US20010009672A1 - Compositions and methods for controlling deposition of water-insoluble - Google Patents
Compositions and methods for controlling deposition of water-insoluble Download PDFInfo
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- US20010009672A1 US20010009672A1 US09/205,692 US20569298A US2001009672A1 US 20010009672 A1 US20010009672 A1 US 20010009672A1 US 20569298 A US20569298 A US 20569298A US 2001009672 A1 US2001009672 A1 US 2001009672A1
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- 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
- A61K8/55—Phosphorus compounds
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- 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
- A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
- A61K8/463—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfuric acid derivatives, e.g. sodium lauryl sulfate
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- 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
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
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- 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
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
- A61K8/442—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof substituted by amido group(s)
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- 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
- A61K8/55—Phosphorus compounds
- A61K8/553—Phospholipids, e.g. lecithin
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- 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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/731—Cellulose; Quaternized cellulose derivatives
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- 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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/86—Polyethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/02—Preparations for cleaning the hair
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- 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
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/54—Polymers characterized by specific structures/properties
- A61K2800/542—Polymers characterized by specific structures/properties characterized by the charge
- A61K2800/5426—Polymers characterized by specific structures/properties characterized by the charge cationic
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- 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
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/59—Mixtures
- A61K2800/596—Mixtures of surface active compounds
Definitions
- the present invention relates to compositions and delivery systems based on a combination of organic phospholipids capable of forming bilayers in aqueous solution; amphoteric surfactants; nonionic surfactants; and cationic polymers, wherein the combination of these ingredients allows water-insoluble ingredients to be incorporated into aqueous solutions.
- the deposition of the water-insoluble ingredients on the keratinous substances can be controlled by varying the amounts of certain of the above components.
- Organic phospholipids play an important role in the cosmetics and pharmaceutical industries because of their outstanding physiological properties, such as, for example, emulsifying, softening, and anti-oxidant effects.
- organic phospholipids When hydrolyzed, organic phospholipids yield phosphoric acid, an alcohol, a fatty acid, and a nitrogenous base.
- Most phospholipids are amphipathic, i.e., have polar “heads” and non-polar “tails.”
- most phospholipids tend to arrange spontaneously into a bilayer when suspended in an aqueous environment, with the polar heads contacting the water and the non-polar tails contacting each other.
- Most naturally occurring phospholipids prefer to form vesicular bilayers in water solutions. In such a bilayer vesicle, no non-polar part of the phospholipid has any contact with the water solution.
- phospholipids typically are water-insoluble and incompatible with many water soluble anionic compounds, such as anionic surfactants. While they can be solubilized in water at low levels by a range of surfactants, this is often not easily accomplished.
- solubilization has been accomplished conventionally using specific solubilizing agents in aqueous alcoholic solutions.
- U.S. Pat. No. 4,874,553 to Hager et al. discusses methods of rendering phospholipid mixtures water-soluble or water-dispersible by using certain amine compounds as solubilizing agents.
- U.S. Pat. No. 4,174,296 to Kass describes a method of improving the solubility of phospholipid compounds in water, in particular lecithin compounds, by mixing lecithin with specific single solubilizing agents, including amphoteric and anionic surfactants. These methods require alcohol for cosolubilization. Alcohol solutions have the drawback of disrupting any bilayer formation by altering the solution such that the alcohol functions as a secondary solvent.
- Lecithins and other phospholipids have been used in the pharmaceutical industry to formulate carriers for water-insoluble drugs.
- water-insoluble material is encapsulated by vesicles composed of phospholipids such as lecithin.
- I. Ribosa et al. in “Physico-chemical modifications of liposome structures through interaction with surfactants,” Int'l Journal of Cosmetic Science 14:131-149 (1992), also discuss solubilization of phospholipids via the interaction of liposomes with surfactants. Lau and Ribosa, however, investigated only dilute solutions of pure liposomes.
- organic phospholipids such as lecithin
- these phospholipids are toxicologically safe. It would thus be desirable for cosmetic and pharmaceutical applications to provide delivery systems that include such organic phospholipids as a carrier for other lipophilic ingredients, without the need for alcohols and other similar solvents.
- Gerstein presents some problems, however. Many hair care and hair setting products are formulated at acidic pH because of a desire for such products to be compatible with the pH of the scalp and hair surface. Gerstein does not disclose a pH at which its system is formulated, but if the Gerstein system is acidified, the polymer will precipitate out of solution. In addition, the Gerstein system does not carry and there is no suggestion that it could carry any additional lipophilic ingredients in its mixture of anionic surfactant, amphoteric surfactant, and styling polymer. Further, Gerstein does not describe the incorporation of its styling polymer into any products other than the disclosed styling shampoo, nor does Gerstein suggest that such incorporation would be possible.
- the present invention is drawn to a composition made up of at least one organic phospholipid capable of forming bilayers in aqueous solution, at least one amphoteric surfactant, at least one nonionic surfactant, and at least one cationic polymer.
- the amphoteric and nonionic surfactants are each present in an amount by weight equal to or greater than the amount of the organic phospholipid.
- the present invention relates to an aqueous delivery system for water-insoluble materials.
- water-insoluble means one which is insoluble in water but which can be solubilized in accordance with the present invention.
- the delivery (or “carrier”) system includes at least one organic phospholipid capable of forming bilayers in aqueous solution, at least one amphoteric surfactant, at least one nonionic surfactant, at least one cationic polymer, at least one water-insoluble ingredient, and an aqueous phase.
- the amphoteric and nonionic surfactants are each present in an amount by weight equal to or greater than the amount of the organic phospholipid.
- the organic phospholipid, the amphoteric surfactant, and the nonionic surfactant are present in a combined amount sufficient to allow the lipophilic ingredient to be incorporated into the delivery system.
- the present invention is also drawn to a method for treating at least one keratinous substance by preparing an aqueous solution comprising at least one organic phospholipid capable of forming bilayers in aqueous solution; at least one amphoteric surfactant present in an amount by weight equal to or greater than the amount of said at least one phospholipid; at least one nonionic surfactant present in an amount by weight equal to or greater than the amount of said at least one phospholipid; at least one cationic polymer; and at least one water-insoluble ingredient.
- the phospholipid and the two surfactants are present in a combined amount sufficient to allow the water-insoluble ingredient to be incorporated into said aqueous solution.
- the aqueous solution is then applied to the keratinous substance.
- the present invention relates to methods for controlling the deposition of a water-insoluble ingredient on at least one keratinous substance, by preparing an aqueous solution comprising at least one organic phospholipid capable of forming bilayers in aqueous solution; at least one amphoteric surfactant present in an amount by weight equal to or greater than the amount of said at least one phospholipid; at least one nonionic surfactant present in an amount by weight equal to or greater than the amount of said at least one phospholipid; and at least one water-insoluble ingredient.
- the phospholipid and the two surfactants are present in a combined amount sufficient to allow the water-insoluble ingredient to be incorporated into said aqueous solution.
- the amount of the organic phospholipid, the amount of the nonionic surfactant, or both are adjusted in order to control the amount of deposition of the water-insoluble ingredient on the keratinous substance.
- Cationic polymer(s) are optionally included in the aqueous solution, which is then applied to the keratinous substance.
- the present invention allows otherwise water-insoluble materials or ingredients to be solubilized in an aqueous solution. No alcohol is required for cosolubilization, and there is no need for liposome preparation. Further, when the water evaporates, the residue left behind includes the water-insoluble material and/or the phospholipid. Further, the invention allows for control in the amount of material to be deposited.
- composition of the invention is also easy to formulate and can be gentle on the hair, skin, or eyelashes when the surfactants used are mild. Unlike the attempted solubilization of phospholipids in the prior art, the present invention requires the presence of at least one amphoteric surfactant and at least one nonionic surfactant in the concentrated solutions of phospholipid.
- compositions and delivery systems of the present invention can readily deposit the organic phospholipid/water-insoluble substances on the hair, skin, and eyelashes, and, because of their inherent insolubility, can resist being washed off with water. Further, by the presence of the cationic polymer, and/or by adjusting the amount of the organic phospholipid, the nonionic surfactant, or both, the amount of water-insoluble ingredients deposited can be controlled. Accordingly, these compositions and delivery systems can be used in hair shampoos, conditioners, hair dyeing compositions, including oxidative dyes and bleaches, permanent waving compositions, curl relaxing compositions, hair setting compositions, bath and body products, sunscreens, or cosmetics such as mascaras and foundations.
- Load is defined as the weight of added hydrophobe (water-insoluble material) divided by the weight of the phospholipid expressed as a percentage.
- 1 g of hydrophobe in a composition with 5 g phospholipid is a 1 ⁇ 5 or 20% load.
- 50% is considered a high load and can be achieved with certain hydrophobes and surfactant combinations.
- an organized structure is formed between the organic phospholipid and the nonionic surfactant and is solubilized by the amphoteric surfactant.
- the organized structure can incorporate other water-insoluble materials or hydrophobes.
- the structure remains organized, as evidenced by the clarity of the solution, exhibiting a slight Tyndall light scattering effect, and, when concentrated, showing lamellar anisotropic structures under polarized light.
- the invention is drawn to a composition
- a composition comprising at least one organic phospholipid capable of forming bilayers in aqueous solution, at least one amphoteric surfactant, at least one nonionic surfactant, and at least one cationic polymer, where the amphoteric and nonionic surfactants are each present in an amount by weight equal to or greater than the amount of the phospholipid.
- the preferred organic phospholipids capable of forming bilayers in aqueous solution are lecithins.
- Lecithins are mixtures of phospholipids, i.e., of diglycerides of fatty acids linked to an ester of phosphoric acid.
- lecithins are diglycerides of stearic, palmitic, and oleic acids linked to the choline ester of phosphoric acid.
- Lecithin is usually defined either as pure phosphatidyl cholines or as crude mixtures of phospholipids which include phosphatidyl choline, phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl inositol, other phospholipids, and a variety of other compounds such as fatty acids, triglycerides, sterols, carbohydrates, and glycolipids.
- the lecithin used in the present invention may be present in the form of a liquid, powder, or granules.
- Lecithins useful in the invention include, but are not limited to, soy lecithin and hydroxylated lecithin.
- ALCOLEC S is a fluid soy lecithin
- ALCOLEC F 100 is a powder soy lecithin
- ALCOLEC Z3 is a hydroxylated lecithin, all of which are available from the American Lecithin Company.
- lecithin is preferably used in an amount greater than 0 to about 3% by weight relative to the total weight of the composition, preferably from about 0.05% to about 1% by weight. Since lecithin itself is not a pure raw material and may have free glycerides, glycerin, fatty acids, and soaps, adjustments in this ratio may need to be made, i.e., one source of lecithin may require different ratios of nonionic and amphoteric surfactants than another to achieve maximum clarity of solution.
- the composition of the invention forms a clear solution, though the purpose of the invention is achieved just as effectively with a slightly cloudy solution.
- the following multifunctional biomimetic phospholipids manufactured by Mona Industries may be useful: PHOSPHOLIPID PTC, PHOSPHOLIPID CDM, PHOSPHOLIPID SV, PHOSPHOLIPID GLA, and PHOSPHOLIPID EFA.
- amphoteric surfactants useful in the present invention include, but are not limited to, betaines, sultaines, hydroxysultaines, alkyl amphodiacetates, alkyl amphodipropionates, and imidazolines, or salts thereof. It is recognized that other fatty acid condensates such as those formed with amino acids, proteins, and the like are suitable.
- Cocamphodipropionate is particularly preferred, for example, MIRANOL C2M-SF Conc. (disodium cocamphodipropionate), in its salt-free form, available from Rhône-Poulenc. Also preferred is CROSULTAINE C-50 (cocamidopropyl hydroxysultaine), available from Croda.
- the amphoteric surfactants are preferably present in the composition in an amount ranging from greater than 0 to about 9% by weight relative to the total weight of the composition. Preferably, the amphoteric surfactants are present in an amount ranging from about 0.15% to about 3% by weight.
- the amphoteric surfactants are preferably present in the composition in the same range.
- Other amphoteric surfactants useful in the present invention include disodium wheatgermimido PEG-2 sulfosuccinate, available under the trade name MACKANATE WGD from Mcintyre Group Ltd. and disodium soyamphodiacetate, available under the trade name MACKAM 2S from Mcintyre Group Ltd.
- the nonionic surfactants useful in the present invention are preferably formed from a fatty alcohol, a fatty acid, or a glyceride with a C 8 to C 24 carbon chain, preferably a C 12 to C 18 carbon chain, more preferably a C 16 to C 18 carbon chain, derivatized to yield a Hydrophilic-Lipophilic Balance (HLB) of at least 10.
- HLB Hydrophilic-Lipophilic Balance
- Such derivatives can be polymers such as ethoxylates, propoxylates, polyglucosides, polyglycerins, polylactates, polyglycolates, polysorbates, and others that would be apparent to one of ordinary skill in the art.
- Such derivatives may also be mixed polymers of the above, such as ethoxylate/propoxylate species, where the total HLB is preferably greater than or equal to 10.
- the nonionic surfactants contain ethoxylate in a molar content of from 10-25, more preferably from 10-20 moles.
- the nonionic surfactant is preferably present in an amount of greater than 0 to about 20% by weight relative to the weight of the whole composition. More preferably, the nonionic surfactant is present in an amount of about 0.2% to about 5% by weight.
- Cationic polymers useful in the present invention include, but are not limited to, polyquaternium 4, polyquaternium 6, polyquaternium 7, polyquaternium 10, polyquaternium 11, polyquaternium 16, polyquaternium 22, polyquaternium 28, polyquaternium 32, and guar hydroxypropyltrimonium chloride.
- Preferred cationic polymers include POLYMER JR-125 and POLYMER JR-400, hydroxyethyl cellulosic polymers (polyquaternium 10) available from AMERCHOL; JAGUAR C13-S, guar hydroxypropyltrimonium chloride, available from Meyhall; and MERQUAT 100, a dimethyl dialkyl ammonium chloride (polyquaternium 6) available from CALGON.
- the cationic polymer is preferably present in an amount of about 0.1% to about 5.0% relative to the total weight of the inventive composition.
- the organic phospholipid capable of forming bilayers in aqueous solution, the amphoteric surfactant, and the nonionic surfactant are present in the composition such that the nonionic surfactant and the amphoteric surfactant are each present in an amount by weight greater than the amount of phospholipid.
- the amount of phospholipid in the composition is kept fixed while the amounts of the amphoteric and nonionic surfactants are increased.
- the phospholipid, amphoteric surfactant, and nonionic surfactant are present in a combined amount sufficient to allow at least one water-insoluble ingredient to be incorporated into an aqueous solution.
- the phospholipid, amphoteric surfactant and nonionic surfactant are preferably present in the composition in a ratio ranging from about 1:2:2 and above by weight relative to the whole composition, i.e., where the amounts of the surfactants can be increased independently of each other but the amount of phospholipid stays fixed.
- the ratio is considered to be “above” 1:2:2 when the amount of either of the surfactants increases.
- the inventive composition when used in a delivery system for a lipophilic material, the composition also includes water, and the ratio preferably ranges from about 1:3:2 and above.
- the ratio is preferably about 1:3:3 and above, and more preferably above about 1:3:4.
- the loading capability for hydrophobes carried by the delivery system of the present invention can be increased if the ratio of nonionic surfactant to phospholipid is minimized, with the bilayers still being solubilized, because an excess of nonionic surfactant may disrupt the organized structure.
- the composition of the present invention comprises ALCOLEC S (soy lecithin), MIRANOL C2M-SF Conc. (disodium cocamphodipropionate, an amphoteric surfactant), ARLASOLVE 200 (IsoCeteth-20, a nonionic surfactant) in a ratio of 5:15:10 (1:3:2) when a lipophilic water-insoluble ingredient is employed, and 5:15:20 (1:3:4) when a water-insoluble polymer, resin, or latex is employed, wherein the ratios are calculated by weight relative to the whole composition.
- ALCOLEC S synthetic lecithin
- MIRANOL C2M-SF Conc. sodium cocamphodipropionate, an amphoteric surfactant
- ARLASOLVE 200 IsoCeteth-20, a nonionic surfactant
- compositions of the invention contain, in addition to the cationic polymer, a lecithin (L), an amphoteric surfactant (A), and a nonionic surfactant (N), referred to as the “LAN.”
- lecithin is particularly preferred, the types of amphoteric and nonionic surfactants may vary.
- the LAN When used as an ingredient in further formulations, the LAN is compatible and generally gives clear solutions with anionic surfactants such as alkyl sulfates and ethoxylated alkyl sulfates. Other anionic surfactants such as sulfosuccinates may also be used.
- anionic surfactants such as alkyl sulfates and ethoxylated alkyl sulfates.
- Other anionic surfactants such as sulfosuccinates may also be used.
- LAN compositions can resist storage at 45° C. for three months or more, which would predict that they have a shelf life at room temperature of at least three years.
- the present invention relates to an aqueous delivery or carrier system comprising at least one organic phospholipid capable of forming bilayers in aqueous solution, at least one amphoteric surfactant present in an amount greater than or equal to the amount of the phospholipid, at least one nonionic surfactant preferably present in an amount greater than or equal to the amount of the phospholipid, at least one cationic polymer, at least one water-insoluble ingredient, and an aqueous phase.
- the phospholipid, amphoteric surfactant, and nonionic surfactant are present in a combined amount sufficient to allow the water-insoluble ingredient(s) to be incorporated into or solubilized by the aqueous system.
- the amount sufficient for solubilization may vary depending on the type of composition; for example, shampoo and mascara formulations require a lower concentration of LAN than do conditioner, deep treatment, bleach, permanent wave, dye, and relaxant compositions.
- the cationic polymer acts to increase the deposition of both the LAN and its carried ingredient on their ultimate destination, preferably the hair, eyelashes, or skin.
- Water-insoluble materials or ingredients useful in the compositions or delivery systems of the present invention include, but are not limited to the following:
- Lipophilic “ingredients” or “materials” such as silicones, oil-soluble vitamins such as Vitamin E and Vitamin A, sunscreens, ceramides and natural oils:
- the lipophilic ingredients may be in the form of sunscreens, bacteriostats, moisturizers, colors, topical pharmaceuticals and the like.
- Preferred lipophilic ingredients include: Vitamin E, Vitamin E Acetate, Vitamin A Palmitate, olive oil, mineral oil, 2-oleamido-1,3-octadecanediol, octylmethoxy cinnamate, octyl salicylate, and silicones such as dimethicone, cyclomethicone, phenyl trimethicone, dimethiconol, dimethicone copolyol, and laurylmethicone copolyol.
- the lipophilic ingredients will, for example, moisturize or condition the skin, hair, and/or eyelashes and leave behind no oily feel.
- Water-insoluble polymers, resins, and latexes which are unneutralized or partially neutralized wherein the polymers and resins include but are not limited to those containing carboxyl moieties, such as acrylates and other carboxy polymers.
- carboxyl moieties such as acrylates and other carboxy polymers.
- water-insoluble polymers and resins have to be neutralized to about 90% of their carboxyl moieties to make them water soluble for the purpose of formulating products in aqueous solution and for the purpose of making products which have good non-build-up properties, i.e., can be easily washed off the hair after use.
- little or no neutralization is needed to dissolve these polymers/resins.
- an unneutralized or partially neutralized water-insoluble polymer or resin is solubilized because it is neutralized by the amphoteric surfactant contained in the presently claimed delivery system, but the amphoteric surfactant acting alone will not solubilize the polymer or resin in water and allow the pH to be acidic.
- the polymer or resin is neutralized by the amphoteric surfactant alone, when one attempts to acidify the solution to prepare a hair care composition with acidic pH, as is desirable, the carboxyl moieties of the polymer or resin become unneutralized and precipitation occurs. It is the combination of the organic phospholipid, the amphoteric surfactant, and the nonionic surfactant of the present invention which achieves the solubility of the water-insoluble polymers or resins.
- latexes As for latexes, they generally have been used in cosmetics in an unneutralized form since they are used for their milky (insoluble) appearance. In the context of the present invention, however, water-insoluble latexes are neutralized to an alkaline pH and dissolve, producing a clear solution. To the best of the inventors' knowledge, neutralized latexes have not previously been used in cosmetic compositions.
- non-neutralized or partially-neutralized polymers or resins where such substances are applied to the hair or skin from an alcoholic or aqueous/alcoholic system, their washability from the hair leaves a great deal to be desired.
- the polymers or resins can easily be rinsed off from the hair (no build-up) while providing strong hold for curls, if curls are what is desired.
- AMPHOMER LV-71 from National Starch (octylacrylamide/acrylates/butylaminoethyl methacrylate copolymer),
- OMNIREZ-2000 from ISP PVM/MA half ethyl ester copolymer
- LUVIMER 100P from BASF (t-butyl acrylate/ethyl acrylate/methacrylic acid), and
- LUVIMER 36D from BASF (ethyl acrylate/t-butyl acrylate/methacrylic acid), and
- ACUDYNE 258 from Rohm & Haas (acrylic acid/methacrylic acid/acrylates/methacrylates/hydroxy ester acrylates).
- the aqueous phase of the inventive delivery system can contain additional ingredients such as anionic surfactants, organic salts, inorganic salts, proteins, hair dyes, water-soluble polymers, quaternary ammonium compounds, complex and simple carbohydrates, amino acids, preservatives and fragrances.
- additional ingredients such as anionic surfactants, organic salts, inorganic salts, proteins, hair dyes, water-soluble polymers, quaternary ammonium compounds, complex and simple carbohydrates, amino acids, preservatives and fragrances.
- the composition preferably has a pH ranging from 4-12 for maximum stability and clarity. The more concentrated the solution, the better the delivery.
- this blend is diluted with water or the blend is used as an ingredient in another composition, then the pH has a broader range, i.e., preferably ranges from 2-12, and a wider variety of additives can be included in the solution.
- water When water is added to a concentrated LAN, it may appear to form a cloudy solution at first if a large amount of water is added at once. The LAN will eventually go into solution, however, and become clear or at least clearer. The time to clear decreases as the LAN ratio increases. Once the organized structure of the LAN forms, the addition of more water does not affect clarity.
- the blends can be freeze-dried to hygroscopic solids that redissolve into water. Encapsulation of such solids so that they do not pick up and retain excess moisture is also contemplated. Such encapsulated solids can have desirable storage properties and would be easy to dissolve into water at various dilutions. Understandably, the need for dilution varies depending on the water-insouble material to be employed.
- the present invention relates to a method for treating at least one keratinous substance by preparing an aqueous solution comprising at least one organic phospholipid capable of forming bilayers in aqueous solution; at least one amphoteric surfactant present in an amount by weight equal to or greater than the amount of said at least one phospholipid; at least one nonionic surfactant present in an amount by weight equal to or greater than the amount of said at least one phospholipid; at least one cationic polymer; and at least one water-insoluble ingredient, wherein the phospholipid, amphoteric surfactant, and nonionic surfactant are present in a combined amount sufficient to allow the water-insoluble ingredient to be incorporated into the aqueous solution; and applying the aqueous solution to the keratinous substance.
- the keratinous substance is preferably hair, skin, or eyelashes.
- the type of treatment envisioned by the claimed method may include shampooing, conditioning, dyeing, bleaching, permanent waving, relaxing, setting, moisturizing, and making-up the hair, skin, or eyelashes.
- Another embodiment of the present invention is drawn to a process for preparing the aqueous system of the present invention.
- This process comprises: (a) combining the at least one organic phospholipid, amphoteric surfactant, and nonionic surfactant as described above to obtain a mixture, (b) heating the mixture obtained in step (a), and (c) adding an aqueous solution to the heated mixture to obtain the desired carrier system.
- Water-insoluble ingredients may be added in step (a).
- the cationic polymer may be added in Step (c) in the aqueous solution.
- the carrier system obtained can carry a high load (i.e., 50% is considered a high load) of the organic phospholipid/water-insoluble ingredient.
- the mixture is preferably heated at a temperature of 65° C. to 85° C., depending on the melting points of the solid surfactants.
- the preparation of the carrier system of the present invention may be carried out as follows.
- Lecithin (L) is dispersed in water.
- the water-insoluble material is combined with nonionic surfactant(s) (N) at appropriate ratios and added to the lecithin/water dispersion.
- An amphoteric surfactant (A) is added and the mixture is heated, preferably to a temperature of from 75° C. to 85° C.
- the combination of these ingredients results in a solution which is clear to slightly hazy and is referred to as the “LAN,” which can then be used as a “raw material” to make finished products.
- the cationic polymer is added in aqueous solution during the formulation of finished products.
- lecithin, amphoteric surfactant(s) and nonionic surfactant(s) can be weighed to appropriate ratios and heated to 70° C. with stirring. A sWater is then added at the same temperature.
- Another alternative method of preparation comprises adding the water-insoluble ingredient with mixing after solutions have cooled. This last alternative method helps protect heat-sensitive water-insoluble ingredients.
- compositions may vary from clear to slightly hazy and are infinitely dilutable with water.
- the slight haze can be overcome by adjusting the ratio of lecithin to the surfactants, adjusting pH, or reducing concentrations of water-insoluble ingredients.
- the present invention relates to methods for controlling the deposition of a water-insoluble ingredient on at least one keratinous substance by preparing an aqueous solution comprising at least one organic phospholipid capable of forming bilayers in aqueous solution; at least one amphoteric surfactant present in an amount by weight equal to or greater than the amount of said at least one phospholipid; at least one nonionic surfactant present in an amount by weight equal to or greater than the amount of said at least one phospholipid; and at least one water-insoluble ingredient.
- the phospholipid and the two surfactants are present in a combined amount sufficient to allow the water-insoluble ingredient(s) to be incorporated into said aqueous solution.
- the amount of the organic phospholipid, the amount of the nonionic surfactant, or both are adjusted in order to control the amount of deposition of the water-insoluble ingredient on the keratinous substance.
- Cationic polymer(s) are optionally included in the aqueous solution, which is then applied to the keratinous substance. While, as discussed supra, addition of cationic polymer(s) into this system increases the deposition of the water-insoluble ingredient(s), the deposition can also be effectively controlled by varying the quantities of L, N, or both in the LAN system, with or without the cationic polymer.
- the amount of the nonionic surfactant component in the LAN/water-insoluble ingredient system By varying the amount of the nonionic surfactant component in the LAN/water-insoluble ingredient system, the amount of the water-insoluble ingredient deposited on hair can be controlled. Since, as discussed above, the nonionic surfactant is necessary to incorporate the water-insoluble ingredient(s) into the LAN system, a high quantity of nonionic surfactant in a LAN solution results in the water-insoluble ingredient(s) having a higher tendency to stay in the LAN solution. In other words, the less nonionic surfactant present in the LAN solution, the easier it is for the water-insoluble ingredient(s) to come out of solution and thus be deposited on, e.g., hair. Therefore, the amount of the LAN/water-insoluble ingredient(s) deposited on hair, skin, or eyelashes can be controlled by the quantity of the nonionic surfactant in the LAN system.
- the amount of the organic phospholipid, which is preferably lecithin, in the LAN system By adjusting the amount of the organic phospholipid, which is preferably lecithin, in the LAN system, the deposition of water-insoluble ingredients on various hair types can be controlled. Since lecithin is lipophilic, it is more attracted to the hydrophobic surface of normal hair (i.e., hair with less damage) than it is to the hydrohilic surface of bleached hair (considered to be “damaged” hair). In other words, higher amounts of lecithin favor the deposition of lipophiles on normal hair and lower lecithin amounts favor deposition on damaged hair.
- the organic phospholipid which is preferably lecithin
- composition and delivery system of the present invention can be used as an ingredient itself in, for example, shampoos, conditioners (rinse-off and leave-in), deep treatments for hair, body washes, bath gels, hair dyeing compositions, permanent wave formulations, relaxers, make-up preparations, particularly mascara and foundation, and skin creams or lotions.
- shampoos conditioners (rinse-off and leave-in)
- deep treatments for hair body washes
- bath gels hair dyeing compositions
- permanent wave formulations permanent wave formulations
- relaxers make-up preparations
- make-up preparations particularly mascara and foundation
- skin creams or lotions particularly mascara and foundation
- skin creams or lotions particularly mascara and foundation
- skin creams or lotions particularly mascara and foundation
- the inventive compositions or delivery systems are used as shampoos
- at least one anionic surfactant may also be included in the shampoo formulation, as it is a typical shampoo ingredient.
- the system of the present invention can be used to formulate hair products, e.g., for normal hair, color-treated hair, dry hair, fine hair, and damaged hair.
- the LAN can be used to create a regimen comprising shampoo, conditioner, and deep treatment, (i.e., deep conditioner). Additional nonionic, amphoteric, and also anionic surfactants can be added to the LAN.
- the concentration of the LAN is increased within each regimen from shampoo to conditioner to deep treatment.
- the deep treatment formulations have the most concentrated hydrophobe-carrying LAN.
- the LAN systems of the invention can be further associated, in the hair products described above, with proteins including hydrolyzed soy protein, lauryidimonium hydrolyzed soy protein (cationic Soya protein) and wheat amino acids.
- the proteins could also include corn, wheat, milk, or silk proteins, collagens, keratins, or others.
- taurine and arginine hydrochloride may be associated therein to maximize protein binding to the hair.
- Cationic proteins or proteins in general may be stabilizers for the LAN and, like the cationic polymers discussed above, enhance its delivery by changing the charge on the surface of the LAN structure.
- the skin and the hair attract cationic ingredients, and proteins are generally substantive to these tissues.
- nonionic emulsifiers such as glyceryl stearate and PEG-100 stearate can be used, and the LAN may be treated as a water-insoluble, particularly a lipophilic, ingredient itself.
- ingredients in the LAN hair care compositions may include isoparaffins, sodium chloride, propylene glycol, preservatives such as phenoxyethanol, methylparaben, ethylparaben, and propylparaben, pH adjusters such as phosphoric acid, humectants such as trehalose, and emollients such as octyldodecanol.
- preservatives such as phenoxyethanol, methylparaben, ethylparaben, and propylparaben
- pH adjusters such as phosphoric acid
- humectants such as trehalose
- emollients such as octyldodecanol.
- shampoos, conditioners, and deep treatments within the scope of the present invention may be used on hair which has been treated, e.g., with color (dye or bleach) or chemicals (permanent wave or straightening), or which is dry or fine and show significant substantivity for the hair.
- color die or bleach
- chemicals permanent wave or straightening
- Cationic species are known to form a complex with anionic surfactants wherein the resulting solids precipitate out of the solution upon addition of water.
- a LAN composition was incorporated in a cationic polymer-anionic surfactant system (e.g., an anionic shampoo containing cationic conditioning agents), it also precipitated along with the cationic-anionic complex.
- a clear shampoo containing LAN, a cationic polymer (POLYMER JR 125), and an anionic surfactant (SLES) was prepared and was found to give a precipitate upon dilution with water.
- the precipitate was obtained by centrifugation; the amount of the solid was determined gravimetrically and its phosphorus content (evidence of lecithin) was analyzed by atomic absorption.
- a second shampoo was prepared which contained the same ingredients but no LAN. Analysis of the two shampoos showed that when LAN was present, more precipitate with a higher phosphorus content was obtained, an indication that the precipitate contains a high amount of LAN. See results in Table 1 below.
- Example 1 it was shown that LAN precipitated in an anionic system containing cationic polymers. In a similar system additionally containing a water-insoluble ingredient, the presence of the cationic polymers increased the deposition of LAN and its carried ingredients on hair.
- Example 1 was repeated with LAN (1:3:4) containing 0.5% silicone (Dow Corning 200) as the water-insoluble ingredient.
- Shampoo 1 was a control that contained the cationic polymer (MERQUAT 100) but no LAN/OMC.
- Shampoo 2 contained the cationic polymer and the LAN/OMC.
- Shampoo 3 contained only the LAN/OMC and not the cationic polymer. Hair was treated with the above shampoos for 3 minutes, then rinsed for 30 seconds. The hair was shampooed and rinsed an additional 4 times (total shampoo: 5 times). The hair was extracted with alcohol and the extracted OMC determined by UV-Vis. The amount of OMC found on the tested hair, after adjusting from the control, was found to be 3 times higher when the cationic polymer was present. See Table 4 below: TABLE 4 TREATMENT ⁇ g OMC/g Hair Shampoo 2: containing LAN/OMC and MERQUAT 100 29.40 Shampoo 3: containing LAN/OMC and no MERQUAT 9.27 100
- the acqueous systems further contained LAN/OMC as defined in Example 3 and the cationic polymer (POLYMER JR 400).
- Solution 1 contained the cationic polymer and the LAN/OMC complex as defined in Example 3.
- Solution 2 contained the LAN/OMC only.
- Solution 3 contained LAN only.
- the composition of each solution is shown below in Table 5.
- TABLE 5 SOLUTION 1 SOLUTION 2 SOLUTION 3 POLYMER JR-400 0.5 — — LAN/OMC 10 10 — LAN — — 10 Water 89.5 90 90
- Solution 3 containing LAN without the sunscreen or the cationic polymer, acted as a control.
- N controls deposition more efficiently than L.
- High Deposition -------------------------------------------------------------------------------------> Low Deposition Virgin Hair High L-Low N Low L-Low N High L-High N Low L-High N Damaged Hair Low L-Low N High L-Low N Low L-High N High L-High N
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Priority Applications (16)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/205,692 US20010009672A1 (en) | 1998-12-04 | 1998-12-04 | Compositions and methods for controlling deposition of water-insoluble |
CN99814052A CN1391459A (zh) | 1998-12-04 | 1999-12-03 | 控制水不溶性组分沉积的组合物和方法 |
CZ20011850A CZ20011850A3 (cs) | 1998-12-04 | 1999-12-03 | Prostředky a způsoby pro řízení depozice sloľek nerozpustných ve vodě |
AU31076/00A AU3107600A (en) | 1998-12-04 | 1999-12-03 | Compositions and methods for controlling deposition of water-insoluble ingredients |
HU0200555A HUP0200555A3 (en) | 1998-12-04 | 1999-12-03 | Hair care composition and method for controlling deposition of water-insoluble ingredients |
PL99348023A PL348023A1 (en) | 1998-12-04 | 1999-12-03 | Compositions and methods for controlling deposition of water-insoluble ingredients |
CA002352460A CA2352460A1 (en) | 1998-12-04 | 1999-12-03 | Compositions and methods for controlling deposition of water-insoluble ingredients |
EP99965089A EP1135096A1 (en) | 1998-12-04 | 1999-12-03 | Compositions and methods for controlling deposition of water-insoluble ingredients |
SK696-2001A SK6962001A3 (en) | 1998-12-04 | 1999-12-03 | Compositions and methods for controlling deposition of water-insoluble ingredients |
KR1020017006926A KR20010081061A (ko) | 1998-12-04 | 1999-12-03 | 수불용성 성분의 침착을 조절하기 위한 조성물 및 방법 |
JP2000586292A JP2002531478A (ja) | 1998-12-04 | 1999-12-03 | 水不溶性成分の沈着を調整する組成物および方法 |
PCT/US1999/028546 WO2000033798A1 (en) | 1998-12-04 | 1999-12-03 | Compositions and methods for controlling deposition of water-insoluble ingredients |
BR9915872-8A BR9915872A (pt) | 1998-12-04 | 1999-12-03 | Composições e processos para o controle de deposição de ingredientes insolúveis em água |
ARP990106190A AR021549A1 (es) | 1998-12-04 | 1999-12-06 | Composiciones y metodos para controlar la deposicion de ingredientes insolubles en agua |
NO20012638A NO20012638L (no) | 1998-12-04 | 2001-05-29 | Blandinger og fremgangsmåter for å kontrollere avsetning av vann-ulöselige ingredienser |
US09/934,488 US6524614B2 (en) | 1998-12-04 | 2001-08-23 | Compositions and methods for controlling deposition of water-insoluble ingredients |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US09/205,692 US20010009672A1 (en) | 1998-12-04 | 1998-12-04 | Compositions and methods for controlling deposition of water-insoluble |
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US09/934,488 Continuation US6524614B2 (en) | 1998-12-04 | 2001-08-23 | Compositions and methods for controlling deposition of water-insoluble ingredients |
US09/934,488 Continuation-In-Part US6524614B2 (en) | 1998-12-04 | 2001-08-23 | Compositions and methods for controlling deposition of water-insoluble ingredients |
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US09/934,488 Expired - Lifetime US6524614B2 (en) | 1998-12-04 | 2001-08-23 | Compositions and methods for controlling deposition of water-insoluble ingredients |
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US09/934,488 Expired - Lifetime US6524614B2 (en) | 1998-12-04 | 2001-08-23 | Compositions and methods for controlling deposition of water-insoluble ingredients |
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US (2) | US20010009672A1 (es) |
EP (1) | EP1135096A1 (es) |
JP (1) | JP2002531478A (es) |
KR (1) | KR20010081061A (es) |
CN (1) | CN1391459A (es) |
AR (1) | AR021549A1 (es) |
AU (1) | AU3107600A (es) |
BR (1) | BR9915872A (es) |
CA (1) | CA2352460A1 (es) |
CZ (1) | CZ20011850A3 (es) |
HU (1) | HUP0200555A3 (es) |
NO (1) | NO20012638L (es) |
PL (1) | PL348023A1 (es) |
SK (1) | SK6962001A3 (es) |
WO (1) | WO2000033798A1 (es) |
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US20040013617A1 (en) * | 2002-07-19 | 2004-01-22 | Donald Rick | Sunless tanning composition |
US20040120919A1 (en) * | 2002-12-20 | 2004-06-24 | L'oreal | Hair compositions |
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US7622104B2 (en) * | 2001-08-20 | 2009-11-24 | L'oreal S.A. | Methods for relaxing and re-waving hair comprising at least one reducing agent and at least one hydroxide compound |
IL162227A0 (en) | 2001-12-21 | 2005-11-20 | Rhodia | Stable surfactant compositions for suspending components |
US7087559B2 (en) | 2002-12-16 | 2006-08-08 | Avon Products, Inc. | Non-foaming cleaning and conditioning hair care compositions |
US20040173719A1 (en) * | 2003-03-05 | 2004-09-09 | Mitchell Jed D. | Magnetized beverage container holder |
WO2004082611A2 (en) * | 2003-03-14 | 2004-09-30 | L'oreal | Poss and eposs containing cosmetics and personal care products |
CA2533294A1 (en) * | 2003-07-22 | 2005-02-03 | Rhodia, Inc. | New branched sulfates for use in personal care formulations |
US20050125913A1 (en) * | 2003-12-11 | 2005-06-16 | Saroja Narasimhan | Method and compositions for coloring hair |
EP1747260A4 (en) * | 2004-04-15 | 2008-07-30 | Rhodia | Structured surfactant compositions |
BRPI0514461A (pt) * | 2004-08-17 | 2008-06-10 | Rhodia | composições de tensoativo estruturadas com ph baixo |
JP2008512498A (ja) * | 2004-09-13 | 2008-04-24 | ロレアル | 改善された付着性及び/又は柔軟性を有するposs含有化粧品用組成物と改善された化粧品用組成物の製造方法 |
DE102004048752A1 (de) * | 2004-10-05 | 2006-04-06 | Cognis Ip Management Gmbh | Flüssige Tensidmischungen |
US20060280710A1 (en) * | 2005-06-08 | 2006-12-14 | L'oreal | Volumizing hair compositions |
US8128916B2 (en) * | 2005-06-16 | 2012-03-06 | L'oréal | Aqueous fatty quaternary amine-containing carrier systems for water-insoluble materials |
US8128917B2 (en) | 2005-06-16 | 2012-03-06 | L'oréal | Aqueous polyamine-containing carrier systems for water-insoluble materials |
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US20060292100A1 (en) * | 2005-06-16 | 2006-12-28 | L'oreal | Aqueous phospholipid-containing carrier systems for water-insoluble materials |
US20070224153A1 (en) * | 2006-03-16 | 2007-09-27 | Librizzi Joseph J | High-deposition compositions and uses thereof |
US7696140B2 (en) * | 2006-10-04 | 2010-04-13 | L'oreal S.A. | Composition containing a phospholipid and quaternary ammonium polymer |
US20080124296A1 (en) * | 2006-11-22 | 2008-05-29 | L'oreal S.A. | Compositions containing microspheres |
CA2681998A1 (en) * | 2007-03-23 | 2008-10-02 | Rhodia Inc. | Structured surfactant compositions |
EP2282716A2 (en) * | 2008-04-23 | 2011-02-16 | Basf Se | Delivery of hydrophobic benefit agents from bodywashes and the like onto a keratinous substrate |
DE102008001661A1 (de) | 2008-05-08 | 2009-11-12 | Beiersdorf Ag | Haarpflegeformulierungen mit kationisch amphoteren Polymeren |
US8539938B2 (en) * | 2009-03-12 | 2013-09-24 | Ford Global Technologies, Llc | Fuel systems and methods for controlling fuel systems in a vehicle with multiple fuel tanks |
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ITMI20110644A1 (it) * | 2011-04-14 | 2012-10-15 | Giuliani Spa | Sistema per il rilascio prolungato di agenti cosmetici |
JP2016222614A (ja) * | 2015-06-01 | 2016-12-28 | 池田物産株式会社 | 2剤式毛髪化粧料 |
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-
1998
- 1998-12-04 US US09/205,692 patent/US20010009672A1/en not_active Abandoned
-
1999
- 1999-12-03 SK SK696-2001A patent/SK6962001A3/sk unknown
- 1999-12-03 BR BR9915872-8A patent/BR9915872A/pt not_active Application Discontinuation
- 1999-12-03 HU HU0200555A patent/HUP0200555A3/hu unknown
- 1999-12-03 WO PCT/US1999/028546 patent/WO2000033798A1/en not_active Application Discontinuation
- 1999-12-03 JP JP2000586292A patent/JP2002531478A/ja active Pending
- 1999-12-03 EP EP99965089A patent/EP1135096A1/en not_active Withdrawn
- 1999-12-03 KR KR1020017006926A patent/KR20010081061A/ko not_active Application Discontinuation
- 1999-12-03 CN CN99814052A patent/CN1391459A/zh active Pending
- 1999-12-03 CA CA002352460A patent/CA2352460A1/en not_active Abandoned
- 1999-12-03 PL PL99348023A patent/PL348023A1/xx unknown
- 1999-12-03 CZ CZ20011850A patent/CZ20011850A3/cs unknown
- 1999-12-03 AU AU31076/00A patent/AU3107600A/en not_active Abandoned
- 1999-12-06 AR ARP990106190A patent/AR021549A1/es unknown
-
2001
- 2001-05-29 NO NO20012638A patent/NO20012638L/no not_active Application Discontinuation
- 2001-08-23 US US09/934,488 patent/US6524614B2/en not_active Expired - Lifetime
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040013617A1 (en) * | 2002-07-19 | 2004-01-22 | Donald Rick | Sunless tanning composition |
US20040120919A1 (en) * | 2002-12-20 | 2004-06-24 | L'oreal | Hair compositions |
EP1430870A3 (en) * | 2002-12-20 | 2005-02-09 | L'oreal | Hair compositions |
KR100632160B1 (ko) * | 2002-12-20 | 2006-10-11 | 로레알 | 모발 조성물 |
US8367047B2 (en) | 2002-12-20 | 2013-02-05 | L'oreal | Hair compositions |
Also Published As
Publication number | Publication date |
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EP1135096A1 (en) | 2001-09-26 |
KR20010081061A (ko) | 2001-08-25 |
SK6962001A3 (en) | 2001-12-03 |
CA2352460A1 (en) | 2000-06-15 |
HUP0200555A3 (en) | 2002-11-28 |
AU3107600A (en) | 2000-06-26 |
NO20012638D0 (no) | 2001-05-29 |
AR021549A1 (es) | 2002-07-24 |
CZ20011850A3 (cs) | 2001-11-14 |
US20020009425A1 (en) | 2002-01-24 |
WO2000033798A1 (en) | 2000-06-15 |
US6524614B2 (en) | 2003-02-25 |
HUP0200555A2 (en) | 2002-08-28 |
PL348023A1 (en) | 2002-05-06 |
BR9915872A (pt) | 2001-08-21 |
NO20012638L (no) | 2001-08-06 |
WO2000033798B1 (en) | 2000-07-27 |
CN1391459A (zh) | 2003-01-15 |
JP2002531478A (ja) | 2002-09-24 |
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