Wo 2008/107347 A2
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(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date PCT (10) International Publication Number 12 September 2008 (12.09.2008) WO 2008/107347 A2 (51) International Patent Classification: (74) Common Representative: CIBA HOLDING INC.; A61K 8/04 (2006.01) A61K 8/42 (2006.01) Patent Department, Klybeckstrasse 141, CH-4057 Basel A61K 8/35 (2006.01) A61K 8/49 (2006.01) (CH). A61K 8/41 (2006.01) A61Q 17/04 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/EP2008/052336 AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, (22) International Filing Date: EG, ES, FT, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, 27 February 2008 (27.02.2008) IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, (25) Filing Language: English MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, (26) Publication Language: English SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, (30) Priority Data: ZA, ZM, ZW 07103670.1 7 March 2007 (07.03.2007) EP (84) Designated States (unless otherwise indicated, for every (71) Applicant (for all designated States except US): CIBA kind of regional protection available): ARIPO (BW, GH, HOLDING INC. [CWCH]; Klybeckstrasse 141, CH-4057 GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, Basel (CH). ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, (72) Inventors; and FR, GB, GR, HR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, (75) Inventors/Applicants (for US only): DESHAYES, NO, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, Cyrille [FR/FR]; 52, rue de Village-Neuf, F-68128 CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). Rosenau (FR). EHLIS, Thomas [DE/DE]; Har- riet-Straub-Strasse 23, 79100 Freiburg (DE). GRUME- Published: LARD, Julie [FR/FR]; 2, rue de Mulhouse, F-68330 — without international search report and to be republished Huningue (FR). upon receipt of that report (54) Title: METHOD FOR THE STABILIZATION OF ORGANIC MICRONIZED UV ABSORBERS (57) Abstract: Disclosed is the use of amines and amides for the stabilization of a cosmetic composition comprising: (a) an organic micronized UV absorber selected from a benzophenone derivative and (b) a dibenzoylmethane derivative. The use of the amines and amides results in the stabilization of the end-product formulations. Method for the stabilization of organic micronized UV absorbers The present invention relates to a method of stabilization of organic micronized UV absorb ers, specific cosmetic compositions and the use of these cosmetic composition for preventing the human hair or skin from the harmful effect of UV radiation Cosmetic compositions comprising micronized amino substituted hydroxyphenyl benzophe- none derivatives (as described for example in WO 2004/052837) and Butyl methoxydiben- zoylmethane (Avobenzone) represent very effectual UV absorber compositions. However, mixing together these specific UV actives results in the formation of new and larger scaled crystals and/or particles. This crystallization affects the efficacy of the UV-filter combination and the sensory aspect of the end-product Surprisingly it has been found that the crystallization can be slowed, limited and/or prevented by the use of amines, amides, alkanolamides and more preferably alkanolamines in the m i cronized product or within the end-product formulation. As a result, a stabilization of the end- product formulation is achieved. Therefore, the present invention refers to the use of amines and amides for the stabilization of a cosmetic composition comprising (a) an organic micronized UV absorber selected from a benzophenone derivative and (b) a dibenzoylmethane derivative. The benzophenone UV absorbers preferably correspond to formula ( 1 ) , wherein Ri and R2 independently from each other are; Ci-C 2oalkyl; C2-C2oalkenyl; C3-Ci 0cycloalkyl; C3-Ciocycloalkenyl; or R1 and R2 together with the linking nitrogen atom form a 5- or 6- membered heterocyclic ring; n-i is a number from 1 to 4 ; , R3 is a saturated or unsaturated heterocyclic radical; hydroxy-Ci-C 5alkyl; cyclohexyl option ally substituted with one or more CrC 5alkyl; phenyl optionally substituted with a hetero cyclic radical, aminocarbonyl or d-C 5alkylcarboxy; R3 is an alkylene-, cycloalkylene alkenylene or phenylene radical which is optionally inter rupted by -O-; -NH-; a carbonyl- or carboxy group; a radical of formula *— CH— C≡ C-CH — * or R3 together with A forms a bivalent radical of the formula (1a) ; wherein n2 is a number from 1 to 3 ; R3 is an alkantriyl radical; R3 is an alkanetetrayl radical; A is -O-; Or-N(R 5)-; and R5 is hydrogen; Ci-C 5alkyl; or hydroxy-Ci-C 5alkyl. Ci-C 20alkyl denotes a linear or branched, unsubstituted or substituted alkyl group such as, for example, methyl, ethyl, propyl, isopropyl, n-butyl, n-hexyl, cyclohexyl, n-decyl, n-dodecyl, n- octadecyl, eicosyl, methoxyethyl, ethoxypropyl, 2-ethylhexyl, hydroxyethyl, chloropropyl, N,N- diethylaminopropyl, cyanoethyl, phenethyl, benzyl, p-tert-butylphenethyl, p-tert-octyl- phenoxyethyl, 3-(2,4-di-tert-amylphenoxy)-propyl, ethoxycarbonylmethyl-2-(2-hydroxy- ethoxy)ethyl or 2-furylethyl. C2-C20alkenyl is for example allyl, methallyl, isopropenyl, 2-butenyl, 3-butenyl, isobutenyl, n- penta-2,4-dienyl, 3-methyl-but-2-enyl, n-oct-2-enyl, n-dodec-2-enyl, iso-dodecenyl, n-dodec- 2-enyl or n-octadec-4-enyl. C3-Ci 0cycloalkyl is for example cyclopropyl, cyclobutyl, cyclopentyl, cycloheptyl, cyclooctyl, cyclononyl or cyclodecyl and preferably cyclohexyl. These radicals may be substituted, for example by one or more or equal or different d-C 4alkyl radicals, preferably by methyl, and/or hydroxy. If cycloalkyl radicals are substituted by one or more radicals, they are preferably substituted by one, two or four, preferably by one or two equal or radicals. C3-Ci 0cycloalkenyl is for example cyclopropenyl, cyclobutenyl, cyclopentenyl, cycloheptenyl, cycloocentyl, cyclononenyl or cyclodecenyl and preferably cyclohexenyl. These radicals may be substituted with one or more equal or different Ci-C 4alkyl radical, preferably with methyl, and/or hydroxy. If cycloalkenyl radicals are substituted with one or more radicals they are preferably substituted with one, two, three or four, preferably with one or two equal or differ ent radicals. Hydroxy-substituted Ci-C 5alkyl groups are for example hydroxymehtyl, hydroxyethyl, hy- droxypropyl, hydroxybutyl or hydroxypentyl. An alklyene radical is preferably a CrC^alkylene radical, like for example methylene, ethyl ene, propylene, butylene, hexylene or octylene. The alklyene radicals may optionally be substituted by one or more Ci-C 5alkyl radicals. If R1 and R2 are heterocyclic radicals, these comprise one, two, three or four equal or differ ent ring hetero atoms. Special preference is given to heterocycles which contain one, two or three, especially one or two, identical or different hetero atoms. The heterocycles may be mono- or poly-cyclic, for example mono-, bi- or tri-cyclic. They are preferably mono- or bi- cyclic, especially monocyclic. The rings preferably contain 5, 6 or 7 ring members. Examples of monocyclic and bicyclic heterocyclic systems from which radicals occurring in the com pounds of formula ( 1 ) or (2) may be derived are, for example, pyrrol, furan, thiophene, imida zole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, pyridine, pyridazine, pyrimidine, pyrazine, pyran, thiopyran, 1,4-dioxane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, indole, benzothiophene, ben- zofuran, pyrrolidine, piperidine, piperazine, morpholine and thiomorpholine. Preference is given to compounds of formula ( 1 ), wherein - A- Ri and R2 independently from each other are hydrogen; d-C 2oalkyl; C2-C2oalkenyl; C3- Ciocycloalkyl; C3-Ciocycloalkenyl; or R1 and R2 together with the linking nitrogen atom form a 5- or 6-membered heterocyclic ring; n-i is a number from 1 to 4 ; , R3 is a saturated or unsaturated heterocyclic radical; hydroxy-Ci-C 5alkyl; Cyclohexyl substi tuted with one or more CrC 5alkyl; R is an alkylene-, cycloalkylene- or alkenylene radical which is optionally interrupted by a carbonyl- or carboxy group; R3 is an alkantriyl radical; R3 is an alkanetetrayl radical; A is -O-; Or-N(R 5)-; and R5 is hydrogen; Ci-C 5alkyl; or hydroxy-Ci-C 5alkyl. Of preferred interest are compounds of formula (1), wherein Ri and R2 are CrC 20alkyl, preferably Ci-C 5alkyl; and most preferably ethyl. Preferably Ri and R2 in formula (1) have the same definition. If in formula ( 1 ) n-i is 1, compounds are preferred, wherein R3 is a saturated or unsaturated heterocyclic radical, most preferably a saturated hetero- cyclic radical. Among these compounds are those preferred, wherein R3 is a monocyclic radical of 5 , 6 or 7 ring members with one or more heteroatoms, prefera bly wherein R3 is morphonlinyl; piperazinyl; piperidyl; pyrazolidinyl; imadazolidinyl; or pyrrolidinyl. When n-i is 1 further compounds of formula (1) are of interest wherein R3 is an unsaturated heterocyclic radical, preferably a polycyclic radical. Most preferred are compounds of formula (1), wherein R3 is a radical of formula (1a) | —j-R5 , and R5 is polycyclic heteroaromatic radical with one or 2 heteroatoms. Of preferred interest are compounds of formula ( 1), wherein R3 is a radical of formula (1b) <f — J j H-R 6 , wherein R6 is hydrogen; or d-C 5alkyl. R3 is preferably a d-C^alkylene radical, most preferably a C2-C8alkylene radical.