., emulsifiers having an HLB of from about 2 to about 6), in which case the type and amount of each emulsifier present in the mixture is selected such that the effective HLB of the resultant oil-in-water emulsifier component is at least about 6.
  • HLB hydrophilic-lipophilic balance
  • Suitable oil-in-water emulsifiers include, but are not limited to, sorbitol derivatives, such as sorbitan monolaurate and polysorbate 20; ethoxylated alcohols such as laureth-23, ethoxylated fatty acids such as PEG-1000 stearate; amidoamine derivatives such as stearamidoethyl diethylamine; sulfate esters such as sodium lauryl sulfate; phosphate esters such as DEA cetyl phosphate; fatty acid amine salts such as TEA stearate; and mixtures thereof.
  • sorbitol derivatives such as sorbitan monolaurate and polysorbate 20
  • ethoxylated alcohols such as laureth-23, ethoxylated fatty acids such as PEG-1000 stearate
  • amidoamine derivatives such as stearamidoethyl diethylamine
  • sulfate esters such
  • the emulsion may also be a water-in-oil emulsion.
  • a water-in-oil emulsifier refers to any cosmetically acceptable emulsifier having an HLB of no greater than 6, preferably from about 2 to about 4.
  • Suitable water-in-oil emulsifiers include, but are not limited to, sorbitan derivatives such as sorbitan laurate and sorbitan palmitate; alkoxylated alcohols such as laureth-4; hydroxylated derivatives of polymeric silicones, such as dimethicone copolyol; alkylated derivatives of hydroxylated polymeric silicones, such as cetyl dimethicone copolyol; glyceryl esters such as polyglyceryl-4 isostearate; beeswax derivatives such as sodium isostearoyl-2 lactylate; lecithin; and mixtures thereof.
  • sorbitan derivatives such as sorbitan laurate and sorbitan palmitate
  • alkoxylated alcohols such as laureth-4
  • hydroxylated derivatives of polymeric silicones such as dimethicone copolyol
  • alkylated derivatives of hydroxylated polymeric silicones such as cety
  • the skin enhancing effects of the whitening compositions of the present invention may also have incorporated active agents which are used for skin treatment, or which are routinely applied topically.
  • active agents which may form part of the composition include, but are not limited to, those that improve or eradicate age spots, keratoses and wrinkles, analgesics, anesthetics, anti-acne agents, antibacterials, antiyeast agents, antifungal agents, antiviral agents, antidandruff agents, antidermatitis agents, antipruritic agents, antiemetics, antimotion sickness agents, anti-inflammatory agents, antihyperkeratolytic agents, anti-dry skin agents, antiperspirants, antipsoriatic agents, antiseborrheic agents, hair conditioners and hair treatment agents, antiaging agents, antiwrinkle agents, antiasthmatic agents and bronchodilators, sunscreen agents, antihistamine agents, wound-healing agents, vitamins, corticosteroids, or hormones.
  • useful active agents include retinoids, topical cardiovascular agents, clotrimazole, ketoconazole, miconozole, griseofulvin, hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, erythromycin, tetracyciine, clindamycin, meclocyline, hydroquinone, minocycline, naproxen, ibuprofen, theophylline, cromolyn, albuterol, retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocortisone 21 -acetate, hydrocortisone 17-valerate, hydrocortisone 17- butyrate, betamethasone valerate, betamethasone diproprionate, triamcinolone acetonide, fluocinonide, clobetasol, proprionate, benzoyl peroxide, crotamiton, prop
  • compositions may also comprise additional preservatives, fragrances, emollients, antiseptics, antiinflammatories, antibacterials, stabilizers, antioxidants, vitamins, pigments, dyes, humectants, and propellants, as well as other classes of materials the presence of which in the compositions may be cosmetically, medicinally, or otherwise desired.
  • additional preservatives such components can be found in the CTFA International Cosmetics Ingredients Dictionary, supra.
  • suitable preservatives are BHA, BHT, propyl paraben, butyl paraben or methyl paraben or an isomer, homolog, analog or derivative thereof
  • the whitening compositions of the present invention can be topically applied for spot treatment.
  • the composition can be applied to areas of uneven skin tones, dark spots or freckles when they appear or on a continuing as needed basis.
  • a preferred method of obtaining the benefits of the whitening composition is via chronic topical application of a safe and effective amount of the whitening composition of the present invention. It is suggested as an example, that topical application range from about every other day to about 1 to 3 times daily, preferably from about once daily to about 2 times daily, most preferably about once or twice per day.
  • the period of topical application may be over the lifetime of the user, preferably for a period of at least about one month, more preferably from about three months to about twenty years, more preferably from about six months to about ten years, more preferably still from about one year to about five years, thereby resulting in the achievement of a whitening effect on the skin.
  • the treatment regimen employed can vary depending upon the user's level of melanocyte activity producing melanin and enzymatic activity destroying melanin.
  • the compositions of the present invention are ideal for spot treatment they can be used on the entire face if needed or they can be used on other areas of the skin.
  • compositions of the present invention are applied to the skin by covering the area desired to be whitened and blending the composition into such area of the skin.
  • the whitening compositions are preferably used after a cleansing regimen.
  • the cleansing regimen may consist of cleansing the skin with a soap or other form of cleanser, removing soap residue with a toner or clarifying lotion, and applying a moisturizing cream or lotion to the skin.
  • the whitening compositions are applied to the desired areas of the skin to be whitened such as areas of the skin where the tone of the skin is uneven or other types of spots that may be found on the skin.
  • Liposomes and SalisomesTM (salicylic acid-containing liposomes) containing lactic acid and salicylic acid respectively are provided by Collaborative Laboratories, East Setauket, NY.
  • the liposomes, SalisomesTM, and the whitening composition are prepared as follows:
  • composition of the present invention which follows is obtained according to the procedure below. The following steps are performed successively at room temperature (20°
  • the constituents of PHASE I (hereinafter referred to as “the oil phase”) are mixed together, followed by addition of the PHASE II constituent by sprinkling while mixing with a mixer.
  • Licorice is dissolved in butylene glycol and added to the oil phase.
  • a pH test determines that the pH of the composition does not drift indicating that the liposome and the SalisomeTM are stable.
  • a lack of crystallization substantiates further that the magnesium ascorbyl phosphate is stable in the composition due to the stability of the lactic acid in the liposome and the salicylic acid in the SalisomeTM.

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  • General Health & Medical Sciences (AREA)
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  • Cosmetics (AREA)

Abstract

La présente invention porte sur des compositions pharmaceutiques ou cosmétiques stables contenant au moins un hydroxyacide encapsulé dans une combinaison vésiculaire lamellaire avec un agent de blanchiment. L'invention porte également sur un procédé de préparation d'une composition pharmaceutique ou cosmétique stable qui consiste à encapsuler l'hydroxyacide dans un excipient pharmaceutique ou cosmétique contenant un agent de blanchiment.
PCT/US1998/022685 1998-01-16 1998-10-26 Compositions de blanchiment stabilisees et leur procede de preparation WO1999036053A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AU12010/99A AU1201099A (en) 1998-01-16 1998-10-26 Stabilized whitening compositions and method of preparing same
KR10-1999-7008377A KR100483391B1 (ko) 1998-01-16 1998-10-26 안정화된 미백 조성물 및 이의 제조 방법
CA002283574A CA2283574A1 (fr) 1998-01-16 1998-10-26 Compositions de blanchiment stabilisees et leur procede de preparation
JP53717599A JP3563413B2 (ja) 1998-01-16 1998-10-26 安定化白化組成物及びその製造方法

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FR2789329A1 (fr) * 1999-02-05 2000-08-11 Oreal Composition cosmetique et/ou dermatologique constituee par une emulsion du type huile-dans-l'eau formee de vesicules lipidiques dispersees dans une phase aqueuse contenant au moins un actif acide hydrophile
WO2001066105A1 (fr) * 2000-03-07 2001-09-13 Young Pharmaceuticals, Inc. Procede et composition pour eclaircir la peau
WO2001070189A1 (fr) * 2000-03-21 2001-09-27 Unilever Plc Procede et composition destines a l'eclaircissement de la peau utilisant des acides carboxyliques
WO2003041665A1 (fr) * 2001-11-09 2003-05-22 The Nisshin Oillio, Ltd. Composition sous forme de gel
FR2873292A1 (fr) * 2004-07-23 2006-01-27 Jean Noel Colombani Composes et methodes pour controler la prise d'alcool
WO2009016064A1 (fr) * 2007-07-31 2009-02-05 Basf Se Utilisation de nanodispersions pour protéger des ingrédients solubles dans l'eau dans des formulations à but cosmétique
US20110201578A1 (en) * 2010-02-14 2011-08-18 Nyangenya Maniga Composition and methods for the treatment of pseudofolliculitis barbae and skin irritation
WO2012100366A1 (fr) * 2011-01-25 2012-08-02 The Procter And Gamble Company Liposome et composition d'hygiène corporelle le contenant
CN102821742A (zh) * 2010-03-31 2012-12-12 株式会社爱茉莉太平洋 黑色素抑制剂及含有该抑制剂的化妆品组合物
WO2017001617A1 (fr) * 2015-06-30 2017-01-05 Sequessome Technology Holdings Limited Formulations mélangées
WO2018134714A1 (fr) * 2017-01-21 2018-07-26 R&R Salons Pvt. Ltd. Composition de soin de la peau blanchissante à base de dihydromyricétine, de niacinamide et d'un modificateur de ph

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KR100482355B1 (ko) * 2002-05-02 2005-04-14 주식회사 알로에마임 디팔미토일하이드록시프롤린과 소이이소플라본을 함유한리포좀 또는 나노에멀젼 및 이를 함유한 화장료 조성물 및그 제조방법
JP4799907B2 (ja) * 2005-04-22 2011-10-26 サンスター株式会社 乳化型化粧料
FR2894961B1 (fr) * 2005-12-16 2008-05-16 Oreal Utilisation de ceramides pour depigmenter la peau
KR101252552B1 (ko) * 2006-02-01 2013-04-08 (주)아모레퍼시픽 비타민ｃ 또는 비타민ｃ 유도체를 함유한 미백 화장료조성물
JP6725207B2 (ja) * 2015-03-24 2020-07-15 小林製薬株式会社 皮膚色素沈着抑制剤
KR102565469B1 (ko) * 2022-08-31 2023-08-16 주식회사 한국리포좀 비타민 c가 포집된 리포좀 및 이의 제조방법

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Cited By (18)

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Publication number Priority date Publication date Assignee Title
EP1027878A1 (fr) * 1999-02-05 2000-08-16 L'oreal Composition cosmétique et/ou dermatologique constituée par une émulsion du type huile-dans-eau formée de vésicules lipidiques dispersées dans une phase aqueuse contenant au moins un actif acide hydrophile
US6416768B1 (en) 1999-02-05 2002-07-09 L'oreal Cosmetic and/or dermatological composition consisting of an emulsion of the oil-in-water type formed from lipid vesicles dispersed in an aqueous phase containing at least one hydrophilic acidic active agent
FR2789329A1 (fr) * 1999-02-05 2000-08-11 Oreal Composition cosmetique et/ou dermatologique constituee par une emulsion du type huile-dans-l'eau formee de vesicules lipidiques dispersees dans une phase aqueuse contenant au moins un actif acide hydrophile
WO2001066105A1 (fr) * 2000-03-07 2001-09-13 Young Pharmaceuticals, Inc. Procede et composition pour eclaircir la peau
WO2001070189A1 (fr) * 2000-03-21 2001-09-27 Unilever Plc Procede et composition destines a l'eclaircissement de la peau utilisant des acides carboxyliques
WO2003041665A1 (fr) * 2001-11-09 2003-05-22 The Nisshin Oillio, Ltd. Composition sous forme de gel
EP2258354A1 (fr) * 2004-07-23 2010-12-08 JNC Innovations Composés et méthodes pour contrôler la prise d'alcool.
FR2873292A1 (fr) * 2004-07-23 2006-01-27 Jean Noel Colombani Composes et methodes pour controler la prise d'alcool
WO2006018521A3 (fr) * 2004-07-23 2006-04-13 Jean-Noel Colombani Composes et methodes pour controler la prise d'alcool.
WO2009016064A1 (fr) * 2007-07-31 2009-02-05 Basf Se Utilisation de nanodispersions pour protéger des ingrédients solubles dans l'eau dans des formulations à but cosmétique
US20110201578A1 (en) * 2010-02-14 2011-08-18 Nyangenya Maniga Composition and methods for the treatment of pseudofolliculitis barbae and skin irritation
CN102821742A (zh) * 2010-03-31 2012-12-12 株式会社爱茉莉太平洋 黑色素抑制剂及含有该抑制剂的化妆品组合物
WO2012100366A1 (fr) * 2011-01-25 2012-08-02 The Procter And Gamble Company Liposome et composition d'hygiène corporelle le contenant
WO2017001617A1 (fr) * 2015-06-30 2017-01-05 Sequessome Technology Holdings Limited Formulations mélangées
US10744090B2 (en) 2015-06-30 2020-08-18 Sequessome Technology Holdings Limited Multiphasic compositions
EA038613B1 (ru) * 2015-06-30 2021-09-23 Секвессом Текнолоджи Холдингс Лимитед Смешанные составы
US11547665B2 (en) 2015-06-30 2023-01-10 Sequessome Technology Holdings Limited Multiphasic compositions
WO2018134714A1 (fr) * 2017-01-21 2018-07-26 R&R Salons Pvt. Ltd. Composition de soin de la peau blanchissante à base de dihydromyricétine, de niacinamide et d'un modificateur de ph

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CA2283574A1 (fr) 1999-07-22
JP2000511945A (ja) 2000-09-12
KR20000076280A (ko) 2000-12-26
AU1201099A (en) 1999-08-02
TWI236911B (en) 2005-08-01
KR100483391B1 (ko) 2005-04-15
JP3563413B2 (ja) 2004-09-08

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