US20040009213A1 - Water-based delivery systems - Google Patents

Water-based delivery systems Download PDF

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Publication number
US20040009213A1
US20040009213A1 US10/388,371 US38837103A US2004009213A1 US 20040009213 A1 US20040009213 A1 US 20040009213A1 US 38837103 A US38837103 A US 38837103A US 2004009213 A1 US2004009213 A1 US 2004009213A1
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Prior art keywords
delivery system
dihydroxypropyl
acid
hydroxy
hydroxyethyl
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US10/388,371
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English (en)
Inventor
Thomas Skold
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Collagenex Pharmaceuticals Inc
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Collagenex Pharmaceuticals Inc
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Priority to US10/388,371 priority Critical patent/US20040009213A1/en
Assigned to COLLAGENEX PHARMACEUTICALS, INC. reassignment COLLAGENEX PHARMACEUTICALS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SKOLD, THOMAS
Publication of US20040009213A1 publication Critical patent/US20040009213A1/en
Priority to US10/957,320 priority patent/US20050129722A1/en
Priority to US12/082,406 priority patent/US20090081139A1/en
Priority to US12/290,455 priority patent/US8029810B2/en
Abandoned legal-status Critical Current

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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
    • A61K8/68—Sphingolipids, e.g. ceramides, cerebrosides, gangliosides
    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55—Phosphorus compounds
    • A61K8/553—Phospholipids, e.g. lecithin
    • 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
    • A61K8/63—Steroids; Derivatives thereof
    • 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
    • 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
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • 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
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • 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
    • 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
    • A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid

Definitions

  • the present invention relates to a novel topical and mucosal delivery systems for drugs or any other active substance.
  • the main demands on human skin are to prevent loss of water, and to prevent water and other matter of the environment from entering the body indiscriminately.
  • the human skin thus forms a selectively permissible physical barrier between the human body and its surroundings.
  • the barrier function has been shown to reside in the stratum corneum.
  • the stratum corneum is the topmost layer of the skin, and is built of corneocytes.
  • Corneocytes are cells that contain extensively cross-linked proteins, surrounded by a highly resistant cell envelope.
  • the corneocytes are embedded in a bed of specific lipid structures of long chain lipids. These long chain lipids are organized as bilamellar structures stacked on top of each other. The bilamellar structures fill the intercellular spaces between the corneocytes.
  • the skin has been described as a mosaic barrier model.
  • This model envisages barrier lipids to exist predominantly in crystalline (gel) form.
  • Such a form provides water impermeable domains, which are surrounded by so-called grain borders of lipids in a liquid crystalline state.
  • This arrangement provides an effective, water tight barrier that still allows a minute but controlled loss of water through the liquid crystalline interdomains. This controlled water loss is enough to keep the keratin of the stratum corneum hydrated.
  • the liquid character of the interdomain grain borders allows passage of hydrophilic and hydrophobic molecules on down-hill gradients, i.e. passage by passive diffusion.
  • Dermal delivery systems are compositions which deliver active substances to, or through, the skin. These compositions typically contain skin permeation enhancers. Permeation enhancers may induce structural transformations of the bilamellar structure in the liquid crystalline interdomain regions, and thus promote transdermal delivery of, for example, pharmacological substances.
  • Typical dermal delivery systems have an alcohol or petroleum base, with little consideration given to the biological properties of the vehicle itself.
  • emulsified fatty acids can inherit certain detergent properties if their structure is significantly altered from those in the normal skin.
  • the detergent properties can lead to disruption of the normal barrier function, which is counteractive to the potential benefit of the delivery system. Disruption of the normal barrier function often causes the stratum corneum to lose its natural potential to function properly as a barrier. As a result, the skin becomes either too dry or too permeable to environmental substances.
  • barrier ointments Other conventional delivery systems that are thought to protect the skin from harmful substances are barrier ointments.
  • the purpose of barrier ointments is to provide a film, and thereby create a layer which is impermeable to environmental substances. Due to the impermeability, though, these ointments both increase the body temperature of the treated body part, as well as prevent perspiration, and thus render an uncomfortable sensation.
  • the dermal delivery systems described above are not formulated to deliver a substance to, or through, the human skin without permanently disrupting the stratum corneum's natural barrier function.
  • the invention relates to a water-based delivery system for an active substance, characterized by enhancing skin barrier restoration in the stratum corneum comprising water, a fatty acid, cholesterol, and a ceramide.
  • the delivery system also comprises at least one skin lipid precursor.
  • the invention relates to delivery system for an active substance comprising water and lipophilic components, wherein the lipophilic components comprise fatty acids, cholesterol, and a ceramide/phospholipid portion, and wherein the lipophilic components are in the form of lipid particles, and gas spheres or vesicles.
  • This delivery system can also comprise at least one skin lipid precursor.
  • FIG. 1 is a diagram showing the gas spheres, lipid particles, vesicles and hydrophilic phase of the delivery systems.
  • FIG. 2 is a diagram showing the components of the gas spheres of the delivery systems.
  • FIG. 3 is a diagram showing the components of the lipid particles and of the vesicles of the delivery systems.
  • FIG. 4 is a diagram showing the location of active substances within the various microcompartments of the delivery systems.
  • the present invention provides an improved topical delivery system (skin preparation) formulated to deliver a substance to, or through, the human skin without permanently disrupting the stratum corneum's natural barrier function. Additionally, the topical delivery system of the present invention provides unique skin barrier restoration properties.
  • the topical delivery system of the present invention is a water-based formulation comprising hydrophilic and lipophilic components.
  • the delivery system comprises a water content exceeding 50%, such as more than 55%, 60%, 65%, 70%, 75%, 76%, 77%, 78%, 79%, 80%, 85%, 87%, 90%, 94%, 95% and 98%.
  • the water content is between 60-80%, more preferably, between 70 and 80%.
  • the topical delivery system is preferably designed, in its choice and composition of lipids, to resemble the normal lipid organization of the stratum corneum (horny layer), as much as possible.
  • the system blends with the lipids naturally present in the stratum comeum, and easily penetrates the lipid bilayer of the skin. In doing so, the system carries along with it one or more active substances to be administered.
  • the system enhances penetration of active substances into and/or through the stratum corneum, while the normal barrier properties of the stratum corneum are left intact, and/or are even functionally enhanced.
  • the lipophilic component (i.e. lipids) of the system comprises fatty acids, cholesterol and a ceramide/phospholipid portion.
  • the lipids are similar to those which make up the normal stratum comeum.
  • the preferred ratio of the ceramide/phospholipid portion:cholesterol:fatty acid is in the range of approximately 2:1:1.5 to approximately 2.95:0.5:0.5.
  • the ratio is approximately 2:1:1; more preferably the ratio is approximately 2.35:1:1.
  • the fatty acids of the present invention can be any fatty acid, mixtures of fatty acids, salts of fatty acids, or mixtures of fatty acids and salts of fatty acids.
  • the fatty acids can be saturated or unsaturated. Additionally, the fatty acids can comprise precursors of fatty acids. In a preferred embodiment, the fatty acids comprise ten, twelve, fourteen, sixteen, eighteen, twenty, twenty-two, or twenty-four carbon atoms, or any mixture of such fatty acids. A fatty acid mixture with a predominant portion of fatty acids which comprise a chain of sixteen or eighteen carbon atoms is most preferred.
  • the delivery system can be prepared from a mixture of fatty acids of the following composition: at most about 2% of a component comprising a chain of fourteen carbon atoms, between about 47 and about 52% of a component comprising a chain of sixteen carbon atoms, between about 43 and about 48% of a component comprising a chain of eighteen carbon atoms, and at most about 1% of a component comprising a chain of twenty carbon atoms.
  • Suitable saturated fatty acids for use in the delivery system include lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, and lignoceric acid.
  • suitable unsaturated fatty acids include oleic acid, palmitoleic acid, linoleic acid, linolenic acid, and arachidonic acid.
  • the delivery system contains an essential portion, such as about 90%, of such fatty acids.
  • the preferred fatty acids are the essential fatty acids (EFAs).
  • EFAs are essential for the plasma membrane formation of all cells. In keratinocytes, EFA deficiency makes cells hyperproliferative. Supplementation of EFAs reverses the hyperproliferation. EFAs also enhance lipid biosynthesis of the epidermis and provide lipids for the barrier formation of the epidermis.
  • the essential fatty acids are preferably chosen from linoleic acid, ⁇ -linolenic acid, homo- ⁇ -linolenic acid, columbinic acid, eicosa-(n-6,9,13)-trienoic acid, arachidonic acid, timnodonic acid, hexaenoic acid, and mixtures thereof.
  • the delivery system also comprises cholesterol, or derivatives of cholesterol such as, for example, lipid esters of cholesterol.
  • the ceramide/phospholipid portion can comprise 100% ceramide, 100% phospholipids, or any other percent combination of ceramide and phospholipids.
  • the ceramide/phospholipid portion can comprise 95% ceramide and 5% phospholipids, 90% ceramide and 10% phospholipids, 85% ceramide and 15% phospholipids, or 80% ceramide and 20% phospholipids.
  • the ceramide component of the delivery system can be any ceramide or any mixture of ceramides.
  • ceramides include pseudoceramides and neoceramides.
  • the ceramide may be any of ceramide 1-7; and/or mixtures thereof. 5 Some specific examples of ceramides include ceramide 1, ceramide 3, ceramide 4, ceramide 5, ceramide 6A, cerebrosides and ceramide 6B.
  • pseudoceramides include:
  • neoceramides include:
  • the phospholipid component may contain any phospholipid or mixtures of phospholipids.
  • the phospholipid component comprises phosphatidylcholine (PC).
  • PC phosphatidylcholine
  • Other examples of phospholipids include distearoylphosphatidylcholine (DSPC 18), phosphatidic acid, inositol phosphate, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, and phosphatidylethanolamine.
  • the phospholipid component can comprise one or more lysophospholipids.
  • Lysophospholipids are single chain phospholipids.
  • Examples of lysophospholipids include lysophosphatidylcholines, such as monopalmitoylphosphatidylcholine (MPPC); lysophosphatidylglycerols; lysophosphatidylethanolamines; lysophosphatidylinositols; lysophosphatidylserines; and lysophosphatidic acid. Mixtures of different types of phospholipids and/or lysophospholipids can also be used.
  • MPPC monopalmitoylphosphatidylcholine
  • lysophosphatidylglycerols lysophosphatidylglycerols
  • lysophosphatidylethanolamines lysophosphatidylinositols
  • the present system also comprises skin lipid precursors.
  • the lipid precursors include any compound that promotes in situ cholesterol, ceramide or sphingolipid synthesis.
  • the preferred lipid precursors are mevalonic acid, which promotes in situ cholesterol synthesis; and 25-hydroxycholecalciferol, which promotes in situ ceramide synthesis in the skin.
  • Other preferred precursors are palmitoyl CoA and serine, which together are converted to 3-ketosphinganine, which promotes in situ ceramide synthesis in the skin.
  • the overall content of lipid in the system can be maintained in a range as low as approximately 2-20%. Therefore, the water content of the delivery system can be as high as 80-98%.
  • the high water content enables the skin to “breathe” normally, and enhances its ability to restore its normal barrier function rapidly.
  • lipid precursors useful in the present invention include, for example: acylceramides; deoxyacetein cimifugoside, adapalene, adenosine, aloe derived lectins, 3-aminopropyl dihydrogen phosphate, anise extracts, ascorbic acid and derivatives thereof, ascorbyl palmitate, asiatic acid, benzoic acid derivatives, biotin, butanoyl betulinic acid, cathecholamines, coenzyme Q10, dehydrocholesterol, dehydroascorbic acid and derivatives thereof, estrogen and derivatives, eythrobic acid, genistein, lipoic acid, 4-methoxysalicylic acid, N-acetylcysteine, panthetine, pregnenolone and derivatives, retinal, retinoates, retinal, retinyl acetate, retinyl glucuronate, retinyl lino
  • an alkaline compound or buffer system
  • alkaline compounds include triethanolamine (TEA), sodium hydroxide, sodium acetate, and sodium bicarbonate.
  • buffer systems include carbonic acid/potassium carbonate, phosphoric acid/potassium phosphate, and acetic acid/sodium acetate.
  • the fatty acids of the final delivery system can be in a free state or can form a salt.
  • the portion of fatty acids which is in a free state is partially dependent on the pH of the formulation.
  • the level of free fatty acid increases as the pH of the formulation decreases.
  • the pH of the formulation can vary.
  • the pH of the formulation is about 6.5 to 7.8.
  • the delivery system comprises triethanolamine (TEA). It is preferred to adapt the molar ratio between the fatty acids and triethanolamine to enable a certain portion of the fatty acids in the final delivery system to form a triethanolaminium salt, while another portion of the acid exists as free fatty acid.
  • the delivery system is prepared from fatty acids and triethanolamine in which the molar ratio of the fatty acids to the triethanolamine is higher than about 2:1, preferably higher than about 3:1.
  • the delivery system comprises a combined content of a fatty acid, cholesterol, a ceramide/phospholipid portion, and skin lipid precursors between about 2-20%.
  • a preferred low end of this range is about 2%, 3%, 4%, 5%, 6%, 7% or 8%.
  • a preferred high end of this range is about 13%, 14%, 15%, 16%, 17%, 18%, 19% and 20%.
  • the amounts of the components of the delivery system are as follows: fatty acid: 0.5-10%; cholesterol: 0.5-10%; a ceramide/phospholipid portion: 0.005-20%; and lipid precursors: 0.000001-10%.
  • the formulation does not contain any irritating ingredients.
  • irritating ingredients include alcohols, such as isopropanol and ethanol; short chain fatty acids; and detergents.
  • the formulation contains less than 10% alcohol, more preferably less than 5% alcohol, most preferably less than 1% alcohol, and optimally no alcohol.
  • the temporary disarray in the lipid bilayer will temporarily break up the organized structure of the bilayer and create micelles of lipids with areas between them, or surrounding them, through which lipophobic/hydrophilic substances and/or compositions can enter through the stratum corneum.
  • the lipid composition of the formulation resembles the natural lipid composition of the skin, the so introduced new lipids will after a short time of creative chaos easily blend in with the natural lipid building stones of the lipid bilayer, and thus not permanently damage the barrier function of the skin.
  • the normal barrier function of the cornea stratum rapidly returns. (That is, the skin barrier restoration is rapid.)
  • the rapid return may be enhanced by the lipid precursors of the formulation.
  • the in situ promotion of cholesterol synthesis in the stratum corneum, the in situ promotion of ceramide synthesis in the stratum corneum, and/or the in situ promotion of sphingolipid synthesis in the stratum corneum may allow for the rapid skin barrier restoration.
  • a delivery system preferably comprises a combination of: Fatty Acid (C16-24) 0.5-10% Phospholipid 0.5-10% Cholesterol 0.5-7% Lipid precursor: 0.000001-10% Mevalonic acid and/or 25-Hydroxycholecalciferol Ceramide 0.005%-7%
  • Another preferred embodiment of the delivery system comprises: Fatty Acid (C16-24) 0.5-10% Phospholipid 0.5-10% Cholesterol 0.5-7% Lipid precursor: 0.000001-10% Mevalonic acid and/or 25-Hydroxycholecalciferol Ceramide 0.005%-7% Glycerine 0-5% Propylene glycol 0-48% PVP (e.g., M weight 40.000) 0-5% TEA 0-3%
  • An even more preferred embodiment of the delivery system comprises: Fatty Acid (C16-24) 2% Phospholipid 4.5% Cholesterol 2% Lipid precursor: 0.000001-10% Mevalonic acid and/or 1% or 0.01% 25-Hydroxycholecalciferol 0.015% or 0.0015% Ceramide 3 0.015% Glycerine 3% Propylene glycol 4% PVP (M weight 40.000) 2% TEA 0.5%
  • An even more preferred embodiment of the delivery system comprises: Fatty Acid (C16-24) 2% Phospholipid 4.5% Cholesterol 2% Lipid precursor: 0.000001-10% Mevalonic acid and/or 1% or 0.01% 25-Hydroxycholecalciferol 0.015% or 0.0015% Ceramide 3 0.015% Glycerine 3% Propylene glycol 4% PVP (M weight 40.000) 2% TEA 0.5% Ceramide 1 0.025%
  • the topical delivery system according to the present invention further comprises one or more cosmetically and/or therapeutically active substances.
  • Active substances are defined as agents other than emollients and other than ingredients that merely improve the physical characteristics of the formulation.
  • active substances include sunscreens, tanning agents, skin anti-wrinkling agents, anti-dandruff agents, anti-acne agents, hair growth stimulants and vitamins.
  • Therapeutically active substances include, but are not limited to, substances which treat conditions such as eczema, dry skin, itchy skin, fungal infection, acne, skin cancer, hair loss, louse infection, psoriasis, and skin lesions (i.e. wounds).
  • Therapeutically active substances also include substances for transdermal delivery, for example, interleukin, hormones, vaccines, nicotine, interferon, pain killers, peptides, proteins and vitamins.
  • Active substances also include steroid hormones.
  • Steroid hormones inhibit inflammation and hyperproliferation of the epidermis thus resulting in normalization of hypersensitive skin conditions.
  • steroid hormones include, but are not limited to, glucocorticoids, androgens and estrogens.
  • sunscreens include those materials commonly employed to block ultraviolet light.
  • Illustrative compounds are derivatives of PABA, cinnamate and salicylate.
  • octyl methoxycinnamate and 2-hydroxy-4-methoxybenzophenone also known as oxybenzone
  • Octyl methoxycinnamate and 2-hydroxy-4-methoxybenzophenone are commercially available under the trademarks, Parsol MCX and Benzophenone-3, respectively.
  • the exact amount of sunscreen employed in the systems can vary depending upon the degree of protection desired from the sun's UV radiation.
  • vitamins include vitamin A and vitamin E, preferably in the form of an ester of a fatty acid, such as vitamin A palmitate (retinyl palmitate) and vitamin E linoleate (tocopheryl linoleate).
  • esters of vitamins A and E may also be utilized, such as any of the fatty acids mentioned above and below.
  • Preservatives may also be included in the formulations of the present invention. Suitable preservatives include alkyl esters of p-hydroxybenzoic acid, hydantoin derivatives, propionate salts, and a variety of quaternary ammonium compounds. Particularly preferred preservatives of this invention are methyl paraben, propyl paraben, imidazolidinyl urea, sodium dehydroxyacetate and benzyl alcohol. Preservatives are typically used in amounts up to about 2% by weight of the formulation.
  • adjunct minor components may also be incorporated into the formulations of the present invention. These components may include thickeners, coloring agents, opacifiers and perfumes. For example, any thickening agent can be included in the formulation to adjust the viscosity of the formulation. Examples of suitable thickening agents include glycerol and xanthan gum. Some additional adjunct minor components include chalk, talc, Fullers earth, kaolin, starch, smectites clays, chemically modified magnesium aluminium silicate, organically modified montmorillonite clay, hydrated aluminium silicate, fumed silica, aluminium starch octenyl succinate and mixtures thereof. Amounts of these adjunct minor components may range anywhere from 0.001 up to 20% by weight of the formulation (i.e. composition).
  • the delivery system can be in any form, such as a cream, a lotion, a gel, and an aerosol foam.
  • the amount of certain adjunct minor components used in a particular formulation varies depending on the desired form of the delivery system, as would be known by a skilled artisan.
  • the amount of thickening agent used to prepare an aerosol foam formulation is about 10 to 20% of the amount used to prepare a cream formulation.
  • emulsifiers are added to an aerosol foam formulation, such as, for example, laureth 4.
  • the present invention provides a mucosal delivery system formulated to deliver a substance to, or through, a human mucous membrane without permanently disturbing the integrity of the mucous membrane.
  • the mucous membrane is the moist tissue that lines some organs and body cavities (such as nose, mouth, lungs, rectum, stomach and vagina) and secretes mucous.
  • the mucosal delivery system comprises the lipophilic and hydrophilic components, as described above. The particular formulations of the mucosal delivery systems are varied to accommodate the particular environment of the mucosa, as would be known by a skilled artisan.
  • the lipophilic components of the topical or mucosal delivery system form three types of particles: gas spheres, vesicles, and lipid particles. These three types of particles are within a hydrophilic phase (i.e. aqueous medium). See FIG. 1.
  • the gas spheres are lipid monolayers that enclose air bubbles. These monolayers are formed from the lipophilic components. Negatively charged carboxylate groups stud the outer surfaces of these gas spheres. See FIG. 2. Preferably, these gas spheres are approximately 1 ⁇ m to approximately 500 ⁇ m in diameter.
  • the vesicles are lipid bilayers enclosing a hydrophilic core. These bilayers are formed from the lipophilic components. Negatively charged carboxylate groups stud the inner and outer surfaces of the vesicles. See FIG. 3. The vesicles can range from approximately 0.02 ⁇ m to approximately 0.5 ⁇ m in diameter.
  • the lipid particles are lipid monolayers enclosing fatty acids. These monolayers are formed from the lipophilic components. See FIG. 3.
  • the lipid particles are less than approximately 1 to approximately 150 ⁇ m in diameter.
  • the lipid particles may be in the form of individual lipid particles, or the lipid particles may aggregate to form crystals.
  • the various particles of the delivery system provide microcompartments with different properties. Due to these different microcompartments, the delivery system can be used to deliver both hydrophilic and lipophilic active substances.
  • a water soluble active substance can be located in the hydrophilic core of the vesicles, or can be located in the hydrophilic phase of the system.
  • a lipid soluble active substance can be located within the monolayer of the gas spheres, within the bilayer of the vesicles, or within the monolayer or within the core of the lipid particles. See FIG. 4.
  • the delivery systems comprise three phases, i.e. a foam phase, a vesicle phase and a hydrophilic phase.
  • the foam phase comprises the gas spheres and the lipid particles.
  • the vesicle phase comprises the vesicles and the lipid particles.
  • the hydrophilic phase comprises water and hydrophilic components.
  • the delivery system is produced from three portions (i.e. fractions), in particular a hydrophilic portion and two lipophilic portions.
  • the two lipophilic portions comprise the lipophilic components as defined above. Both lipophilic portions are immersed in aqueous media.
  • One portion is made into the foam phase.
  • the other portion is made into the vesicle phase.
  • the foam phase portion and the vesicle phase portion can be in a ratio from about 1:7 to about 7:1.
  • the foam phase portion and the vesicle phase portion are approximately equal in amount.
  • the foam phase is formed by mixing the foam phase portion at about 65 to 85° C.
  • the pH is set to the range of about 5.5 to 8.2. The mixing is performed under conditions so as to allow gas spheres to form.
  • the vesicle phase is formed by gently mixing the vesicle phase portion at about 65 to 85° C.
  • the pH is set to the range of about 5.5 to 8.2.
  • the vesicle phase portion is homogenized. Homogenization can be accomplished with, for example, a high pressure homogenizer or a sonicator.
  • the pressure of the homogenizer can be set, for example, from about 10,000 to 40,000 psi.
  • the vesicle phase is produced under conditions which do not allow any gas to enter the formulation, such as in a vacuum.
  • the lipid particles, and/or lipid particle crystals form as a by-product of the formation of the foam phase and vesicle phase.
  • the foam phase or vesicle phase up to 30% of the lipophilic components can be in the form of lipid particles and/or lipid particle crystals.
  • the hydrophilic phase is formed by mixing together water soluble components with water (i.e. hydrophilic portion).
  • water soluble components include propylene glycol, glycerol, polyvinylpyrrolidone, and thickeners, e.g., xanthan gum.
  • the foam phase, vesicle phase and hydrophilic phases are mixed together. Preferably, an equal amount of each phase is used in the formulation.
  • the foam phase, vesicle phase and hydrophilic phases can be mixed together in any order.
  • the foam phase and the vesicle phase can be first mixed together, and then the resulting mixture can be mixed with the hydrophilic phase.
  • the foam phase can be first mixed with the hydrophilic phase, and then the vesicle phase can be added.
  • One or more active substances can be added to the foam phase portion, the vesicle phase portion, the hydrophilic portion, or a combination of these portions.
  • the specific components of a formulation, and the formulation process can be varied to obtain delivery systems which allow for different rates of the release, and degrees of penetration, of active substance(s).
  • the phase of the system in which an active substance is placed affects release and penetration rates.
  • a major portion of the active substance is placed within the vesicle phase portion.
  • the size of the vesicles can be controlled via the formulation process. For example, during processing, as the homogenizing pressure and duration increases, the vesicle size decreases.
  • An additional factor which affects release and penetration rates is the type of phospholipids used in the formulation. For example, penetration can be enhanced by including a greater portion of unsaturated phospholipids within the formulation.
  • phospholipids which include elevated levels of surface active single chain agents enhance penetration.
  • Surface active single chain agents at about a level of 2% to 10% of the phospholipids are considered to be at an elevated level.
  • Examples of surface active agents are lysophospholipids.
  • An example of a phospholipid formulation comprises 95% phosphatidylcholine and 1.2% lysophosphatidylcholine. Such a formulation is sold as EPIKURON® 200 SH.
  • a phospholipid formulation which provides enhanced penetration comprises 95% phosphatidylcholine and 3% lysophosphatidylcholine. Such a formulation is sold as EPIKURON® 200.
  • the concentration of free fatty acid is also an important parameter affecting penetration rates.
  • a relatively high level of free fatty acid enhances penetration of hydrophilic active substances.
  • Penetration rates can also be enhanced by the addition of certain adjuvants.
  • an anionic surfactant can be added to the foam phase portion.
  • incorporation of glyceryldilaurate into the vesicle bilayers creates more flexible vesicles which can enhance penetration.
  • Additional factors which affect release and penetration rates include: the ratio between the different lipid components; the ratio between the foam phase, the vesicle phase and the hydrophilic phase; and the ratio between the amounts of active substances within each phase.
  • the lipophilic components of the delivery system form only two of the above-defined particles. That is, the formulation comprises only the gas spheres and lipid particles; or the formulation comprises only the vesicles and lipid particles.
  • the delivery system is produced from a hydrophilic portion and a lipophilic portion.
  • the lipophilic portion is made either into the foam phase or the vesicle phase, as described above.
  • the vesicle phase is produced under conditions which do not allow any gas to enter the formulation, such as in a vacuum.
  • the foam phase or vesicle phase is mixed with the hydrophilic phase.
  • an equal amount of either the foam phase or vesicle phase, and the hydrophilic phase is used in the formulation.
  • the phospholipid, cholesterol, palmitic acid and ceramide components are mixed together with water, and agitated at a temperature of 70-80° C.
  • the following additional components are added: mevalonic acid lactone, 25-hydroxycholecalciferol, propylene glycol, glycerine, PVP, TEA added along with water, and sodium hydroxide.
  • Sodium hydroxide is added to adjust viscosity and stabilize the formulation. Water is then added, and the formulation is agitated well. The formulation is then cooled down.
  • An active substance can be dissolved in both the lipid phase and/or the water phase, depending on the solubility and concentration of the active substance.
  • the components are mixed and heated to the temperature range of 65 to 85° C. while gently stirring.
  • the pH is set to the range of 5.5 to 8.2 by the use of sodium hydroxide.
  • the resulting mixture is then homogenized. Homogenization can be accomplished by, for example, a homogenizer set at a high pressure (e.g. 10,000 to 40,000 psi); or by a sonicator.
  • the size of the vesicles is partially dependent upon how long the resulting mixture is agitated. For example, to obtain an average vesicle size of 0.140 ⁇ m, the resulting mixture is agitated for 60 minutes at about 70° C. The mixture is then allowed to cool to below 40° C.
  • the components are mixed and heated to the temperature range of 65 to 85° C. while stirring.
  • the pH is set to the range of 5.5 to 8.2 by the use of sodium hydroxide.
  • the composition is mixed vigorously for 1 minute. Mixing can be done with ULTRATURRAX® from IKA Werke, Janke & Kunkel GmbH & Co KG (Staufen, Germany). The composition is then allowed to cool to below 40° C.
  • the components are mixed and heated to the temperature range of 65 to 85° C. while stirring.
  • the pH is set to the range of 5.5 to 8.2 by use of sodium hydroxide. Once homogeneous, the composition is then allowed to cool to below 40° C.
  • the three fractions are mixed together in any order.
  • the foam fraction is added to the vesicle fraction and gently mixed.
  • the hydrophilic fraction is added.
  • the resulting mixture is gently blended for several minutes to obtain a homogeneous solution.
  • the delivery system of this example is in the form of a cream.
  • the total amount of xanthan gum in the final formulation is reduced from 2% to about 0.3%.
  • an emulsifier is added, such as laureth 4.
  • the emulsifier makes up about 0.7% of the final formulation.
  • enhancing skin barrier restoration can be measured by tape and/or acetone striping of stratum corneum skin lipid content before, during and after a treatment period with the present invention and other systems. Then HPLC analysis of skin lipid content of stratum corneum is conducted.

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US12/082,406 US20090081139A1 (en) 2002-03-13 2008-04-09 Water-based delivery systems
US12/290,455 US8029810B2 (en) 2002-03-13 2008-10-30 Water-based delivery systems

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070154403A1 (en) * 2006-01-05 2007-07-05 Thomas Skold Oral, Pulmonary and Transmucosal Delivery Composition
US20080152636A1 (en) * 2006-09-08 2008-06-26 Kaneka Corporation Composition containing reduced coenzyme Q10 and lysolecithin
WO2009101412A1 (fr) * 2008-02-13 2009-08-20 Cipla Limited Composition pharmaceutique topique
US20090226491A1 (en) * 2002-03-13 2009-09-10 Thomas Skold Water-based delivery systems
US20090247630A1 (en) * 2006-05-31 2009-10-01 Claire Mallard Dermatological compositions comprising at least one naphthoic acid compound and at least one film-forming agent and treatment of keratinization disorders therewith
KR101752312B1 (ko) * 2016-11-22 2017-06-29 주식회사 씨엠에스랩 사카라이드아이소머레이트, 하이드롤라이즈드루핀프로테인 및 각질세포간지질 모사체를 유효성분으로 담지한 베지클 및 이를 포함하는 피부 외용제 조성물
US10137073B2 (en) * 2016-01-02 2018-11-27 L'oreal Cosmetic compositions comprising ceramides and cholesterol
US10406088B2 (en) 2015-01-20 2019-09-10 TetraDerm Group LLC Versatile topical drug delivery vehicle and multifactorial tissue moisturizer that provides mucosal and skin barrier restoration

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2855049B1 (fr) * 2003-05-19 2006-07-21 Oreal Composition comprenant un precurseur de ceramide a base 6-hydroxy-sphingenine et un activeur de la voie des 6-hydroxylases, utilisation pour renforcer la fonction barriere de la peau
FR2855048B1 (fr) * 2003-05-19 2006-07-21 Oreal Composition comprenant un precurseur de ceramide a base phytosphingosine et un activeur de la voie des 4-hydroxylases, utilisation pour renforcer la fonction barriere de la peau
FR2855047B1 (fr) * 2003-05-19 2007-11-30 Oreal Composition comprenant une base sphingoide, un activateur de la voie des 4-et/ou des 6-hydroxylases et un acide gras, utilisation pour renforcer la fonction barriere de la peau
WO2006133829A2 (fr) * 2005-06-17 2006-12-21 Dsm Ip Assets B.V. Utilisation de 25-hydroxy-vitamine d3
JP5196833B2 (ja) * 2007-04-07 2013-05-15 ヤヱガキ醗酵技研株式会社 機能性食品素材とその製造方法
JP2009143897A (ja) * 2007-11-19 2009-07-02 Neochemir Inc ニキビ治療剤
NZ598906A (en) 2009-08-21 2014-08-29 Targeted Delivery Technologies Ltd Vesicular formulations
US8846723B2 (en) 2010-07-29 2014-09-30 Eastman Chemical Company Esters of O-substituted hydroxy carboxylic acids and preparations thereof
US8613940B2 (en) 2010-09-03 2013-12-24 Eastman Chemical Company Carbonate derivatives as skin care
US9163296B2 (en) 2011-01-25 2015-10-20 Tenaris Coiled Tubes, Llc Coiled tube with varying mechanical properties for superior performance and methods to produce the same by a continuous heat treatment
IT1403689B1 (it) 2011-02-07 2013-10-31 Dalmine Spa Tubi in acciaio ad alta resistenza con eccellente durezza a bassa temperatura e resistenza alla corrosione sotto tensioni da solfuri.
US8329938B2 (en) * 2011-02-21 2012-12-11 Eastman Chemical Company Hydroxyalkanoic acid and hydroxyalkanoice acid oligomer esters of retinol
GB201205642D0 (en) 2012-03-29 2012-05-16 Sequessome Technology Holdings Ltd Vesicular formulations
US9803256B2 (en) 2013-03-14 2017-10-31 Tenaris Coiled Tubes, Llc High performance material for coiled tubing applications and the method of producing the same
EP2789700A1 (fr) 2013-04-08 2014-10-15 DALMINE S.p.A. Tuyaux en acier sans soudure trempé et revenu à paroi lourde et procédé de fabrication des tuyaux d'acier
KR102197204B1 (ko) 2013-06-25 2021-01-04 테나리스 커넥션즈 비.브이. 고크롬 내열철강
CN105358134B (zh) * 2013-07-01 2019-05-31 株式会社新药 多层状乳化物结构的经皮药物传递系统
GB201313735D0 (en) * 2013-07-31 2013-09-11 Pro Bono Internat Trading Ltd Vesicles
JP2016529242A (ja) * 2013-07-31 2016-09-23 シクエスサム テクノロジー ホールディングス リミテッド ベシクル
KR101509582B1 (ko) * 2013-10-30 2015-04-14 한국콜마주식회사 감마-리놀레닉산 함유 항염증 및 피부보습 화장용 조성물
WO2015072564A1 (fr) * 2013-11-17 2015-05-21 株式会社メドレックス Agent transdermique en solution colloïdale
WO2015095010A2 (fr) * 2013-12-18 2015-06-25 International Flora Technologies, Ltd. Mimétiques de sébum humain dérivés de sources botaniques et procédés de préparation associés
JP6356446B2 (ja) * 2014-03-14 2018-07-11 富士フイルム株式会社 セラミド分散組成物
KR101455684B1 (ko) * 2014-04-29 2014-11-04 주식회사 씨엠에스랩 피부 장벽 개선 및 피부 재생 효과를 갖는 액정유화 화장료 조성물
ES2895910T3 (es) 2015-06-30 2022-02-23 Sequessome Tech Holdings Limited Composiciones multifásicas
KR101750238B1 (ko) * 2016-04-27 2017-06-27 (주)네오팜 항노화용 조성물
WO2018123003A1 (fr) * 2016-12-28 2018-07-05 小林製薬株式会社 Composition pour application externe destinée à l'inhibition de la mélanogenèse
KR101910962B1 (ko) * 2017-01-05 2018-10-24 주식회사 마크로케어 세라마이드 액정 조성물 및 이의 제조방법
US10434554B2 (en) 2017-01-17 2019-10-08 Forum Us, Inc. Method of manufacturing a coiled tubing string
TWI658840B (zh) * 2017-05-23 2019-05-11 大江生醫股份有限公司 乳化微脂粒組成物及其製備方法
KR102485259B1 (ko) 2018-03-27 2023-01-06 (주)아모레퍼시픽 모발 상태 개선용 액상 지질 복합 조성물
KR102078667B1 (ko) * 2018-06-18 2020-02-19 주식회사 고운세상코스메틱 7-데하이드로콜레스테롤, 콜레스테롤 및 스테아린산이 히알루론산-세라마이드 엔피 복합체의 내상에 봉입된 나노에멀젼을 함유하는 화장료 조성물 및 그의 제조방법
EP4119196A4 (fr) 2020-03-09 2024-04-17 Takasago Perfumery Co Ltd Agent favorisant la croissance de céramides
JP7406057B2 (ja) * 2021-03-03 2023-12-27 東洋ビューティ株式会社 外用微粒子カプセル製剤及び皮膚外用剤

Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4508703A (en) * 1982-02-17 1985-04-02 Parfums Christian Dior Production of pulverulent mixtures of lipidic and hydrophobic constituents
US5196190A (en) * 1990-10-03 1993-03-23 Zenith Technology Corporation, Limited Synthetic skin substitutes
US5206020A (en) * 1991-01-15 1993-04-27 Elizabeth Arden Company, Division Of Conopco, Inc. Synthetic pseudoceramide and cosmetic compositions thereof
US5468475A (en) * 1992-11-17 1995-11-21 Pola Chemical Industries Inc. Cosmetic composition with choline derivative
US5534499A (en) * 1994-05-19 1996-07-09 The University Of British Columbia Lipophilic drug derivatives for use in liposomes
US5631012A (en) * 1994-09-02 1997-05-20 Shanni; David Cosmetic preparations for moisturizing human skin containing specific lipids
US5733572A (en) * 1989-12-22 1998-03-31 Imarx Pharmaceutical Corp. Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles
US5776480A (en) * 1994-12-14 1998-07-07 L'oreal Cosmetic or dermatological composition containing a mixture of ceramides for moisturizing the skin
US5817856A (en) * 1995-12-11 1998-10-06 Yissum Research Development Company Of The Hebrew University Of Jerusalem Radiation-protective phospholipid and method
US5820873A (en) * 1994-09-30 1998-10-13 The University Of British Columbia Polyethylene glycol modified ceramide lipids and liposome uses thereof
US5993830A (en) * 1997-01-17 1999-11-30 Ponsus Ab Cosmetic skin preparation
US6153209A (en) * 1999-09-28 2000-11-28 The Procter & Gamble Company Article having a transferable breathable skin care composition thereon
US6497888B1 (en) * 1999-10-14 2002-12-24 L'ORéAL S.A. Process for limiting the penetration into the skin and/or the keratinous fibres of an active cosmetic and/or pharmaceutical agent
US6586000B2 (en) * 1999-12-16 2003-07-01 Dermatrends, Inc. Hydroxide-releasing agents as skin permeation enhancers
US6730288B1 (en) * 1998-09-11 2004-05-04 Connetics Australia Pty Ltd Mousse composition
US6824785B1 (en) * 2000-02-09 2004-11-30 C. Neil Kitson Skin treatment composition and methods of use
US6932963B2 (en) * 2000-06-23 2005-08-23 Nicholas V. Perricone Treatment of skin wounds using polyenylphosphatidylcholine and alkanolamines

Family Cites Families (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4610868A (en) 1984-03-20 1986-09-09 The Liposome Company, Inc. Lipid matrix carriers for use in drug delivery systems
US4568703A (en) * 1984-07-27 1986-02-04 Bp Chemicals Limited Process for the production of polymers containing isocyanurate and or oxazolidone linkages
JPS62169711A (ja) * 1986-01-22 1987-07-25 Shiseido Co Ltd 皮膚化粧料
US5320906A (en) 1986-12-15 1994-06-14 Vestar, Inc. Delivery vehicles with amphiphile-associated active ingredient
US5628936A (en) 1987-03-13 1997-05-13 Micro-Pak, Inc. Hybrid paucilamellar lipid vesicles
JPH0720857B2 (ja) 1988-08-11 1995-03-08 テルモ株式会社 リポソームおよびその製法
US6132763A (en) 1988-10-20 2000-10-17 Polymasc Pharmaceuticals Plc Liposomes
WO1992003122A1 (fr) 1990-08-24 1992-03-05 Gregor Cevc Composition d'application de fines gouttelettes de substances actives
US5665379A (en) 1990-09-28 1997-09-09 Pharmacia & Upjohn Aktiebolag Lipid particle forming matrix, preparation and use thereof
US5298246A (en) 1991-01-09 1994-03-29 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Stable pharmaceutical composition and method for its production
WO1994000127A1 (fr) 1992-06-19 1994-01-06 The Regents Of The University Of California Lipides pour l'humidification de l'epiderme et la restauration de la fonction de barriere
EP0711558A1 (fr) 1994-10-21 1996-05-15 Unilever Plc Des compositions pour application topique sur la peau, les cheveux et les argles
CA2204493C (fr) 1994-11-04 2009-04-14 Hermann Katinger Application de superoxide dismutase dans des liposomes
DE4439815C2 (de) 1994-11-08 2001-06-07 Mann & Hummel Filter Filter, insbesondere Flüssigkeitsfilter
US20020048596A1 (en) 1994-12-30 2002-04-25 Gregor Cevc Preparation for the transport of an active substance across barriers
WO1996037192A1 (fr) * 1995-05-26 1996-11-28 Vesifact Ag Compositions pharmaceutiques et cosmetiques contenant des sphingolipides et des glycolipides
US6056973A (en) 1996-10-11 2000-05-02 Sequus Pharmaceuticals, Inc. Therapeutic liposome composition and method of preparation
IN184589B (fr) * 1996-10-16 2000-09-09 Alza Corp
WO1998017253A1 (fr) * 1996-10-23 1998-04-30 The Regents Of The University Of California Procede et compositions utilises pour interrompre la fonction de la barriere epitheliale
IT1292142B1 (it) 1997-06-12 1999-01-25 Maria Rosa Gasco Composizione farmaceutica in forma di microparticelle lipidiche solide atte alla somministrazione parenterale
IT1296914B1 (it) 1997-12-01 1999-08-03 Maria Rosa Gasco Composizione farmaceutica comprendente microparticelle atte al passaggio transmucosale ed al superamento della barriera
TR200101790T2 (tr) 1998-12-23 2001-10-22 Idea Ag. Yayılgan olmayan in vivo topik uygulamalar için geliştirilmiş formül
DE19923246A1 (de) 1999-05-20 2000-12-07 Tyco Electronics Logistics Ag Ferrule für einen Lichtwellenleiter und Verfahren zum Befestigen der Ferrule an dem Lichtwellenleiter
KR19990078610A (ko) 1999-07-03 1999-11-05 김현준 피부보호용조성물
WO2001001962A1 (fr) 1999-07-05 2001-01-11 Idea Ag. Procede d'amelioration du transport a travers des barrieres semi-permeables compatibles
KR100371491B1 (ko) * 1999-07-27 2003-02-07 주식회사 두산 피부 보호용 크림조성물
NZ534377A (en) 2002-03-13 2008-04-30 Collagenex Pharm Inc Water-based topical delivery system consisting of cholesterol, fatty acids water and a phospholipid/ceramide portion.
US20050129722A1 (en) 2002-03-13 2005-06-16 Collagenex Pharmaceuticals, Inc. Water-based delivery systems
US20040105881A1 (en) 2002-10-11 2004-06-03 Gregor Cevc Aggregates with increased deformability, comprising at least three amphipats, for improved transport through semi-permeable barriers and for the non-invasive drug application in vivo, especially through the skin

Patent Citations (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4508703A (en) * 1982-02-17 1985-04-02 Parfums Christian Dior Production of pulverulent mixtures of lipidic and hydrophobic constituents
US5733572A (en) * 1989-12-22 1998-03-31 Imarx Pharmaceutical Corp. Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles
US5196190A (en) * 1990-10-03 1993-03-23 Zenith Technology Corporation, Limited Synthetic skin substitutes
US5206020A (en) * 1991-01-15 1993-04-27 Elizabeth Arden Company, Division Of Conopco, Inc. Synthetic pseudoceramide and cosmetic compositions thereof
US5468475A (en) * 1992-11-17 1995-11-21 Pola Chemical Industries Inc. Cosmetic composition with choline derivative
US5534499A (en) * 1994-05-19 1996-07-09 The University Of British Columbia Lipophilic drug derivatives for use in liposomes
US5631012A (en) * 1994-09-02 1997-05-20 Shanni; David Cosmetic preparations for moisturizing human skin containing specific lipids
US5820873A (en) * 1994-09-30 1998-10-13 The University Of British Columbia Polyethylene glycol modified ceramide lipids and liposome uses thereof
US5776480A (en) * 1994-12-14 1998-07-07 L'oreal Cosmetic or dermatological composition containing a mixture of ceramides for moisturizing the skin
US5817856A (en) * 1995-12-11 1998-10-06 Yissum Research Development Company Of The Hebrew University Of Jerusalem Radiation-protective phospholipid and method
US5993830A (en) * 1997-01-17 1999-11-30 Ponsus Ab Cosmetic skin preparation
US6730288B1 (en) * 1998-09-11 2004-05-04 Connetics Australia Pty Ltd Mousse composition
US6153209A (en) * 1999-09-28 2000-11-28 The Procter & Gamble Company Article having a transferable breathable skin care composition thereon
US6497888B1 (en) * 1999-10-14 2002-12-24 L'ORéAL S.A. Process for limiting the penetration into the skin and/or the keratinous fibres of an active cosmetic and/or pharmaceutical agent
US6586000B2 (en) * 1999-12-16 2003-07-01 Dermatrends, Inc. Hydroxide-releasing agents as skin permeation enhancers
US6824785B1 (en) * 2000-02-09 2004-11-30 C. Neil Kitson Skin treatment composition and methods of use
US6932963B2 (en) * 2000-06-23 2005-08-23 Nicholas V. Perricone Treatment of skin wounds using polyenylphosphatidylcholine and alkanolamines

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US20090226491A1 (en) * 2002-03-13 2009-09-10 Thomas Skold Water-based delivery systems
US8029810B2 (en) 2002-03-13 2011-10-04 Thomas Skold Water-based delivery systems
US20070154403A1 (en) * 2006-01-05 2007-07-05 Thomas Skold Oral, Pulmonary and Transmucosal Delivery Composition
US20090247630A1 (en) * 2006-05-31 2009-10-01 Claire Mallard Dermatological compositions comprising at least one naphthoic acid compound and at least one film-forming agent and treatment of keratinization disorders therewith
US8937098B2 (en) * 2006-05-31 2015-01-20 Galderma Research & Development Dermatological compositions comprising at least one naphthoic acid compound and at least one film-forming agent and treatment of keratinization disorders therewith
US20080152636A1 (en) * 2006-09-08 2008-06-26 Kaneka Corporation Composition containing reduced coenzyme Q10 and lysolecithin
WO2009101412A1 (fr) * 2008-02-13 2009-08-20 Cipla Limited Composition pharmaceutique topique
US10406088B2 (en) 2015-01-20 2019-09-10 TetraDerm Group LLC Versatile topical drug delivery vehicle and multifactorial tissue moisturizer that provides mucosal and skin barrier restoration
US10137073B2 (en) * 2016-01-02 2018-11-27 L'oreal Cosmetic compositions comprising ceramides and cholesterol
KR101752312B1 (ko) * 2016-11-22 2017-06-29 주식회사 씨엠에스랩 사카라이드아이소머레이트, 하이드롤라이즈드루핀프로테인 및 각질세포간지질 모사체를 유효성분으로 담지한 베지클 및 이를 포함하는 피부 외용제 조성물
EP3338759A1 (fr) * 2016-11-22 2018-06-27 CMS Lab Inc. Vésicules contenant un isomérat de saccharide, de la protéine de lupin hydrolysée et des mimétiques lipidiques mimétiques lipidiques intercornéocytaires en tant que principe actif et composition pour application externe cutanée les contenant
US10307361B2 (en) 2016-11-22 2019-06-04 Cms Lab Inc. Vesicles containing saccharide isomerate, hydrolyzed lupine protein, and intercorneocyte lipid mimetics as active ingredient, and composition for skin external application comprising the same

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ES2411656T3 (es) 2013-07-08
KR20040091116A (ko) 2004-10-27
US8029810B2 (en) 2011-10-04
JP2005522463A (ja) 2005-07-28
WO2003077861A3 (fr) 2005-03-24
EP1534213A4 (fr) 2005-10-26
US20090226491A1 (en) 2009-09-10
CA2476859C (fr) 2011-09-20
US20090081139A1 (en) 2009-03-26
CA2476859A1 (fr) 2003-09-25
EP1534213B1 (fr) 2013-04-24
AU2003233396B2 (en) 2007-05-24
KR101076335B1 (ko) 2011-10-26
JP4806519B2 (ja) 2011-11-02
NZ534377A (en) 2008-04-30
WO2003077861A2 (fr) 2003-09-25
AU2003233396A1 (en) 2003-09-29
EP1534213A2 (fr) 2005-06-01

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