+

WO1995008349A1 - Composition contenant des acides polyinsatures omega 3 et/ou omega 6 ayant de 12 a 22 atomes de carbone - Google Patents

Composition contenant des acides polyinsatures omega 3 et/ou omega 6 ayant de 12 a 22 atomes de carbone Download PDF

Info

Publication number
WO1995008349A1
WO1995008349A1 PCT/GB1994/002076 GB9402076W WO9508349A1 WO 1995008349 A1 WO1995008349 A1 WO 1995008349A1 GB 9402076 W GB9402076 W GB 9402076W WO 9508349 A1 WO9508349 A1 WO 9508349A1
Authority
WO
WIPO (PCT)
Prior art keywords
carrier medium
ingredient
ingredients
skin
carrier
Prior art date
Application number
PCT/GB1994/002076
Other languages
English (en)
Inventor
Ian Flockhart
Ali Altunkaya
John William Hopewell
Original Assignee
Ian Flockhart
Ali Altunkaya
John William Hopewell
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
Priority claimed from GB939319818A external-priority patent/GB9319818D0/en
Priority claimed from GB9408548A external-priority patent/GB9408548D0/en
Application filed by Ian Flockhart, Ali Altunkaya, John William Hopewell filed Critical Ian Flockhart
Priority to AU77871/94A priority Critical patent/AU7787194A/en
Priority to EP94928444A priority patent/EP0755267A1/fr
Publication of WO1995008349A1 publication Critical patent/WO1995008349A1/fr

Links

Classifications

    • 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
    • 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
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin

Definitions

  • composition containing omega 3 and/or omega 6 polyunsaturated adds having from 12 to 22 carbon atoms
  • the fatty compound is stated to be any of the essential fatty acids which occur naturally in the form of their glyceride esters in fats and oils.
  • Specific examples of fatty compounds for use as penetration enhancers are oleic or linoleic acids or C- . 3 alkyl esters thereof.
  • the acknowledgement of prior art in this application also refers to a number of other types of carrier media which act as penetration enhancers.
  • radiotherapy is considered to be a useful palliative and, in some cases, beneficial treatment regime.
  • compositions which contains linoleic acid, gamma-linolenic acid and/or dihomo-gamma- linolenic acid to the damaged skin or to the area of the patient to be irradiated.
  • the composition can contain from 0.1 to 20% by weight of the active acid components, optionally in the form of a glyceride ester thereof.
  • the glyceride esters are merely used as a convenient form by which the free acid moieties can be presented to the metabolic chain of the patient.
  • EP 0416855 The active components in EP 0416855 are applied as such or in a conventional cream, oil, gel or lotion carrier medium, which as stated above deliver an active ingredient only to the epidermal surface of the skin.
  • the proposal in EP 0416855 would present the active components in a form likely to penetrate at most only into the outer stratum corneum of the epidermis .
  • the glyceride esters of unsaturated acids of the omega-3 and omega-6 series are remarkably effective in the transdermal transport of a wide range of medicaments when used as a carrier medium in combination with at least two other ingredients selected from Vitamins of the A to E series, gel matrix forming materials and skin moisturisers .
  • such carrier media alone or in combination with other medicaments are remarkably effective in the treatment of skin damage, notably radiation or burn damage.
  • the present invention provides a carrier medium suitable for the transme branal application of a medicament to a mammal or for topical application to the actual or intended locus of damage to the skin of the mammal, for example by ionising radiation, treatment, which carrier medium comprises as essential ingredients :
  • vitamins selected from the series A, B, C, D, or E, or a physiologically acceptable derivative or precursor thereof;
  • one or more physiologically acceptable natural and/or synthetic materials which form a matrix within which the other ingredients of the carrier medium are dispersed, notably natural or synthetic waxes, greases, polyalkylene ether glycols or alkylene glycols or fatty acid esters thereof and/or fatty acid esters of long chain alcohols or glycols; and
  • the invention further provides a method for enhancing the transmembranal administration of a dermatologically and/or pharmaceutically active component to a mammal, which method comprises applying the active component in a carrier medium of the invention to a locus on the mammal.
  • the invention further provides a method for the manufacture of a transmembranally administerable dermatological and/or pharmaceutical composition containing an active component, which method comprises the incorporation of the active component in a carrier medium of the invention.
  • the composition can contain a wide range of dermatologically and/or pharmaceutically active components and these can be present in a wide range of amounts.
  • the invention offers the ability to apply medicaments transdermally in effective amounts and also to use lower concentrations, for example from 0.1 to 2%, of the medicament, which is of advantage where large areas of the skin are to be treated.
  • concentrations for example from 0.1 to 2%
  • higher proportions for example from 5 to 10% by weight, of the active component may be used if desired and acceptable.
  • the carrier medium provides more than 50% by weight of the total composition.
  • the combination of the essential ingredients of the carrier medium possesses surprisingly great dermatological and skin repair properties in its own right and it may therefore not be necessary to incorporate an additional active medicament in the carrier medium to achieve useful therapeutic results.
  • the carrier medium can provide up to 100% of the overall composition.
  • the essential ingredients 1 for use in the carrier medium of the invention are conveniently those obtained from a marine and/or vegetable seed oil which contain gamma-3 and/or gamma-6 forms of eicosapentaenoic acids, notably those containing linoleic and/or linolenic glyceride esters or mixed esters. It is preferred that ingredient 1 contain a glyceride ester of linoleic and/or linolenic acid containing at least two acid moieties, preferably a mixed ester of linoleic and gamma-linolenic acids.
  • a particularly preferred ester for present use is the di-linoleoyl-mono- gamma-linoleyl ester of glycerol (DGLA) .
  • DGLA di-linoleoyl-mono- gamma-linoleyl ester of glycerol
  • ingredient 1 used in the present invention contains at least 15% by weight of the DGLA, and levels of 25% or more of DGLA in ingredient 1 can readily be achieved when a synthetic product is used.
  • Suitable materials containing ingredients 1 for present use can be obtained by the pressing or other extraction of fish or vegetable seeds to provide an oil which can be used in its commercially available form or can be purified or treated further to extract the desirable ingredient 1.
  • Suitable fish oils include purified oils derived from fish livers or from fatty fish, for example tuna, herring, mackerel, cod and commercially available blends thereof.
  • Suitable vegetable seed oils are those natural oils extracted, for example by pressing and subsequent purification, from evening primrose seeds (Oenothera sp) , borage seeds (Borago sp) , blackcurrants, oil rape seeds and brassica seeds. Such materials may be used in their commercially available forms and purity and mixtures of the fish and vegetable seed oil may be used.
  • ingredients 1 esters may be synthetic materials prepared using the appropriate conventional starting materials and techniques .
  • a particularly preferred ester for present use is the mixture of the linoleoyl and gamma-linoleyl acid esters in oil of evening primrose, which may be used in its commercially available form and purity.
  • OEP oil of evening primrose
  • the carrier medium preferably contains from 20 to 95%, preferably 2.5 to 50%, notably 5 to 25%, by weight of ingredient 1. Typically, ingredient 1 will provide from 3 to 23% by weight of DGLA in the carrier medium.
  • Vitamin essential ingredients 2 for use in the carrier medium of the invention are selected from those in the series Vitamins A, B, C, D and E and their salts, esters and precursors thereof, notably D-pantothenol as a precursor for Vitamin B5 and carotenoids as precursors for Vitamin A.
  • Preferred Vitamins for present use are Vitamins A, B5 and E.
  • Vitamins will often be available in mixed stereoisomeric forms and these may be used if desired. However, it is preferred to isolate specific isomers to enhance the desired activity of the Vitamin. Thus, in the case of Vitamin A, it is preferred to use an all trans form of the Vitamin and its caretenoid precursors or derivatives; in the case of Vitamin E, it is preferred to use the DL-alpha form of the Vitamin.
  • the Vitamins or their precursors or derivatives for present use can be obtained from natural sources or may be synthetic or semi-synthetic and are commercially available. As stated above, it may be desired to isolate specific stereoscopic isomers from a commercially available mixture of isomers in order to enhance the desired activity of the Vitamin. Such isolation and transformation into a desired isomer form may be achieved using conventional techniques.
  • the Vitamins when present, provide a total weight of vitamins in the carrier medium of from 0.1 to 20%, typically 1 to 5%, by weight of the carrier medium. It is also preferred to provide the individual Vitamins in the carrier medium in amounts of from 1 to 5% by weight of Vitamin E or Vitamin E acetate, 0.1 to 5% by weight of Vitamin A and from 1 to 5% by weight of D-pantothenol or Vitamin B5.
  • Ingredients 3 are natural or synthetic animal or vegetable type materials which have film forming and occlusive properties so as to form a matrix within which the other materials of the carrier medium are dispersed.
  • Such materials include waxes or greases, preferably those in which at least part of the ester groupings present have been saponified, either before incorporation into the carrier media of the invention and/or during the adjustment of the pH of the carrier media at described below.
  • the waxes or greases can be used in the form of a partial alkali metal, alkaline earth metal salt or salt of a strong physiologically acceptable organic base thereof.
  • Typical suitable materials are lanolin, bees wax, carnauba wax, Japan waxes, candelila wax and hydrocarbon resins or waxes, for example Emulsifying wax BP or USP NF wax, polawax or synchrowaxes .
  • the polyalkylene ether glycols or alkylene glycols may also be used to provide ingredient 3 and typically have a molecular weight in the range 100 to 600,000, preferably 200 to 6000.
  • ether glycols and glycols provide the carrier with occlusive properties as well as providing matrix forming and solvent and transdermal properties. Their inclusion in the carrier medium is especially preferred when the carrier medium is to be used to administer a medicament over a prolonged period where drying out of the skin could occur.
  • the ether glycols and glycols also provide a stable viscous gel consistency to the composition. Where the ether glycol or glycol has a short chain, for example 2 to 5 carbon atoms, the ether glycol or glycol may also serve as a solvent or co-solvent for other components of the carrier medium.
  • the polyalkylene-ether-glycol for use as ingredient 3 are preferably those of the empirical formula HO- (C n H 2n 0) m -0H, where n has an average value of from 2 to 6 and m has an average value of from 2 to 30 or more, in which the alkylene groups can be straight or branched chain, saturated or unsaturated, and in which the hydroxyl groups can be primary, secondary and/or tertiary.
  • Ingredient 3 may also be a physiologically acceptable alkylene-glycol, notably one of the empirical formula HO- (C p H 2p ) q -0H, where ⁇ o has a value of from 2 to 6 and g has an average value of from 1 to 30, in which the alkylene groups can be straight or branched, saturated or unsaturated, and the hydroxyl groups can be primary, secondary and/or tertiary; or mixtures of such polyalkylene ether glycols and/or alkylene glycols .
  • a physiologically acceptable alkylene-glycol notably one of the empirical formula HO- (C p H 2p ) q -0H, where ⁇ o has a value of from 2 to 6 and g has an average value of from 1 to 30, in which the alkylene groups can be straight or branched, saturated or unsaturated, and the hydroxyl groups can be primary, secondary and/or tertiary; or mixtures of such polyalkylene ether
  • Ingredient 3 may also be provided by a fatty acid ester of the above glycols or ether glycols, notably esters with saturated or unsaturated acids containing from 12 to 24 carbon atoms, for example stearic, myristic or palmitic acids or the esters of such acids with long chains alcohols, notably straight or branched chain alkanols containing from 8 to 18 carbon atoms.
  • a fatty acid ester of the above glycols or ether glycols notably esters with saturated or unsaturated acids containing from 12 to 24 carbon atoms, for example stearic, myristic or palmitic acids or the esters of such acids with long chains alcohols, notably straight or branched chain alkanols containing from 8 to 18 carbon atoms.
  • the wax, grease, polyalkylene ether glycols, alkylene glycols and/or fatty acids esters when present, are typically present in a total amount of from 0.25 to about 30% by weight of the total carrier medium, preferably 1 to 25%, and mixtures of waxes, greases, glycols, ether glycols and esters may be used.
  • Ingredient 4 is a physiologically acceptable material having skin moisturising properties, ie. it is a compound or mixture of compounds which maintains or increases the hydration of the stratum corneum of the skin. In some cases this property may be possessed by ingredient 1 and part of ingredient 1 may provide at least part of ingredient 4.
  • a number of other materials are known to possess this property and specific examples include: urea; lactic, ascorbic or glycollic acids and salts and esters thereof; cholesterol; liposomes and niosones; pyrrolidone carboxylic acid and salts thereof; mono- and poly-aminosaccharides; chitins and chemically modified chitins which contain ether and extra alkyl groups; hyaluronic acid; and lower alkyl glycols and glycerol . Mixtures of such skin moisturising agents may be used for ingredient 4, if desired.
  • the skin moisturising agent ingredient 4 when present, is present in an amount of up to about 10%, for example from 0.1 to 5%, preferably from 0.1 to 2% by weight of the carrier medium.
  • the carrier medium often interact with one another synergistically to enhance the transmembranal transport property of the carrier medium. This effect is particularly marked when the carrier medium contains all four of the essential ingredients.
  • the carrier medium contain from 20 to 95% of ingredient 1; from 0.5 to 20% of ingredient 2 ; from 0.25 to 30% of ingredient 3; and from 0.1 to 5% of ingredient 4 ; all percentages being by weight of the active component in each ingredient based on the weight of the carrier medium, the remainder of the carrier medium typically being water or a water based gel or matrix having the other ingredients uniformly distributed throughout it.
  • the essential ingredients of the carrier medium may provide the sole ingredients of the carrier for an active medicament component which is dissolved, emulsified, dispersed or suspended therein. However, it is preferred that the carrier medium contain other ingredients to assist the performance of the carrier and the active components.
  • Typical of such other ingredients are: 5. one or more materials having anti-bacterial and/or anti-fungal properties; and 6. a long chain alcohol .
  • the ingredient 5 can be selected from a wide range of materials which exhibit anti-fungal and/or anti-bacterial properties.
  • it is a plant extract and the plant extract also exhibits preservative properties at dosage rates of the ingredient which are physiologically acceptable. That is, the plant extract exhibits physiologically useful effects at a dosage rate similar to the rate at which the other ingredients are applied to the skin in the overall composition.
  • the amount of the plant extract required to achieve useful effects does not imbalance the overall composition.
  • Suitable ingredients 5 include essential oils as defined at page 670 of Martindale, The Extra Pharmacopoeia, 28th edition. Such essential oils include those derived from the foliage of plants and trees and are typified as containing terpenoid compounds . These may be hydrocarbon terpenes or oxygen containing compounds, for example terpene alcohols, ketones or oxides . Specific preferred terpene compounds include a-pinene, a-terpinene, limonene, 1,8-cineol, gamma- terpinene, p-cymene, l-terpinen-4-ol, aromadendrene, a- terpineol, and mixtures thereof.
  • the terpene compounds for present use may be synthetic or naturally occurring, as when a eucalyptus type tree oil is used, notably the oil from Melaleuca alternifolia tree, known as Tea Tree Oil.
  • Ingredient 5 may also or in addition be a natural vegetable oil, for example a saturated or mono- or polyunsaturated oil as specified in PCT Application No US92/10673, or a synthetic oil.
  • a natural vegetable oil for example a saturated or mono- or polyunsaturated oil as specified in PCT Application No US92/10673, or a synthetic oil.
  • Ingredient 5 may be used as the naturally occurring mixture of materials containing the active ingredient, or may be used in the form of an isolated and refined extract containing a raised proportion of the active ingredient or as an individual synthetically prepared single compound or mixture of isomers .
  • Ingredient 5, when present, is typically present in up to 15%, for example from 0.1 to 10%, preferably 0.5 to 5%, notably from 0.5 to 2.5%, by weight of active ingredient based on the weight of the carrier medium and serves primarily as a penetration assistant and preservative against bacterial contamination of the composition and also to confer skin disinfecting properties on the carrier medium.
  • the long chain alcohol ingredient 6 is preferably a physiologically acceptable straight chain aliphatic alcohol containing from 9 to 24 carbon atoms, for example a C 8 -C 14 aliphatic monohydric alcohol, notably a C 9 . 12 alcohol.
  • Specific examples of alcohols for use as ingredient 6 are lauryl or dodecyl alcohol, which, latter may be derived from propylene tetramer.
  • the alcohol serves as a lubrifacient to aid direct application of the composition to the skin and also assists transdermal penetration of the medicament. The presence of the long chain alcohol is therefore preferred when the composition would otherwise be excessively viscous and is particularly desirable when the polyalkylene ether glycol or alkylene glycol ingredient 3 is also present .
  • the long chain alcohol ingredient 6, when present, is present in an amount of up to about 30%, for example from 1 to 25%, preferably 1 to 10%, by weight of the carrier medium.
  • the carrier medium may contain other ingredients normally present in topically applied compositions. Typically these will provide less than 50%, for example from 0.1 to 35%, by weight of the total carrier medium.
  • Such other ingredients include for example solvents or co-solvents, such as water, low molecular weight alcohols, eg. ethyl or propyl alcohols or glycols, and liquid silicones, eg. cyclomethicone; hydrocarbon resin thickeners or cellulose derivative gelling agents; and penetration enhancers, such as long chain acids, esters, glycols or saccharide derivatives.
  • solvents or co-solvents such as water, low molecular weight alcohols, eg. ethyl or propyl alcohols or glycols, and liquid silicones, eg. cyclomethicone
  • hydrocarbon resin thickeners or cellulose derivative gelling agents eg. cyclomethicone
  • penetration enhancers such as long chain acids, esters, glycols or saccharide derivatives.
  • Particularly preferred fatty acids and esters thereof for present use are those of the empirical formula Alk-OOCAcid where Alk denotes a straight or branched alkyl group containing from 2 to 18 carbon atoms and Acid denotes a saturated or unsaturated straight or branched chain alkyl group which may carry one or more Alk-OOC- substituents .
  • Typical of such fatty acid esters are C x to C 18 alkyl esters of oleic acid or oleic acid itself.
  • ingredients which may also be present include, for example, a pH controlling agent such as sodium, potassium, ammonium or an alkaline-earth metal hydroxide, or an organic base of the primary, secondary or tertiary amine type, to give a final pH in the range 4.5 - 9.0 and more preferably 6.5 - 7.5.
  • a pH controlling agent such as sodium, potassium, ammonium or an alkaline-earth metal hydroxide, or an organic base of the primary, secondary or tertiary amine type, to give a final pH in the range 4.5 - 9.0 and more preferably 6.5 - 7.5.
  • ingredients in the carrier media of the invention may be used in the form of the free active ingredients. However, they may also be used in the form of a physiologically acceptable salt, ester or other derivative, metabolite or precursor thereof. Thus, the ingredients may be present in the form of an alkyl ester, acetate or acyl derivative, an alkali or alkaline earth metal salt or an amine salt or complex thereof. Specifically, ingredient 1 may be present in the form of a salt or ester thereof, notably a mono-, di or triglyceride ester which may contain mixed acid moieties as is the case with the preferred ingredient 1 DGLA.
  • ingredients are capable of providing more than one effect, for example ingredient 1 may provide some moisturising effect and the essential oil ingredient 5 may also provide anti-pruritic effect, in which case the amount of one or more of the other ingredients may be appropriately reduced.
  • the oils containing ingredients 1 and 5 are often obtained from natural materials and will therefore differ in composition and be a mixture of the desired ingredient with other materials. Such mixtures may be used without the need to isolate the specified ingredient and the percentages given above are in terms of the desired active ingredient in such mixtures, Where the mixture contains large amounts of physiologically acceptable other components, these may themselves provide beneficial other properties, for example fragrance, to the composition.
  • the essential ingredients of the carrier medium often interact synergistically to achieve a greater than expected effect in preventing or reducing the effects of ionising radiation on normal tissue cells and in repairing other damage to the skin.
  • the prevention of desquamation and the acceleration of healing of desquamated skin is generally more pronounced with compositions containing one or more ingredients 1, Vitamins and ingredients from at least three of the other groups 3 to 6, than with formulations which omit more than one of the ingredients from groups 1 to 4.
  • the carrier media of the invention are remarkably effective in their own right, notably when containing ingredients 1, 2 and 3, in aiding repair to cuts, abrasions, open wounds or other traumatisations of the skin and in the treatment of other disorders of the skin, such as dermatitis, eczema, psoriasis and a wide range of types of damage to the dermis and are indicated as potentially effective in the treatment of some skin cancers; and to a lesser extent, the sub-dermal layers of the skins, for example due to viral and other infections or to metastatic disease.
  • the invention also provides a method for the treatment of or the prophylaxis of damage to normal tissue cells by ionising, photo- or UV radiation, open wound type trauma to the skin, or of viral and other infections of the skin, which method comprises applying a pharmaceutically effective amount of a carrier medium of the invention to the known or expected site of the damage to the skin of a mammal.
  • the carrier medium of the invention may be used as such in the repair of skin damage or in the treatment of radiation and other burns.
  • the carrier media of the invention find widespread use in the topical application of a wide range of medicaments in the treatment of a wide range of skin and other conditions.
  • the compositions find use in the treatment of skin conditions such as the treatment of wounds, sores, burns, lesions and abrasions of the skin, particularly in the prevention or treatment of burns caused by ionic or UVA or UVB radiation.
  • the carrier media of the invention also find use in the administration of drugs which are to be transported across the skin and act systemically throughout the body of a patient.
  • compositions containing such essential oils may be self preserving and assist the prevention of infection in open wounds or abrasions due to these properties of the essential oil ingredient.
  • suitable medicaments include radiation protectors, for example thiol compounds such as N- acetylcysteamine, N-acetylcysteine and glutathione; radiation repair agents, for example methylsulphonyl methane, bisabolol and chamazulene; benzocaine, lidocaine, tetracaine as local anaesthetics; benzydamine, naproxen, ibuprofen, ketoprofen, indomethacin, diclofenac, fenclofenac, piroxicam as anti-inflammatory agents or mild analgesics; allantoin as an enhancer of skin repair regrowth; and tranquillisers and sedatives of the phenothiazine or butyrophenone type.
  • radiation protectors for example thiol compounds such as N- acetylcysteamine, N-acetylcysteine and glutathione
  • radiation repair agents for example methylsulphony
  • the invention may also be applied to precursors of the active medicaments, for example an acetate or acyl derivative, an alkali metal salt or an amine salt or complex thereof.
  • medicament will be used herein to denote in general terms a active ingredient of a medicament, its analogues and precursors thereof, whether alone or in admixture with one another.
  • composition of the invention thus finds widespread use in the treatment of a wide range of conditions for which the medicaments have been indicated, eg. in the application of methotrexate in the treatment of proliferative skin disorders including: psoriasis; primary malignant disease, for example squamous cell carcinoma, basal cell carcinoma, malignant melanoma, Kaposis sarcoma etc.; and secondary deposits in the skin and neoplasms due to or associated with warts, herpes simplex, human papilloma virus etc..
  • a medicament is also present, this will typically be present in from 0.1 to 10% by weight of the total composition.
  • the carrier media and the compositions of the invention can be prepared using a wide range of techniques, for example by admixing and stirring together the desired amounts of the various ingredients to form a cream, paste or gel.
  • the ingredients can be pre-dissolved or suspended in one or more of the other ingredients, for example in a propylene glycol solvent, to aid formation of a stable gel or emulsion.
  • the pH of the carrier medium can be adjusted by the addition of a suitable pH regulator after the other ingredients have been incorporated and before the final carrier medium has been achieved.
  • the carrier media of the invention with or without the presence of a medicament are applied to the affected area of, or the predicted area of radiation or other damage to, the skin of a mammal, for example of horse, pig, cattle or human being, by applying the carrier medium or total composition as a coating over the affected area.
  • the medicament is one which is to be absorbed through the skin and is to act systemically elsewhere in the body
  • the composition can be applied at any convenient locus on the skin. This can be achieved by applying the carrier or composition directly in the required amount as a cream, paste or gel to the skin.
  • the carrier or composition can be applied as a spray, foam, mousse or gel from a pressurised dispenser having an appropriate valved spray outlet.
  • the carrier or composition can then be spread over and/or massaged into the skin.
  • the carrier or composition may also be applied to an adhesive plaster, pad, gauze or other backing support member, which is then applied over the treated area.
  • the coating of the composition on the skin or on the support member can have applied thereto a vapour barrier film, for example a plastic film or a spray on film-forming resin, for example a synthetic skin type composition, which serves to retain water and other fluids in the composition and the skin.
  • a vapour barrier film for example a plastic film or a spray on film-forming resin, for example a synthetic skin type composition, which serves to retain water and other fluids in the composition and the skin.
  • a polyalkylene ether glycol or alkylene glycol ingredient 3 is present in sufficient amounts in the carrier medium, this may impart sufficient occlusive properties for the use of a vapour barrier membrane not to be necessary.
  • compositions of the invention also find use where it is desired to apply a medicament across other membranes than the skin.
  • the compositions can be ingested to apply the active ingredient across the buccal mucosa and other portions of the gastrointestinal tract.
  • the amount of the composition applied will be sufficient to apply the biologically effective amount of the active ingredient (s) therein to the affected area of the skin or to achieve the desired therapeutic effect or dosage application. This amount will vary according to the treatment required and the content of active ingredient in the composition. The optimal amount required to achieve the desired biological effect can readily be established as is known from a knowledge of these.
  • the cream was mixed with a solution of Tea Tree oil in ethanol (ingredient 5, 1 part oil in 10 parts ethanol) and, as a lubrifacient to aid preparation of the mixture and application of the composition to the skin, an emollient ester of polypropylene glycol and myristic acid (5 parts by weight, ingredient 3) .
  • the mixture was stirred continuously for one hour to give a creamy base and packed into a sealed container until used (Formulation I) .
  • compositions were prepared as in Example 1, but using other active ingredients as follows:
  • Example 2 as Example 1, but including 5% by weight of Vitamin E acetate.
  • Example 3 as Example 1, but including 1% by weight methylsulphonylmethane.
  • Example 4 as Example 2, but including 1% by weight of methylsulphonylmethane.
  • Example 5 as Example 1 but also containing 0.02% by weight Vitamin A, 5% by weight Vitamin E acetate and 0.5% alpha- bisabolol .
  • Example 6 as Example 1 but also containing 3% by weight of benzydamine hydrochloride.
  • Example 7 as Example 2, but containing 1% by weight of benzydamine hydrochloride.
  • Female Large White pigs (approx 25 Kg bodyweight) were used and 15 skin sites of approximately 25 mm diameter were marked out by tattoo using India ink on both flanks of each pig. After a week, each site was irradiated with a single dose of 35 Gy of beta radiation from a Sr 90 /Y 90 plaque at a dose rate of approximately 3 Gy per minute.
  • each formulation was applied and spread uniformly over each site.
  • the treatment allocation was randomised to each site and also between two pigs.
  • the treatment with each formulation was replicated between 6 and 9 times.
  • the severity of the acute reaction of the skin patches to the radiation was assessed on a graded score and compared with untreated sites. Reduction in the severity of desquamation compared to untreated sites was seen in all cases and a reduction in the time for healing of moist desquamation sites was observed in all case.
  • the mean healing times from 6 to 9 replications for each formulation being assessed are set out below.
  • a hydrogel carrier was prepared as described under Formulation II in Example 1 of our co-pending PCT Application Number GB92/01950 - Example 8.
  • This hydrogel did not contain any of the Vitamins (essential ingredient 2 of the carrier medium of the invention) nor did it contain any oil of evening primrose (essential ingredient 1) .
  • Into samples of this hydrogel were incorporated 5% by weight of Vitamin E acetate (Example 9) and 5% by weight of Vitamin E acetate and 0.5% by weight of alpha-bisabolol (Example 10) .
  • a further formulation (Example 11) was prepared unsing a conventional cream base carrier which contained 20% by weight of oil of evening primrose and other ingredients as in Example 1, but omitted the vitamins and moisturising ingredients 2 and 4 from the formulation.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention se rapporte à un milieu porteur démontrant des propriétés thérapeutiques et rehaussant la capacité de transport transmembranaire d'un médicament. Ce milieu porteur comprend comme constituants essentiels : 1. un ou plusieurs acide(s) polyinsaturé(s), physiologiquement acceptable(s), des séries oméga-3 et/ou oméga-6 contenant 12 à 22 atomes de carbone, ou un de leurs dérivés ou précurseurs physiologiquement acceptable; et au moins deux constituants choisis parmi : 2. une ou plusieurs vitamine(s) choisie(s) dans les groupe A, B, C, D ou E, ou un de leurs dérivés ou précurseurs physiologiquement acceptable; 3. une ou plusieurs matière(s) naturelle(s) ou synthétique(s), physiologiquement acceptable(s), formant une matrice dans laquelle les autres constituants du milieu porteur sont dispersés; et 4. une ou plusieurs matières possédant des propriétés d'hydratation de la peau. L'invention se rapporte également à un procédé de fabrication dudit milieu porteur ainsi qu'à des procédés de traitement d'une peau soumise à des rayonnements ou ayant subi d'autres brûlures ou dommages, ces procédés utilisant le milieu porteur seul ou en combinaison avec un médicament.
PCT/GB1994/002076 1993-09-23 1994-09-23 Composition contenant des acides polyinsatures omega 3 et/ou omega 6 ayant de 12 a 22 atomes de carbone WO1995008349A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU77871/94A AU7787194A (en) 1993-09-23 1994-09-23 Composition containing omega 3 and/or omega 6 polyunsaturated acids having from 12 to 22 carbon atoms
EP94928444A EP0755267A1 (fr) 1993-09-23 1994-09-23 Composition contenant des acides polyinsatures omega 3 et/ou omega 6 ayant de 12 a 22 atomes de carbone

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB9319818.2 1993-09-23
GB939319818A GB9319818D0 (en) 1993-09-23 1993-09-23 Composition
GB9408548A GB9408548D0 (en) 1994-04-29 1994-04-29 Composition
GB9408548.7 1994-04-29

Publications (1)

Publication Number Publication Date
WO1995008349A1 true WO1995008349A1 (fr) 1995-03-30

Family

ID=26303575

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1994/002076 WO1995008349A1 (fr) 1993-09-23 1994-09-23 Composition contenant des acides polyinsatures omega 3 et/ou omega 6 ayant de 12 a 22 atomes de carbone

Country Status (3)

Country Link
EP (1) EP0755267A1 (fr)
AU (1) AU7787194A (fr)
WO (1) WO1995008349A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997039749A3 (fr) * 1996-04-25 1997-12-04 Abbott Lab Procede de prevention et de traitement de la cachexie et de l'anorexie
US5891925A (en) * 1997-06-27 1999-04-06 Abbott Laboratories Diagnostic method for assessing the serum cholesterol response to low diets
WO2002085327A3 (fr) * 2001-04-18 2002-12-19 Oraltech Pharmaceuticals Inc Utilisation d'anti-inflammatoires non steroidiens pour la prevention et le traitement d'anomalies cellulaires de l'appareil genital feminin
EP1550441A1 (fr) * 2004-01-05 2005-07-06 Bionics Pharma Gmbh Compositions pour une thérapie synergique et topique de la douleur neuromusculaire
EP1625844A1 (fr) * 2003-05-16 2006-02-15 Lotus Pharmaceutical Co., Ltd. Composition a usage externe administree par voie percutanee
US9943495B2 (en) 2005-02-14 2018-04-17 Suntory Holdings Limited Composition containing dihomo-γ-linolenic acid (DGLA) as the active ingredient

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57131716A (en) * 1981-01-28 1982-08-14 Hiroshi Sekimoto Cosmetic for exclusive use to plantar skin
DE3246265A1 (de) * 1982-12-14 1984-06-14 Veronica 8000 München Rudder Dermatotherapeutikum zur anregung und foerderung des haarwuchses
JPH0344322A (ja) * 1989-07-13 1991-02-26 Shiseido Co Ltd マイクロエマルション製剤及びその製造法
EP0467218A2 (fr) * 1990-07-17 1992-01-22 Beiersdorf Aktiengesellschaft Combinaison d'agents actifs pour le soin de la peau

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57131716A (en) * 1981-01-28 1982-08-14 Hiroshi Sekimoto Cosmetic for exclusive use to plantar skin
DE3246265A1 (de) * 1982-12-14 1984-06-14 Veronica 8000 München Rudder Dermatotherapeutikum zur anregung und foerderung des haarwuchses
JPH0344322A (ja) * 1989-07-13 1991-02-26 Shiseido Co Ltd マイクロエマルション製剤及びその製造法
EP0467218A2 (fr) * 1990-07-17 1992-01-22 Beiersdorf Aktiengesellschaft Combinaison d'agents actifs pour le soin de la peau

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Week 8238, Derwent World Patents Index; AN 82-80257E *
DATABASE WPI Week 9114, Derwent World Patents Index; AN 91-099139 *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7223736B2 (en) 1996-04-25 2007-05-29 Abbott Laboratories Composition for the prevention and treatment of cachexia
US6077828A (en) * 1996-04-25 2000-06-20 Abbott Laboratories Method for the prevention and treatment of cachexia and anorexia
US6326355B1 (en) 1996-04-25 2001-12-04 Abbott Laboratories Method for the prevention and treatment of cachexia and anorexia
US6387883B1 (en) 1996-04-25 2002-05-14 Abbott Laboratories Method for the prevention and treatment of cachexia and anorexia
WO1997039749A3 (fr) * 1996-04-25 1997-12-04 Abbott Lab Procede de prevention et de traitement de la cachexie et de l'anorexie
US5891925A (en) * 1997-06-27 1999-04-06 Abbott Laboratories Diagnostic method for assessing the serum cholesterol response to low diets
WO2002085327A3 (fr) * 2001-04-18 2002-12-19 Oraltech Pharmaceuticals Inc Utilisation d'anti-inflammatoires non steroidiens pour la prevention et le traitement d'anomalies cellulaires de l'appareil genital feminin
EP1625844A4 (fr) * 2003-05-16 2009-05-13 Lotus Pharmaceutical Co Ltd Composition a usage externe administree par voie percutanee
EP1625844A1 (fr) * 2003-05-16 2006-02-15 Lotus Pharmaceutical Co., Ltd. Composition a usage externe administree par voie percutanee
EP1550441A1 (fr) * 2004-01-05 2005-07-06 Bionics Pharma Gmbh Compositions pour une thérapie synergique et topique de la douleur neuromusculaire
US9943495B2 (en) 2005-02-14 2018-04-17 Suntory Holdings Limited Composition containing dihomo-γ-linolenic acid (DGLA) as the active ingredient
US10342773B2 (en) 2005-02-14 2019-07-09 Suntory Holdings Limited Composition containing dihomo-γ-linolenic acid (DGLA) as the active ingredient
EP1852114B1 (fr) * 2005-02-14 2019-09-18 Suntory Holdings Limited Composition contenant de l'acide dihomo-y-linolénique (dgla) en tant que principe actif
EP3581178A1 (fr) * 2005-02-14 2019-12-18 Suntory Holdings Limited Composition contenant de l'acide dihomo-(gamma)-linolénique (dgla) en tant qu'ingrédient actif

Also Published As

Publication number Publication date
EP0755267A1 (fr) 1997-01-29
AU7787194A (en) 1995-04-10

Similar Documents

Publication Publication Date Title
US6645510B1 (en) Method of treating topical ailments
US7390507B2 (en) Compositions and methods for the treatment of radiation burns and other traumatic skin conditions
US8536228B2 (en) Transdermal compositions
US8691298B2 (en) Stabilized formulation comprising omega-3 fatty acids and use of the fatty acids for skin care and/or wound care
US20030104018A1 (en) Skin product having micro-spheres, and processes for the production thereof
US9931366B2 (en) Topical pharmaceutical bases for wound and scar treatment
RU2339362C2 (ru) Продукт для ухода за кожей, содержащий жирные кислоты таллового масла и растительные масла, для сухой и шелушащейся кожи и лечения псориаза, дерматита и экземы
US20050123576A1 (en) Mupirocin compositions for topical use, an improved process of making same and methods of using same
WO1995008349A1 (fr) Composition contenant des acides polyinsatures omega 3 et/ou omega 6 ayant de 12 a 22 atomes de carbone
US20140350106A1 (en) Urea Silicone Gel for Scars and Hydration Treatment and Method of Using Same
WO1993007874A1 (fr) Composition medicamenteuse pour application locale
EP3383362A1 (fr) Composition pour le soin de la peau
EP0609330A1 (fr) Composition pour application locale
IE47494B1 (en) An erythormycin compound,a process for preparing the compound and compositions containing the compound useful in the treatment of acne
US9913908B2 (en) Transdermal pharmaceutical bases for treating ear disorders
JP2008162937A (ja) ピセアタノール（ｐｉｃｅａｔａｎｎｏｌ）及びビタミンＡ類（ｒｅｔｉｎｏｉｄｓ）を含有する化粧品組成物
AU2023218930B2 (en) Compositions for topical treatment of radiation dermatitis
US12059393B2 (en) Compositions for topical treatment of radiation dermatitis
US20240139138A1 (en) Composition of and method for treating injury and/or skin conditions
KR20250007557A (ko) 피부 장벽 보호 전달 시스템 및 이의 방법
BG65352B1 (bg) Средство за лечение на псориазис
SK18652000A3 (sk) Farmaceutická kompozícia na báze erytromycínových solí mastných kyselín s 12 až 22 atómami uhlíka vo zvyšku mastnej kyseliny a použitie týchto erytromycínových solí mastných kyselín na topické liečenie kožných ochorení
WO2012046047A1 (fr) Composition destinée à être utilisée dans le traitement de l'acné
CZ20004496A3 (cs) Farmaceutická kompozice na bázi erythromycinu ve formě soli mastné kyseliny obsahující ve zbytku mastné kyseliny 12 až 22 uhlíkových atomů a použití erythromycinu ve formě této soli k topickému léčení kožních nemocí

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AM AT AU BB BG BR BY CA CH CN CZ DE DK ES FI GB GE HU JP KE KG KP KR KZ LK LT LU LV MD MG MN MW NL NO NZ PL PT RO RU SD SE SI SK TJ TT UA US UZ VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): KE MW SD SZ AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN 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)
WWE Wipo information: entry into national phase

Ref document number: 1994928444

Country of ref document: EP

ENP Entry into the national phase

Ref country code: US

Ref document number: 1996 615244

Date of ref document: 19960701

Kind code of ref document: A

Format of ref document f/p: F

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: 1994928444

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: CA

WWW Wipo information: withdrawn in national office

Ref document number: 1994928444

Country of ref document: EP

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载