US 20020031482A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2002/0031482 A1 SCHREER et al. (43) Pub. Date: Mar. 14, 2002

(54) COMBINATION OF ERYTHRULOSE AND A (30) Foreign Application Priority Data REDUCING SUGAR WITH SELF-TANNING PROPERTIES Mar. 5, 1997 (CH)...... 518/97 (76) Inventors: THOMAS SCHREIER, BUBENDORF Publication Classification (CH), ROLAND JERMANN, LAUFEN (CH) (51) Int. Cl." ...... A61K 31/70; A61K 7/42; A61K 7/44; A61K 6/00; A61K 7/00 Correspondence Address: (52) U.S. Cl...... 424/59; 424/401; 424/60; PENNIE & EDMONDS 514/23: 514/937; 514/938 1155 AVENUE OF THE AMERICAS NEW YORK, NY 100362711 (57) ABSTRACT The invention relates to an active ingredient combination (*) Notice: This is a publication of a continued pros containing erythrulose and a further reducing Sugar with ecution application (CPA) filed under 37 Self-browning properties, for example dihydroxyacetone, CFR 1.53(d). which combination is used for artificially tanning the skin. (21) Appl. No.: 09/380,651 Compared with compounds containing, for example, only dihydroxyacetone, Said active ingredient combination and (22) PCT Filed: Feb. 27, 1998 cosmetic compounds based thereon result in an even and longer-lasting colouring of the skin and prevent Skin dehy (86) PCT No.: PCT/CH98/00083 dration and uneven flaking. Patent Application Publication Mar. 14, 2002 US 2002/0031482 A1 Fig. 1

%dE

ERYHTHRULOSE + DHA

days

Fig. 2

% drying out

days US 2002/0031482 A1 Mar. 14, 2002

COMBINATION OF ERYTHRULOSE AND A 0008. The active substance combination contains a ratio REDUCING SUGAR WITH SELF-TANNING of erythrulose to reducing Sugar of about 10:1 to 1:10, PROPERTIES advantageously about ca. 1:1 to 1:3; 1:2 being particularly preferred. 0001. The present invention relates to a combination of 0009. A cosmetic formulation uses about 1-5% erythru erythrulose in D- or L-form or as the racemate and at least lose and about 1-15% reducing Sugar, advantageously about one additional reducing Sugar having Self-tanning properties 1.5% erythrulose and 3.5% reducing Sugar. and cosmetic compositions containing these for the artificial tanning of the skin. The cosmetic compositions bring about 0010. The stability of erythrulose with a reducing Sugar a more even and longer-lasting coloration of the skin and in a cosmetic formulation depends on many factors. The prevent the drying out and uneven peeling thereof compared active Substance combination can be used in O/W (e.g. to known compositions that, for example, contain dihy cream or lotion) and also W/O emulsions and other types of droxyacetone alone. cosmetic formulations (e.g. multiple emulsions Such as O/W/O or W/O/W emulsions, gels, ointments, aerosols). 0002 Hydroxyketones and hydroxyaldehydes are known The Stability of the active Substances can be quantitatively active Substances for Self-tanning agents. The active Sub determined using chromatography. To do this, the emulsion stances generally processed into creams react with free is diluted, membrane filtered and analysed using HPLC. amino groups of the Stratum corneum and result in brown 0011. The oily phase in emulsions can, for example, ish-coloured pigments that are bound to proteins of the contain hydrocarbon oils Such as paraffin oil or mineral oils, Stratum corneum. This conversion of reducing Sugars with waxes. Such as beeSWax or paraffin wax, Silicon oils. Such as amino acids, peptides or proteins, known as the Maillard cyclomethicone or dimethicone, fatty alcohols Such as reaction, leads to compounds having a carbonyl function Stearyl alcohol or cetyl alcohol, natural oils Such as jojoba that polymerise to brown melanoids. oil, Sesame oil or Sunflower oil, fatty acid esterS Such as 0003. The hitherto most frequently used active substance isopropyl myristate or glyceryl Stearate or mono-, di- or is dihydroxyacetone (hereinafter referred to as “DHA"). The triglycerides Such as for example caprylic / capric acid fast tanning active Substance (4-7 hours) does, however, triglyceride. have Some disadvantages. The skin colour achieved is 0012. In the case of oil-in-water emulsions, the oil phase yellowish-brown, which produces an unnatural colour, par advantageously comprises 5-45% by weight, in particular ticularly in pale skin. In addition, the tan is irregular and Soon pales again because the top-most layers of the epider about 10-30% by weight of the total formulation. mis are quickly shed. 0013 AS emulsifiers for oil-in-water and water-in-oil emulsions it is possible to use emulsifiers known perse, Such 0004. It has now been found that a combination of as Silicons, Sesquioleates, Sorbitan esters, alkoxylated Sor DHA-or another reducing Sugar having Similar proper bitan and fatty acid esters, alkoxylated mono-, di- and ties-with erythrulose does not display the above disadvan triglycerides, optionally alkoxylated polymerS Such as croSS tages. This may be attributed to the fact that erythrulose dyes polymers of ethylene oxide and propylene oxide, optionally the skin more slowly (the colour takes about 20-24 hours to alkoxylated fatty alcohols, fatty acids, esters of natural oil develop) and less intensively, but instead also penetrates derivatives, etherS Such as polyethylene glycol(n)Stearyl lower layers of the Stratum corneum where it is also able to ether and polyethylene cetyl(n)Stearyl ether. react with the free amino groups. This not only results in more even tanning, but also in a retarded effect, with the 0014. The emulsifiers are advantageously used in result that the tan lasts longer. Moreover the skin becomes amounts of 0.115% by weight related to the total formula less dried out than, for example, with DHA alone. The tion. Synergistic effect, that will Subsequently also be shown with reference to examples, of the active Substance combination 0015 The formulations of the invention may also contain erythrulose/other reducing Sugars, Such as for example additional auxiliary Substances Such as for example Stabi liserS Such as mannitol or cyclodextrin, moisturizerS Such as DHA, was not predictable. glycerol and propylene glycol, thickening agents Such as 0005 Erythrulose alone can also be used as sole active acrylic acid polymers or cellulose derivatives, antioxidants Substance for slightly tanning day creams. The advantage of Such as tocopheryl acetate, pH-correcting agents Such as erythrulose compared to other reducing Sugars having a Sodium phosphate, film-forming agents Such as PVP, pre Self-tanning effect, in particular DHA, lies in the fact that the Servatives Such as phenoxyethanol and paraben, colorants, skin is tanned more evenly and without forming undesirable fragrances, Softeners, antiseptics, bactericides, Vitamins, StreakS. pigments,-propellants as well as other compounds that are cosmetically or medicinally desirable. Examples of other 0006 Erythrulose is a C4-ketosugar of the general struc compounds of this nature are set out in the CTFA Interna tural formula 1,3,4-trihydroxy-butan-2-one that occurs natu tional Cosmetic Ingredient Dictionary, 6" edition, The Cos rally or that can be prepared chemically or biotechnologi metic, Toiletry and Fragrance ASSociation, Inc., Washington cally in a manner known per se. Erythrulose can be used in D.C., 1995. D- or L-form or also as the racemate. DHA is a C3-ketosugar having the general Structural formula 1,3-dihydroxy-propan 0016 Lipophilic systems are quite generally more suit 2-one that can be prepared in a manner known per Se. able for cosmetic formulations of Self-tanning agents. Tan ning can be accelerated and the colour intensity significantly 0007. Other reducing Sugars having self-tanning proper increased by adding penetration enhancers. The following ties that can be used in combination with erythrulose are, for have proved to be particularly Suitable as penetration example, glucose, Xylose, fructose, reose, ribose, arabinose, enhancers: dimethicone, cyclomethicone, propylene glycol allose, tallose, altrose, mannose, galactose, lactose, Sucrose, dipelargonate, propylene glycol or ethoxy diglycol. The erythrose and glyceraldehyde. colour intensity measured was up to 55% higher with US 2002/0031482 A1 Mar. 14, 2002

formulations containing penetration enhancers as compared EXAMPLE 3 to the basic formulation without penetration enhancers. 0.025) A self 0017 Synthetic oils such as Miglyol 812, isopropyl palmitate and Silicon oils and natural lipids Such as jojoba oil 0026 -tanning white lotion is prepared by analogy with and Sesame oil are particularly compatible with the active Example 2, except that 3.00% erythrulose and 2.00% DHA Substance combination and are therefore particularly pre are used. AS in Example 2, this produces a lotion that is ferred. agreeable to use. 0.018 Gels can also be used as formulation base for the EXAMPLE 4 compositions of the invention. Carbomers, cellulose deriva tives and other gellants can be contained as gel-forming 0027. A self-tanning cream is prepared by mixing Substances. together an oily phase composed of 1.00% Cremophor A6 (Ceteareth 6 and stearyl alcohol), 1.00% Cremophor A25 0.019 Insofar as the cosmetic formulation is intended to (Ceteareth 25), 3.00% Cutina GMS (glyceryl Stearate), provide both a Self-tanning effect and also protection against 10.00% paraffin oil, 5.00% jojoba oil and 1.00% cetyl Solar radiation, it-is also possible to add to the formulation alcohol and heating to 70° C. and mixing together an one or Several SunScreens, Such as for example octyl meth aqueous phase composed of 48.50% demineralised water, oxycinnamate and/or butyl methoxydibenzoylmethane. 0.50% Phenonip and 5.00% propylene glycol and heating to 75 C. The aqueous phase is then added to the oily phase 0020 When processing the active substances into cos with stirring and cooled to 50 C., homogenised and cooling metic formulations, care must be taken to ensure that the continued to 30° C. and an additional aqueous phase com active Substances are only added at lower temperatures of posed of 15.00% demineralised water, 5.00% cyclodextrin, about <40 C. and that the pH value 5 is not exceeded in the 1.50% erythrulose and 3.50% dihydroxyacetone is then cosmetic formulations, this being easily achieved through added to the mixture and Stirred until cold. This produces a buffering. cream that is agreeable to use. 0021. The active substance combination of the invention, or the cosmetic formulations based thereon, can be applied EXAMPLE 5 to the human skin in conventional manner. 0028. A self-tanning O/W cream with Sunscreen is pre 0022. The invention will now be explained in greater pared by mixing together an oily phase composed of 5.00% detail with reference to examples, the percentages in each of a mixture of glyceryl Stearate and PEG-100-stearate, case constituting % by weight. 1.00% cetyl alcohol, 2.00% stearic acid, 4.00% dimethicone, 2.00% cyclomethicone, 3.00% caprylic / capric acid trig EXAMPLE 1. lyceride, 1.00% jojoba oil, 4.00% isopropyl palmitate, 2.00% octyl methoxycinnamate and 1.00% butyl methoxy 0023. A self-tanning body lotion is prepared by mixing dibenzoylmethane, heating to 75 C. and adding an aqueous together an oily phase composed of 12.00% Cutina GMS phase heated to 80 C. composed of 51.20% demineralised (glyceryl Stearate), 1.50% Eumulgin B1 (Ceteareth-12), water, 0.50% Phenonip, 6.00% propylene glycol and 2.00% 1.50% Eumulgin B2 (Ceteareth-20), 4.00% isopropyl glycerol and Stirring thoroughly. The emulsion obtained is myristate, 7.00% paraffin oil and 4.00% Miglyol 812 cooled to 50° C. and homogenised. At 30° C. an additional (caprylic / capric acid triglyceride) and heating to 70° C. and aqueous phase composed of 10.00% demineralised water, mixing together an aqueous phase composed of 51.20% 1.50% erythrulose and 3.50% dihydroxyacetone is then demineralised water, 0.50% Phenonip and 3.00% glycerol added and Stirred thoroughly. and heating to 75 C. The aqueous phase is then added to the oily phase with Stirring and cooled to 50 C., homogenised EXAMPLE 6 and cooling continued to 30° C. and an additional aqueous phase composed of 10.00% demineralised water, 1.50% 0029. A self-tanning W/O/W cream is prepared by pre erythrulose and 3.50% dihydroxyacetone is then added to paring an aqueous solution of 2.00% Poloxamer, 0.10% the mixture and stirred until cold. This produces a body Phenonip, 16.02% demineralised water, 0.38% magnesium lotion that is agreeable to use. sulfate heptahydrate, 1.40% xanthan gum, 0.10% Phenonip, and 20.00% demineralised water and adding 60.00% of a EXAMPLE 2 previously prepared W/O emulsion consisting of an oily phase containing 3.30% of a mixture of Sorbitan ester and 0024. A self-tanning white lotion is prepared by mixing polyglycerol ester, 3.00% polyglycerol ester, 15.00% iso together an oily phase composed of 1.50% Arlatone 983 S hexadecan, 14.00% caprylic / capric acid triglyceride and an (PEG-5 glyceryl stearate), 2.20% Arlatone 985 (PEG-5 acqueous phase with 55.50% demineralised water, 0.20% glyceryl stearate), 1.50% Brij 76 (Steareth-10), 5.00% Mig Phenonip, 0.70% magnesium sulfate heptahydrate, 2.50% lyol 812 (caprylic / capric acid triglyceride), 4.00% paraffin erythrulose and 5.80% DHA and homogenising. oil and 1.00% silicon oil AK500 (dimethicone) and heating to 70° C. and mixing together an aqueous phase composed EXAMPLE 7 of 59.30% demineralised water, 0.50% Phenonip and 10.00% propylene glycol and heating to 75 C. The aqueous 0030) A self-tanning gel is prepared by mixing together phase is then added to the oily phase with Stirring and cooled 1.00% PVM (copolymer composed of vinyl chloride and to 50 C., homogenised and cooling continued to 30° C. and vinylmethyl ether) / MA-decadien crosspolymer, 0.50% an additional aqueous phase composed of 10.00% deminera Phenonip and 83.50% demineralised water, adjusting the pH lised water, 1.50% erythrulose and 3.50% dihydroxyacetone to 3.7 with sodium hydroxide solution and adding 15% of a is then added to the mixture and stirred until cold. This mixture of 66.70% demineralised water, 10.00% erythrulose produces a lotion that is agreeable to use. and 23.30% DHA. US 2002/0031482 A1 Mar. 14, 2002

EXAMPLE 8 shows the percentage colour difference of the combination 0.031) A self-tanning day cream is prepared by mixing of erythrulose and DHA compared to DHA. The use of DHA together 5.00% Arlacel 165 (glyceryl Stearate, PEG-100 alone colours the skin faster during the first few dayS. stearate), 1.00% cetyl alcohol, 2.00% stearic acid, 4.00% However, from the 10" day on, the intensity of coloration of Dow Corning 200 silicon (dimethicone polymethylsiloxan), the combination erythrulose and DHA was greater. After 2.00% Belsil CM 020 (cyclomethicone), 3.00% Miglyol 812 application was discontinued, the difference in the intensity (caprylic / capric acid triglyceride), 1.00% jojoba oil, 4.00% of coloration of the combination of erythrulose and DHA isopropyl palmitate, 2.00% Parsol MCX (octyl methoxycin compared to DHA alone was increasingly more marked namate) and 1.00% butyl methoxydibenzoylmethane and because of the delayed decrease in coloration. This shows heating this oily phase to 70° C. In parallel thereto, 57.20% that erythrulose produces a visible retarded effect. deionised water, 0.50% Phenonip, 6.00% propylene glycol 0040. The skin coloration achieved with erythrulose and and 2.00% glycerol are mixed and this acqueous phase is DHA does not show any streak formation and the skin shows heated to 75 C. The aqueous phase is then added to the oily no peeling due to greater drying out. phase with stirring and the mixture cooled to 50 C., 0041. Measurements show that the use of erythrulose and homogenised and cooled further to 30° C. A mixture com DHA in an O/W emulsion causes up to 30% less drying out posed of 5.00% deionised water and -4.00% erythrulose is of the skin (FIG. 2). The skin feels less dry. When using the then added and Stirred until cold, whereupon the entire combination of erythrulose and DHA in comparison to the mixture is then reacted with 0.30% Belamie O/241710. DHA emulsion, the test subjects did not feel any skin 0.032 This produces a day cream that with daily appli tightness. cation gives the skin a slightly brownish coloration and healthy appearance. The Sunscreens also protect the skin 1. An active Substance combination for the artificial from the effects of harmful UV radiation. tanning of the skin containing a combination of erythrulose in D- or L-form or also as the racemate with an additional EXAMPLE 9 reducing Sugar having Self-tanning properties. 0033) To investigate the synergistic effect of erythrulose 2. An active Substance combination according to claim 1 and DHA on the tanning of the Skin a tanning Study was characterised in that the ratio between erythrulose and the conducted to compare an O/W lotion containing 1.5% additional reducing Sugar having Self-tanning properties lies erythrulose and 3.5% DHA according to Example 1 with a between 10:1 to 1:10, advantageously at about 1:1 to 1:3, ca. lotion containing DHA. 1:2 being particularly preferred. 3. An active Substance combination according to claim 1 0034) Fields measuring 10x14 cm were marked on the or claim 2 characterised in that DHA is used as additional back of 4 male and 4 female subjects. The subjects were reducing Sugar having Self-tanning properties. neither allowed to Sunbathe nor to visit a Solarium during the 4. A cosmetic formulation containing an active Substance entire period of the Study. combination according to one of claims 1 or 2 characterised 0035. Before the measurements, the subjects were accli in that 1-5% erythrulose and 1-15% of an additional reduc matised for 15 min in a skin laboratory at 26-28 C. and ing Sugar having Self-tanning properties, advantageously 40-50% air humidity. Immediately after measuring the ini about 1.5% erythrulose and 3.5% of an additional reducing tial value on day 0, the marked test fields were treated with Sugar having Self-tanning properties are used. 0.3 ml of the appropriate lotion with light rubbing in. This 5. A cosmetic formulation containing an active Substance procedure was repeated on the following 9 days. No more combination according to one of claims 1 or 2 characterised lotion was applied after the 10" day. in that DHA is used as additional reducing Sugar having 0036) From the first day to the 20" day the colour Self-tanning properties. changes as well as the skin moisture were in each case 6. A cosmetic formulation according to one of claims 4 or measured immediately before the next application. The skin 5 in the form of an O/W emulsion. moisture was measured using the CM 820 Corneometer 7. A cosmetic formulation according to claim 6 charac (Courage and Khazaka). The skin colour was measured terised in that the oily phase amounts to 5-45% by weight, using the Minolta CR 300 Chromameter. in particular about 10-30% by weight of the total formula 0037. The skin colour was quantified using the “CIE tion. L*a*b* colour system”. This defines the colours in a three 8. A cosmetic formulation according to one of claims 4-7 dimensional colour co-ordinate System. The a value corre characterised in that it contains at least one penetration sponds to the red-green axis, the b value to the yellow-blue enhancer. axis and the L* value to the pale-dark axis. The Smaller the 9. A cosmetic formulation according to one of claims 4-8 L* value, the darker the colour. The difference between two characterised in that it contains at least one compound acting measuring points in this three-dimensional colour coordi as Sunscreen, advantageously octyl methoxycinnamate and/ nate System can be calculated from the absolute values using or butyl methoxydibenzoylmethane. the following formula: 10. A proceSS for the topical use of an active Substance combination according to one of claims 1-3 or of a cosmetic formulation according to one of claims 4-9, by topically 0.038. The value calculated using this formula is a param applying to the skin an effective amount of an active eter for the colour change of the skin. Substance combination or of a cosmetic formulation. 0039 FIG. 1 shows the different influence of the two formulations tested on the colour intensity. The diagram