[1]This is a continuation of application Ser. No. 08/473,360, filed Jun. 7, 1995 abandoned.
[2]The present invention relates to a composition composed of an aqueous dispersion of vesicles of certain nonionic amphiphilic lipids, which are stabilized and do not degrade during storage. This composition is especially advantageous in cosmetics and dermopharmacy.
[3]It is known that certain amphiphilic lipids possess the property of forming mesomorphic phases, the state of organization of which is intermediate between the crystalline state and the liquid state, and that some of these are capable of swelling in the presence of an aqueous solution to form a lamellar phase and then, after agitation, to form vesicles or spherules dispersed in an aqueous phase. These vesicles are composed of a membrane consisting of substantially concentric lamellae containing one or more multimolecular layers, preferably bimolecular, encapsulating an aqueous phase.
[4]The abovementioned vesicles may be prepared by many processes. According to a first process, which is, for example, described by Bangham et al. (J. Mol. Bio., 13, 1965--pages 238 to 262), the lipid phase is dissolved in a volatile solvent, a thin film of lipid phase is formed on the walls of a flask by evaporation of the solvent, the phase to be encapsulated is introduced onto the lipid film and the mixture is agitated mechanically until the dispersion of vesicles having the desired size is obtained; an aqueous dispersion of vesicles encapsulating an aqueous phase is thereby obtained, the encapsulated aqueous phase and the aqueous dispersion phase being identical. According to a second, so-called "lipid co-melting" process, described, for example, in FR-A-2,315,991, the lipid phase is prepared by mixing the amphiphilic lipid or lipids and the possible additives at a temperature at which the mixture is molten, if the mixture is not liquid at room temperature; a lamellar phase is formed by introduction of the aqueous phase to be encapsulated; the lamellar phase is then dispersed in the form of vesicles, using an ultradisperser, a homogenizer or ultrasound, in an aqueous dispersion phase. In a variant of this process, the formation of the lamellar phase does not constitute a separate stage of the process. The vesicles obtained by these two processes are generally of the "multilamellate" type. To obtain vesicles of the "monolamellate" type, the teaching of FR-A-2,543,018 may be used.
[5]Irrespective of the process used, the vesicles are obtained in the form of a dispersion in an aqueous phase.
[6]In a known manner, vesicles of amphiphilic lipids can contain cosmetic or pharmaceutical active agents, either in the encapsulated aqueous phase if the said active agents are water-soluble, or in the lipid membrane if they are fat-soluble. Active agents may also be present in the aqueous dispersion phase.
[7]The amphiphilic lipids used for obtaining the vesicles are lipids of the general formula:
[9]in which formula X represents a hydrophilic group and Y represents a lipophilic group. The amphiphilic lipids can be ionic lipids for which the group X is ionic, or nonionic lipids for which the group X is nonionic.
[10]In a known manner, for the manufacture of vesicles, it is possible to use mixtures of ionic amphiphilic lipids, mixtures of nonionic amphiphilic lipids and mixtures of these two types of lipids.
[11]The proposal has been made, for example, in FR-A 2,315,991, to prepare the vesicles consisting of polyol esters, oxyethylenated or otherwise, from nonionic amphiphilic lipids. The vesicles prepared with the said esters are advantageous in cosmetics and dermopharmacy since they are biodegradable in and on the skin. However, they possess a major drawback: in the presence of water, a hydrolysis of the ester groups in the lipid membrane is observed, this hydrolysis phenomenon being especially extensive when the pH diverges from a value close to neutrality. To remedy this drawback, it has been proposed to introduce a saline buffer solution maintaining the pH at a value between 6 and 7, and preferably in the region of 6.5, into the aqueous phase of dispersion of the vesicles. However, the introduction of saline buffers into compositions used in cosmetics or in dermopharmacy possesses many drawbacks. Saline buffers are incompatible with many additives or active agents commonly used in cosmetics; in particular, they lower the viscosity of compositions containing an anionic gelling agent such as the vinylcarboxylic mixtures marketed by the company "Goodrich" under the name "Carbopol"; they also cause precipitation of proteins. The presence of a saline buffer reduces the electrical charge (zeta potential) of the vesicles, thereby bringing about their flocculation. Furthermore, the presence of the said saline buffer causes a strong corrosion of metals, especially steels, constituting the surfaces of the homogenizers used for the manufacture of the vesicles. Lastly, cosmetic compositions containing a saline buffer impart a rougher feel after application to the skin.
[12]According to the present invention, a means has been found which enables dispersions in which the vesicles are stable in water to be obtained with certain polyol esters; these dispersions can consequently be stored and used for the preparation of cosmetic or dermopharmaceutical compositions without the need to introduce a saline buffer.
[13]According to the present application, it was found that, by combining in the lipid phase constituting the membrane of the vesicles certain polyol esters with at least one ionic lipid selected from a certain group, vesicles stable to hydrolysis were obtained.
[14]The subject of the present invention is, consequently, a composition composed of an aqueous dispersion of vesicles consisting of a membrane of lipid phase encapsulating an aqueous phase, the lipid phase comprising nonionic amphiphilic lipids and at least one ionic amphiphilic lipid, characterized in that:
[15]the nonionic amphiphilic lipids consist of a mixture of esters of at least one polyol chosen from the group composed of polyethylene glycol containing from 1 to 60 ethylene oxide units, sorbitan, sorbitan bearing 2 to 60 ethylene oxide units, glycerol bearing 2 to 30 ethylene oxide units, polyglycerols containing 2 to 15 glycerol units, sucroses, and glucoses bearing 2 to 30 ethylene oxide units and of at least one fatty acid containing a saturated or unsaturated, linear or branched C5 -C17 alkyl chain, the number of alkyl chains per polyol group being between 1 and 10; and in that
[16]the ionic amphiphilic lipid or lipids is/are chosen from the group composed of those which impart a pH of between 5.5 and 7.5 to the dispersion;
[17]the weight ratio of the quantity of nonionic amphiphilic lipids to that of ionic amphiphilic lipid or lipids in the lipid phase being between 50:1 and 50:25 and the weight ratio of the lipid phase to the aqueous dispersion phase being between 1:1,000 and 300:1,000.
[18]It was found that, in the composition according to the invention, the vesicles obtained were stable in water, in the absence of buffered saline solutions, after storage for 2 months at temperatures between room temperature and 45° C.; they consequently have sufficient stability to be able to be used in cosmetic and dermopharmaceutical compositions.
[19]The composition according to the invention hence makes it possible to benefit from the advantage of polyol esters, which is that of being degradable under the action of the pH of the skin or by the enzymes of the skin. Their degradation gives rise to products which, in most cases, have a cosmetic or dermopharmaceutical action on the skin. In effect, free fatty acids such as palmitic acid or stearic acid have a bacteriostatic activity, and polyols such as glycerol, polyglycerols, sorbitol or sucrose are humectants and can, where appropriate, provide a supply of energy.
[20]The vesicles obtained afford a good degree of encapsulation of water-soluble substances and low permeability. They hence permit the encapsulation of water-soluble active agents. Furthermore, the gradual degradation of the vesicles on the skin permits a controlled release of the water-soluble active agents possibly contained in the encapsulated aqueous phase or the fat-soluble active agents possibly contained in the lipid phase.
[21]The dispersions of the vesicles of the composition according to the invention may be prepared by any known process for the manufacture of vesicles of amphiphilic lipids, and more especially by the so-called "lipid co-melting" process, enabling them to be prepared simply on an industrial scale.
[22]In the present application and the claims, the expression "mixture of esters" not only covers mixtures of pure esters of different chemical families, but also covers any product which contains several chemically pure polyol esters of the same family in variable proportions, This applies especially to products having a statistical formula in their hydrophilic portion, for example a polyglycerol ester of formula см. иллюстрацию в PDF-документе where n is a statistical value and which can contain various proportions of esters for which n=1, n=2, n=3, n=4, etc; this also applies to esters containing several alkyl chains in their lipophilic portion, such as cocoates, which contain from C5 to C17 alkyl chains, or isostearates, where the C17 alkyl chains are a complex mixture of isomeric forms; it likewise applies to products consisting of mixtures of mono-, di-, tri- or polyesters of the same polyol. It should be noted that a product which contained only a single ester capable of forming vesicles and impurities of some other type could not be used according to the invention.
[23]Commercial esters which are usable alone according to the invention, since they are in actual fact mixtures of esters, are, for example, the following:
[24]the partial esters of sorbitan (or sorbitol anhydride) and of fatty acid sold by the company "ICI" under the trade names Span 20, 40, 60 and 80®;
[25]the sorbitan isostearate sold by the company "Nikko" under the trade name SI 10 R NIKKOL®;
[26]the sorbitan stearate bearing 4 ethylene oxide units sold by the company ICI under the name TWEEN 61®;
[27]the polyethylene glycol stearate containing 8 ethylene oxide units sold by the company ICI under the name MYRJ 45®;
[28]the polyethylene glycol monostearate of formula
[29]OHCH2 (CH2 OCH2)n --CH2 OH
[30]in which formula n is equal to 4, sold by the company Nikko under the name MYS 4®;
[31]the polyethylene glycol stearate of molecular weight 400, chemical grade or grade produced by biotechnology, sold by the company Unichema;
[32]the diglyceryl stearate bearing 4 ethylene oxide units sold by the company Hoechst under the name HOSTACERINE DGS®;
[33]the tetraglycerol stearate sold by the company Nikko under the name TETRAGLYN 1S®;
[34]the diglyceryl isostearate sold by the company Solvay;
[35]the diglyceryl stearate sold by the company Nihon under the name EMALEX DSG 2®;
[36]the sucrose mono-, di- and tripalmitostearates sold by the company Croda under the names F50, F70, F110 and F160 CRODESTA®;
[37]the mixture of sucrose mono- and dipalmitostearates sold by the company Grillo under the name Grilloten PSE 141 G®;
[38]the mixture of sucrose stearate and sucrose cocoate sold by the company ICI under the name Arlatone 2121®;
[39]the methylglucose distearate bearing 20 ethylene oxide units sold by the company Amerchol under the name GLUCAM E 20 DISTEARATE®.
[40]Mixtures with one another of these different products, which are already mixtures, or mixtures of these products with pure products may naturally be used.
[41]The ionic amphiphilic lipid or lipids combined with the nonionic amphiphilic lipids according to the invention is/are preferably selected from the group composed of:
[42](1) neutralized anionic lipids, these anionic lipids preferably being chosen from:
[43]the alkali metal salts of dicetyl phosphate and of dimyristyl phosphate, especially the Na and K salts;
[44]the alkali metal salts of cholesterol sulphate, especially the Na salt;
[45]the alkali metal salts of cholesterol phosphate, especially the Na salt;
[46]mono- and disodium acylglutamates;
[47]phosphatidic acid sodium salt;
[48](2) amphoteric lipids, these amphoteric lipids preferably being phospholipids, especially pure soya bean phosphatidylethanolamine;
[49](3) alkylsulphonic derivatives, these derivatives preferably being the compounds of the formula: см. иллюстрацию в PDF-документе in which formula R represents C16 H33 and C18 H37 radicals taken mixed or separately and M is an alkali metal, preferably sodium.
[50]It is possible, in a known manner, to incorporate in the lipid phase constituting the lipid membrane of the vesicles at least one additive whose main function is to decrease the permeability of the vesicles, to prevent their flocculation and their fusion and to increase the degree of encapsulation.
[51]According to the invention, it is possible to add to the lipid phase at least one additive preferably chosen from the group composed of:
[52]sterols, and in particular phytosterols and cholesterol,
[53]long-chain alcohols and diols,
[54]long-chain amines and their quaternary ammonium derivatives.
[55]These additives can optionally have cosmetic and/or dermopharmaceutical activity. This applies, for example, to cholesterol.
[56]The vesicles of the compositions according to the invention can contain, in a known manner, one or more active compound(s) having cosmetic and/or dermopharmaceutical activity, which, depending on their solubility properties, can have different locations. If the active agents are water-soluble, they are introduced into the encaspulated aqueous phase of the vesicles. If the active agents are fat-soluble, they are introduced into the lipid phase constituting the membrane. If the active agents are amphiphilic, they distribute between the lipid phase and the encapsulated aqueous phase, with a partition coefficient which varies according to the nature of the amphiphilic active agent and the respective compositions of the lipid phase and of the encapsulated aqueous phase.
[57]The water-soluble active agents are, for example, glycerol, sorbitol, erythrulose and antibiotics. The fat-soluble or partially fat-soluble (amphiphilic) active agents are chosen from those which do not significantly increase the permeability of the vesicles, do not cause their flocculation and their fusion and do not decrease the degree of encapsulation. It is advantageous to use fat-soluble active agents which also constitute additives.
[58]Preferred fat-soluble active agents according to the invention are chosen from the group composed of:
[60]glycoceramides, especially those obtained from wheat germ and
[61]natural or synthetic ceramides, preferably those described in French Patent Application No. 91/02,091 filed on 21st Feb. 1991, which are of the formula: см. иллюстрацию в PDF-документе in which formula: R1 represents a C11 -C21 alkyl or alkenyl radical,
[63]a saturated C11 -C23 hydrocarbon radical,
[64]a mixture of saturated, linear C11 -C19 hydrocarbon radicals bearing at least one ethylenic unsaturation, and preferably one or two, in which mixture the proportion of saturated radicals cannot exceed 35%, the ceramide of formula (I) being in the form of a racemic mixture of erythro and threo diastereoisomers in erythro/threo proportions of between 85:15 and 60:40.
[65]According to the invention, it is preferable to introduce into the lipid phase constituting the membrane a mixture of ceramide(s) and cholesterol. In effect, the use of this mixture is especially advantageous, since it enables the lipids of the skin to be reconstituted when the vesicles of the dispersion according to the invention degrade on the skin.
[66]The active agents introduced, be they hydrophilic, lipophilic or amphiphilic, can have highly variable cosmetic and/or dermopharmaceutical activities (or "functions"), which are given in Table I below:
[68]The different active agents used can all be fat-soluble, water-soluble or amphiphilic, or can belong to at least two of these categories. The active agents introduced can have the same function or different functions. It should be noted that some active agents have several functions.
[69]The aqueous phase of the dispersion of the composition according to the invention can also contain a dispersion of droplets of a water-immiscible liquid, as described in French Patents 2,485,921 and 2,490,504. It has, in effect, been found that the vesicles according to the invention stabilize the dispersion of droplets of water-immiscible liquid without it being necessary to introduce a conventional emulsifier.
[70]The water-immiscible liquid, which can be present in the form of a dispersion in the aqueous dispersion phase, can, in particular, be chosen from the group composed of:
[71]animal or vegetable oils composed of esters of a fatty acid and of polyols, especially liquid triglycerides, for example sunflower, maize, soya bean, gourd, grape-pip, jojoba, sesame and hazelnut oils, fish oils, glycerol tricaprocaprylate, or vegetable or animal oils of formula R9 COOR10, in which formula R9 represents the residue of a higher fatty acid containing from 7 to 19 carbon atoms and R10 represents a branched hydrocarbon chain containing from 3 to 20 carbon atoms, for example Purcellin oil;
[72]natural or synthetic essential oils such as, for example, eucalyptus, lavandin, lavender, vetiver, Litsea cubeba, lemon, sandal wood, rosemary, chamomile, savory, nutmeg, cinnamon, hyssop, caraway, orange, geraniol, cade and bergamot oils;
[73]hydrocarbons such as hexadecane and liquid petrolatum;
[74]halocarbons, in particular fluorocarbons such as fluoroamines, for example perfluorotributylamine, fluorinated hydrocarbons, for example perfluorodecahydronaphthalene, fluoro esters and fluoro ethers;
[75]silicones, for example polysiloxanes, polydimethylsiloxanes and fluorosilicones;
[76]esters of an inorganic acid and of an alcohol; and
[77]ethers and polyethers.
[78]The aqueous dispersion phase can also contain water-soluble cosmetic and/or dermopharmaceutical active agents. The water-immiscible liquid can optionally contain a fat-soluble active agent.
[79]The aqueous dispersion phase can also contain adjuvants having neither cosmetic activity nor dermopharmaceutical activity of their own, but which are used for the formulation of the dispersion in the form of a lotion, cream or serum. These adjuvants are, in particular, selected from the group composed of gelling agents, preservatives, colorants, pigments, fillers, opacifiers and perfumes.
[80]Among gelling agents which are usable, there may be mentioned cellulose derivatives such as hydroxyethylcellulose, derivatives of algae such as satiagum, natural gums such as tragacanth, and synthetic polymers, especially the mixtures of polyvinylcarboxylic acids marketed by the company Goodrich under the name Carbopol and the mixture of Na acrylate/acrylamide copolymers marketed by the company Hoechst under the name Hostacherin PN 73®.
[81]Among pigments which are usable according to the invention, special mention may be made of pigments coated with silicones, with fluorinated compounds such as perfluoroalkyl phosphates or polytetrafluoroethylene (sold under the trade name Tefon®) or with amino acids; these coated pigments can be, in particular, oxides of iron or of titanium. As an example, there may be mentioned products sold by the company Wackherr under the trade name COVAFLUOR®, which are, in particular, oxides of iron or of titanium coated with perfluoroalkyl phosphate; there may also be mentioned the products sold by the company Clark Color under the trade name TEFLON TREATED PIGMENTS®, which are, in particular, oxides of iron or of titanium coated with polytetrafluoroethylene.
[82]Among fillers which are usable according to the invention, special mention may be made of talc, mica, starch powder, nylon powder and silica powder.
[83]In the composition according to the invention, the vesicles generally have an average diameter of between 10 and 5,000 nm. When the aqueous phase contains a dispersion of droplets of water-immiscible liquid, these droplets advantageously have an average diameter of between 100 and 10,000 nm.
[84]The examples below, given purely by way of illustration and without implied limitation, enable a better understanding of the invention to be gained.
[85]In all the examples given below, the dispersions of vesicles are prepared by the so-called "lipid co-melting" process, in which:
[86]in a first phase, the lipid phase is prepared by mixing in liquid form the different amphiphilic lipids of which it is composed, where appropriate combined with fat-soluble active agents or additives, and the lipid phase obtained is brought into contact with an aqueous phase containing, where appropriate, water-soluble active agents, so as to obtain a lamellar phase,
[87]in a second phase, an aqueous dispersion phase containing, where appropriate, a water-immiscible liquid and different additives is added to the hydrated lamellar phase obtained,
[88]and in a third phase, the mixture is subjected to vigorous agitation in a homogenizer to obtain vesicles dispersed in an aqueous dispersion phase.
EXAMPLE 1
[89]By way of comparison, vesicles were prepared from a lipid phase containing, as a nonionic lipid, one or other of the following two products A and B:
[90]A) Sorbitan palmitate marketed by the company ICI under the name SPAN 40®, which is a mixture containing predominantly sorbitan monopalmitate and small quantities of sorbitan di-, tri- and tetrapalmitate;
[91]B) The chemically pure compound of formula:
[92]C15 H31 CO(OCH2 CHOHCH2)2 OH
[93]When the product A is used, the composition obtained as described below is within the scope of the invention, whereas this is not the case with the product B.
[94]The composition has the following formulation:
[96]A dispersion containing vesicles 250 nm in-size was obtained after homogenization.
[97]The two dispersions obtained were subjected to a stability test by subjecting them to 5 successive cycles of temperature variation between -20° C. and +20° C., each cycle proceeding in the following manner:
[99]2 hours from -20° to +20° C.
[101]The temperature changes take place with a gradient of 0.33° C./min.
[102]At the end of the cycles, the dispersion of vesicles containing the nonionic lipid A according to the invention and that of vesicles containing the chemically pure nonionic lipid B (composition not forming part of the invention) were observed by eye and using an optical microscope. It was found that the vesicles containing the nonionic lipid A according to the invention are intact, while the vesicles containing the nonionic lipid B are massively recrystallized.
EXAMPLES 2 to 6
[103]By way of comparison, compositions containing a dispersion of vesicles in which the lipid phase contains an ionic lipid forming part of the invention, and compositions containing a dispersion in which the livid phase contains an ionic lipid not forming part of the invention, were prepared.
[104]The formulation of the lipid phases used in the different examples is given in Table II below:
[106]The diameter of the vesicles at time T0 immediately after their formation and after 2 months of storage at room temperature (RT), at 37° C. and at 45° C. were measured using an AMTECH BI 90 ® laser granulometer; the results are given in Table III below:
[108]This Table III shows that the presence of an acidic anionic lipid not forming part of the invention (Examples 2 and 3) does not enable the vesicles to be stabilized, while a neutralized anionic lipid according to the invention (Examples 4 to 6) enables the vesicles to be stabilized.
EXAMPLE 7
[109]Biodegradability of the vesicles according to the invention under the effect of the enzymes of superficial layers of human skin.
[110]A vesicular composition having the following formulation (% by weight) was prepared:
[112]The pH of the aqueous dispersion phase is 6.0 and the diameter of the vesicles is 260 nm.
[113]In addition, an enzymatic liquor was prepared by treatment of an area of the skin of the back measuring 4×4 cm which has undergone 8 successive strips. The enzymatic material is extracted with acetone and then liophilized. The powder obtained is dissolved in 0.5 ml of the above dispersion of vesicles.
[114]The palmitic acid released into the reaction mixture after 0 to 7 days of incubation at 37° C. is assayed. The assay of palmitic acid released is performed by two processes:
[115]1) by high performance thin-layer chromatography under the following conditions:
[116]Eluent: Hexane/petroleum ether/acetic acid 80:20:3 (by volume)
[117]Visualizing agent: 4% (by weight) copper sulphate in 15% (by weight) orthophosphoric acid
[118]Treatment: Carbonization at 180° C. for 5 minutes
[119]Reading: Shimadzu densitometer at 540 nm.
[120]2) using Bohringer enzyme kit No. 10 82 914 for assay of free fatty acids calibrated on palmitic acid.
[121]The two assays give concordant results.
[122]In Table IV below, the quantity of palmitic acid released is given in % relative to the total present at the start in the form of sorbitan palmirate.
[124]The vesicles according to the invention hence permit a delayed release of the active agents present in the vesicles, either in the encapsulated aqueous phase, or in the lipid membrane.
EXAMPLE 8
[125]Day cream for the face intended for the care of dry skins.
[126]The cream is prepared by the process defined above.
[127]In a first phase, the formulation used for the vesicular composition is as follows:
[129]In a second phase, the formulation of the dispersion of oil is as follows:
[131]In a third phase, the two formulations are mixed as described above to obtain the composition according to the invention.
[132]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance and radiance of skin of the face, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 9
[133]Anti-ageing day cream for the face.
[134]A cream having the following formulation is prepared as in Example 8:
[136]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance and radiance of the skin of the face, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 10
[137]Anti-ageing serum for the face.
[138]A serum having the following formulation is prepared:
[140]After application twice a day for three weeks, a marked firming of the skin is noted.
EXAMPLE 11
[141]Anti-ageing serum for the face.
[142]A serum having the following formulation is prepared:
[144]It was observed that the vesicles contained in the serum remained stable after 3 months of storage. After application twice a day for 3 weeks, a marked firming of the skin is noted.
EXAMPLE 12
[145]Day cream for the face.
[146]A cream having the following formulation was prepared:
[148]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance and radiance of the skin of the face, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 13
[149]Day cream for the face.
[150]A cream having the following formulation was prepared:
[152]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance and radiance of the skin of the face, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 14
[153]Day cream for the face.
[154]A cream having the following formulation is prepared:
[156]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance and radiance of the skin of the face, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 15
[157]Day cream for the face.
[158]A cream having the following formulation is prepared:
[160]After decomposition of the sorbitan palmirate and sorbitan laurate by the enzymes of the skin, this cream makes it possible to treat the skin with palmitic acid, lauric acid, sorbitol, a ceramide and cholesterol, and provides the skin with especially effective protection. Applied daily for 20 days to a tired skin, this cream gives noticeable results.
EXAMPLE 16
[162]A serum having the following formulation is prepared:
[164]After decomposition of the sorbitan palmirate and the sorbitan laurate by the enzymes of the skin, this serum makes it possible to treat the skin with palmitic acid, lauric acid, sorbitol, a ceramide and cholesterol, and provides the skin with especially effective protection. Applied daily for 20 days to a tired skin, this serum gives noticeable results.
EXAMPLE 17
[165]Day cream for the face.
[166]A cream having the following formulation is prepared:
[168]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance and radiance of the skin of the face, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 18
[170]A milk having the following formulation is prepared:
[172]Applied once a day to the body on subjects having firm skin, this milk gives an improvement in the appearance and radiance of the skin, which becomes noticeably more hydrated and smoother after 20 days of application.
EXAMPLE 19
[173]Day cream for the face intended for the nourishment of lacklustre skin.
[174]A cream having the following formulation is prepared:
[176]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the radiance of the skin of the face, which becomes more radiant.
EXAMPLE 20
[177]Hydrating milk for the body
[178]A milk having the following formulation is prepared:
[180]Applied once a day to the body on subjects having firm skin, this milk gives an improvement in the appearance and radiance of the skin, which becomes noticeably more hydrated and smoother after 20 days of application.
EXAMPLE 21
[181]Anti-ageing day cream for the face.
[182]A cream having the following formulation is prepared:
[184]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance and radiance of the skin of the face, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 22
[185]Day cream for the face and neck intended for the care of tired skins.
[186]A cream having the following formulation is prepared:
[188]After a week of daily application every morning to the carefully cleansed face and neck, an improvement is seen in the appearance and radiance of the skin of the face and neck, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 23
[189]Anti-ageing fluid for the face.
[190]A fluid having the following formulation is prepared:
[192]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance and radiance of the skin of the face, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 24
[193]Anti-ageing serum for the face.
[194]A serum having the following formulation is prepared:
[196]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance and radiance of the skin of the face, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 25
[198]A milk having the following formulation is prepared:
[200]Applied once a day to the body on subjects having firm skin, this milk gives an improvement in the appearance and radiance of the skin, which becomes noticeably more hydrated and smoother after 20 days of application.
EXAMPLE 26
[201]Day cream for the face.
[202]A cream having the following formulation is prepared:
[204]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance and radiance of the skin of the face, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 27
[205]Night cream for the face intended for the nourishment of lacklustre skins.
[206]A cream having the following formulation is prepared:
[208]After a week of daily application every night to the carefully cleansed face of a subject having lacklustre skin, an improvement is seen in the radiance of the skin, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 28
[209]Anti-ageing day cream for the face.
[210]A cream having the following formulation is prepared:
[212]After a week of daily application every morning to the carefully cleansed face and neck, an improvement is seen in the appearance and radiance of the skin of the face and neck, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 29
[213]Anti-ageing day cream for the face and neck intended for the care of tired skins.
[214]A cream having the following formulation is prepared:
[216]After a week of daily application every morning to the carefully cleansed face and neck, an improvement is seen in the appearance and radiance of the skin of the face and neck, which becomes smoother, firmer and more hydrated with a more radiant complexion.
EXAMPLE 30
[217]Day cream for the face.
[218]A cream having the following formulation is prepared as in Example 8:
[220]The two formulations defined above are mixed as described in Example 8 to obtain the composition according to the invention.
[221]After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance of the skin of the face, which becomes smoother, firmer and more hydrated.
EXAMPLE 31
[222]A make-up foundation having the following composition is prepared:
[224]The procedure consists in adding the pigments (phase C) to 1/3 of the mixture (vesicular dispersion+oils) (phases A and B), the dispersion being produced beforehand in a conventional manner using a high pressure homogenizer. The whole is mixed for 1 h 30 min, and the remainder of the vesicular dispersion (phase A), the preservatives (phase D), the fillers (phase E) and the neutralized gel (Phase F) are then added successively, homogenizing for 5 min after each introduction.
[225]A natural-beige make-up foundation is thereby obtained. After a week of daily application every morning to the carefully cleansed face, an improvement is seen in the appearance of the skin of the face, which becomes smoother, firmer and more hydrated.
[226]It was found that, in the creams, milks or sera of Examples 8 to 31, the lipid vesicles remained stable after 3 months of storage.
