Abstract:
A lipid layer forming composition comprises a volatile silicone oil of a boiling point above 180° C., a polar lipid, optionally a C 2 -C 4  aliphatic alcohol, optionally a pharmacologically or cosmetically active agent or a protective agent. The lipid layer forming composition can be applied to a biological surface by spraying, dipping or brushing to form a stable polar lipid layer on the surface.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to a lipid layer forming composition optionally comprising a pharmacologically or cosmetically active agent or a protective agent for administration onto a surface of a living organism, in particular onto a membrane, such as the skin or a mucous membrane. The present invention also relates to a method of forming a lipid layer on a surface. The present invention furthermore relates to a layer capable of carrying a biologically active agent disposed on a surface of a living organism or a tissue or organ thereof and to a surface covered with such a lipid layer. 
       BACKGROUND OF THE INVENTION 
       [0002]    In the pharmaceutical and cosmetic fields there is a need of a lipid composition capable of incorporating lipids and pharmacologically or cosmetically active compounds and of being evenly applicable to biological surfaces, in particular in form of a thin coherent layer. The lipid composition should be of low viscosity to facilitate delivery, in particular by spraying. While the viscosity of such a composition can be substantially reduced by adding a volatile solvent, the initially formed unstable coherent layer comprising lipid, pharmacologically or cosmetically active agent and solvent should change to a stable coherent layer by evaporation of the solvent within a time period as short as possible. 
         [0003]    While a high solvent content is beneficial by reducing viscosity it requires more time for evaporation. In other words, a high solvent content in a lipid composition of the aforementioned kind extends the time period during which the applied composition is comparatively unstable. By “comparatively unstable” is understood the stability of an applied composition comprising substantial amounts of solvent in respect of the stability of the same composition after evaporation of all or substantially all solvent. Examples of such compositions include compositions for topical administration of pharmaceutically active compounds and compositions for skin care. Compositions rich in lipids are prone to form liquid crystals, a formation which is accompanied by high viscosity caused by high degree of local order. 
         [0004]    WO 01/87344 A1 discloses a pharmaceutical or cosmetic composition comprising one or more pharmaceutically or cosmetically active agent, one or more organosilicon compound based on oligomeric or polymeric diorganosiloxane, and one or more phospholipid. When applied to the skin, the composition of WO 01/87344 A1 penetrates directly within a short period of time into the skin or into the external layers of plants treated with it, so that it cannot be rubbed off since it is rapidly absorbed into the interior of the body. For embodiments intended to be used topically in humans or animals the organosilicon compound of the composition has a boiling point varying between 15° C. and 150° C. at ambient pressure. 
       OBJECTS OF THE INVENTION 
       [0005]    It is an object of the invention to provide a lipid composition for administration onto a surface of a living organism which is easily applicable and capable of forming a coherent stable oily lipid layer on the surface. 
         [0006]    It is another object of the invention to provide such a lipid composition capable of carrying a biologically active agent. 
         [0007]    Still another object of the invention is to provide such a lipid composition that does not cause swelling when applied to the skin. 
         [0008]    A further object of the invention is to provide such a lipid composition that does not cause irritation nor give a burning feeling when applied on the skin. 
         [0009]    Further objects of the invention will be evident from the following summary of the invention, preferred embodiments thereof described in form of examples, a drawing illustrating some of the preferred embodiments, as well as from the appended claims. 
       SUMMARY OF THE INVENTION 
       [0010]    The present invention is based on the insight that silicone oils of a boiling point of 180° C. or higher, in particular of a boiling point of 200° C. or higher, can be used as an evaporating component of lipid carrier compositions for topical application, the compositions additionally comprising polar lipid and lower alcohol. “Evaporating component” indicates the capacity of silicone oils to evaporate, in spite of their high boiling point, within a short time upon application of the composition to the skin or other surface at ambient temperature or at a higher temperature. By their evaporation and the evaporation of the lower alcohol a layer of polar lipid is formed on the skin or other surface. 
         [0011]    According to the present invention is disclosed a lipid carrier composition of the aforementioned kind, comprising or substantially consisting of polar lipid, volatile silicone oil of the invention, and a lower alcohol. The lipid carrier composition of the invention is useful for providing a stable coherent polar lipid layer on a surface of a living organism. 
         [0012]    By incorporation of a pharmacologically or cosmetically active agent or a protective agent the lipid carrier composition of the invention is transformed to a pharmaceutical or cosmetic lipid composition of the invention or a protective lipid composition of the invention. The pharmaceutical, cosmetic or protective lipid composition of the invention comprising an active agent of the aforementioned kind can be used for delivering the agent on a surface of a living organism on which it is applied. A preferred surface is the skin or a mucous membrane such as the nasal or gastric mucous membrane. Another preferred surface is a plant surface, such as the surface of a grain or seed. 
         [0013]    The present invention is based on the finding that a particular class of solvents, volatile silicone oils, optionally in combination with a lower aliphatic alcohol, are particularly useful in formulating a lipid carrier composition comprising a polar lipid. After application onto a biological surface the lipid carrier composition of the invention forms an unstable polar lipid layer from which the volatile silicone oil and, if present, the lower aliphatic alcohol, evaporates readily, leaving a stable lipid layer substantially consisting of polar lipid. Correspondingly, a stable polar lipid layer comprising a pharmaceutically or cosmetically active agent is formed by incorporating the active agent into the lipid carrier composition of the invention, applying it to a biological surface, and allowing the solvent or combination of solvents to evaporate. The low viscosity of the carrier composition of the invention and the pharmaceutical or cosmetic composition of the invention seems to be due to the inability of polar lipids to form lyotropic liquid crystals, such as lamellar, hexagonal and various cubic phases of high viscosity. The lipid carrier composition and the pharmaceutical or cosmetic composition of the invention are clear and of low viscosity even at concentrations of polar lipid as high as 20% by weight. 
         [0014]    In contrast, polar lipid compositions corresponding to those of the invention but in which the silicone oil component is substituted by a corresponding amount of water are slightly viscous dispersions at low polar lipid concentrations or thick gels at higher polar lipid concentration tested, for instance 20% by weight of the composition. The high viscosity of the latter composition does not allow administration by spraying. By using the volatile silicone oil as the diluent instead of water, it is possible to incorporate a surprisingly high amount of polar lipid while only insignificantly affecting viscosity. 
         [0015]    Silicone oils of personal care grade or pharmaceutical grade useful in the invention are known in the art. Examples of useful silicone oils include dekamethylcyclopentasiloxane (Dow Corning® 245 Fluid) and dodekamethylcyclohexasiloxane (Dow Corning ® 246 Fluid). While pentasiloxanes and hexasiloxanes are preferred, hepta- and octasiloxanes are also potentially useful. The silicone oils may be cyclic siloxanes, that is, cyclomethicones, or linear siloxanes, that is, dimethicones. The silicone oils of the invention can be used in pure form or in admixture. While permethyl substitution is preferred, one or more methyl groups of a siloxane can be substituted by lower alkyl, in particular by ethyl, propyl or isopropyl. Siloxanes partially or fully substituted by lower trifluoroalkyl, in particular trifluoromethyl and pentafluoroethyl, are also useful in the invention. 
         [0016]    In addition to chemical inertness the usefulness of the silicone oil of the invention is determined by its volatility. In spite of its high boiling point above 180° C., in particular above 200° C., the silicone oil of the invention evaporates readily due to the low heat of vaporization of this class of compounds. In the invention a silicone oil having a heat of vaporization (kJ/kg) at 25° C. of from about 100 kJ/kg to about 300 kJ/kg, more preferred of from about 120 kJ/kg to about 200 kJ/kg is particularly useful. Even more preferred is a silicone oil having a heat of vaporization of from 140 kJ/kg to about 180 kJ/kg at 25° C. 
         [0017]    The silicone oil of the invention provides the carrier composition and the pharmaceutical or cosmetic composition of the invention with at least the following advantageous features: i) the ability to incorporate high contents of polar lipid material; ii) the formation of thermodynamically stable solutions; iii) the low viscosity of the solutions formed making them suitable for, e.g., spraying, dropping, painting or instilling. 
         [0018]    The lower aliphatic alcohol of the invention is a C 2  to C 4  alcohol or a mixture of such alcohols. Preferred examples of alcohols are ethanol and 2-propanol. Other useful alcohols are glycerol and 1,2-propanediol. Solvents other than lower alcohols may also be used, such as dimethyl sulfoxide and N-methyl-2-pyrrolidone. In applications with less stringent biocompatibility requirements solvents such chloroform, dichloromethane, pyridine, hexane, and methanol can be used. 
         [0019]    The polar lipid of the invention is preferably a membrane lipid such as a phospholipid, a glycolipid, a sphingolipid or a mixture thereof. A particularly preferred phospholipid is phosphatidyl choline. Other preferred phospholipids are phosphatidyl ethanolamine and phosphatidyl inositol. A particularly preferred glycolipid is galactolipid. A preferred galactolipid is digalactosyl-1,2-diacylglycerol as such or in admixture with other galactolipids and/or phospholipids and/or sphingolipids. 
         [0020]    Technical scale commercial polar lipids useful in the invention contain substantial amounts of non-polar lipids, so as to be composed of up to about 50 to 60% by weight of non-polar lipid. Thus, according to a further preferred aspect of the invention, the polar lipid component of the carrier composition or the pharmaceutical or cosmetic composition of the invention comprises a non-polar lipid in an amount of up to 30% by weight or more, such as up to 50% or 60% by weight and even up to 75% by weight. Non-polar lipids as components of polar lipids are preferably mono- and diglycerides and their mixtures, in particular monoglycerides. In a polar lipid of the invention a higher proportion of mono- and diglyceride, in particular of monoglyceride, can be tolerated than one of triglyceride. 
         [0021]    The use of a lower aliphatic alcohol such as absolute ethanol for the dissolution of the oily polar lipid of the invention is particularly useful with a lipid of a low chain-melting temperature. The chain-melting temperature is the temperature at which the acyl chains of a membrane lipid undergo a phase transition in an excess of water, from a solid-like state to a melted or liquid-like state. Membrane lipid materials like Lipoid S75, Lipoid S45, Phospholipon 50, Lipoid 5100, and DOPC all have chain-melting temperatures below 0° C. and can thus be readily dissolved in C 2  to C 4  alcohol, in particular ethanol, at concentrations up to 50% by weight and even higher. 
         [0022]    To produce the carrier composition of the invention the polar lipid, in particular a membrane lipid mixture such as a lecithin or fractionated oat oil, is dissolved in C 2  to C 4  alcohol and then diluted with a volatile silicone oil, resulting in a low-viscous, sprayable, homogenous liquid. A typical example of such a composition is one consisting of 49% DC 345, 37% fractionated oat oil (LTP Lipid Technologies Provider AB, Sweden), and 14% by weight of absolute ethanol. Fractionated oat oil is obtained from crude oat oil and is enriched in polar lipids. It typically contains about 50% by weight of non-polar lipid, such as triacylglycerol and diacylglycerol, and about 50% by weight of polar lipid, such as phospholipid and galactolipid. Typically, the content of digalactosyldiacylglycerol in a fractionated oat oils is about 20% by weight. Suitable fractionated oat oils are disclosed, for instance, in WO 99/44585 A1. 
         [0023]    Lipids like phosphatidyl ethanolamine, for instance dioleylphosphatidyl ethanolamine (DOPE), or sphingolipid, for instance sphingomyelin, can also be used as a polar lipid of the invention as such or in admixture with other polar lipids. DOPE has a chain-melting temperature of −16° C. in water and can be dissolved in absolute ethanol at 50% by weight or higher at elevated temperatures (&gt;60° C.). Such solution can be diluted with volatile silicone oil such as DC 345, resulting in a clear, low-viscous liquid. 
         [0024]    Although small amounts of water, such as 1% or 2% and even up to about 5% by weight can be tolerated, the lipid carrier composition of the invention is preferably substantially water-free, in particular has a water content of less than 5% by weight, preferably of less than 2% or 1% by weight and even less than 0.5% by weight or 0.2% by weight. 
         [0025]    The pharmacologically or cosmetically active agent or the protective agent can be incorporated in the lipid carrier composition in an amount of from 0% to 2% by weight or to 5% by weight and even up to 25% by weight or more in respect of total non-volatile components of the carrier composition, in particular polar lipid, remaining upon evaporation of its volatile components. 
         [0026]    The pharmacologically active agent for incorporation into the lipid carrier composition of the invention is preferably selected from the group consisting of: antimicrobial agent, antibiotic; antimycotic agent; antibacterial agent; antifungal agent; antiviral agent; antiseptic; anti-phlogistic; anti-pruritic agent; anti-psoriatic agent; antitussive agent; anti-alopecia agent; anti-acne agent; anti-inflammatory agent; antiulcer agent; local anaesthetic; immune response modifying agent. 
         [0027]    In particular, the pharmacologically active agent of the invention is selected from: antibacterial agents, such as oxyetracycline, fusidic acid, gentamycine, mupirocin, retapamulin (and pharmaceutically acceptable salts and derivatives thereof); antimycotic agents, such as nystatin, clotrimazole, miconazole, econazole, ketoconazole, bifonazole, and combinations of imidazole and triazole derivatives, ciclopirox, terbinafine, fluconazole, and amorolfine (and pharmaceutically acceptable salts and derivatives thereof); antiviral agents, such as aciclovir, valaciclovir, penciclovir, famciclovir, foscarnet (sodium phosphoneformate hexahydrate) and docosanol (and pharmaceutically acceptable salts and derivatives thereof); antiseptics, such as chlorhexidine and hydrogen peroxide; anti-inflammatory agents (glucocorticoids), such as hydrocortisone, clobetasone, triamcinolone, betamethasone, momethasone, and clobetasol (and pharmaceutically acceptable salts and derivatives thereof); antiphlogistics/analgesics (NSAID&#39;s), such as acetylsalicylic acid, diclofenac, and ibuprofen (and pharmaceutically acceptable salts and derivatives thereof); antipruritic agents, such as glucocorticoids, for example, hydrocortisone, clobetasone, and betamethasone, and local anaesthetics, for example, lidocaine and prilocaine (and pharmaceutically acceptable salts and derivatives thereof); antipsoriatic agents, such as calcipotriol and cyclosporine A (and pharmaceutically acceptable salts and derivatives thereof); agents for treatment of eczema and atopic dermatitis: tacrolimus and pimecrolimus (and pharmaceutically acceptable salts and derivatives thereof); antiglaucomateous agents, such as timolol, betaxolol, latanoprost, bimatoprost, and travoprost (and pharmaceutically acceptable salts and derivatives thereof); local anaesthetics, such as lidocaine, prilocaine, ropivacaine, mepivacaine, bupivacaine, levobupivacaine, benzocaine, and tetracaine (and pharmaceutically acceptable salts and derivatives thereof); agents for erectile dysfunction, such as alprostadil (prostaglandin E1) (and pharmaceutically acceptable salts and derivatives thereof); anti-dandruff agents, such as selenium sulphides, piroctone oleamine and ketoconazole; anti-alopecia agents, such as minoxidil (and pharmaceutically acceptable salts and derivatives thereof); anti-acne agents, such as tretinoin (retinoic acid), adapalene, benzoyl peroxide, clindamycin, azelaic acid (and pharmaceutically acceptable salts and derivatives thereof); wound healing agents, such as fusidic acid (and pharmaceutically acceptable salts and derivatives thereof). 
         [0028]    The cosmetically active agent for incorporation into the lipid carrier composition of the invention is preferably selected from the group consisting of: antiperspirant; antisudoral agent; antidandruff agent; glidant; moisturizing agent. 
         [0029]    The protective agent for incorporation into the lipid carrier composition of the invention is preferably selected from the group consisting of: insect repellent; UV absorbing agent; antifungal agent; antibacterial agent; antiviral agent. 
         [0030]    Examples of other agents for incorporation into the lipid carrier composition of the invention are: insect repellents, such as N,N-diethyl-m-toluamide (DEET), icaridine, and ethyl butyl acetylaminopropionate (and salts and derivatives thereof); UV sunscreens, both physical and chemical, such as titanium dioxide, benzophenon-3, butyl methoxydibenzoylmethane, ethyl hexyl methoxycinnamate, and 4-aminobenzoic acid (PABA) (and salts and derivatives thereof); tanning agents, such as dihydroxyacetone. 
         [0031]    The cosmetically active agent for incorporation into the lipid carrier composition of the invention is preferably selected from the group consisting of: antiperspirant; antisudoral agent; antidandruff agent; glidant; moisturizing agent. Preferred antidandruff agents include piroctone oleamine and ketoconazole. 
         [0032]    In addition to the pharmacologically active agent, the cosmetically active agent or the protective agent the respective composition of the invention can contain a counterirritant, in particular one selected from methyl salicylate, capsaicin, camphor and menthol. 
         [0033]    According to the present invention is also disclosed a pharmaceutical composition for administration onto a surface of a living organism comprising a pharmacologically active agent in the lipid carrier composition of the invention. 
         [0034]    According to the present invention is furthermore disclosed a cosmetic composition comprising a cosmetically active agent in the lipid carrier composition of the invention. 
         [0035]    The pharmacologically or cosmetically active agent can be dissolved or dispersed in the carrier composition or in the silicone oil, the lower alcohol, if present, and/or the oily polar lipid used for formulating the pharmaceutical or cosmetic composition of the invention. 
         [0036]    According to a preferred aspect of the invention the carrier composition of the invention comprises or consists of from 10% by weight to 30% by weight of phospholipid, from 10% by weight to 30% by weight of C 2  to C 4  alcohol, in particular ethanol, the remainder being a volatile silicone oil, with the proviso that the content of volatile silicone oil is 50% by weight or more. 
         [0037]    According to a further preferred aspect of the invention, the pharmaceutical, cosmetic or protective composition of the invention comprises or consists of from 10% by weight to 30% by weight of phospholipid, from 10% by weight to 30% by weight of C 2  to C 4  alcohol, in particular ethanol, from 0.01% by weight to 30% by weight, in particular from 0.01% by weight to 1% by weight or to 2% by weight or to 5% by weight, of pharmaceutically or cosmetically active agent or of protective agent, the remainder being a volatile silicone oil, with the proviso that the content of volatile silicone oil is 40% by weight or more. 
         [0038]    According to another preferred aspect of the invention is disclosed a pharmaceutical carrier composition, that is, a composition of the invention which does not comprise pharmaceutically or cosmetically agent or protective agent but into which such agent can be incorporated. The carrier composition can comprise or consist of from about 30% by weight to about 90% by weight of silicone oil, from about 5% by weight to about 45% by weight of polar lipid, and from about 5% by weight to about 45% by weight of C 2  to C 4  alcohol, in particular ethanol, optionally 5% by weight or less of water, in particular less than 1% by weight of water . 
         [0039]    According to still another preferred aspect of the invention is disclosed a pharmaceutical, cosmetic or protective carrier composition substantially consisting of polar lipid, volatile silicone oil and ethanol in per cent by weight proportions comprised by area F in the phase diagram of  FIG. 3 , optionally comprising 5% by weight or less, in particular 1% by weight or less, of water. 
         [0040]    By addition of a desired amount of pharmaceutical, cosmetic or protective agent of the invention, in particular of from 0.01% by weight to 2% by weight or to 5% by weight and even up to 15% by weight or up to 25 by weight in respect of polar lipid, the carrier composition of the invention can be transformed into the pharmaceutical, cosmetic or protective composition of the invention. 
         [0041]    The pharmaceutical, cosmetic or protective composition of the invention can be applied to a dry or a humid biological surface by any suitable method, such as by spraying, dipping, brushing, dropping, rubbing in. 
         [0042]    The invention will now be described in greater detail by reference to a number of Examples illustrated in a drawing. 
     
    
     
       SHORT DESCRIPTION OF THE FIGURES 
         [0043]      FIG. 1  is a ternary phase diagram of a carrier composition of the invention; 
           [0044]      FIG. 2  is a diagram showing change in transepidermal water loss (TEWL) for three compositions of the invention and vaseline as reference; 
           [0045]      FIG. 3  is another ternary phase diagram of lipid layer forming compositions of the invention including carrier compositions and compositions comprising active agent. 
       
    
    
     DESCRIPTION OF PREFERRED EMBODIMENTS 
     Materials 
       [0046]      
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Silicone oils and lipids used in the formulation experiments 
               
             
          
           
               
                 Short name 
                 Supplier, trade name 
                 Chemical name, CAS No. 
                 Lot No. 
               
               
                   
               
               
                 DC 345 
                 Dow Corning ® 345 
                 Dekamethylcyclopentasiloxane, 
                 5627357 
               
               
                   
                 Fluid 
                 541-02-6 
               
               
                 DC 245 
                 Dow Corning ® 245 
                 Dekamethylcyclopentasiloxane, 
                 5480964 
               
               
                   
                 Fluid 
                 541-02-6 
               
               
                 DC 246 
                 Dow Corning ® 246 
                 Dodekamethylcyclohexasiloxane, 
                 5264620 
               
               
                   
                 Fluid 
                 540-97-6 
               
               
                 DMPC 
                 Lipoid DMPC 
                 Dimyristoyl phosphatidylcholine, 
                 562212-1/13 
               
               
                   
                   
                 13699-48-4 
               
               
                 DPPC 
                 Lipoid DPPC 
                 Dipalmitoyl phosphatidylcholine, 
                 563086-1/94 
               
               
                   
                   
                 2644-64-6 
               
               
                 DOPC 
                 Lipoid DOPC 
                 Dioleoyl phosphatidylcholine, 
                 566073-1/32 
               
               
                   
                   
                 10015-85-7 
               
               
                 DMPG 
                 Lipoid DMPG, Na salt 
                 Dimyristoyl phosphatidylglycerol 
                 602081-1/10 
               
               
                   
                   
                 sodium salt, 200880-40-6 
               
               
                 DPPG 
                 Lipoid DPPG, Na salt 
                 Dipalmitoyl phosphatidylglycerol 
                 603032-1/36 
               
               
                   
                   
                 sodium salt, 200880-41-7 
               
               
                 DMPE 
                 Lipoid DMPE 
                 Dimyristoyl phosphatidyl- 
                 699201-1/05 
               
               
                   
                   
                 ethanolamine, 20255-95-2 
               
               
                 DPPE 
                 Lipoid DPPE 
                 Dipalmitoyl phosphatidyl- 
                 653004-1/19 
               
               
                   
                   
                 ethanolamine, 3026-45-7 
               
               
                 DOPE 
                 Lipoid DOPE 
                 Dioleoylphosphatidyl 
                 656006-01/012 
               
               
                   
                   
                 ethanolamine, 2462-63-7 
               
               
                 MOG 
                 Fluka (Sigma-Aldrich), 
                 Monooleoylglycerol, 25496-72-4 
                 1384627 
               
               
                   
                 Monoolein 
               
               
                 MCM 
                 Aarhus Karlshamn, 
                 Medium chain monoglycerides 
                 8192270 
               
               
                   
                 Akoline MCM 
               
               
                 CPL-GL 
                 LTP, CPL ®- 
                 Chromatographically purified 
                 KGL06002 
               
               
                   
                 Galactolipid 
                 galactolipids 
               
               
                 O65 
                 Swedish Oat Fiber, 
                 Galactolipid enriched oat oil 
                 PL 090219 
               
               
                   
                 Oatwell 65 oat oil 
               
               
                 Chol 
                 Sigma-Aldrich, 
                 Cholesterol, 57-88-5 
                 057K0683 
               
               
                   
                 Cholesterol 
               
               
                 IPM 
                 Croda, Crodamol IPM 
                 Isopropyl myristate, 110-27-0 
                 LB03845 
               
               
                 S45 
                 Lipoid S45 
                 Soy bean lecithin, 8002-43-5 
                 745303-1/926 
               
               
                 S75 
                 Lipoid S75 
                 Soy bean lecithin, 8002-43-5 
                 776132-07/918 
               
               
                 S100 
                 Lipoid S100 
                 Soy bean lecithin, 8002-43-5 
                 790551-7/910 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Active substances used in the formulation experiments*) 
               
             
          
           
               
                 Active substance 
                 CAS No. 
                 Supplier 
                 Lot No. 
               
               
                   
               
               
                 Lidocaine 
                 137-58-6 
                 Sigma-Aldrich 
                 047K0080 
               
               
                 Hydrocortisone 
                 50-23-7 
                 Sigma-Aldrich 
                 010M1568 
               
               
                 Dihydroxyacetone 
                 96-26-4 
                 Sigma-Aldrich 
                 04306BJ-409 
               
               
                 LL-37 
                 — 
                 PolyPeptide 
                 1013/11 
               
               
                   
                   
                 Laboratories A/S 
               
               
                 DPK-060 
                 — 
                 Dermagen 
                 0508074339 
               
               
                 Oxytocin acetate 
                 50-56-6 
                 Sigma-Aldrich 
                 068K8762 
               
               
                   
               
               
                 *)Further information is given in the EXAMPLES 
               
             
          
         
       
     
         [0047]    Alcohols used in the formulation experiments were ethanol 99.9% (“EtOH”, VWR), 2-propanol HPLC grade (“IPA”, Rathburn), glycerol 99.5% (“Gro”, VWR) and 1,2-propanediol, Ph. Eur. (“PD”, Fluka/Sigma-Aldrich). The materials used in the formulation experiments were provided by the following suppliers: Dow Corning Corp., Midland, Mich., USA; Lipoid GmbH, Ludwigshafen, Germany; Aarhus Karlshamn Sweden AB, Karlshamn, Sweden; LTP Lipid Technologies Provider AB, Karlshamn, Sweden; Swedish Oat Fiber AB, Väröbacka, Sweden; Sigma-Aldrich, St. Louis, Mo., USA; Croda, Goole, East Yorkshire, UK; Rathburn Chemicals Ltd, Walkerburn, Scotland, UK; VWR International AB, Spånga, Sweden; PolyPeptide Laboratories A/S, Hillerød, Denmark; Dermagen AB, Lund, Sweden. 
       EXAMPLE 1 
     Formulation of a Local Anaesthetic: Lidocaine and Lidocaine Hydrochloride 
     Composition A: 
       [0048]      
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                   
                   
               
               
                   
                 Ingredient 
                 % (w/w) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Lidocaine (Sigma L7757) 
                 3.9 
               
               
                   
                 Phospholipid (Lipoid S75) 
                 19.5 
               
               
                   
                 Absolute ethanol 
                 19.5 
               
               
                   
                 Volatile silicone oil (DC 345) 
                 57.1 
               
               
                   
                   
               
             
          
         
       
     
       Composition B: 
       [0049]      
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                   
                   
               
               
                   
                 Ingredient 
                 % (w/w) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Lidocaine hydrochloride (Sigma L5647) 
                 2.0 
               
               
                   
                 Phospholipid (Lipoid S75) 
                 20.0 
               
               
                   
                 Absolute ethanol 
                 20.0 
               
               
                   
                 Volatile silicone oil (DC 345) 
                 58.0 
               
               
                   
                   
               
             
          
         
       
     
         [0050]    The phospholipid was dissolved in absolute ethanol at a concentration of 50.0% (w/w). Complete dissolution of the phospholipid was promoted by short ultrasonication in a bath-type sonicator at about 40° C. 
         [0051]    To a pre-weighed amount of lidocaine and lidocaine hydrochloride, respectively, was added the ethanolic phospholipid solution. The mixtures were gently heated and sonicated until clear solutions had been formed. The solutions were diluted with volatile silicone oil to obtain light brown to yellow solutions, which were stored in air-tight glass vials at room temperature. The appearance of compositions (compositions A and B) was unchanged for more than a month at room temperature. No signs of phase separation or precipitation and subsequent sedimentation were observed. This indicates excellent physical stability. 
       EXAMPLE 2 
     Formulation of a Local Anaesthetic: Benzocaine 
       [0052]    A pre-weighed amount of benzocaine was dissolved in a 50% (w/w) ethanolic phospholipid, prepared as described in Example 1. The solution was diluted with the volatile silicone oil. The resulting clear, light brown to yellow solution was stored in an air-tight glass vial at room temperature. The appearance of the composition (composition C) was unchanged for more than a month at room temperature. No signs of phase separation or precipitation and subsequent sedimentation were observed, which indicates excellent physical stability. 
       Composition C: 
       [0053]      
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                   
                   
               
               
                   
                 Ingredient 
                 % (w/w) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Benzocaine (Fluka 06952) 
                 4.0 
               
               
                   
                 Phospholipid (Lipoid S75) 
                 20.2 
               
               
                   
                 Absolute ethanol 
                 20.2 
               
               
                   
                 Volatile silicone oil (DC 345) 
                 55.6 
               
               
                   
                   
               
             
          
         
       
     
       EXAMPLE 3 
     Formulation of an Insect Repellent: N,N-diethyl-m-toluamide (DEET) 
     Composition D: 
       [0054]      
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                   
                   
               
               
                   
                 Ingredient 
                 % (w/w) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 DEET (Aldrich D10,095-1) 
                 13.4 
               
               
                   
                 Phospholipid (Lipoid S75) 
                 16.7 
               
               
                   
                 Absolute ethanol 
                 16.7 
               
               
                   
                 Volatile silicone oil (DC 345) 
                 53.2 
               
               
                   
                   
               
             
          
         
       
     
         [0055]    To a pre-weighed amount of DEET was added 50% (w/w) ethanolic phospholipid prepared as described in Example 1. The obtained clear solution was diluted with the volatile silicone oil. The resulting clear, light brown to yellow solution was stored in an air-tight glass vial at room temperature. The appearance of the composition (composition D) was unchanged for more than a month at room temperature. No signs of phase separation or precipitation and subsequent sedimentation were observed, which indicates excellent physical stability. 
       EXAMPLE 4 
     Formulation of an Antifungal Agent: Econazole Nitrate 
       [0056]      
         [0000]    
       
         
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                   
                 Compo- 
                 Compo- 
                 Compo- 
               
               
                   
                 sition E: 
                 sition F: 
                 sition G: 
               
               
                 Ingredient 
                 % (w/w) 
                 % (w/w) 
                 % (w/w) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Econazole nitrate (Sigma E4632) 
                 2.3 
                 1.1 
                 1.5 
               
               
                 Phospholipid (Lipoid S75) 
                 29.1 
                 14.5 
                 21.2 
               
               
                 Absolute ethanol 
                 29.1 
                 14.5 
                 21.2 
               
               
                 Volatile silicone oil (DC 345) 
                 39.5 
                 69.9 
                 56.1 
               
               
                   
               
             
          
         
       
     
         [0057]    Three compositions (E, F, G) were prepared. To pre-weighed amounts of econazole nitrate was added 50% (w/w) ethanolic phospholipid prepared as described in Example 1. After treatment in a bath-type sonicator at about 37° C., the obtained clear golden brown solutions were diluted with the volatile silicone oil. The resulting clear, light golden brown solutions were stored in air-tight glass vials at room temperature. composition F was prepared by diluting a portion of composition E with volatile silicone oil. 
         [0058]    The appearance of compositions E and F changed within a few days (slight sedimentation was observed in both samples) and therefore cannot be considered stable. On the other hand, the appearance of Composition G was unchanged for more than a month at room temperature. No signs of phase separation or precipitation and subsequent sedimentation were observed, indicating excellent physical stability. 
       EXAMPLE 5 
     Formulation of a Glucocorticoid: Betamethasone 17-Valerate 
       [0059]    Three compositions (H, I, J) were prepared. To pre-weighed amounts of betamethasone 17-valerate was added 50% (w/w) ethanolic phospholipid prepared as described in Example 1. After treatment in a bath-type sonicator at about 37° C., clear golden brown solutions were obtained. The solutions were diluted with the volatile silicone oil and the resulting mixtures stored in air-tight glass vials at room temperature. 
         [0060]    Composition I was prepared by diluting a portion of Composition H with volatile silicone oil. Composition I was unstable since it formed immediately a milky dispersion, which separated within a few days. Compositions H and J formed clear, light golden brown solutions. They showed no signs of phase separation or precipitation and subsequent sedimentation after storage for one month at room temperature. This indicates excellent physical stability. 
         [0000]    
       
         
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                   
                 Compo- 
                 Compo- 
                 Compo- 
               
               
                   
                 sition H: 
                 sition I: 
                 sition J: 
               
               
                 Ingredient 
                 % (w/w) 
                 % (w/w) 
                 % (w/w) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Betamethasone 17-valerate 
                 0.5 
                 0.1 
                 0.1 
               
               
                 (Sigma B0515) 
               
               
                 Phospholipid (Lipoid S75) 
                 13.3 
                 2.7 
                 21.1 
               
               
                 Absolute ethanol 
                 13.3 
                 2.7 
                 21.1 
               
               
                 Volatile silicone oil (DC 345) 
                 72.9 
                 94.5 
                 57.7 
               
               
                   
               
             
          
         
       
     
       EXAMPLE 6 
     Formulation of an Anti-Psoriatic Agent: Cyclosporin A 
     Composition K: 
       [0061]      
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                   
                   
               
               
                   
                 Ingredient 
                 % (w/w) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Cyclosporin A (Sigma, 30024) 
                 0.4 
               
               
                   
                 Phospholipid (Lipoid S75) 
                 16.0 
               
               
                   
                 Absolute ethanol 
                 16.0 
               
               
                   
                 Volatile silicone oil (DC 345) 
                 67.6 
               
               
                   
                   
               
             
          
         
       
     
         [0062]    To a pre-weighed amount of cyclosporin A was added a 50% (w/w) ethanolic phospholipid solution, prepared as described in Example 1. After treatment in a bath-type sonicator at about 35° C., a clear solution was obtained. The solution was diluted with the volatile silicone oil to form a clear, light brown to yellow solution, which was stored in an air-tight glass vial at room temperature. The appearance of the composition (composition K) was unchanged for more than a month at room temperature. No signs of phase separation or precipitation and subsequent sedimentation were observed. This indicates excellent physical stability. 
       EXAMPLE 7 
     Formulation of an Anti-Alopecia Agent: Minoxidil 
       [0063]    Three compositions (M, N, O) were prepared. To pre-weighed amounts of minoxidil was added a 33% (w/w) ethanolic phospholipid solution, ethanol, and 50% (w/w) ethanolic phospholipid. After treatment in a bath-type sonicator at about 35° C., the resulting mixtures were diluted with the volatile silicone oil and stored in air-tight glass vials at room temperature. 
         [0000]    
       
         
               
               
               
               
             
               
               
               
               
             
           
               
                   
               
               
                   
                 Compo- 
                 Compo- 
                 Compo- 
               
               
                   
                 sition M: 
                 sition N: 
                 sition O: 
               
               
                 Ingredient 
                 % (w/w) 
                 % (w/w) 
                 % (w/w) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 Minoxidil (Tripharma) 
                 0.67 
                  0.98 
                 0.65 
               
               
                 Phospholipid (Lipoid S75) 
                 21.98 
                 — 
                 17.75 
               
               
                 Absolute ethanol 
                 21.98 
                 40.27 
                 35.49 
               
               
                 Volatile silicone oil (DC 345) 
                 55.37 
                 58.75 
                 46.11 
               
               
                   
               
             
          
         
       
     
         [0064]    The appearance of composition O stayed unchanged for more than two months at room temperature, i.e., no signs of phase separation or precipitation and subsequent sedimentation were observed. This indicates excellent physical stability. Composition M did not show complete dissolution of minoxidil, whereas Composition N started to precipitate shortly after preparation. Thus compositions M and N did not meet the criteria of one-month stability when stored in a closed container at room temperature. 
       EXAMPLE 8 
     Miscibility Test 
       [0065]    Presented in Table 3 are miscibility data of ethanolic phospholipid solutions with either volatile silicone oil or water. The mixtures with a low content of PL/ethanol in the silicone oil had a clear appearance immediately after preparation, but separated within a month at room temperature. The composition with a concentration of PL/ethanol of 20% was miscible with the volatile silicone oil, did not change in appearance during this time period and can thus be considered to be physically stable. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Dilution of ethanolic phospholipid (PL; Lipoid S75) solutions with volatile silicone 
               
               
                 oil (DC 345) and water, respectively. All percentages are by weight 
               
             
          
           
               
                 Composition 
                   
                 Volatile 
                   
                   
                 Conc. 
                 Conc. 
                 Appearance 
                 Appearance 
               
               
                 of EtOH 
                 EtOH 
                 silicone 
                   
                 Conc. 
                 of 
                 of 
                 directly after 
                 after one 
               
               
                 solution 
                 solution 
                 oil 
                 Water 
                 of PL 
                 ethanol 
                 diluent 
                 dilution 
                 month at RT 
               
               
                   
               
             
          
           
               
                 75.0% PL 
                 1.01 g 
                 1.60 g 
                 — 
                 29.0% 
                 9.7% 
                 61.3% 
                 Opaque 
                 — 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dispersion, clear 
               
               
                   
                   
                   
                   
                   
                   
                   
                 on warming 
               
               
                 75.0% PL 
                 1.01 g 
                 2.22 g 
                 — 
                 23.5% 
                 7.8% 
                 68.7% 
                 Opaque 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dispersion, clear 
               
               
                   
                   
                   
                   
                   
                   
                   
                 on warming 
               
               
                 50.0% PL 
                 5.00 g 
                 7.50 g 
                 — 
                 20.0% 
                 20.0% 
                 60.0% 
                 Clear, low- 
                 Unchanged 
               
               
                   
                   
                   
                   
                   
                   
                   
                 viscous light 
               
               
                   
                   
                   
                   
                   
                   
                   
                 brown solution 
               
               
                 50.0% PL 
                 5.00 g 
                 — 
                 7.52 g 
                 20.0% 
                 20.0% 
                 60.0% 
                 Viscous gel 
                 Unchanged 
               
               
                 50.0% PL 
                 0.50 g + 
                 7.51 g 
                 — 
                 2.0% 
                 38.0% 
                 60.0% 
                 Clear, low- 
               
               
                   
                 4.51 g 
                   
                   
                   
                   
                   
                 viscous light 
               
               
                   
                 neat 
                   
                   
                   
                   
                   
                 yellow, opaque 
               
               
                   
                 EtOH 
                   
                   
                   
                   
                   
                 solution 
               
               
                 50.0% PL 
                 0.50 g 
                 4.51 g 
                 — 
                 5.0% 
                 5.0% 
                 90.0% 
                 Clear, low- 
                 Phase 
               
               
                   
                   
                   
                   
                   
                   
                   
                 viscous light 
                 separation 
               
               
                   
                   
                   
                   
                   
                   
                   
                 yellow solution 
               
               
                 50.0% PL 
                 0.50 g 
                 — 
                 4.52 g 
                 5.0% 
                 5.0% 
                 90.0% 
                 Homogeneous 
                 Unchanged 
               
               
                   
                   
                   
                   
                   
                   
                   
                 viscous 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dispersion 
               
               
                 33.3% PL 
                 0.50 g 
                 4.50 g 
                 — 
                 3.3% 
                 6.7% 
                 90.0% 
                 Clear, low- 
                 Phase 
               
               
                   
                   
                   
                   
                   
                   
                   
                 viscous light 
                 separation 
               
               
                   
                   
                   
                   
                   
                   
                   
                 yellow solution 
               
               
                 33.3% PL 
                 0.50 g 
                 — 
                 4.52 g 
                 3.3% 
                 6.7% 
                 90.0% 
                 Homogeneous 
                 Unchanged 
               
               
                   
                   
                   
                   
                   
                   
                   
                 dispersion 
               
               
                   
               
             
          
         
       
     
         [0066]    The phospholipid of Table 1 is Lipoid S75 manufactured by Lipoid GmbH, Ludwigshafen, Germany. This phospholipid material from soybean contains about 68-73% of phosphatidyl choline (PC). Other suitable phospholipid materials are, for example, Lipoid S45, Phospholipon 50, and Lipoid S100, all made from soybean and manufactured by Lipoid GmbH, covering a range of PC content of about 50% up to 100% Further suitable phospholipids are the synthetic dioleyl phosphatidylcholine (DOPC), dimyristyl phosphatidylcholine (DMPC), and dipalmitoyl phosphatidylcholine (DPPC). 
       EXAMPLE 9 
     Phase Diagram 
       [0067]      FIG. 1  illustrates an exemplary phase diagram of the ternary system of the polar lipid carrier composition of the invention: polar lipid (Lipoid S75)/C 2 -C 4  alcohol (ethanol)/silicone oil (DC 345). Incorporation of small amounts of a pharmacologically or cosmetically active agent of the invention or of a protective agent of the invention will only insignificantly affect the area of stability. Carrier composition CC consisting of 40% by weight of polar lipid Lipoid S75, 30% by weight of ethanol and 30% by weight of silicone oil DC 345 is an example of a stable carrier composition. 
       EXAMPLE 10 
     Phospolipid Based Carrier Compositions 
       [0068]    Phospholipid was dissolved in mixtures of DC 345 volatile silicone oil and alcohol. The lipid was accurately weighed and mixed with silicone oil and alcohol. The mixture was gently agitated at 40° C. until a homogenous, clear and colourless or slightly yellow liquid was obtained. Table 4a shows examples of compositions based on phosphatidyl cholines and Table 4b compositions based on phosphatidyl ethanolamines. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 4a 
               
             
             
               
                   
               
               
                 Carrier compositions based on phosphatidyl cholines 
               
             
          
           
               
                 Composition 
                 Lipid 
                 % w/w 
                 DC 345, % w/w 
                 EtOH, % w/w 
               
               
                   
               
             
          
           
               
                 PC-1 
                 DMPC 
                 3.8 
                 91.4 
                 4.8 
               
               
                 PC-2 
                 DMPC 
                 7.9 
                 82.9 
                 9.2 
               
               
                 PC-3 
                 DMPC 
                 16.5 
                 62.6 
                 20.9 
               
               
                 PC-4 
                 DMPC 
                 33.3 
                 33.4 
                 33.4 
               
               
                 PC-5 
                 DOPC 
                 23.0 
                 57.8 
                 19.3 
               
               
                 PC-6 
                 DOPC 
                 22.4 
                 38.8 
                 38.8 
               
               
                 PC-7 
                 DPPC 
                 16.5 
                 41.7 
                 41.7 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 4b 
               
             
             
               
                   
               
               
                 Carrier compositions based on phosphatidyl ethanolamines 
               
             
          
           
               
                   
                   
                   
                 DC 345, 
                 EtOH, 
                 IPA, 
               
               
                 Composition 
                 Lipid 
                 % w/w 
                 % w/w 
                 % w/w 
                 % w/w 
               
               
                   
               
             
          
           
               
                 PE-1 
                 DOPE 
                 4.5 
                 90.7 
                   
                 4.8 
               
               
                 PE-2 
                 DOPE 
                 4.6 
                 90.6 
                 4.9 
               
               
                 PE-3 
                 DOPE 
                 7.0 
                 83.7 
                 9.3 
               
               
                 PE-4 
                 DOPE 
                 10.3 
                 80.8 
                 9.0 
               
               
                 PE-5 
                 DOPE 
                 14.9 
                 63.8 
                 21.3 
               
               
                   
               
             
          
         
       
     
       EXAMPLE 11 
     Acylglycerol Based Carrier Compositions 
       [0069]    Commercially available monoglyceride products are mixtures of monoacyl-, diacyl- and small amounts of triacylglycerols. The acylglycerol products were dissolved in mixtures of DC 345 volatile silicone oil and alcohol. The lipid was accurately weighed and mixed with silicone oil and alcohol. The mixture was gently agitated at 40° C. until a homogenous, clear and colourless liquid was obtained. Table 5 shows examples of compositions based on acylglycerols. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Carrier compositions based on acylglycerols 
               
             
          
           
               
                   
                   
                   
                 DC 345, 
                 EtOH, 
                 IPA, 
               
               
                 Composition 
                 Lipid 
                 % w/w 
                 % w/w 
                 % w/w 
                 % w/w 
               
               
                   
               
             
          
           
               
                 MG-1 
                 MCM 
                 13.6 
                 86.4 
                   
                   
               
               
                 MG-2 
                 MCM 
                 9.8 
                 87.5 
                   
                 2.7 
               
               
                 MG-3 
                 MCM 
                 21.6 
                 74.5 
                 3.9 
               
               
                 MG-4 
                 MCM 
                 41.2 
                 44.1 
                 14.7 
               
               
                 MG-5 
                 MOG 
                 4.7 
                 92.9 
                   
                 2.5 
               
               
                 MG-6 
                 MOG 
                 4.6 
                 91.7 
                 3.7 
               
               
                 MG-7 
                 MOG 
                 3.6 
                 91.6 
                 4.8 
               
               
                 MG-8 
                 MOG 
                 9.6 
                 81.3 
                 9.0 
               
               
                 MG-9 
                 MOG 
                 19.0 
                 60.7 
                 20.2 
               
               
                 MG-10 
                 MOG 
                 38.3 
                 30.8 
                 30.8 
               
               
                   
               
             
          
         
       
     
       EXAMPLE 12 
     Carrier Compositions Based on Cholesterol 
       [0070]    Compositions comprising cholesterol were prepared by mixing with DC 345 volatile silicone oil and alcohol. The lipid was accurately weighed and mixed with silicone oil and alcohol. The mixture was gently agitated at 40° C. until a homogenous, clear and colourless liquid was obtained. Table 6 shows examples of compositions based on cholesterol. 
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 Carrier compositions based on cholesterol 
               
             
          
           
               
                 Composition 
                 Cholesterol, % w/w 
                 DC 345, % w/w 
                 EtOH, % w/w 
               
               
                   
               
             
          
           
               
                 Chol-1 
                 1.4 
                 88.8 
                 9.9 
               
               
                 Chol-2 
                 2.1 
                 73.4 
                 24.5 
               
               
                 Chol-3 
                 3.0 
                 48.5 
                 48.5 
               
               
                   
               
             
          
         
       
     
       EXAMPLE 13 
     Carrier Compositions Based on Galactolipid Rich Materials 
       [0071]    Two examples of galactolipid rich materials were used to prepare mixtures with DC 345 volatile silicone oil and alcohols. The lipid was accurately weighed and mixed with silicone oil and alcohols. The mixture was gently agitated at 40° C. until a homogenous, clear and slightly yellow to brownish yellow liquid was obtained. Table 7 shows examples of compositions based on galactolipid rich lipids. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 Carrier compositions based on galactolipid rich materials 
               
             
          
           
               
                   
                   
                   
                 DC 345, 
                 EtOH, 
                 IPA, 
               
               
                 Composition 
                 Lipid 
                 % w/w 
                 % w/w 
                 % w/w 
                 % w/w 
               
               
                   
               
             
          
           
               
                 GL-1 
                 CPL-GL 
                 4.9 
                 71.3 
                 23.8 
                   
               
               
                 GL-2 
                 CPL-GL 
                 36.0 
                 32.0 
                 32.0 
               
               
                 GL-3 
                 O65 
                 3.3 
                 73.4 
                 4.7 
                 18.7 
               
               
                   
               
             
          
         
       
     
       EXAMPLE 14  
     Carrier Compositions Based on Lipid Combinations 
       [0072]    The ability to combine lipids with different properties in volatile silicon oil/alcohol mixtures was tested. The lipid materials were accurately weighed and mixed with silicone oil and alcohol. The mixture was gently agitated at 40° C. until a homogenous, clear and colourless or slightly yellow liquid was obtained. Table 8 shows examples of compositions based on various combinations of lipids. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 Carrier compositions based on lipid combinations 
               
             
          
           
               
                 Compo- 
                   
                 % 
                   
                 % 
                 DC 345, 
                 EtOH, 
                 IPA, % 
               
               
                 sition 
                 Lipid 1 
                 w/w 
                 Lipid 2 
                 w/w 
                 % w/w 
                 % w/w 
                 w/w 
               
               
                   
               
             
          
           
               
                 Comb-1 
                 IPM 
                 8.9 
                 DOPC 
                 8.3 
                 78.7 
                 4.1 
                   
               
               
                 Comb-2 
                 IPM 
                 9.0 
                 DOPE 
                 5.2 
                 81.5 
                 4.3 
               
               
                 Comb-3 
                 MCM 
                 6.9 
                 DOPC 
                 5.8 
                 82.9 
                 4.4 
               
               
                 Comb-4 
                 MOG 
                 10.3 
                 DOPC 
                 0.9 
                 85.1 
                   
                 3.7 
               
               
                 Comb-5 
                 MCM 
                 8.9 
                 Chol 
                 1.0 
                 79.8 
                 10.3 
               
               
                   
               
             
          
         
       
     
       EXAMPLE 15 
     Carrier Compositions Based on Commercially Available Lecithin 
       [0073]      
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 9 
               
             
             
               
                   
               
               
                 Carrier compositions based on lecithin 
               
             
          
           
               
                   
                   
                   
                 DC 345, 
                 EtOH, 
                 IPA, 
               
               
                 Composition 
                 Lecithin 
                 % w/w 
                 % w/w 
                 % w/w 
                 % w/w 
               
               
                   
               
             
          
           
               
                 Lec-1 
                 S45 
                 5.6 
                 89.7 
                 4.7 
                   
               
               
                 Lec-2 
                 S45 
                 9.9 
                 81.1 
                 9.0 
               
               
                 Lec-3 
                 S45 
                 30.3 
                 52.3 
                 17.4 
               
               
                 Lec-4 
                 S45 
                 35.8 
                 32.1 
                 32.1 
               
               
                 Lec-5 
                 S75 
                 14.8 
                 76.5 
                 4.0 
                 4.7 
               
               
                 Lec-6 
                 S75 
                 25.4 
                 63.4 
                 7.0 
                 4.2 
               
               
                 Lec-7 
                 S75 
                 16.3 
                 75.3 
                 8.4 
               
               
                 Lec-8 
                 S75 
                 43.4 
                 42.5 
                 14.2 
               
               
                 Lec-9 
                 S75 
                 39.3 
                 30.4 
                 30.4 
               
               
                 Lec-10 
                 S100 
                 13.1 
                 65.2 
                 21.7 
               
               
                 Lec-11 
                 S100 
                 27.3 
                 36.3 
                 36.3 
               
               
                   
               
             
          
         
       
     
         [0074]    Commercially available lecithin products are in mixtures of polar lipids (mainly phospholipids) and non-polar lipids (mainly triglycerides). The materials used in the following examples are all obtained from soy beans and contain phosphatidyl choline as the main polar lipid. The lipid was accurately weighed and mixed with silicone oil and alcohol. The mixture was gently agitated at 40° C. until a homogenous, clear and yellow or brownish yellow liquid was obtained. Table 9 shows examples of compositions based on lecithins. 
       EXAMPLE 16 
     Carrier Compositions with Different Silicone Oils 
       [0075]    The possibility to use different volatile silicone oils was tested by replacing DC 345 by two other silicone oils, DC 245 and DC 246. The lipid was weighed and mixed with silicone oil and alcohol. The mixture was gently agitated at 40° C. until a homogenous, clear and colourless liquid was obtained. Table 10 shows examples of compositions comprising DC 245 and DC 246. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 10 
               
             
             
               
                   
               
               
                 Carrier compositions with volatile silicone oils DC 245 and DC 246 
               
             
          
           
               
                   
                 Silicone 
                   
                   
                   
                 EtOH, % 
                 IPA, 
               
               
                 Composition 
                 oil 
                 % w/w 
                 Lipid 
                 % w/w 
                 w/w 
                 % w/w 
               
               
                   
               
             
          
           
               
                 Sil-1 
                 DC 245 
                 81.8 
                 DOPE 
                 9.1 
                 9.1 
                   
               
               
                 Sil-2 
                 DC 245 
                 88.0 
                 MCM 
                 5.1 
                   
                 6.9 
               
               
                 Sil-3 
                 DC 245 
                 94.0 
                 MCM 
                 2.2 
                   
                 3.8 
               
               
                 Sil-4 
                 DC 246 
                 83.3 
                 DOPE 
                 7.4 
                 9.3 
               
               
                   
               
             
          
         
       
     
       EXAMPLE 17 
     Carrier Compositions Based on Lipids and Small Amounts of Water 
       [0076]      
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 11 
               
             
             
               
                   
               
               
                 Carrier compositions with small amounts of water 
               
             
          
           
               
                   
                   
                   
                 Water, 
                 DC345, 
                 EtOH, % 
                 IPA, % 
               
               
                 Composition 
                 Lipid 
                 % w/w 
                 % w/w 
                 % w/w 
                 w/w 
                 w/w 
               
               
                   
               
             
          
           
               
                 Wat-1 
                 DMPC 
                 7.0 
                 4.7 
                 79.5 
                 8.8 
                   
               
               
                 Wat-2 
                 DMPG 
                 2.3 
                 5.3 
                 69.4 
                 23.1 
               
               
                 Wat-3 
                 DOPE 
                 6.8 
                 2.5 
                 58.1 
                 14.9 
                 17.7 
               
               
                 Wat-4 
                 S75 
                 9.7 
                 4.4 
                 53.7 
                 10.8 
                 21.5 
               
               
                 Wat-5 
                 S75 
                 5.5 
                 2.0 
                 72.9 
                 8.1 
                 11.4 
               
               
                   
               
             
          
         
       
     
         [0077]    The possibility to add small amounts of water to the vehicles of the invention was tested. The lipid was accurately weighed and mixed with silicone oil and alcohol. A small amount of water and optionally isopropanol was added. The mixture was gently agitated at 40° C. until a homogenous, clear and colourless or brownish yellow liquid was obtained. Table 11 shows examples of compositions with small amounts of water. 
       EXAMPLE 18  
     DPK-060 Peptide Compositions in Silicone Oil/Lipid Vehicles 
       [0078]    Accurately weighed amounts of the peptide DPK-060 were dissolved in mixtures of lipid, glycerol, 1,2-propanediol and ethanol at 40° C. under agitation. Silicone oil (DC 345) and isopropanol was added and the mixture was gently agitated at 40° C. until a homogenous, clear and colourless to brownish yellow liquid was obtained. Table 12 presents representative examples of DPK-060 compositions. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 12 
               
             
             
               
                   
               
               
                 DPK-060 peptide compositions in silicone oil/lipid vehicles 
               
             
          
           
               
                   
                 DPK- 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 060 
                   
                 % 
                 Gro % 
                 PD % 
                 DC 345 
                 EtOH % 
                 IPA % 
                 % active/ 
               
               
                 Composition 
                 % w/w 
                 Lipid 
                 w/w 
                 w/w 
                 w/w 
                 % w/w 
                 w/w 
                 w/w 
                 nonvol.* 
               
               
                   
               
             
          
           
               
                 KL-DPK-21 
                 0.033 
                 S75 
                 3.9 
                 6.4 
                   
                 58.2 
                 13.0 
                 18.5 
                 0.32 
               
               
                 KL-DPK-22 
                 0.199 
                 S75 
                 5.7 
                 10.1 
                 2.8 
                 39.3 
                 12.5 
                 29.3 
                 1.06 
               
               
                 KL-DPK-23 
                 0.056 
                 S45 
                 3.9 
                 6.6 
                   
                 56.8 
                 12.5 
                 20.1 
                 0.53 
               
               
                 KL-DPK-24 
                 0.129 
                 S45 
                 5.8 
                 9.8 
                 2.9 
                 39.5 
                 12.6 
                 29.3 
                 0.69 
               
               
                 KL-DPK-25 
                 0.095 
                 DOPC 
                 3.8 
                 6.6 
                   
                 56.2 
                 13.0 
                 20.3 
                 0.90 
               
               
                 KL-DPK-26 
                 0.272 
                 DOPC 
                 6.8 
                 10.3 
                 2.8 
                 40.8 
                 13.1 
                 26.0 
                 1.34 
               
               
                 KL-DPK-27 
                 0.036 
                 065 
                 4.0 
                 6.3 
                   
                 54.3 
                 11.6 
                 23.7 
                 0.35 
               
               
                 KL-DPK-28 
                 0.058 
                 065 
                 5.6 
                 9.6 
                 2.8 
                 38.9 
                 11.4 
                 31.5 
                 0.32 
               
               
                 KL-DPK-29 
                 0.096 
                 DOPE 
                 4.4 
                 6.9 
                   
                 57.8 
                 12.9 
                 17.9 
                 0.84 
               
               
                 KL-DPK-31 
                 0.125 
                 DMPC 
                 4.3 
                 6.4 
                   
                 57.1 
                 12.7 
                 19.3 
                 1.15 
               
               
                 KL-DPK-40 
                 0.167 
                 S75 
                 4.6 
                 6.3 
                 6.1 
                 42.6 
                 13.9 
                 26.3 
                 0.98 
               
               
                 KL-DPK-42 
                 0.184 
                 S45 
                 5.7 
                 10.1 
                 2.9 
                 40.0 
                 11.5 
                 29.5 
                 0.97 
               
               
                 KL-DPK-43 
                 0.188 
                 DOPC 
                 5.7 
                 9.5 
                 3.7 
                 40.9 
                 11.9 
                 28.0 
                 0.98 
               
               
                 KL-DPK-45 
                 0.192 
                 DOPE 
                 5.9 
                 10.3 
                 3.1 
                 41.7 
                 11.8 
                 27.1 
                 0.99 
               
               
                 KL-DPK-47 
                 0.189 
                 DMPC 
                 5.9 
                 10.2 
                 3.1 
                 40.9 
                 11.5 
                 28.2 
                 0.97 
               
               
                 KL-DPK-49 
                 0.168 
                 SM 
                 4.1 
                 6.5 
                   
                 56.0 
                 12.7 
                 20.6 
                 1.57 
               
               
                 KL-DPK-50 
                 — 
                 S75 
                 4.7 
                 6.2 
                 6.1 
                 42.8 
                 13.7 
                 26.4 
                 — 
               
               
                 (placebo) 
               
               
                 KL-DPK-51 
                 — 
                 DOPE 
                 4.2 
                 6.6 
                   
                 58.9 
                 13.2 
                 17.1 
                 — 
               
               
                 (placebo) 
               
               
                 KL-DPK-52 
                 0.105 
                 DOPE 
                 4.0 
                 6.6 
                   
                 57.6 
                 13.0 
                 18.7 
                 0.98 
               
               
                 KL-DPK-53 
                 0.107 
                 DMPC 
                 4.2 
                 6.6 
                   
                 58.3 
                 13.0 
                 17.7 
                 0.97 
               
               
                   
               
               
                 *Concentration of DPK-060 in % w/w of the non-volatile part of the composition 
               
             
          
         
       
     
       EXAMPLE 19 
     LL-37 Peptide Compositions in Silicone Oil/Lipid Vehicles 
       [0079]    Accurately weighed amounts of the peptide LL-37 were dissolved in mixtures of lipid, glycerol and ethanol at 40° C. under agitation. Silicone oil (DC 345) and isopropanol was added and the mixture was gently agitated at 40° C. until a homogenous, clear and slightly yellow to brownish yellow liquid was obtained. Table 13 presents representative examples of LL-37 compositions. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 13 
               
             
             
               
                   
               
               
                 LL-37 peptide compositions in silicone oil/lipid vehicles 
               
             
          
           
               
                   
                   
                   
                   
                   
                   
                   
                   
                 % 
               
               
                   
                 LL-37 
                   
                 % 
                 Gro 
                 DC 345 
                 EtOH 
                 IPA % 
                 active/ 
               
               
                 Composition 
                 % w/w 
                 Lipid 
                 w/w 
                 % w/w 
                 % w/w 
                 % w/w 
                 w/w 
                 nonvol* 
               
               
                   
               
             
          
           
               
                 KL-LL37-1 
                 0.202 
                 S75 
                 6.9 
                 7.1 
                 48.5 
                 23.3 
                 14.0 
                 1.42 
               
               
                 KL-LL37-2 
                 0.184 
                 DOPE 
                 5.3 
                 8.0 
                 49.3 
                 26.2 
                 11.1 
                 1.37 
               
               
                   
               
               
                 *Concentration of LL-37 in % w/w of the non-volatile part of the composition 
               
             
          
         
       
     
       EXAMPLE 20 
     Oxytocin Compositions in Silicone Oil/Lipid Vehicles 
       [0080]    Accurately weighed amounts of oxytocin were dissolved in mixtures of lipid, glycerol and ethanol at 40° C. under agitation. Silicone oil (DC 345) and optionally isopropanol was added and the mixture was gently agitated at 40° C. until a homogenous, clear and colourless to brownish yellow liquid was obtained. Table 14 presents representative examples of oxytocin compositions. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 14 
               
             
             
               
                   
               
               
                 Oxytocin compositions in silicone oil/lipid vehicles 
               
             
          
           
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 % 
               
               
                   
                 Oxytocin 
                   
                 % 
                   
                 % 
                 Gro % 
                 DC 345 % 
                 EtOH % 
                 IPA % 
                 active/ 
               
               
                 Composition 
                 % w/w 
                 Lipid 1 
                 w/w 
                 Lipid 2 
                 w/w 
                 w/w 
                 w/w 
                 w/w 
                 w/w 
                 nonvol* 
               
               
                   
               
             
          
           
               
                 Ox-1 
                 0.139 
                 DOPE 
                 5.9 
                 MCM 
                 10.8 
                   
                 70.6 
                 12.6 
                   
                 0.83 
               
               
                 Ox-2 
                 0.090 
                 DOPE 
                 4.4 
                 MCM 
                 10.0 
                 8.1 
                 46.4 
                 8.3 
                 22.8 
                 0.40 
               
               
                 Ox-3 
                 0.126 
                 MCM 
                 22.1 
                   
                   
                   
                 66.3 
                 11.5 
                   
                 0.56 
               
               
                 Ox-4 
                 0.094 
                 MCM 
                 3.9 
                   
                   
                 8.6 
                 48.8 
                 7.1 
                 31.5 
                 0.74 
               
               
                 Ox-5 
                 0.078 
                 MCM 
                 5.1 
                   
                   
                   
                 58.2 
                 23.4 
                 13.2 
                 1.51 
               
               
                 Ox-6 
                 0.100 
                 MOG 
                 25.6 
                   
                   
                   
                 64.0 
                 10.3 
                   
                 0.39 
               
               
                 Ox-7 
                 0.161 
                 S75 
                 6.6 
                   
                   
                   
                 80.0 
                 13.3 
                   
                 2.40 
               
               
                 Ox-8 
                 0.088 
                 S75 
                 5.0 
                   
                   
                 8.5 
                 51.7 
                 8.6 
                 26.1 
                 0.65 
               
               
                 Ox-9 
                 0.129 
                   
                   
                   
                   
                 8.6 
                 51.0 
                 8.9 
                 31.4 
                 1.47 
               
               
                 Ox-10 
                 0.178 
                   
                   
                   
                   
                   
                 85.8 
                 14.0 
                   
                 100 
               
               
                   
               
               
                 *Concentration of oxytocin in % w/w of the non-volatile part of the composition 
               
             
          
         
       
     
       EXAMPLE 21 
     Hydrocortisone Compositions in Silicone Oil/Lipid Vehicles 
       [0081]    An accurately weighed amount of hydrocortisone was dissolved in a mixture of lipid and ethanol at 40° C. under agitation. Silicone oil (DC 345) and isopropanol was added and the mixture was gently agitated at 40° C. until a homogenous, clear and yellow liquid was obtained. Table 15 presents a representative example of hydrocortisone compositions. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 15 
               
             
             
               
                   
               
               
                 Hydrocortisone composition in silicone oil/lipid vehicles 
               
             
          
           
               
                   
                 Hydro- 
                   
                   
                   
                   
                   
                 % 
               
               
                 Compo- 
                 cortisone 
                   
                 % 
                 DC 345 
                 EtOH 
                 IPA % 
                 active/ 
               
               
                 sition 
                 % w/w 
                 Lipid 
                 w/w 
                 % w/w 
                 % w/w 
                 w/w 
                 nonvol* 
               
               
                   
               
               
                 HC-1 
                 0.093 
                 S75 
                 4.8 
                 65.2 
                 14.8 
                 15.1 
                 1.93 
               
               
                   
               
               
                 *Concentration of hydrocortisone in % w/w of the non-volatile part of the composition 
               
             
          
         
       
     
       EXAMPLE 22 
     Dihydroxyacetone Compositions in Silicone Oil/Lipid Vehicles 
       [0082]    An accurately weighed amount of dihydroxyacetone was dissolved in a mixture of lipid and ethanol at 40° C. under agitation. Silicone oil (DC 345) and isopropanol was added and the mixture was gently agitated at 40° C. until a homogenous, clear and yellow liquid was obtained. Table 16 presents a representative example of dihydroxyacetone compositions. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 16 
               
             
             
               
                   
               
               
                 Dihydroxyacetone composition in silicone oil/lipid vehicles 
               
             
          
           
               
                   
                 Dihydroxy- 
                   
                   
                   
                 EtOH 
                 IPA 
                 % 
               
               
                 Compo- 
                 acetone 
                   
                 % 
                 DC 345 
                 % 
                 % 
                 active/ 
               
               
                 sition 
                 % w/w 
                 Lipid 
                 w/w 
                 % w/w 
                 w/w 
                 w/w 
                 nonvol* 
               
               
                   
               
               
                 DA-1 
                 1.03 
                 MCM 
                 4.4 
                 76.8 
                 8.9 
                 8.8 
                 19.0 
               
               
                   
               
               
                 *Concentration of dihydroxyacetone in % w/w of the non-volatile part of the composition 
               
             
          
         
       
     
       EXAMPLE 23 
     Lidocaine Compositions in Silicone Oil/Lipid Vehicles 
       [0083]    An accurately weighed amount of lidocaine was dissolved in a mixture of lipid and ethanol at 40° C. under agitation. Silicone oil (DC 345) and optionally isopropanol was added and the mixture was gently agitated at 40° C. until a homogenous, clear and colourless to yellow liquid was obtained. Table 17 presents representative examples of lidocaine compositions. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 17 
               
             
             
               
                   
               
               
                 Lidocaine compositions in silicone oil/lipid vehicles 
               
             
          
           
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 % 
               
               
                   
                 Lidocaine 
                   
                 % 
                   
                 % 
                 DC 345 
                 EtOH % 
                 IPA % 
                 active/ 
               
               
                 Composition 
                 %/w/w 
                 Lipid 1 
                 w/w 
                 Lipid 2 
                 w/w 
                 % w/w 
                 w/w 
                 w/w 
                 nonvol* 
               
               
                   
               
             
          
           
               
                 KL-LK-1 
                 0.7 
                 S75 
                 7.6 
                   
                   
                 65.4 
                 7.5 
                 18.8 
                 8.8 
               
               
                 KL-LK-2 
                 0.8 
                 S75 
                 2.8 
                   
                   
                 59.8 
                 11.4 
                 25.3 
                 22.2 
               
               
                 KL-LK-6 
                 11.5 
                 S75 
                 13.7 
                   
                   
                 65.3 
                 9.5 
                   
                 45.8 
               
               
                 KL-LK-7 
                 5.1 
                 DOPE 
                 1.3 
                   
                   
                 88.7 
                 5.0 
                   
                 79.9 
               
               
                 KL-LK-8 
                 5.1 
                 DOPE 
                 10.2 
                   
                   
                 74.9 
                 9.8 
                   
                 33.0 
               
               
                 KL-LK-9 
                 4.7 
                 MCM 
                 1.1 
                 Chol 
                 0.5 
                 87.8 
                 5.9 
                   
                 74.4 
               
               
                 KL-LK-10 
                 4.8 
                   
                   
                   
                   
                 90.3 
                 4.9 
                   
                 100 
               
               
                 KL-LK-11 
                 5.0 
                 MCM 
                 8.9 
                 Chol 
                 1.0 
                 75.2 
                 10.0 
                   
                 33.5 
               
               
                 KL-LK-12 
                 5.0 
                 S75 
                 15.0 
                   
                   
                 70.1 
                 9.9 
                   
                 25.0 
               
               
                 KL-LK-13 
                 5.0 
                 DOPE 
                 5.2 
                   
                   
                 79.6 
                 10.2 
                   
                 48.7 
               
               
                 KL-LK-14 
                 5.0 
                   
                   
                   
                   
                 85.0 
                 10.0 
                   
                 100 
               
               
                 KL-LK-16 
                 20.2 
                 MCM 
                 20.8 
                   
                   
                 50.4 
                 8.6 
                   
                 49.4 
               
               
                   
               
               
                 *Concentration of lidocaine in % w/w of the non-volatile part of the composition 
               
             
          
         
       
     
       EXAMPLE 24 
     Control of Transepidermal Water Loss 
       [0084]    Three lipid layer forming compositions of the invention termed A, B, C (Table 18) were tested for their effect on transepidermal water loss (TEWL) from a skin surface. Their effect was compared with that of white vaseline (ACO hud, Sweden), a conventional agent for TEWL. The compositions were applied to the skin of ten healthy individuals, 5 women and 5 men; mean age 34 years, SD 18 years, who showed no evidence of skin disease. Prior to application, the volar aspects of their forearms were rapidly cleansed with paper tissue soaked in pure alcohol. Five rectangular areas of 2×2 cm were marked on the volar forearm with a pencil and measured for basal TEWL. The compositions and vaseline were applied to the areas in a randomized manner; one of the areas was left as an untreated control. Two dosages were studied, 3 μl/cm 2  and 6 μl/cm 2 . Vaseline was used in half of the amount, i.e. 1.5 μl/cm 2  and 3 μl/cm 2 . The high dose was applied on the right forearm, and the low dose on the left forearm. The products were dispensed onto the surface by means of a displacement micro-pipette (Gilson). The compositions were applied in small droplets onto the area; evaporation was facilitated by slightly blowing at the surface. Vaseline was spread by fingertip. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 18 
               
             
             
               
                   
               
               
                 Compositions tested for control of transepidermal 
               
               
                 water loss (% by weight) 
               
             
          
           
               
                 Composition # 
                 MCM 
                 Polar lipid 
                 EtOH 
                 DC345 
               
               
                   
               
               
                 1 
                   
                 15  
                 10 
                 75 
               
               
                   
                   
                 (S75) 
               
               
                 2 
                 9 
                 1 
                 10 
                 80 
               
               
                   
                   
                 (Chol) 
               
               
                 3 
                   
                 5 
                 10 
                 85 
               
               
                   
                   
                 (DOPE) 
               
               
                   
               
             
          
         
       
     
         [0085]    TEWL was measured before application and 30 min after application by use of DermaLab equipment (open chamber; Cortex Technology, Hadsund, Denmark). The recorded reduction of transepidermal water loss is shown in  FIG. 2 . The composition 1 of the invention was comparable in effect to Vaseline while compositions 2 and 3 of the invention exerted no significant effect on TEWL.