WO2000002535A1 - Improved stable topical ascorbic acid compositions - Google Patents
Improved stable topical ascorbic acid compositions Download PDFInfo
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- WO2000002535A1 WO2000002535A1 PCT/US1999/014389 US9914389W WO0002535A1 WO 2000002535 A1 WO2000002535 A1 WO 2000002535A1 US 9914389 W US9914389 W US 9914389W WO 0002535 A1 WO0002535 A1 WO 0002535A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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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
- A61K8/58—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
- A61K8/585—Organosilicon 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
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
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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
- A61K8/89—Polysiloxanes
- A61K8/891—Polysiloxanes saturated, e.g. dimethicone, phenyl trimethicone, C24-C28 methicone or stearyl dimethicone
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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
- A61K8/89—Polysiloxanes
- A61K8/891—Polysiloxanes saturated, e.g. dimethicone, phenyl trimethicone, C24-C28 methicone or stearyl dimethicone
- A61K8/893—Polysiloxanes saturated, e.g. dimethicone, phenyl trimethicone, C24-C28 methicone or stearyl dimethicone modified by an alkoxy or aryloxy group, e.g. behenoxy dimethicone or stearoxy dimethicone
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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
- A61K8/89—Polysiloxanes
- A61K8/895—Polysiloxanes containing silicon bound to unsaturated aliphatic groups, e.g. vinyl dimethicone
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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
- A61K8/89—Polysiloxanes
- A61K8/896—Polysiloxanes containing atoms other than silicon, carbon, oxygen and hydrogen, e.g. dimethicone copolyol phosphate
- A61K8/898—Polysiloxanes containing atoms other than silicon, carbon, oxygen and hydrogen, e.g. dimethicone copolyol phosphate containing nitrogen, e.g. amodimethicone, trimethyl silyl amodimethicone or dimethicone propyl PG-betaine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- 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
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- 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
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- 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
- A61Q19/08—Anti-ageing preparations
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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
- A61Q5/006—Antidandruff preparations
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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
- A61K2800/52—Stabilizers
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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
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/75—Anti-irritant
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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
- A61Q5/12—Preparations containing hair conditioners
Definitions
- This invention concerns a topical formulation of a bio-available form of high levels of ascorbic acid (Vitamin C) that exhibits significant activity, but simultaneously is stable to oxidation from atmospheric oxygen, and is safe in use.
- Vitamin C ascorbic acid
- U.S. Patent No. 2,400,171 discloses the conversion of ascorbic acid to its calcium or zinc salt to maintain stable aqueous solutions in the pH range of 7 to 7.3.
- U.S. Patent No. 2,442,461 discloses stabilizing aqueous solutions of calcium ascorbate by adding an aliphatic thiocarboxylic acid, and maintaining the pH of the solution in the range of 5.2 to 5.6.
- U.S. Patent No. 2,585,580 (Opplt) discloses the stabilization of ascorbic acid with thio-sugars, and maintaining the pH of the resulting solution in the range of 4.0 to 6.5.
- U.S. Patent No. 4,367, 157 discloses stabilizing aqueous ascorbic acid solutions in the pH range of 4 to 7 by adding monothioglycerol.
- U.S. Patent No. 4,372,874 discloses adding a desiccant to a solution of ascorbic acid to entrap water and provide a residual water content below 0.5 weight percent, thereby forming a stable form of ascorbic acid.
- U.S. Patent No. 5,140,043 discloses the stabilization of at least 1 % (w/v) ascorbic acid by combining this material with equal parts water and a carrier comprising an alkylene glycol, and optionally a hydroxyalkylcellulose at a pH no greater than 3.5.
- U.S. Patent No. 5,296,249 disclosed micron sized particles of ascorbic acid in a suspension medium in which the particles were insoluble.
- U.S. Patent No. 5,308,621 showed fine, particulate ascorbic acid suspended in a pharmaceutical carrier (such as a glycol or petroleum jelly) for transdermal systemic administration.
- U.S. Patent No. 5,587, 149 describes a polyethylene glycol-in-oil emulsion of ascorbic acid.
- Ascorbic acid is biologically significant for many reasons, and has been found to have several different activities in the skin, as pointed out by Englard and Seifter, "The Biochemical Functions of Ascorbic Acid” in Ann. Rev. Nutri. 6:365 (1986).
- This vitamin has been found to be an antioxidant in blocking the lipid peroxidation of the skin, as demonstrated by Kunert and Tappel, "The Effect of Vitamin C on In-Vivo Lipid Peroxidation in Guinea Pigs as Measured by Pentane and Ethane Production” in Lipids 18:271 (1983).
- Kunert and Tappel "The Effect of Vitamin C on In-Vivo Lipid Peroxidation in Guinea Pigs as Measured by Pentane and Ethane Production” in Lipids 18:271 (1983).
- Kunert and Tappel "The Effect of Vitamin C on In-Vivo Lipid Peroxidation in Guinea Pigs as Measured by Pentane and Ethane Production” in Lipids 18:271 (1983).
- ascorbic acid is important to the skin, it is difficult to stabilize in topical preparations (such as dermatological, ophthamological or cosmetic formulations), particularly at the higher concentrations needed for maximum activity.
- topical preparations such as dermatological, ophthamological or cosmetic formulations
- the difficulties in preparing a stable topical preparation stem from the fact that ascorbic acid is an ⁇ - ketolactone having a double bond between the second and third carbon atoms of the structure, and hydroxyl groups at the second and third carbon atoms, and is therefore a moderately strong reducing agent.
- the pK of the molecule is 4.2, which means that one of the hydroxyl groups is 50% ionized at this pH value. At higher pH values the ascorbate anion becomes notoriously unstable.
- This instability is a result of several factors including stereochemical strain due to polar repulsion, the tendency of the molecule to disproportionate to dehydroascorbic acid (or dehydroascorbate anion) and ascorbic acid (or ascorbate anion) in the presence of a one-electron oxidant, or by a simple hydration reaction due to the attack of either a hydronium ion (or hydrogen ion) or a hydroxyl ion on the molecule, which opens the lactone ring structure.
- solid, particulate ascorbic acid in a silicone-based, non-aqueous vehicle has been found to provide a stable formulation that delivers ascorbic acid to the skin in such a way that it is still active in performing its desired functions.
- the solid ascorbic acid is substantially completely insoluble in the silicone-based vehicle, and the vehicle provides an ideal reservoir for delivering the ascorbic acid into the skin where it is more soluble in the moisture-laden levels of the skin. Regardless of the reason for the effect, it has unexpectedly been found that the combination of the solid ascorbic acid dispersed in the silicone- based vehicle delivers the intended effect on the skin while simultaneously being safe and effective.
- the vehicle consists essentially of the silicone vehicle, such as silicone oil, which can (but does not have to) comprise up to 90, 99 or even 99.9% of the composition.
- the preparation also contains materials such as other vitamins, cosmetic ingredients, herbal ingredients and/or medicaments as desired. Due to the non-polar nature of the vehicle, the ascorbic acid is not solublized in the vehicle. Therefore, the preparation is best described as a suspension of ascorbic acid in the vehicle. This lack of solubility minimizes or precludes ionization of the ascorbic acid molecule, which results in a significant enhancement in the stability of this biologically active substance.
- silicone based nonaqueous vehicle in which to deliver high levels of ascorbic acid to the skin does not require the presence of additional ingredients such as metal chelators [for example ethylenediamine tetraacetic acid (EDTA), diethylene triaminepentaacetic acid (DTP A) or ethylenediamine di-(o- hydroxyphenylacetic acid) (EDDHA)] in order to enhance the stability of ascorbic acid against oxidation by trace quantities of metal ions in the water, and other ingredients commonly used in topical preparations.
- metal chelators for example ethylenediamine tetraacetic acid (EDTA), diethylene triaminepentaacetic acid (DTP A) or ethylenediamine di-(o- hydroxyphenylacetic acid) (EDDHA)
- silicone gels or solids are the preferred silicone-based vehicles from which to formulate the non-aqueous, preferably anhydrous
- the present invention permits economical preparations of ascorbic acid even at high levels (greater than 1 % w/w ascorbic acid).
- Stable topical preparations can be formulated even at levels of up to 40% (w/w) ascorbic acid (or more) using this technology.
- the only factor limiting the maximum quantity of ascorbic acid that can be included in this preparation is the amount of the non-aqueous medium needed to thoroughly disperse the quantity of ascorbic acid desired.
- compositions may include one or more anti-irritants in order to reduce this stinging potential.
- incorporation of such a material into the composition may, at least in some cases, allow the composition to be more readily tolerated even by those individuals who could not otherwise apply an ascorbic acid preparation to their skin because of irritation and/or persistent stinging.
- the topical composition comprises a particulate ascorbic acid, and a silicone vehicle (such as an oil, gel or solid) in a sufficient amount to suspend (substantially without solubilizing) an effective amount of the particulate ascorbic acid, and substantially excluding environmental oxygen and moisture from the composition.
- a silicone vehicle such as an oil, gel or solid
- the particulate ascorbic acid consists essentially of solid ascorbic acid particles having a particle size of less than about 20 ⁇ m, for example less than about 12 ⁇ m.
- the silicone vehicle comprises at least 50% by weight of the composition, for example at least 80% by weight of the composition, and even up to 99% or 99.9% of the composition.
- the silicone oil is an organosiloxane, such as one or more of a polyorganosiloxane selected from the group consisting of polysilicone-11, dimethicone and cyclomethicone.
- the particulate ascorbic acid is present in an amount of at least 0.1 % of undissolved ascorbic acid, for example at least 1 % of undissolved ascorbic acid, for example 2 to 30%, 5 to 20%, 8 to 12%, or even as much as 40% or more of ascorbic acid.
- the silicone oil substantially excludes moisture, and the ascorbic acid is substantially insoluble in the silicone oil, hence the composition is substantially free of dissolved ascorbic acid or water.
- composition may optionally include Vitamin E or Vitamin A, where the Vitamin E may be in the form of tocopherol or its esters (for example tocopheryl acetate), and Vitamin A may be in the form of retinol or its ester or acids (for example retinyl palmitate or retinoic acid).
- Vitamin E may be in the form of tocopherol or its esters (for example tocopheryl acetate)
- Vitamin A may be in the form of retinol or its ester or acids (for example retinyl palmitate or retinoic acid).
- the composition includes an anhydrous silicone carrier, in an amount of 50-80% by weight, which is substantially free of water or environmental (for example atmospheric) oxygen, and particulate ascorbic acid, in an amount of 0.1-40% by weight, having a particle size of less than about 12.5 ⁇ m, and which is stable to oxidation of ascorbic acid by environmental oxygen.
- the composition may comprise one of more of Vitamin A and Vitamin E, and other ingredients to be delivered to the skin, such as herbal ingredients and medicaments, or materials designed to reduce stinging or irritation of the skin to which the composition is applied.
- the silicone oil vehicle may include dimethicone, cyclomethicone, poly silicone - 11, or mixtures of these and other organosiloxane materials in any given ratio in order to achieve the desired consistency and application characteristics depending upon the intended application (e.g., to a particular area such as the skin, hair, or eyes).
- the stabilized ascorbic acid suspension of the present invention includes a silicone vehicle (such as an oil, gel or solid) that is ideally substantially anhydrous (e.g. less than 0.1 % water), supports a suspension of ascorbic acid, and is not hygroscopic so that it does not absorb sufficient water from the atmosphere to initiate the decomposition of ascorbic acid in the suspension.
- a silicone vehicle such as an oil, gel or solid
- supports a suspension of ascorbic acid supports a suspension of ascorbic acid, and is not hygroscopic so that it does not absorb sufficient water from the atmosphere to initiate the decomposition of ascorbic acid in the suspension.
- Particular embodiments of the vehicle also substantially exclude metal ions (such as zinc ions) or other materials (such as organic chemical ingredients with double bonds) that would react with or oxidize the ascorbic acid.
- the vehicle is also substantially non-polar, and does not have significant solvating power for ascorbic acid (as do polar organic solvents such as alcohols).
- Gel or solid forms of the silicone vehicle are particularly preferred because they maintain a more uniform suspension (and dosage) of the ascorbic acid in the product throughout its shelf life.
- emulsifiers would not be suitable solvents, because an emulsifier must have some water solubility in order to stabilize the interface between the oil and water phases.
- silicone copolyol emulsifiers would have some water solubility, and also absorb water from the atmosphere (via its polyol functionality).
- the silicone vehicle may be a volatile or non-volatile silicone.
- the formulation incorporates volatile silicone oils (such as cyclomethicone) to achieve a consistency that is aesthetically pleasing when applied to the face.
- volatile silicone oils such as cyclomethicone
- other formulations such as pharmaceutical formulations, or products to be applied to the body instead of the face
- other than volatile silicone oils may be used.
- Poly silicone- 11 is a cross-linked silicone rubber formed by the reaction of vinyl- terminated silicone and methylhydrodimethyl siloxane in the presence of cyclomethicone.
- the ingredients listed in Table 1 can be obtained from the suppliers shown in Table 2:
- Method of Making Combine the Poly silicone - 11, dimethicone and cyclomethicone in a container.
- the tocopheryl acetate and retinyl palmitate are added as appropriate and mixed until uniform.
- the solids (ascorbic acid) are dispersed into this mixture with appropriate agitation.
- the ascorbic acid is ground into the mixture using a three-roll mill until the particle size of the solid ascorbic acid particles is small enough that the particles are not gritty when applied to the skin (particle size less than 12.5 microns as measured by a Hagman gauge). Mix until uniform, then package the resulting white to off-white formulation in containers.
- Ultrafine ascorbic acid can be use to replace the granular ascorbic acid.
- Using this material eliminates the need to pass the batch through a device to reduce the particle size.
- Roche Vitamins and Fine Chemicals lists the following specification for this material, which is sold under the name ascorbic acid USP, FCC (Vitamin C; L-ascorbic acid) Ultra-Fine Powder (Product Code No. 6045653), in which 100% of the powder passes through a No. 100 U.S. Standard Sieve (a standard USP and FCC testing procedure). Alternatively, more than 80% of the material passes through a No. 325 U.S. Sieve.
- the product made by Example 4 is a white to off-white cream-gel having no appreciable odor, a viscosity of 30,000 to 150,000 CPS, and a specific gravity of 0.97-1.03.
- Example 5 The product made in Example 4 was stored under conditions of elevated temperature and humidity in order to check for the stability of the ascorbic acid. Ascorbic acid stability was determined by the absence of an off-white to brown coloration characteristic of degraded ascorbic acid. The product used was manufactured under laboratory conditions and packaged without special precautions to exclude air or oxygen from contacting the product (i.e. , without blanketing the resulting product with nitrogen to reduce the potential of oxidation by air or oxygen). The results of this stability study are shown in Table 3. TABLE 3 Coloration of Samples Stored at Varying Conditions
- the stability of the samples stored at 40°C/80% relative humidity are indicative of a formulation that is stable for a period of time equivalent to 8 times its stable storage period. Therefore, the data in Table 3 confirms that the ascorbic acid formulation of the present invention will remain stable for at least 8 months at ambient temperature. In particular embodiments, it is preferred that the formulation in Example 4 containing 10 (w/w) % ascorbic acid will remain stable for at least 2 years without the need for any special handling procedures during the manufacturing and packaging processes, or during handling by the consumer.
- a product made in accordance with Example 4 was tested for antioxidant activity in human skin cell cultures using ultraviolet light from a solar simulator as the source of free radicals within the skin cells.
- Antioxidant activity was evaluated in cell culture using the Epiderm Skin Model (EPI- 100) from the Mattek Corporation of Ashland, MA. These cell cultures of neonatal foreskin were cultured in accordance with the manufacturer's directions, and were assayed for percent cellular viability by measuring the amount of 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide
- MTT Minimal Erythemal Dose
- the cell cultures were also evaluated for the production of Prostaglandin E2 (PGE2) using an assay kit obtained from Perspective Diagnostics of Cambridge, MA. As with the assay for percent cellular viability, the cell cultures were exposed to a dose of ultraviolet light at a rate of
- UV light Exposure of the skin to ultraviolet (UV) light is known to generate free radicals in skin cells.
- the endpoints used to measure the antioxidant activity were the (1) the number of viable cells remaining after exposure to the UV light as determined by the conversion of 3-(4,5- dimethylthazol-2-yl)-2,5-diphenyltetralium bromide (MTT) to extractable formazin crystals by the viable cells; and (2) the amount of Prostaglandin E2 (PGE2) produced by the cells in response to the exposure to the UV light.
- MTT 3-(4,5- dimethylthazol-2-yl)-2,5-diphenyltetralium bromide
- PGE2 Prostaglandin E2
- Example 4 The formulation of Example 4 was also subjected to a clinical test on human subjects in which the skin was subjectively and objectively measured for product efficacy. Each of 20 subjects in the test applied the formulation in Example 4 to one side of the face twice daily for a period of 3 months. The side of the face to which the formulation was applied was randomly assigned by the study investigator to eliminate any bias. Subjects were subjectively evaluated for irritation and objectively measured for changes in elasticity and texture. Elasticity changes were evaluated by the use of a CUTOMETERTM, which measures the ability to elastically deform the skin under a vacuum. Changes in fine lines and wrinkles were evaluated by image analysis of skin replicas taken on the treated and untreated site at each visit. The results of these evaluations are shown in Table 5.
- siloxanes refers to organosiloxanes or polyorganosiloxanes, which are any of a large group of siloxane polymers based on a structure in which silicon and oxygen atoms alternate with various organic radicals attached to the silicon, as described for example in Remington: The Science and Practice of Pharmacy, 19 th edition, pages 867-868, and as shown below:
- the organosiloxanes may be liquids, semisolids, or solids depending on the molecular weight and degree of polymerization, as known in the art.
- a silicone oil is the preferred vehicle.
- a "silicone oil” is a liquid organosiloxane.
- a “suspension” is a system in which small particles (such as ascorbic acid particles) are substantially uniformly dispersed in a liquid, gel, or cream medium. An emulsion is specifically excluded from the definition of a suspension. A solid may be formed from the suspension.
- a "volatile silicone oil” is a silicone oil have a low heat of vaporization, i.e. normally less than about 50 cal per gram of silicone oil.
- Typical suitable volatile silicone oils include cyclomethicones such as Dow Corning 344 Fluid, Dow Corning 345 Fluid, Dow Corning 244 Fluid, and Dow Corning 245 Fluid; as well as Volatile Silicon 7207, a trademark of Union Carbide Corp., Danbury, CT., low viscosity di harmonyones, i.e. dimethicones having a viscosity of about 50 cst or less, especially dimethicones such as Dow Corning 200-0.5 cst Fluid.
- the Dow Corning Fluids are available from Dow Corning Corporation, Midland, MI 48640.
- Cyclomethicone and dimethicone are names given by the Third Edition of the CTFA Cosmetic Ingredient Dictionary to cyclic dimethyl polysiloxane compounds and a mixture of fully methylated linear siloxane polymers end-blocked with trimethylsiloxy units, respectively.
- Other volatile silicone oils having a low heat of vaporization such as those available from General Electric Co., Silicone Products Div., Waterford, N.Y. and SWS Silicones Div. of Stauffer Chemical Co., Adrian, MI, can also be used in the compositions of the invention.
- the term "effective amount of ascorbic acid” means an amount sufficient to reduce fine lines and wrinkles in the skin, or to increase elasticity, or both. In the disclosed embodiments of this invention, that effective amount can be at least about 0.1 % of ascorbic acid, for example about 0.1-30% , or at least about 1 %, 10%, or even 40% of ascorbic acid.
- an “effective amount” of Vitamin A, Vitamin C, or Vitamin E is an amount sufficient to have an antioxidant effect, as measured by the methods of Example 6, that is an increase in cellular viability or a reduction in the production of PGE2.
- an “effective amount” of silicone oil is an amount sufficient to substantially exclude environmental (for example atmospheric) water or oxygen.
- a “nonaqueous" composition is one that is substantially water free. While water is not intentionally added to a nonaqueous composition, no attempt is made to remove water from the ingredients used in the compositions, since it is not necessary that the compositions be completely anhydrous. However, it is desired that the amount of free water in the composition be less than about 1 % , or even less than 0.1 % (at which point is would be considered substantially anhydrous).
- a “topical” composition is one that is suitable for application to the skin, and includes pharmaceutical and cosmetic formulations.
- a pharmaceutical composition is one that is intended to deliver therapeutic substances, and can include conventional preparations for administration on the skin (topical or dermatologic), or in the eye (ophthalmic), among others.
- the nonaqueous ascorbic acid compositions of the invention can contain conventional amounts of one or more cosmetic waxes, cosmetic emollients, and even sunscreening agents.
- the compositions may also contain perfumes, preservatives, dyes, softeners, physical reflectors and antioxidants, as well as any other class of materials whose presence may be cosmetically or otherwise desirable.
- Cosmetic antioxidants include propyl, octyl and dodecyl esters of gallic acid, butylated hydroxyanisole (usually as a mixture of ortho and meta isomers), butylated hydroxytoluene and nordihydroguaiaretic acid.
- antioxidants have been added to ascorbic acid compositions in the past, it is unnecessary to add antioxidants to the ascorbic acid compositions of the present invention, because the silicone vehicle substantially excludes atmospheric water and oxygen from the composition.
- the present invention can also include compositions to which such preservatives are added.
- compositions of the present invention may be in the form of a liquid, gel or semi- solid.
- the selection of ingredient type and amount is dictated by the nature of the composition, i.e. gel or semi-solid, and is within the skill of cosmetic chemists.
- larger amounts of wax may be incorporated into the semi-solid compositions of the present invention than into the liquid ones.
- suitable cosmetic waxes include ozokerite, lanolin alcohol, paraffin wax, bayberry wax, polyethylene wax, especially AC 617 available from Allied-Signal Corp., Morristown, N.J. ; Polawax (a reaction product of higher fatty alcohols and ethylene oxide available from Croda, Inc., New York., N.Y.
- Typical suitable cosmetic emollients include mineral oil, especially mineral oils having a viscosity in the range of 50 to 500 SUS, lanolin oil, coconut oil, cocoa butter, olive oil, almond oil, macadamia nut oil, aloe extract, jojoba oil, safflower oil, corn oil, liquid lanolin, cottonseed oil, and peanut oil.
- Suitable cosmetic emollients include Purcellin oil, perhydrosqualene, castor oil, polybutene, odorless mineral spirits, sweet almond oil, avocado oil, calophyllum oil, ricin oil, vitamin E acetate, olive oil, mineral spirits, linolenic alcohol, oleyl alcohol, the oil of cereal germs, such as the oil of wheat germ, and esters such as isopropyl myristate, butyl myristate, hexadecyl stearate, decyl oleate, acetyl glycerides, the octanoates and benzoates of (C12-C15) alcohols, the octanoates and decanoates of alcohols and polyalcohols such as those of glycol and glycerol, ricin oleates of alcohols and poly alcohols, such as those of isopropyl adipate, hexyl laurate and oc
- Suitable cosmetic emollients which are solids or semi-solids at ambient temperatures may be used if admixed with one or more of the cosmetic emollients listed above, in amounts sufficient to provide liquid topical compositions.
- Such solid or semi-solid cosmetic emollients included hydrogenated lanolin, hydroxylated lanolin, acetylated lanolin, petrolatum, isopropyl lanolate, cetyl myristate, myristyl myristate, myristyl lactate, cetyl alcohol, isostearyl alcohol and isocetyl lanolate.
- the ascorbic acid composition can also include other ingredients to be delivered to the skin, such as herbal ingredients and medicaments.
- herbal ingredients and medicaments are shown in the following Tables 6 and 7:
- composition can also include additional silicone-based materials, such as phenyl trimethicone or trimethylsilylamodimethicone, in order to achieve the desired application characteristic needed for application of the ascorbic acid to any intended body site (i. e. , skin, hair, eyes, etc.).
- additional silicone-based materials such as phenyl trimethicone or trimethylsilylamodimethicone
- Examples 8 to 11 show such alternative formulations.
- the composition may also contain a material or mixture of materials that reduces the stinging and/or irritation potential of the preparation upon application, such as any one or a combination of a variety of anesthetics, antipruritics, and counterirritants. Examples of such materials (and amounts in which they would be used) are shown in the following Table 8, and are further described in the Handbook of Non-Prescription Drugs, Ninth Edition, E.G. Feldman (editor) (American Pharmaceutical Association, Washington, D.C., 1990): TABLE 8
Abstract
Description
Claims
Priority Applications (4)
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CA002336799A CA2336799C (en) | 1998-07-10 | 1999-06-25 | Improved stable topical ascorbic acid compositions |
EP99931905A EP1096922A4 (en) | 1998-07-10 | 1999-06-25 | Improved stable topical ascorbic acid compositions |
AU48316/99A AU4831699A (en) | 1998-07-10 | 1999-06-25 | Improved stable topical ascorbic acid compositions |
JP2000558796A JP4716567B2 (en) | 1998-07-10 | 1999-06-25 | Improved and stable topical ascorbic acid composition |
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US09/113,535 | 1998-07-10 | ||
US09/113,535 US6146664A (en) | 1998-07-10 | 1998-07-10 | Stable topical ascorbic acid compositions |
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WO2000002535A1 true WO2000002535A1 (en) | 2000-01-20 |
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PCT/US1999/014389 WO2000002535A1 (en) | 1998-07-10 | 1999-06-25 | Improved stable topical ascorbic acid compositions |
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US (1) | US6146664A (en) |
EP (1) | EP1096922A4 (en) |
JP (1) | JP4716567B2 (en) |
AU (1) | AU4831699A (en) |
CA (1) | CA2336799C (en) |
WO (1) | WO2000002535A1 (en) |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US7700076B2 (en) | 2002-10-25 | 2010-04-20 | Foamix, Ltd. | Penetrating pharmaceutical foam |
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US8119150B2 (en) | 2002-10-25 | 2012-02-21 | Foamix Ltd. | Non-flammable insecticide composition and uses thereof |
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US20080138296A1 (en) | 2002-10-25 | 2008-06-12 | Foamix Ltd. | Foam prepared from nanoemulsions and uses |
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US7820145B2 (en) | 2003-08-04 | 2010-10-26 | Foamix Ltd. | Oleaginous pharmaceutical and cosmetic foam |
US7575739B2 (en) | 2003-04-28 | 2009-08-18 | Foamix Ltd. | Foamable iodine composition |
US7824566B2 (en) | 2003-07-08 | 2010-11-02 | Scheidler Karl J | Methods and compositions for improving light-fade resistance and soil repellency of textiles and leathers |
US8795693B2 (en) | 2003-08-04 | 2014-08-05 | Foamix Ltd. | Compositions with modulating agents |
US8486374B2 (en) | 2003-08-04 | 2013-07-16 | Foamix Ltd. | Hydrophilic, non-aqueous pharmaceutical carriers and compositions and uses |
US20050065091A1 (en) * | 2003-09-18 | 2005-03-24 | Gholam Peyman | Stabilized ocular solutions |
US20050112158A1 (en) * | 2003-11-17 | 2005-05-26 | Clariant Internatinonal, Ltd. | Method for synthesis of silylated ascorbic acid derivatives |
US7179841B2 (en) * | 2004-01-13 | 2007-02-20 | L'oreal Usa Creative, Inc. | Stabilized ascorbic acid compositions and methods therefor |
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US9439857B2 (en) | 2007-11-30 | 2016-09-13 | Foamix Pharmaceuticals Ltd. | Foam containing benzoyl peroxide |
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US9849142B2 (en) | 2009-10-02 | 2017-12-26 | Foamix Pharmaceuticals Ltd. | Methods for accelerated return of skin integrity and for the treatment of impetigo |
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US8174881B2 (en) | 2009-11-24 | 2012-05-08 | Micron Technology, Inc. | Techniques for reducing disturbance in a semiconductor device |
US20170065533A1 (en) * | 2011-01-24 | 2017-03-09 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Nanoparticles for dermal and systemic delivery of drugs |
US20120225107A1 (en) * | 2011-03-04 | 2012-09-06 | Caridad Hechavarria | Stable skin and scar treatment composition |
US9687465B2 (en) | 2012-11-27 | 2017-06-27 | Sol-Gel Technologies Ltd. | Compositions for the treatment of rosacea |
ES2539520B1 (en) * | 2013-12-30 | 2016-06-06 | Laboratorios Viñas S.A. | Topical application pharmaceutical composition in the form of a micronized suspension and corresponding method and uses |
MX2020012139A (en) | 2016-09-08 | 2021-01-29 | Vyne Pharmaceuticals Inc | Compositions and methods for treating rosacea and acne. |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5902591A (en) * | 1997-04-03 | 1999-05-11 | La Prairie Sa | Stable topical cosmetic/pharmaceutical emulsion compositions containing ascorbic acid |
Family Cites Families (68)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US33845A (en) * | 1861-12-03 | Improvement in harvesting-machines | ||
US2400171A (en) * | 1935-09-26 | 1946-05-14 | Frances R Ruskin | Stabilized metal ascorbates |
US2442461A (en) * | 1944-03-09 | 1948-06-01 | Hoffmann La Roche | Stable solutions of calcium ascorbate |
US2585580A (en) * | 1947-06-12 | 1952-02-12 | Opplt Jan | Stabilizing ascorbic acid with thio-sugars |
SU551030A1 (en) * | 1975-11-11 | 1977-03-25 | Краснодарский Научно-Исследовательский Институт Пищевой Промышленности | Skin cream |
US4372874A (en) * | 1976-09-13 | 1983-02-08 | Modrovich Ivan Endre | Stabilization of hydrolysis prone labile organic reagents in liquid media |
US4454112A (en) * | 1977-12-27 | 1984-06-12 | Henkel Corporation | Sunscreen composition containing tocopherol acetylsalicylate |
US4209449A (en) * | 1978-11-30 | 1980-06-24 | Mona Industries | Phosphate quaternary compounds |
US4503002A (en) * | 1978-11-30 | 1985-03-05 | Mona Industries, Inc. | Phosphate quaternary compounds |
US4367157A (en) * | 1979-05-10 | 1983-01-04 | Sherman Laboratories, Inc. | Soft contact lens ambient temperature disinfectant solution containing ascorbic acid or salt thereof |
DE3024870C2 (en) * | 1980-07-01 | 1985-01-10 | Th. Goldschmidt Ag, 4300 Essen | Process for making a stable emulsion |
DE3586859D1 (en) * | 1984-03-07 | 1993-01-07 | Roshdy Ismail | AGENTS FOR TREATING AND PROTECTING THE SKIN. |
US4563346A (en) * | 1984-03-14 | 1986-01-07 | Charles Of The Ritz Group Ltd. | Topical delivery system and skin treatment compositions employing such system |
DE3436177A1 (en) * | 1984-10-03 | 1986-04-03 | Goldschmidt Ag Th | USE OF POLYOXYALKYLENE-POLYSILOXANE-COPOLYMERISATES WITH LONG-CHAIN ALKYL RESIDUES BONDED TO SILICON ATOMS AS EMULSIFIERS FOR THE PRODUCTION OF W / O EMULSIONS |
US4695452A (en) * | 1984-10-10 | 1987-09-22 | Gannis Peter M | Cosmetic stick |
US4603046A (en) * | 1985-08-23 | 1986-07-29 | Charles Of The Ritz Group Ltd. | Improved sunscreen or sunblock composition |
US4784845A (en) * | 1985-09-16 | 1988-11-15 | American Cyanamid Company | Emulsion compostions for the parenteral administration of sparingly water soluble ionizable hydrophobic drugs |
US4847267A (en) * | 1986-03-17 | 1989-07-11 | Charles Of The Ritz Group Ltd. | Skin treatment composition and method |
NL8601767A (en) | 1986-07-07 | 1988-02-01 | Schreuder Chem Adviesbureau | SKIN TANNING AGENT. |
US4833259A (en) * | 1986-09-15 | 1989-05-23 | Hoffmann-La Roche Inc. | Light screening agents |
US5141665A (en) * | 1987-03-31 | 1992-08-25 | Sherman Laboratories, Inc. | Cleaning, conditioning, storing and wetting system and method for rigid gas permeable contact lenses and other contact lenses |
PH25566A (en) * | 1987-04-01 | 1991-08-08 | Plough | Non-aqueous suncare composition having high spf values |
US4826691A (en) * | 1987-08-03 | 1989-05-02 | Berkley, Inc. | Carrier for fish attractant |
US4954332A (en) * | 1987-10-22 | 1990-09-04 | The Procter & Gamble Company | Photoprotection compositions comprising tocopherol sorbate and an anti-inflammatory agent |
US4904698A (en) * | 1988-02-11 | 1990-02-27 | Ocusoft Inc. | Eyelid cleansing composition |
US4940574A (en) * | 1988-12-22 | 1990-07-10 | Plough, Inc. | Non-aqueous high SPF sunscreen oils |
US5140043A (en) * | 1989-04-17 | 1992-08-18 | Duke University | Stable ascorbic acid compositions |
US5444096A (en) * | 1989-06-02 | 1995-08-22 | Helene Curtis, Inc. | Stable anhydrous topically-active composition and suspending agent therefor |
US5008100A (en) * | 1989-08-11 | 1991-04-16 | Elizabeth Arden Co., Division Of Conopco, Inc. | Oil-in-water emulsions containing polyethylene |
US5290555A (en) * | 1989-09-14 | 1994-03-01 | Revlon Consumer Products Corporation | Cosmetic compositions with structural color |
US5153230A (en) * | 1989-10-06 | 1992-10-06 | Perfective Cosmetics, Inc. | Topical skin cream composition |
WO1991007944A1 (en) * | 1989-12-04 | 1991-06-13 | Richardson-Vicks, Inc. | Photoprotective compositions |
US5162378A (en) * | 1990-04-20 | 1992-11-10 | Revlon Consumer Products Corporation | Silicone containing water-in-oil microemulsions having increased salt content |
US5670160A (en) * | 1990-08-24 | 1997-09-23 | Schulke & Mayr Gmbh | Preservatives and their use |
US5308621A (en) * | 1991-02-18 | 1994-05-03 | Commonwealth Scientific And Industrial Research Organisation | Ascorbic acid composition and transdermal administration method |
US5230836A (en) * | 1991-06-20 | 1993-07-27 | Kalamazoo Holdings, Inc. | Low micron-sized ascorbic acid particles, especially a suspension thereof in a medium in which they are insoluble, and the use thereof as an antioxidant for mediums in which the particles remain insoluble |
US5378461A (en) * | 1991-07-12 | 1995-01-03 | Neigut; Stanley J. | Composition for the topical treatment of skin damage |
US5215976A (en) * | 1991-10-28 | 1993-06-01 | Mona Industries, Inc. | Phospholipids useful as spermicidal agents |
US5286719A (en) * | 1991-10-28 | 1994-02-15 | Mona Industries, Inc. | Phospholipid virucidal compositions |
JPH0680964A (en) * | 1991-12-27 | 1994-03-22 | Sogo Yatsukou Kk | Active-oxygen scavenger |
GB9204388D0 (en) * | 1992-02-29 | 1992-04-15 | Tioxide Specialties Ltd | Water-in-oil emulsions |
DE4206732A1 (en) * | 1992-03-04 | 1993-09-09 | Goldschmidt Ag Th | LIQUID, STORAGE STABLE, MULTIPLE EMULSION OF THE TYPE O / W / O |
US5663205A (en) * | 1992-05-22 | 1997-09-02 | Senju Pharmaceutical Co. Ltd. | Pharmaceutical composition for use in glaucoma treatment |
DE4223464A1 (en) * | 1992-07-16 | 1994-01-20 | Bayer Ag | Cosmetic sunscreen |
EP0595209A3 (en) * | 1992-10-23 | 1996-07-17 | R I T A Corp An Illinois Corp | Cosmetic composition |
US5374362A (en) * | 1992-11-18 | 1994-12-20 | Mcfarland; Steven M. | UV light protection formula for fabric, leather, vinyl and wood surfaces |
US5482705A (en) * | 1993-06-18 | 1996-01-09 | Hoffmann, Jr.; Carl R. | Cold-water (fresh or salt) and no-water shaving lotion |
US5516506A (en) * | 1993-11-19 | 1996-05-14 | Bernel Chemical Co. | Emollients for sunscreens and other dermatological products |
EP0732969B1 (en) * | 1993-12-06 | 1998-11-11 | Stepan Company | Water-in-oil emulsions containing increased amounts of oil and methods for preparing same |
FR2715565B1 (en) * | 1994-01-31 | 1996-03-15 | Oreal | Stabilized cosmetic or dermatological composition containing several precursors of the same active ingredient to maximize its release, its use. |
FR2715563B1 (en) * | 1994-01-31 | 1996-03-15 | Oreal | Stabilized emulsion, intended to hydrate the skin and its use. |
US5505935A (en) * | 1994-05-09 | 1996-04-09 | Elizabeth Arden Company, Division Of Conopco, Inc. | Sunscreen compositions |
US5543136A (en) * | 1994-06-16 | 1996-08-06 | Nuskin International, Inc. | Sunscreen emulsions |
CA2193087C (en) * | 1994-06-23 | 2002-01-08 | Greg George Hillebrand | Topical compositions comprising n-acetyl-l-cysteine |
US5482714A (en) * | 1994-07-08 | 1996-01-09 | Healthpoint Medical Limited Partnership | Water impermeable skin protectant based upon reverse water emulsion |
FR2725448B1 (en) * | 1994-10-07 | 1997-01-03 | Oreal | NOVEL SOLAR FILTERS, PHOTOPROTECTIVE COSMETIC COMPOSITIONS CONTAINING THEM AND USES |
US5445823A (en) * | 1994-10-20 | 1995-08-29 | The Procter & Gamble Company | Dermatological compositions and method of treatment of skin lesions therewith |
FR2727114B1 (en) * | 1994-11-17 | 1996-12-27 | Oreal | NOVEL SOLAR FILTERS, PHOTOPROTECTIVE COSMETIC COMPOSITIONS CONTAINING THEM AND USES THEREOF |
US5599533A (en) * | 1994-12-15 | 1997-02-04 | Estee Lauder, Inc. | Stable water-in-oil emulsion system |
US5759523A (en) * | 1994-12-22 | 1998-06-02 | The Procter & Gamble Company | Detergent compositions comprising a dimethicone copolyol |
US5560917A (en) * | 1995-02-01 | 1996-10-01 | Maybelline Intermediate Company | Cosmetic makeup composition |
US5587149A (en) * | 1995-02-06 | 1996-12-24 | R.P. Scherer Corporation | Topical application emulsions |
US5843411A (en) * | 1997-02-06 | 1998-12-01 | Topix Pharmaceuticals Inc. | Stabilization of ascorbic acid, ascorbic acid derivatives and/or extracts containing ascorbic acid for topical use |
US5750123A (en) * | 1996-06-28 | 1998-05-12 | Chesebrough-Pond's Co., Division Of Conopco, Inc. | Vitamin C delivery system |
US5738859A (en) * | 1997-01-17 | 1998-04-14 | Abbe Cosmetic Group International, Inc. | Cosmetic composition |
US5804168A (en) * | 1997-01-29 | 1998-09-08 | Murad; Howard | Pharmaceutical compositions and methods for protecting and treating sun damaged skin |
CA2270073A1 (en) * | 1997-09-16 | 1999-03-25 | E-L Management Corp. | Stable anhydrous formulation |
US6194452B1 (en) * | 1997-11-07 | 2001-02-27 | Howard Murad | Stable pharmaceutical compositions including ascorbic acid and methods of using same |
-
1998
- 1998-07-10 US US09/113,535 patent/US6146664A/en not_active Expired - Lifetime
-
1999
- 1999-06-25 WO PCT/US1999/014389 patent/WO2000002535A1/en active Application Filing
- 1999-06-25 JP JP2000558796A patent/JP4716567B2/en not_active Expired - Lifetime
- 1999-06-25 CA CA002336799A patent/CA2336799C/en not_active Expired - Lifetime
- 1999-06-25 EP EP99931905A patent/EP1096922A4/en not_active Withdrawn
- 1999-06-25 AU AU48316/99A patent/AU4831699A/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5902591A (en) * | 1997-04-03 | 1999-05-11 | La Prairie Sa | Stable topical cosmetic/pharmaceutical emulsion compositions containing ascorbic acid |
Non-Patent Citations (1)
Title |
---|
See also references of EP1096922A4 * |
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US6261566B1 (en) | 1999-10-22 | 2001-07-17 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Cosmetic compositions containing mulberry extract and retinoids |
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EP1688130A1 (en) * | 2000-03-03 | 2006-08-09 | Australian Importers, Ltd. | Micronized vitamin C formulation |
EP1263415A1 (en) * | 2000-03-03 | 2002-12-11 | Australian Importers, Ltd. | Micronized vitamin c formulation |
EP1263415A4 (en) * | 2000-03-03 | 2003-05-02 | Australian Imp Ers Ltd | Micronized vitamin c formulation |
US7101563B1 (en) | 2000-03-03 | 2006-09-05 | Australian Importers, Ltd. | Micronized vitamin C formulation |
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Also Published As
Publication number | Publication date |
---|---|
CA2336799A1 (en) | 2000-01-20 |
EP1096922A1 (en) | 2001-05-09 |
JP4716567B2 (en) | 2011-07-06 |
AU4831699A (en) | 2000-02-01 |
US6146664A (en) | 2000-11-14 |
EP1096922A4 (en) | 2004-05-19 |
JP2002520267A (en) | 2002-07-09 |
CA2336799C (en) | 2008-07-29 |
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