Abstract:
The present invention provides a nanoemulsion, that includes: 
     an oily phase dispersed in an aqueous phase; and 
     at least one anionic surfactant selected from the group including phosphoric acid fatty esters and oxyethylenated derivatives thereof, and mixtures thereof; wherein 
     the oily phase includes oil globules having a number-average size of less than 100 nm; 
     wherein the oily phase includes at least one oil having a molecular weight of greater than 400; and wherein a weight ratio of the oily phase to the surfactant ranges from 2 to 10. The invention also provides a process for making the nanoemulsion, and methods for its use. The nanoemulsion is ideally transparent and stable on storage. It can ideally contain large amounts of oil while retaining good transparency and good cosmetic properties. The nanoemulsion is particularly useful in compositions, including topical, pharmaceutical, dermatological, cosmetic, opthalmic, and opthalmologic. The composition is also particularly useful in applications to the skin, hair, scalp, mucous membranes, and eyes.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a nanoemulsion based on an anionic surfactant chosen from phosphoric acid fatty esters and their oxyethylenated derivatives and on at least one oil having a molecular weight of greater than 400, the ratio by weight of the amount of oily phase to the amount of surfactant ranging from 2 to 10. 
     The invention also relates to a process for the preparation of the nanoemulsion and to its uses, in particular in the cosmetics, dermatological and/or ophthalmological fields. This nanoemulsion is stable on storage and can contain large amounts of oil while retaining good transparency and while having good cosmetic properties. 
     2. Discussion of the Background 
     Nanoemulsions are oil-in-water emulsions, the oil globules of which have a very fine particle size, i.e. a number-average size of less than 100 nm. They are generally manufactured by mechanical fragmentation of an oily phase in an aqueous phase in the presence of a surfactant. In the case of nanoemulsions, the very small size of the oily globules is obtained in particular by virtue of at least one pass through a high-pressure homogenizer. The small size of the globules confers on them cosmetically advantageous properties which distinguish them from conventional emulsions: they are transparent and exhibit a novel texture. They can also carry active principles more efficiently. 
     Transparent microemulsions are known in the art. In contrast to nanoemulsions, microemulsions are not, strictly speaking, emulsions. Rather, microemulsions are transparent solutions of micelles swollen by oil, which oil is generally a very-short-chain oil (e.g. hexane or decane) and which is solubilized by virtue of the joint presence of a significant amount of surfactants and of cosurfactants which form the micelles. The size of the swollen micelles is very small owing to the small amount of oil which they can solubilize. This very small size of the micelles is the cause of their transparency, as with nanoemulsions. However, in contrast to nanoemulsions, microemulsions are spontaneously formed by mixing the constituents, without contributing mechanical energy other than simple magnetic stirring. The major disadvantages of microemulsions are related to their necessarily high proportion of surfactants, leading to intolerance and resulting in a sticky feel during application to the skin. Furthermore, their formulation range is generally very narrow and their temperature stability very limited. 
     Nanoemulsions, which contain an amphiphilic lipid phase composed of phospholipids, water and oil are known in the art. These emulsions exhibit the disadvantage of being unstable on storage at conventional storage temperatures, namely between 0 and 45° C. They lead to yellow compositions and produce rancid smells which develop after several days of storage. 
     Nanoemulsions stabilized by a lamellar liquid crystal coating, obtained by the combination of a hydrophilic surfactant and of a lipophilic surfactant, are also known. However, these combinations are difficult to prepare. Furthermore, the nanoemulsions obtained exhibit a waxy and film-forming feel which is not very pleasant for the user. 
     EP-A-728,460 discloses nanoemulsions based on fluid non-ionic amphiphilic lipids. However, these nanoemulsions disadvantageously exhibit a sticky effect during application to the skin. 
     The need therefore remains for nanoemulsions which have neither the disadvantages of known nanoemulsions nor the disadvantages of microemulsions. 
     SUMMARY OF THE INVENTION 
     It has now been found that, surprisingly, the use of an anionic surfactant chosen from phosphoric acid fatty esters and their oxyethylenated derivatives and of at least one oil having a molecular weight of greater than 400 (=400 grams per mole) makes it possible to obtain novel nanoemulsions exhibiting all the advantages of known nanoemulsions, such as described above, without their disadvantages. 
     Accordingly, the first embodiment of the present invention relates to a nanoemulsion that includes: 
     an oily phase dispersed in an aqueous phase; and 
     at least one anionic surfactant selected from the group including phosphoric acid fatty esters and oxyethylenated derivatives thereof, and mixtures thereof; wherein 
     said oily phase includes oil globules having a number-average size of less than 100 nm; 
     wherein said oily phase includes at least one oil having a molecular weight of greater than 400; and 
     wherein a weight ratio of said oily phase to said surfactant ranges from 2 to 10. 
     Another embodiment of the present invention relates to a composition selected from the group consisting of a topical composition, an ophthalmic vehicle, a pharmaceutical composition, dermatological composition, a cosmetic, and an opthalmological composition, and mixtures thereof, that includes the above-noted nanoemulsion. 
     Another embodiment of the present invention relates to a method of caring for, treating and/or making up the skin, face and/or scalp, that includes applying to the skin, face and/or scalp the above-noted nanoemulsion. 
     Another embodiment of the present invention relates to a method of caring for and/or treating the hair, that includes applying to the hair the above-noted nanoemulsion. 
     Another embodiment of the present invention relates to a method of caring for and/or moisturizing the skin, mucous membranes and/or scalp, that includes applying to the skin, mucous membranes and/or scalp the above-noted nanoemulsion. 
     Another embodiment of the present invention relates to a process for preparing the above-noted nanoemulsion, that includes: 
     mixing an aqueous phase and an oily phase with stirring at temperature ranging from 10 to 80° C. to form a mixture; and 
     homogenizing the mixture at a pressure ranging from 6×10 7  Pa to 18×10 7  Pa. 
     DETAILED DESCRIPTION OF THE INVENTION 
     Various other objects, features and attendant advantages of the present invention will be more fully appreciated as the same becomes better understood from the following detailed description of the preferred embodiments of the invention. 
     The nanoemulsions according to the invention preferably have a transparent to bluish appearance. Their transparency is measured by a transmittance coefficient at 600 nm preferably ranging from 10 to 90%, more preferably 20 to 85% or else by a turbidity ranging preferably from 60 to 600 NTU and preferably from 70 to 300 NTU, which turbidity is measured with a Hach Model.2100 P portable turbidimeter. These ranges include all values and subranges therebetween. 
     The oil globules of the nanoemulsions of the invention have a number-average size of less than 100 nm and preferably ranging from 20 to 75 nm and more preferably from 40 to 60 nm. These ranges include all values and subranges therebetween. The decrease in the size of the globules makes it possible to promote the penetration of the active principles into the surface layers of the skin (carrier effect). 
     The anionic surfactant which can be used in the nanoemulsion of the invention is chosen from phosphoric acid fatty esters, the oxyethylenated derivatives of these esters, their salts and their mixtures. According to a preferred embodiment of the invention, the nanoemulsion of the invention is devoid of any surfactant other than phosphoric acid fatty esters and/or their oxyethylenated derivatives. 
     The phosphoric acid fatty esters and their oxyethylenated derivatives which can be used as surfactants in the nanoemulsion according to the invention are preferably chosen from the group consisting of the esters formed from phosphoric acid and from at least one alcohol having a saturated or unsaturated, linear or branched alkyl chain having from 8 to 22 carbon atoms and the esters formed from phosphoric acid and from at least one ethoxylated alcohol having a saturated or unsaturated, linear or branched alkyl chain having from 8 to 22 carbon atoms and having from 2 to 40 oxyethylene groups, their salts and their mixtures. More preferably, a mixture of one or more of these phosphoric acid esters may be used in the nanoemulsion of the invention. 
     These esters are preferably chosen from esters of phosphoric acid and of C 9 -C 15  alcohols or their salts, such as the potassium salt of C 9 -C 15  alkyl phosphate sold under the name Arlatone MAP by the company ICI, esters of phosphoric acid and of stearyl and/or isostearyl alcohols, such as the phosphate of stearyl/isostearyl alcohols (CTFA name: Octyldecyl phosphate) sold under the name Hostaphat CG120 by the company Hoechst Celanese, esters of phosphoric acid and of cetyl alcohol and their oxyethylenated derivatives, such as the product sold under the name Crodafos CES (mixture of cetearyl alcohol, of dicetyl phosphate and of ceteth-10 phosphate) by the company Croda, or esters of phosphoric acid and of tridecyl alcohol and their oxyethylenated derivatives, such as the product sold under the name Crodafos T10 (CTFA name: Trideceth-10 phosphate) by the company Croda. The oxyethylenated derivatives of phosphoric acid and of a fatty alcohol can be prepared in accordance with the description given in Patent Application WO-A-96/14145, the contents of which are incorporated in the present application by way of reference. 
     The phosphoric acid fatty esters used as surfactants are preferably employed in the neutralized form at a pH of approximately 7, the neutralization agent preferably being chosen from inorganic bases, such as sodium hydroxide, potassium hydroxide or ammonia, and organic bases, such as mono-, di- and triethanolamine, aminomethyl-1,3-propanediol, N-methylglucamine, basic amino acids, such as arginine and lysine, and their mixtures. 
     Preferably, the amount of surfactant in the nanoemulsion of the invention can range, for example, from 0.2 to 15% by weight and more preferably from 1 to 8% by weight with respect to the total weight of the nanoemulsion. These ranges include all values and subranges therebetween. 
     The ratio by weight of the amount of the oily phase to the amount of surfactant ranges from 2 to 10 and preferably from 3 to 6. The term “amount of oily phase” is understood here to mean the total amount of the constituents of this phase without including the amount of surfactant. 
     The nanoemulsion according to the invention contains at least one oil with a molecular weight of greater than 400. The oils with a molecular weight of greater than 400 can preferably be chosen from oils of animal or vegetable origin, mineral oils, synthetic oils and silicone oils, and their mixtures. More preferred oils of this type include, for example, isocetyl palmitate, isocetyl stearate, avocado oil or jojoba oil. 
     In addition, the oily phase can optionally contain other oils and in particular oils having a molecular weight of less than 400. Preferably, these oils are also chosen from oils of animal or vegetable origin, mineral oils, synthetic oils and silicone oils. More preferred oils of this type include, for example, as oils with a molecular weight of less than 400, of isododecane, isohexadecane, volatile silicone oils, isopropyl myristate, isopropyl palmitate or C 11 -C 3  isoparaffin. 
     The oily phase can also contain fatty substances other than the oils indicated above, such as fatty alcohols, for example stearyl, cetyl and behenyl alcohols, fatty acids, for example stearic, palmitic and behenic acids, oils of fluorinated type, waxes, gums and their mixtures. 
     The nanoemulsions in accordance with the invention contain an amount of oily phase preferably ranging from 2 to 40% and more preferably from 5 to 30% by weight with respect to the total weight of the nanoemulsion, the proportion of oil(s) having a molecular weight of greater than 400 preferably representing at least 40% and more preferably at least 50% by weight of the oily phase. These ranges include all values and subranges therebetween. 
     According to a more preferred embodiment of the invention, the nanoemulsion of the invention additionally contains one or more ionic amphiphilic lipids. 
     Preferred ionic amphiphilic lipids which can be used in the nanoemulsions of the invention may be chosen from the group formed by anionic amphiphilic lipids and alkylsulphonic derivatives. 
     Preferably, the anionic amphiphilic lipids can be chosen from the group formed by: 
     the alkaline salts of dicetyl and dimyristyl phosphate; 
     the alkaline salts of cholesterol sulphate; 
     the alkaline salts of cholesterol phosphate; 
     lipoamino acids and their salts, such as mono- and disodium acylglutamates, such as the disodium salt of N-stearoyl-L-glutamic acid sold under the name Acylglutamate HS21 by the company Ajinomoto; 
     the sodium salts of phosphatidic acid; 
     phospholipids; 
     and their mixtures. 
     The alkylsulphonic derivatives can be preferably chosen from the alkylsulphonic derivatives of formula (I):                           
     in which R represents an alkyl radical having from 16 to 22 carbon atoms, more preferably the C 16 H 33  and C 18 H 37  radicals, taken as a mixture or separately, and M is an alkali metal, most preferably sodium. 
     According to a preferred embodiment of the invention, a lipoamino acid is used as ionic amphiphilic lipid. 
     The ionic amphiphilic lipids can be introduced into either phase of the nanoemulsion. 
     When they are present in the nanoemulsion of the invention, they may be used in concentrations preferably ranging from 0.01 to 5% by weight and more particularly from 0.25 to 1% by weight with respect to the total weight of the nanoemulsion. These ranges include all values and subranges therebetween. 
     The emulsions in accordance with the present invention can contain additives for improving the transparency of the formulation. 
     These additives are preferably chosen from the group formed by: 
     lower alcohols having from 1 to 8 carbon atoms and more preferably from 2 to 6 carbon atoms, such as ethanol; 
     glycols, such as glycerol, propylene glycol, 1,3-butylene glycol, dipropylene glycol, pentylene glycol, iaoprene glycol and polyethylene glycols having from 4 to 16 and preferably from 8 to 12 ethylene oxide units; 
     sugars, such as glucose, fructose, maltose, lactose or sucrose. 
     The above-noted additives may preferably be used as a mixture. When they are present in the nanoemulsion of the invention, they can be used at concentrations preferably ranging from 0.01 to 30% by weight, more preferably from 0.3 to 25%, and most preferably from 5 to 20% by weight with respect to the total weight of the nanoemulsion. The amount of alcohol(s) and/or of sugar(s) preferably ranges from 5 to 20% and more preferably from 10 to 15% by weight with respect to the total weight of the nanoemulsion and the amount of glycol(s) preferably ranges from 5 to 15% by weight with respect to the total weight of the nanoemulsion. These ranges include all values and subranges therebetween. 
     To obtain preservative-free emulsions, it is preferred to use the alcohols as defined above at concentrations greater than or equal to 15% by weight with respect to the total weight of the nanoemulsion. 
     The nanoemulsions defined above can be used in any field where this type of composition is useful. They can are particularly useful in compositions for topical use and, most particularly, in particular cosmetic or dermatological compositions. They can also be used as ophthalmic vehicles. In addition, they are especially useful in the pharmaceutical field, e.g. a pharmaceutical composition which can be administered orally, parenterally or transcutaneously. 
     A preferred embodiment of the invention is therefore a composition for topical use, characterized in that it contains a nanoemulsion as defined above. 
     Preferably, a composition for topical or pharmaceutical use contains a physiologically acceptable medium, i.e. one that is compatible with the skin, mucous membranes, scalp, eyes and/or hair. 
     Another preferred embodiment of the invention is an ophthalmic vehicle, characterized in that it contains a nanoemulsion as defined above. 
     Another preferred embodiment of the invention is a pharmaceutical composition, characterized in that it contains a nanoemulsion as defined above. 
     Preferably, the nanoemulsions of the invention may optionally contain water-soluble or fat-soluble active principles having a cosmetic, dermatological or ophthalmic activity. The fat-soluble active principles are in the oily globules of the emulsion, whereas the water-soluble active principles are in the aqueous phase of the emulsion. Preferred examples of active principles include vitamins, such as vitamin E, and their derivatives and in particular their esters, provitamins, such as panthenol, humectants and sun screen agents. 
     Preferable ophthalmic active principles include, for example, antiglaucoma agents, such as betaxolol; antibiotics, such as acyclovir; antiallergics; anti-inflammatory agents, such as ibuprofen and its salts, diclofenac and its salts, or indomethacin; or antiviral agents. 
     The nanoemulsions in accordance with the invention can be provided in the form of a lotion, serum, cream, milk or toilet water and can contain adjuvants commonly used in the cosmetics, dermatological and ophthalmic fields, such as, for example, gelling agents, preservatives, antioxidants and fragrances. They can also be provided in the form of an eye lotion, in particular for ophthalmological applications. 
     Preferred gelling agents which can be used include cellulose derivatives, algal derivatives, natural gums and synthetic polymers, such as polymers and copolymers of carboxyvinyl acids, for example those sold under the name Carbopol by the company Goodrich. 
     Another preferred embodiment of the invention is a process for the preparation of a nanoemulsion as defined above, this process including the mixing of the aqueous phase and the oily phase with vigorous stirring at a temperature ranging from 10 to 80° C. and then a homogenization of the mixture at a pressure preferably ranging from 6×10 7  Pa to 18×10 7  Pa (high-pressure homogenization). The shearing (e.g. mixing or stirring) preferably ranges from 2×10 6  s −1  to 5×10 8  s −1  and better still from 1×10 8  s −1  to 3×10 8  s −1  (s −1  signifies second −1 ). The nanoemulsion of the invention can be most preferably used, for example, for caring for, treating or making up the skin, face and/or scalp. 
     Another preferred embodiment of the invention is therefore the cosmetic use of the nanoemulsion as defined above for caring for, treating and/or making up the skin, face and/or scalp. 
     Preferably, the nanoemulsion of the invention can also be used for caring for and/or treating the hair. It makes it possible to obtain a deposit of oil on the hair, which renders the latter glossier and more resistant to styling, without, however, making it lank. It also makes it possible, as a pretreatment, to improve the effects of dyeing or permanent waving. 
     Another preferred embodiment of the invention is therefore the cosmetic use of the nanoemulsion as defined above for caring for and/or treating the hair. 
     The nanoemulsion according to the invention is excellent for moisturizing the skin, mucous membranes and/or scalp and is particularly suited to the treatment of dry skin. 
     Another preferred embodiment of the invention is therefore a cosmetic process for caring for and/or moisturizing the skin, mucous membranes and/or scalp, characterized in that a nanoemulsion as defined above is applied to the skin, mucous membranes and/or scalp. 
     Another preferred embodiment relates to the use of the nanoemulsion according to the invention in the manufacture of a dermatological composition intended for the treatment of dry skin. 
     Another preferred embodiment relates to the use of the nanoemulsion according to the invention in the manufacture of an ophthalmological composition. 
    
    
     EXAMPLES 
     Having generally described this invention, a further understanding can be obtained by reference to certain specific examples which are provided herein for purposes of illustration only and are not intended to be limiting unless otherwise specified. The amounts shown are as % by weight. 
     Example: Fluid Made-up Remover 
     
       
         
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                 Oily phase: 
                   
               
               
                   
                 Disodium salt of N-stearoyl-L-glutamic acid 
                  0.5% 
               
               
                   
                 (Acylglutamate HS21 from the company Ajinomoto) 
               
               
                   
                 Isocetyl stearate (M.W. = 508) 
                 10% 
               
               
                   
                 Isopropyl palmitate (M.W. = 298) 
               
               
                   
                 Aqueous phase: 
               
               
                   
                 Hostaphat CG120 (Company Hoechst Celanese) 
                  4.5% 
               
               
                   
                 NAOH (1N) 
                  5 
               
               
                   
                 Glycerol 
                  5% 
               
               
                   
                 Dipropylene glycol 
                 10% 
               
               
                   
                 Water 
                 60% 
               
               
                   
                   
               
             
          
         
       
     
     A transparent nanoemulsion is obtained; and the size of the globules of which is 57 nm and the turbidity of which is 250 NTU. 
     Obviously, numerous modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described herein. 
     This application is based on French Patent Application 98 16370, filed on Dec. 23, 1998, the entire contents of which are hereby incorporated by reference.