WO2000072817A1 - Emulsion eau dans huile comprenant un gel de silicone contenant de la vitamine c - Google Patents

Emulsion eau dans huile comprenant un gel de silicone contenant de la vitamine c Download PDF

Info

Publication number
WO2000072817A1
WO2000072817A1 PCT/US2000/013810 US0013810W WO0072817A1 WO 2000072817 A1 WO2000072817 A1 WO 2000072817A1 US 0013810 W US0013810 W US 0013810W WO 0072817 A1 WO0072817 A1 WO 0072817A1
Authority
WO
WIPO (PCT)
Prior art keywords
emulsion
silicone
water
agents
oil
Prior art date
Application number
PCT/US2000/013810
Other languages
English (en)
Inventor
Chris R. Stahl
Frederick W. Woodin, Jr.
John Kung
Jue-Chen Liu
Original Assignee
Neutrogena Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Neutrogena Corporation filed Critical Neutrogena Corporation
Priority to AU51461/00A priority Critical patent/AU5146100A/en
Publication of WO2000072817A1 publication Critical patent/WO2000072817A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/06—Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/04—Dispersions; Emulsions
    • A61K8/06—Emulsions
    • A61K8/064—Water-in-oil emulsions, e.g. Water-in-silicone emulsions
    • 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
    • A61K8/31—Hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35—Ketones, e.g. benzophenone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A61K8/447—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof containing sulfur
    • 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
    • A61K8/466—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfonic acid derivatives; Salts
    • 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
    • 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
    • A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/676—Ascorbic acid, i.e. vitamin C
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • 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
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
    • C08J3/09—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in organic liquids
    • C08J3/091—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in organic liquids characterised by the chemical constitution of the organic liquid
    • C08J3/098—Other compounds
    • 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
    • A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2383/00—Characterised by the use of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen, or carbon only; Derivatives of such polymers
    • C08J2383/04—Polysiloxanes

Definitions

  • Ascorbic acid (Vitamin C) is well known for its collagen stimulation, free radical scavenging, and tyrosinase inhibiting activities in the skin. Because of its powerful anti-oxidant properties, ascorbic acid is very sensitive to oxygen and, thus, difficult to stabilize. The degradation of ascorbic acid in the product is observable to consumers by the yellowing or browning of the product and/or the existence of a malodor. Since ascorbic acid rapidly degrades in these formulations, the consumer, thus, is not receiving all, if any, of the therapeutic benefit of the vitamin.
  • ascorbic acid destabilizes in the presence of water
  • its inclusion in an emulsion system often compromises the aesthetics of the emulsion due to the formation of a brown color.
  • Its inclusion in an anhydrous composition is also undesirable because of the composition's greasy and heavy texture.
  • the present invention relates topical water-in-oil emulsion (e.g., where the continuous oil phase contains the oil soluble agents and the discontinuous water phase contains the water soluble agents) comprising a silicone gel containing ascorbic acid.
  • the silicone gel protects the ascorbic acid from degradation, thereby, providing the consumer the benefit of the vitamin.
  • the emulsion of the present invention can have a significant (e.g., over 50%, by weight) water content.
  • the invention features a water-in- silicone emulsion comprising a silicone gel, wherein the silicone gel comprises a volatile liquid, a silicone polymer, and ascorbic acid.
  • the silicone polymer is polysilicone-11.
  • the volatile liquid is a silicone fluid (e.g., cyclomethicone) .
  • the silicone gel further comprises petrolatum and/or a second liquid (e.g., a silicone liquid such as dimethicone) .
  • the silicone gel further comprises a porous silica (e.g., having a pore volume of 0.1 to about 1 ml/g, a particle diameter of between 1 - 20 microns, and/or an oil absorbence of between 10-500 ml/lOOg) .
  • a porous silica e.g., having a pore volume of 0.1 to about 1 ml/g, a particle diameter of between 1 - 20 microns, and/or an oil absorbence of between 10-500 ml/lOOg
  • the silicone gel comprises by weight: (a) about 0.01% to about 99% (e.g., about 10% and 90%) of the volatile liquid (e.g., cyclomethicone);
  • silicone polymer e.g., polysilicone-11
  • the silicone gel further comprises by weight: (d) about 0.001% to about 60% (e.g., about 0.001% to about 30%) of petrolatum and/or (e) about 0.001% to about 50% (e.g., about 0.001% to about 30%) of porous silica.
  • the emulsion (e.g., within the water phase, oil phase, or the silisone gel) further comprises a dermatologically active agent such as a retinoid (e.g., retinol, retinal, retinoic acid, retinyl acetate, and retinyl palmitate) or an ⁇ -hydroxy acid, a ⁇ -hydroxy acid, or poly-hydroxy acid such as glycolic acid, salicylic acid, lactic acid, citric acid, malic acid, and azaleic acid.
  • a dermatologically active agent such as a retinoid (e.g., retinol, retinal, retinoic acid, retinyl acetate, and retinyl palmitate) or an ⁇ -hydroxy acid, a ⁇ -hydroxy acid, or poly-hydroxy acid such as glycolic acid, salicylic acid, lactic acid, citric acid, malic acid, and azaleic acid.
  • a dermatologically active agent such as a retinoi
  • the water-in-oil emulsion comprises by weight: (a) about 0.001% to about 50% (e.g., about 5% to about 50%) of the silicone gel; (b) about 0.001% to about 90% (e.g., about 5% to about 50%) of water; and (c) about 0.001% to about 50% of an oil such as a hydrocarbon or silicone liquid.
  • the hydrocarbon is a member selected from the group consisting of branched or straight chained C8-C40 (e.g., C12—20) hydrocarbons (e.g., isododecane, isoparaffins, isoeicosane, and isohexadecane) and said silicone liquid is selected from the group consisting of cyclomethicone and dimethicone, or mixtures thereof.
  • C8-C40 e.g., C12—20
  • silicone liquid is selected from the group consisting of cyclomethicone and dimethicone, or mixtures thereof.
  • the composition further comprises a sunscreen, e.g., about 0.001% to about 50% (e.g., about 0.001 to about 20%) of sunscreen (e.g., titanium dioxide, phenylbenzimidazole sulfonic acid, octyl methoxycinnamate, avobenzone, or mixtures thereof) .
  • sunscreen e.g., titanium dioxide, phenylbenzimidazole sulfonic acid, octyl methoxycinnamate, avobenzone, or mixtures thereof
  • the oil-phase and/or the water phase of the emulsion comprise an antioxidant (e.g., N- acetyl-L-cysteine) .
  • the present invention features method of preventing or treating skin disorders (e.g., protecting skin from photo-damage, preventing collagen breakdown, eliminating free radicals, stimulating collagen synthesis, reducing skin discoloration, evening skin tones, firming the skin, and reducing the signs of skin aging) , the method comprising applying to the skin (e.g., the hands or face) of a subject an effective amount of the above mentioned emulsion.
  • the emulsion is applied to the skin one to three times daily.
  • the present invention relates to a novel water-in- oil emulsion comprising a silicone gel that both stabilizes and delivers ascorbic acid.
  • the gel also possessing oil-absorbing (e.g., sebum absorbing) properties.
  • the silicone gel is made, in one embodiment, by dispersing oil swellable silicone polymer (e.g., polysilicone-11) in a volatile liquid (e.g., silicone fluid such as cyclomethicone) or a volatile liquid mixed with other ingredients (e.g., dimethicone and/or petrolatum) .
  • a volatile liquid e.g., silicone fluid such as cyclomethicone
  • other ingredients e.g., dimethicone and/or petrolatum
  • Ascorbic acid is then dispersed in the silicone gel, e.g., by either (i) adding ascorbic acid powder to the silicone gel and milling the mixture to ensure homogeneous distribution of the ascorbic acid in the gel or (ii) dissolving the ascorbic acid in a solvent (e.g., a polar solvent such as polyethylene glycols) and then uniformly dispersing the ascorbic acid solution in the silicone gel.
  • a solvent e.g., a polar solvent such as polyethylene glycols
  • Ascorbic acid is available from a number of commercial sources such as Roche in Parsippany, New Jersey.
  • a silicone gel containing ascorbic acid i.e., Gransil PSAA is also available from Grant Industries in Elmwood Park, NJ.
  • the silicone gel Upon spreading on skin (e.g., the hands or facial skin) , the silicone gel releases the volatile liquid, delivers ascorbic acid to the skin, and absorbs non- volatile excess skin oil present on the skin (e.g., the oil is absorbed by the oil -swellable silicone polymer and, if present, porous silica) .
  • the composition's ability to absorb sebum helps the skin maintain an environment that is less conducive to clogged pores, thereby, inhibiting the formation of comedones.
  • the silicone gel may also contain porous silica that further enhances the oil -absorbing properties of the gel.
  • the gel additionally has the ability to scatter incoming rays of light in all directions. By diminishing reflected light, the skin, thus, has a smooth matte appearance.
  • volatile refers to those liquids that have a measurable vapor pressure at ambient temperature.
  • volatile liquids include branched or straight chained hydrocarbons (e.g., C3-C20 hydrocarbons such as isoparaffins, isoeicosane, isohexadecane and isododecane) and silicone fluids.
  • volatile silicone fluids include the following: cyclic and linear polydimethylsiloxanes containing from about 3 to about 9 (e.g., from about 4 to about 5) silicone atoms such as cyclomethicones ; Dow Corning 200, Dow Coring 344, and Dow Corning 345 (manufactured by Dow Corning, Midland, MI) ; Silicone 7158 and 7207 (manufactured by Union Carbide, Houston, TX) ; SF 1202 (manufactured by General Electric) ; and S S-03314 (manufactured by SWS Silicones, Inc.) .
  • cyclomethicone refers to cyclotrisiloxane, cyclotetrasiloxane, cyclopentasiloxane, cyclohexasilxane, or mixtures thereof .
  • the silicone polymers of the present invention may have an average molecular weight in excess of 10,000
  • silicone polymers include crosslinked siloxane (ew.g., dimethicone or a dimethicone derivative) copolymers such as stearyl methyl-dimethyl siloxane copolymer (Gransil SR-CYC, available from Grant Industries) ; Polysilicone-11 (i.e., a crosslinked silicone rubber formed by the reaction of vinyl terminated silicone and ethylhydrodimethyl siloxane in the presence of cyclomethicone) , cetearyl dimethicone/vinyl dimethicone crosspolymer (i.e., a copolymer of cetearyl dimethicone crosslinked with vinyl dimethyl polysiloxane) , dimethicone/phenyl vinyl dimethicone crosspolymer (i.e., copolymer of dimethylpolysiloxane crosslinked with phenyl vinyl dimethylsiloxane).
  • crosslinked siloxane ew.
  • the silicone gels may also be purchased from commercial suppliers such as Grant Industries. Examples of such gels include cyclomethicone (and) polysilicone-11 (Gransil GCM5) , cyclotetrasiloxane (D4) (and) petrolatum (and) polysilicone-11 (Gransil PS-4) , cyclopentasiloxane (D5) (and) petrolatum (and) polysilicone-11 (Gransil PS-5) , cyclopentasiloxane (D5) (and) dimethicone (and) polysilicone-11 (Gransil DMCM-5) , cyclotetrasiloxane (D4) (and) dimethicone (and) polysilicone-11 (Gransil DMCM-4) , polysilicone-11 (and) isododecane (Gransil IDS) , and cyclomethicone (and) polysilicone-11 (and) petrolatum (and) phytosphin
  • the water-in-oil emulsion may also contain other cosmetically acceptable agents that are numerous and varied, but are also well known to one skilled in the art.
  • the emulsion i.e., the composition
  • the emulsion comprises one or more of the members selected from the group consisting of acidifying agents, alkalizing agents, aerosol propellants, antimicrobial agents, antioxidants, buffering agents, chelating agents, coloring additives, dermatologically active agents, dispersing agents, emollients, emulsifying agents, humectants, fragrances, masking agents, preservatives, sugars, sunscreen agents, surfactants, suspending agents, and thickening agents. These ingredients are discussed below.
  • Acidifying and alkalizing agents are added to obtain the desired pH of the water phases of the composition.
  • acidifying agents included acetic acid, citric acid, glacial acetic acid, malic acid, and proprionic acid.
  • alkalizing agent include edetol , potassium carbonate, potassium hydroxide, sodium borate, sodium carbonate, and sodium hydroxide.
  • Other acidifying or alkalizing agents are listed on page 1653 of the ICT Handbook. Aerosol propellants are used when the composition is to be administered as an aerosol under pressure.
  • aerosol propellants include halogenated hydrocarbons such as dichlorodifluoromethane, dichlorotetrafluoroethane, and trichloromonofluoromethane, nitrogen, and volatile hydrocarbons such as butane, propane, isobutane, or mixtures thereof.
  • halogenated hydrocarbons such as dichlorodifluoromethane, dichlorotetrafluoroethane, and trichloromonofluoromethane
  • nitrogen such as butane, propane, isobutane, or mixtures thereof.
  • volatile hydrocarbons such as butane, propane, isobutane, or mixtures thereof.
  • Other propellants are listed on page 1655 of the ICT Handbook.
  • Anti-microbial agents are used when the area that the composition is to be applied is prone to microbial infection, e.g., by bacteria, fungal, or protozoa.
  • examples of such agents include benzyl alcohol, chlorobutanol , phenylethyl alcohol, phenylmercuric acetate, potassium sorbate, and sorbic acid, benzoic acid, butyl paraben, ethyl paraben, methyl paraben, propyl paraben, and sodium benzoate.
  • Other antimicrobial agents are listed on page 1612 of the ICT Handbook .
  • Antioxidants are used to protect ingredients (e.g., ascorbic acid in the silicone gel) of the composition from oxidizing agents that are included within or come in contact with the composition.
  • antioxidants include water soluble antioxidants such as grape seed extract, camellia oleifera extract, N-acetyl- L-cysteine, ascorbic acid, sodium sulfite, sodium formaldehyde, isoascorbic acid, cysteine hydrochloride, 1, 4-diazobicyclo- (2 , 2 , 2) -octane, and mixtures thereof.
  • oil -soluble antioxidants examples include ascorbyl palmitate, butytlated hydroxyanisole, butylated hydroxytoluene, potassium propyl gallate, octyl gallate, dodecyl gallate, phenyl - ⁇ -napthyl-amine, and tocopherols such as ⁇ -tocopherol .
  • Other antioxidants are listed on pages 1612-13 of the ICT Handbook.
  • Buffering agents are used to maintain an established pH of the water phase of the composition.
  • buffering agents included triethanolamine sodium citrate, calcium acetate, potassium metaphosphate, potassium phosphate monobasic, and tartaric acid.
  • Other buffering agents are listed on page 1653 of the ICT Handbook.
  • Chelating agents are used to maintain the ionic strength of the composition and/or bind to destructive compounds and metals that are included within or come in contact with the composition.
  • Examples of chelating agents included dihydroxy ethyl glycine, citric acid, tartaric acid, edatate dipotassium, edetate disodium, edetic acid, and ethylenediamine tetracetic acid (EDTA) and its salts (e.g., tetrasodium EDTA).
  • EDTA ethylenediamine tetracetic acid
  • Other chelating agents are listed on page 1626 of the ICT Handbook. Coloring additives are used to add color to the composition.
  • coloring additives examples include titanium dioxide, FDC colors such as Yellow #5, yellow iron oxide, red iron oxide, black iron oxide, caramel, carmine, fluorescein derivatives, methoxsalen, trioxsalen, carbon black, azo dyes, anthraquinone dyes, blue azulenes, guajazulene, chamuzulene, erythrosin, bengal rose, phloxin, cyanosin, daphinin, eosin G, cosin 10B, and Acid Red 51.
  • FDC colors such as Yellow #5, yellow iron oxide, red iron oxide, black iron oxide, caramel, carmine, fluorescein derivatives, methoxsalen, trioxsalen, carbon black, azo dyes, anthraquinone dyes, blue azulenes, guajazulene, chamuzulene, erythrosin, bengal rose, phloxin, cyanosin, daphinin, eos
  • Dermatologically active agents include agents for treating wound healing, inflammation, acne, psoriasis, cutaneous aging, skin cancer, impetigo, herpes, chickenpox, dermatitis, pain, itching, and skin irritation.
  • dermatologically active agents include hydrocortisone, dexamethesone, panthenol , phenol, tetracycline hydrochloride, yeast, hexylresorcinol , lamin, kinetin, betamethasone, triamcinolone, fluocinolone, methylprednisolone, retinoids such as retinol and retinoic acid, dapsone, sulfasalazine, resorcinol , salicylic acid, benzoyl peroxide, erythromycin-benzoyl peroxide, erythromycin, clindamycin, mupirocin, griseofulvin, azoles such as miconazole,
  • dispersing and suspending agents examples include quarternium-18 hectorite, polyhydroxy stearic acid, poligeenan and silicon dioxide. Other dispersing and suspending agents agents are listed on page 1690-91 of the ICT Handbook.
  • Emollients are agents that soften and smooth the skin.
  • emollients include hydrocarbon oils and waxes (e.g., natural and synthetic waxes) such as mineral oil, petrolatum, microcrystaline wax, polyethylene, triglyceride esters such as those of castor oil, cocoa butter, safflower oil, cottonseed oil, corn oil, olive oil, cod liver oil, almond oil, avocado oil, palm oil, sesame oil, squalene, and soybean oil, acetylated monoglycerides, ethoxylated glycerides, fatty acids, alkyl esters of fatty acids, alkenyl esters of fatty acids, fatty alcohols, fatty alcohol ethers, ether-esters, lanolin and derivatives of lanolin, polyhydric alcohol esters, wax esters such as beeswax, vegetable waxes, phospholidds, and sterols.
  • Other emollients are listed on
  • Emulsifying agents are used for preparing emulsions of the present invention.
  • emulsifying agents used for preparing water-in-oil emulsions include cyclomethicone (and) dimethicone copolyol , cetyl dimethicone copolyol, polyglyceryl-4 isostearate, hexyl laurate, PEG-30 dipolyhydroxystearate, and PEG-40 sorbitan peroleate.
  • Other emulsion are listed on pages 1679-87 of the ICT Handbook.
  • Emulsion stabilizers are listed on pages 1634-35 of the ICT Handbook.
  • Humectants are agents that promote the retention of moisture, e.g., moisturizers.
  • humectants include sorbitol, matricaria extract, aloe barbadensis gel, glycerin, glycereth 5 lactate, glycereth 7 triacetate, glycereth 7 diisononoate, hexanetriol, hexylene glycol, propylene glycol , dipropylene glycol , alkoxylated glucose, D-panthenol, 1-2-pantandiol , 2- methyl-1 , 3-propanediol , and derivatives thereof, and hyaluronic acid.
  • Other humectants are listed on pages 1661-62 of the ICT Handbook.
  • fragrances examples include peppermint, rose oil, rose water, aloe vera, clove oil, menthol, camphor, eucalyptus oil, and other plant extracts.
  • Certain fragrances may require a solubilizer, e.g., PPG-5- ceteareth-20.
  • PPG-5- ceteareth-20 may be used.
  • masking agents may be used.
  • An example of a masking agent includes ethylene brassylate.
  • Other fragrances and masking agents are listed on pages 1639- 40 of the ICT Handbook.
  • Preservatives are used to protect the composition from degradation.
  • preservatives include liquipar oil, phenoxyethanol , methyl paraben, propyl paraben, butyl paraben, isopropyl paraben, isobutyl paraben, diazolidinyl urea, imidazolidinyl urea, diazolindyl urea, benzalkonium chloride, benzethonium chloride, phenol, and mixtures thereof (e.g., the paraben mixture Liquipar Oil) .
  • Other preservatives are listed on pages 1654-55 of the ICT Handbook.
  • sugars include monosaccharides, disaccharides, and polysccharides such as glucose, xylose, fructose, reose, ribose, pentose, arabinose, allose, tallose, altrose, mannose, galactose, lactose, sucrose, erythrose, glyceraldehyde, or any combination thereof .
  • Sunscreen agents are agents used to block or reduce the amount of ultraviolet radiation impinging on the skin (e.g., by absorption, scattering, and reflection of the ultraviolet radiation).
  • Segarin, et al . , Cosmetics Science and Technology, Chapter VIII, pages 189, et seq. discloses numerous examples of sunscreen agents.
  • sunscreen agents include both organic compounds and their salts such as phenylbenzimidazole sulfonic aicd, octyl methoxycinnamate, octyl salicylate, benzophenone-3 homosalate, octocrylene, avobenzone, and menthyl anthranilate, as well as inorganic particulate materials such as zinc oxide and titanium dioxide.
  • sunscreen agents are listed on page 1672 of the ICT Handbook.
  • the composition will contain from about 1% to about 50%, by weight, of sunscreen agent (s) .
  • the exact amounts will vary depending on the sunscreen used and the desired sun-protection factor (SPF) , e.g., and SPF of at least 15 or an SPF of at least 30.
  • SPF sun-protection factor
  • Surfactants are agents used to stabilize multi- component compositions, e.g., used as wetting agents, antifoam agents, emulsifiers, dispersing agents, and penetrants.
  • surfactants include methyl gluceth 20, decyl polyglucoside, lapyrium chloride, laureth 4, laureth 9, monoethanolamine, nonoxynol 4, nonoxynol 9, nonoxynol 10, nonoxynol 15, nonoxynol 30, poloxalene, polyoxyl 8, 40, and 50 stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, polysorbate 80, and polysorbate 85, sodium lauryl sulfate, sorbitan and its derivatives.
  • Other surfactants are listed on page 1672-90 of the ICT Handbook .
  • the emulsion that may be in a number of different delivery forms, e.g., a spray, mist, aerosol, shampoo, hair conditioner, mousse, semi-solid cream, liquid lotion, gel, or other suitable forms intended to be applied to the skin of a subject (e.g., a human) .
  • Water-in-oil emulsions e.g., ratio of about 8:1 to about 1:100 such as about 3:1 to about 1:10 of water to oil
  • the actual ratio of the two phases will depend on the consistency of the desired final product.
  • the viscosity of the compositions of the present invention may be different dependent upon the type of formulation being prepared, e.g., a liquid formulation will have a lower viscosity than a cream formulation. Typically, the viscosity of liquid formulations of the present invention will range from 5,000 to 25,000 cps.
  • Bulking agents may be used to increase the viscosity of the composition. Examples of bulking/thickening agents are talc, quaternium-18 hectorite, and paraffin wax. Other bulking agents are listed on page 1625-26 of the ICT Handbook. Other viscosity increasing agents are listed on pages 1693-97 of the ICT Handbook. Viscosity decreasing agents are listed on pages 1692-92 of the ICT Handbook.
  • the emulsion of the present invention may be prepared using methodology that is well known by an artisan of ordinary skill (e.g., by using well-known mixing and blending procedures) .
  • each phase of the emulsion may be separately prepared with all of the components contained in their appropriate phases.
  • the emulsion is then formed by adding one phase to the other phase with agitation.
  • the emulsion of the present invention may be packaged in a container that is well known by an artisan of ordinary skill.
  • the emulsion is preferably packaged in a container that minimizes exposure to oxygen (e.g., aluminum or laminate tubes) .
  • the tubes may be purged with an inert gas, such as nitrogen or argon, before sealing.
  • compositions of the present invention can be prepared in an analogous manner by a person of ordinary skill in the art .
  • Quaternium-18 hectorite (Bentone 38CG; Rheox, Hightstown, NJ) ; Cetyl Dimethicone Copolyol (and) polyglyceryl-4 isostearate (and) hexyl laurate (Abil WE- 09); Goldschmidt, Hopewell, NJ) ; Butylene Glycol (and) water (and) camellia oleifera extract (Actiquench GTB-20; Active Organics, Dallas, TX) ; and Cyclomethicone (and) Petrolatum (and) Polysilicone-11 (and) Ascorbic Acid (weight percentages between the ingredients as follows- (70:15:10:5)- Gransil PSAA or (65:15:15:5)- Gransil PSAA15-05 MV) , Grant Industries, Elmwood Park, NJ) . .
  • the cyclomethicone used the silicone gel was cyclotetratasiloxane, but other
  • phase A quaternium-18 hectorite was homogeneously dispersed in the isohexadecane in the main closed kettle.
  • a Krieger or Fryma type kettle may be used in order to draw a vacuum during processing to protect the ascorbic acid from oxidation.
  • the remainder of the Phase A ingredients were then added to the main kettle.
  • the resulting mixture was heated to 65°C until the paraffin wax melted.
  • the mixture was then cooled to 45°C ("Phase A Mixture" ) .
  • Phase B ingredients were combined in a second kettle, mixed until homogenous, and heated to 45°C ("Phase B Mixture”) .
  • the Phase B Mixture was then added to the main kettle containing the Phase A Mixture and allowed to mix until the emulsion formed.
  • the resulting mixture was then homogenized with a Gifford-Wood homogenizer (Model IL, Hudson, NH) until a glossy white cream formed (“Phase AB Mixture” ) .
  • the Phase AB Mixture was cooled to 50°C, and tocopherol was then added to the mixture.
  • the resulting Composition 1 had a 1% ascorbic acid activity, a viscosity of 55,000 cps, and a sunscreen activity estimated at SPF 15.
  • Butylene Glycol and water (and) grape seed extract (Actiphyte Grape Seed BG50P; Active Organics, Dallas, TX) ; and N-acetyl-L-cysteme (Tanabe USA, San Diego, CA) .
  • This Composition 2 was manufactured according to the procedure set forth m Example 1. This composition contains various antioxidants in both the water and oil phases. It also contains an artificial yellow color. No discoloration of the cream was observable following one month of accelerated stability at either 40°C or 50°C. Composition 2 also had a 1% ascorbic acid activity, a viscosity of 20,000 cps, and a sunscreen activity estimated at SPF 15.
  • This Composition 3 was manufactured according to the procedure set forth in Example 1.
  • the resulting Composition 1 had a higher level of ascorbic acid activity (i.e., 2%), a viscosity of 190,000 cps, and a sunscreen activity estimated at an SPF 15.
  • Camellia Oleifera Extract was purchased as Green Tea Extract from Dragoco, Totowa, NJ.
  • This Composition 4 was manufactured according to the procedure set forth in Example 1, but isododecane was used in place of isohexadecane.
  • This composition contains avobenzone (Parsol 1789, Roche, Parsippany, NJ) for additional UVA protection.
  • the addition of C12-15 akyl benzoate assists in the solubility of the avobenzone.
  • the resulting in Composition 4 had a 1% ascorbic acid activity, a viscosity of 14,000, and a sunscreen activity estimated SPF 15.
  • the retinol (and) polysorbate 20 was purchased from BASF m Mt. Olive, NJ.
  • This Composition 5 was manufactured according to the procedure set forth in Example 1, but isododecane was used instead of isohexadecane.
  • the resulting Composition 5 contained retinol for enhanced skin conditioning properties.
  • the Composition also had 1 % ascorbic acid activity, a viscosity of 31,000, and a sunscreen activity estimated at SPF 15.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dermatology (AREA)
  • Cosmetics (AREA)

Abstract

L'invention concerne une émulsion eau dans huile comprenant un gel de silicone, lequel contient un liquide volatil, un polymère silicone et de l'acide ascorbique. Elle concerne également des procédés d'utilisation d'une telle émulsion dans le traitement des affections de la peau.
PCT/US2000/013810 1999-05-28 2000-05-19 Emulsion eau dans huile comprenant un gel de silicone contenant de la vitamine c WO2000072817A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU51461/00A AU5146100A (en) 1999-05-28 2000-05-19 Water-in-oil emulsion comprising a silicone gel containing vitamin

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US32252699A 1999-05-28 1999-05-28
US09/322,526 1999-05-28

Publications (1)

Publication Number Publication Date
WO2000072817A1 true WO2000072817A1 (fr) 2000-12-07

Family

ID=23255274

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/013810 WO2000072817A1 (fr) 1999-05-28 2000-05-19 Emulsion eau dans huile comprenant un gel de silicone contenant de la vitamine c

Country Status (2)

Country Link
AU (1) AU5146100A (fr)
WO (1) WO2000072817A1 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1216687A3 (fr) * 2000-12-22 2003-04-02 Mibelle AG Cosmetics Agent traitant pour les cheveux
WO2003053372A1 (fr) * 2001-12-19 2003-07-03 Dow Corning Corporation Stabilisation des vitamines dans des emulsions eau dans l'huile de silicone (e-h)
EP1704853A2 (fr) * 2005-03-24 2006-09-27 Neutrogena Corporation Composition d'émulsion du type eau-dans-silicone
WO2006131401A2 (fr) * 2005-06-10 2006-12-14 Galderma S.A. Methode de liberation controlee d'un medicament a travers la peau
EP1745773A1 (fr) * 2005-07-11 2007-01-24 L'Oréal Composition photoprotectrice comprenant une phase aqueuse et une cire apolaire de bas point de fusion
EP1904021A1 (fr) * 2005-07-11 2008-04-02 Make-up Art Cosmetics Inc. Compositions cosmetiques a emulsion eau dans silicone instables, de faible viscosite et leurs procedes d'utilisation
CN100428923C (zh) * 2003-10-06 2008-10-29 株式会社资生堂 外用组合物
WO2009112492A2 (fr) * 2008-03-10 2009-09-17 Chanel Parfums Beaute Compositions d’émulsions cosmétiques eau dans huile
US7772214B2 (en) 2000-07-10 2010-08-10 The Procter & Gamble Company Emulsion cosmetic compositions comprising an emulsifying crosslinked siloxane elastomer
US7776348B2 (en) 2002-06-26 2010-08-17 L'oreal S.A. Water-in-oil emulsion foundation
US7959935B2 (en) * 2002-05-03 2011-06-14 Children's Hospital Medical Center Simulated vernix compositions for skin cleansing and other applications
CN103142438A (zh) * 2013-03-21 2013-06-12 上海滇虹药业有限公司 一种水包油乳膏及其制备方法
WO2015170063A1 (fr) * 2014-05-07 2015-11-12 The Boots Company Plc Émulsion eau-dans-huile pour le soin de la peau

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5623017A (en) * 1996-02-08 1997-04-22 Dow Corning Corporation Clear silicone gels
EP0827983A2 (fr) * 1996-09-05 1998-03-11 General Electric Company Gels élastomères contenant des silicones volatiles à bas poids moléculaire
WO1999024011A1 (fr) * 1997-11-07 1999-05-20 Howard Murad Compositions pharmaceutiques stables comprenant de l'acide ascorbique et procedes se rapportant a leur utilisation

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5623017A (en) * 1996-02-08 1997-04-22 Dow Corning Corporation Clear silicone gels
EP0827983A2 (fr) * 1996-09-05 1998-03-11 General Electric Company Gels élastomères contenant des silicones volatiles à bas poids moléculaire
WO1999024011A1 (fr) * 1997-11-07 1999-05-20 Howard Murad Compositions pharmaceutiques stables comprenant de l'acide ascorbique et procedes se rapportant a leur utilisation

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7772214B2 (en) 2000-07-10 2010-08-10 The Procter & Gamble Company Emulsion cosmetic compositions comprising an emulsifying crosslinked siloxane elastomer
EP1216687A3 (fr) * 2000-12-22 2003-04-02 Mibelle AG Cosmetics Agent traitant pour les cheveux
US6843984B2 (en) 2000-12-22 2005-01-18 Mibelle Ag Cosmetics Hair treatment products
US6861061B2 (en) 2001-12-19 2005-03-01 Dow Corning Corporation Stabilization of vitamins in water-in silicone oil (W/O) emulsions
WO2003053372A1 (fr) * 2001-12-19 2003-07-03 Dow Corning Corporation Stabilisation des vitamines dans des emulsions eau dans l'huile de silicone (e-h)
US7959935B2 (en) * 2002-05-03 2011-06-14 Children's Hospital Medical Center Simulated vernix compositions for skin cleansing and other applications
US7776348B2 (en) 2002-06-26 2010-08-17 L'oreal S.A. Water-in-oil emulsion foundation
CN100428923C (zh) * 2003-10-06 2008-10-29 株式会社资生堂 外用组合物
EP1704853A2 (fr) * 2005-03-24 2006-09-27 Neutrogena Corporation Composition d'émulsion du type eau-dans-silicone
EP1704853A3 (fr) * 2005-03-24 2007-01-24 Neutrogena Corporation Composition d'émulsion du type eau-dans-silicone
WO2006131401A2 (fr) * 2005-06-10 2006-12-14 Galderma S.A. Methode de liberation controlee d'un medicament a travers la peau
WO2006131401A3 (fr) * 2005-06-10 2007-03-15 Galderma Sa Methode de liberation controlee d'un medicament a travers la peau
AU2006256860B2 (en) * 2005-06-10 2012-04-19 Galderma S.A. Controlled release of a drug through skin on the basis of a topical composition comprising a drug, a film-forming silicone and at least one volatile solvent
CN101247787B (zh) * 2005-06-10 2011-10-05 盖尔德玛公司 以包含药物、成膜聚硅氧烷和至少一种挥发性溶剂为基础的经皮药物的控制释放
EP1745773A1 (fr) * 2005-07-11 2007-01-24 L'Oréal Composition photoprotectrice comprenant une phase aqueuse et une cire apolaire de bas point de fusion
EP1904021A4 (fr) * 2005-07-11 2011-06-08 Make Up Art Cosmetics Inc Compositions cosmetiques a emulsion eau dans silicone instables, de faible viscosite et leurs procedes d'utilisation
JP2009500450A (ja) * 2005-07-11 2009-01-08 メイク−アップ アート コスメティクス インコーポレーテッド 低粘性の不安定なシリコーン中水型エマルジョン化粧用組成物およびその使用方法
EP1904021A1 (fr) * 2005-07-11 2008-04-02 Make-up Art Cosmetics Inc. Compositions cosmetiques a emulsion eau dans silicone instables, de faible viscosite et leurs procedes d'utilisation
US8282947B2 (en) 2005-07-11 2012-10-09 Make-up Art Cosmetics, Inc. Low viscosity, unstable water-in-silicone emulsion cosmetic compositions and methods of use thereof
WO2009112492A3 (fr) * 2008-03-10 2010-04-15 Chanel Parfums Beaute Compositions d’émulsions cosmétiques eau dans huile
WO2009112492A2 (fr) * 2008-03-10 2009-09-17 Chanel Parfums Beaute Compositions d’émulsions cosmétiques eau dans huile
US8597628B2 (en) 2008-03-10 2013-12-03 Chanel Parfums Beaute Cosmetic water-in-oil emulsion compositions
CN103142438A (zh) * 2013-03-21 2013-06-12 上海滇虹药业有限公司 一种水包油乳膏及其制备方法
WO2015170063A1 (fr) * 2014-05-07 2015-11-12 The Boots Company Plc Émulsion eau-dans-huile pour le soin de la peau
CN106456527A (zh) * 2014-05-07 2017-02-22 博姿有限公司 护肤用油包水乳液
JP2017514919A (ja) * 2014-05-07 2017-06-08 ザ ブーツ カンパニー ピーエルシーＴｈｅ Ｂｏｏｔｓ Ｃｏｍｐａｎｙ Ｐｕｂｌｉｃ Ｌｉｍｉｔｅｄ Ｃｏｍｐａｎｙ スキンケア用油中水型エマルション

Also Published As

Publication number Publication date
AU5146100A (en) 2000-12-18

Similar Documents

Publication Publication Date Title
CA2374442C (fr) Gel de silicone contenant de l'acide salicylique
US20060159645A1 (en) Method of providing lubricious surfaces
AU2018204550B2 (en) Foaming skincare formulations
EP1060736B1 (fr) Mousse auto-bronzant
CA2311696C (fr) Composition de bronzage renfermant du carmin
JP2008088188A (ja) 紫外光の傷害作用からの高効率皮膚保護を備える組成物
WO2002056852A1 (fr) Produits cosmetiques
KR20060014396A (ko) 겔 네트워크 중 활성제를 포함하는 개인 케어 제품
MXPA04002645A (es) Composiciones de filtro solar.
WO2005065136A2 (fr) Émulsions huile dans silicone et compositions en contenant
US20100092412A1 (en) Self tanning compositions containing dihydroxyacetone, a retinoid and ascorbic acid glucoside as a stabilizer
JP4072296B2 (ja) アスコルビン酸を安定化するためのシリコーンゴムの使用およびこれらの成分を含有する新規組成物
WO2000072817A1 (fr) Emulsion eau dans huile comprenant un gel de silicone contenant de la vitamine c
WO2014184315A1 (fr) Composition cosmétique comprenant une huile silicone et des particules de polyméthacrylate de méthyle
WO2005107695A1 (fr) Compositions cosmetiques comprenant de la fecule de manioc
EP2095808A1 (fr) Compositions auto-bronzantes contenant des huiles
EP2068818B1 (fr) Compositions cosmétiques à base d'éthylène brassylate
US5976521A (en) Anti-acne cosmetic compositions
KR20240044028A (ko) 불소화합물, 비이온성 계면활성제 및 양쪽성 계면활성제를 안정적으로 포함하는 수중유형 화장료 조성물
WO2018081259A1 (fr) Excellentes propriétés de résistance à l'eau et d'amplification de spf avec une association de polyester-5 et de copolymère styrène/acrylates/méthacrylate d'ammonium
US20180116943A1 (en) Excellent Water Resistance and SPF Boosting Properties with an association of Polyester-5 and Styrene/Acrylates/Ammonium Methacrylate copolymer

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP