WO1993011095A1 - Uva-absorbing sunscreen metal complexes - Google Patents
Uva-absorbing sunscreen metal complexes Download PDFInfo
- Publication number
- WO1993011095A1 WO1993011095A1 PCT/US1992/009694 US9209694W WO9311095A1 WO 1993011095 A1 WO1993011095 A1 WO 1993011095A1 US 9209694 W US9209694 W US 9209694W WO 9311095 A1 WO9311095 A1 WO 9311095A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sunscreen
- acid ester
- group
- aluminum
- ethylhexyl
- Prior art date
Links
- 239000000516 sunscreening agent Substances 0.000 title claims abstract description 155
- 230000000475 sunscreen effect Effects 0.000 title claims abstract description 136
- 229910052751 metal Inorganic materials 0.000 title claims abstract description 42
- 239000002184 metal Substances 0.000 title claims abstract description 42
- 239000000203 mixture Substances 0.000 claims abstract description 118
- NZZIMKJIVMHWJC-UHFFFAOYSA-N dibenzoylmethane Chemical compound C=1C=CC=CC=1C(=O)CC(=O)C1=CC=CC=C1 NZZIMKJIVMHWJC-UHFFFAOYSA-N 0.000 claims abstract description 49
- 230000005855 radiation Effects 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 26
- 125000005647 linker group Chemical group 0.000 claims abstract description 25
- 150000001768 cations Chemical class 0.000 claims abstract description 21
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims abstract description 16
- -1 2-ethylhexyl Chemical group 0.000 claims description 60
- 239000002253 acid Substances 0.000 claims description 33
- 150000002148 esters Chemical class 0.000 claims description 33
- REDXJYDRNCIFBQ-UHFFFAOYSA-N aluminium(3+) Chemical compound [Al+3] REDXJYDRNCIFBQ-UHFFFAOYSA-N 0.000 claims description 27
- 229910052782 aluminium Inorganic materials 0.000 claims description 26
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 239000003446 ligand Substances 0.000 claims description 17
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 16
- 229960004050 aminobenzoic acid Drugs 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- KLMDYFUUSKOJAX-UHFFFAOYSA-K aluminum;acetate;dihydroxide Chemical compound CC(=O)O[Al](O)O KLMDYFUUSKOJAX-UHFFFAOYSA-K 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 12
- 150000001450 anions Chemical class 0.000 claims description 10
- AFDXODALSZRGIH-UHFFFAOYSA-N p-coumaric acid methyl ether Natural products COC1=CC=C(C=CC(O)=O)C=C1 AFDXODALSZRGIH-UHFFFAOYSA-N 0.000 claims description 10
- ALYNCZNDIQEVRV-UHFFFAOYSA-N aniline-p-carboxylic acid Natural products NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 9
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 8
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052787 antimony Inorganic materials 0.000 claims description 8
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 claims description 8
- 239000010949 copper Substances 0.000 claims description 8
- 229910052802 copper Inorganic materials 0.000 claims description 8
- 229910052742 iron Inorganic materials 0.000 claims description 8
- 239000010936 titanium Substances 0.000 claims description 8
- 229910052719 titanium Inorganic materials 0.000 claims description 8
- 229910052725 zinc Inorganic materials 0.000 claims description 8
- 239000011701 zinc Substances 0.000 claims description 8
- 150000001298 alcohols Chemical class 0.000 claims description 7
- 150000003863 ammonium salts Chemical class 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 6
- HQQUTGFAWJNQIP-UHFFFAOYSA-K aluminum;diacetate;hydroxide Chemical compound CC(=O)O[Al](O)OC(C)=O HQQUTGFAWJNQIP-UHFFFAOYSA-K 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 239000004408 titanium dioxide Substances 0.000 claims description 6
- MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 claims description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 5
- XTEGARKTQYYJKE-UHFFFAOYSA-M Chlorate Chemical compound [O-]Cl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-M 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 5
- 235000021355 Stearic acid Nutrition 0.000 claims description 5
- 229940083916 aluminum distearate Drugs 0.000 claims description 5
- RDIVANOKKPKCTO-UHFFFAOYSA-K aluminum;octadecanoate;hydroxide Chemical compound [OH-].[Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O RDIVANOKKPKCTO-UHFFFAOYSA-K 0.000 claims description 5
- 229910052791 calcium Inorganic materials 0.000 claims description 5
- 239000011575 calcium Substances 0.000 claims description 5
- 150000001735 carboxylic acids Chemical class 0.000 claims description 5
- 238000000576 coating method Methods 0.000 claims description 5
- 150000002009 diols Chemical class 0.000 claims description 5
- DLAHAXOYRFRPFQ-UHFFFAOYSA-N dodecyl benzoate Chemical compound CCCCCCCCCCCCOC(=O)C1=CC=CC=C1 DLAHAXOYRFRPFQ-UHFFFAOYSA-N 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000011777 magnesium Substances 0.000 claims description 5
- 229910052749 magnesium Inorganic materials 0.000 claims description 5
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 5
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 5
- 239000011591 potassium Substances 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 239000008117 stearic acid Substances 0.000 claims description 5
- 229910052712 strontium Inorganic materials 0.000 claims description 5
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 claims description 5
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 claims description 4
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 claims description 4
- KGKQNDQDVZQTAG-UHFFFAOYSA-N 8-methylnonyl 2,2-dimethylpropanoate Chemical compound CC(C)CCCCCCCOC(=O)C(C)(C)C KGKQNDQDVZQTAG-UHFFFAOYSA-N 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052684 Cerium Inorganic materials 0.000 claims description 4
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 claims description 4
- 241000282412 Homo Species 0.000 claims description 4
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 4
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims description 4
- 229910052776 Thorium Inorganic materials 0.000 claims description 4
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 4
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 claims description 4
- 229940063655 aluminum stearate Drugs 0.000 claims description 4
- 229910052788 barium Inorganic materials 0.000 claims description 4
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052790 beryllium Inorganic materials 0.000 claims description 4
- ATBAMAFKBVZNFJ-UHFFFAOYSA-N beryllium atom Chemical compound [Be] ATBAMAFKBVZNFJ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052797 bismuth Inorganic materials 0.000 claims description 4
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims description 4
- ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 claims description 4
- 239000011248 coating agent Substances 0.000 claims description 4
- 229940031578 diisopropyl adipate Drugs 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229910052733 gallium Inorganic materials 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 4
- 229910052738 indium Inorganic materials 0.000 claims description 4
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 claims description 4
- 229910052746 lanthanum Inorganic materials 0.000 claims description 4
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 4
- 229910052750 molybdenum Inorganic materials 0.000 claims description 4
- 239000011733 molybdenum Substances 0.000 claims description 4
- 229910052758 niobium Inorganic materials 0.000 claims description 4
- 239000010955 niobium Substances 0.000 claims description 4
- GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 claims description 4
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 4
- LLYCMZGLHLKPPU-UHFFFAOYSA-M perbromate Chemical compound [O-]Br(=O)(=O)=O LLYCMZGLHLKPPU-UHFFFAOYSA-M 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 229910052715 tantalum Inorganic materials 0.000 claims description 4
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 claims description 4
- 229910052718 tin Inorganic materials 0.000 claims description 4
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 claims description 4
- 229910052721 tungsten Inorganic materials 0.000 claims description 4
- 239000010937 tungsten Substances 0.000 claims description 4
- 229910052726 zirconium Inorganic materials 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- YBGZDTIWKVFICR-JLHYYAGUSA-N Octyl 4-methoxycinnamic acid Chemical compound CCCCC(CC)COC(=O)\C=C\C1=CC=C(OC)C=C1 YBGZDTIWKVFICR-JLHYYAGUSA-N 0.000 claims description 3
- 229910006069 SO3H Inorganic materials 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 235000010233 benzoic acid Nutrition 0.000 claims description 3
- SXDBWCPKPHAZSM-UHFFFAOYSA-M bromate Inorganic materials [O-]Br(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-M 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 239000001177 diphosphate Substances 0.000 claims description 3
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 3
- 235000011180 diphosphates Nutrition 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 3
- 239000006210 lotion Substances 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000007935 neutral effect Effects 0.000 claims description 3
- 239000013110 organic ligand Substances 0.000 claims description 3
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 3
- 150000004072 triols Chemical class 0.000 claims description 3
- 239000011787 zinc oxide Substances 0.000 claims description 3
- ZXDDPOHVAMWLBH-UHFFFAOYSA-N 2,4-Dihydroxybenzophenone Chemical compound OC1=CC(O)=CC=C1C(=O)C1=CC=CC=C1 ZXDDPOHVAMWLBH-UHFFFAOYSA-N 0.000 claims description 2
- TYYHDKOVFSVWON-UHFFFAOYSA-N 2-butyl-2-methoxy-1,3-diphenylpropane-1,3-dione Chemical compound C=1C=CC=CC=1C(=O)C(OC)(CCCC)C(=O)C1=CC=CC=C1 TYYHDKOVFSVWON-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 2
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 claims description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 claims description 2
- 229920000388 Polyphosphate Polymers 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims description 2
- LCKIEQZJEYYRIY-UHFFFAOYSA-N Titanium ion Chemical compound [Ti+4] LCKIEQZJEYYRIY-UHFFFAOYSA-N 0.000 claims description 2
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 claims description 2
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 claims description 2
- JPUHCPXFQIXLMW-UHFFFAOYSA-N aluminium triethoxide Chemical compound CCO[Al](OCC)OCC JPUHCPXFQIXLMW-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 239000000908 ammonium hydroxide Substances 0.000 claims description 2
- 229960005193 avobenzone Drugs 0.000 claims description 2
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 claims description 2
- VAROLYSFQDGFMV-UHFFFAOYSA-K di(octanoyloxy)alumanyl octanoate Chemical compound [Al+3].CCCCCCCC([O-])=O.CCCCCCCC([O-])=O.CCCCCCCC([O-])=O VAROLYSFQDGFMV-UHFFFAOYSA-K 0.000 claims description 2
- 150000001991 dicarboxylic acids Chemical class 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 claims description 2
- 150000004662 dithiols Chemical class 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 2
- 239000007764 o/w emulsion Substances 0.000 claims description 2
- FMJSMJQBSVNSBF-UHFFFAOYSA-N octocrylene Chemical group C=1C=CC=CC=1C(=C(C#N)C(=O)OCC(CC)CCCC)C1=CC=CC=C1 FMJSMJQBSVNSBF-UHFFFAOYSA-N 0.000 claims description 2
- 229960000601 octocrylene Drugs 0.000 claims description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 2
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- 230000005923 long-lasting effect Effects 0.000 description 1
- NEMFQSKAPLGFIP-UHFFFAOYSA-N magnesiosodium Chemical compound [Na].[Mg] NEMFQSKAPLGFIP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
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- 229960002216 methylparaben Drugs 0.000 description 1
- ZLQJVGSVJRBUNL-UHFFFAOYSA-N methylumbelliferone Natural products C1=C(O)C=C2OC(=O)C(C)=CC2=C1 ZLQJVGSVJRBUNL-UHFFFAOYSA-N 0.000 description 1
- 235000011929 mousse Nutrition 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- QZGIWPZCWHMVQL-UIYAJPBUSA-N neocarzinostatin chromophore Chemical compound O1[C@H](C)[C@H](O)[C@H](O)[C@@H](NC)[C@H]1O[C@@H]1C/2=C/C#C[C@H]3O[C@@]3([C@@H]3OC(=O)OC3)C#CC\2=C[C@H]1OC(=O)C1=C(O)C=CC2=C(C)C=C(OC)C=C12 QZGIWPZCWHMVQL-UIYAJPBUSA-N 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- 238000009828 non-uniform distribution Methods 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
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- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 229940101267 panthenol Drugs 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 235000020957 pantothenol Nutrition 0.000 description 1
- 239000011619 pantothenol Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940100460 peg-100 stearate Drugs 0.000 description 1
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- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000008845 photoaging Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- RMGVATURDVPNOZ-UHFFFAOYSA-M potassium;hexadecyl hydrogen phosphate Chemical compound [K+].CCCCCCCCCCCCCCCCOP(O)([O-])=O RMGVATURDVPNOZ-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000007665 sagging Methods 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 229910021647 smectite Inorganic materials 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940100459 steareth-20 Drugs 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 1
- 235000021286 stilbenes Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000037072 sun protection Effects 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 229940066765 systemic antihistamines substituted ethylene diamines Drugs 0.000 description 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
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- 235000019155 vitamin A Nutrition 0.000 description 1
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- 239000011720 vitamin B Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/26—Aluminium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/27—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/28—Zirconium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/29—Titanium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/58—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/60—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in meta- or para- positions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/06—Aluminium compounds
- C07F5/069—Aluminium compounds without C-aluminium linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/58—Metal complex; Coordination compounds
Definitions
- the present invention relates to sunscreen complexes, more particularly to sunscreen metal complexes, having enhanc i.e. both increased and broadened, UVA absorption.
- Th complexes comprise a sunscreen moiety complexed to a cation species, preferably a metal cation, in which the sunscreen moie further comprises a dibenzoylmethane UVA-absorbing chromophore, UVB-absorbing chromophore, and a linking group connecting the t chromophores.
- sunscreen moie further comprises a dibenzoylmethane UVA-absorbing chromophore, UVB-absorbing chromophore, and a linking group connecting the t chromophores.
- the damaging effects of sunlight on skin are well documente
- the major short term hazard of prolonged exposure to sunlight erythema i.e. sunburn.
- the 290 to 320 nanometer waveleng ultraviolet radiation range designated as the "UVB” waveleng range, tends to be the primary cause of erythema.
- the 320 to 4 nanometer wavelength ultraviolet radiation range designated the "UVA” wavelength range, also produces erythema.
- Another long term hazard of ultraviolet radiation is prem ture aging of the skin. This condition is characterized wrinkling and yellowing of the skin, along with other physic changes such as cracking, telangiectasis (spider vessels), sol keratoses (growths), ecchymoses (subcutaneous hemorrhagic l sions), and loss of elasticity (sagging).
- the adverse effec associated with exposure to UVA and UVB wavelength radiation a more fully discussed in DeSimone, "Sunscreen and Suntan Products" Handbook of Nonprescription Drugs. 7th Ed., Chapter 26, pp 499-511 (American Pharmaceutical Association, Washington, D.C.
- compositions containing a high level of these agents are opaque, generally unattractive in color, and are viewed as unacceptabl for usage on more than just the nose or tops of the ears. Furthermore, these agents are very susceptible to rub-off o wear-off resulting in little or no protection.
- sunscreen agents exert their effects through chemical means, i.e., they absorb ultraviolet radiation so that it cannot penetrate the skin. Sunscreens present the user with several problems. For example, they must be on the surface of the skin at the time of exposure to be effective. Sunscreens are preventative so one must anticipate being in the sun. To be most effective, sunscreens must be on the skin as a continuous uniform film. Delivering such a film to the surface of the skin is very difficult.
- UVB absorbers Most commercially-available sunscreen agents are primarily UVB absorbers.
- the number of UVA absorbers is more limited with benzophenones and dibenzoylmethanes being the most well-known.
- It is a still further object of the present invention provide processes for the preparation of sunscreen meta complexes. It is another object of the present invention to provid topical sunscreen compositions containing sunscreen meta complexes for providing protection for the skin from the damagin effects of UV radiation.
- It is still another object of the present invention t provide sunscreen compositions containing sunscreen meta complexes which are not readily absorbed by the skin; which hav increased sunscreen protection and decreased chance for allergy irritation, or toxicity problems resulting from daily or regula use; which are less susceptible to rub off; and which are cos eti cally acceptable.
- the present invention relates to a sunscreen complex havin the general structure:
- X is a UVA-absorbing chromophore having the general structure:
- Z is a UVB-absorbing chromophore selected from the group consisting of:
- each A is a substituent independently selected from the gro consisting of R, -OR, -NR2 or -SO3H; each A 1 is independentl -OR or -NR2; each A2 is independently -OR or -O2C-RI; each is independently -CN or -CO2 I; and each R is independentl H, straight or branched chain alkyl having from about 1 about 20 carbon atoms, (CH2CH2 ⁇ ) q -H, or (CH2CH(CH3)0) q - wherein q is an integer from 1 to about 8; and each Rl i independently straight or branched chain alkyl having fr about 1 to about 20 carbon atoms; and
- G is a linking moiety selected from the group consisting of
- linking moiety which is a chemical bon which covalently bonds the X and Z chromophor moieties such that the electron systems of th X and Z moieties are directly coupled;
- (B) m is an integer selected from 1, 2, 3 or 4;
- (C) M is a metal cation, an ammonium cation, or a substituted ammonium cation
- n is an integer selected from 1, 2, 3, or 4;
- (E) L is a ligand comprising a neutral or negatively charge organic or inorganic moiety
- (F) p is an integer selected from 0, 1, 2, 3 or 4.
- the present invention further relates to processes fo preparing these sunscreen complexes, to compositions containin these complexes, and to methods for providing enhanced protectio to the skin of humans or lower animals from the effects of ultraviolet radiation.
- sunscreen complexes useful in the present invention are those having the general structure:
- [X - G - Z] m represents a sunscreen moiety having two distinct chromophores which are linked together, wherein X represents a dibenzoylmethane UVA-absorbing chromophore, Z represents a UVB-absorbing chromophore, and G represents a linking group.
- m represents the number of sunscreen moieties present in the complex.
- (M) ⁇ represents a cationic species such as a metal, or alternatively ammonium or substituted ammonium, where n designates the number of these species present in the complex.
- (L) p represents a ligand, which is optionally present in the complex, where p designates the number of ligands present in the complex.
- the sunscreen complexes of the present invention preferably absorb light in the visible wavelength range (i.e. above about 400 n ) only weakly or not at all.
- the complexes are therefore either only lightly colored (e.g., light yellow or cream colored) or are essentially white. This is desirable for cosmetic reasons.
- the sunscreen metal complexes preferably do not have a € of greater than about 500 for any wavelength above about 400 nm, and most preferably the € is essentially zero for any wavelength above about 400 nm.
- the sunscreen complexes useful in the present invention have several desirable properties relative to a simple mixture of a UVA-absorbing molecule with a UVB-absorbing molecule.
- One benefit is the certainty of providing both UVA and UVB protection at the same site on the skin.
- a mixture of molecules may lack this uniformity due to non-uniform distribution onto the skin surface and/or selective penetration by one type of molecule through the skin versus the other type of molecule.
- a related benefit is tha the sunscreen agents of the present invention provide a constan relative proportion of UVA to UVB protection because one chromo phore cannot be more readily lost from the skin (e.g., by a highe rate of rub-off or skin penetration) than the other chromophore
- Another benefit is that the sunscreen complexes of the presen invention are absorbed more slowly by the skin than mixtures o the independent chromophores. This translates into longer dura tion of protection for the skin, and less potential for ski irritation resulting from absorption by the skin.
- sunscreen agents useful in the present invention provide thi long-lasting, constant UV radiation protection at least as effec tively as a freshly-applied mixture of independent chromophores and in some instances the protection is stronger and more broad spectrum than the mixture.
- the ability of the compounds of th present invention, and of mixtures of independent chromophores, t absorb UV radiation may be measured by in vitro methods know generally in the art, such as those taught in Sayre et al . , " Comparison of in vivo and in vitro Testing of Sunscreening Formu las", Photochem. Photobiol..
- Some of th compounds of the present invention may also be more resistant t wash-off by water, more resistant to removal by sweating, and mor resistant to rubbing/toweling.
- TX - G - Zl Sunscreen Moiety may also be more resistant t wash-off by water, more resistant to removal by sweating, and mor resistant to rubbing/toweling.
- the sunscreen moieties which comprise the sunscreen complexe of the present invention are those moieties which have tw distinct chromophores which are covalently linked together.
- Thi covalent linkage can be such that the two chromophore moieties ar directly coupled, i.e., their electrons are shared Alternatively, this covalent linkage can be such that the tw chromophore moieties do not have their electron systems directl coupled with each other.
- one of the chromophores is characterize as being effective for strongly absorbing radiation in the UV range when that chromophore is isolated in an independen molecule.
- the other chromophore is characterized as bein effective for absorbing radiation predominantly within the UV range when that chromophore is isolated in an independent mole ⁇ cule.
- the sunscreen moieties useful in the complexes of th present invention have the general structure: [X - G - Z].
- the X group is a UVA-absorbing, dibenzoylmethane chromophore.
- This UVA-absorbing chromophore when isolated as an independent chromophore, would exhibit at least one absorption maximum (designated herein as ⁇ max, and described more fully hereinafter) within the wavelength range of from about 320 to about 400 nm.
- This absorption maximum would exhibit a molar absorptivity value (designated herein as " € ", and calculated as described hereinafter) of at least about 9,000, preferably at least about 20,000, and most preferably at least about 30,000.
- the Z group in the above general structure is a UVB-absorbing chromophore that is a substituted, carbonyl-containing, aromatic ring-containing species.
- This UVB-absorbing chromophore when isolated as an independent chromophore, would exhibit a molar absorptivity value, € , of at least about 4,000, preferably at least about 15,000, and most preferably at least about 25,000, for at least one wavelength within the range of from about 290 to about 320 nm.
- the Z group when present as the sole chromophore in a molecule as hereinafter defined, the Z group exhibits at least one absorption maximum ⁇ max within the range of from about 290 to about 320 nm.
- This absorption maximum preferably has a molar absorptivity value of at least about 4,000, more preferably at least about 15,000, and most preferably at least about 25,000.
- the Z group when present as the sole chromophore in a molecule as hereinafter defined, the Z group furthermore should not exhibit a ⁇ max having a € greater than about 9,000 for any wavelength above about 320 nm.
- the third component of the above general structure i.e., the
- the G group covalently bonds the X and Z chromophores.
- the G group separates the electron systems of the two chromophores such that the two chromophores do not have their electron systems directly coupled with each other.
- the G linking group may be a straight or branched chain alky group having from about 1 to about 6 carbon atoms, a straight o branched chain alkyloxy group having from about 1 to about carbon atoms, or straight or branched alkylamino group having fro about 1 to about 6 carbon atoms.
- G is a linking moiety which is a chemical bon which covalently bonds the two X and Z chromophores such that th electron systems of these chromophores are directly coupled, i.e. electrons are shared.
- G selected from a single bond, or atoms or groups of atoms which have free electrons which may b shared with both chromophore moieties, such as -0- and -NR (wherein R is H, straight or branched chain alkyl having fro about 1 to about 20 carbon atoms, (CH 2 CH 2 0)q-H, o (CH 2 CH(CH 3 )0)q-H, wherein m is an integer from 1 to about 8, an preferably q»l to about 3).
- R is H, straight or branched chain alkyl having fro about 1 to about 20 carbon atoms, (CH 2 CH 2 0)q-H, o (CH 2 CH(CH 3 )0)q-H, wherein m is an integer from 1
- sunscreen moieties which comprise the complexes of th instant invention are fully disclosed in U.S. Patent Nos. 5,041,282, 4,999,186 and 4,937,370, which have already bee incorporated by reference herein. Also, European Patent Application No. 416,837, to Haffey et al., published March 13, 1991, and U.S. Application Serial No. 404,751, filed September 8, 1989, to Haffey et al . further describes these sunscreen moieties; these two references are incorporated herein by reference.
- the number of sunscreen moieties present is designated by m, wherein m is an integer selected from 1 through 8, more preferably m is an integer selected from 1 through 4, even more preferably m is an integer selected from 1 through 3, and most preferably m is 2.
- the complexes of the instant invention can exist as a mixture of different species in which the m value varies.
- the average m value is a noninteger average of the m values for the species present.
- Examples of the X, UVA-absorbing dibenzoylmethane chromophores useful in the sunscreen compounds of the present invention include those of the following general structure:
- A is preferably R, where R i preferably straight or branched chain alkyl having from 1 to abou 4 carbon atoms. A is most preferably H.
- the dibenzoylmethan chromophore is represented as a 1,3-diketone it should b understood that this representation in no way excludes othe tautomeric forms of the functional group such as the e ⁇ ol form Thus whenever the 1,3-diketone form is designated, it i understood that all appropriate enol tautomers are als contemplated and included herein. These tautomeric enol forms o the dibenzoylmethane chromophore can be represented by th following tautomeric structures.
- the dibenzoylmethane chromophore can lose a hydrogen atom to form the corresponding anionic species. This phenomenon is more likely at higher pH values (i.e. alkaline pH values) and when the dibenzoylmethane chromophore is complexed to a cationic species such as a metal.
- a cationic species such as a metal.
- UVB-absorbing Z chromophore moieti useful in the sunscreen compounds of the present inventi include:
- each Al is independently -OR o NR2; each A2 is independently -OR or O2C-RI; each A i independently -CN or -CO2R 1 ; and each R and Rl are as describe hereinbefore for the substituted X, UVA-absorbing chromophores.
- Preferred as the Z, UVB-absorbing chromophore moiety are the groups:
- each R is independently selected from H or straight or branched chain alkyl having from about 1 to about 20 carbon atoms
- Al is -0CH 3 , -0CH 2 CH 3 , OH, or -NR 2 (wherein each R is independently selected from H or straight or branched chain alkyl having from about 1 to about 20 carbon atoms).
- Particularly preferred is one R group having more than about 2 carbon atoms (especially branched-chain alkyl groups, e.g., 2-ethylhexyl), and the other R group being methyl or ethyl, especially methyl.
- both R groups are the same alkyl group, e.g., methyl and more preferably, 2-ethylhexyT.
- a 1 is
- the G linking groups useful in the compounds of the present invention include the generically described structure:
- each W 1 and W 2 is, independently, selected from a single bond, preferably 0 or NR (wherein R is as described hereinbefore); s is an integer of 1 or greater, preferably s equals an integer from 1 to about 6; t is an integer of 1 or greater, preferably t is 1 or 2; and each R 2 group is independently selected from the group consisting of H, OH, or straight or branched chain alkyl having from 1 to about 20 carbon atoms, preferably R 2 is H, OH, methyl or ethyl .
- Useful G linking moiety groups include: -0-(-CH 2 -) s -0-, wherein s is an integer from 1 to about 6; -NH-(-CH 2 -) s -NH-, wherein s is an integer from 1 to about 6; -(-0-CH 2 CH 2 -) s -0-, wherein s is 1 or 2; -(-NH-CH 2 CH 2 -) S -NH-, wherein s is 1 or 2; -(-0-CH 2 -CH-) s -0-, wherein s is 1 or 2; CH 3 -(-NH-CH 2 -CH-)s-NH-, wherein s is 1 or 2; and
- a particularly preferred G group is -0CH 2 CH 2 0-.
- the G linking group is represented by an atom or substituted atom such as -0- or -NR- (wherein R is H, straight or branched chain alkyl having from about 1 to about 20 carbon atoms, (CH2CH2 ⁇ ) q -H or (CH2CH(CH3)0) q -H, wherein q is an integer from 1 to about 8, and preferably q * 1 to about 3).
- R is H, straight or branched chain alkyl having from about 1 to about 20 carbon atoms, (CH2CH2 ⁇ ) q -H or (CH2CH(CH3)0) q -H, wherein q is an integer from 1 to about 8, and preferably q * 1 to about 3).
- G is - 0 - or - NH -.
- G is - 0 -.
- Preferred sunscreen moieties useful in the complexes of the instant invention are 4-N,N(2-ethylhexyl)methylaminobenzoic acid ester with 4-hydroxydibenzoylmethane, 4-N,N-di-(2- ethylhexyl)-4-aminobenzoic acid ester with 4-hydroxydiben- zoyl - methane, 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, 4-N,N-di-(2-ethyl- hexyl)4-aminobenzoic acid ester with 4-(2-hydroxy- ethoxy)- dibenzoylmethane, 4-N,N-dimethylaminobenzoic acid ester with 4-hy- droxydibenzoyl ethane, 4-N,N-dimethylamino- benzo
- the sunscreen moieties of the complexes of the present invention can be prepared from comrnercially-available, chromophore-containing molecules. Typically, the synthesis of the sunscreen agents will be achieved by an esterification or amidation reaction. Synthesis techniques which are generally applicable for synthesizing sunscreen agents of the present invention are taught, for example, in U.S. Patent 4,002,733, issued January 11, 1977, to Degen et al . ; and in U.S. Patent 4,115,547, issued September 19, 1978, to Degen et al . ; the dis ⁇ closures of both these patents being incorporated herein by reference. Representative procedures for synthesizing the sun- screen agents of the present invention are provided in the Exam ⁇ ples hereinafter.
- independent chromophore means the chromophore moiety (i.e., either the X or Z group) when it is bonded to -0-R 3 (wherein R 3 represents a short chain alkyl group, e.g., methyl or ethyl; preferably methyl) rather than the chromo ⁇ phore moiety being bonded to the G linking moiety within the X-G-Z compound.
- the independent chromophores of the sunscreen moiety 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane are the ethyl ester of 4-N,N-(2-ethylhexyl)methylaminobenzoic acid and 4-methoxydiben- zoylmethane.
- molar absorptivity value is a quantitative measure of the ability of a molecule to absorb ultra ⁇ violet light at a specified wavelength.
- the molar absorptivity value is expressed at a particular wavelength of light as the molar absorption coefficient (represented herein by “6 " which is expressed in units of liter/mole cm), which is calculated by the equation:
- a € - lc wherein "1" is the path length (in centimeters) of the absorbing media through which the light passes; "c” is the concentration of the chromophore molecule (in moles per liter); and "A” is the "absorbance".
- the absorbance is calculated from the observed difference in the intensity of the particular wavelength of light before and after passing through the chromophore-molecule-contain- ing absorbing media. Thus, the absorbance is calculated by the equation:
- I wherein "I 0 " is the intensity of a particular wavelength of in ⁇ cident radiation on an absorbing path; and "I” is the intensity of the same particular wavelength of transmitted radiation which has passed through the absorbing path.
- absorption maximum means a wavelength of radiation at which the chromophore-containing molecule has the greatest molar absorptivity value relative to wavelengths immediately above and below the absorption maximum wavelength.
- absorption maxima are provided for representative sunscreen compounds of the present invention in the Examples hereinafter.
- the sunscreen complexes of the present invention comprise a cationic species, preferably a metal, or alternatively ammonium or substituted ammonium, represented by the general structure (M) n .
- metal cations useful in the complexes of the present invention include alkali metal (e.g., sodium and potassium), alkaline earth metal (e.g., calcium and magnesium), and transition and heavy metals (e.g., aluminum and strontium).
- alkali metal e.g., sodium and potassium
- alkaline earth metal e.g., calcium and magnesium
- transition and heavy metals e.g., aluminum and strontium
- Preferred for use in the complexes of the instant invention are the metals selected from the group consisting of aluminum, zinc, calcium, magnesium, copper, iron, barium, strontium, zirconium, titanium, tin, beryllium, gallium, indium, lanthanum, manganese, antimony, bismuth, cerium, thorium, niobium, tantalum, antimony, molybdenum, tungsten, lithium, sodium, potassium and mixtures thereof.
- the sunscreen complexes of the instant invention can also comprise complexes with other cationic species such as ammonium, substituted ammonium (e.g., mono-, di-, tri- and tetra- alkyl and alkoxy substituted), and cations of diamines (e.g., tetra- alkyl and alkoxy substituted ethylene diamines).
- preferred cation species include metals selected from the group consisting of aluminum, titanium, copper, iron, and zinc.
- the sunscreen complexes of the present invention aluminum cations having a valence of 3 + are most preferred.
- the number of M species present in the complex is designated by n, wherein n is an integer selected from 1 through 4, more preferably n is an integer selected from 1 through 3, even more preferably n is an integer selected from 1 and 2, and most preferably n is 1.
- the complexes of the instant invention can exist as a mixture of different species having different n values.
- the average n value is a noninteger weighted average of the n values for the species present.
- the M species can be derived from any suitable sources.
- the cation can be derived from a wide variety of salts.
- salts include metal oxides, hydroxides, fluorides, chlorides, bromides, iodides, carbonates, bicarbonates, phosphates, hydrogen phosphates, dihydrogen phosphates, alkoxides (e.g., isopropoxide), sulfates, hydrogensulfates, nitrates, sulfites, nitrites, borates, chlorates, bromates, perchlorates, perbro ates, diphosphates, polyphosphates, thiocyanates, carboxylates (preferably, acetates and stearates), and mixtures thereof.
- the ammonium or substituted ammonium species can be derived from a wide variety of ammonium and substituted ammonium sources such as salts (e.g., chlorides, bromides, hydroxides, and the like).
- salts e.g., chlorides, bromides, hydroxides, and the like.
- compositions of the instant invention preferred sources of the cationic species include aluminum monoacetate, aluminum diacetate, aluminum stearate, and mixtures thereof. Expecially preferred is aluminum monoacetate. (Dp Ligand
- the sunscreen complexes of the present invention optionally comprise an organic or inorganic ligand represented by the general structure (L)p.
- organic or inorganic ligand represented by the general structure (L)p.
- Both neutral and anionic ligands are useful in the complexes of the present invention.
- Useful organic ligands include, but are not limited to, those selected from the group consisting of carboxylic acids, dicarboxylic acids, and polycarboxylic acids and their anions; amines, diamines, and polyamines; alcohols, diols, and polyols and their anions; thiols, dithiols, and polythiols and their anions; amino acids and their anions; any other pharmaceutically-acceptable organic ligands, and mixtures thereof.
- Useful inorganic ligands include, but are not limited to, water and hydroxide anion, halide (e.g., fluoride, chloride, bromide, and iodide), carbonate, bicarbonate, phosphate, hydrogen phosphate, dihydrogen phosphate, sulfate, hydrogen sulfate, nitrate, sulfite, nitrite, borate, chlorate, bromate, perchlorate, perbromate, diphosphate, polyphsophate, thiocyanate, any other phar aceutically-acceptable inorganic ligands, and mixtures thereof.
- pharmaceutically-acceptable organic and inorganic ligands as used herein is meant those organic and inorganic ligands which are acceptable from a toxicity viewpoint.
- ligands selected from water, hydroxide anion, and carboxylic acids having from about 2 to about 22 carbon atoms arid their anions are preferred.
- Other preferred ligands include ethoxide and isopropoxide.
- Especially preferred among the carboxylic acids and their anions are acetic acid and the acetate anion, octanoic acid and the octanoate anion, and stearic acid and the stearate anion.
- the number of ligands present in the complex is designated by p, wherein p is an integer selected from 0 through 4, more preferably p is an integer selected from 0 through 3, even more preferably p is an integer selected from 0 through 2, even more preferably p is an integer selected from 0 and 1, and most preferably p is 0.
- the complexes of the instant invention can exist as a mixture of different species having different p values.
- the average p value is a noninteger weighted average of the p values of the species present.
- sunscreen metal complexes of the present invention include, for example: Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-hydroxydibenzoylmethane; Aluminum (III) Complex of 4-N,N-di-(2-ethylhexyl)aminobenzoic acid ester with 4-hydroxydibenzoylmethane;
- the sunscreen metal complexes of the present invention can be prepared as described in the Examples below. In further embodiments, these complexes can then be directly formulated into a desired carrier. Alternatively, these sunscreen complexes can be isolated before being formulated into the desired carrier. In yet another alternative, these sunscreen complexes can be prepared directly in the desired carrier.
- the sunscreen metal complex is prepared by combining a sunscreen compound and a metal salt in a suitable solvent selected from the group consisting of water, acetone, ethyl acetate, methyl t-butyl ether, Ci-C ⁇ alcohols, diols, triols, C12-15 alcohols benzoate, dimethyl isosorbide, chlorinated solvents (e.g., methylene chloride), isodecyl neopentanoate, diisopropyl adipate, and mixtures thereof.
- a suitable solvent selected from the group consisting of water, acetone, ethyl acetate, methyl t-butyl ether, Ci-C ⁇ alcohols, diols, triols, C12-15 alcohols benzoate, dimethyl isosorbide, chlorinated solvents (e.g., methylene chloride), isodecyl neopentanoate, diisopropyl adipate, and mixtures thereof
- Preferred metal salts include those selected from the group consisting of salts of aluminum, zinc, calcium, magnesium, copper, iron, barium, strontium, zirconium, titanium, tin, beryllium, gallium, indium, lanthanum, manganese, antimony, bismuth, cerium, thorium, niobium, tantalum, antimony, molybdenum, tungsten, lithium, sodium, potassium, and mixtures thereof. More preferred are salts of aluminum, titanium, copper, iron, zinc, and mixtures thereof.
- salts of aluminum with those selected from the group consisting of aluminum acetate, aluminum diacetate, aluminum stearate, aluminum distearate, aluminum octanoate, aluminum ethoxide, aluminum isopropoxide, and mixtures thereof, being more preferred, and aluminum monoacetate being most preferred.
- ammonium and substituted ammonium chlorides, bromides, and hydroxides can be employed.
- a base can be added in order to facilitate the dissolution of the sunscreen compound.
- the sunscreen compound and the base are prereacted in the solvent system before the metal salt is added.
- Preferred bases include sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium bicarbonate, sodium carbonate, and mixtures thereof.
- the solvent system can be heated to its boiling point if required. Where the sunscreen metal complex is isolated and purified, this is preferably accomplished by filtration and evaporation of the filtrate. Additionally, the complex can be further purified by recrystallization from a suitable solvent. The Examples given below provide representative preparations of the sunscreen metal complexes and compositions containing them.
- compositions Containing Sunscreen Metal Complexes One or more of the sunscreen complexes of the present invention can be incorporated into a variety of carriers, including pharmaceutical and cosmetic carriers, paints, coatings, polymeric maxtrices, fiber matrices, and the like. Preferably, the complexes are incorporated into pharmaceutical and cosmetic carriers.
- the sunscreen metal complexes of the present invention typically comprise from about 0.1% to about 30.0% by weight of the sunscreen compositions of the present invention, preferably from about 1% to about 20%, and most preferably from about 5% to about 15%.
- the compositions of the instant invention can comprise the following components. Pharmaceut cal1y-Acceotable Cam ' ers
- compositions of the instant invention can comprise a safe and effective amount of a topical pharmaceutically-acceptable carrier or diluent which can be of a variety of different forms.
- “safe and effective” is meant an amount sufficient to act as a suitable vehicle for the sunscreen metal complexes and any other components, but not so much as to cause any side effects or skin reactions.
- “Pharmaceutically-acceptable” means that the carrier is suitable for topical application to the skin without causing any untoward safety or toxicity concerns. In other words, these carriers are suitable for use on humans and lower animals.
- the topical carrier can be in the form of an emulsion including, but not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone emulsions.
- emulsions can cover a broad range of consistencies including thin lotions (which can also be suitable for spray or aerosol delivery), creamy lotions, light creams, heavy creams, and the like.
- suitable topical carriers include anhydrous liquid solvents such as oils and alcohols; aqueous-based single phase liquid solvents (e.g. hydro-alcoholic solvent systems); anhydrous solids and semisolids (such as gels and sticks); and aqueous based gel and mousse systems. Examples of topical carrier systems useful in the present invention are described in the following four references all of which are incorporated herein by reference in their entirety: "Sun Products Formulary" Cosmetics & Toiletries, vol. 105, pp.
- the pharmaceutically-acceptable topical carriers typically comprise from about 0.1% to about 99.8% by weight of the sunscreen compositions of the present invention, preferably from about 80% to about 99%, and most preferably from about 85% to about 95%.
- a preferred topical carrier of the compositions of the instant invention is an oil-in-water type emulsion.
- the pH of these oil-in-water emulsion compositions herein is preferably in the range of from about 3.5 to about 9. Additionally, the mean particle size of the dispersed oil phase materials can be in the range of from about 1 to about 10 microns with greater than about 75% of the particles being less than about 12 microns. Additional Sunscreens
- sunscreening agents include, but are not limited to, for example: Ethylhexyl-p-methoxycinnamate (available as Parsol MCX from Givaudan Corporation), p-Aminobenzoic acid, its salts and its derivatives (ethyl, isobutyl, glyceryl esters; p-dimethylamino- benzoic acid; 2-ethylhexyl N,N-dimethylaminobenzoate; p-Methoxy- cinnamic Acid Diethanolamine Salt (available as Bernel Hydro from Bernel Chemical Co.); Anthranilates (i.e., o-aminobenzoates; methyl, octyl , amyl , menth
- sunscreens include the solid physical sunblocks such as titanium dioxide (micronized titanium dioxide, 0.03 microns, 0.035 microns, 0.050 microns, and other suitable sizes), zinc oxide, silica, iron oxide and the like. Without being limited by theory, it is believed that these inorganic materials provide a sunscreening benefit through reflecting, scattering, and absorbing harmful UV, visible, and infrared radiation.
- Other useful sunscreens are those having both a UVA and a UVB absorbing chromophore in the same molecule as disclosed in U.S. Patent Nos. 5,041,282, 4,999,186 and 4,937,370, and European Patent Application No. 416,837, which have already been incorporated by reference herein.
- these additional sunscreens can comprise from zero to about 20% of the composition, preferably from about 0.5% to about 10%. Exact amounts will vary depending upon the sunscreen chosen and the desired Sun Protection Factor (SPF). SPF is a commonly used measure of photoprotection of a sunscreen against erythema. See. Federal Register. Vol. 43, No. 166, pp. 38206-38269, August 25, 1978.
- compositions can also contain one or more artificial tanning ingredients such as dihydroxyacetone, tyrosine, amino acids, and amino acid derivatives.
- artificial tanning ingredients can be incorporated into the compositions of the instant invention at levels from about 0.1% to about 10%, and preferably at levels from about 0.1% to about 5%.
- compositions of the instant invention is a thickener.
- thickeners which can be employed include, but are not limited to, xanthan gum, magnesium aluminum silicate, guar gum, cationic guar gum, Rhamsan Gum (available from Kelco Chemical Co.), kelp, algin and alginate salts, starch and starch derivatives, hydroxypropylcellulose, hydroxyethylcellulose, carboxymethylcellulose, methylcellulose, ethylcellulose, smectite clay thickeners such as hectorite and bentonite, sodium magnesium silicate and mixtures thereof.
- thickeners examples include magnesium aluminum silicate and xanthan gum and mixtures thereof.
- the compositions of the instant invention comprise from about 0.1% to about 5% thickener, preferably from about 0.25% to about 2%, and most preferably from about 0.5% to about 1%.
- compositions of the instant invention can also optionally contain one or more humectants/moisturizers.
- humectants/moisturizers can be employed and can be present at a level of from about 0.5% to about 30%, more preferably from about 2% to about 8% and most preferably from about 3% to about 5%.
- These materials include urea; guanidine; glycolic acid and glycolate salts (e.g. ammonium and quaternary alkyl ammonium); lactic acid and lactate salts (e.g.
- Preferred humectants/moisturizers for use in the compositions of the present invention are the C3-C6 diols and triols. Especially preferred is the triol, glycerin.
- Emollients The compositions of the present invention can also optionally comprise at least one emollient.
- suitable emollients include, but are not limited to, volatile and non-volatile silicone oils, highly branched hydrocarbons, and non-polar fatty acid and fatty alcohol esters, and mixtures thereof.
- Emollients useful in the instant invention are further described in U.S. Patent No. 4,919,934, to Deckner et al., issued April 24 1990, which is incorporated herein by reference in its entirety.
- the emollients can typically comprise in total from about 1% to about 50%, preferably from about 1% to about 25%, and more preferably from about 1% to about 10% by weight of the compositions of the present invention.
- emulsifiers can include any of a wide variety of nonionic, cationic, anionic, and zwitterionic emulsifiers disclosed in the prior patents and other references.
- Suitable emulsifier types include esters of glycerin, esters of propylene glycol, fatty acid esters of polyethylene glycol, fatty acid esters of polypropylene glycol, esters of sorbitol, esters of sorbitan anhydrides, carboxylic acid copolymers, esters and ethers of glucose, ethoxylated ethers, ethoxylated alcohols, alkyl phosphates, polyoxyethylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps and mixtures thereof.
- Suitable emulsifiers can include, but are not limited to, polyethylene glycol 20 sorbitan monolaurate (Polysorbate 20), polyethylene glycol 5 soya sterol , Steareth-20, Ceteareth-20, PPG-2 methyl glucose ether distearate, Ceteth-10, Polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate, Polysorbate 60, glyceryl stearate, PEG-100 stearate, and mixtures thereof.
- the emulsifiers can be used individually or as a mixture of two or more and comprise from about 0.1% to about 10%, preferably from about 1% to about 7%, and most preferably from about 1% to about 5% of the compositions of the present invention.
- compositions of the present invention can also be included in the compositions of the present invention.
- Non-limiting examples include Vitamin A, and derivatives thereof, ascorbic acid, Vitamin B, biotin, Vitamin D, Vitamin E and derivatives thereof such as tocopheryl acetate, panthothenic acid, and mixtures thereof can also be used.
- Carboxylic Acid Copolvmers include Vitamin A, and derivatives thereof, ascorbic acid, Vitamin B, biotin, Vitamin D, Vitamin E and derivatives thereof such as tocopheryl acetate, panthothenic acid, and mixtures thereof can also be used.
- compositions of the instant invention is a carboxylic copolymer (acrylic acid copolymer).
- Carbomer 1342 available as Carbopol 1342 from B.F. Goodrich. These polymers are more fully described in U.S. Patent
- acrylate/alkyl acrylate crosspoly ers such as Acrylates/C10-C30 Alkyl Acrylate Crosspolymer (available as Pemulen TR-1 and Pemulen
- These polymers comprise from about 0.025% to about 0.75%, preferably from about 0.05% to about 0.25% and most preferably from about 0.075% to about 0.175%.
- Other Optional Components are preferably from about 0.025% to about 0.75%, preferably from about 0.05% to about 0.25% and most preferably from about 0.075% to about 0.175%.
- additional ingredients can be incorporated into the emulsion compositions of the present invention.
- additional ingredients include various polymers for aiding the film-forming properties and substantivity of the composition (such as a copolymer of eicosene and vinyl pyrrolidone, an example of which is available from GAF Chemical Corporation as Ganex V-220R); gums, resins, and thickeners; preservatives for maintaining the antimicrobial integrity of the compositions; antioxidants; chelators and sequestrants; anti-acne agents; keratolyic agents;and agents suitable for aesthetic purposes such as fragrances, pigments, and colorings.
- Other useful materials include acidic materials such as salicylic acid, lactic acid, glycolic acid, benzoic acid, citric acid and the like. Without being limited by theory, it is believed that these acid materials are useful for maintaining the pH of the composition and enhancing product performance.
- the present invention further relates to a method for pro ⁇ tecting the skin of humans or lower animals -from the effects of UVA and UVB wavelength radiation, such as sunburn and premature aging of the skin.
- a method for pro ⁇ tecting the skin of humans or lower animals -from the effects of UVA and UVB wavelength radiation, such as sunburn and premature aging of the skin comprises topically applying to the human or lower animal an effective coating of a sunscreen agent or composition of the present invention.
- ef ⁇ fective coating means a film of sunscreen agent sufficient to substantially reduce the amount of UVA and UVB wavelength light which reaches the skin's surface.
- an effective coating of the skin is from about 0.5 mg sunscreen agent or composition of the present invention/cm 2 skin to about 5 mg sunscreen agent or composition of the present invention/cm 2 skin. See Federal Register, Vol. 43, No.
- EXAMPLE 1 Preparation of the Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)- methylaminobenzoic Acid Ester with 4-(2-hydroxyethoxy)dibenzoyl - methane using Aluminum Diacetate.
- Aluminum diacetate Aldrich Chemical Co., Milwaukee, WI
- the solvents are removed by rotary evaporation to yield the crude sunscreen aluminum complex.
- This crude complex is redissolved in approximately 150 mL of ethyl acetate with heating and is then vacuum filtered using a coarse, sintered glass funnel to remove any undissolved materials, which are washed with ethyl acetate (approximately 2 X 20 mL) .
- a solution of 80 mL of an 11% (w/w) aqueous solution of sodium hydroxide is added to the acetone solution of the sunscreen, and the mixture is vigorously agitated until miscible.
- the sunscreen solution is then slowly added to the aluminum monoacetate solution with stirring, and the mixture is refluxed for approximately 10 minutes.
- the solvents are removed by rotary evaporation to yield the crude sunscreen aluminum complex.
- This crude complex is redissolved in approximately 300 mL of ethyl acetate with heating, and is then vacuum filtered using a coarse, sintered glass funnel to remove any undissolved materials, which are washed with ethyl acetate (approximately 2 X 50 mL).
- the pooled filtrates are extracted with water, dried over sodium sulphate, and evaporated by rotary evaporation to yield the sunscreen aluminum complex as a light yellow, glassy solid. This solid is suitable for incorporation into a sunscreen composition.
- this sunscreen aluminum complex is prepared starting with 1.0 gram of aluminum dioctanoate (Aldrich Chemical Co., Milwaukee, WI). The resulting oil phase solution of the complex is suitable for incorporation into an emulsion or gel composition.
- EXAMPLE 5 Preparation of the Aluminum (III) Complex of 4-N,N(2-ethylhexyl)- methylaminobenzoic Acid Ester with 4-hydroxydibenzoylmethane using Aluminum Monoacetate.
- this sunscreen aluminum complex is prepared using 33.75 grams (0.240 moles) of aluminum monoacetate and 166.36 grams (0.343 moles) of 4-N,N(2-ethylhexyl)- methylaminobenzoic acid ester with 4-hydroxydibenzoyl ethane. A light yellow solid is obtained suitable for incorporation into a sunscreen composition.
- EXAMPLE 6 Preparation of the Aluminum (III) Complex of 4-N,N-di-(2-ethyl- hexyl)-4-aminobenzoic Acid Ester with 4-hydroxydibenzoylmethane using Aluminum Monoacetate.
- this sunscreen aluminum complex is prepared using 33.75 grams (0.240 moles) of aluminum monoacetate and 200.0 grams (0.343 moles) of 4-N,N-di-(2- ethylhexyl)-4-aminobenzoic acid ester with 4-hydroxydibenzoyl- methane.
- a light yellow solid is obtained suitable for incorporation into a sunscreen composition.
- EXAMPLE 7 Preparation of the Aluminum (III) Complex of 4-N,N-di-(2-ethy1- hexyl)-4-aminobenzoic Acid Ester with 4-(2-hydroxyethoxy)- dibenzoylmethane using Aluminum Monoacetate.
- this sunscreen aluminum complex is prepared using 33.75 grams (0.240 moles) of aluminum monoacetate and 215.06 grams (0.343 moles) of 4-N,N-di-(2-ethyl- hexyl)4-aminobenzoic acid ester with 4-(2-hydroxyethoxy)- dibenzoylmethane.
- a light yellow solid is obtained suitable for incorporation into a sunscreen composition.
- EXAMPLE 8 Oil based gel composition containing Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic Acid Ester with 4-(2-hydroxyethoxy)dibenzoylmethane. 4.0 grams of the sunscreen aluminum complex prepared in Example 2 is added to 100 grams of C ⁇ 2-15 Alcohols Benzoate by heating to 90°C. The mixture is cooled to 80°C and 1 gram of dibutyllaurolyl glutamide (available as Coagulen GP-1 from Ajinomoto Co., Inc., Tokyo, Japan) is added to gel the mixture upon cooling. This gel composition is useful for topical application to the skin to provide protection from the harmful effects of ultraviolet radiation.
- analogous gel compositions can be prepared using the other sunscreen metal complexes of the instant invention and using other solvents such as isodecyl neopentanote, diisopropyl adipate, and dimethyl isosorbide.
- other solvents such as isodecyl neopentanote, diisopropyl adipate, and dimethyl isosorbide.
- An emulsion composition is prepared from the following ingredients using standard methods.
- Phase A ingredients are combined and heated to 90°C and then cooled to 80°C.
- Phase B ingredients are added with mixing at 80°C to form the oil phase.
- Phase C ingredients are combined and heated to 80°C.
- the oil phase is added to Phase C with homogenization to form the emulsion.
- the emulsion is cooled with stirring to 40°C.
- the Phase D ingredients are combined and added to the emulsion with mixing. The emulsion is then cooled to room temperature with stirring.
- This emulsion composition is useful for topical application to the skin to provide protection from the harmful effects of ultraviolet radiation.
- the above sunscreen emulsion is prepared using 0.50 grams of aluminum dioctoate in place of the aluminum distearate.
- An emulsion composition is prepared from the following ingredients using standard methods.
- Titanium dioxide 0.50 Phase B Water QS100 Acrylates/C10-30 Alkyl Acrylate
- Phase A ingredients are combined and heated with mixing to 90°C and then cooled to 80°C.
- Phase B ingredients are combined and heated wtih mixing to 80°C.
- Phase A mixture is added to the Phase B mixture with homogenization to form the emulsion.
- the emulsion is cooled with stirring to 40°C.
- the Phase C ingredients are combined and added to the emulsion with mixing.
- the emulsion is then cooled to room temperature with stirring.
- This emulsion composition is useful for topical application to the skin to provide protection from the harmful effects of ultraviolet radiation.
- analogous emulsions are prepared using other isolated sunscreen metal complexes of the instant invention.
- Methylisothiazolinone 0.100 The Phase A ingredients are combined and heated with stirring to 80°C to form the oil phase. Next, the Phase B ingredients are combined and heated with stirring to 80°C. Phase A is added to Phase B with homogenization to form the emulsion which is then cooled to room temperature with stirring. This emulsion composition is useful for topical application to the skin to provide protection from the harmful effects of ultraviolet radiation.
- analogous emulsions are prepared using other isolated sunscreen metal complexes of the instant invention.
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Abstract
The present invention relates to sunscreen complexes, and more particularly to sunscreen metal complexes, having enhanced UVA absorption. These complexes comprise a sunscreen moiety complexed to a metal cation, or alternatively an ammonium or substituted ammonium cation, in which the sunscreen moiety further comprises a dibenzoylmethane UVA-absorbing chromophore, a UVB-absorbing chromophore, and a linking group connecting the two chromophores. These complexes are useful for protecting the skin from the harmful effects of ultraviolet radiation. This invention also relates to methods for preparing these sunscreen metal complexes and to compositions containing these complexes.
Description
UVA-ABSORBING SUNSCREEN METAL COMPLEXES
TECHNICAL FIELD The present invention relates to sunscreen complexes, more particularly to sunscreen metal complexes, having enhanc i.e. both increased and broadened, UVA absorption. Th complexes comprise a sunscreen moiety complexed to a cation species, preferably a metal cation, in which the sunscreen moie further comprises a dibenzoylmethane UVA-absorbing chromophore, UVB-absorbing chromophore, and a linking group connecting the t chromophores. These complexes are useful for protecting the sk from the harmful effects of ultraviolet radiation. This inventi also relates to processes for preparing these sunscreen complex and to compositions containing these complexes.
BACKGROUND OF THE INVENTION The damaging effects of sunlight on skin are well documente The major short term hazard of prolonged exposure to sunlight erythema (i.e. sunburn). The 290 to 320 nanometer waveleng ultraviolet radiation range, designated as the "UVB" waveleng range, tends to be the primary cause of erythema. The 320 to 4 nanometer wavelength ultraviolet radiation range, designated the "UVA" wavelength range, also produces erythema.
In addition to the short term hazard of erythema, there a also long term hazards associated with UV radiation exposure. O of these long term hazards is malignant changes in the sk surface. Numerous epidemiologic studies demonstrate a stro relationship between sunlight exposure and human skin cancer.
Another long term hazard of ultraviolet radiation is prem ture aging of the skin. This condition is characterized wrinkling and yellowing of the skin, along with other physic changes such as cracking, telangiectasis (spider vessels), sol keratoses (growths), ecchymoses (subcutaneous hemorrhagic l sions), and loss of elasticity (sagging). The adverse effec associated with exposure to UVA and UVB wavelength radiation a
more fully discussed in DeSimone, "Sunscreen and Suntan Products" Handbook of Nonprescription Drugs. 7th Ed., Chapter 26, pp 499-511 (American Pharmaceutical Association, Washington, D.C. 1982); Grove and Forbes, "A Method for Evaluating the Photopro tection Action of Sunscreen Agents Against UV-A Radiation" International Journal of Cosmetic Science. 4, pp. 15-24 (1982) and U.S. Patent 4,387,089, DePolo, issued June 7, 1983; th disclosures of all of which are incorporated herein by reference. Both sunscreen agents and physical sunblocks are comrnerciall available to protect the skin from UV radiation. Physica sunblocks scatter, reflect, and absorb ultraviolet radiation See. Sayre, R.M. et al., "Physical Sunscreens", J. Soc. Cosmet Chem.. vol. 41, no. 2, pp. 103-109 (1990). Examples of physical sunblocks include titanium dioxide and zinc oxide. However, compositions containing a high level of these agents are opaque, generally unattractive in color, and are viewed as unacceptabl for usage on more than just the nose or tops of the ears. Furthermore, these agents are very susceptible to rub-off o wear-off resulting in little or no protection. In contrast, sunscreen agents exert their effects through chemical means, i.e., they absorb ultraviolet radiation so that it cannot penetrate the skin. Sunscreens present the user with several problems. For example, they must be on the surface of the skin at the time of exposure to be effective. Sunscreens are preventative so one must anticipate being in the sun. To be most effective, sunscreens must be on the skin as a continuous uniform film. Delivering such a film to the surface of the skin is very difficult.
Most commercially-available sunscreen agents are primarily UVB absorbers. The number of UVA absorbers is more limited with benzophenones and dibenzoylmethanes being the most well-known. U.S. Patent No. 4,489,057 to Welters et al., issued December 18, 1984, and U.S. Patent No. 4,387,089 to DePolo, issued June 7, 1983, both of which are incorporated herein by reference, disclose. dibenzoylmethane sunscreen agents. U.S. Patent No. 5,041,282 to Sabatelli et al., issued August 20, 1991; U.S. Patent No. 4,999,186 to Sabatelli et al., issued March 12, 1991; and U.S.
Patent No. 4,937,370 to Sabatelli, issued June 26, 1990, all thre of which are incorporated herein by reference, disclose nove sunscreen agents and compositions which provide both UVA and UV protection from the same sunscreen molecule. It has been found in the present invention that the U absorption of the dibenzoylmethane chromophore is significantl enhanced when it is complexed to certain cationic species such a metal cations. Thus, it is possible to prepare sunscreen agent having enhanced UVA absorption and which provide UVB protectio from the same molecule.
It is therefore an object of the present invention to provid sunscreen complexes which provide enhanced UVA absorption.
It is another object of the present invention to provid sunscreen metal complexes which provide enhanced UVA absorption. It is a further object of the present invention to provid sunscreen metal complexes having enhanced UVA absorption whic also provide UVB absorption.
It is an even further object of the present invention t provide sunscreen metal complexes which will prevent both acut (erythema) and chronic (photoaging, cancer) effects of exposure t sunlight and other sources of UV radiation.
It is a still further object of the present invention t provide processes for the preparation of sunscreen meta complexes. It is another object of the present invention to provid topical sunscreen compositions containing sunscreen meta complexes for providing protection for the skin from the damagin effects of UV radiation.
It is still another object of the present invention t provide sunscreen compositions containing sunscreen meta complexes which are not readily absorbed by the skin; which hav increased sunscreen protection and decreased chance for allergy irritation, or toxicity problems resulting from daily or regula use; which are less susceptible to rub off; and which are cos eti cally acceptable.
These and other objects will become readily apparent from th detailed description which follows.
SUMMARY OF THE INVENTION The present invention relates to a sunscreen complex havin the general structure:
[ X - G - Z ]m (M)n (L)p wherein (A) [X - G - Z] is a sunscreen moiety wherein
(i) X is a UVA-absorbing chromophore having the general structure:
(ii) Z is a UVB-absorbing chromophore selected from the group consisting of:
and mixtures thereof, wherein in all the preceding formula A is a substituent independently selected from the gro consisting of R, -OR, -NR2 or -SO3H; each A1 is independentl -OR or -NR2; each A2 is independently -OR or -O2C-RI; each is independently -CN or -CO2 I; and each R is independentl H, straight or branched chain alkyl having from about 1 about 20 carbon atoms, (CH2CH2θ)q-H, or (CH2CH(CH3)0)q- wherein q is an integer from 1 to about 8; and each Rl i independently straight or branched chain alkyl having fr about 1 to about 20 carbon atoms; and
(iii) G is a linking moiety selected from the group consisting of
(a) a linking moiety which covalently bonds the and Z chromophore moieties into one molecul and which furthermore separates the X and moieties such that the electron systems o said moieties are not directly coupled, or
(b) a linking moiety which is a chemical bon which covalently bonds the X and Z chromophor moieties such that the electron systems of th X and Z moieties are directly coupled;
(B) m is an integer selected from 1, 2, 3 or 4;
(C) M is a metal cation, an ammonium cation, or a substituted ammonium cation;
(D) n is an integer selected from 1, 2, 3, or 4;
(E) L is a ligand comprising a neutral or negatively charge organic or inorganic moiety; and
(F) p is an integer selected from 0, 1, 2, 3 or 4. The present invention further relates to processes fo preparing these sunscreen complexes, to compositions containin these complexes, and to methods for providing enhanced protectio
to the skin of humans or lower animals from the effects of ultraviolet radiation.
All percentages and ratios used herein are by weight and all measurements are at 25°C, unless otherwise indicated. DETAILED DESCRIPTION OF THE INVENTION
Sunscreen Complexes
The sunscreen complexes useful in the present invention are those having the general structure:
[ X - G - Z ]m (M)n (L)p.. [X - G - Z]m represents a sunscreen moiety having two distinct chromophores which are linked together, wherein X represents a dibenzoylmethane UVA-absorbing chromophore, Z represents a UVB-absorbing chromophore, and G represents a linking group. In this formula m represents the number of sunscreen moieties present in the complex.
(M)π represents a cationic species such as a metal, or alternatively ammonium or substituted ammonium, where n designates the number of these species present in the complex.
(L)p represents a ligand, which is optionally present in the complex, where p designates the number of ligands present in the complex.
The sunscreen complexes of the present invention preferably absorb light in the visible wavelength range (i.e. above about 400 n ) only weakly or not at all. The complexes are therefore either only lightly colored (e.g., light yellow or cream colored) or are essentially white. This is desirable for cosmetic reasons. Thus, the sunscreen metal complexes preferably do not have a € of greater than about 500 for any wavelength above about 400 nm, and most preferably the € is essentially zero for any wavelength above about 400 nm.
The sunscreen complexes useful in the present invention have several desirable properties relative to a simple mixture of a UVA-absorbing molecule with a UVB-absorbing molecule. One benefit is the certainty of providing both UVA and UVB protection at the same site on the skin. A mixture of molecules may lack this uniformity due to non-uniform distribution onto the skin surface and/or selective penetration by one type of molecule through the
skin versus the other type of molecule. A related benefit is tha the sunscreen agents of the present invention provide a constan relative proportion of UVA to UVB protection because one chromo phore cannot be more readily lost from the skin (e.g., by a highe rate of rub-off or skin penetration) than the other chromophore Another benefit is that the sunscreen complexes of the presen invention are absorbed more slowly by the skin than mixtures o the independent chromophores. This translates into longer dura tion of protection for the skin, and less potential for ski irritation resulting from absorption by the skin. Furthermore the sunscreen agents useful in the present invention provide thi long-lasting, constant UV radiation protection at least as effec tively as a freshly-applied mixture of independent chromophores and in some instances the protection is stronger and more broad spectrum than the mixture. (The ability of the compounds of th present invention, and of mixtures of independent chromophores, t absorb UV radiation may be measured by in vitro methods know generally in the art, such as those taught in Sayre et al . , " Comparison of in vivo and in vitro Testing of Sunscreening Formu las", Photochem. Photobiol.. 29, 559-566 (1979), the disclosure of which are incorporated herein by reference.) Some of th compounds of the present invention may also be more resistant t wash-off by water, more resistant to removal by sweating, and mor resistant to rubbing/toweling. TX - G - Zl Sunscreen Moiety
The sunscreen moieties which comprise the sunscreen complexe of the present invention are those moieties which have tw distinct chromophores which are covalently linked together. Thi covalent linkage can be such that the two chromophore moieties ar directly coupled, i.e., their electrons are shared Alternatively, this covalent linkage can be such that the tw chromophore moieties do not have their electron systems directl coupled with each other.
More particularly, one of the chromophores is characterize as being effective for strongly absorbing radiation in the UV range when that chromophore is isolated in an independen molecule. The other chromophore is characterized as bein
effective for absorbing radiation predominantly within the UV range when that chromophore is isolated in an independent mole¬ cule. Thus, the sunscreen moieties useful in the complexes of th present invention have the general structure: [X - G - Z].
In this general structure, the X group is a UVA-absorbing, dibenzoylmethane chromophore. This UVA-absorbing chromophore, when isolated as an independent chromophore, would exhibit at least one absorption maximum (designated herein asλmax, and described more fully hereinafter) within the wavelength range of from about 320 to about 400 nm. This absorption maximum would exhibit a molar absorptivity value (designated herein as "€ ", and calculated as described hereinafter) of at least about 9,000, preferably at least about 20,000, and most preferably at least about 30,000.
The Z group in the above general structure is a UVB-absorbing chromophore that is a substituted, carbonyl-containing, aromatic ring-containing species. This UVB-absorbing chromophore, when isolated as an independent chromophore, would exhibit a molar absorptivity value, € , of at least about 4,000, preferably at least about 15,000, and most preferably at least about 25,000, for at least one wavelength within the range of from about 290 to about 320 nm. Preferably, when present as the sole chromophore in a molecule as hereinafter defined, the Z group exhibits at least one absorption maximum λ max within the range of from about 290 to about 320 nm. This absorption maximum preferably has a molar absorptivity value of at least about 4,000, more preferably at least about 15,000, and most preferably at least about 25,000. Finally, when present as the sole chromophore in a molecule as hereinafter defined, the Z group furthermore should not exhibit a λ max having a € greater than about 9,000 for any wavelength above about 320 nm.
The third component of the above general structure, i.e., the
G group, covalently bonds the X and Z chromophores. In one alternative, the G group separates the electron systems of the two chromophores such that the two chromophores do not have their electron systems directly coupled with each other. For example,
the G linking group may be a straight or branched chain alky group having from about 1 to about 6 carbon atoms, a straight o branched chain alkyloxy group having from about 1 to about carbon atoms, or straight or branched alkylamino group having fro about 1 to about 6 carbon atoms.
Alternatively, G is a linking moiety which is a chemical bon which covalently bonds the two X and Z chromophores such that th electron systems of these chromophores are directly coupled, i.e. electrons are shared. Preferred is G selected from a single bond, or atoms or groups of atoms which have free electrons which may b shared with both chromophore moieties, such as -0- and -NR (wherein R is H, straight or branched chain alkyl having fro about 1 to about 20 carbon atoms, (CH2CH20)q-H, o (CH2CH(CH3)0)q-H, wherein m is an integer from 1 to about 8, an preferably q»l to about 3). Most preferred is G being -NH- and, especially, -0-.
These sunscreen moieties which comprise the complexes of th instant invention are fully disclosed in U.S. Patent Nos. 5,041,282, 4,999,186 and 4,937,370, which have already bee incorporated by reference herein. Also, European Patent Application No. 416,837, to Haffey et al., published March 13, 1991, and U.S. Application Serial No. 404,751, filed September 8, 1989, to Haffey et al . further describes these sunscreen moieties; these two references are incorporated herein by reference. In the sunscreen complexes of the present invention, the number of sunscreen moieties present is designated by m, wherein m is an integer selected from 1 through 8, more preferably m is an integer selected from 1 through 4, even more preferably m is an integer selected from 1 through 3, and most preferably m is 2. Furthermore, it is realized that the complexes of the instant invention can exist as a mixture of different species in which the m value varies. Thus, it is possible to obtain a complex in which the average m value is a noninteger average of the m values for the species present. Examples of the X, UVA-absorbing dibenzoylmethane chromophores useful in the sunscreen compounds of the present invention include those of the following general structure:
In the preceding structure, each A is a substituent independentl selected from the group consisting of R, -OR, -NR , or -S03H; ea R is independently H, straight or branched chain alkyl having fr about 1 to about 20 carbon atoms, (CH2CH20)q-H, p (CH2CH(CH3)0)q-H, wherein p is an integer from 1 to about 8, an preferably q = 1 to about 3. A is preferably R, where R i preferably straight or branched chain alkyl having from 1 to abou 4 carbon atoms. A is most preferably H.
In the sunscreen moiety, even though the dibenzoylmethan chromophore is represented as a 1,3-diketone it should b understood that this representation in no way excludes othe tautomeric forms of the functional group such as the eπol form Thus whenever the 1,3-diketone form is designated, it i understood that all appropriate enol tautomers are als contemplated and included herein. These tautomeric enol forms o the dibenzoylmethane chromophore can be represented by th following tautomeric structures.
Furthermore, it is also realized that the dibenzoylmethane chromophore can lose a hydrogen atom to form the corresponding anionic species. This phenomenon is more likely at higher pH values (i.e. alkaline pH values) and when the dibenzoylmethane chromophore is complexed to a cationic species such as a metal. Thus, whenever the 1,3-diketone form is designated, it is understood that all appropriate anionic forms are also contemplated and included herein. These anionic forms of the dibenzoylmethane chromophore can be represented by the following resonance structures.
Specific examples of the UVB-absorbing Z chromophore moieti useful in the sunscreen compounds of the present inventi include:
In these preceding formulae, each Al is independently -OR o NR2; each A2 is independently -OR or O2C-RI; each A i independently -CN or -CO2R1; and each R and Rl are as describe hereinbefore for the substituted X, UVA-absorbing chromophores.
Preferred as the Z, UVB-absorbing chromophore moiety are the groups:
wherein each R is independently selected from H or straight or branched chain alkyl having from about 1 to about 20 carbon atoms, and Al is -0CH3, -0CH2CH3, OH, or -NR2 (wherein each R is independently selected from H or straight or branched chain alkyl having from about 1 to about 20 carbon atoms). Particularly preferred is one R group having more than about 2 carbon atoms (especially branched-chain alkyl groups, e.g., 2-ethylhexyl), and the other R group being methyl or ethyl, especially methyl. Alternatively preferred, both R groups are the same alkyl group, e.g., methyl and more preferably, 2-ethylhexyT. Preferably A1 is
Especially preferred is:
The G linking groups useful in the compounds of the present invention include the generically described structure:
-(-Wi-(-CRV)s-k-W2- wherein each W1 and W2 is, independently, selected from a single bond, preferably 0 or NR (wherein R is as described hereinbefore); s is an integer of 1 or greater, preferably s equals an integer from 1 to about 6; t is an integer of 1 or greater, preferably t is 1 or 2; and each R2 group is independently selected from the group consisting of H, OH, or straight or branched chain alkyl having from 1 to about 20 carbon atoms, preferably R2 is H, OH, methyl or ethyl .
Useful G linking moiety groups include:
-0-(-CH2-)s-0-, wherein s is an integer from 1 to about 6; -NH-(-CH2-)s-NH-, wherein s is an integer from 1 to about 6; -(-0-CH2CH2-)s-0-, wherein s is 1 or 2; -(-NH-CH2CH2-)S-NH-, wherein s is 1 or 2; -(-0-CH2-CH-)s-0-, wherein s is 1 or 2; CH3 -(-NH-CH2-CH-)s-NH-, wherein s is 1 or 2; and
CH3 -(-0-CH2CHCH2-)s-0-, wherein s is 1 or 2. OH
A particularly preferred G group is -0CH2CH20-.
Alternatively, the G linking group is represented by an atom or substituted atom such as -0- or -NR- (wherein R is H, straight or branched chain alkyl having from about 1 to about 20 carbon atoms, (CH2CH2θ)q-H or (CH2CH(CH3)0)q-H, wherein q is an integer from 1 to about 8, and preferably q * 1 to about 3). Most preferred is G being - 0 - or - NH -. Especially preferred is when G is - 0 -.
Preferred sunscreen moieties useful in the complexes of the instant invention are 4-N,N(2-ethylhexyl)methylaminobenzoic acid ester with 4-hydroxydibenzoylmethane, 4-N,N-di-(2- ethylhexyl)-4-aminobenzoic acid ester with 4-hydroxydiben- zoyl - methane, 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, 4-N,N-di-(2-ethyl- hexyl)4-aminobenzoic acid ester with 4-(2-hydroxy- ethoxy)- dibenzoylmethane, 4-N,N-dimethylaminobenzoic acid ester with 4-hy- droxydibenzoyl ethane, 4-N,N-dimethylamino- benzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, 4-methoxycinnamic acid ester with 4-hydroxydibenzoylmethane, 4-methoxycinnamic acid ester with 4-(2-hydroxyethoxy)diben- zoylmethane, and mixtures thereof.
The sunscreen moieties of the complexes of the present invention can be prepared from comrnercially-available, chromophore-containing molecules. Typically, the synthesis of the sunscreen agents will be achieved by an esterification or amidation reaction. Synthesis techniques which are generally applicable for synthesizing sunscreen agents of the present invention are taught, for example, in U.S. Patent 4,002,733,
issued January 11, 1977, to Degen et al . ; and in U.S. Patent 4,115,547, issued September 19, 1978, to Degen et al . ; the dis¬ closures of both these patents being incorporated herein by reference. Representative procedures for synthesizing the sun- screen agents of the present invention are provided in the Exam¬ ples hereinafter.
The term "independent chromophore", as used herein, means the chromophore moiety (i.e., either the X or Z group) when it is bonded to -0-R3 (wherein R3 represents a short chain alkyl group, e.g., methyl or ethyl; preferably methyl) rather than the chromo¬ phore moiety being bonded to the G linking moiety within the X-G-Z compound. For example, the independent chromophores of the sunscreen moiety 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane are the ethyl ester of 4-N,N-(2-ethylhexyl)methylaminobenzoic acid and 4-methoxydiben- zoylmethane.
The term "molar absorptivity value", as used herein, is a quantitative measure of the ability of a molecule to absorb ultra¬ violet light at a specified wavelength. The molar absorptivity value is expressed at a particular wavelength of light as the molar absorption coefficient (represented herein by "6 " which is expressed in units of liter/mole cm), which is calculated by the equation:
A € - lc wherein "1" is the path length (in centimeters) of the absorbing media through which the light passes; "c" is the concentration of the chromophore molecule (in moles per liter); and "A" is the "absorbance". The absorbance is calculated from the observed difference in the intensity of the particular wavelength of light before and after passing through the chromophore-molecule-contain- ing absorbing media. Thus, the absorbance is calculated by the equation:
A = log10 Io
I wherein "I0" is the intensity of a particular wavelength of in¬ cident radiation on an absorbing path; and "I" is the intensity of
the same particular wavelength of transmitted radiation which has passed through the absorbing path.
The calculation of the molar absorptivity value for a par¬ ticular wavelength of light is well-known in the art, and is taught in more detail in Atlas of Spectral Data and Physical Constants for Organic Compounds. 2nd Ed., Vol. I, pp. 399-408 (Grasselli and Ritchey, Editors; CRC Press, Inc., Cleveland, Ohio, 1975), the disclosures of which are incorporated herein by refer¬ ence. Instruments useful for making the intensity measurements for the calculation of the molar absorptivity value are also well-known in the art (eg., Varion DMS-100, Beckman DU-7, and Philips PU8800).
The term "absorption maximum", as used herein, means a wavelength of radiation at which the chromophore-containing molecule has the greatest molar absorptivity value relative to wavelengths immediately above and below the absorption maximum wavelength. Thus, in the typical spectrum of UV-radiation absorp¬ tion, an absorption maximum is easily identified as a peak in the graph of the spectrum generated by the instrument measuring the UV absorption. Absorption maxima (designated herein as λ max) are provided for representative sunscreen compounds of the present invention in the Examples hereinafter.
The sunscreen complexes of the present invention comprise a cationic species, preferably a metal, or alternatively ammonium or substituted ammonium, represented by the general structure (M)n.
Examples of metal cations useful in the complexes of the present invention include alkali metal (e.g., sodium and potassium), alkaline earth metal (e.g., calcium and magnesium), and transition and heavy metals (e.g., aluminum and strontium). Preferred for use in the complexes of the instant invention are the metals selected from the group consisting of aluminum, zinc, calcium, magnesium, copper, iron, barium, strontium, zirconium, titanium, tin, beryllium, gallium, indium, lanthanum, manganese, antimony, bismuth, cerium, thorium, niobium, tantalum, antimony, molybdenum, tungsten, lithium, sodium, potassium and mixtures thereof. These metal cations are useful in any of their possible valence states
and in combinations of these states (i.e. where for example some of the metal cations are in one of the cation's allowable valence states, and some of the metal cations are in another of the metal cation's allowable valence states, etc.). Alternatively, the sunscreen complexes of the instant invention can also comprise complexes with other cationic species such as ammonium, substituted ammonium (e.g., mono-, di-, tri- and tetra- alkyl and alkoxy substituted), and cations of diamines (e.g., tetra- alkyl and alkoxy substituted ethylene diamines). In the sunscreen complexes of the present invention preferred cation species include metals selected from the group consisting of aluminum, titanium, copper, iron, and zinc.
In the sunscreen complexes of the present invention, aluminum cations having a valence of 3+ are most preferred. In the sunscreen complexes of the present invention, the number of M species present in the complex is designated by n, wherein n is an integer selected from 1 through 4, more preferably n is an integer selected from 1 through 3, even more preferably n is an integer selected from 1 and 2, and most preferably n is 1. Furthermore, it is realized that the complexes of the instant invention can exist as a mixture of different species having different n values. Thus, it is possible to obtain a complex in which the average n value is a noninteger weighted average of the n values for the species present. In the compositions of the present invention the M species can be derived from any suitable sources. For example, when the M species of the complexes is a metal cation, the cation can be derived from a wide variety of salts. Examples of salts include metal oxides, hydroxides, fluorides, chlorides, bromides, iodides, carbonates, bicarbonates, phosphates, hydrogen phosphates, dihydrogen phosphates, alkoxides (e.g., isopropoxide), sulfates, hydrogensulfates, nitrates, sulfites, nitrites, borates, chlorates, bromates, perchlorates, perbro ates, diphosphates, polyphosphates, thiocyanates, carboxylates (preferably, acetates and stearates), and mixtures thereof. Alternatively, when the M species is ammonium or substituted ammonium, the ammonium or substituted ammonium species can be derived from a wide variety of
ammonium and substituted ammonium sources such as salts (e.g., chlorides, bromides, hydroxides, and the like).
For the compositions of the instant invention preferred sources of the cationic species include aluminum monoacetate, aluminum diacetate, aluminum stearate, and mixtures thereof. Expecially preferred is aluminum monoacetate. (Dp Ligand
The sunscreen complexes of the present invention optionally comprise an organic or inorganic ligand represented by the general structure (L)p. Both neutral and anionic ligands are useful in the complexes of the present invention. Useful organic ligands include, but are not limited to, those selected from the group consisting of carboxylic acids, dicarboxylic acids, and polycarboxylic acids and their anions; amines, diamines, and polyamines; alcohols, diols, and polyols and their anions; thiols, dithiols, and polythiols and their anions; amino acids and their anions; any other pharmaceutically-acceptable organic ligands, and mixtures thereof. Useful inorganic ligands include, but are not limited to, water and hydroxide anion, halide (e.g., fluoride, chloride, bromide, and iodide), carbonate, bicarbonate, phosphate, hydrogen phosphate, dihydrogen phosphate, sulfate, hydrogen sulfate, nitrate, sulfite, nitrite, borate, chlorate, bromate, perchlorate, perbromate, diphosphate, polyphsophate, thiocyanate, any other phar aceutically-acceptable inorganic ligands, and mixtures thereof. By the term "pharmaceutically-acceptable" organic and inorganic ligands as used herein is meant those organic and inorganic ligands which are acceptable from a toxicity viewpoint.
For the sunscreen complexes of the present invention, ligands selected from water, hydroxide anion, and carboxylic acids having from about 2 to about 22 carbon atoms arid their anions are preferred. Other preferred ligands include ethoxide and isopropoxide. Especially preferred among the carboxylic acids and their anions are acetic acid and the acetate anion, octanoic acid and the octanoate anion, and stearic acid and the stearate anion. In the sunscreen complexes of the present invention, the number of ligands present in the complex is designated by p,
wherein p is an integer selected from 0 through 4, more preferably p is an integer selected from 0 through 3, even more preferably p is an integer selected from 0 through 2, even more preferably p is an integer selected from 0 and 1, and most preferably p is 0. Furthermore, it is realized that the complexes of the instant invention can exist as a mixture of different species having different p values. Thus, it is possible to obtain a complex in which the average p value is a noninteger weighted average of the p values of the species present. Preferred examples of sunscreen metal complexes of the present invention include, for example: Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-hydroxydibenzoylmethane; Aluminum (III) Complex of 4-N,N-di-(2-ethylhexyl)aminobenzoic acid ester with 4-hydroxydibenzoylmethane;
Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane; Aluminum (III) Complex 4-N,N-di-(2-ethylhexyl)aminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane; Aluminum (III) Complex of 4-N,N-dimethylaminobenzoic acid ester with 4-hydroxydibenzoylmethane; Aluminum (III) Complex 4-N,N-dimethylaminobenzoic acid ester with
4-(2-hydroxyethoxy)dibenzoylmethane; Aluminum (III) Complex of 4-methoxycinnamic acid ester with 4-hy- droxydibenzoylmethane;
Aluminum (III) Complex 4-methoxycinnamic acid ester with
4-(2-hydroxyethoxy)dibenzoylmethane; Iron (III) Complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane; Copper (II) Complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane; Titanium (IV) Complex of 4-N,N-(2-ethylhexyl)methylaminoben- zoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane; and mixtures thereof.
Preoaratioπ of Sunscreen Complexes
The sunscreen metal complexes of the present invention can be prepared as described in the Examples below. In further embodiments, these complexes can then be directly formulated into a desired carrier. Alternatively, these sunscreen complexes can be isolated before being formulated into the desired carrier. In yet another alternative, these sunscreen complexes can be prepared directly in the desired carrier.
In general, the sunscreen metal complex is prepared by combining a sunscreen compound and a metal salt in a suitable solvent selected from the group consisting of water, acetone, ethyl acetate, methyl t-butyl ether, Ci-Cβ alcohols, diols, triols, C12-15 alcohols benzoate, dimethyl isosorbide, chlorinated solvents (e.g., methylene chloride), isodecyl neopentanoate, diisopropyl adipate, and mixtures thereof. Preferred solvents include water, acetone, ethyl acetate, methylene chloride, ethanol, and mixtures thereof. Preferred metal salts include those selected from the group consisting of salts of aluminum, zinc, calcium, magnesium, copper, iron, barium, strontium, zirconium, titanium, tin, beryllium, gallium, indium, lanthanum, manganese, antimony, bismuth, cerium, thorium, niobium, tantalum, antimony, molybdenum, tungsten, lithium, sodium, potassium, and mixtures thereof. More preferred are salts of aluminum, titanium, copper, iron, zinc, and mixtures thereof. Especially preferred are salts of aluminum, with those selected from the group consisting of aluminum acetate, aluminum diacetate, aluminum stearate, aluminum distearate, aluminum octanoate, aluminum ethoxide, aluminum isopropoxide, and mixtures thereof, being more preferred, and aluminum monoacetate being most preferred. Alternatively ammonium and substituted ammonium chlorides, bromides, and hydroxides can be employed.
Additionally, at least one equivalent of a base can be added in order to facilitate the dissolution of the sunscreen compound. Preferably, the sunscreen compound and the base are prereacted in the solvent system before the metal salt is added. Preferred bases include sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium bicarbonate, sodium carbonate, and mixtures
thereof. Additionally, the solvent system can be heated to its boiling point if required. Where the sunscreen metal complex is isolated and purified, this is preferably accomplished by filtration and evaporation of the filtrate. Additionally, the complex can be further purified by recrystallization from a suitable solvent. The Examples given below provide representative preparations of the sunscreen metal complexes and compositions containing them.
Compositions Containing Sunscreen Metal Complexes One or more of the sunscreen complexes of the present invention can be incorporated into a variety of carriers, including pharmaceutical and cosmetic carriers, paints, coatings, polymeric maxtrices, fiber matrices, and the like. Preferably, the complexes are incorporated into pharmaceutical and cosmetic carriers.
The sunscreen metal complexes of the present invention typically comprise from about 0.1% to about 30.0% by weight of the sunscreen compositions of the present invention, preferably from about 1% to about 20%, and most preferably from about 5% to about 15%. The compositions of the instant invention can comprise the following components. Pharmaceut cal1y-Acceotable Cam'ers
The compositions of the instant invention can comprise a safe and effective amount of a topical pharmaceutically-acceptable carrier or diluent which can be of a variety of different forms.
By "safe and effective" is meant an amount sufficient to act as a suitable vehicle for the sunscreen metal complexes and any other components, but not so much as to cause any side effects or skin reactions. "Pharmaceutically-acceptable" means that the carrier is suitable for topical application to the skin without causing any untoward safety or toxicity concerns. In other words, these carriers are suitable for use on humans and lower animals. The topical carrier can be in the form of an emulsion including, but not limited to, oil-in-water, water-in-oil, water-in-oil-in-water, and oil-in-water-in-silicone emulsions. These emulsions can cover a broad range of consistencies including thin lotions (which can also be suitable for spray or aerosol delivery), creamy lotions,
light creams, heavy creams, and the like. Other suitable topical carriers include anhydrous liquid solvents such as oils and alcohols; aqueous-based single phase liquid solvents (e.g. hydro-alcoholic solvent systems); anhydrous solids and semisolids (such as gels and sticks); and aqueous based gel and mousse systems. Examples of topical carrier systems useful in the present invention are described in the following four references all of which are incorporated herein by reference in their entirety: "Sun Products Formulary" Cosmetics & Toiletries, vol. 105, pp. 122-139 (December 1990); "Sun Products Formulary", Cosmetics & Toiletries, vol. 102, pp. 117-136 (March 1987); U.S. Patent No. 4,960,764 to Figueroa et al . , issued October 2, 1990; and U.S. Patent No. 4,254,105 to Fukuda et al . , issued March 3, 1981. The pharmaceutically-acceptable topical carriers, in total, typically comprise from about 0.1% to about 99.8% by weight of the sunscreen compositions of the present invention, preferably from about 80% to about 99%, and most preferably from about 85% to about 95%. A preferred topical carrier of the compositions of the instant invention is an oil-in-water type emulsion. The pH of these oil-in-water emulsion compositions herein is preferably in the range of from about 3.5 to about 9. Additionally, the mean particle size of the dispersed oil phase materials can be in the range of from about 1 to about 10 microns with greater than about 75% of the particles being less than about 12 microns. Additional Sunscreens
A wide variety of one or more additional sunscreening agents are suitable for use in the present invention. Segarin, et al . , at Chapter VIII, pages 189 et seq., of Cosmetics Science and Technology, disclose numerous suitable agents. Specific suitable sunscreening agents include, but are not limited to, for example: Ethylhexyl-p-methoxycinnamate (available as Parsol MCX from Givaudan Corporation), p-Aminobenzoic acid, its salts and its derivatives (ethyl, isobutyl, glyceryl esters; p-dimethylamino- benzoic acid; 2-ethylhexyl N,N-dimethylaminobenzoate; p-Methoxy- cinnamic Acid Diethanolamine Salt (available as Bernel Hydro from
Bernel Chemical Co.); Anthranilates (i.e., o-aminobenzoates; methyl, octyl , amyl , menthyl , phenyl , benzyl, phenylethyl, linalyl, terpinyl, and cyclohexenyl esters); Salicylates (octyl, amyl, phenyl, benzyl, menthyl, glyceryl, and dipropyleneglycol esters); Cinnamic acid derivatives (menthyl and benzyl esters, -phenyl cinnamonitrile; butyl cinnamoyl pyruvate); Dihydroxy- cinnamic acid derivatives (umbel!iferone, methylumbelliferone, methylaceto-u belliferone); Trihydroxycinnamic acid derivatives (esculetin, methylesculetin, daphnetin, and the glucosides, esculin and daphnin); Hydrocarbons (diphenylbutadiene, stilbene); Dibenzalacetone and benzalacetophenone; 2-Phenylbenzimidazole-5- sulfonic acid and its salts; Naphtholsulfonates (sodium salts of 2-naphthol 3,6-disulfonic and of 2-naphthol-6,8-disulfonic acids); Dihydroxy-naphthoic acid and its salts; o- and p-Hydroxybiphenyl- disulfonates; Coumarin derivatives (7-hydroxy, 7-methyl, 3- phenyl); Diazoles (2-acetyl-3-bromoindazole, phenyl benzoxazole, methyl naphthoxazole, various aryl benzothiazoles); Quinine salts (bisulfate, sulfate, chloride, oleate, and tannate); Quinoline derivatives (8-hydroxyquinoline salts, 2-phenylquinoline); Hydroxy- or methoxy-substituted benzophenones; Uric and vilouric acids; Tannic acid and its derivatives (e.g., hexaethylether); (Butyl carbityl) (6-propyl piperonyl) ether; Hydroquinone; Benzophenones (Oxybenzene, Sulisobenzone, Dioxybenzone, Benzo- resorcinol, 2,2',4,4'-Tetra- hydroxybenzophenone, 2,2'-Dihy- droxy-4,4'-dimethoxybenzophenone, Octabenzone; 4-Isopropyldiben¬ zoylmethane; Butylmethoxydibenzoylmethane; Octocrylene; 4-iso- propyldibenzoylmethane; and camphor derivatives such as methyl benzylidene or benzyl dene camphor; triethanolamine salicylate; and mixtures thereof. Other sunscreens include the solid physical sunblocks such as titanium dioxide (micronized titanium dioxide, 0.03 microns, 0.035 microns, 0.050 microns, and other suitable sizes), zinc oxide, silica, iron oxide and the like. Without being limited by theory, it is believed that these inorganic materials provide a sunscreening benefit through reflecting, scattering, and absorbing harmful UV, visible, and infrared radiation.
Other useful sunscreens are those having both a UVA and a UVB absorbing chromophore in the same molecule as disclosed in U.S. Patent Nos. 5,041,282, 4,999,186 and 4,937,370, and European Patent Application No. 416,837, which have already been incorporated by reference herein.
Generally, these additional sunscreens can comprise from zero to about 20% of the composition, preferably from about 0.5% to about 10%. Exact amounts will vary depending upon the sunscreen chosen and the desired Sun Protection Factor (SPF). SPF is a commonly used measure of photoprotection of a sunscreen against erythema. See. Federal Register. Vol. 43, No. 166, pp. 38206-38269, August 25, 1978.
In addition to these sunscreen agents, the compositions can also contain one or more artificial tanning ingredients such as dihydroxyacetone, tyrosine, amino acids, and amino acid derivatives. Typically, artificial tanning ingredients can be incorporated into the compositions of the instant invention at levels from about 0.1% to about 10%, and preferably at levels from about 0.1% to about 5%. Thickeners
Another optional component of the compositions of the instant invention is a thickener. Examples of such thickeners which can be employed include, but are not limited to, xanthan gum, magnesium aluminum silicate, guar gum, cationic guar gum, Rhamsan Gum (available from Kelco Chemical Co.), kelp, algin and alginate salts, starch and starch derivatives, hydroxypropylcellulose, hydroxyethylcellulose, carboxymethylcellulose, methylcellulose, ethylcellulose, smectite clay thickeners such as hectorite and bentonite, sodium magnesium silicate and mixtures thereof. Examples of suitable thickeners are disclosed in Lochhead, R.Y., "Encyclopedia of Polymers and Thickeners", Cosmetics & Toiletries, vol. 103, no. 12, pp. 99-129 (1988); Meer, G., "Natural Gum Polymers as Ingredients in Cosmetics", Cosmetics & Toiletries, vol. 99, no. 6, pp. 61-64 (1984); and Freeland, M.S. "Cationic Guar Gum", Cosmetics & Toiletries, vol. 99, no. 6, pp. 83-87 (1984); these three references are incorporated herein by reference in their entirety. Preferred thickeners include
magnesium aluminum silicate and xanthan gum and mixtures thereof. The compositions of the instant invention comprise from about 0.1% to about 5% thickener, preferably from about 0.25% to about 2%, and most preferably from about 0.5% to about 1%. Humectaπts/Moisturizers
The compositions of the instant invention can also optionally contain one or more humectants/moisturizers. A variety of humectants/moisturizers can be employed and can be present at a level of from about 0.5% to about 30%, more preferably from about 2% to about 8% and most preferably from about 3% to about 5%. These materials include urea; guanidine; glycolic acid and glycolate salts (e.g. ammonium and quaternary alkyl ammonium); lactic acid and lactate salts (e.g. ammonium and quaternary alkyl ammonium); polyhydroxy alcohols such as sorbitol, glycerin, hexanetriol, propylene glycol, hexylene glycol and the like; polyethylene glycol; sugars and starches; sugar and starch derivatives (e.g. alkoxy!ated glucose); panthenol ; hyaluronic acid; lactamide monoethanolamine; acetamide monoethanolamine; and mixtures thereof. Preferred humectants/moisturizers for use in the compositions of the present invention are the C3-C6 diols and triols. Especially preferred is the triol, glycerin.
Emollients The compositions of the present invention can also optionally comprise at least one emollient. Examples of suitable emollients include, but are not limited to, volatile and non-volatile silicone oils, highly branched hydrocarbons, and non-polar fatty acid and fatty alcohol esters, and mixtures thereof. Emollients useful in the instant invention are further described in U.S. Patent No. 4,919,934, to Deckner et al., issued April 24 1990, which is incorporated herein by reference in its entirety.
The emollients can typically comprise in total from about 1% to about 50%, preferably from about 1% to about 25%, and more preferably from about 1% to about 10% by weight of the compositions of the present invention.
Emulsifier..
Another optional component of the compositions of the instant invention is at least one emulsifier. Suitable emulsifiers can include any of a wide variety of nonionic, cationic, anionic, and zwitterionic emulsifiers disclosed in the prior patents and other references. S_ee McCutcheon's, Detergents and Emulsifiers. North American Edition (1986), published by Allured Publishing Corpor¬ ation; U.S. Patent No. 5,011,681, to Ciotti et al , issued April 30, 1991; U.S. Patent No. 4,421,769, to Dixon et al., issued December 20, 1983; and U.S. Patent No. 3,755,560, to Dickert et al., issued August 28, 1973; these four references are incorporated herein by reference in their entirety.
Suitable emulsifier types include esters of glycerin, esters of propylene glycol, fatty acid esters of polyethylene glycol, fatty acid esters of polypropylene glycol, esters of sorbitol, esters of sorbitan anhydrides, carboxylic acid copolymers, esters and ethers of glucose, ethoxylated ethers, ethoxylated alcohols, alkyl phosphates, polyoxyethylene fatty ether phosphates, fatty acid amides, acyl lactylates, soaps and mixtures thereof. Suitable emulsifiers can include, but are not limited to, polyethylene glycol 20 sorbitan monolaurate (Polysorbate 20), polyethylene glycol 5 soya sterol , Steareth-20, Ceteareth-20, PPG-2 methyl glucose ether distearate, Ceteth-10, Polysorbate 80, cetyl phosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate, Polysorbate 60, glyceryl stearate, PEG-100 stearate, and mixtures thereof.
The emulsifiers can be used individually or as a mixture of two or more and comprise from about 0.1% to about 10%, preferably from about 1% to about 7%, and most preferably from about 1% to about 5% of the compositions of the present invention. Vitamins
Optionally, various vitamins can also be included in the compositions of the present invention. Non-limiting examples include Vitamin A, and derivatives thereof, ascorbic acid, Vitamin B, biotin, Vitamin D, Vitamin E and derivatives thereof such as tocopheryl acetate, panthothenic acid, and mixtures thereof can also be used.
Carboxylic Acid Copolvmers
Another optional component of the compositions of the instant invention is a carboxylic copolymer (acrylic acid copolymer). Most preferred is Carbomer 1342 (available as Carbopol 1342 from B.F. Goodrich). These polymers are more fully described in U.S. Patent
No. 4,509,949, to Huang et al., issued April 5, 1985, and U.S.
Patent No. 2,798,053, to Brown, issued July 2, 1957, these patents being incorporated herein by reference. Also useful are the acrylate/alkyl acrylate crosspoly ers such as Acrylates/C10-C30 Alkyl Acrylate Crosspolymer (available as Pemulen TR-1 and Pemulen
TR-2 from Goodrich). Reference to Include Pemulens.
These polymers comprise from about 0.025% to about 0.75%, preferably from about 0.05% to about 0.25% and most preferably from about 0.075% to about 0.175%. Other Optional Components
A variety of additional ingredients can be incorporated into the emulsion compositions of the present invention. Non-limiting examples of these additional ingredients include various polymers for aiding the film-forming properties and substantivity of the composition (such as a copolymer of eicosene and vinyl pyrrolidone, an example of which is available from GAF Chemical Corporation as Ganex V-220R); gums, resins, and thickeners; preservatives for maintaining the antimicrobial integrity of the compositions; antioxidants; chelators and sequestrants; anti-acne agents; keratolyic agents;and agents suitable for aesthetic purposes such as fragrances, pigments, and colorings. Other useful materials include acidic materials such as salicylic acid, lactic acid, glycolic acid, benzoic acid, citric acid and the like. Without being limited by theory, it is believed that these acid materials are useful for maintaining the pH of the composition and enhancing product performance.
Method for Preventing Sunburn The present invention further relates to a method for pro¬ tecting the skin of humans or lower animals -from the effects of UVA and UVB wavelength radiation, such as sunburn and premature aging of the skin. Such a method comprises topically applying to the human or lower animal an effective coating of a sunscreen
agent or composition of the present invention. The term "ef¬ fective coating", as used herein, means a film of sunscreen agent sufficient to substantially reduce the amount of UVA and UVB wavelength light which reaches the skin's surface. Typically, an effective coating of the skin is from about 0.5 mg sunscreen agent or composition of the present invention/cm2 skin to about 5 mg sunscreen agent or composition of the present invention/cm2 skin. See Federal Register, Vol. 43, No. 166, pp. 38206-38269, August 25, 1978. The following examples further describe and demonstrate the preferred embodiments within the scope of the present invention. The examples are given solely for the purpose of illustration, and are not to be construed as limitations of the present invention since many variations thereof are possible without departing from its spirit and scope.
EXAMPLE 1 Preparation of the Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)- methylaminobenzoic Acid Ester with 4-(2-hydroxyethoxy)dibenzoyl - methane using Aluminum Diacetate. In a 1000-mL flask, 3.5 grams (0.0216 moles) of aluminum diacetate (Aldrich Chemical Co., Milwaukee, WI), is added to approximately 500 mL of absolute ethanol and heated to boiling for approximately 10 minutes. In a separate 500-mL flask, 20.0 grams (0.038 moles) of 4-N,N-(2-ethylhexyl )methylaminobenzoic Acid Ester with 4-(2-hydroxyethoxy)dibenzoylmethane is added to approximately 100 mL of acetone and heated to boiling for approximately 10 minutes. Next, a solution of 10 mL of an 11% (w/w) aqueous solution of sodium hydroxide is added to the acetone solution of the sunscreen, and the mixture is vigorously agitated until miscible. The sunscreen solution is then slowly added to the aluminum diacetate solution with stirring, and the mixture is refluxed for approximately 10 minutes. Next, the solvents are removed by rotary evaporation to yield the crude sunscreen aluminum complex. This crude complex is redissolved in approximately 150 mL of ethyl acetate with heating and is then vacuum filtered using a coarse, sintered glass funnel to remove any undissolved materials, which are washed with ethyl acetate
(approximately 2 X 20 mL) . (Alternatively, other suitable solvents such as chloroform, methylene chloride, or methyl t-butyl ether can be used for this redissolving step.) The pooled filtrates are extracted with water (approximately Z X 100 L), dried over sodium sulphate, and evaporated by rotary evaporation to yield the sunscreen aluminum complex as a light yellow, glassy solid. This solid is suitable for incoporation into a sunscreen composition.
Characterization: Elemental Analysis: 2.62% Aluminum.
UV-Vis Spectrum: ^max = 30 nm, A - 0.7579 λmax = 362 nm, A - 0.6916 (10 ppm in 50:50 DMSO.Chloroform) iH NMR (300 MHz, CDC13): 0.95(m), 1.35(m), 1.80(m), 3.00(s), 3.25(d), 4.30(t), 4.63(t), 6.60(d), 6.95(d), 7.25(s), 7.40(m), 7.90(d), 8.10(d). 1 c NMR (75.47 MHz, CDU3): 10.64, 13.94, 23.01, 23.91, 28.62, 30.61, 37.74, 39.38, 56.53, 62.20, 66.32, 93.35, 110.4, 114.12, 115.90, 127.73, 128.05, 129.85, 131.12, 131.39, 138.87, 152.78, 161.61, 166.66, 183.87, 184.03. Mass Spectral Analysis: Parent ion m/z » 1083.
EXAMPLE Z Preparation of the Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)- methylaminobenzoic Acid Ester with 4-(2-hydroxyethoxy)dibenzoyl- methane using Aluminum Monoacetate.
In a 1000-mL flask, 33.75 grams (0.240 moles) of aluminum monoacetate (basic, stabilized with boric acid: Aldrich Chemical Co., Milwaukee, WI) is added to approximately 300 mL of absolute ethanol and heated to boiling for approximately 10 minutes. In a separate 500-mL flask, 182.4 grams (0.343 moles) of 4-N,N-(2-ethylhexyl)methylaminobenzoic Acid Ester with 4-(2-hydroxyethoxy)dibenzoylmethane is added to approximately 200 mL of acetone and heated to boiling for approximately 10 minutes. Next, a solution of 80 mL of an 11% (w/w) aqueous solution of sodium hydroxide is added to the acetone solution of the sunscreen, and the mixture is vigorously agitated until miscible. The sunscreen solution is then slowly added to the aluminum
monoacetate solution with stirring, and the mixture is refluxed for approximately 10 minutes. Next, the solvents are removed by rotary evaporation to yield the crude sunscreen aluminum complex. This crude complex is redissolved in approximately 300 mL of ethyl acetate with heating, and is then vacuum filtered using a coarse, sintered glass funnel to remove any undissolved materials, which are washed with ethyl acetate (approximately 2 X 50 mL). The pooled filtrates are extracted with water, dried over sodium sulphate, and evaporated by rotary evaporation to yield the sunscreen aluminum complex as a light yellow, glassy solid. This solid is suitable for incorporation into a sunscreen composition.
EXAMPLE 3 Preparation of the Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)- ethylaminobenzoic Acid Ester with 4-(2-hydroxyethoxy)dibenzoyl- methane using Aluminum Distearate.
In a 500-mL flask 2.0 grams (3.28 mmoles) of aluminum distearate (Aldrich Chemical Co., Milwaukee, WI) is added to 100-ml of Cj2-15 alcohols benzoate and the mixture is heated to 90°C until dissolved. Next, 2.0 grams (3.78 mmoles) of 4-N,N-(2- ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyeth- oxy)dibenzoylmethane is added with stirring to form the sunscreen aluminum complex. This oil phase solution of the sunscreen metal complex is suitable for incorporation into an emulsion or gel composition. (Alternatively, other solvents useful in this preparation include dimethyl isosorbide, isodecyl neopentanoate, and diisopropyl adipate.)
EXAMPLE 4 Preparation of the Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)- ethylaminobenzoic Acid Ester with 4-(2-hydroxyethoxy)dibenzoyl- methane using Aluminum Dioctanoate.
Using the procedue given in Example 3, this sunscreen aluminum complex is prepared starting with 1.0 gram of aluminum dioctanoate (Aldrich Chemical Co., Milwaukee, WI). The resulting oil phase solution of the complex is suitable for incorporation into an emulsion or gel composition.
EXAMPLE 5 Preparation of the Aluminum (III) Complex of 4-N,N(2-ethylhexyl)- methylaminobenzoic Acid Ester with 4-hydroxydibenzoylmethane using Aluminum Monoacetate. Using the procedure of Example 2 this sunscreen aluminum complex is prepared using 33.75 grams (0.240 moles) of aluminum monoacetate and 166.36 grams (0.343 moles) of 4-N,N(2-ethylhexyl)- methylaminobenzoic acid ester with 4-hydroxydibenzoyl ethane. A light yellow solid is obtained suitable for incorporation into a sunscreen composition.
EXAMPLE 6 Preparation of the Aluminum (III) Complex of 4-N,N-di-(2-ethyl- hexyl)-4-aminobenzoic Acid Ester with 4-hydroxydibenzoylmethane using Aluminum Monoacetate. Using the procedure of Example 2 this sunscreen aluminum complex is prepared using 33.75 grams (0.240 moles) of aluminum monoacetate and 200.0 grams (0.343 moles) of 4-N,N-di-(2- ethylhexyl)-4-aminobenzoic acid ester with 4-hydroxydibenzoyl- methane. A light yellow solid is obtained suitable for incorporation into a sunscreen composition.
EXAMPLE 7 Preparation of the Aluminum (III) Complex of 4-N,N-di-(2-ethy1- hexyl)-4-aminobenzoic Acid Ester with 4-(2-hydroxyethoxy)- dibenzoylmethane using Aluminum Monoacetate. Using the procedure of Example 2 this sunscreen aluminum complex is prepared using 33.75 grams (0.240 moles) of aluminum monoacetate and 215.06 grams (0.343 moles) of 4-N,N-di-(2-ethyl- hexyl)4-aminobenzoic acid ester with 4-(2-hydroxyethoxy)- dibenzoylmethane. A light yellow solid is obtained suitable for incorporation into a sunscreen composition.
EXAMPLE 8 Oil based gel composition containing Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic Acid Ester with 4-(2-hydroxyethoxy)dibenzoylmethane. 4.0 grams of the sunscreen aluminum complex prepared in Example 2 is added to 100 grams of Cχ2-15 Alcohols Benzoate by heating to 90°C. The mixture is cooled to 80°C and 1 gram of
dibutyllaurolyl glutamide (available as Coagulen GP-1 from Ajinomoto Co., Inc., Tokyo, Japan) is added to gel the mixture upon cooling. This gel composition is useful for topical application to the skin to provide protection from the harmful effects of ultraviolet radiation.
Alternatively, analogous gel compositions can be prepared using the other sunscreen metal complexes of the instant invention and using other solvents such as isodecyl neopentanote, diisopropyl adipate, and dimethyl isosorbide. EXAMPLE 9
Sunscreen emulsion prepared via the in situ preparation of the Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic Acid Ester with 4-(2-hydroxyethoxy)dibenzoylmethane.
An emulsion composition is prepared from the following ingredients using standard methods.
Ingredient Percent (w/w)
Phase A c12-15 Alcohols Benzoate 9.00
Aluminum Stearate 1.00 4-N,N-(2-ethylhexyl)methylamino- benzoic acid ester with 4-(2-hydroxy- ethoxy)dibenzoylmethane 1.00
Phase B Isodecyl Noepentanoate 3.00 Isohexadecane 2.00
DEA-Cetyl Phosphate 1.80
Dimethicone 0.75
Cyclomethicone 0.50
Aluminum Starch Octenylsuccinate 1.00 Cetyl Alcohol 1.40
Stearic Acid 1.00
Ethylparaben 0.15
Titanium dioxide 0.50
Phase C ater QS100
Acrylates/C10-30 Alkyl Acrylate
Crosspolymer 0.075
Carbomer 951 Carbomer 954 Methylparaben Hexylene Glycol Glycerol
Disodium EDTA
The Phase A ingredients are combined and heated to 90°C and then cooled to 80°C. Next, the Phase B ingredients are added with mixing at 80°C to form the oil phase. In another vessel, the Phase C ingredients are combined and heated to 80°C. The oil phase is added to Phase C with homogenization to form the emulsion. The emulsion is cooled with stirring to 40°C. Next, the Phase D ingredients are combined and added to the emulsion with mixing. The emulsion is then cooled to room temperature with stirring.
This emulsion composition is useful for topical application to the skin to provide protection from the harmful effects of ultraviolet radiation. Alternatively, the above sunscreen emulsion is prepared using 0.50 grams of aluminum dioctoate in place of the aluminum distearate.
EXAMPLE 10 Sunscreen emulsion prepared with the isolated Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic Acid Ester with 4-(2-hydroxyethoxy)dibenzoylmethane.
An emulsion composition is prepared from the following ingredients using standard methods.
Ingredient Percent .w/w) Phase A
Aluminum Complex of 4-N,N-(2-ethyl- hexyl)methylaminobenzoic acid ester
with 4-(2-hydroxyethoxy)dibenzoylmethane
(Prepared as in Example 2) 6.00 c12-15 Alcohols Benzoate 9.00
Isodecyl Neopentanoate 3.00 Isohexadecane 2.00
DEA-Cetyl Phosphate 1.80
Dimethicone 0.75
Cyclomethicone 0.50
Aluminum Starch Octenylsuccinate 1.00 Cetyl Alcohol 1.40
Stearic Acid 1.00
Ethylparaben 0.15
Titanium dioxide 0.50 Phase B Water QS100 Acrylates/C10-30 Alkyl Acrylate
Crosspolymer 0.075
Carbomer 951 0.050
Carbomer 954 0.050 Methylparaben 0.30
Hexylene Glycol 0.50
Glycerol 1.00
Disodium EDTA 0.050 Phase C Fragrnace 0.14
Fragrance 0.21
Benzyl Alcohol 0.30
Triethanolamine 0.175
Water 1.40 The Phase A ingredients are combined and heated with mixing to 90°C and then cooled to 80°C. In a separate vessel, the Phase B ingredients are combined and heated wtih mixing to 80°C. The
Phase A mixture is added to the Phase B mixture with homogenization to form the emulsion. The emulsion is cooled with stirring to 40°C. Next, the Phase C ingredients are combined and added to the emulsion with mixing. The emulsion is then cooled to room temperature with stirring.
This emulsion composition is useful for topical application to the skin to provide protection from the harmful effects of ultraviolet radiation.
Alternatively, analogous emulsions are prepared using other isolated sunscreen metal complexes of the instant invention.
EXAMPLE 11 Sunscreen emulsion prepared with the isolated Aluminum (III) Complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic Acid Ester with' 4-(2-hy- droxyethoxy)dibenzoylmethane. Ingredient Percent fw/w)
Phase A Isosteareth-20 3.00
Cetyl Alcohol 1.50
Stearic Acid 1.50 c12-15 Alcohols Benzoate 7.00
Dimethyl Isosorbide 7.00
Aluminum Complex of 4-N,N-(2-ethyl- hexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane (Prepared as in Example 2) 6.00
Phase B Water QS100
Methylchloroisothiazolinone (and)
Methylisothiazolinone 0.100 The Phase A ingredients are combined and heated with stirring to 80°C to form the oil phase. Next, the Phase B ingredients are combined and heated with stirring to 80°C. Phase A is added to Phase B with homogenization to form the emulsion which is then cooled to room temperature with stirring. This emulsion composition is useful for topical application to the skin to provide protection from the harmful effects of ultraviolet radiation.
Alternatively, analogous emulsions are prepared using other isolated sunscreen metal complexes of the instant invention.
WHAT IS CLAIMED IS:
Claims
A sunscreen complex having the general structure:
[ X - G - Z ]m (M)n (L)p wherein (A) [ X - G - Z ] is a sunscreen moiety wherein
(i) X is a UVA-absorbing chromophore having the general structure:
(ii) Z is a UVB-absorbing chromophore selected from the group consisting of:
0 -C-CHrCH ~m >
and mixtures thereof, wherein in all the preceding formulae, A is a substituent independently selected from the group consisting of R,
-OR, -NR2 or -SO3H; each Al is independently -OR or -NR2; each A2 is independently -OR or -O2C-R ; each A3 is independently -CN or -CO2 I and each R is independently
H, straight or branched chain alkyl having from 1 to 20 carbon atoms, (CH2CH2θ)q-H, or (CH2CH(CH3)0)q-H, wherein q is an integer from 1 to 8; and each R is independently straight or branched chain alkyl having from 1 to 20 carbon atoms; and
(iii) G is a linking moiety selected from the group consisting of
(a) a linking moiety which covalently bonds the X and Z chromophore moieties into one molecule and which furthermore separates the X and Z moieties such that the electron systems of said moieties are not directly coupled, or
(b) a linking moiety which is a chemical bond which covalently bonds the X and Z chromophore moieties such that the electron systems of the X and Z moieties are directly coupled;
(B) m is an.integer selected from 1, 2, 3 or 4;
(C) M is a metal cation, an ammonium cation, or a substituted ammonium cation;
(D) n is an integer selected from 1, 2, 3, or 4;
(E) L is a ligand comprising a neutral or negatively charged organic or inorganic moiety; and
(F) p is an integer selected from 0, 1,
2,
3 or 4. A sunscreen complex according to Claim 1 wherein in the X, UVA-absorbing chromophore A is H, and wherein the Z, UVB-absorbing chromophore is selected from the group consisting of:
and mixtures thereof, wherein each R is independently selected from H or straight or branched chain alkyl having from 1 to 20 carbon atoms, preferably wherein each R is independently selected from methyl or 2-ethylhexyl , and wherein A is selected from -OCH3 or -OCH2CH3.
A sunscreen complex according to Claim 2 wherein the G linking moiety is selected from the group consisting of -0-, -NR- or -(-Wl-(-CR22-)s-)t-W2-, wherein each Wl and W2 are, independently, selected from the group consisting of a single bond, or an atom selected from the group of 0 or NR; s is an integer of zero or greater, t is an integer of zero or greater, each R2 group is independently selected from the group consisting of H, OH, or straight or branched chain alkyl having from 1 to 20 carbon atoms; and R is H, or straight or branched chain alkyl having from 1 to 20 carbon atoms, preferably wherein the G linking moiety is selected from the group of moieties consisting of:
-0-
-NH-
-NCH3- -0-(-CH2-)s-°-» wherein s is an integer from 1 to 6; -NH-(-CH2-)s-NH-, wherein s is an integer from 1 to 6; -(-0-CH2CH2-)s-0-> wherein s is 1 or 2; -(-NH-CH2CH2-)s-NH-, wherein s is 1 or 2; -(-0-CH2-CH-)s-0-, wherein s is 1 or 2;
CH3 -(-NH-CH2-CH-)S-NH-, wherein s is 1 or 2;
CH3 -(-0-CH2CHC2H-)s-0-, wherein s is 1 or 2; and
OH mixtures thereof, more preferably wherein the G linking moiety is -0- or -0-(CH2-)s-0-> wherein s is an integer from 1 to 6, most preferably wherein the G linking moiety is -0- or -OCH2CH2O-.
4. A sunscreen complex according to Claim 3 wherein the
[X - G - Z] sunscreen moiety is selected from the group consisting of 4-N,N(2-ethylhexyl)methylaminobenzoic acid ester with 4-hydroxydibenzoylmethane, 4-N,N-di-(2- ethylhexyl)-4-aminobenzoic acid ester with 4-hydroxydiben- zoylmethane, 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, 4-N,N-di-(2-ethyl- hexyl)4-aminobenzoic acid ester with 4-(2-hydroxy- ethoxy)- dibenzoylmethane, 4-N,N-dimethylaminobenzoic acid ester with 4-hydroxydibenzoylmethane, 4-N,N-dimethylamino- benzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, 4-methoxycinnamic acid ester with 4-hydroxydibenzoyl ethane, 4-methoxycinnamic acid ester with 4-(2-hydroxyethoxy)diben- zoylmethane, and mixtures thereof.
5. A sunscreen complex according to Claim 4 wherein M is a metal cation selected from the group consisting of aluminum, zinc, calcium, magnesium, copper, iron, barium, strontium, zirconium, titanium, tin, beryllium, gallium, indium, lanthanum, manganese, antimony, bismuth, cerium, thorium, niobium, tantalum, antimony, molybdenum, tungsten, lithium, sodium, potassium, and mixtures thereof, and wherein said metal cation has a valence of 1, 2, 3, or 4, preferably wherein said metal cation is selected from aluminum, titanium, copper, iron, zinc, and mixtures thereof, and wherein said metal cation has a valence of 1, 2, 3, or 4, and more preferably wherein said metal cation is aluminum with a valence of 3+.
6. A sunscreen complex accoridng to Claim 5 wherein said ligand, L, is selected from the group of organic ligands consisting of carboxylic acids, dicarboxylic acids, and polycarboxylic acids and their anions; amines, dia ines, and polyamines; alcohols, diols, and polyols and their anions; thiols, dithiols, and polythiols and their anions; amino acids and their anions; or the group of inorganic ligands consisting of water and hydroxide anion, fluoride, chloride, bromide, iodide, carbonate, bicarbonate, phosphate, hydrogen phosphate, dihydrogen phosphate, sulfate, hydrogen sulfate, nitrate, sulfite, nitrite, borate, chlorate, bromate, perchlorate, perbromate, diphosphate, polyphosphate, thiocyanate, and mixtures thereof, preferably wherein said ligand, L, is selected from the group consisting of water, hydroxide anion, carboxylic acids, carboxylic acid anions, and mixtures thereof, more preferably wherein said carboxylic acid or carboxylic acid anion has from 2 to 22carbon atoms, most preferably wherein said carboxylic acid or carboxylic acid anion is selected from acetic acid or acetate anion, octanoic acid or octanoate anion, stearic acid or stearate anion, and mixtures thereof.
7. A sunscreen complex according to Claim 6 wherein m is an integer selected from 1, 2, or 3, and n is 1, preferably wherein m is 2 and n is 1.
8. A sunscreen complex selected from the group consisting of the aluminum (III) complex of 4-N,N(2-ethylhexyl)methyl- a inobenzoic acid ester with 4-hydroxydibenzoylmethane, the aluminum (III) complex of 4-N,N-di-(2-ethylhexyl)-4-amino- benzoic acid ester with 4-hydroxydibenzoylmethane, the aluminum (III) complex of 4-N,N-(2-ethylhexyl)methylamino- benzoic acid ester with 4-(2-hydroxyethoxy)dibenzoyl ethane, the aluminum (III) complex of 4-N,N-di-(2-ethyτhexyl)4-amino- benzoic acid ester with 4-(2-hydroxyethoxy)dibenzpylmethane, the aluminum (III) complex of 4-N,N-dimethylaminobenzoic acid ester with 4-hydroxydibenzoylmethane, the aluminum (III) com¬ plex of 4-N, -di ethylaminoben- zoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, the aluminum (III) com¬ plex of 4-methoxycinnamic acid ester with 4-hydroxydibenzoyl- methane, the aluminum (III) complex of 4-methoxycinnamic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, the iron (III) complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, the copper (II) complex of 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, titanium (IV) complex of 4,N,N-(2ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, and mixtures thereof.
9. A sunscreen composition comprising:
(a) from 0.1% to 30% of one or more sunscreen complexes of Claims 1; (b) from 0% to 20% of a second sunscreen or mixture of sunscreens selected from the group consisting of 2-ethylhexyl p-methoxycinnamate, 2-ethylhexyl N,N-dimethyl-p-aminobenzoate, p-amino- benzoic acid, octocrylene, 2-phenylbenzimidozole-5- sulfonic acid, oxybenzone, homomenthyl salicylate, octyl salicylate, sulisobenzone, amyl p-methoxy¬ cinnamate, amyl N,N-dimethyl-p-aminobenzoate, butyl methoxydibenzoylmethane, 4-isopropyldibenzoyl¬ methane, 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester of 2,4-dihydroxybenzophenone; N,N-di-(2- ethylhexyl)-4-aminobenzoic acid ester with 4-hy- droxydibenzoylmethane; 4-N,N(2-ethylhexyl)methyl-
•3 aminobenzoic acid ester with 4-hydroxydibenzoyl- ethane; 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester of 2-hydroxy-4-(2-hydroxyethoxy)benzophenone; 4-N,N-(2-ethylhexyl) methylaminobenzoic acid ester of 4-(2-hydroxyethoxy)dibenzoylmethane;
N-N-di-(2-ethylhexyl)-4-aminobenzoic acid ester of 2-hydroxy-4-(2-hydroxyethoxy)benzophenone, and N,N-di-(2-ethylhexyl)4-aminobenzoic acid ester of 4-(2-hydroxyethoxy)dibenzoylmethane, titanium dioxide, zinc oxide, iron oxide, and mixtures thereof; and (b) a pharmaceutically-acceptable sunscreen carrier.
10. A sunscreen composition according to Claim 9 wherein said carrier is selected from an oil-in-water emulsion, water-in-oil emulsion, an oil, an aqueous-based lotion or gel, o an anhydrous gel .
11. A method for protecting the skin of humans or lower animals from the effects of UVA and UVB wavelength radiation, said method comprising topically applying to the skin of the human or lower animal on a substantially daily basis an effective coating of a sunscreen composition according to Claim 9.
12. A process for preparing a sunscreen complex which comprises combining a sunscreen compound of general formula [X - G - Z] with a salt in a suitable solvent, wherein (A) X is a UVA-absorbing moiety having the general structure:
0
~C- ( 0> -NR2
'C-CH -CH- (ύ) -Al
and mixtures thereof, wherein in all the preceding formulae, A is a substituent independently selected from the group consisting of R, -OR, -NR2 or -SO3H, or its pharmaceutically-acceptable salt or ester; each A is indepen¬ dently -OR or -NR2; each A2 is independently -OR or -O2C-RI; each A3 is independently -CN or -CO2R ; and each R is indepen¬ dently H, straight or branched chain alkyl having from 1 to 20 carbon atoms, (CH2CH2θ)q-H, or (CH2CH(CH3)0)q-H, wherein q is an integer from 1 to 8; and each R is independently straight or branched chain alkyl having from 1 to 20 carbon atoms; (C) G is a linking moiety selected from the group consisting of
(i) a linking moiety which covalently bonds the X and Z chromophore moieties into one molecule and which furthermore separates the X and Z moieties such that the electron systems of said moieties are not directly coupled, or
(ii) a linking moiety which is a chemical bond which covalently bonds the X and Z chromophore moieties such that the electron systems of the X and Z moieties are directly coupled; and
(D) said salt is selected from salts of aluminum, zinc, calcium, magnesium, copper, iron, barium, strontium, zirconium, titanium, tin, beryllium, gallium, indium, lanthanum, manganese, antimony, bismuth, cerium, thorium, niobium, tantalum, antimony, molybdenum, tungsten, lithium, sodium, potassium, ammonium, substituted ammonium, and mixtures thereof.
13. A process according to Claim 12 wherein said salt is selected from aluminum, titanium, copper, iron, zinc, and mixtures thereof, preferably wherein said salt is an aluminum salt, more preferably wherein said aluminum salt is selected from the group consisting of aluminum monoacetate, aluminum diacetate, aluminum stearate, aluminum distearate, aluminum octanoate, aluminum ethoxide, aluminum isopropoxide, and mixtures thereof, most preferably wherein said aluminum salt is aluminum monoacetate.
14. A process according to Claim 13 wherein in the X UVA-absorbing chromophore A is H, and wherein the Z UVB-absorbing chromophore is selected from the group consisting of: e> NR2 or
15. A process according to Claim 14 wherein the G linking moiety is selected from the group consisting of -0-, -NR- or -(-Wl-(-CR22-)s-)t-W2-, wherein each Wl and W2 are, independently, selected from the group consisting of a single bond, or an atom selected from the group of 0 or NR; s is an integer of zero or greater, t is an integer of zero or greater, each R2 group is independently selected from the group consisting of H, OH, or straight or branched chain alkyl having from 1 to 20 carbon atoms; and R is H, or straight or branched chain alkyl having from about 1 to 20 carbon atoms, preferably wherein the G linking moiety is selected from the group of moieties consisting of: -0- -NH- -NCH3- -0-(-CH2-)s-0-. wherein s is an integer from 1 to 6; -NH-(-CH2-)s-NH-, wherein s is an integer from 1 to 6; -(-0-CH2CH2-)s-0-, wherein s is 1 or 2; -(-NH-CH2CH2-)s-NH-, wherein s is 1 or 2; -(-0-CH2-CH-)s-0-, wherein s is 1 or 2; CH3 -(-NH-CH2-CH-)S-NH-, wherein s is 1 or 2;
CH3 -(-0-CH2CHC2H-)s-0-, wherein s is 1 or 2; and
OH mixtures thereof, more preferably wherein the linking G moiety is -0- or -0-(CH2-)s_0-> wherein s is an integer from 1 to 6, and most preferably wherein the G linking moiety is -0- or -O-CH2CH2-O-.
16. A process according to Claim 15 wherein the [X - G - Z] sunscreen compound is selected from the group consisting of 4-N,N(2-ethylhexyl)methylaminobenzoic acid ester with 4-hydroxydibenzoylmethane, 4-N,N-di-(2-ethylhexyl)-4- inobenzoic acid ester with 4-hydroxydibenzoylmethane, 4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, 4-N,N-di-(2-ethyl- hexyl)4-aminobenzoic acid ester with 4-(2-hydroxyethoxy)- dibenzoylmethane, 4-N,N-dimethylaminobenzoic acid ester with 4-hydroxydibenzoylmethane, 4-N,N-dimethylaminobenzoic acid ester with 4-(2-hydroxyethoxy)dibenzoylmethane, 4-methoxy- cinnamic acid ester with 4-hydroxydibenzoylmethane, 4-methoxycinnamic acid ester with 4-(2-hydroxyethoxy)diben- zoyl ethane, and mixtures thereof.
17. A process according to Claim 16 wherein said solvent is selected from the group consisting of water, acetone, ethyl acetate, methyl t-butyl ether, C1-C6 alcohols, diols, triols, C12-15 alcohols benzoate, methylene chloride, dimethyl isosorbide, methylene chloride, isodecyl neopentanoate, diisopropyl adipate, and mixtures thereof.
18. A process according to Claim 17 wherein said sunscreen compound is first reacted with at least one equivalent of a base selected from the group consisting of sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium bicarbonate, sodium carbonate, and mixtures thereof before being combined with the salt.
19. A process according to Claim 18 which further comprises an isolation and purification step, preferably wherein said isolation and purification step is accomplished by filtration and evaporation.
20. A process of preparing a sunscreen composition comprising the steps of
(a) preparing a sunscreen complex according to the process recited in Claim 12, and
(b) adding the resulting sunscreen complex to a pharmaceutically-acceptable carrier.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US80066491A | 1991-11-27 | 1991-11-27 | |
US800,664 | 1991-11-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1993011095A1 true WO1993011095A1 (en) | 1993-06-10 |
Family
ID=25179019
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1992/009694 WO1993011095A1 (en) | 1991-11-27 | 1992-11-12 | Uva-absorbing sunscreen metal complexes |
Country Status (4)
Country | Link |
---|---|
CN (1) | CN1073947A (en) |
AU (1) | AU3072292A (en) |
PT (1) | PT101101A (en) |
WO (1) | WO1993011095A1 (en) |
Cited By (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996015772A2 (en) * | 1994-11-24 | 1996-05-30 | Lancaster Group Gmbh | Sun-protection preparation with increased light-protection factor |
WO2002095393A2 (en) * | 2001-05-24 | 2002-11-28 | National Research Council Of Canada | Drug evolution: drug design at hot spots |
EP2196189A1 (en) | 2001-12-07 | 2010-06-16 | L'oreal | Cosmetic sunscreen compositions based on synergistic filter mixture and their use |
AU2007287592B2 (en) * | 2006-08-23 | 2010-07-29 | Unilever Plc | Sunscreen composition |
WO2012101204A1 (en) | 2011-01-28 | 2012-08-02 | Momentive Performance Materials Gmbh | Uv-photo-protecting cosmetic composition |
WO2014010099A1 (en) | 2012-07-13 | 2014-01-16 | L'oreal | Composite pigment and method for preparing the same |
WO2014010098A1 (en) | 2012-07-13 | 2014-01-16 | L'oreal | Cosmetic composition comprising composite particles |
WO2014010100A1 (en) | 2012-07-13 | 2014-01-16 | L'oreal | Cosmetic composition comprising composite sunscreen particles |
WO2014009097A1 (en) | 2012-07-13 | 2014-01-16 | L'oreal | Cosmetic composition containing screening composite particles |
WO2014111566A2 (en) | 2013-01-21 | 2014-07-24 | L'oreal | Cosmetic or dermatological composition comprising a merocyanine and an insoluble organic uv-screening agent and/or an insoluble inorganic uv- screening agent |
WO2016030839A1 (en) | 2014-08-28 | 2016-03-03 | L'oreal | Gel composition and gel comprising a uv filter |
WO2016083404A1 (en) | 2014-11-24 | 2016-06-02 | L'oreal | Cosmetic composition comprising a synthetic phyllosilicate and a polyol and/or a uv filter |
WO2016198581A1 (en) | 2015-06-11 | 2016-12-15 | L'oreal | Composition comprising a uv-screening agent, an anionic crosslinked hydrophilic polymer, a surfactant having an hlb less than or equal to 5 and a silicone copolymer |
WO2019096960A1 (en) | 2017-11-15 | 2019-05-23 | L'oreal | Compositions comprising at least one acrylic polymer and at least one insoluble organic screening agent |
FR3083093A1 (en) | 2018-06-28 | 2020-01-03 | L'oreal | PHOTOPROTECTOR COMPOSITION COMPRISING COLLOIDAL SILICA PARTICLES |
FR3090329A1 (en) | 2018-12-21 | 2020-06-26 | L'oreal | Composition comprising a UV filter, an anionic crosslinked hydrophilic polymer, a surfactant having an HLB less than or equal to 5 and a non-volatile alkane |
FR3103705A1 (en) | 2019-11-29 | 2021-06-04 | L'oreal | A composition comprising a UV filter, a block polymer containing a phosphonic acid group and a hydrocarbon oil |
FR3103704A1 (en) | 2019-11-29 | 2021-06-04 | L'oreal | Composition comprising a UV filter, an ethylenic polymer with a phosphonic acid group and a hydrocarbon oil |
US11523976B2 (en) | 2012-07-13 | 2022-12-13 | L'oreal | Composite pigment and method for preparing the same |
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EP0220934A2 (en) * | 1985-10-23 | 1987-05-06 | Stepan Company | Aluminium carboxylates |
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-
1992
- 1992-11-12 WO PCT/US1992/009694 patent/WO1993011095A1/en active Application Filing
- 1992-11-12 AU AU30722/92A patent/AU3072292A/en not_active Abandoned
- 1992-11-27 CN CN 92111850 patent/CN1073947A/en active Pending
- 1992-11-27 PT PT10110192A patent/PT101101A/en not_active Application Discontinuation
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GB1387281A (en) * | 1972-01-11 | 1975-03-12 | C A Lab Inc | Ultra-violet light absorber compositions |
EP0220934A2 (en) * | 1985-10-23 | 1987-05-06 | Stepan Company | Aluminium carboxylates |
EP0251398A2 (en) * | 1986-06-27 | 1988-01-07 | The Procter & Gamble Company | Novel chromophores, sunscreen compositions and methods for preventing sunburn |
Cited By (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996015772A2 (en) * | 1994-11-24 | 1996-05-30 | Lancaster Group Gmbh | Sun-protection preparation with increased light-protection factor |
WO1996015772A3 (en) * | 1994-11-24 | 1996-07-25 | Lancaster Group Ag | Sun-protection preparation with increased light-protection factor |
US5885558A (en) * | 1994-11-24 | 1999-03-23 | Lancaster Group Gmbh | Sun protection preparation with an increased sun protection factor |
WO2002095393A2 (en) * | 2001-05-24 | 2002-11-28 | National Research Council Of Canada | Drug evolution: drug design at hot spots |
WO2002095393A3 (en) * | 2001-05-24 | 2003-05-22 | Ca Nat Research Council | Drug evolution: drug design at hot spots |
EP2196189A1 (en) | 2001-12-07 | 2010-06-16 | L'oreal | Cosmetic sunscreen compositions based on synergistic filter mixture and their use |
AU2007287592B2 (en) * | 2006-08-23 | 2010-07-29 | Unilever Plc | Sunscreen composition |
WO2012101204A1 (en) | 2011-01-28 | 2012-08-02 | Momentive Performance Materials Gmbh | Uv-photo-protecting cosmetic composition |
WO2014010100A1 (en) | 2012-07-13 | 2014-01-16 | L'oreal | Cosmetic composition comprising composite sunscreen particles |
US11266584B2 (en) | 2012-07-13 | 2022-03-08 | L'oreal | Cosmetic composition comprising composite sunscreen particles |
WO2014010099A1 (en) | 2012-07-13 | 2014-01-16 | L'oreal | Composite pigment and method for preparing the same |
WO2014009097A1 (en) | 2012-07-13 | 2014-01-16 | L'oreal | Cosmetic composition containing screening composite particles |
WO2014010098A1 (en) | 2012-07-13 | 2014-01-16 | L'oreal | Cosmetic composition comprising composite particles |
US11523976B2 (en) | 2012-07-13 | 2022-12-13 | L'oreal | Composite pigment and method for preparing the same |
WO2014111566A2 (en) | 2013-01-21 | 2014-07-24 | L'oreal | Cosmetic or dermatological composition comprising a merocyanine and an insoluble organic uv-screening agent and/or an insoluble inorganic uv- screening agent |
WO2016030839A1 (en) | 2014-08-28 | 2016-03-03 | L'oreal | Gel composition and gel comprising a uv filter |
WO2016083404A1 (en) | 2014-11-24 | 2016-06-02 | L'oreal | Cosmetic composition comprising a synthetic phyllosilicate and a polyol and/or a uv filter |
WO2016198581A1 (en) | 2015-06-11 | 2016-12-15 | L'oreal | Composition comprising a uv-screening agent, an anionic crosslinked hydrophilic polymer, a surfactant having an hlb less than or equal to 5 and a silicone copolymer |
WO2019096960A1 (en) | 2017-11-15 | 2019-05-23 | L'oreal | Compositions comprising at least one acrylic polymer and at least one insoluble organic screening agent |
FR3083093A1 (en) | 2018-06-28 | 2020-01-03 | L'oreal | PHOTOPROTECTOR COMPOSITION COMPRISING COLLOIDAL SILICA PARTICLES |
FR3090329A1 (en) | 2018-12-21 | 2020-06-26 | L'oreal | Composition comprising a UV filter, an anionic crosslinked hydrophilic polymer, a surfactant having an HLB less than or equal to 5 and a non-volatile alkane |
FR3103705A1 (en) | 2019-11-29 | 2021-06-04 | L'oreal | A composition comprising a UV filter, a block polymer containing a phosphonic acid group and a hydrocarbon oil |
FR3103704A1 (en) | 2019-11-29 | 2021-06-04 | L'oreal | Composition comprising a UV filter, an ethylenic polymer with a phosphonic acid group and a hydrocarbon oil |
Also Published As
Publication number | Publication date |
---|---|
CN1073947A (en) | 1993-07-07 |
PT101101A (en) | 1994-02-28 |
AU3072292A (en) | 1993-06-28 |
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