Nanoemulsion based on phosphoric acid fatty acid esters and its uses in the cosmetics, dermatological, pharmaceutical, and/or ophthalmological fields

The present invention provides a nanoemulsion, that includes: PA1 an oily phase dispersed in an aqueous phase; and PA1 at least one anionic surfactant selected from the group including phosphoric acid fatty esters and oxyethylenated derivatives thereof, and mixtures thereof; wherein PA1 the oily phase includes oil globules having a number-average size of less than 100 nm; PA1 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.

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.degree. 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.degree. C. to form a mixture; and
 homogenizing the mixture at a pressure ranging from 6.times.10.sup.7 Pa to
 18.times.10.sup.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.sub.9 -C.sub.15 alcohols or their salts, such as the potassium salt of
 C.sub.9 -C.sub.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.sub.11 -C.sub.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):
 ##STR1##
 in which R represents an alkyl radical having from 16 to 22 carbon atoms,
 more preferably the C.sub.16 H.sub.33 and C.sub.18 H.sub.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.degree. C. and then a homogenization of
 the mixture at a pressure preferably ranging from 6.times.10.sup.7 Pa to
 18.times.10.sup.7 Pa (high-pressure homogenization). The shearing (e.g.
 mixing or stirring) preferably ranges from 2.times.10.sup.6 s.sup.-1 to
 5.times.10.sup.8 s.sup.-1 and better still from 1.times.10.sup.8 s.sup.-1
 to 3.times.10.sup.8 s.sup.-1 (s.sup.-1 signifies second.sup.-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.