EP4326251A1 - Compositions comprising cannabidiol and, optionally, bisabolol - Google Patents
Compositions comprising cannabidiol and, optionally, bisabololInfo
- Publication number
- EP4326251A1 EP4326251A1 EP21724198.3A EP21724198A EP4326251A1 EP 4326251 A1 EP4326251 A1 EP 4326251A1 EP 21724198 A EP21724198 A EP 21724198A EP 4326251 A1 EP4326251 A1 EP 4326251A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- peg
- sodium
- dimethicone
- acid
- cannabidiol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 81
- RGZSQWQPBWRIAQ-CABCVRRESA-N (-)-alpha-Bisabolol Chemical compound CC(C)=CCC[C@](C)(O)[C@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-CABCVRRESA-N 0.000 title claims abstract description 48
- RGZSQWQPBWRIAQ-LSDHHAIUSA-N alpha-Bisabolol Natural products CC(C)=CCC[C@@](C)(O)[C@@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-LSDHHAIUSA-N 0.000 title claims abstract description 43
- 229940036350 bisabolol Drugs 0.000 title claims abstract description 39
- QHMBSVQNZZTUGM-UHFFFAOYSA-N Trans-Cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 229950011318 cannabidiol Drugs 0.000 title claims abstract description 38
- ZTGXAWYVTLUPDT-UHFFFAOYSA-N cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CC=C(C)C1 ZTGXAWYVTLUPDT-UHFFFAOYSA-N 0.000 title claims abstract description 38
- PCXRACLQFPRCBB-ZWKOTPCHSA-N dihydrocannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)C)CCC(C)=C1 PCXRACLQFPRCBB-ZWKOTPCHSA-N 0.000 title claims abstract description 38
- WTVHAMTYZJGJLJ-UHFFFAOYSA-N (+)-(4S,8R)-8-epi-beta-bisabolol Natural products CC(C)=CCCC(C)C1(O)CCC(C)=CC1 WTVHAMTYZJGJLJ-UHFFFAOYSA-N 0.000 title claims abstract description 37
- HHGZABIIYIWLGA-UHFFFAOYSA-N bisabolol Natural products CC1CCC(C(C)(O)CCC=C(C)C)CC1 HHGZABIIYIWLGA-UHFFFAOYSA-N 0.000 title claims abstract description 37
- QHMBSVQNZZTUGM-ZWKOTPCHSA-N cannabidiol Chemical compound OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-ZWKOTPCHSA-N 0.000 title claims abstract description 37
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- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 8
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- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 2
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- 238000002560 therapeutic procedure Methods 0.000 claims 6
- XMGQYMWWDOXHJM-JTQLQIEISA-N (+)-α-limonene Chemical compound CC(=C)[C@@H]1CCC(C)=CC1 XMGQYMWWDOXHJM-JTQLQIEISA-N 0.000 claims 2
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- -1 terpene phenols Chemical class 0.000 description 194
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- 229910052700 potassium Inorganic materials 0.000 description 75
- 229910019142 PO4 Inorganic materials 0.000 description 65
- 235000021317 phosphate Nutrition 0.000 description 65
- 239000010452 phosphate Substances 0.000 description 62
- 229920006037 cross link polymer Polymers 0.000 description 60
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 56
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- 239000000194 fatty acid Substances 0.000 description 34
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- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical compound [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 description 1
- 229910010271 silicon carbide Inorganic materials 0.000 description 1
- 229920005573 silicon-containing polymer Polymers 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 229940083037 simethicone Drugs 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
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- ZVAMTQAGWMKBDA-UHFFFAOYSA-M sodium 2-[methyl(16-methylheptadecanoyl)amino]ethanesulfonate Chemical compound [Na+].CC(C)CCCCCCCCCCCCCCC(=O)N(C)CCS([O-])(=O)=O ZVAMTQAGWMKBDA-UHFFFAOYSA-M 0.000 description 1
- KHQIUIBOIDUCHG-UHFFFAOYSA-M sodium 2-hydroxy-3-[2-hydroxyethyl-[2-(octadecanoylamino)ethyl]amino]propane-1-sulfonate Chemical compound CCCCCCCCCCCCCCCCCC(=O)NCCN(CCO)CC(CS(=O)(=O)[O-])O.[Na+] KHQIUIBOIDUCHG-UHFFFAOYSA-M 0.000 description 1
- GCRIFWNODNDUCG-UHFFFAOYSA-M sodium 2-hydroxy-3-[2-hydroxyethyl-[2-(octanoylamino)ethyl]amino]propane-1-sulfonate Chemical compound [Na+].CCCCCCCC(=O)NCCN(CCO)CC(O)CS([O-])(=O)=O GCRIFWNODNDUCG-UHFFFAOYSA-M 0.000 description 1
- NSOYBHZIQVUIDA-UHFFFAOYSA-M sodium 3-[2-(decanoylamino)ethyl-(2-hydroxyethyl)amino]-2-hydroxypropane-1-sulfonate Chemical compound CCCCCCCCCC(=O)NCCN(CCO)CC(CS(=O)(=O)[O-])O.[Na+] NSOYBHZIQVUIDA-UHFFFAOYSA-M 0.000 description 1
- CQQFHQIXAHHOHI-UHFFFAOYSA-M sodium 3-[2-(dodecanoylamino)ethyl-(2-hydroxyethyl)amino]-2-hydroxypropane-1-sulfonate Chemical compound CCCCCCCCCCCC(=O)NCCN(CCO)CC(CS(=O)(=O)[O-])O.[Na+] CQQFHQIXAHHOHI-UHFFFAOYSA-M 0.000 description 1
- 229940031688 sodium c14-16 olefin sulfonate Drugs 0.000 description 1
- 229960005480 sodium caprylate Drugs 0.000 description 1
- 229940114536 sodium capryloamphopropionate Drugs 0.000 description 1
- 229940080236 sodium cetyl sulfate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940080272 sodium coco-sulfate Drugs 0.000 description 1
- 229940080279 sodium cocoate Drugs 0.000 description 1
- 229940079781 sodium cocoyl glutamate Drugs 0.000 description 1
- 229940065859 sodium cocoyl glycinate Drugs 0.000 description 1
- 229940079776 sodium cocoyl isethionate Drugs 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- BTURAGWYSMTVOW-UHFFFAOYSA-M sodium dodecanoate Chemical compound [Na+].CCCCCCCCCCCC([O-])=O BTURAGWYSMTVOW-UHFFFAOYSA-M 0.000 description 1
- 229940080264 sodium dodecylbenzenesulfonate Drugs 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- 229940091855 sodium lauraminopropionate Drugs 0.000 description 1
- 229940082004 sodium laurate Drugs 0.000 description 1
- 229940102544 sodium laureth-13 carboxylate Drugs 0.000 description 1
- 229940078455 sodium lauroyl aspartate Drugs 0.000 description 1
- 229940014786 sodium lauroyl hydroxypropyl sulfonate Drugs 0.000 description 1
- 229940048106 sodium lauroyl isethionate Drugs 0.000 description 1
- 229940007636 sodium lauroyl methyl isethionate Drugs 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 229940045885 sodium lauroyl sarcosinate Drugs 0.000 description 1
- 229940045790 sodium lauryl glycol carboxylate Drugs 0.000 description 1
- 229940075560 sodium lauryl sulfoacetate Drugs 0.000 description 1
- 229940048107 sodium methyl 2-sulfolaurate Drugs 0.000 description 1
- 229940048109 sodium methyl cocoyl taurate Drugs 0.000 description 1
- MDSQKJDNWUMBQQ-UHFFFAOYSA-M sodium myreth sulfate Chemical compound [Na+].CCCCCCCCCCCCCCOCCOCCOCCOS([O-])(=O)=O MDSQKJDNWUMBQQ-UHFFFAOYSA-M 0.000 description 1
- 229940045845 sodium myristate Drugs 0.000 description 1
- 229940077092 sodium myristoyl glutamate Drugs 0.000 description 1
- 229940045888 sodium myristoyl isethionate Drugs 0.000 description 1
- 229940060304 sodium myristoyl sarcosinate Drugs 0.000 description 1
- 229950005425 sodium myristyl sulfate Drugs 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 1
- 229940080315 sodium octoxynol-2 ethane sulfonate Drugs 0.000 description 1
- 229940023574 sodium palmate Drugs 0.000 description 1
- 229940045870 sodium palmitate Drugs 0.000 description 1
- 229940065179 sodium propoxyhydroxypropyl thiosulfate silica Drugs 0.000 description 1
- IJRHDFLHUATAOS-DPMBMXLASA-M sodium ricinoleate Chemical compound [Na+].CCCCCC[C@@H](O)C\C=C/CCCCCCCC([O-])=O IJRHDFLHUATAOS-DPMBMXLASA-M 0.000 description 1
- 229940080350 sodium stearate Drugs 0.000 description 1
- 229940066718 sodium stearoamphoacetate Drugs 0.000 description 1
- 229940045898 sodium stearoyl glutamate Drugs 0.000 description 1
- 229940045905 sodium tallowate Drugs 0.000 description 1
- 229940104256 sodium taurate Drugs 0.000 description 1
- 229940102541 sodium trideceth sulfate Drugs 0.000 description 1
- FCBUGCHAVCFTHW-NTISSMGPSA-N sodium;(2s)-2-(tetradecanoylamino)pentanedioic acid Chemical compound [Na].CCCCCCCCCCCCCC(=O)N[C@H](C(O)=O)CCC(O)=O FCBUGCHAVCFTHW-NTISSMGPSA-N 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- WNFHGZLVUQBPMA-MHFWOIHZSA-M sodium;(2s,3s,4s,5s)-2,3,4,5-tetrahydroxy-6-oxohexanoate Chemical compound [Na+].O=C[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)C([O-])=O WNFHGZLVUQBPMA-MHFWOIHZSA-M 0.000 description 1
- KLIFRVSZGDONER-FERBBOLQSA-M sodium;(4s)-4-(hexadecanoylamino)-5-hydroxy-5-oxopentanoate Chemical compound [H+].[Na+].CCCCCCCCCCCCCCCC(=O)N[C@H](C([O-])=O)CCC([O-])=O KLIFRVSZGDONER-FERBBOLQSA-M 0.000 description 1
- KDHFCTLPQJQDQI-BDQAORGHSA-M sodium;(4s)-4-amino-5-octadecanoyloxy-5-oxopentanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC(=O)[C@@H](N)CCC([O-])=O KDHFCTLPQJQDQI-BDQAORGHSA-M 0.000 description 1
- BCGXTKYOBWQPCN-PPHPATTJSA-M sodium;(4s)-5-hydroxy-4-(octanoylamino)-5-oxopentanoate Chemical compound [H+].[Na+].CCCCCCCC(=O)N[C@H](C([O-])=O)CCC([O-])=O BCGXTKYOBWQPCN-PPHPATTJSA-M 0.000 description 1
- WYPBVHPKMJYUEO-NBTZWHCOSA-M sodium;(9z,12z)-octadeca-9,12-dienoate Chemical compound [Na+].CCCCC\C=C/C\C=C/CCCCCCCC([O-])=O WYPBVHPKMJYUEO-NBTZWHCOSA-M 0.000 description 1
- NTVDGBKMGBRCKB-UHFFFAOYSA-M sodium;12-hydroxyoctadecanoate Chemical compound [Na+].CCCCCCC(O)CCCCCCCCCCC([O-])=O NTVDGBKMGBRCKB-UHFFFAOYSA-M 0.000 description 1
- FRHNXUKHAUWMOQ-UHFFFAOYSA-M sodium;16-methylheptadecanoate Chemical compound [Na+].CC(C)CCCCCCCCCCCCCCC([O-])=O FRHNXUKHAUWMOQ-UHFFFAOYSA-M 0.000 description 1
- QEFQJSBCERPHSO-UHFFFAOYSA-M sodium;2-(2-decoxyethoxy)acetate Chemical compound [Na+].CCCCCCCCCCOCCOCC([O-])=O QEFQJSBCERPHSO-UHFFFAOYSA-M 0.000 description 1
- XBBJMKQUXMZDPR-UHFFFAOYSA-M sodium;2-(2-dodecoxyethoxy)acetate Chemical compound [Na+].CCCCCCCCCCCCOCCOCC([O-])=O XBBJMKQUXMZDPR-UHFFFAOYSA-M 0.000 description 1
- UIGBPGNEWMRLGK-UHFFFAOYSA-M sodium;2-(2-hydroxydodecoxy)acetate Chemical compound [Na+].CCCCCCCCCCC(O)COCC([O-])=O UIGBPGNEWMRLGK-UHFFFAOYSA-M 0.000 description 1
- IKGKWKGYFJBGQJ-UHFFFAOYSA-M sodium;2-(dodecanoylamino)acetate Chemical compound [Na+].CCCCCCCCCCCC(=O)NCC([O-])=O IKGKWKGYFJBGQJ-UHFFFAOYSA-M 0.000 description 1
- BCISDMIQYBCHAT-UHFFFAOYSA-M sodium;2-(dodecanoylamino)ethanesulfonate Chemical compound [Na+].CCCCCCCCCCCC(=O)NCCS([O-])(=O)=O BCISDMIQYBCHAT-UHFFFAOYSA-M 0.000 description 1
- ZUFONQSOSYEWCN-UHFFFAOYSA-M sodium;2-(methylamino)acetate Chemical compound [Na+].CNCC([O-])=O ZUFONQSOSYEWCN-UHFFFAOYSA-M 0.000 description 1
- KKDONKAYVYTWGY-UHFFFAOYSA-M sodium;2-(methylamino)ethanesulfonate Chemical compound [Na+].CNCCS([O-])(=O)=O KKDONKAYVYTWGY-UHFFFAOYSA-M 0.000 description 1
- MCFLGJDKSROECH-KVVVOXFISA-M sodium;2-[(z)-octadec-9-enoyl]oxyethanesulfonate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC(=O)OCCS([O-])(=O)=O MCFLGJDKSROECH-KVVVOXFISA-M 0.000 description 1
- WIMLNTLINAPZNO-UHFFFAOYSA-M sodium;2-[1-(1-propoxypropan-2-yloxy)propan-2-yloxy]acetate Chemical compound [Na+].CCCOCC(C)OCC(C)OCC([O-])=O WIMLNTLINAPZNO-UHFFFAOYSA-M 0.000 description 1
- KLYDBHUQNXKACI-UHFFFAOYSA-M sodium;2-[2-(2-tridecoxyethoxy)ethoxy]ethyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCOCCOCCOCCOS([O-])(=O)=O KLYDBHUQNXKACI-UHFFFAOYSA-M 0.000 description 1
- UOZFSLAMWIZUEN-UHFFFAOYSA-M sodium;2-[2-(decanoylamino)ethyl-(2-hydroxyethyl)amino]acetate Chemical compound [Na+].CCCCCCCCCC(=O)NCCN(CCO)CC([O-])=O UOZFSLAMWIZUEN-UHFFFAOYSA-M 0.000 description 1
- BVAQZSBSTBYZPX-UHFFFAOYSA-M sodium;2-[2-(dodecanoylamino)ethyl-(2-hydroxyethyl)-[2-hydroxy-3-[hydroxy(oxido)phosphoryl]oxypropyl]azaniumyl]acetate Chemical compound [Na+].CCCCCCCCCCCC(=O)NCC[N+](CCO)(CC([O-])=O)CC(O)COP(O)([O-])=O BVAQZSBSTBYZPX-UHFFFAOYSA-M 0.000 description 1
- HVFAVOFILADWEZ-UHFFFAOYSA-M sodium;2-[2-(dodecanoylamino)ethyl-(2-hydroxyethyl)amino]acetate Chemical compound [Na+].CCCCCCCCCCCC(=O)NCCN(CCO)CC([O-])=O HVFAVOFILADWEZ-UHFFFAOYSA-M 0.000 description 1
- NHAKWXFEEKSYPL-UHFFFAOYSA-M sodium;2-[2-[2-(2-hexoxyethoxy)ethoxy]ethoxy]acetate Chemical compound [Na+].CCCCCCOCCOCCOCCOCC([O-])=O NHAKWXFEEKSYPL-UHFFFAOYSA-M 0.000 description 1
- CEZNRMAOOQIHOP-UHFFFAOYSA-M sodium;2-[2-[2-(2-tridecoxyethoxy)ethoxy]ethoxy]acetate Chemical compound [Na+].CCCCCCCCCCCCCOCCOCCOCCOCC([O-])=O CEZNRMAOOQIHOP-UHFFFAOYSA-M 0.000 description 1
- ACZURWACGCXVLA-UHFFFAOYSA-M sodium;2-[2-[2-[2-[2-[2-[2-[2-(2-octoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetate Chemical compound [Na+].CCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCC([O-])=O ACZURWACGCXVLA-UHFFFAOYSA-M 0.000 description 1
- FCZYGJBVLGLYQU-UHFFFAOYSA-M sodium;2-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethoxy]ethanesulfonate Chemical compound [Na+].CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCS([O-])(=O)=O)C=C1 FCZYGJBVLGLYQU-UHFFFAOYSA-M 0.000 description 1
- ZKBGPOVFSMIXBF-UHFFFAOYSA-M sodium;2-[2-hydroxyethyl-[2-(octadecanoylamino)ethyl]amino]acetate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)NCCN(CCO)CC([O-])=O ZKBGPOVFSMIXBF-UHFFFAOYSA-M 0.000 description 1
- YASOXPMFSCKYDU-UHFFFAOYSA-M sodium;2-[2-hydroxyethyl-[2-(octanoylamino)ethyl]amino]acetate Chemical compound [Na+].CCCCCCCC(=O)NCCN(CCO)CC([O-])=O YASOXPMFSCKYDU-UHFFFAOYSA-M 0.000 description 1
- IDXHDUOOTUFFOX-UHFFFAOYSA-M sodium;2-[2-hydroxyethyl-[2-(tetradecanoylamino)ethyl]amino]acetate Chemical compound [Na+].CCCCCCCCCCCCCC(=O)NCCN(CCO)CC([O-])=O IDXHDUOOTUFFOX-UHFFFAOYSA-M 0.000 description 1
- UKWMFBTXDPSTCV-UHFFFAOYSA-M sodium;2-[decanoyl(methyl)amino]ethanesulfonate Chemical compound [Na+].CCCCCCCCCC(=O)N(C)CCS([O-])(=O)=O UKWMFBTXDPSTCV-UHFFFAOYSA-M 0.000 description 1
- CAVXVRQDZKMZDB-UHFFFAOYSA-M sodium;2-[dodecanoyl(methyl)amino]ethanesulfonate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CCS([O-])(=O)=O CAVXVRQDZKMZDB-UHFFFAOYSA-M 0.000 description 1
- AUHKUMFBHOJIMU-UHFFFAOYSA-M sodium;2-[hexadecanoyl(methyl)amino]acetate Chemical compound [Na+].CCCCCCCCCCCCCCCC(=O)N(C)CC([O-])=O AUHKUMFBHOJIMU-UHFFFAOYSA-M 0.000 description 1
- PWWJJDVDTKXWOF-UHFFFAOYSA-M sodium;2-[hexadecanoyl(methyl)amino]ethanesulfonate Chemical compound [Na+].CCCCCCCCCCCCCCCC(=O)N(C)CCS([O-])(=O)=O PWWJJDVDTKXWOF-UHFFFAOYSA-M 0.000 description 1
- KHCOJQDJOCNUGV-UHFFFAOYSA-M sodium;2-[methyl(tetradecanoyl)amino]acetate Chemical compound [Na+].CCCCCCCCCCCCCC(=O)N(C)CC([O-])=O KHCOJQDJOCNUGV-UHFFFAOYSA-M 0.000 description 1
- IZWPGJFSBABFGL-GMFCBQQYSA-M sodium;2-[methyl-[(z)-octadec-9-enoyl]amino]ethanesulfonate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC(=O)N(C)CCS([O-])(=O)=O IZWPGJFSBABFGL-GMFCBQQYSA-M 0.000 description 1
- GWLWWNLFFNJPDP-UHFFFAOYSA-M sodium;2-aminoethanesulfonate Chemical compound [Na+].NCCS([O-])(=O)=O GWLWWNLFFNJPDP-UHFFFAOYSA-M 0.000 description 1
- HLGSTHXLGGPEDB-UHFFFAOYSA-M sodium;2-aminoethanesulfonate;dodecanoic acid Chemical compound [Na+].NCCS(O)(=O)=O.CCCCCCCCCCCC([O-])=O HLGSTHXLGGPEDB-UHFFFAOYSA-M 0.000 description 1
- NVIZQHFCDBQNPH-UHFFFAOYSA-M sodium;2-dodecanoyloxypropane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCC(=O)OC(C)CS([O-])(=O)=O NVIZQHFCDBQNPH-UHFFFAOYSA-M 0.000 description 1
- UAJTZZNRJCKXJN-UHFFFAOYSA-M sodium;2-dodecoxy-2-oxoethanesulfonate Chemical compound [Na+].CCCCCCCCCCCCOC(=O)CS([O-])(=O)=O UAJTZZNRJCKXJN-UHFFFAOYSA-M 0.000 description 1
- HPHSQXYITTYVEY-KVVVOXFISA-M sodium;2-hydroxy-3-[2-hydroxyethyl-[2-[[(z)-octadec-9-enoyl]amino]ethyl]amino]propane-1-sulfonate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC(=O)NCCN(CCO)CC(O)CS([O-])(=O)=O HPHSQXYITTYVEY-KVVVOXFISA-M 0.000 description 1
- UXJCQISMJSCAOK-UHFFFAOYSA-M sodium;2-hydroxy-3-octoxypropane-1-sulfonate Chemical compound [Na+].CCCCCCCCOCC(O)CS([O-])(=O)=O UXJCQISMJSCAOK-UHFFFAOYSA-M 0.000 description 1
- WEXQJKLTLYEHLQ-UHFFFAOYSA-M sodium;2-tetradecanoyloxyethanesulfonate Chemical compound [Na+].CCCCCCCCCCCCCC(=O)OCCS([O-])(=O)=O WEXQJKLTLYEHLQ-UHFFFAOYSA-M 0.000 description 1
- HWCHICTXVOMIIF-UHFFFAOYSA-M sodium;3-(dodecylamino)propanoate Chemical compound [Na+].CCCCCCCCCCCCNCCC([O-])=O HWCHICTXVOMIIF-UHFFFAOYSA-M 0.000 description 1
- LLKGTXLYJMUQJX-UHFFFAOYSA-M sodium;3-[2-carboxyethyl(dodecyl)amino]propanoate Chemical compound [Na+].CCCCCCCCCCCCN(CCC(O)=O)CCC([O-])=O LLKGTXLYJMUQJX-UHFFFAOYSA-M 0.000 description 1
- WMLIJOUAGPIENT-UHFFFAOYSA-M sodium;3-[2-hydroxyethyl-[2-(octanoylamino)ethyl]amino]propanoate Chemical compound [Na+].CCCCCCCC(=O)NCCN(CCO)CCC([O-])=O WMLIJOUAGPIENT-UHFFFAOYSA-M 0.000 description 1
- LOBXNKKFDKXXQW-UHFFFAOYSA-M sodium;3-[dodecanoyl(methyl)amino]propanoate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CCC([O-])=O LOBXNKKFDKXXQW-UHFFFAOYSA-M 0.000 description 1
- DUXXGJTXFHUORE-UHFFFAOYSA-M sodium;4-tridecylbenzenesulfonate Chemical compound [Na+].CCCCCCCCCCCCCC1=CC=C(S([O-])(=O)=O)C=C1 DUXXGJTXFHUORE-UHFFFAOYSA-M 0.000 description 1
- CRPCXAMJWCDHFM-UHFFFAOYSA-M sodium;5-oxopyrrolidine-2-carboxylate Chemical compound [Na+].[O-]C(=O)C1CCC(=O)N1 CRPCXAMJWCDHFM-UHFFFAOYSA-M 0.000 description 1
- MWZFQMUXPSUDJQ-KVVVOXFISA-M sodium;[(z)-octadec-9-enyl] sulfate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCCOS([O-])(=O)=O MWZFQMUXPSUDJQ-KVVVOXFISA-M 0.000 description 1
- FIWQZURFGYXCEO-UHFFFAOYSA-M sodium;decanoate Chemical compound [Na+].CCCCCCCCCC([O-])=O FIWQZURFGYXCEO-UHFFFAOYSA-M 0.000 description 1
- GGXKEBACDBNFAF-UHFFFAOYSA-M sodium;hexadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCC([O-])=O GGXKEBACDBNFAF-UHFFFAOYSA-M 0.000 description 1
- GGHPAKFFUZUEKL-UHFFFAOYSA-M sodium;hexadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCOS([O-])(=O)=O GGHPAKFFUZUEKL-UHFFFAOYSA-M 0.000 description 1
- NWZBFJYXRGSRGD-UHFFFAOYSA-M sodium;octadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCCCOS([O-])(=O)=O NWZBFJYXRGSRGD-UHFFFAOYSA-M 0.000 description 1
- HRQDCDQDOPSGBR-UHFFFAOYSA-M sodium;octane-1-sulfonate Chemical compound [Na+].CCCCCCCCS([O-])(=O)=O HRQDCDQDOPSGBR-UHFFFAOYSA-M 0.000 description 1
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- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Definitions
- the present invention refers to the area of so-called cosmeceuticals and concerns compositions comprising or consisting of Cannabidiol and optionally Bisabolol for a broad spectrum of skin care applications.
- CN 107811190 A (YUNNAN HANMUSEN BIOL TECH) refers to an anti-inflammatory cream, comprising a cannabis sativa leaf extract enriched in Bisabolol and Cannabidiol.
- CA 2971197 A discloses a pharmaceutical topical composi tion comprising Cannabidiol (CBD) and tetrahydrocannabinol (THC) in a molar ratio of 1:1.
- CBD Cannabidiol
- THC tetrahydrocannabinol
- the compositions may include Bisabolol and tocopheryl acetate
- US 2018042890 A (ONE WORLD CANNABIS) refers to a similar composition for treat ing inflammatory skin diseases.
- a first object of the present invention refers to a composition comprising or consist ing of
- Another object of the present invention refers to a composition comprising or con sisting of (a) Cannabidiol and optionally
- Another object of the present invention refers to a composition comprising or con- sisting of
- Another object of the present invention refers to a composition comprising or con sisting of
- Another object of the present invention refers to a composition comprising or con sisting of
- Another object of the present invention refers to a composition comprising or con sisting of (a) Cannabidiol and optionally
- Cannabidiol in general and mixtures of Canna bidiol and Bisabolol in particular are strong modulators of CB2 receptors, support expression of beta-serotonin, modulate expression of the stress-mediator cortisol, show excellent anti- oxidative protection of human cells, modulate and particular down-regulate expression of cytokines like IL8 and PGE2, stimulate hyaluronic acid related gene expression to repair dis turbed or damaged skin barrier and modulate und particular down-regulate sebum produc tion in the sebum glands. Therefore, the compositions according to the present invention represent an "all-in-one active" with regard to the treatment of dysfunctions of human skin triggered in particular by stress.
- Cannabidiol belongs to the cannabinoids representing transformation products and synthetic analogues of some terpene phenols found mainly in the hemp plant (Cannabis sativa or Cannabis indi- ca). Research on cannabinoids led to the discovery of the endocannabinoid system. Phyto- cannabinoids are substances that have similar pharmacological properties to those found in the body. Recent research shows that other plants also produce phytocannabinoids that act on the endocannabinoid system in the same way as the cannabinoids of the hemp plant.
- cannabinoids are used in a variety of applications, such as neuropathic pain and spasticity (preparations made from cannabis flowers), loss of appetite in HIV/AIDS and nau sea and vomiting under chemotherapy (nabilone, dronabinol), and certain forms of childhood epilepsy.
- Cannabidiol (CBD) can be of natural or preferably synthetic origin.
- Synthetic cannabinoids can be produced semi-synthetically, i.e. from natural cannabinoids, or preferably fully synthetically from simple basic substances such as for exam ple limonene.
- Synthetic cannabinoids are used in medicine and in neuroscience to under stand the effects of cannabinoids in the brain.
- a preferred example is a synthetic Cannabidiol with a purity of about 98 % which is sold under the trademark "SymDStressTM".
- Bisabolol (component b) is a monocyclic sesquiterpen alcohol.
- component (a) is an alpha-Bisabolol mixture.
- component (a) is an alpha-Bisabolol isomer or an alpha-Bisabolol mix ture.
- component (a) is a single alpha-Bisabolol isomer or a mixture of alpha- Bisabolol isomers. The following shows as an example the structure of (-)-alpha-Bisabolol.
- the present invention also encompasses as component (a) natural sources containing said monocyclic sesquiterpenes in general and Bisabolol(s) in particular such as essential oils.
- the preferred is chamonille oil and in particular the essential oil obtained for example by water steam distillation of Matricaria chamomitta, or the plant that is known as Manzana Chamonilla, which is particular rich in Bisabolol.
- the essential oil of candeia tree Vanillosmopsis erythropappa
- Alpha-Bisabolol is commercially available for example under the trademark Dragosantol® 100 (Symrise AG).
- Bisabolol(s) produced biotechnologically. Also included in the inven tion are preparations consisting predominantly of Bisabolol and a small amount of at most 5 wt. -percent and typically about 1 wt.-percent of an additive. These additives may, for exam ple, be a ginger extract or tocopherol. Corresponding products are commercially available under the name SymRelief® (Symrise AG). Finally, said monocyclic sesquiterpen alcohol can be of natural or synthetic origin.
- compositions according to the present invention comprising both components may contain Cannabidiol and Bisabolol in ratios by weight of from about 0,1:99,09 to about 20:80, more preferably from about 1:99 to about 10:90 and most preferably from about 2:98 to about 5:95.
- These mixtures (including 1 wt.-percent amount of tocopherol) are sold for ex ample under the trademark SymDStressTM 100 (Symrise).
- compositions according to the present invention can be administered either topically or by oral uptake.
- compositions topical to human skin they are usually formulated as kinds of cosmetic preparations, particularly skin care products such as for ex ample creams, lotions, emulsions, mousses, sprays and the like.
- skin care products such as for ex ample creams, lotions, emulsions, mousses, sprays and the like.
- the preferred galenic form is a capsule.
- the formulations may comprise the compositions according to the present invention - Cannabidiol or mixture of Cannabidiol and Bisabolol - in a working amount of from for example about 0.0001 to about 1 wt.-percent, preferably from about 0.01 to about 0.5 wt.-percent.
- the preparations may also contain antidandruff agents, irritation-preventing agents, irritation-inhibiting agents, antioxidants, adstringents, perspiration-inhibiting agents, anti-itch agents, antiseptic agents, ant-statics, binders, buffers, carrier materials, chelating agents, cell stimulants, cleansing agents, care agents, deodorizing agents, antiperspirants, softeners, emulsifiers, enzymes, essential oils, fibres, film-forming agents, fixatives, foam-forming agents, foam stabilizers, substances for preventing foaming, foam boosters, gelling agents, gel-forming agents, hair care agents, hair-setting agents, hair-straightening agents, moisture- donating agents, moisturizing substances, moisture-retaining substances, bleaching agents, strengthening agents, stain-removing agents, optically brightening agents, impregnating agents, dirt-repellent agents, friction-reducing agents, lubricants, moisturizing creams, oint ments, opacifying agents, plasticizing
- auxiliaries and additives are anionic and/or amphoteric or zwitterionic sur factants.
- Non-ionic and cationic surfactants can be also present in the composition. Suitable examples are mentioned along with the paragraph dealing with emulsifiers.
- Typical examples for anionic and zwitterionic surfactants encompass: Almondami- dopropylamine Oxide, Almondamidopropyl Betaine, Aminopropyl Laurylglutamine, Ammoni um 02-15 Alkyl Sulfate, Ammonium 02-16 Alkyl Sulfate, Ammonium Capryleth Sulfate, Ammonium Cocomonoglyceride Sulfate, Ammonium Coco-Sulfate, Ammonium Cocoyl Isethionate, Ammonium Cocoyl Sarcosinate, Ammonium 02-15 Pareth Sulfate, Ammonium C9-10 Perfluoroalkylsulfonate, Ammonium Dinonyl Sulfosuccinate, Ammonium Dodecylben- zenesulfonate, Ammonium Isostearate, Ammonium Laureth-6 Carboxylate, Ammonium Lau- reth-8 Carboxylate, Ammonium Laureth Sulfate
- the percentage content of surfactants in the preparations may be from 0.1 to 10% by weight and is preferably from 0.5 to 5% by weight, based on the preparation.
- Suitable oil bodies which form constituents of the O/W emulsions, are, for example, Guerbet alcohols based on fatty alcohols having 6 to 18, preferably 8 to 10, carbon atoms, esters of linear C6-C22-fatty acids with linear or branched C6-C22-fatty alcohols or esters of branched C6-C 13-carboxylic acids with linear or branched C6-C 22-fatty alcohols, such as, for example, myristyl myristate, myristyl palmitate, myristyl stearate, myristyl isostearate, myristyl oleate, myristyl behenate, myristyl erucate, cetyl myristate, cetyl palmitate, cetyl stearate, cetyl isostearate, cetyl oleate, cetyl behenate, cetyl erucate, stearyl myristate, steary
- esters of linear C6-C22-fatty acids with branched alcohols in particular 2-ethylhexanol, esters of C18-C38- alkylhydroxy carboxylic acids with linear or branched C6-C 22-fatty alcohols, in particular Dioctyl Malate, esters of linear and/or branched fatty acids with polyhydric alcohols (such as, for example, propylene glycol, dimerdiol or trimertriol) and/or Guerbet alcohols, triglycerides based on C6 -Cio-fatty acids, liquid mono-/di-/triglyceride mixtures based on C6-Cis-fatty acids, esters of C6- C22-fatty al- cohols and/or Guerbet alcohols with aromatic carboxylic acids, in particular benzoic acid, es ters of C2- Ci2-dicarboxylic acids with linear or branched alcohols having 1 to 22 carbon at oms or polyo
- Finsolv® TN linear or branched, sym metrical or asymmetrical dialkyl ethers having 6 to 22 carbon atoms per alkyl group, such as, for example, dicaprylyl ether (Cetiol® OE), ring-opening products of epoxidized fatty acid esters with polyols, silicone oils (cyclomethicones, silicone methicone grades, etc.) and/or aliphatic or naphthenic hydrocarbons, such as, for example, squalane, squalene or dialkylcy- clohexanes.
- dicaprylyl ether such as, for example, dicaprylyl ether (Cetiol® OE), ring-opening products of epoxidized fatty acid esters with polyols, silicone oils (cyclomethicones, silicone methicone grades, etc.) and/or aliphatic or naphthenic hydrocarbons, such as, for example, s
- non-ionic or cationic surfactants may also be added to the preparations as emulsifiers, including for example:
- polyol esters and, in particular, polyglycerol esters such as, for example, polyglycerol polyricinoleate, polyglycerol poly-12-hydroxystearate or polyglycerol dimerate isos tearate. Mixtures of compounds from several of these classes are also suitable;
- Partial glycerides are hydroxystearic acid monoglyceride, hydroxystearic acid diglyceride, isostearic acid monoglyceride, isostearic acid diglyceride, oleic acid monoglyceride, oleic acid diglyceride, ricinoleic acid monoglycer ide, ricinoleic acid diglyceride, linoleic acid monoglyceride, linoleic acid diglyceride, linolenic acid monoglyceride, linolenic acid diglyceride, erucic acid monoglyceride, erucic acid diglyc eride, tartaric acid monoglyceride, tartaric acid diglyceride, citric acid monoglyceride, citric acid diglyceride, malic acid monoglyceride, malic acid diglyceride and technical mixtures thereof which may still contain small quantities of
- Sorbitan esters are sorbitan monoisostearate, sorbitan ses- quiisostearate, sorbitan diisostearate, sorbitan triisostearate, sorbitan monooleate, sorbitan sesquioleate, sorbitan dioleate, sorbitan trioleate, sorbitan monoerucate, sorbitan sesquieru- cate, sorbitan dierucate, sorbitan trierucate, sorbitan monoricinoleate, sorbitan sesquiricino- leate, sorbitan diricinoleate, sorbitan triricinoleate, sorbitan monohydroxystearate, sorbitan sesquihydroxystearate, sorbitan dihydroxystearate, sorbitan trihydroxystearate, sorbitan monotartrate, sorbitan sesquitartrate, sorbitan ditartrate, sorbitan tritartrate, sorbitan monotartrate, sorb
- Polyglycerol esters are Polyglyceryl- 2 Dipolyhydroxystearate (Dehymuls ® PGPH), Polyglycerin-3-Diisostearate (Lameform ® TGI), Polyglyceryl-4 Isostearate (Isolan ® Gl 34), Polyglyceryl-3 Oleate, Diisostearoyl Polyglyceryl-3 Diisostearate (Isolan® PDI), Polyglyceryl-3 Methylglucose Distearate (Tego Care ® 450), Poly- glyceryl-3 Beeswax (Cera Beilina ® ), Polyglyceryl-4 Caprate (Polyglycerol Caprate T2010/90), Polyglyceryl-3 Cetyl Ether (Chimexane ® NL),
- polystyrene resin examples include the mono-, di- and triesters of trimethylol propane or pentaerythritol with lauric acid, cocofatty acid, tallow fatty acid, pal mitic acid, stearic acid, oleic acid, behenic acid and the like optionally reacted with 1 to 30 mol ethylene oxide.
- Cationically active surfactants comprise the hydropho bic high molecular group required for the surface activity in the cation by dissociation in aqueous solution.
- a group of important representatives of the cationic surfactants are the tetraalkyl ammonium salts of the general formula: (R 1 R 2 R 3 R 4 N + ) X .
- R1 stands for Ci-Cs alk(en)yl, R 2 , R 3 and R 4 , independently of each other, for alk(en)yl radicals having 1 to 22 car bon atoms.
- X is a counter ion, preferably selected from the group of the halides, alkyl sulfates and alkyl carbonates.
- Cationic surfactants in which the nitrogen group is substituted with two long acyl groups and two short alk(en)yl groups, are particularly preferred.
- Esterquats A further class of cationic surfactants particularly useful as co-surfactants for the present invention is represented by the so-called esterquats.
- Esterquats are generally understood to be quaternised fatty acid triethanolamine ester salts. These are known com pounds which can be obtained by the relevant methods of preparative organic chemistry.
- International patent application WO 91/01295 A1 according to which triethanolamine is partly esterified with fatty acids in the presence of hy- pophosphorous acid, air is passed through the reaction mixture and the whole is then quaternised with dimethyl sulphate or ethylene oxide.
- German patent DE 4308794 C1 describes a process for the production of solid esterquats in which the quaterni- sation of triethanolamine esters is carried out in the presence of suitable dispersants, prefer ably fatty alcohols.
- esterquats suitable for use in accordance with the invention are products of which the acyl component derives from monocarboxylic acids corresponding to formula RCOOH in which RCO is an acyl group containing 6 to 10 carbon atoms, and the amine component is triethanolamine (TEA).
- monocarboxylic acids are ca- proic acid, caprylic acid, capric acid and technical mixtures thereof such as, for example, so- called head-fractionated fatty acid.
- Esterquats of which the acyl component derives from monocarboxylic acids containing 8 to 10 carbon atoms are preferably used.
- esterquats are those of which the acyl component derives from dicarboxylic acids like malonic acid, suc cinic acid, maleic acid, fumaric acid, glutaric acid, sorbic acid, pimelic acid, azelaic acid, sebac- ic acid and/or dodecanedioic acid, but preferably adipic acid.
- esterquats of which the acyl component derives from mixtures of monocarboxylic acids containing 6 to 22 carbon atoms, and adipic acid are preferably used.
- the molar ratio of mono and dicarboxylic acids in the final esterquat may be in the range from 1:99 to 99:1 and is preferably in the range from 50:50 to 90:10 and more particularly in the range from 70:30 to 80:20.
- other suitable esterquats are quaternized ester salts of mono-/dicarboxylic acid mixtures with diethanolalkyamines or 1,2-dihydroxypropyl dialkylamines.
- the esterquats may be obtained both from fatty acids and from the corre sponding triglycerides in admixture with the corresponding dicarboxylic acids.
- Superfatting agents may be selected from such substances as, for example, lanolin and lecithin and also polyethoxylated or acylated lanolin and lecithin derivatives, polyol fatty acid esters, monoglycerides and fatty acid alkanolamides, the fatty acid alkanolamides also serving as foam stabilizers.
- the consistency factors mainly used are fatty alcohols or hydroxyfatty alcohols con taining 12 to 22 and preferably 16 to 18 carbon atoms and also partial glycerides, fatty acids or hydroxyfatty acids.
- a combination of these substances with alkyl oligoglucosides and/or fatty acid N-methyl glucamides of the same chain length and/or polyglycerol poly-12- hydroxystea rates is preferably used.
- Suitable thickeners are polymeric thickeners, such as Aerosil® types (hydrophilic sili cas), polysaccharides, more especially xanthan gum, guar-guar, agar-agar, alginates and tylo ses, carboxymethyl cellulose and hydroxyethyl cellulose, also relatively high molecular weight polyethylene glycol monoesters and diesters of fatty acids, polyacrylates (for example Carbo- pols® [Goodrich] or Synthalens® [Sigma]), polyacrylamides, polyvinyl alcohol and polyvinyl pyrrolidone, surfactants such as, for example, ethoxylated fatty acid glycerides, esters of fatty acids with polyols, for example pentaerythritol or trimethylol propane, narrow-range fatty alcohol ethoxylates and electrolytes, such as sodium chloride and ammonium chloride.
- Aerosil® types hydrophilic sili cas
- Suitable cationic polymers are, for example, cationic cellulose derivatives such as, for example, the quaternized hydroxyethyl cellulose obtainable from Amerchol under the name of Polymer JR 400®, cationic starch, copolymers of diallyl ammonium salts and acrylamides, quaternized vinyl pyrrolidone/vinyl imidazole polymers such as, for example, Luviquat® (BASF), condensation products of polyglycols and amines, quaternized collagen polypeptides such as, for example, Lauryldimonium Hydroxypropyl Hydrolyzed Collagen (Lamequat® L, Gr inau), quaternized wheat polypeptides, polyethyleneimine, cationic silicone polymers such as, for example, amodimethicone, copolymers of adipic acid and dimethylaminohy- droxypropyl diethylenetriamine (Carta retine ® , Sando
- Suitable anionic, zwitterionic, amphoteric and nonionic polymers are, for example, vinyl acetate/crotonic acid copolymers, vinyl pyrrolidone/vinyl acrylate copolymers, vinyl ace tate/butyl maleate/isobornyl acrylate copolymers, methyl vinylether/maleic anhydride copol ymers and esters thereof, uncrosslinked and polyol-crosslinked polyacrylic acids, acrylamido- propyl trimethylammonium chloride/acrylate copolymers, octylacrylamide/methyl methacry- late/tert.-butylaminoethyl methacrylate/2-hydroxypropyl methacrylate copolymers, polyvinyl pyrrolidone, vinyl pyrrolidone/vinyl acetate copolymers, vinyl pyrroli- done/dimethylaminoethyl methacrylate/vinyl caprol
- Suitable pearlising waxes are, for example, alkylene glycol esters, especially ethylene glycol distearate; fatty acid alkanolamides, especially cocofatty acid diethanolamide; partial glycerides, especially stearic acid monoglyceride; esters of polybasic, optionally hydroxy- substituted carboxylic acids with fatty alcohols containing 6 to 22 carbon atoms, especially long-chain esters of tartaric acid; fatty compounds, such as for example fatty alcohols, fatty ketones, fatty aldehydes, fatty ethers and fatty carbonates which contain in all at least 24 car bon atoms, especially laurone and distearylether; fatty acids, such as stearic acid, hydroxys- tearic acid or behenic acid, ring opening products of olefin epoxides containing 12 to 22 car- bon atoms with fatty alcohols containing 12 to 22 carbon atoms and/or polyols containing 2 to 15 carbon
- Suitable silicones can be chosen from the group consisting of: Acefylline Methylsilanol Mannuronate, Acetylmethionyl Methylsilanol Elastinate Acrylates/Behenyl, Acry- late/Dimethicone Methacrylate Copolymer, Acrylates/Behenyl Methacrylate/Dimethicone Methacrylate Copolymer, Acrylates/Bis-Hydroxypropyl Dimethicone Crosspolymer, Acry- lates/Dimethicone Copolymer, Acrylates/Dimethicone Methacrylate/Ethylhexyl Acrylate Co polymer, Acrylates/Dimethiconol Acrylate Copolymer, Acrylates/Ethylhexyl Acry- late/Dimethicone Methacrylate Copolymer, Acrylates/Octylacrylamide/Diphenyl Amodimethi- cone
- Butyloxyamodimethicone/PEG-60 Copolymer Bis(C13-15 Alkoxy) Hydroxybutamidoamodi- methicone, Bis(C13-15 Alkoxy) PG- Amodimethicone, Bis-(C1-8 Alkyl Lauroyl Lysine Decylcar- boxamide) Dimethicone, Bis-Cetyl Cetyl Dimethicone, Bis-Cetyl/PEG-8 Cetyl PEG-8 Dimethi cone, Bis-Diphenylethyl Disiloxane, Bis-Ethyl Ethyl Methicone, Bis- Gluconamidoethylaminopropyl Dimethicone, Bis-Hydrogen Dimethicone, Bis- Hydroxyethox- ypropyl Dimethicone Bis-Hydroxylauryl, Dimethicone/IPDI Copolymer, Bis- Hydroxy/M ethoxy Amodimethicon
- silicones to be contained in the mixture according to the inven tions are Dimethicone, Cyclomethicone, Phenyl Trimethicone, Cyclohexasiloxane and Cyclo- pentasiloxane.
- Dimethicone Cyclomethicone
- Phenyl Trimethicone Phenyl Trimethicone
- Cyclohexasiloxane Cyclo- pentasiloxane
- waxes may also be present in the preparations, more espe cially natural waxes such as, for example, candelilla wax, carnauba wax, Japan wax, espar- tograss wax, cork wax, guaruma wax, rice oil wax, sugar cane wax, ouricury wax, montan wax, beeswax, shellac wax, spermaceti, lanolin (wool wax), uropygial fat, ceresine, ozocerite (earth wax), petrolatum, paraffin waxes and microwaxes; chemically modified waxes (hard waxes) such as, for example, montan ester waxes, sasol waxes, hydrogenated jojoba waxes and syn thetic waxes such as, for example, polyalkylene waxes and polyethylene glycol waxes.
- candelilla wax carnauba wax, Japan wax, espar- tograss wax, cork wax, guaruma wax, rice oil wax
- Metal salts of fatty acids such as, for example, magnesium, aluminium and/or zinc stearate or ricinoleate may be used as stabilizers.
- Primary sun protection filters in the context of the invention are, for example, organic substances (light filters) which are liquid or crystalline at room temperature and which are capable of absorbing ultraviolet radiation and of releasing the energy absorbed in the form of longer-wave radiation, for example heat.
- the formulations according to the invention advantageously contain at least one UV- A filter and/or at least one UV-B filter and/or a broadband filter and/or at least one inorganic pigment.
- Formulations according to the invention preferably contain at least one UV-B filter or a broadband filter, more particularly preferably at least one UV-A filter and at least one UV-B filter.
- UV filters cited below which can be used within the context of the present inven tion are preferred but naturally are not limiting. UV filters which are preferably used are se lected from the group consisting of one, two, three, four, five or more of the following spe cies:
- the sun protection filter forming component (ii) repre sents a blend of UV-A- and UV-B-filters selected from the group consisting of homosalate, octocrylene, bis-ethylhexyloxyphenol methoxyphenyl triazine, butyl methoxydibenzoylme- thane, ethylhexyl salicylate and mixtures thereof.
- Particular preferred is a blend of all these filters which is commercially available in the market under the trademark NeoHeliopan® Flat (SYMRISE), which also subject to WO 2020 088778 A1.
- Suitable pigments encompass oxides of titanium (T1O2), zinc (ZnO), iron (Fe 2 0s), zirco nium (Zr0 2 ), silicon (S1O2), manganese (e.g. MnO), aluminium (AI2O3), cerium (e.g. Ce 2 0s) and/or mixtures thereof.
- a formulation according to the invention contains a total amount of sunscreen agents, i.e. in particular UV filters and/or inorganic pigments (UV filtering pigments) so that the formulation according to the invention has a light protection factor of greater than or equal to 5 and up to 50.
- sunscreen agents i.e. in particular UV filters and/or inorganic pigments (UV filtering pigments) so that the formulation according to the invention has a light protection factor of greater than or equal to 5 and up to 50.
- UV filters and/or inorganic pigments UV filtering pigments
- Secondary sun protection factors of the antioxidant type interrupt the photochemical reaction chain which is initiated when UV rays penetrate into the skin.
- Typical examples are amino acids (for example glycine, histidine, tyrosine, tryptophane) and derivatives thereof, imidazoles (for example urocanic acid) and derivatives thereof, peptides, such as D,L-carnosine, D-carnosine, L-carnosine and derivatives thereof (for example anserine), carotinoids, carotenes (for example alpha- carotene, beta-carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, liponic acid and derivatives thereof (for example dihydroliponic acid), aurothioglu- cose, propylthiouracil and other thiols (for example thioredoxine, glutathione, cysteine,
- amino acids for example glycine, histidine, tyrosine, tryptophane
- Advantageous inorganic secondary light protection pigments are finely dispersed metal oxides and metal salts which are also mentioned in WO 2005 123101 A1.
- the total quantity of inorganic pigments, in particular hydrophobic inorganic micro-pigments in the finished cosmetic preparation according to the present invention is advantageously from 0.1 to 30% by weight, preferably 0.5 to 10.0% by weight, in each case based on the total weight of the preparation.
- particulate UV filters or inorganic pigments which can optionally be hydrophobed, can be used, such as the oxides of titanium (T1O 2 ), zinc (ZnO), iron (Fe 2 0s), zirconium (Zr0 2 ), silicon (S1O 2 ), manganese (e.g. MnO), aluminium (AI 2 O 3 ), cerium (e.g. Ce 2 0s) and/or mixtures thereof.
- Biogenic active substances include, for example, tocopherol, tocopherol acetate, to copherol palmitate, ascorbic acid, (deoxy)ribonucleic acid and its fragmentation products, b- glucans, retinol, Bisabolol, allantoin, phytantriol, panthenol, AHA acids, amino acids, ceramides, pseudoceramides, essential oils, plant extracts, such as such as prunus extract, bambaranus extract and vitamin complexes.
- Antioxidants interrupt the photochemical reaction chain which is triggered when UV radiation penetrates the skin.
- Typical examples are amino acids (e.g. glycine, histidine, tyro sine, tryptophan) and their derivatives, imidazoles (e.g. urocanic acid) and their derivatives, peptides like D,L-carnosine, D-carnosine, L-carnosine and their derivatives (e.g. anserine), carotenoids, carotenes (e.g. -carotene, lycopene) and their derivates, chlorogenic acid and its derivatives, lipoic acid and its derivatives (e.g.
- thiols e.g. thioredoxin, glutathione, cysteine, cystine, cystamin and their gly- cosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, linoleyl, choles- teryl and glyceryl esters
- Dilaurylthiodipropionate, ditearylthiodipropionate, thiodipropionic acid and its derivatives (esters, ethers, peptides, lipids, nucleotides, nucleo sides and salts) as well as sulfoximine compounds e.g.
- citric acid citric acid, lactic acid, malic acid
- humic acid gallic acid
- bile extracts bilirubin, biliverdin, EDTA, EGTA and their derivatives
- unsaturated fatty acids and their derivatives e.g. linolenic acid, linoleic acid, oleic acid
- folic acid and its derivatives ubiquinone and ubiquinol and their derivatives
- vitamin C and its derivatives e.g. ascorbyl palmitate, Mg-ascorbyl phosphate, ascorbylacetate
- tocoph- erols and derivatives e.g.
- vitamin E acetate
- vitamin A and derivates vitamin A palmitate
- conifer aryl benzoate of benzoic resin rutinic acid and its derivatives, glycosyl rutin, ferulic acid, furfurylidene glucitol, carnosine, butyl hydroxytoluene, butylhydroxyanisole, nor- dihydroguaiac resin acid, nordihydroguajaretic acid, trihydroxybutyrophenone, uric acid and its derivatives, mannose and its derivatives, superoxide dismutase, zinc and its derivatives (e.g. e.g. ZnO, ZnS04) selenium and its derivatives (e.g.
- stilbenes and their derivatives e.g. styrene oxide, trans-stilbene oxide
- derivatives suitable for the invention salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids
- Preferred active ingredients for hair lightening are selected from the group consisting of: kojic acid (5-hydroxy-2-hydroxymethyl-4-pyranone), kojic acid derivatives, preferably kojic acid dipalmitate, arbutin, ascorbic acid, ascorbic acid derivatives, preferably magnesium ascorbyl phosphate, hydroquinone, hydroquinone derivatives, resorcinol, resorcinol deriva tives, preferably 4-alkylresorcinols and 4-(1-phenylethyl)1,3-dihydroxybenzene (phenylethyl resorcinol), cyclohexylcarbamates (preferably one or more cyclohexyl carbamates disclosed in WO 2010/122178 and WO 2010/097480), sulfur-containing molecules, preferably glutathione or cysteine, alpha-hydroxy acids (preferably citric acid, lactic acid, malic acid), salts and esters thereof, N-acetyl
- Advantageous skin and hair tanning active ingredients in this respect are substrates or substrate analogues of tyrosinase such as L-tyrosine, N-acetyl tyrosine, L-DOPA or L- dihydroxyphenylalanine, xanthine alkaloids such as caffeine, theobromine and theophyl-line and derivatives thereof, proopiomelanocortin peptides such as ACTH, alpha-MSH, peptide analogues thereof and other substances which bind to the melanocortin receptor, peptides such as Val-Gly-Val-Ala-Pro-Gly, Lys-lle- Gly-Arg-Lys or Leu-lle-Gly-Lys, purines, pyrimidines, folic acid, copper salts such as copper gluconate, chloride or pyrrolidonate, 1,3,4-oxadiazole- 2-thiols such as 5-pyrazin-2-yl-1
- Flavo- noids which bring about skin and hair tinting or brown-ing (e.g. quercetin, rhamnetin, kaempferol, fisetin, genistein, daidzein, chrysin and api-genin, epicatechin, diosmin and di- osmetin, morin, quercitrin, naringenin, hesperidin, phloridzin and phloretin) can also be used.
- brown-ing e.g. quercetin, rhamnetin, kaempferol, fisetin, genistein, daidzein, chrysin and api-genin, epicatechin, diosmin and di- osmetin, morin, quercitrin, naringenin, hesperidin, phloridzin and phloretin
- the amount of the aforementioned examples of additional active ingredients for the modulation of skin and hair pigmentation (one or more compounds) in the products accord ing to the invention is then preferably 0.00001 to 30 wt.%, preferably 0.0001 to 20 wt.%, par ticularly preferably 0.001 to 5 wt.%, based on the total weight of the preparation.
- Formulations and products according to the present invention may also comprise one or more hair growth activators, i.e. agents to stimulate hair growth.
- Hair growth activators are preferably selected from the group consisting of pyrimidine derivatives such as 2,4- diaminopyrimidine-3-oxide (Aminexil), 2,4-diamino-6-piperidinopyrimidine-3-oxide (Minox idil) and derivatives thereof, 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine and its derivatives, xanthine alkaloids such as caffeine, theobromine and theophylline and derivatives thereof, quercetin and derivatives, dihydroquercetin (taxifolin) and derivatives, potassium channel openers, antiandrogenic agents, synthetic or natural 5-reductase inhibi tors, nicotinic acid esters such as tocopheryl nicotinate, benzyl nicotinate and C1-
- formulations and products according to the present invention may comprise one or more hair growth inhibitors (as described above), i.e. agents to reduce or prevent hair growth.
- Hair growth inhibitors are preferably selected from the group consisting of activin, activin derivatives or activin agonists, ornithine decarboxylase inhibitors such as alpha-difluoromethylornithine or pentacyclic triterpenes like for example ursolic acid, betulin, betulinic acid, oleanolic acid and derivatives thereof, 5alpha-reductase inhibitors, androgen receptor antagonists, S-adenosylmethionine decarboxylase inhibitors, gamma-glutamyl transpeptidase inhibitors, transglutaminase inhibitors, soybean-derived serine protease inhib itors, extracts from microorganisms, algae, different microalgae or plants and plant parts of for example the families Legumi
- Physiological cooling agents are preferably selected from the following list: menthol and menthol derivatives (for example L-menthol, D-menthol, racemic menthol, isomenthol, neoisomenthol, neomenthol) menthylethers (for example (l-menthoxy)-1,2-propandiol, (I- menthoxy)-2-methyl-1,2-propandiol), menthone glyceryl acetal, menthone glyceryl ketal or mixtures of both, menthylesters (for example menthylformiate, menthyhydroxyisobutyrat, menthyllactates, L-menthyl-L-lactate, L-menthyl-D-lactate, menthyl-(2-methoxy)acetate, menthyl-(2-methoxyethoxy)acetate, menthylpyroglutamate), menthylcarbonates (for example menthylpropyleneg
- Physiological warming agents can be selected from the group consisting of capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin, homodihydrocapsaicin nonivamid, and chili extracts.
- Suitable anti-inflammatory agents may be selected from the group formed by:
- steroidal anti-inflammatory substances of the corticosteroid type in particular hydro cortisone, hydrocortisone derivatives such as hydrocortisone 17-butyrate, dexame- thasone, dexamethasone phosphate, methylprednisolone or cortisone,
- non-steroidal anti-inflammatory substances in particular oxicams such as piroxicam or tenoxicam, salicylates such as aspirin, disalcid, solprin or fendosal, acetic acid deriv atives such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin or clindanac, fenamates such as mefenamic, meclofenamic, flufenamic or niflumic, propionic acid derivatives such as ibuprofen, naproxen or benoxaprofen, pyrazoles such as phenyl butazone, oxyphenylbutazone, febrazone or azapropazone,
- oxicams such as piroxicam or tenoxicam
- salicylates such as aspirin, disalcid, solprin or fendosal
- acetic acid deriv atives such as diclofenac, fenclo
- histamine receptor antagonists include serine protease inhibitors (e.g. of Soy extracts), TRPV1 antagonists (e.g. 4-t-Butylcyclohexanol), NK1 antagonists (e.g. Aprepitant, Hydroxy- phenyl Propamidobenzoic Acid), cannabinoid receptor agonists (e.g. Palmitoyl Etha- nolamine) and TRPV3 antagonists.
- serine protease inhibitors e.g. of Soy extracts
- TRPV1 antagonists e.g. 4-t-Butylcyclohexanol
- NK1 antagonists e.g. Aprepitant, Hydroxy- phenyl Propamidobenzoic Acid
- cannabinoid receptor agonists e.g. Palmitoyl Etha- nolamine
- TRPV3 antagonists e.g. Palmitoyl Etha- nolamine
- Suitable anti-microbial agents are, in principle, all substances effective against Gram positive bacteria, such as, for example, 4- hydroxybenzoic acid and its salts and esters, N-(4- chlorophenyl)-N'-(3,4- dichlorophenyl)urea, 2,4,4'-trichloro-2'-hydroxy-diphenyl ether (triclo- san), 4-chloro-3, 5-dimethyl-phenol, 2,2'-methylenebis(6-bromo-4- chlorophenol), 3-methyl- 4-(1-methylethyl)phenol, 2-benzyl-4-chloro-phenol, 3-(4-chlorophenoxy)-1, 2-propanediol, 3- iodo-2-propynyl butylcarbamate, chlorhexidine, 3,4,4'-trichlorocarbanilide (TTC), antibacterial fragrances, thymol, thyme oil, eugenol, oil of cloves, menthol
- Suitable enzyme inhibitors are, for example, esterase inhibitors. These are preferably trialkyl citrates, such as trimethyl citrate, tripropyl citrate, triisopropyl citrate, tributyl citrate and, in particular, triethyl citrate (Hydagen CAT). The substances inhibit enzyme activity, thereby reducing the formation of odour.
- esterase inhibitors such as trimethyl citrate, tripropyl citrate, triisopropyl citrate, tributyl citrate and, in particular, triethyl citrate (Hydagen CAT).
- esterase inhib itors are sterol sulfates or phosphates, such as, for example, lanosterol, cholesterol, campes- terol, stigmasterol and sitosterol sulfate or phosphate, dicarboxylic acids and esters thereof, such as, for example, glutaric acid, monoethyl glutarate, diethyl glutarate, adipic acid, mo noethyl adipate, diethyl adipate, malonic acid and diethyl malonate, hydroxycarboxylic acids and esters thereof, such as, for example, citric acid, malic acid, tartaric acid or diethyl tartrate, and zinc glycinate.
- sterol sulfates or phosphates such as, for example, lanosterol, cholesterol, campes- terol, stigmasterol and sitosterol sulfate or phosphate
- Suitable odour absorbers are substances which are able to absorb and largely retain odour-forming compounds. They lower the partial pressure of the individual components, thus also reducing their rate of diffusion. It is important that perfumes must remain unim paired in this process. Odour absorbers are not effective against bacteria. They comprise, for example, as main constituent, a complex zinc salt of ricinoleic acid or specific, largely odour- neutral fragrances which are known to the person skilled in the art as "fixatives", such as, for example, extracts of labdanum or styrax or certain abietic acid derivatives.
- the odour masking agents are fragrances or perfume oils, which, in addition to their function as odour masking agents, give the deodorants their respective fragrance note.
- Perfume oils which may be men tioned are, for example, mixtures of natural and synthetic fragrances. Natural fragrances are extracts from flowers, stems and leaves, fruits, fruit peels, roots, woods, herbs and grasses, needles and branches, and resins and balsams. Also suitable are animal products, such as, for example, civet and castoreum.
- Typical synthetic fragrance compounds are products of the ester, ether, aldehyde, ketone, alcohol, and hydrocarbon type.
- Fragrance compounds of the ester type are, for example, benzyl acetate, p-tert-butylcyclohexyl acetate, linalyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, allyl cyclohexylpropionate, styrallyl pro pionate and benzyl salicylate.
- the ethers include, for example, benzyl ethyl ether
- the aldehydes include, for example, the linear alkanals having 8 to 18 carbon atoms, citral, citron- ellal, citronellyloxyacetaldehyde, cyclamen aldehyde, hydroxycitronellal, lilial and bourgeonal
- the ketones include, for example, the ionones and methyl cedryl ketone
- the alcohols include anethole, citronellol, eugenol, isoeugenol, geraniol, linaool, phenylethyl alcohol and terpineol
- the hydrocarbons include mainly the terpenes and balsams.
- fragrance oils which are mostly used as aroma components, are also suitable as perfume oils, e.g. sage oil, camomile oil, oil of cloves, melissa oil, mint oil, cinna mon leaf oil, linden flower oil, juniperberry oil, vetiver oil, olibanum oil, galbanum oil, labda- num oil and lavandin oil.
- perfume oils e.g. sage oil, camomile oil, oil of cloves, melissa oil, mint oil, cinna mon leaf oil, linden flower oil, juniperberry oil, vetiver oil, olibanum oil, galbanum oil, labda- num oil and lavandin oil.
- Suitable astringent antiperspirant active ingredients are primarily salts of aluminium, zirconium or of zinc.
- suitable antihydrotic active ingredients are, for example, aluminium chloride, aluminium chlorohydrate, aluminium dichlorohydrate, aluminium sesquichlorohy- drate and complex compounds thereof, e.g. with 1,2- propylene glycol, aluminium hydroxy- allantoinate, aluminium chloride tartrate, aluminium zirconium trichlorohydrate, aluminium zirconium tetrachlorohydrate, aluminium zirconium pentachlorohydrate and complex com pounds thereof, e.g. with amino acids, such as glycine.
- Standard film formers are, for example, chitosan, microcrystalline chitosan, quater- nized chitosan, polyvinyl pyrrolidone, vinyl pyrrolidone/vinyl acetate copolymers, polymers of the acrylic acid series, quaternary cellulose derivatives, collagen, hyaluronic acid and salts thereof and similar compounds.
- Suitable antidandruff agents are Pirocton Olamin (1-hydroxy-4-methyl-6-(2,4,4- trimethylpentyl)-2-(1 H)-pyridinone monoethanolamine salt), Baypival ® (Climbazole), Keto- conazol® (4-acetyl-1- ⁇ 4-[2-(2,4-dichlorophenyl) r-2-(1 H-imidazol-1-ylmethyl)-1,3-dioxylan-c- 4-ylmethoxyphenyl ⁇ -piperazine, ketoconazole, elubiol, selenium disulfide, colloidal sulfur, sulfur polyethylene glycol sorbitan monooleate, sulfur ricinol polyethoxylate, sulfur tar distil late, salicylic acid (or in combination with hexachlorophene), undecylenic acid, monoethano- lamide sulfosuccinate Na salt, Lamepon ® UD (protein/
- Preferred cosmetics carrier materials are solid or liquid at 25°C and 1013 mbar (in cluding highly viscous substances) as for example glycerol, 1,2-propylene glycol, 1,2-butylene glycol, 1,3-propylene glycol, 1,3-butylene glycol, ethanol, water and mixtures of two or more of said liquid carrier materials with water.
- these preparations according to the invention may be produced using preservatives or solubilizers.
- Other preferred liquid carrier substances which may be a component of a preparation according to the invention are se lected from the group consisting of oils such as vegetable oil, neutral oil and mineral oil.
- Preferred solid carrier materials which may be a component of a preparation accord ing to the invention are hydrocolloids, such as starches, degraded starches, chemically or physically modified starches, dextrins, (powdery) maltodextrins (preferably with a dextrose equivalent value of 5 to 25, preferably of 10 - 20), lactose, silicon dioxide, glucose, modified celluloses, gum arabic, ghatti gum, traganth, karaya, carrageenan, pullulan, curdlan, xanthan gum, gellan gum, guar flour, carob bean flour, alginates, agar, pectin and inulin and mixtures of two or more of these solids, in particular maltodextrins (preferably with a dextrose equiva lent value of 15 - 20), lactose, silicon dioxide and/or glucose.
- hydrocolloids such as starches, degraded starches, chemically or physically modified starches, de
- hydrotropes for example ethanol, isopropyl alcohol or polyols
- Suitable polyols preferably contain 2 to 15 carbon atoms and at least two hydroxyl groups.
- the polyols may contain other functional groups, more especially amino groups, or may be modified with nitrogen. Typical examples are
- alkylene glycols such as, for example, ethylene glycol, diethylene glycol, propylene gly col, butylene glycol, hexylene glycol and polyethylene glycols with an average molecu lar weight of 100 to 1000 Dalton;
- methylol compounds such as, in particular, trimethylol ethane, trimethylol propane, trimethylol butane, pentaerythritol and dipentaerythritol;
- lower alkyl glucosides particularly those containing 1 to 8 carbon atoms in the alkyl group, for example methyl and butyl glucoside;
- sugar alcohols containing 5 to 12 carbon atoms for example sorbitol or mannitol
- sugars containing 5 to 12 carbon atoms for example glucose or sucrose
- dialcoholamines such as diethanolamine or 2-aminopropane-1,3-diol.
- Suitable preservatives are, for example, phenoxyethanol, sodium benzoate or sorbic acid, blends of the mentioned ingredients and the other classes of compounds listed in Ap pendix 6, Parts A and B of the Kosmetikverowski ("Cosmetics Directive").
- Alternative prod ucts which could improve the product protection are for example 1,2-alkanediols such as for example 1,2-penatnediol, 1,2-hexanediol, 1,2-octanediol, 1,2-decanediol, 1,2-dodecanediol and mixtures thereof, 4-hydroxy acetophenone.
- Suitable perfume oils are mixtures of natural and synthetic perfumes. Natural per fumes include the extracts of blossoms (lily, lavender, rose, jasmine, neroli, ylang-ylang), stems and leaves (geranium, patchouli, petitgrain), fruits (anise, coriander, caraway, juniper), fruit peel (bergamot, lemon, orange), roots (nutmeg, angelica, celery, cardamom, costus, iris, calmus), woods (pinewood, sandalwood, guaiac wood, cedarwood, rosewood), herbs and grasses (tarragon, lemon grass, sage, thyme), needles and branches (spruce, fir, pine, dwarf pine), resins and balsams (galbanum, elemi, benzoin, myrrh, olibanum, opoponax). Animal raw materials, for example civet and beaver, may also be used.
- Suitable fragrances with woody odor are selected from the group consisting of:
- Suitable fragrances with amber odor are selected from the group consisting of:
- Suitable fragrances with fruity odor are selected from the group consisting of:
- Suitable fragrances with musk odor are selected from the group consisting of:
- Suitable dyes are any of the substances suitable and approved for cosmetic purposes as listed, for example, in the publication "Kosmetician mistakestoff" of the Farbstoff- kommission der Deutschen Deutschen Deutschen Anlagenstician, Verlag Chemie, Weinheim, 1984, pages 81 to 106. Examples include cochineal red A (C.l. 16255), patent blue V (C.l. 42051), indigotin (C.l. 73015), chlorophyllin (C.l. 75810), quinoline yellow (C.l. 47005), titanium dioxide (C.l. 77891), indanthrene blue RS (C.l. 69800) and madder lake (C.l. 58000). Luminol may also be present as a luminescent dye.
- Advantageous coloured pigments are for example titanium dioxide, mica, iron oxides (e.g. Fe2C>3 FesC , FeO(OH)) and/or tin oxide.
- Advantageous dyes are for example carmine, Berlin blue, chromium oxide green, ultramarine blue and/or manga nese violet.
- compositions according to the present inventions are selected from the group of products for treatment, protecting, care and cleansing of the skin and/or hair or as a make-up product, preferably as a leave-on product (meaning that the one or more com pounds stay on the skin and/or hair for a longer period of time, compared to rinse-off prod ucts).
- the formulations according to the invention are preferably in the form of an emulsion, e.g. W/O (water-in-oil), O/W (oil-in-water), W/O/W (water-in-oil-in-water), O/W/O (oil-in- water-in-oil) emulsion, PIT emulsion, Pickering emulsion, emulsion with a low oil content, micro- or nanoemulsion, a solution, e.g.
- a gel including hydrogel, hydrodisper sion gel, oleogel
- spray e.g. pump spray or spray with propellant
- a foam or an impreg nating solution for cosmetic wipes e.g. soap, synthetic detergent, liquid wash ing, shower and bath preparation, bath product (capsule, oil, tablet, salt, bath salt, soap, etc.), effervescent preparation, a skin care product such as e.g.
- an emulsion as described above, ointment, paste, gel (as described above), oil, balsam, serum, powder (e.g. face powder, body powder), eau de perfume, eau de toilette, after-shave, a mask, a pencil, stick, roll-on, pump, aerosol (foaming, non-foaming or post-foaming), a deodorant and/or antiperspirant, mouth wash and mouth rinse, a foot care product (including keratolytic, deodorant), an insect repel lent, a sunscreen, aftersun preparation, a shaving product, aftershave balm, pre- and after shave lotion, a depilatory agent, a hair care product such as e.g.
- shampoo including 2-in- 1 shampoo, anti-dandruff shampoo, baby shampoo, shampoo for dry scalps, concentrated shampoo
- conditioner hair tonic, hair water, hair rinse, styling creme, pomade, perm and setting lotion
- hair spray e.g. gel or wax
- hair smoothing agent detangling agent, relaxer
- hair dye such as e.g. temporary direct-dyeing hair dye, semi-permanent hair dye, permanent hair dye, hair conditioner, hair mousse, eye care product, make-up, make-up re mover or baby product.
- Auxiliary substances and additives can be included in quantities of 5 to 99 % b.w., preferably 10 to 80 % b.w., based on the total weight of the formulation.
- the amounts of cosmetic or dermatological auxiliary agents and additives and perfume to be used in each case can easily be determined by the person skilled in the art by simple trial and error, de pending on the nature of the particular product.
- the preparations can also contain water in a quantity of up to 99 wt. -percent., prefer ably from about 5 to about 80 wt. -percent and more preferably either from about 10 to about 50 or from about 60 to about 80 wt. -percent based on the total weight of the prepara tion.
- compositions are typically encapsulated by means of a solid covering material, which is preferably selected from starches, degraded or chemically or physically modified starches (in particular dextrins and maltodextrins), gelatines, gum arabic, agar-agar, ghatti gum, gellan gum, modified and non-modified celluloses, pullulan, curdlan, carrageenans, alginic acid, alginates, pectin, inulin, xanthan gum and mixtures of two or more of said substances.
- a solid covering material which is preferably selected from starches, degraded or chemically or physically modified starches (in particular dextrins and maltodextrins), gelatines, gum arabic, agar-agar, ghatti gum, gellan gum, modified and non-modified celluloses, pullulan, curdlan, carrageenans, alginic acid, alginates, pectin, inulin, xanthan
- the solid covering material is preferably selected from gelatine (preferred are pork, beef, chicken and/or fish gelatines and mixtures thereof, preferably comprising at least one gelatine with a bloom value of greater than or equal to 200, preferably with a bloom value of greater than or equal to 240), maltodextrin (preferably obtained from maize (corn), wheat, tapioca or potato, preferred maltodextrins have a DE value of 10 - 20), modified cellulose (for example cellulose ether), alginates (for example Na-alginate), carrageenan (beta-, iota-, lambda- and/or kappa carrageenan), gum arabic, curdlan and/or agar-agar.
- gelatine preferred are pork, beef, chicken and/or fish gelatines and mixtures thereof, preferably comprising at least one gelatine with a bloom value of greater than or equal to 200, preferably with a bloom value of greater than or equal to 240
- Gelatine is pref erably used, in particular, because of its good availability in different bloom values.
- Particular ly preferred, especially for oral use are seamless gelatine or alginate capsules, the covering of which dissolves very rapidly in the mouth or bursts when chewing. Production may take place, for example, as described in EP 0389700 A1, US 4,251,195, US 6,214,376, WO 2003 055587 or WO 2004 050069 A1.
- the capsules may also represent micro-capsules.
- Microcapsules are un derstood to be spherical aggregates with a diameter of about 0.1 to about 5 mm which con tain at least one solid or liquid core surrounded by at least one continuous membrane. More precisely, they are finely dispersed liquid or solid phases coated with film-forming polymers, in the production of which the polymers are deposited onto the material to be encapsulated after emulsification and coazervation or interfacial polymerization. In another process, liquid active principles are absorbed in a matrix (“micro-sponge") and, as micro-particles, may be additionally coated with film-forming polymers.
- microscopically small capsules also known as nano-capsules
- multiple-core aggregates also known as microspheres, which con tain two or more cores distributed in the continuous membrane material.
- single core or multiple-core microcapsules may be surrounded by an additional second, third etc. membrane.
- the membrane may consist of natural, semisynthetic or synthetic materials.
- Natu ral membrane materials are, for example, gum arabic, agar agar, agarose, maltodextrins, al- ginic acid and salts thereof, for example sodium or calcium alginate, fats and fatty acids, cetyl alcohol, collagen, chitosan, lecithins, gelatine, albumin, shellac, polysaccharides, such as starch or dextran, polypeptides, protein hydrolysates, sucrose and waxes.
- Semisynthetic membrane materials are inter alia chemically modified celluloses, more particularly cellulose esters and ethers, for example cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, hy- droxypropyl methyl cellulose and carboxymethyl cellulose, and starch derivatives, more par ticularly starch ethers and esters.
- Synthetic membrane materials are, for example, polymers, such as polyacrylates, polyamides, polyvinyl alcohol or polyvinyl pyrrolidone.
- microcapsules examples are the following commercial products (the mem brane material is shown in brackets) Hallcrest Microcapsules (gelatin, gum arabic), Coletica Thalaspheres (maritime collagen), Lipotec Millicapseln (alginic acid, agar agar), Induchem Unispheres (lactose, microcrystalline cellulose, hydroxypropylmethyl cellulose), Unicetin C30 (lactose, microcrystalline cellulose, hydroxypropylmethyl cellulose), Kobo Glycospheres (modified starch, fatty acid esters, phospholipids), Softspheres (modified agar agar) and Kuhs Probiol Nanospheres (phospholipids).
- the active principles are released from the microcapsules by mechanical, thermal, chemical or enzymatic destruction of the membrane, normally during the use of the prepara tions containing the microcapsules.
- a shell is obtained by coazervation, precipitation or polycondensation of anionic and cationic polymers has been quite suitable for the formation of stable capsules.
- a preferred process for the encapsulation of active principles according to the present invention is characterised in that it comprises the steps of
- preferred gel formers are substances which are capa ble of forming gels in aqueous solution at temperatures above 40° C.
- Typical examples of such gel formers are heteropolysaccharides and proteins.
- Preferred thermogelling heteropol ysaccharides are agaroses which may be present in the form of the agar agar obtainable from red algae, even together with up to 30% by weight of non-gel-forming agaropectins.
- the principal constituent of agaroses are linear polysaccharides of Galactose and 3,6-anhydro-L- galactose with alternate 1,3- and 1,4-glycosidic bonds.
- the heteropolysaccharides preferably have a molecular weight of 110,000 to 160,000 and are both odourless and tasteless. Suitable alternatives are pectins, xanthans (including xanthan gum) and mixtures thereof. Other pre ferred types are those which in 1% by weight aqueous solution still form gels that do not melt below 80° C. and solidify again above 40° C. Examples from the group of thermogelling proteins are the various gelatines.
- alginic acid is a mixture of car boxyl-containing polysaccharides with the following idealized monomer unit:
- the average molecular weight of the alginic acid or the alginates is in the range from 150,000 to 250,000.
- Salts of alginic acid and complete and partial neutralization products thereof are understood
- the alkali metal salts preferably sodium alginate ("algin") and the ammonium and alkaline earth metal salts.
- Mixed alginates for example so dium/magnesium or sodium/calcium alginates, are particularly preferred.
- carboxymethyl celluloses and anionic chitosan deriv atives for example the carboxylation and above all succinylation products are also suitable for this purpose.
- Chitosans are biopolymers which belong to the group of hydrocolloids. Chemically, they are partly de-acetylated chitins differing in their molecular weights which contain the following - idealized - monomer unit:
- chitosans are cationic biopolymers under these conditions.
- the positively charged chi- tosans are capable of interacting with oppositely charged surfaces and are therefore used in cosmetic hair-care and body-care products and pharmaceutical preparations.
- a 1 to 10 and preferably 2 to 5% by weight aqueous solution of the gel former, preferably agar agar, is normally prepared and heated under reflux.
- a second aqueous solution containing the cationic polymer, preferably chitosan, in quantities of 0.1 to 2 and preferably 0.25 to 0.5% by weight and the active princi ple in quantities of 0.1 to 25 and preferably 0.25 to 10% by weight is added in the boiling heat, preferably at 80 to 100 ° C; this mixture is called the matrix.
- the charging of the microcapsules with active principles may also comprise 0.1 to 25% by weight, based on the weight of the capsules.
- water-insoluble constituents for example inorganic pigments
- inorganic pigments may also be added at this stage to adjust viscosity, generally in the form of aque ous or aqueous/alcoholic dispersions.
- emulsifiers and/or solubilisers to the matrix.
- the matrix After its preparation from gel former, cationic polymer and active principle, the matrix optionally is very finely dis persed in an oil phase with intensive shearing in order to produce small particles in the sub sequent encapsulation process. It has proved to be particularly advantageous in this regard to heat the matrix to temperatures in the range from 40 to 60° C while the oil phase is cooled to 10 to 20° C.
- the actual encapsulation i.e. formation of the membrane by contacting the cationic polymer in the matrix with the anionic polymers, takes place in the third step.
- the resulting aqueous preparations gener ally have a microcapsule content of 1 to 10% by weight.
- the solution of the polymers can contain other ingredients, for example emulsifiers or preservatives.
- emulsifiers or preservatives for example emulsifiers or preservatives.
- microcapsules with a mean diameter of preferably 1 to 3 mm are obtained. It is advisable to sieve the capsules to ensure a uniform size distribution.
- the microcapsules thus obtained may have any shape within production-related limits, but are preferably substantially spherical.
- Another object of the present invention refers to a non-therapeutic method for modulation of the endocannabinoid system of a human being, and/or enhancing the mood of a human being - protecting endogenous cells of a human being against oxidative stress and/or oxidative damages prophylaxis and treatment of a human being against skin redness prophylaxis and treatment of a disturbed skin barrier and/or dry skin of a human being prophylaxis and treatment of excessive sebum production of a human being comprising or consisting of the following steps:
- composition comprising or consisting of Cannabidiol and optionally Bisabolol
- composition according to the methods as described above can be effected either by topical application or oral uptake.
- Another object of the present invention refers to the non-therapeutic use of composi tion comprising or consisting of
- a final object of the present invention is directed to the use of a composition comprising or consisting of (a) Cannabidiol and optionally
- compositions can be administered to the human body for example topically as a component of a cosmetic formulation such as for example a cream, lotion, emulsion, mousse and the like.
- a cosmetic formulation such as for example a cream, lotion, emulsion, mousse and the like.
- capsules comprising the compositions are the preferred embodiment.
- the cannabinoid receptor types 1 and 2 are G protein- coupled receptor from the cannabinoid receptor family that in humans are encoded by the CNR2 gene. Both receptors inhibit the activity of adenylyl cyclase through their Gi/Go a subunits. CB2 can also couple to stimulatory Gcc s subunits leading to an increase of intracellular cAMP, as has been shown for human leukocytes. Through their Gp Y subunits, CB2 receptors are also known to be coupled to the MAPK-ERK pathway, a complex and highly conserved signal transduction pathway, which regulates a number of cellular processes in mature and developing tissue.
- the CB2 receptors are mainly found on white blood cells, in the tonsils and in the spleen.
- the immune cells also express CB1, although there are fewer of them than CB2.
- CB2 activation is considered having positive effects on the course of Alzheimer's disease through various mechanisms, including the reduction of local, microglia-mediated inflammation and an increased rate of beta-amyloid removal.
- 293T-CB2 cells were transient transfect with CRE-luc plasmid. After 24 h the cells were treated with Forskolin and WIN55, 212-2 (ImM) and the test compounds. After 6 h luciferase activity was measured in the cell lysates. CB2 antagonist is reflected by reversing WIN-induced inhibition of Forskolin-mediated CRE-Luc activation
- Moisturisation is a key property of cosmetic skin care formulations and strengthens its barrier function to protect it from intruding pathogenic bacteria and other noxes.
- Hyalu ronic acid contributes in moisturisation as it has high water capturing activity.
- Gene expression is the process by which information from a gene is used in the syn thesis of a functional gene product. These products are often proteins. Stressors or Signals acting on cells are transferred and processed resulting in gene expression. Based on the spe cific gene expression alterations, conclusions about intracellular processes can be drawn.
- Hyaluronic acid is a glycosaminoglycan (GAG) and is a major contributor in moisturisation in the skin synthesized by fibroblasts in the dermis and epidermis. It exhibits high water binding capacity and thus captures ambient water on the skin surface subse quently moisturizing it.
- moisturisation was determined by Gene Expression Analysis using quantitative Real Time Polymerase Chain Reaction (qPCR)
- Hyaluronic acid also known as hyaluronan or hyaluronate is a large linear non- sulfated glycosaminoglycan (GAG) with a molecular weight between 106 and 107 Da. It is a major component of connective tissues and thus distributed ubiquitously in the organism.
- Hyaluronan is synthesized by fibroblasts and other specialized connective tissue cells.
- Hyaluronan is especially important for the structure and organization of extracellular matrices.
- the hyaluronan network acts as an osmotic buffer and is responsible for water ho meostasis as well as it regulates protein distribution via the formation of flow and diffusion barriers. Additionally, hyaluronan interacts with proteins and cell surfaces and thus has a strong influence on cell proliferation, differentiation and tissue repair.
- Hyaluronic acid concentration produced in response to a specific compound was determined using the ELISA technique. Human dermal skin fibroblasts were seeded on cell culture plastic for 96 h. Subsequently cells were treated with test compound for 72h. Then, cells were lysed and subjected to the ELISA assay. Here, a specific antibody was immobilized on plastic dishes and captured the HA from the cell lysate. After removing the supernatant and several washing steps the bound HA was detected by an enzyme linked detection anti body specifically binding HA. By addition of the enzyme substrate the amount of immobilized HA was made visible by a color reaction. Table 3 shows HA stimulation in response to Can nabidiol and Bisabolol treatment.
- Inflammation in the skin occurs after UV or chemical exposure, microbial infection or wounding to form a defence against pathogens.
- inflammation in response to UV is associated with degenerative processes in the skin resulting in photoaging, wrinkle and age spot formation.
- IL8 inflammatory mediator interleukin 8
- PGE2 prostaglandin E2
- Interleukin 8 or CXCL8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells.
- IL8 is initially produced as a precursor which undergoes cleavage to create several active IL8 isoforms.
- In- terleukin-8 plays a key role as inflammation mediator to recruit and activate neutrophils, for example, in association with gingivitis, psoriasis and other diseases.
- IL8 secretion is increased by various kinds of stress including UV & oxidant stress, which thereby cause the recruitment of inflammatory cells and induces a further increase in oxidant stress mediators, making it a key parameter in localized inflammation.
- Prostaglandin E2 is a principal mediator of inflammation and is produced in response to NFkB signalling activated by IL1 alpha/beta and IL8 stimulation.
- PGE2 Prostaglandin E2
- COX cyclooxygenase
- PGES terminal prosta glandin E synthases
- Selective COX-2 and NFkB/IL8 inhibitors reduce PGE2 production to diminish inflammation. Therefore, inhibition of PGE2 is an important target for the screen ing of anti-inflammatory substances.
- the ELISA assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of a protein in a liquid sample using antibodies directed against the protein to be measured.
- the protein of interest is immobilized on a solid surface, e.g. a microtiter plate.
- This protein is then detected by a specific antibody, forming a complex with the pro tein.
- This antibody is conjugated covalently to an enzyme or to a secondary antibody that is linked to an enzyme.
- the excess proteins and antibodies that are non-specifically bound are removed by washing steps.
- the amount of bound antibody is quantified by adding an enzy matic substrate to produce a visible signal, which indicates the quantity of the protein of in terest in the sample.
- IL8 produced and secreted by cells was determined in an enzyme linked immunosorbance assay (ELISA) from cell supernatants utiliz ing antibodies detecting the IL8.
- the assay was performed on HaCaT cells by addition of test substances and their incubation for 6h (37°C). Afterwards, inflammation was triggered with IL1 alpha for 24h or 2h, respectively, and IL8 was measured.
- the quantitative sandwich enzyme immunoassay technique was employed. A monoclonal antibody specific for human IL8 was pre-coated onto a microplate. Standards and samples/supernatants were pi petted into the wells and any IL8 present was bound by the immobilized antibody.
Abstract
Suggested is a composition comprising or consisting of (a) Cannabidiol and optionally (b) Bisabolol for use as a medicament for prophylaxis and treatment of various dysfunctions of human skin triggered particularly by stress.
Description
COMPOSITIONS COMPRISING CANNABIDIOL AND, OPTIONALLY, BISABOLOL
AREA OF INVENTION
[0001] The present invention refers to the area of so-called cosmeceuticals and concerns compositions comprising or consisting of Cannabidiol and optionally Bisabolol for a broad spectrum of skin care applications.
BACKGROUND OF THE INVENTION
[0002] Psychodermatology is a relatively new discipline that studies how specific emotional stimuli, such as stress, depression or anxiety, which arise in the brain as electrical impulses, affect the condition of human skin. According to the November 2020 "Symrise Stress Explora tion Survey, 5 countries", 40% of consumers surveyed with sensitive skin attributed it to psy chological influences, particularly stress. However, it is known that stress hormones induce the release of cortisol, which can lead to peripheral stress responses in the skin, such as in flammation, oxidative cell stress, skin barrier damage and excess sebum production. The re sult is skin sensitivity, eczema, wrinkling, oily skin feeling and acne, to name just a few nega tive manifestations.
[0003] A study by Mintel ( https://www.ncbi.nim.nih.gov/pmc/artides/PMC4082169.) in Great Britain now shows that 85% of respondents confirmed that visible disturbances of the skin appearance have a direct negative impact on their self-confidence, which triggers additional stress. This then closes the circle.
RELEVANT PRIOR ART
[0004] CN 107811190 A (YUNNAN HANMUSEN BIOL TECH) refers to an anti-inflammatory cream, comprising a cannabis sativa leaf extract enriched in Bisabolol and Cannabidiol.
[0005] CA 2971197 A (ONE WORLD CANNABIS) discloses a pharmaceutical topical composi tion comprising Cannabidiol (CBD) and tetrahydrocannabinol (THC) in a molar ratio of 1:1. The compositions may include Bisabolol and tocopheryl acetate
[0006] US 2018042890 A (ONE WORLD CANNABIS) refers to a similar composition for treat ing inflammatory skin diseases.
OBJECT OF THE INVENTION
[0007] Therefore, it has been the object of the present invention providing new actives or active compositions for prophylaxis and/or treatment of various dysfunctions of human skin triggered by emotional stimuli, in particular stress.
BRIEF DESCRIPTION OF THE INVENTION
[0008] A first object of the present invention refers to a composition comprising or consist ing of
(a) Cannabidiol and optionally (b) Bisabolol for use as a medicament for prophylaxis and/or treatment of inflammation, preferably of mi croglia-mediated inflammation of mature and developing tissue.
[0009] Another object of the present invention refers to a composition comprising or con sisting of (a) Cannabidiol and optionally
(b) Bisabolol for use as a medicament for prophylaxis and/or treatment of depressions, stress and anxiety states.
[0010] Another object of the present invention refers to a composition comprising or con- sisting of
(a) Cannabidiol and optionally
(b) Bisabolol for use as a medicament for protection of endogenous cells against oxidative stress and/or oxidative damages. [0011] Another object of the present invention refers to a composition comprising or con sisting of
(a) Cannabidiol and optionally
(b) Bisabolol for use as a medicament for prophylaxis and/or treatment of skin redness. [0012] Another object of the present invention refers to a composition comprising or con sisting of
(a) Cannabidiol and optionally
(b) Bisabolol
for use as a medicament for prophylaxis and/or treatment of disturbed skin barriers and/or dry skin.
[0013] Another object of the present invention refers to a composition comprising or con sisting of (a) Cannabidiol and optionally
(b) Bisabolol for use as a medicament for prophylaxis and/or treatment of excessive sebum production.
[0014] Surprisingly it has been observed that Cannabidiol in general and mixtures of Canna bidiol and Bisabolol in particular are strong modulators of CB2 receptors, support expression of beta-serotonin, modulate expression of the stress-mediator cortisol, show excellent anti- oxidative protection of human cells, modulate and particular down-regulate expression of cytokines like IL8 and PGE2, stimulate hyaluronic acid related gene expression to repair dis turbed or damaged skin barrier and modulate und particular down-regulate sebum produc tion in the sebum glands. Therefore, the compositions according to the present invention represent an "all-in-one active" with regard to the treatment of dysfunctions of human skin triggered in particular by stress.
[0015] For the sake of good order, it is emphasized that all the above-mentioned preferred embodiments, in particular with respect to mixtures and mixing ratios as well as indications, apply to the methods and uses according to the present invention. Therefore, repetition is not necessary at this point.
Cannabidiol
[0016] Cannabidiol (component a)
belongs to the cannabinoids representing transformation products and synthetic analogues of some terpene phenols found mainly in the hemp plant (Cannabis sativa or Cannabis indi- ca). Research on cannabinoids led to the discovery of the endocannabinoid system. Phyto- cannabinoids are substances that have similar pharmacological properties to those found in the body. Recent research shows that other plants also produce phytocannabinoids that act
on the endocannabinoid system in the same way as the cannabinoids of the hemp plant. Medically, cannabinoids are used in a variety of applications, such as neuropathic pain and spasticity (preparations made from cannabis flowers), loss of appetite in HIV/AIDS and nau sea and vomiting under chemotherapy (nabilone, dronabinol), and certain forms of childhood epilepsy.
[0017] Cannabidiol (CBD) according to the present invention can be of natural or preferably synthetic origin. Synthetic cannabinoids can be produced semi-synthetically, i.e. from natural cannabinoids, or preferably fully synthetically from simple basic substances such as for exam ple limonene. Synthetic cannabinoids are used in medicine and in neuroscience to under stand the effects of cannabinoids in the brain. A preferred example is a synthetic Cannabidiol with a purity of about 98 % which is sold under the trademark "SymDStress™".
Bisabolol
[0018] Bisabolol (component b)
is a monocyclic sesquiterpen alcohol. Preferably component (a) is an alpha-Bisabolol mixture. Even more preferably, component (a) is an alpha-Bisabolol isomer or an alpha-Bisabolol mix ture. Most preferably, component (a) is a single alpha-Bisabolol isomer or a mixture of alpha- Bisabolol isomers. The following shows as an example the structure of (-)-alpha-Bisabolol.
[0019] The present invention, however, also encompasses as component (a) natural sources containing said monocyclic sesquiterpenes in general and Bisabolol(s) in particular such as essential oils. The preferred is chamonille oil and in particular the essential oil obtained for example by water steam distillation of Matricaria chamomitta, or the plant that is known as Manzana Chamonilla, which is particular rich in Bisabolol. Also preferred is the essential oil of candeia tree ( Vanillosmopsis erythropappa), known for the high content of (-)-alpha-Bisabolol. Alpha-Bisabolol is commercially available for example under the trademark Dragosantol® 100 (Symrise AG).
[0020] Also preferred is Bisabolol(s) produced biotechnologically. Also included in the inven tion are preparations consisting predominantly of Bisabolol and a small amount of at most 5 wt. -percent and typically about 1 wt.-percent of an additive. These additives may, for exam ple, be a ginger extract or tocopherol. Corresponding products are commercially available
under the name SymRelief® (Symrise AG). Finally, said monocyclic sesquiterpen alcohol can be of natural or synthetic origin.
[0021] Compositions according to the present invention comprising both components may contain Cannabidiol and Bisabolol in ratios by weight of from about 0,1:99,09 to about 20:80, more preferably from about 1:99 to about 10:90 and most preferably from about 2:98 to about 5:95. These mixtures (including 1 wt.-percent amount of tocopherol) are sold for ex ample under the trademark SymDStress™ 100 (Symrise).
COSMETIC PREPARATIONS
The compositions according to the present invention can be administered either topically or by oral uptake. In case of applying the compositions topical to human skin, they are usually formulated as kinds of cosmetic preparations, particularly skin care products such as for ex ample creams, lotions, emulsions, mousses, sprays and the like. For oral uptake the preferred galenic form is a capsule. The formulations may comprise the compositions according to the present invention - Cannabidiol or mixture of Cannabidiol and Bisabolol - in a working amount of from for example about 0.0001 to about 1 wt.-percent, preferably from about 0.01 to about 0.5 wt.-percent.
[0022] The preparations may also contain antidandruff agents, irritation-preventing agents, irritation-inhibiting agents, antioxidants, adstringents, perspiration-inhibiting agents, anti-itch agents, antiseptic agents, ant-statics, binders, buffers, carrier materials, chelating agents, cell stimulants, cleansing agents, care agents, deodorizing agents, antiperspirants, softeners, emulsifiers, enzymes, essential oils, fibres, film-forming agents, fixatives, foam-forming agents, foam stabilizers, substances for preventing foaming, foam boosters, gelling agents, gel-forming agents, hair care agents, hair-setting agents, hair-straightening agents, moisture- donating agents, moisturizing substances, moisture-retaining substances, bleaching agents, strengthening agents, stain-removing agents, optically brightening agents, impregnating agents, dirt-repellent agents, friction-reducing agents, lubricants, moisturizing creams, oint ments, opacifying agents, plasticizing agents, covering agents, polish, gloss agents, polymers, powders, proteins, re-oiling agents, abrading agents, silicones, hair promotion agents, cool ing agents, skin-cooling agents, warming agents, skin-warming agents, stabilizers, UV- absorbing agents, UV filters, detergents, thickeners, vitamins, oils, waxes, fats, phospholipids, saturated fatty acids, mono- or polyunsaturated fatty acids, cc-hydroxy acids, polyhydroxy fatty acids, liquefiers, dyestuffs, colour-protecting agents, pigments, odoriferous substances, polyols, surfactants, electrolytes, organic solvents or silicone derivatives and the like as addi tional auxiliaries and additives.
Surfactants
[0023] Preferred auxiliaries and additives are anionic and/or amphoteric or zwitterionic sur factants. Non-ionic and cationic surfactants can be also present in the composition. Suitable examples are mentioned along with the paragraph dealing with emulsifiers.
[0024] Typical examples for anionic and zwitterionic surfactants encompass: Almondami- dopropylamine Oxide, Almondamidopropyl Betaine, Aminopropyl Laurylglutamine, Ammoni um 02-15 Alkyl Sulfate, Ammonium 02-16 Alkyl Sulfate, Ammonium Capryleth Sulfate, Ammonium Cocomonoglyceride Sulfate, Ammonium Coco-Sulfate, Ammonium Cocoyl Isethionate, Ammonium Cocoyl Sarcosinate, Ammonium 02-15 Pareth Sulfate, Ammonium C9-10 Perfluoroalkylsulfonate, Ammonium Dinonyl Sulfosuccinate, Ammonium Dodecylben- zenesulfonate, Ammonium Isostearate, Ammonium Laureth-6 Carboxylate, Ammonium Lau- reth-8 Carboxylate, Ammonium Laureth Sulfate, Ammonium Laureth-5 Sulfate, Ammonium Laureth-7 Sulfate, Ammonium Laureth-9 Sulfate, Ammonium Laureth-12 Sulfate, Ammonium Lauroyl Sarcosinate, Ammonium Lauryl Sulfate, Ammonium Lauryl Sulfosuccinate, Ammoni um Myreth Sulfate, Ammonium Myristyl Sulfate, Ammonium Nonoxynol-4 Sulfate, Ammoni um Nonoxynol-30 Sulfate, Ammonium Oleate, Ammonium Palm Kernel Sulfate, Ammonium Stearate, Ammonium Tallate, AMPD-lsostearoyl Hydrolyzed Collagen, AMPD-Rosin Hydro lyzed Collagen, AMP-lsostearoyl Hydrolyzed Collagen, AMP-lsostearoyl Hydrolyzed Keratin, AMP-lsostearoyl Hydrolyzed Soy Protein, AMP-lsostearoyl Hydrolyzed Wheat Protein, Aprico- tamidopropyl Betaine, Arachidic Acid, Arginine Hexyldecyl Phosphate, Avocadamidopropyl Betaine, Avocado Oil Glycereth-8 Esters, Babassu Acid, Babassuamidopropylamine Oxide, Babassuamidopropyl Betaine, Beeswax Acid, Behenamidopropyl Betaine, Behenamine Oxide, Beheneth-25, Beheneth-30, Behenic Acid, Behenyl Betaine, Bis- Butyldimethicone Polyglycer- yl-3, Butoxynol-5 Carboxylic Acid, Butoxynol-19 Carboxylic Acid, Butyldimoniumhydroxypro- pyl Butylglucosides Chloride, Butyldimoniumhydroxypropyl Laurylglucosides Chloride, Butyl Glucoside, Butylglucoside Caprate, Butylglucosides Hydroxypropyltrimonium Chloride, Bu- tyloctanoic Acid, C18-36 Acid, C20-40 Acid, C30-50 Acid, C16-22 Acid Amide MEA, Calcium Dodecylbenzenesulfonate, Calcium Lauroyl Taurate, C9-16 Alkane/Cycloalkane, 00-14 Alkyl Benzenesulfonic Acid, Cl 2-14 Alkyl Diaminoethylglycine HCL, C9-15 Alkyl Phosphate, Can dida Bombicola/Glucose/Methyl Rapeseedate Ferment, Canolamidopropyl Betaine, Capric Acid, Caproic Acid, Caproyl Ethyl Glucoside, Capryl/Capramidopropyl Betaine, Capryleth-4 Carboxylic Acid, Capryleth-6 Carboxylic Acid, Capryleth-9 Carboxylic Acid, Caprylic Acid, Capryloyl Collagen Amino Acids, Capryloyl Glycine, Capryloyl Hydrolyzed Collagen, Capryloyl Hydrolyzed Keratin, Capryloyl Keratin Amino Acids, Capryloyl Silk Amino Acids, Capry- lyl/Capryl Glucoside, Caprylyl/Capryl Wheat Bran/Straw Glycosides, Caprylyl Glucoside, Capry- lyl Glyceryl Ether, Caprylyl Pyrrolidone, Carnitine, Ceteareth-20, Ceteareth-23, Ceteareth-24, Ceteareth-25, Ceteareth-27, Ceteareth-28, Ceteareth-29, Ceteareth-30, Ceteareth-33, Ce- teareth-34, Ceteareth-40, Ceteareth-50, Ceteareth-55, Ceteareth-60, Ceteareth-80, Ceteareth- 100, Ceteareth-25 Carboxylic Acid, Ceteareth-2 Phosphate, Ceteareth-4 Phosphate, Ce-
teareth-5 Phosphate, Ceteareth-10 Phosphate, Ceteth-20, Ceteth-23, Ceteth-24, Ceteth-25, Ceteth-30, Ceteth-40, Ceteth-45, Ceteth-150, Ceteth-8 Phosphate, Ceteth-10 Phosphate, Ce- teth-20 Phosphate, Cetoleth-22, Cetoleth-24, Cetoleth-25, Cetoleth-30, Cetyl Betaine, Chry santhemum Sinense Flower Extract, Cl 2-14 Hydroxyalkyl Hydroxyethyl Beta-Alanine, C 12-14 Hydroxyalkyl Hydroxyethyl Sarcosine, Cocamidoethyl Betaine, Cocamidopropylamine Oxide, Cocamidopropyl Betainamide MEA Chloride, Cocamidopropyl Betaine, Cocamidopropyl Hy- droxysultaine, Cocamine Oxide, Cocaminobutyric Acid, Cocaminopropionic Acid, Coceth-7 Carboxylic Acid, Coceth-4 Glucoside, Cocoamphodipropionic Acid, Cocobetainamido Am- phopropionate, Coco-Betaine, Cocodimonium Hydroxypropyl Hydrolyzed Rice Protein, Coco- dimonium Hydroxypropyl Hydrolyzed Soy Protein, Cocodimonium Hydroxypropyl Hydrolyzed Wheat Protein, Coco-Glucoside, Cocoglucosides Hydroxypropyltrimonium Chloride, Coco- Hydroxysultaine, Coco-Morpholine Oxide, Coconut Acid, Coconut Oil Glycereth-8 Esters, Co- co/Oleamidopropyl Betaine, Coco-Sultaine, Coco/Sunfloweramidopropyl Betaine, Cocoylcho- line Methosulfate, Cocoyl Glutamic Acid, Cocoyl Hydrolyzed Collagen, Cocoyl Hydrolyzed Keratin, Cocoyl Hydrolyzed Oat Protein, Cocoyl Hydrolyzed Rice Protein, Cocoyl Hydrolyzed Silk, Cocoyl Hydrolyzed Soy Protein, Cocoyl Hydrolyzed Wheat Protein, Cocoyl Sarcosine, Corn Acid, Cottonseed Acid, Cottonseed Oil Glycereth-8 Esters, CIO-16 Pareth-1, Cl 0-16 Pa- reth-2, Cl 1-13 Pareth-6, Cl 1-13 Pareth-9, Cl 1-13 Pareth-10, Cl 1-15 Pareth-30, Cl 1-15 Pa- reth-40, C12-13 Pareth-1, C12-13 Pareth- 23, C12-14 Pareth-5, C12-14 Pareth-9, C13-15 Pa- reth-21, C14-15 Pareth-8, C20-22 Pareth-30, C20- 40 Pareth-40, C20-40 Pareth-95, C22-24 Pareth-33, C30-50 Pareth-40, C9-11 Pareth-6 Carboxylic Acid, C9-11 Pareth-8 Carboxylic Acid, Cl 1-15 Pareth-7 Carboxylic Acid, 02-13 Pareth-5 Carboxylic Acid, 02-13 Pareth-7 Carbox ylic Acid, 02-13 Pareth-8 Carboxylic Acid, 02-13 Pareth-12 Carboxylic Acid, 02-15 Pareth- 7 Carboxylic Acid, 02-15 Pareth-8 Carboxylic Acid, 02-15 Pareth- 12 Carboxylic Acid, 04- 15 Pareth-8 Carboxylic Acid, C6-10 Pareth-4 Phosphate, 02-13 Pareth-2 Phosphate, 02-13 Pareth-10 Phosphate, 02-15 Pareth-6 Phosphate, 02-15 Pareth-8 Phosphate, 02-15 Pa- reth-10 Phosphate, 02-16 Pareth-6 Phosphate, C4-18 Perfluoroalkylethyl Thiohydroxypro- pyltrimonium Chloride, Cupuassuamidopropyl Betaine, DEA-C12-13 Alkyl Sulfate, DEA-C12- 15 Alkyl Sulfate, DEA-Ceteareth-2 Phosphate, DEA-Cetyl Sulfate, DEA- Cocoamphodipropio- nate, DEA-C12-13 Pareth-3 Sulfate, DEA-Cyclocarboxypropyloleate, DEA- Dodecylbenzene- sulfonate, DEA-lsostearate, DEA-Laureth Sulfate, DEA-Lauryl Sulfate, DEA- Linoleate, DEA- Methyl Myristate Sulfonate, DEA-Myreth Sulfate, DEA-Myristate, DEA-Myristyl Sulfate, DEA- Oleth-5 Phosphate, DEA-Oleth-20 Phosphate, DEA PG-Oleate, Deceth-7 Carboxylic Acid, De- ceth-7 Glucoside, Deceth-9 Phosphate, Decylamine Oxide, Decyl Betaine, Decyl Glucoside, Decyltetradeceth-30, Decyltetradecylamine Oxide, Diammonium Lauramido-MEA Sulfosuc- cinate, Diammonium Lauryl Sulfosuccinate, Diammonium Oleamido PEG2 Sulfosuccinate, Dibutoxymethane, Di-CI 2-15 Pareth-2 Phosphate, Di-CI 2-15 Pareth-4 Phosphate, Di-CI 2-15 Pareth-6 Phosphate, Di- 02-15 Pareth-8 Phosphate, Di-CI 2-15 Pareth-10 Phosphate, Di- dodecyl Butanetetracarboxylate, Diethylamine Laureth Sulfate, Diethylhexyl Sodium Sulfosuc cinate, Dihydroxyethyl C8-10 Alkoxypropylamine Oxide, Dihydroxyethyl C9-11 Alkoxypropyl- amine Oxide, Dihydroxyethyl 02-15 Alkoxypropylamine Oxide, Dihydroxyethyl Cocamine
Oxide, Dihydroxyethyl Lauramine Oxide, Dihydroxyethyl Stearamine Oxide, Dihydroxyethyl Tallowamine Oxide, Dimethicone PEG-7 Phosphate, Dimethicone PEG-10 Phosphate, Dime- thicone PEG/PPG-7/4 Phosphate, Dimethicone PEG/PPG-12/4 Phosphate, Dimethi- cone/Polyglycerin-3 Crosspolymer, Dimethicone Propyl PG- Betaine, Dimyristyl Phosphate, Dioleoylamidoethyl Hydroxyethylmonium Methosulfate, DIPA- Hydrogenated Cocoate, DIPA- Lanolate, DIPA-Myristate, Dipotassium Capryloyl Glutamate, Dipotassium Lauryl Sulfosuccin- ate, Dipotassium Undecylenoyl Glutamate, Disodium Babassuamido MEA-Sulfosuccinate, Disodium Caproamphodiacetate, Disodium Caproamphodipropionate, Disodium Capryloam- phodiacetate, Disodium Capryloamphodipropionate, Disodium Capryloyl Glutamate, Disodi um Cetearyl Sulfosuccinate, Disodium Cetyl Phenyl Ether Disulfonate, Disodium Cetyl Sul- fosuccinate, Disodium Cocamido MEA-Sulfosuccinate, Disodium Cocamido MIPA PEG-4 Sul fosuccinate, Disodium Cocamido MIPA-Sulfosuccinate, Disodium Cocamido PEG-3 Sulfosuc cinate, Disodium Coceth-3 Sulfosuccinate, Disodium Cocoamphocarboxyethylhydroxypropyl- sulfonate, Disodium Cocoamphodiacetate, Disodium Cocoamphodipropionate, Disodium Coco-Glucoside Sulfosuccinate, Disodium Coco-Sulfosuccinate, Disodium Cocoyl Butyl Gluceth-10 Sulfosuccinate, Disodium Cocoyl Glutamate, Disodium Cl 2-14 Pareth-1 Sulfosuc cinate, Disodium Cl 2-14 Pareth-2 Sulfosuccinate, Disodium C 12-15 Pareth Sulfosuccinate, Disodium C12-14 Sec-Pareth-3 Sulfosuccinate, Disodium Cl 2-14 Sec-Pareth-5 Sulfosuccinate, Disodium C12-14 Sec-Pareth-7 Sulfosuccinate, Disodium Cl 2-14 Sec-Pareth-9 Sulfosuccinate, Disodium Cl 2-14 Sec-Pareth-12 Sulfosuccinate, Disodium Deceth-5 Sulfosuccinate, Disodium Deceth-6 Sulfosuccinate, Disodium Decyl Phenyl Ether Disulfonate, Disodium Dihydroxyethyl Sulfosuccinylundecylenate, Disodium Ethylene Dicocamide PEG-15 Disulfate, Disodium Hy drogenated Cottonseed Glyceride Sulfosuccinate, Disodium Hydrogenated Tallow Glutamate, Disodium Hydroxydecyl Sorbitol Citrate, Disodium Isodecyl Sulfosuccinate, Disodium Isos- tearamido MEA-Sulfosuccinate, Disodium Isostearamido MIPA-Sulfosuccinate, Disodium Isos- tearoamphodiacetate, Disodium Isostearoamphodipropionate, Disodium Isostearyl Sulfosuc cinate, Disodium Laneth-5 Sulfosuccinate, Disodium Lauramido MEA-Sulfosuccinate, Disodi um Lauramido MIPA Glycol Sulfosuccinate, Disodium Lauramido PEG2 Sulfosuccinate, Diso dium Lauramido PEG-5 Sulfosuccinate, Disodium Laureth-5 Carboxyamphodiacetate, Disodi um Laureth-7 Citrate, Disodium Laureth Sulfosuccinate, Disodium Laureth-6 Sulfosuccinate, Disodium Laureth-9 Sulfosuccinate, Disodium Laureth-12 Sulfosuccinate, Disodium Lau- riminobishydroxypropylsulfonate, Disodium Lauriminodiacetate, Disodium Lauriminodipropi- onate, Disodium Lauriminodipropionate Tocopheryl Phosphates, Disodium Lauroamphodiac- etate, Disodium Lauroamphodipropionate, Disodium N- Lauroyl Aspartate, Disodium Lauroyl Glutamate, Disodium Lauryl Phenyl Ether Disulfonate, Disodium Lauryl Sulfosuccinate, Diso dium Myristamido MEA-Sulfosuccinate, Disodium Nonoxynol-10 Sulfosuccinate, Disodium Oleamido MEA-Sulfosuccinate, Disodium Oleamido MIPA-Sulfosuccinate, Disodium Oleami- do PEG2 Sulfosuccinate, Disodium Oleoamphodipropionate, Disodium Oleth-3 Sulfosuccin ate, Disodium Oleyl Phosphate, Disodium Oleyl Sulfosuccinate, Disodium Palmitamido PEG2 Sulfosuccinate, Disodium Palmitoleamido PEG2 Sulfosuccinate, Disodium PEG-4 Cocamido MIPA-Sulfosuccinate, Disodium PEG-12 Dimethicone Sulfosuccinate, Disodium PEG-8 Palm
Glycerides Sulfosuccinate, Disodium PPG-2-lsodeceth-7 Carboxyamphodiacetate, Disodium Ricinoleamido MEA-Sulfosuccinate, Disodium Sitostereth-14 Sulfosuccinate, Disodium Soyamphodiacetate, Disodium Stearamido MEA-Sulfosuccinate, Disodium Steariminodi- propionate, Disodium Stearoamphodiacetate, Disodium Stearoyl Glutamate, Disodium Stearyl Sulfosuccinamate, Disodium Stearyl Sulfosuccinate, Disodium 2-Sulfolaurate, Disodium 2- Sulfopalmitate, Disodium Tallamido MEA-Sulfosuccinate, Disodium Tallowamido MEA- Sulfosuccinate, Disodium Tallowamphodiacetate, Disodium Tallowiminodipropionate, Disodi um Tallow Sulfosuccinamate, Disodium Tridecylsulfosuccinate, Disodium Undecylenamido MEA-Sulfosuccinate, Disodium Undecylenamido PEG2 Sulfosuccinate, Disodium Un- decylenoyl Glutamate, Disodium Wheat Germamido MEA-Sulfosuccinate, Disodium Wheat Germamido PEG2 Sulfosuccinate, Disodium Wheatgermamphodiacetate, Di-TEA-Cocamide Diacetate, Di-TEA-Oleamido PEG2 Sulfosuccinate, Di-TEA-Palmitoyl Aspartate, Ditridecyl So dium Sulfosuccinate, Dodecylbenzene Sulfonic Acid, Erucamidopropyl Hydroxysultaine, Ethylhexeth-3 Carboxylic Acid, Ethyl PEG-15 Cocamine Sulfate, Glyceryl Capryl Ether, Hex- yldecanoic Acid, Hydrogenated Coconut Acid, Hydrogenated Laneth-25, Hydrogenated Men haden Acid, Hydrogenated Palm Acid, Hydrogenated Palm Kernel Amine Oxide, Hydrogenat ed Tallow Acid, Hydrogenated Tallowamine Oxide, Hydrogenated Tallow Betaine, Hydrogen ated Talloweth-25, Hydrogenated Tallowoyl Glutamic Acid, Hydrolyzed Candida Bombicola Extract, Hydroxyceteth-60, Hydroxyethyl Acetomonium PG-Dimethicone, Hydroxyethylbutyl- amine Laureth Sulfate, Hydroxyethyl Carboxymethyl Cocamidopropylamine, Hydroxyethyl Hydroxypropyl Cl 2-15 Alkoxypropylamine Oxide, Hydroxylauryl/Hydroxymyristyl Betaine, Hydroxystearic Acid, Hydroxysuccinimidyl C10-40 Isoalkyl Acidate, Hydroxysuccinimidyl C21- 22 Isoalkyl Acidate, Hydroxysultaines, IPDI/PEG-15 Soyamine Oxide Copolymer, IPDI/PEG-15 Soyethonium Ethosulfate Copolymer, IPDI/PEG-15 Soy Glycinate Copolymer, lsoceteth-30, lsolaureth-4 Phosphate, lsopolyglyceryl-3 Dimethicone, lsopolyglyceryl-3 Dimethiconol, Iso- propanolamine Lanolate, Isopropylamine Dodecylbenzenesulfonate, Isostearamidopropyla- mine Oxide, Isostearamidopropyl Betaine, Isostearamidopropyl Morpholine Oxide, Isos- teareth-8, lsosteareth-16, lsosteareth-22, lsosteareth-25, lsosteareth-50, Isostearic Acid, Isos- tearoyl Hydrolyzed Collagen, Jojoba Oil PEG-150 Esters, Jojoba Wax PEG-80 Esters, Jojoba Wax PEG-120 Esters, Laneth-20, Laneth-25, Laneth-40, Laneth-50, Laneth-60, Laneth-75, Lan olin Acid, Lauramidopropylamine Oxide, Lauramidopropyl Betaine, Lauramidopropyl Hy droxysultaine, Lauramine Oxide, Lauraminopropionic Acid, Laurdimoniumhydroxypropyl Decylglucosides Chloride, Laurdimoniumhydroxypropyl Laurylglucosides Chloride, Laureth- 16, Laureth-20, Laureth-21, Laureth-23, Laureth-25, Laureth-30, Laureth-38, Laureth-40, Lau- reth-3 Carboxylic Acid, Laureth-4 Carboxylic Acid, Laureth-5 Carboxylic Acid, Laureth- 6 Car boxylic Acid, Laureth-8 Carboxylic Acid, Laureth-10 Carboxylic Acid, Laureth-11 Carboxylic Acid, Laureth-12 Carboxylic Acid, Laureth-13 Carboxylic Acid, Laureth-14 Carboxylic Acid, Laureth-17 Carboxylic Acid, Laureth-6 Citrate, Laureth-7 Citrate, Laureth-1 Phosphate, Lau- reth-2 Phosphate, Laureth-3 Phosphate, Laureth-4 Phosphate, Laureth-7 Phosphate, Laureth- 8 Phosphate, Laureth-7 Tartrate, Laurie Acid, Laurimino Bispropanediol, Lauriminodipropionic Acid, Lauroamphodipropionic Acid, Lauroyl Beta-Alanine, Lauroyl Collagen Amino Acids, Lau-
royl Ethyltrimonium Methosulfate, Lauroyl Hydrolyzed Collagen, Lauroyl Hydrolyzed Elastin, Lauroyl Methyl Glucamide, Lauroyl Sarcosine, Lauroyl Silk Amino Acids, Lauryl Betaine, Lauryl Dimethicone/Polyglycerin-3 Crosspolymer, Lauryldimoniumhydroxypropyl Cocoglucosides Chloride, Lauryl Glucoside, Laurylglucosides Hydroxypropyltrimonium Chloride, Lauryl Glycol Hydroxypropyl Ether, Lauryl Hydroxysultaine, Lauryl Malamide, Lauryl Methylglucamide, Lau- ryl/Myristyl Glycol Hydroxypropyl Ether, Lauryl/Myristyl Wheat Bran/Straw Glycosides, Lauryl Polyglyceryl-3 Polydimethylsiloxyethyl Dimethicone, Lauryl Pyrrolidone, Lauryl Sultaine, Lino- leic Acid, Linolenic Acid, Linseed Acid, Lysine Cocoate, Macadamia Seed Oil Glycereth-8 Es ters, Magnesium Coceth Sulfate, Magnesium Coco-Sulfate, Magnesium Isododecylbenzene- sulfonate, Magnesium Laureth-11 Carboxylate, Magnesium Laureth Sulfate, Magnesium Lau- reth-5 Sulfate, Magnesium Laureth-8 Sulfate, Magnesium Laureth-16 Sulfate, Magnesium Laureth-3 Sulfosuccinate, Magnesium Lauryl Hydroxypropyl Sulfonate, Magnesium Lauryl Sulfate, Magnesium Methyl Cocoyl Taurate, Magnesium Myreth Sulfate, Magnesium Oleth Sulfate, Magnesium/TEA-Coco-Sulfate, Manicouagan Clay, MEA-Cocoate, MEA-Laureth-6 Carboxylate, MEA- Laureth Sulfate, MEA-Lauryl Sulfate, MEA PPG-6 Laureth-7 Carboxylate, MEA-PPG-8-Steareth-7 Carboxylate, MEA-Undecylenate, Meroxapol 108, Meroxapol 174, Meroxapol 178, Meroxapol 254, Meroxapol 255, Meroxapol 258, Meroxapol 314, Methoxy PEG-450 Amidoglutaroyl Succinimide, Methoxy PEG-450 Amido Hydroxysuccinimidyl Suc- cinamate, Methoxy PEG-450 Maleimide, Methyl Morpholine Oxide, Milkamidopropyl Amine Oxide, Milkamidopropyl Betaine, Minkamidopropylamine Oxide, Minkamidopropyl Betaine, MIPA Cl 2-15 Pareth Sulfate, MIPA-Dodecylbenzenesulfonate, MIPA-Laureth Sulfate, MIPA- Lauryl Sulfate, Mixed Isopropanolamines Lanolate, Mixed Isopropanolamines Lauryl Sulfate, Mixed Isopropanolamines Myristate, Morpholine Oleate, Morpholine Stearate, Myreth-3 Car boxylic Acid, Myreth-5 Carboxylic Acid, Myristalkonium Chloride, Myristamidopropylamine Oxide, Myristamidopropyl Betaine, Myristamidopropyl Dimethylamine Phosphate, Myristami- dopropyl Hydroxysultaine, Myristamidopropyl PG-Dimonium Chloride Phosphate, Myrista- mine Oxide, Myristaminopropionic Acid, Myristic Acid, Myristoyl Ethyltrimonium Methosul fate, Myristoyl Glutamic Acid, Myristoyl Hydrolyzed Collagen, Myristoyl Sarcosine, Myristyl Betaine, Myristyl/Cetyl Amine Oxide, Myristyldimoniumhydroxypropyl Cocoglucosides Chlo ride, Myristyl Glucoside, Myristyl Phosphate, Nonoxynol-20, Nonoxynol-23, Nonoxynol-25, Nonoxynol-30, Nonoxynol-35, Nonoxynol-40, Nonoxynol-44, Nonoxynol-50, Nonoxynol-100, Nonoxynol-120, Nonoxynol-5 Carboxylic Acid, Nonoxynol-8 Carboxylic Acid, Nonoxynol-10 Carboxylic Acid, Nonoxynol-3 Phosphate, Nonoxynol-4 Phosphate, Nonoxynol-6 Phosphate, Nonoxynol-9 Phosphate, Nonoxynol-10 Phosphate, Nonyl Nonoxynol-30, Nonyl Nonoxynol- 49, Nonyl Nonoxynol-100, Nonyl Nonoxynol-150, Nonyl Nonoxynol-7 Phosphate, Nonyl Nonoxynol-8 Phosphate, Nonyl Nonoxynol-9 Phosphate, Nonyl Nonoxynol-10 Phosphate, Nonyl Nonoxynol-11 Phosphate, Nonyl Nonoxynol-15 Phosphate, Nonyl Nonoxynol-24 Phosphate, Oatamidopropyl Betaine, Octoxynol-16, Octoxynol-25, Octoxynol-30, Octoxynol- 33, Octoxynol-40, Octoxynol-70, Octoxynol-20 Carboxylic Acid, Octyldodeceth-20, Oc- tyldodeceth-25, Octyldodeceth-30, Oleamidopropylamine Oxide, Oleamidopropyl Betaine, Oleamidopropyl Hydroxysultaine, Oleamine Oxide, Oleic Acid, Oleoyl Hydrolyzed Collagen,
Oleoyl Sarcosine, Oleth-20, Oleth-23, Oleth-24, Oleth-25, Oleth-30, Oleth-35, Oleth-40, Oleth-44, Oleth-50, Oleth-3 Carboxylic Acid, Oleth-6 Carboxylic Acid, Oleth-10 Carboxylic Acid, Oleyl Betaine, Olivamidopropylamine Oxide, Olivamidopropyl Betaine, Olive Acid, Oli- voyl Hydrolyzed Wheat Protein, Ophiopogon Extract Stearate, Ozonized Oleth-10, Ozonized PEG-10 Oleate, Ozonized PEG-14 Oleate, Ozonized Polysorbate 80, Palm Acid, Pal- mamidopropyl Betaine, Palmeth-2 Phosphate, Palmitamidopropylamine Oxide, Palmitami- dopropyl Betaine, Palmitamine Oxide, Palmitic Acid, Palmitoyl Collagen Amino Acids, Pal- mitoyl Glycine, Palmitoyl Hydrolyzed Collagen, Palmitoyl Hydrolyzed Milk Protein, Palmitoyl Hydrolyzed Wheat Protein, Palmitoyl Keratin Amino Acids, Palmitoyl Oligopeptide, Palmitoyl Silk Amino Acids, Palm Kernel Acid, Palm Kernelamidopropyl Betaine, Peach Kernel Oil Glycereth-8 Esters, Peanut Acid, PEG- 10 Castor Oil, PEG-40 Castor Oil, PEG-44 Castor Oil, PEG-50 Castor Oil, PEG-54 Castor Oil, PEG-55 Castor Oil, PEG-60 Castor Oil, PEG-80 Castor Oil, PEG-100 Castor Oil, PEG200 Castor Oil, PEG-11 Cocamide, PEG-6 Cocamide Phosphate, PEG-4 Cocamine, PEG-8 Cocamine, PEG-12 Cocamine, PEG-150 Dibehenate, PEG-90 Diisos tearate, PEG-75 Dilaurate, PEG-150 Dilaurate, PEG-75 Dioleate, PEG-150 Dioleate, PEG-75 Distearate, PEG-120 Distearate, PEG-150 Distearate, PEG-175 Distearate, PEG-190 Distearate, PEG250 Distearate, PEG-30 Glyceryl Cocoate, PEG-40 Glyceryl Cocoate, PEG-78 Glyceryl Co- coate, PEG-80 Glyceryl Cocoate, PEG-30 Glyceryl Isostearate, PEG-40 Glyceryl Isostearate, PEG-50 Glyceryl Isostearate, PEG-60 Glyceryl Isostearate, PEG-90 Glyceryl Isostearate, PEG23 Glyceryl Laurate, PEG-30 Glyceryl Laurate, PEG25 Glyceryl Oleate, PEG-30 Glyceryl Oleate, PEG-30 Glyceryl Soyate, PEG25 Glyceryl Stearate, PEG-30 Glyceryl Stearate, PEG-40 Glyceryl Stearate, PEG-120 Glyceryl Stearate, PEG200 Glyceryl Stearate, PEG28 Glyceryl Tallowate, PEG- 80 Glyceryl Tallowate, PEG-82 Glyceryl Tallowate, PEG-130 Glyceryl Tallowate, PEG200 Glycer yl Tallowate, PEG-45 Hydrogenated Castor Oil, PEG-50 Hydrogenated Castor Oil, PEG-54 Hy drogenated Castor Oil, PEG-55 Hydrogenated Castor Oil, PEG-60 Hydrogenated Castor Oil, PEG-80 Hydrogenated Castor Oil, PEG-100 Hydrogenated Castor Oil, PEG200 Hydrogenated Castor Oil, PEG-30 Hydrogenated Lanolin, PEG-70 Hydrogenated Lanolin, PEG-50 Hydrogen ated Palmamide, PEG2 Isostearate, PEG-3 Isostearate, PEG-4 Isostearate, PEG-6 Isostearate, PEG-8 Isostearate, PEG-10 Isostearate, PEG-12 Isostearate, PEG20 Isostearate, PEG-30 Isos tearate, PEG-40 Isostearate, PEG- 26 Jojoba Acid, PEG-40 Jojoba Acid, PEG- 15 Jojoba Alcohol, PEG26 Jojoba Alcohol, PEG-40 Jojoba Alcohol, PEG-35 Lanolin, PEG-40 Lanolin, PEG-50 Lano lin, PEG-55 Lanolin, PEG-60 Lanolin, PEG- 70 Lanolin, PEG-75 Lanolin, PEG-85 Lanolin, PEG- 100 Lanolin, PEG-150 Lanolin, PEG-75 Lanolin Oil, PEG2 Lauramide, PEG-3 Lauramine Oxide, PEG20 Laurate, PEG-32 Laurate, PEG-75 Laurate, PEG-150 Laurate, PEG-70 Mango Glycerides, PEG20 Mannitan Laurate, PEG-8 Methyl Ether Dimethicone, PEG-120 Methyl Glucose Diole ate, PEG-80 Methyl Glucose Laurate, PEG-120 Methyl Glucose Trioleate, PEG-4 Montanate, PEG-30 Oleamine, PEG20 Oleate, PEG23 Oleate, PEG-32 Oleate, PEG-36 Oleate, PEG-75 Ole ate, PEG-150 Oleate, PEG20 Palmitate, PEG-150 Polyglyceryl-2 Tristearate, PEG/PPG-28/21 Acetate Dimethicone, PEG/PPG-24/18 Butyl Ether Dimethicone, PEG/PPG-3/17 Copolymer, PEG/PPG-5/35 Copolymer, PEG/PPG-8/55 Copolymer, PEG/PPG-10/30 Copolymer, PEG/PPG- 10/65 Copolymer, PEG/PPG-12/35 Copolymer, PEG/PPG-16/17 Copolymer, PEG/PPG-20/9
Copolymer, PEG/PPG-20/20 Copolymer, PEG/PPG-20/60 Copolymer, PEG/PPG- 20/65 Copol ymer, PEG/PPG-22/25 Copolymer, PEG/PPG-28/30 Copolymer, PEG/PPG-30-35 Copolymer, PEG/PPG-30/55 Copolymer, PEG/PPG-35/40 Copolymer, PEG/PPG-50/40 Copolymer, PEG/PPG-150/35 Copolymer, PEG/PPG- 160/30 Copolymer, PEG/PPG- 190/60 Copolymer, PEG/PPG-200/40 Copolymer, PEG/PPG-300/55 Copolymer, PEG/PPG-20/22 Methyl Ether Di- methicone, PEG26-PPG-30 Phosphate, PEG/PPG-4/2 Propylheptyl Ether, PEG/PPG-6/2 Propylheptyl Ether, PEG-7/PPG-2 Propylheptyl Ether, PEG/PPG-8/2 Propylheptyl Ether, PEG/PPG- 10/2 Propylheptyl Ether, PEG/PPG- 14/2 Propylheptyl Ether, PEG/PPG-40/2 Propylheptyl Ether, PEG/PPG- 10/2 Ricinoleate, PEG/PPG-32/3 Ricinoleate, PEG-55 Propylene Glycol Oleate, PEG25 Propylene Glycol Stearate, PEG-75 Propylene Glycol Stearate, PEG-120 Propylene Glycol Stearate, PEG-5 Rapeseed Sterol, PEG-10 Rapeseed Sterol, PEG-40 Ricinole- amide, PEG-75 Shea Butter Glycerides, PEG-75 Shorea Butter Glycerides, PEG20 Sorbitan Co- coate, PEG20 Sorbitan Isostearate, PEG-40 Sorbitan Lanolate, PEG-75 Sorbitan Lanolate, PEG- 10 Sorbitan Laurate, PEG-40 Sorbitan Laurate, PEG-44 Sorbitan Laurate, PEG-75 Sorbitan Laurate, PEG-80 Sorbitan Laurate, PEG20 Sorbitan Oleate, PEG-80 Sorbitan Palmitate, PEG-40 Sorbitan Stearate, PEG-60 Sorbitan Stearate, PEG-160 Sorbitan Triisostearate, PEG-40 Soy Sterol, PEG2 Stearamide Carboxylic Acid, PEG-9 Stearamide Carboxylic Acid, PEG20 Stearate, PEG23 Stearate, PEG25 Stearate, PEG-30 Stearate, PEG-32 Stearate, PEG-35 Stearate, PEG-36 Stearate, PEG-40 Stearate, PEG-45 Stearate, PEG-50 Stearate, PEG-55 Stearate, PEG-75 Stea rate, PEG-90 Stearate, PEG-100 Stearate, PEG- 120 Stearate, PEG-150 Stearate, PEG-45 Stea rate Phosphate, PEG20 Tallate, PEG-50 Tallow Amide, PEG2 Tallowamide DEA, PEG20 Tal- lowate, PEG-66 Trihydroxystearin, PEG200 Trihydroxystearin, PEG-60 Tsubakiate Glycerides, Pelargonic Acid, Pentadoxynol-200, Pheneth-6 Phosphate, Poloxamer 105, Poloxamer 108, Poloxamer 182, Poloxamer 183, Poloxamer 184, Poloxamer 188, Poloxamer 217, Poloxamer 234, Poloxamer 235, Poloxamer 237, Poloxamer 238, Poloxamer 288, Poloxamer 334, Polox amer 335, Poloxamer 338, Poloxamine 908, Poloxamine 1508, Polydimethylsiloxy PEG/PPG- 24/19 Butyl Ether Silsesquioxane, Polydimethylsiloxy PPG-13 Butyl Ether Silsesquioxane, Poly- glyceryl-6 Caprate, Polyglyceryl-10 Dilaurate, Polyglyceryl-20 Heptacaprylate, Polyglyceryl-20 Hexacaprylate, Polyglyceryl-2 Lauryl Ether, Polyglyceryl- 10 Lauryl Ether, Polyglyceryl-20 Octai- sononanoate, Polyglyceryl-6 Pentacaprylate, Polyglyceryl- 10 Pentacaprylate, Polyglyceryl-3 Polydimethylsiloxyethyl Dimethicone, Polyglyceryl-6 Tetracaprylate, Polyglyceryl-10 Tetra- laurate, Polyglyceryl-6 Tricaprylate, Polyglyceryl-10 Trilaurate, Polyquaternium- 77, Polyqua- ternium-78, Polyquaternium-79, Polyquaternium-80, Polyquaternium-81, Polyquaternium- 82, Pomaderris Kumerahou Flower/Leaf Extract, Poria Cocos Extract, Potassium Abietoyl Hydro lyzed Collagen, Potassium Babassuate, Potassium Behenate, Potassium C9-15 Alkyl Phos phate, Potassium Cl 1-15 Alkyl Phosphate, Potassium Cl 2-13 Alkyl Phosphate, Potassium Cl 2-14 Alkyl Phosphate, Potassium Caprate, Potassium Capryloyl Glutamate, Potassium Capryloyl Hydrolyzed Rice Protein, Potassium Castorate, Potassium Cocoate, Potassium Co- coyl Glutamate, Potassium Cocoyl Glycinate, Potassium Cocoyl Hydrolyzed Casein, Potassium Cocoyl Hydrolyzed Collagen, Potassium Cocoyl Hydrolyzed Corn Protein, Potassium Cocoyl Hydrolyzed Keratin, Potassium Cocoyl Hydrolyzed Oat Protein, Potassium Cocoyl Hydrolyzed
Potato Protein, Potassium Cocoyl Hydrolyzed Rice Bran Protein, Potassium Cocoyl Hydro lyzed Rice Protein, Potassium Cocoyl Hydrolyzed Silk, Potassium Cocoyl Hydrolyzed Soy Pro tein, Potassium Cocoyl Hydrolyzed Wheat Protein, Potassium Cocoyl Hydrolyzed Yeast Pro tein, Potassium Cocoyl PCA, Potassium Cocoyl Sarcosinate, Potassium Cocoyl Taurate, Potas sium Cornate, Potassium Cyclocarboxypropyloleate, Potassium Dihydroxyethyl Cocamine Oxide Phosphate, Potassium Dimethicone PEG-7 Phosphate, Potassium Dodecylbenzenesul- fonate, Potassium Hempseedate, Potassium Hydrogenated Cocoate, Potassium Hydrogenat ed Palmate, Potassium Hydrogenated Tallowate, Potassium Hydroxystearate, Potassium Isos tearate, Potassium Lanolate, Potassium Laurate, Potassium Laureth-3 Carboxylate, Potassium Laureth-4 Carboxylate, Potassium Laureth-5 Carboxylate, Potassium Laureth-6 Carboxylate, Potassium Laureth-10 Carboxylate, Potassium Laureth Phosphate, Potassium Lauroyl Collagen Amino Acids, Potassium Lauroyl Glutamate, Potassium Lauroyl Hydrolyzed Collagen, Potassi um Lauroyl Hydrolyzed Pea Protein, Potassium Lauroyl Hydrolyzed Soy Protein, Potassium Lauroyl PCA, Potassium Lauroyl Pea Amino Acids, Potassium Lauroyl Sarcosinate, Potassium Lauroyl Silk Amino Acids, Potassium Lauroyl Wheat Amino Acids, Potassium Lauryl Phos phate, Potassium Lauryl Sulfate, Potassium Linoleate, Potassium Meta phosphate, Potassium Methyl Cocoyl Taurate, Potassium Myristate, Potassium Myristoyl Glutamate, Potassium Myristoyl Hydrolyzed Collagen, Potassium Octoxynol-12 Phosphate, Potassium Oleate, Potas sium Oleoyl Hydrolyzed Collagen, Potassium Olivate, Potassium Olivoyl Hydrolyzed Oat Pro tein, Potassium Olivoyl Hydrolyzed Wheat Protein, Potassium Olivoyl/Lauroyl Wheat Amino Acids, Potassium Olivoyl PCA, Potassium Palmate, Potassium Palmitate, Potassium Palmitoyl Hydrolyzed Corn Protein, Potassium Palmitoyl Hydrolyzed Oat Protein, Potassium Palmitoyl Hydrolyzed Rice Protein, Potassium Palmitoyl Hydrolyzed Sweet Almond Protein, Potassium Palmitoyl Hydrolyzed Wheat Protein, Potassium Palm Kernelate, Potassium Peanutate, Potas sium Rapeseedate, Potassium Ricinoleate, Potassium Safflowerate, Potassium Soyate, Potas sium Stearate, Potassium Stearoyl Hydrolyzed Collagen, Potassium Tallate, Potassium Tal lowate, Potassium Taurate, Potassium Taurine Laurate, Potassium Trideceth-3 Carboxylate, Potassium Trideceth-4 Carboxylate, Potassium Trideceth-7 Carboxylate, Potassium Trideceth- 15 Carboxylate, Potassium Trideceth-19 Carboxylate, Potassium Trideceth-6 Phosphate, Po tassium Trideceth-7 Phosphate, Potassium Tsubakiate, Potassium Undecylenate, Potassium Undecylenoyl Hydrolyzed Collagen, Potassium Undecylenoyl Hydrolyzed Rice Protein, PPG- 30- Buteth-30, PPG-36-Buteth-36, PPG-38-Buteth-37, PPG-30-Capryleth-4 Phosphate, PPG- 10 Cetyl Ether Phosphate, PPG-2 C9-11 Pareth-8, PPG-1-Deceth-5, PPG-3-Deceth-2 Carbox ylic Acid, PPG-30 Ethylhexeth-4 Phosphate, PPG-20-Glycereth-30, PPG-2 Hydroxyethyl Co- co/lsostearamide, PPG-2- lsodeceth-8, PPG-2-lsodeceth-10, PPG-2-lsodeceth-18, PPG-2- lsodeceth-25, PPG-4-lsodeceth-10, Propyltrimonium Hydrolyzed Collagen, Quaternium-24, Quaternium-52, Quaternium-87, Rapeseed Acid, Rice Bran Acid, Rice Oil Glycereth-8 Esters, Ricinoleamidopropyl Betaine, Ricinoleic Acid, Ricinoleth-40, Safflower Acid, Sapindus Oa- huensis Fruit Extract, Saponaria Officinalis Root Powder, Saponins, Sekken-K, Sekken-Na/K, Sekken Soji, Sekken Soji-K, Sesame Oil Glycereth-8 Esters, Sesamidopropylamine Oxide, Ses- amidopropyl Betaine, Shea Butteramidopropyl Betaine, Shea Butter Glycereth-8 Esters, Sodi-
um Arachidate, Sodium Arganampohoacetate, Sodium Astrocaryum Murumuruate, Sodium Avocadoate, Sodium Babassuamphoacetate, Sodium Babassuate, Sodium Babassu Sulfate, Sodium Behenate, Sodium Bisglycol Ricinosulfosuccinate, Sodium Bis- Hydroxyethylglycinate Coco-Glucosides Crosspolymer, Sodium Bis-Hydroxyethylglycinate Lauryl- Glucosides Cross polymer, Sodium Borageamidopropyl PG-Dimonium Chloride Phosphate, Sodium Butoxynol- 12 Sulfate, Sodium Butylglucosides Hydroxypropyl Phosphate, Sodium Cl 3-17 Alkane Sul fonate, Sodium C 14-18 Alkane Sulfonate, Sodium C12-15 Alkoxypropyl Iminodipropionate, Sodium Cl 0-16 Alkyl Sulfate, Sodium Cl 1-15 Alkyl Sulfate, Sodium Cl 2-13 Alkyl Sulfate, So dium 02-15 Alkyl Sulfate, Sodium Cl 2-18 Alkyl Sulfate, Sodium C16-20 Alkyl Sulfate, Sodi um C9-22 Alkyl Sec Sulfonate, Sodium C14-17 Alkyl Sec Sulfonate, Sodium Caprate, Sodium Caproamphoacetate, Sodium Caproamphohydroxypropylsulfonate, Sodium Caproampho- propionate, Sodium Caproyl Methyltaurate, Sodium Caprylate, Sodium Capryleth-2 Carbox- ylate, Sodium Capryleth-9 Carboxylate, Sodium Capryloamphoacetate, Sodium Capryloam- phohydroxypropylsulfonate, Sodium Capryloamphopropionate, Sodium Capryloyl Glutamate, Sodium Capryloyl Hydrolyzed Wheat Protein, Sodium Caprylyl PG-Sulfonate, Sodium Caprylyl Sulfonate, Sodium Castorate, Sodium Ceteareth-13 Carboxylate, Sodium Cetearyl Sulfate, Sodium Ceteth-13 Carboxylate, Sodium Cetyl Sulfate, Sodium Cocamidopropyl PG-Dimonium Chloride Phosphate, Sodium Cocaminopropionate, Sodium Coceth Sulfate, Sodium Coceth- 30 Sulfate, Sodium Cocoabutteramphoacetate, Sodium Cocoa Butterate, Sodium Cocoam- phoacetate, Sodium Cocoamphohydroxypropylsulfonate, Sodium Cocoamphopropionate, Sodium Cocoate, Sodium Coco/Babassu/Andiroba Sulfate, Sodium Coco/Babassu Sulfate, Sodium Cocoglucosides Hydroxypropyl Phosphate, Sodium Cocoglucosides Hy droxy propyl - sulfonate, Sodium Coco-Glucoside Tartrate, Sodium Cocoglyceryl Ether Sulfonate, Sodium Coco/Hydrogenated Tallow Sulfate, Sodium Cocoiminodiacetate, Sodium Cocomonoglycer- ide Sulfate, Sodium Cocomonoglyceride Sulfonate, Sodium Coco PG-Dimonium Chloride Phosphate, Sodium Coco-Sulfate, Sodium Coco Sulfoacetate, Sodium Cocoyl Alaninate, Sodi um Cocoyl Amino Acids, Sodium Cocoyl Collagen Amino Acids, Sodium Cocoyl Glutamate, Sodium Cocoyl Glutaminate, Sodium Cocoyl Glycinate, Sodium Cocoyl/Hydrogenated Tallow Glutamate, Sodium Cocoyl Hydrolyzed Collagen, Sodium Cocoyl Hydrolyzed Keratin, Sodium Cocoyl Hydrolyzed Rice Protein, Sodium Cocoyl Hydrolyzed Silk, Sodium Cocoyl Hydrolyzed Soy Protein, Sodium Cocoyl Hydrolyzed Sweet Almond Protein, Sodium Cocoyl Hydrolyzed Wheat Protein, Sodium Cocoyl Hydrolyzed Wheat Protein Glutamate, Sodium Cocoyl Isethio- nate, Sodium Cocoyl Methylaminopropionate, Sodium Cocoyl Oat Amino Acids, Sodium Co- coyl/Palmoyl/Sunfloweroyl Glutamate, Sodium Cocoyl Proline, Sodium Cocoyl Sarcosinate, Sodium Cocoyl Taurate, Sodium Cocoyl Threoninate, Sodium Cocoyl Wheat Amino Acids, Sodium Cl 2-14 Olefin Sulfonate, Sodium C 14-16 Olefin Sulfonate, Sodium C14- 18 Olefin Sulfonate, Sodium Cl 6-18 Olefin Sulfonate, Sodium Cornamphopropionate, Sodium Cotton- seedamphoacetate, Sodium Cl 3-15 Pareth-8 Butyl Phosphate, Sodium C9-11 Pareth-6 Car boxylate, Sodium Cl 1-15 Pareth-7 Carboxylate, Sodium C12-13 Pareth-5 Carboxylate, Sodi um C 12-13 Pareth-8 Carboxylate, Sodium Cl 2-13 Pareth-12 Carboxylate, Sodium C 12-15 Pareth-6 Carboxylate, Sodium Cl 2-15 Pareth-7 Carboxylate, Sodium Cl 2-15 Pareth-8 Car-
boxylate, Sodium C 14-15 Pareth-8 Carboxylate, Sodium Cl 2-14 Sec-Pareth-8 Carboxylate, Sodium C14-15 Pareth-PG Sulfonate, Sodium Cl 2-13 Pareth-2 Phosphate, Sodium Cl 3-15 Pareth-8 Phosphate, Sodium C9-15 Pareth-3 Sulfate, Sodium C10-15 Pareth Sulfate, Sodium Cl 0-16 Pareth-2 Sulfate, Sodium 02-13 Pareth Sulfate, Sodium 02-15 Pareth Sulfate, Sodi um 02-15 Pareth-3 Sulfate, Sodium 03-15 Pareth-3 Sulfate, Sodium 02-14 Sec-Pareth-3 Sulfate, Sodium 02-15 Pareth-3 Sulfonate, Sodium 02-15 Pareth-7 Sulfonate, Sodium 02- 15 Pareth-15 Sulfonate, Sodium Deceth-2 Carboxylate, Sodium Deceth Sulfate, Sodium Decylbenzenesulfonate, Sodium Decylglucosides Hydroxypropyl Phosphate, Sodium Decyl- glucosides Hydroxypropylsulfonate, Sodium Dilaureth-7 Citrate, Sodium Dilaureth-10 Phos phate, Sodium Dilinoleamidopropyl PG-Dimonium Chloride Phosphate, Sodium Dilinoleate, Sodium Dioleth-8 Phosphate, Sodium Dodecylbenzenesulfonate, Sodium Ethyl 2- Sul- folaurate, Sodium Glyceryl Oleate Phosphate, Sodium Grapeseedamidopropyl PG-Dimonium Chloride Phosphate, Sodium Grapeseedamphoacetate, Sodium Grapeseedate, Sodium Hempseedamphoacetate, Sodium Hexeth-4 Carboxylate, Sodium Hydrogenated Cocoate, Sodium Hydrogenated Cocoyl Methyl Isethionate, Sodium Hydrogenated Palmate, Sodium Hydrogenated Tallowate, Sodium Hydrogenated Tallowoyl Glutamate, Sodium Hydroxylau- ryldimonium Ethyl Phosphate, Sodium Hydroxypropyl Palm Kernelate Sulfonate, Sodium Hy- droxypropylphosphate Decylglucoside Crosspolymer, Sodium Hydroxypropylphosphate Lau- rylglucoside Crosspolymer, Sodium Hydroxypropylsulfonate Cocoglucoside Crosspolymer, Sodium Hydroxypropylsulfonate Decylglucoside Crosspolymer, Sodium Hydroxypropyl sulfonate Laurylglucoside Crosspolymer, Sodium Hydroxystearate, Sodium Isostearate, Sodi um lsosteareth-6 Carboxylate, Sodium Isosteareth- 11 Carboxylate, Sodium Isostearoampho- acetate, Sodium Isostearoamphopropionate, Sodium N- Isostearoyl Methyltaurate, Sodium Laneth Sulfate, Sodium Lanolate, Sodium Lardate, Sodium Lauramido Diacetate, Sodium Lau- raminopropionate, Sodium Laurate, Sodium Laureth-3 Carboxylate, Sodium Laureth-4 Car boxylate, Sodium Laureth-5 Carboxylate, Sodium Laureth-6 Carboxylate, Sodium Laureth-8 Carboxylate, Sodium Laureth-11 Carboxylate, Sodium Laureth-12 Carboxylate, Sodium Lau- reth-13 Carboxylate, Sodium Laureth-14 Carboxylate, Sodium Laureth-16 Carboxylate, Sodi um Laureth-17 Carboxylate, Sodium Laureth Sulfate, Sodium Laureth-5 Sulfate, Sodium Lau- reth- 7 Sulfate, Sodium Laureth-8 Sulfate, Sodium Laureth-12 Sulfate, Sodium Laureth-40 Sulfate, Sodium Laureth-7 Tartrate, Sodium Lauriminodipropionate, Sodium Lauroamphoace- tate, Sodium Lauroamphohydroxypropylsulfonate, Sodium Lauroampho PG-Acetate Phos phate, Sodium Lauroamphopropionate, Sodium Lauroyl Aspartate, Sodium Lauroyl Collagen Amino Acids, Sodium Lauroyl Glycine Propionate, Sodium Lauroyl Hydrolyzed Collagen, So dium Lauroyl Hydrolyzed Silk, Sodium Lauroyl Hydroxypropyl Sulfonate, Sodium Lauroyl Isethionate, Sodium Lauroyl Methylaminopropionate, Sodium Lauroyl Methyl Isethionate, Sodium Lauroyl Millet Amino Acids, Sodium Lauroyl/Myristoyl Aspartate, Sodium Lauroyl Oat Amino Acids, Sodium Lauroyl Sarcosinate, Sodium Lauroyl Silk Amino Acids, Sodium Lauroyl Taurate, Sodium Lauroyl Wheat Amino Acids, Sodium Lauryl Diethylenediaminoglycinate, Sodium Lauryl Glucose Carboxylate, Sodium Laurylglucosides Hydroxypropyl Phosphate, So dium Laurylglucosides Hydroxypropylsulfonate, Sodium Lauryl Glycol Carboxylate, Sodium
Lauryl Hydroxyacetamide Sulfate, Sodium Lauryl Phosphate, Sodium Lauryl Sulfate, Sodium Lauryl Sulfoacetate, Sodium Linoleate, Sodium Macadamiaseedate, Sodium Mangoampho- acetate, Sodium Mangoseedate, Sodium/MEA Laureth-2 Sulfosuccinate, Sodium Methoxy PPG-2 Acetate, Sodium Methyl Cocoyl Taurate, Sodium Methyl Lauroyl Taurate, Sodium Me thyl Myristoyl Taurate, Sodium Methyl Oleoyl Taurate, Sodium Methyl Palmitoyl Taurate, So dium Methyl Stearoyl Taurate, Sodium Methyl 2-Sulfolaurate, Sodium Methyl 2- Sulfopalmi- tate, Sodium Methyltaurate Isopalmitamide, Sodium Methyltaurine Cocoyl Methyltaurate, Sodium Myreth Sulfate, Sodium Myristate, Sodium Myristoamphoacetate, Sodium Myristoyl Glutamate, Sodium Myristoyl Hydrolyzed Collagen, Sodium Myristoyl Isethionate, Sodium Myristoyl Sarcosinate, Sodium Myristyl Sulfate, Sodium Nonoxynol-6 Phosphate, Sodium Nonoxynol-9 Phosphate, Sodium Nonoxynol-1 Sulfate, Sodium Nonoxynol-3 Sulfate, Sodium Nonoxynol-4 Sulfate, Sodium Nonoxynol-6 Sulfate, Sodium Nonoxynol-8 Sulfate, Sodium Nonoxynol-10 Sulfate, Sodium Nonoxynol-25 Sulfate, Sodium Octoxynol-2 Ethane Sulfonate, Sodium Octoxynol-2 Sulfate, Sodium Octoxynol-6 Sulfate, Sodium Octoxynol-9 Sulfate, Sodi um Oleate, Sodium Oleoamphoacetate, Sodium Oleoamphohydroxypropylsulfonate, Sodium Oleoamphopropionate, Sodium Oleoyl Hydrolyzed Collagen, Sodium Oleoyl Isethionate, So dium Oleth Sulfate, Sodium Oleyl Methyl Isethionate, Sodium Oleyl Sulfate, Sodium Olivam- phoacetate, Sodium Olivate, Sodium Olivoyl Glutamate, Sodium Palmamphoacetate, Sodium Palmate, Sodium Palm Glyceride Sulfonate, Sodium Palmitate, Sodium Palmitoyl Hydrolyzed Collagen, Sodium Palmitoyl Hydrolyzed Wheat Protein, Sodium Palmitoyl Sarcosinate, Sodi um Palm Kernelate, Sodium Palm Kerneloyl Isethionate, Sodium Palmoyl Glutamate, Sodium Passiflora Edulis Seedate, Sodium Peanutamphoacetate, Sodium Peanutate, Sodium PEG-6 Cocamide Carboxylate, Sodium PEG-8 Cocamide Carboxylate, Sodium PEG-4 Cocamide Sul fate, Sodium PEG-3 Lauramide Carboxylate, Sodium PEG-4 Lauramide Carboxylate, Sodium PEG-8 Palm Glycerides Carboxylate, Sodium Pentaerythrityl Hydroxypropyl Iminodiacetate Dendrimer, Sodium Propoxy PPG-2 Acetate, Sodium Rapeseedate, Sodium Ricebranampho- acetate, Sodium Ricinoleate, Sodium Ricinoleoamphoacetate, Sodium Rose Hipsamphoace- tate, Sodium Rosinate, Sodium Safflowerate, Sodium Saffloweroyl Hydrolyzed Soy Protein, Sodium Sesameseedate, Sodium Sesamphoacetate, Sodium Sheabutteramphoacetate, Sodi um Soyate, Sodium Soy Hydrolyzed Collagen, Sodium Stearate, Sodium Stearoamphoacetate, Sodium Stearoamphohydroxypropylsulfonate, Sodium Stearoamphopropionate, Sodium Stearoyl Casein, Sodium Stearoyl Glutamate, Sodium Stearoyl Hyaluronate, Sodium Stearoyl Hydrolyzed Collagen, Sodium Stearoyl Hydrolyzed Corn Protein, Sodium Stearoyl Hydrolyzed Silk, Sodium Stearoyl Hydrolyzed Soy Protein, Sodium Stearoyl Hydrolyzed Wheat Protein, Sodium Stearoyl Lactalbumin, Sodium Stearoyl Methyl Isethionate, Sodium Stearoyl Oat Pro tein, Sodium Stearoyl Pea Protein, Sodium Stearoyl Soy Protein, Sodium Stearyl Dimethyl Glycine, Sodium Stearyl Sulfate, Sodium Sunflowerseedamphoacetate, Sodium Surfactin, So dium Sweetalmondamphoacetate, Sodium Sweet Almondate, Sodium Tallamphopropionate, Sodium Tallate, Sodium Tallowamphoacetate, Sodium Tallowate, Sodium Tallow Sulfate, So dium Tamanuseedate, Sodium Taurate, Sodium Taurine Cocoyl Methyltaurate, Sodium Tau rine Laurate, Sodium/TEA-Lauroyl Collagen Amino Acids, Sodium/TEA-Lauroyl Hydrolyzed
Collagen, Sodium/TEA-Lauroyl Hydrolyzed Keratin, Sodium/TEA- Lauroyl Keratin Amino Ac ids, Sodium/TEA-Undecylenoyl Collagen Amino Acids, Sodium/TEA- Undecylenoyl Hydro lyzed Collagen, Sodium/TEA-Undecylenoyl Hydrolyzed Corn Protein, Sodium/TEA- Undecylenoyl Hydrolyzed Soy Protein, Sodium/TEA-Undecylenoyl Hydrolyzed Wheat Protein, Sodium Theobroma Grandiflorum Seedate, Sodium Trideceth-3 Carboxylate, Sodium Tride- ceth-4 Carboxylate, Sodium Trideceth-6 Carboxylate, Sodium Trideceth-7 Carboxylate, Sodi um Trideceth-8 Carboxylate, Sodium Trideceth-12 Carboxylate, Sodium Trideceth-15 Carbox ylate, Sodium Trideceth-19 Carboxylate, Sodium Trideceth Sulfate, Sodium Tridecylbenzene- sulfonate, Sodium Tridecyl Sulfate, Sodium Trimethylolpropane Hydroxypropyl Iminodiace- tate Dendrimer, Sodium Undeceth-5 Carboxylate, Sodium Undecylenate, Sodium Undecylen- oamphoacetate, Sodium Undecylenoamphopropionate, Sodium Undecylenoyl Glutamate, Sodium Wheat Germamphoacetate, Sorbeth-160 Tristearate, Soy Acid, Soyamidopropylamine Oxide, Soyamidopropyl Betaine, Soybean Oil Glycereth-8 Esters, Stearamidopropylamine Ox ide, Stearamidopropyl Betaine, Stearamine Oxide, Steareth-15, Steareth-16, Steareth-20, Steareth-21, Steareth-25, Steareth-27, Steareth-30, Steareth- 40, Steareth-50, Steareth-80, Steareth-100, Steareth-2 Phosphate, Steareth-3 Phosphate, Stearic Acid, Stearoxypropyltri- monium Chloride, Stearoyl Glutamic Acid, Stearoyl Sarcosine, Stearyl Betaine, Stearyldimoni- um hydroxypropyl Butylglucosides Chloride, Stearyldimoniumhydroxypropyl Decylglucosides Chloride, Stearyldimoniumhydroxypropyl Laurylglucosides Chloride, Sulfated Castor Oil, Sul- fated Coconut Oil, Sulfated Glyceryl Oleate, Sulfated Olive Oil, Sulfated Peanut Oil, Sunflow- eramide MEA, Sunflower Seed Acid, Sunflowerseedamidopropyl Hydroxyethyldimonium Chloride, Sunflower Seed Oil Glycereth-8 Esters, Tall Oil Acid, Tallow Acid, Tallowamidoprop- ylamine Oxide, Tallowamidopropyl Betaine, Tallowamidopropyl Hydroxysultaine, Tallowamine Oxide, Tallow Betaine, Tallow Dihydroxyethyl Betaine, Tallowoyl Ethyl Glucoside, TEA-Abietoyl Hydrolyzed Collagen, TEA-C12-14 Alkyl Phosphate, TEA-C10-15 Alkyl Sulfate, TEA-C11-15 Alkyl Sulfate, TEA- C12-13 Alkyl Sulfate, TEA-C12-14 Alkyl Sulfate, TEA-C12-15 Alkyl Sulfate, TEA C 14-17 Alkyl Sec Sulfonate, TEA-Canolate, TEA-Cocamide Diacetate, TEA-Cocoate, TEA- Coco-Sulfate, TEA-Cocoyl Alaninate, TEA-Cocoyl Glutamate, TEA-Cocoyl Glutaminate, TEA- Cocoyl Glycinate, TEA-Cocoyl Hydrolyzed Collagen, TEA-Cocoyl Hydrolyzed Soy Protein, TEA- Cocoyl Sarcosinate, TEA- Dimethicone PEG-7 Phosphate, TEA-Dodecylbenzenesulfonate, TEA- Hydrogenated Cocoate, TEA- Hydrogenated Tallowoyl Glutamate, TEA-lsostearate, TEA- Isostearoyl Hydrolyzed Collagen, TEA- Lauraminopropionate, TEA-Laurate, TEA- Laurate/Myristate, TEA-Laureth Sulfate, TEA-Lauroyl Collagen Amino Acids, TEA-Lauroyl Glu tamate, TEA-Lauroyl Hydrolyzed Collagen, TEA-Lauroyl Keratin Amino Acids, TEA-Lauroyl Me- thylaminopropionate, TEA-Lauroyl/Myristoyl Aspartate, TEA- Lauroyl Sarcosinate, TEA-Lauryl Phosphate, TEA-Lauryl Sulfate, TEA-Myristaminopropionate, TEA- Myristate, TEA-Myristoyl Hydrolyzed Collagen, TEA-Oleate, TEA-Oleoyl Hydrolyzed Collagen, TEA- Oleoyl Sarcosinate, TEA-Oleyl Sulfate, TEA-Palmitate, TEA-Palm Kernel Sarcosinate, TEA-PEG-3 Cocamide Sulfate, TEA-Rosinate, TEA-Stearate, TEA-Tallate, TEA-T ridecylbenzenesulfonate, TEA- Undecylenate, TEA-Undecylenoyl Hydrolyzed Collagen, Tetramethyl Decynediol, Tetrasodium Dicarboxyethyl Stearyl Sulfosuccinamate, TIPA-Laureth Sulfate, TIPA-Lauryl Sulfate, TIPA-Myristate, TIPA-
Stearate, Tocopheryl Phosphate, Trehalose Undecylenoate, TM-C12-15 Pareth-2 Phosphate, TM-C12-15 Pareth-6 Phosphate, TM-C12-15 Pareth-8 Phosphate, TM-C12-15 Pareth-10 Phosphate, Trideceth-20, Trideceth-50, Trideceth-3 Carboxylic Acid, Trideceth-4 Carboxylic Acid, Trideceth-7 Carboxylic Acid, Trideceth-8 Carboxylic Acid, Trideceth-15 Carboxylic Acid, Trideceth-19 Carboxylic Acid, Trideceth-10 Phosphate, Tridecylbenzenesulfonic Acid, Trilau- reth-9 Citrate, Trimethylolpropane Hydroxypropyl Bis-Hydroxyethylamine Dendrimer, Triso dium Lauroampho PG-Acetate Chloride Phosphate, Undecanoic Acid, Undeceth-5 Carboxylic Acid, Undecylenamidopropylamine Oxide, Undecylenamidopropyl Betaine, Undecylenic Acid, Undecylenoyl Collagen Amino Acids, Undecylenoyl Glycine, Undecylenoyl Hydrolyzed Colla gen, Undecylenoyl Wheat Amino Acids, Undecyl Glucoside, Wheat Germ Acid, Wheat Ger- mamidopropylamine Oxide, Wheat Germamidopropyl Betaine, Yucca Schidigera Leaf/Root/Stem Extract, Yucca Schidigera Stem Extract, Zinc Coceth Sulfatea and Zinc Coco- Sulfate.
[0025] Preferred are one or more compounds selected from the group consisting of Sodium Laureth Sulfate, Cocamidopropyl Betaine, Sodium Cocoamphoacetate, CocoGlucoside and Ammonium Lauryl Sulfosuccinate.
[0026] The percentage content of surfactants in the preparations may be from 0.1 to 10% by weight and is preferably from 0.5 to 5% by weight, based on the preparation.
Oil bodies
[0027] Suitable oil bodies, which form constituents of the O/W emulsions, are, for example, Guerbet alcohols based on fatty alcohols having 6 to 18, preferably 8 to 10, carbon atoms, esters of linear C6-C22-fatty acids with linear or branched C6-C22-fatty alcohols or esters of branched C6-C 13-carboxylic acids with linear or branched C6-C 22-fatty alcohols, such as, for example, myristyl myristate, myristyl palmitate, myristyl stearate, myristyl isostearate, myristyl oleate, myristyl behenate, myristyl erucate, cetyl myristate, cetyl palmitate, cetyl stearate, cetyl isostearate, cetyl oleate, cetyl behenate, cetyl erucate, stearyl myristate, stearyl palmitate, stearyl stearate, stearyl isostearate, stearyl oleate, stearyl behenate, stearyl erucate, isostearyl myristate, isostearyl palmitate, isostearyl stearate, isostearyl isostearate, isostearyl oleate, isostearyl behenate, isostearyl oleate, oleyl myristate, oleyl palmitate, oleyl stearate, oleyl isostearate, oleyl oleate, oleyl behenate, oleyl erucate, behenyl myristate, behenyl palmitate, behenyl stearate, behenyl isostearate, behenyl oleate, behenyl behenate, behenyl erucate, erucyl myristate, erucyl palmitate, erucyl stearate, erucyl isostearate, erucyl oleate, erucyl be henate and erucyl erucate. Also suitable are esters of linear C6-C22-fatty acids with branched alcohols, in particular 2-ethylhexanol, esters of C18-C38- alkylhydroxy carboxylic acids with linear or branched C6-C 22-fatty alcohols, in particular Dioctyl Malate, esters of linear and/or branched fatty acids with polyhydric alcohols (such as, for example, propylene glycol, dimerdiol or trimertriol) and/or Guerbet alcohols, triglycerides based on C6 -Cio-fatty acids, liquid mono-/di-/triglyceride mixtures based on C6-Cis-fatty acids, esters of C6- C22-fatty al-
cohols and/or Guerbet alcohols with aromatic carboxylic acids, in particular benzoic acid, es ters of C2- Ci2-dicarboxylic acids with linear or branched alcohols having 1 to 22 carbon at oms or polyols having 2 to 10 carbon atoms and 2 to 6 hydroxyl groups, vegetable oils, branched primary alcohols, substituted cyclohexanes, linear and branched C6-C22-fatty alco hol carbonates, such as, for example, Dicaprylyl Carbonate (Cetiol® CC), Guerbet carbonates, based on fatty alcohols having 6 to 18, preferably 8 to 10, carbon atoms, esters of benzoic acid with linear and/or branched C6-C22-alcohols (e.g. Finsolv® TN), linear or branched, sym metrical or asymmetrical dialkyl ethers having 6 to 22 carbon atoms per alkyl group, such as, for example, dicaprylyl ether (Cetiol® OE), ring-opening products of epoxidized fatty acid esters with polyols, silicone oils (cyclomethicones, silicone methicone grades, etc.) and/or aliphatic or naphthenic hydrocarbons, such as, for example, squalane, squalene or dialkylcy- clohexanes.
Emulsifiers
[0028] Other non-ionic or cationic surfactants may also be added to the preparations as emulsifiers, including for example:
• products of the addition of 2 to 30 mol ethylene oxide and/or 0 to 5 mol propylene oxide onto linear Cs-22 fatty alcohols, onto C12-22 fatty acids and onto alkyl phenols con taining 8 to 15 carbon atoms in the alkyl group;
• C12/18 fatty acid monoesters and diesters of addition products of 1 to 30 mol ethylene oxide onto glycerol;
• glycerol mono- and diesters and sorbitan mono- and diesters of saturated and unsatu rated fatty acids containing 6 to 22 carbon atoms and ethylene oxide addition products thereof;
• addition products of 15 to 60 mol ethylene oxide onto castor oil and/or hydrogenated castor oil;
• polyol esters and, in particular, polyglycerol esters such as, for example, polyglycerol polyricinoleate, polyglycerol poly-12-hydroxystearate or polyglycerol dimerate isos tearate. Mixtures of compounds from several of these classes are also suitable;
• addition products of 2 to 15 mol ethylene oxide onto castor oil and/or hydrogenated castor oil;
• partial esters based on linear, branched, unsaturated or saturated C6/22 fatty acids, ricin- oleic acid and 12-hydroxystearic acid and glycerol, polyglycerol, pentaerythritol, - dipentaerythritol, sugar alcohols (for example sorbitol), alkyl glucosides (for example methyl glucoside, butyl glucoside, lauryl glucoside) and polyglucosides (for example cellulose);
• mono-, di and trialkyl phosphates and mono-, di- and/or tri-PEG-alkyl phosphates and
salts thereof;
• wool wax alcohols;
• polysiloxane/polyalkyl polyether copolymers and corresponding derivatives;
• mixed esters of pentaerythritol, fatty acids, citric acid and fatty alcohol and/or mixed esters of Ce-22 fatty acids, methyl glucose and polyols, preferably glycerol or polyglycer ol,
• polyalkylene glycols and
• glycerol carbonate.
[0029] The addition products of ethylene oxide and/or propylene oxide onto fatty alcohols, fatty acids, alkylphenols, glycerol mono- and diesters and sorbitan mono- and diesters of fatty acids or onto castor oil are known commercially available products. They are homo- logue mixtures of which the average degree of alkoxylation corresponds to the ratio between the quantities of ethylene oxide and/or propylene oxide and substrate with which the addi tion reaction is carried out. C 12/1 s fatty acid monoesters and diesters of addition products of ethylene oxide onto glycerol are known as lipid layer enhancers for cosmetic formulations. The preferred emulsifiers are described in more detail as follows:
[0030] Partial glycerides. Typical examples of suitable partial glycerides are hydroxystearic acid monoglyceride, hydroxystearic acid diglyceride, isostearic acid monoglyceride, isostearic acid diglyceride, oleic acid monoglyceride, oleic acid diglyceride, ricinoleic acid monoglycer ide, ricinoleic acid diglyceride, linoleic acid monoglyceride, linoleic acid diglyceride, linolenic acid monoglyceride, linolenic acid diglyceride, erucic acid monoglyceride, erucic acid diglyc eride, tartaric acid monoglyceride, tartaric acid diglyceride, citric acid monoglyceride, citric acid diglyceride, malic acid monoglyceride, malic acid diglyceride and technical mixtures thereof which may still contain small quantities of triglyceride from the production process. Addition products of 1 to 30 and preferably 5 to 10 mol ethylene oxide onto the partial gly cerides mentioned are also suitable.
[0031] Sorbitan esters. Suitable sorbitan esters are sorbitan monoisostearate, sorbitan ses- quiisostearate, sorbitan diisostearate, sorbitan triisostearate, sorbitan monooleate, sorbitan sesquioleate, sorbitan dioleate, sorbitan trioleate, sorbitan monoerucate, sorbitan sesquieru- cate, sorbitan dierucate, sorbitan trierucate, sorbitan monoricinoleate, sorbitan sesquiricino- leate, sorbitan diricinoleate, sorbitan triricinoleate, sorbitan monohydroxystearate, sorbitan sesquihydroxystearate, sorbitan dihydroxystearate, sorbitan trihydroxystearate, sorbitan monotartrate, sorbitan sesquitartrate, sorbitan ditartrate, sorbitan tritartrate, sorbitan monocitrate, sorbitan sesquicitrate, sorbitan dicitrate, sorbitan tricitrate, sorbitan monomale- ate, sorbitan sesquimaleate, sorbitan dimaleate, sorbitan trimaleate and technical mixtures thereof. Addition products of 1 to 30 and preferably 5 to 10 mol ethylene oxide onto the sorbitan esters mentioned are also suitable.
[0032] Polyglycerol esters. Typical examples of suitable polyglycerol esters are Polyglyceryl- 2 Dipolyhydroxystearate (Dehymuls® PGPH), Polyglycerin-3-Diisostearate (Lameform® TGI), Polyglyceryl-4 Isostearate (Isolan® Gl 34), Polyglyceryl-3 Oleate, Diisostearoyl Polyglyceryl-3 Diisostearate (Isolan® PDI), Polyglyceryl-3 Methylglucose Distearate (Tego Care® 450), Poly- glyceryl-3 Beeswax (Cera Beilina®), Polyglyceryl-4 Caprate (Polyglycerol Caprate T2010/90), Polyglyceryl-3 Cetyl Ether (Chimexane® NL), Polyglyceryl-3 Distearate (Cremophor® GS 32) and Polyglyceryl Polyricinoleate (Admul® WOL 1403), Polyglyceryl Dimerate Isostearate and mixtures thereof. Examples of other suitable polyolesters are the mono-, di- and triesters of trimethylol propane or pentaerythritol with lauric acid, cocofatty acid, tallow fatty acid, pal mitic acid, stearic acid, oleic acid, behenic acid and the like optionally reacted with 1 to 30 mol ethylene oxide.
[0033] Tetraalkyl ammonium salts. Cationically active surfactants comprise the hydropho bic high molecular group required for the surface activity in the cation by dissociation in aqueous solution. A group of important representatives of the cationic surfactants are the tetraalkyl ammonium salts of the general formula: (R1R2R3R4N+) X . Here R1 stands for Ci-Cs alk(en)yl, R2, R3 and R4, independently of each other, for alk(en)yl radicals having 1 to 22 car bon atoms. X is a counter ion, preferably selected from the group of the halides, alkyl sulfates and alkyl carbonates. Cationic surfactants, in which the nitrogen group is substituted with two long acyl groups and two short alk(en)yl groups, are particularly preferred.
[0034] Esterquats. A further class of cationic surfactants particularly useful as co-surfactants for the present invention is represented by the so-called esterquats. Esterquats are generally understood to be quaternised fatty acid triethanolamine ester salts. These are known com pounds which can be obtained by the relevant methods of preparative organic chemistry. Reference is made in this connection to International patent application WO 91/01295 A1, according to which triethanolamine is partly esterified with fatty acids in the presence of hy- pophosphorous acid, air is passed through the reaction mixture and the whole is then quaternised with dimethyl sulphate or ethylene oxide. In addition, German patent DE 4308794 C1 describes a process for the production of solid esterquats in which the quaterni- sation of triethanolamine esters is carried out in the presence of suitable dispersants, prefer ably fatty alcohols.
[0035] Typical examples of esterquats suitable for use in accordance with the invention are products of which the acyl component derives from monocarboxylic acids corresponding to formula RCOOH in which RCO is an acyl group containing 6 to 10 carbon atoms, and the amine component is triethanolamine (TEA). Examples of such monocarboxylic acids are ca- proic acid, caprylic acid, capric acid and technical mixtures thereof such as, for example, so- called head-fractionated fatty acid. Esterquats of which the acyl component derives from monocarboxylic acids containing 8 to 10 carbon atoms, are preferably used. Other esterquats are those of which the acyl component derives from dicarboxylic acids like malonic acid, suc cinic acid, maleic acid, fumaric acid, glutaric acid, sorbic acid, pimelic acid, azelaic acid, sebac- ic acid and/or dodecanedioic acid, but preferably adipic acid. Overall, esterquats of which the
acyl component derives from mixtures of monocarboxylic acids containing 6 to 22 carbon atoms, and adipic acid are preferably used. The molar ratio of mono and dicarboxylic acids in the final esterquat may be in the range from 1:99 to 99:1 and is preferably in the range from 50:50 to 90:10 and more particularly in the range from 70:30 to 80:20. Besides the quater- nised fatty acid triethanolamine ester salts, other suitable esterquats are quaternized ester salts of mono-/dicarboxylic acid mixtures with diethanolalkyamines or 1,2-dihydroxypropyl dialkylamines. The esterquats may be obtained both from fatty acids and from the corre sponding triglycerides in admixture with the corresponding dicarboxylic acids. One such pro cess, which is intended to be representative of the relevant prior art, is proposed in European patent EP 0750606 B1. To produce the quaternised esters, the mixtures of mono- and dicar boxylic acids and the triethanolamine - based on the available carboxyl functions - may be used in a molar ratio of 1.1:1 to 3:1. With the performance properties of the esterquats in mind, a ratio of 1.2:1 to 2.2:1 and preferably 1.5:1 to 1.9:1 has proved to be particularly ad vantageous. The preferred esterquats are technical mixtures of mono-, di- and triesters with an average degree of esterification of 1.5 to 1.9.
Superfatting agents and consistency factors
[0036] Superfatting agents may be selected from such substances as, for example, lanolin and lecithin and also polyethoxylated or acylated lanolin and lecithin derivatives, polyol fatty acid esters, monoglycerides and fatty acid alkanolamides, the fatty acid alkanolamides also serving as foam stabilizers.
[0037] The consistency factors mainly used are fatty alcohols or hydroxyfatty alcohols con taining 12 to 22 and preferably 16 to 18 carbon atoms and also partial glycerides, fatty acids or hydroxyfatty acids. A combination of these substances with alkyl oligoglucosides and/or fatty acid N-methyl glucamides of the same chain length and/or polyglycerol poly-12- hydroxystea rates is preferably used.
Thickening agents and rheology additives
[0038] Suitable thickeners are polymeric thickeners, such as Aerosil® types (hydrophilic sili cas), polysaccharides, more especially xanthan gum, guar-guar, agar-agar, alginates and tylo ses, carboxymethyl cellulose and hydroxyethyl cellulose, also relatively high molecular weight polyethylene glycol monoesters and diesters of fatty acids, polyacrylates (for example Carbo- pols® [Goodrich] or Synthalens® [Sigma]), polyacrylamides, polyvinyl alcohol and polyvinyl pyrrolidone, surfactants such as, for example, ethoxylated fatty acid glycerides, esters of fatty acids with polyols, for example pentaerythritol or trimethylol propane, narrow-range fatty alcohol ethoxylates and electrolytes, such as sodium chloride and ammonium chloride.
Polymers
[0039] Suitable cationic polymers are, for example, cationic cellulose derivatives such as, for example, the quaternized hydroxyethyl cellulose obtainable from Amerchol under the name of Polymer JR 400®, cationic starch, copolymers of diallyl ammonium salts and acrylamides, quaternized vinyl pyrrolidone/vinyl imidazole polymers such as, for example, Luviquat® (BASF), condensation products of polyglycols and amines, quaternized collagen polypeptides such as, for example, Lauryldimonium Hydroxypropyl Hydrolyzed Collagen (Lamequat® L, Gr inau), quaternized wheat polypeptides, polyethyleneimine, cationic silicone polymers such as, for example, amodimethicone, copolymers of adipic acid and dimethylaminohy- droxypropyl diethylenetriamine (Carta retine®, Sandoz), copolymers of acrylic acid with dime thyl diallyl ammonium chloride (Merquat® 550, Chemviron), polyaminopolyamides and cross- linked water-soluble polymers thereof, cationic chitin derivatives such as, for example, quaternized chitosan, optionally in microcrystalline distribution, condensation products of dihaloalkyls, for example dibromobutane, with bis-dialkylamines, for example bis- dimethylamino-1, 3-propane, cationic guar gum such as, for example, Jaguar®CBS, Jaguar®C- 17, Jaguar®C-16 of Celanese, quaternized ammonium salt polymers such as, for example, Mirapol® A-15, Mirapol® AD-1, Mirapol® AZ-1 of Miranol and the various polyquaternium types (for example 6, 7, 32 or 37) which can be found in the market under the tradenames Rheocare® CC or Ultragel® 300.
[0040] Suitable anionic, zwitterionic, amphoteric and nonionic polymers are, for example, vinyl acetate/crotonic acid copolymers, vinyl pyrrolidone/vinyl acrylate copolymers, vinyl ace tate/butyl maleate/isobornyl acrylate copolymers, methyl vinylether/maleic anhydride copol ymers and esters thereof, uncrosslinked and polyol-crosslinked polyacrylic acids, acrylamido- propyl trimethylammonium chloride/acrylate copolymers, octylacrylamide/methyl methacry- late/tert.-butylaminoethyl methacrylate/2-hydroxypropyl methacrylate copolymers, polyvinyl pyrrolidone, vinyl pyrrolidone/vinyl acetate copolymers, vinyl pyrroli- done/dimethylaminoethyl methacrylate/vinyl caprolactam terpolymers and optionally deri- vatized cellulose ethers and silicones.
Pearlizing waxes
[0041] Suitable pearlising waxes are, for example, alkylene glycol esters, especially ethylene glycol distearate; fatty acid alkanolamides, especially cocofatty acid diethanolamide; partial glycerides, especially stearic acid monoglyceride; esters of polybasic, optionally hydroxy- substituted carboxylic acids with fatty alcohols containing 6 to 22 carbon atoms, especially long-chain esters of tartaric acid; fatty compounds, such as for example fatty alcohols, fatty ketones, fatty aldehydes, fatty ethers and fatty carbonates which contain in all at least 24 car bon atoms, especially laurone and distearylether; fatty acids, such as stearic acid, hydroxys- tearic acid or behenic acid, ring opening products of olefin epoxides containing 12 to 22 car-
bon atoms with fatty alcohols containing 12 to 22 carbon atoms and/or polyols containing 2 to 15 carbon atoms and 2 to 10 hydroxyl groups and mixtures thereof.
Silicones
[0042] Suitable silicones can be chosen from the group consisting of: Acefylline Methylsilanol Mannuronate, Acetylmethionyl Methylsilanol Elastinate Acrylates/Behenyl, Acry- late/Dimethicone Methacrylate Copolymer, Acrylates/Behenyl Methacrylate/Dimethicone Methacrylate Copolymer, Acrylates/Bis-Hydroxypropyl Dimethicone Crosspolymer, Acry- lates/Dimethicone Copolymer, Acrylates/Dimethicone Methacrylate/Ethylhexyl Acrylate Co polymer, Acrylates/Dimethiconol Acrylate Copolymer, Acrylates/Ethylhexyl Acry- late/Dimethicone Methacrylate Copolymer, Acrylates/Octylacrylamide/Diphenyl Amodimethi- cone Copolymer, Acrylates/Polytrimethylsiloxymethacrylate Copolymer, Acrylates/Propyl Tri- methicone Methacrylate Copolymer, Acrylates/Stearyl Acrylate/Dimethicone Methacrylate Copolymer, Acrylates/Tridecyl Acrylate/Triethoxysilylpropyl Methacrylate/Dimethicone Meth acrylate Copolymer, Acrylates/Trifluoropropylmethacrylate/Polytrimethyl Siloxymethacrylate Copolymer, Amino Bispropyl Dimethicone, Aminoethylaminopropyl Dimethicone, Aminopro- pyl Dimethicone, Aminopropyl Phenyl Trimethicone, Aminopropyl Triethoxysilane, Ammoni um Dimethicone PEG-7 Sulfate, Amodimethicone, Amodimethicone Hydroxystearate, Amodimethicone/Silsesquioxane Copolymer, Ascorbyl Carboxydecyl Trisiloxane, Ascorbyl Methylsilanol Pectinate, Behenoxy Dimethicone, Behentrimonium Dimethicone PEG-8 Phthalate, Behenyl Dimethicone, Bisamino PEG/PPG-41/3 Aminoethyl PG-Propyl Dimethi cone, Bis-Aminopropyl/Ethoxy Aminopropyl Dimethicone, Bis(Butylbenzoate) Diaminotriazine Aminopropyltrisiloxane, Bis-Butyldimethicone Polyglyceryl-3, Bis-
Butyloxyamodimethicone/PEG-60 Copolymer, Bis(C13-15 Alkoxy) Hydroxybutamidoamodi- methicone, Bis(C13-15 Alkoxy) PG- Amodimethicone, Bis-(C1-8 Alkyl Lauroyl Lysine Decylcar- boxamide) Dimethicone, Bis-Cetyl Cetyl Dimethicone, Bis-Cetyl/PEG-8 Cetyl PEG-8 Dimethi cone, Bis-Diphenylethyl Disiloxane, Bis-Ethyl Ethyl Methicone, Bis- Gluconamidoethylaminopropyl Dimethicone, Bis-Hydrogen Dimethicone, Bis- Hydroxyethox- ypropyl Dimethicone Bis-Hydroxylauryl, Dimethicone/IPDI Copolymer, Bis- Hydroxy/M ethoxy Amodimethicone, Bis-Hydroxypropyl Dimethicone Behenate, Bis-Hydroxypropyl Dimethi- cone/SMDI Copolymer, Bis-lsobutyl PEG-14/Amodimethicone Copolymer, Bis-lsobutyl PEG- 15/Amodimethicone Copolymer, Bis-lsobutyl PEG/PPG-20/35/Amodimethicone Copolymer, Bis- Isobutyl PEG/PPG-10/7/Dimethicone Copolymer, Bis-lsobutyl PEG24/PPG-7/Dimethicone Copolymer, Bis-PEG-1 Dimethicone, Bis-PEG-4 Dimethicone, Bis-PEG-8 Dimethicone, Bis- PEG-12 Dimethicone, Bis-PEG20 Dimethicone, Bis-PEG- 12 Dimethicone Beeswax, Bis-PEG-12 Dimethicone Candelillate, Bis-PEG-15 Dimethicone/IPDI Copolymer, Bis-PEG-15 Methyl Ether Dimethicone, Bis- PEG-18 Methyl Ether Dimethyl Silane, Bis-PEG/PPG-14/14 Dimethicone, Bis-PEG/PPG-15/5 Dimethicone, Bis-PEG/PPG-18/6 Dimethicone, Bis-PEG/PPG-20/20 Dime thicone, Bis-PEG/PPG- 16/16 PEG/PPG-16/16 Dimethicone, Bis-PEG/PPG-20/5 PEG/PPG-20/5 Dimethicone, Bisphenylhexamethicone, Bis-Phenylpropyl Dimethicone, Bispolyethylene Dime-
thicone, Bis- (Polyglyceryl-3 Oxyphenylpropyl) Dimethicone, Bis-(Polyglyceryl-7 Oxy- phenylpropyl) Dimethicone, Bis-PPG-15 Dimethicone/IPDI Copolymer, Bis(PPG-7 Unde- ceneth-21) Dimethicone, Bis-Stearyl Dimethicone, Bis-Trimethoxysilylethyl Tetramethyl- disiloxyethyl Dimethicone, Bis-Vinyldimethicone, Bis-Vinyl Dimethicone/Dimethicone Copol ymer, Borage Seed Oil PEG-7 Dimethicone Esters, Butyl Acrylate/C6-14 Perfluoroalkylethyl Acrylate/Mercaptopropyl Dimethicone Copolymer, Butyl Acrylate/Hydroxypropyl Dimethi cone Acrylate Copolymer, Butyl Dimethicone Acrylate/Cyclohexylmethacrylate/Ethylhexyl Acrylate Copolymer, Butyldimethicone Methacrylate/Methyl Methacrylate Crosspolymer, t- Butyl Dimethyl Silyl Grape Seed Extract, Butyl Polydimethylsiloxyl Eth ylene/Pro pylene/Vinylnorbornene Copolymer, C6-8 Alkyl C3-6 Alkyl Glucoside Dimethicone, C20-24 Alkyl Dimethicone, C24-28 Alkyl Dimethicone, C26-28 Alkyl Dimethicone, C30-45 Alkyl Dimethicone, C30-60 Alkyl Dimethicone, C32 Alkyl Dimethicone, C30-45 Alkyl Dimethi- cone/Polycyclohexene Oxide Crosspolymer, C26-28 Alkyldimethylsilyl Polypropylsilsesquiox- ane, C30-45 Alkyldimethylsilyl Polypropylsilsesquioxane, C20-24 Alkyl Methicone, C24-28 Alkyl Methicone, C26-28 Alkyl Methicone, C30-45 Alkyl Methicone, C20-28 Alkyl Per- fluorodecylethoxy Dimethicone, C26-54 Alkyl Tetradecyl Dimethicone, Capryl Dimethicone, Caprylyl Dimethicone Ethoxy Glucoside, Caprylyl Methicone, Caprylyl Trimethicone, Carboxy- decyl Trisiloxane, Castor Oil Bis-Hydroxypropyl Dimethicone Esters Cerotyl Dimethicone, Ce- tearyl Dimethicone Crosspolymer, Cetearyl Dimethicone/Vinyl Dimethicone Crosspolymer, Cetearyl Methicone, Cetrimonium Carboxydecyl PEG-8 Dimethicone, Cetrimonium Dimethi cone PEG-7 Phthalate, Cetyl Behenyl Dimethicone, Cetyl Dimethicone, Cetyl Dimethicone/Bis- Vinyldimethicone Crosspolymer, Cetyl Hexacosyl Dimethicone, Cetyloxy Dimethicone, Cetyl PEG-8 Dimethicone, Cetyl PEG/PPG-15/15 Butyl Ether Dimethicone, Cetyl PEG/PPG-7/3 Dime thicone, Cetyl PEG/PPG-10/1 Dimethicone, Cetyl Triethylmonium Dimethicone PEG-8 Phthalate, Cetyl Triethylmonium Dimethicone PEG-8 Succinate, Copper Acetyl Tyrosinate Me- thylsilanol, Copper PCA Methylsilanol, C4-14 Perfluoroalkylethoxy Dimethicone, Cycloethox- ymethicone, Cycloheptasiloxane, Cyclohexasiloxane, Cyclomethicone, Cyclopentasiloxane, Cyclophenylmethicone, Cyclotetrasiloxane,mCyclovinylmethicone, Cystine Bis-PG-Propyl Silanetriol, DEA PG-Propyl PEG/PPG-18/21 Dimethicone, Diisostearoyl Trimethylolpropane Siloxy Silicate, Dilauroyl Trimethylolpropane Siloxy Silicate, Dilinoleamidopropyl Dimethyla- mine Dimethicone PEG-7 Phosphate, Dimethicone, Dimethicone Crosspolymer, Dimethicone Crosspolymer-3, Dimethicone/Divinyldimethicone/Silsesquioxane Crosspolymer, Dimethicone Ethoxy Glucoside, Dimethicone Hydroxypropyl Trimonium Chloride, Dimethi- cone/Mercaptopropyl Methicone Copolymer, Dimethicone PEG-15 Acetate Dimethicone PEG-8 Adipate, Dimethicone PEG-7 Avocadoate, Dimethicone PEG-8 Avocadoate, Dimethi cone PEG-8 Beeswax, Dimethicone PEG-8 Benzoate, Dimethicone PEG-8 Borageate, Dimethi cone PEG-7 Cocoate, Dimethicone/PEG-10 Crosspolymer, Dimethicone/PEG-10/15 Crosspol ymer, Dimethicone/PEG-15 Crosspolymer, Dimethicone PEG-7 Isostearate, Dimethicone PEG- 8 Isostearate, Dimethicone PEG-7 Lactate, Dimethicone PEG-8 Lanolate, Dimethicone PEG-8 Laurate, Dimethicone PEG-8 Meadowfoamate, Dimethicone PEG-7 Octyldodecyl Citrate, Di methicone PEG-7 Olivate, Dimethicone PEG-8 Olivate, Dimethicone PEG-7 Phosphate, Dime-
thicone PEG-8 Phosphate, Dimethicone PEG-10 Phosphate, Dimethicone PEG-7 Phthalate, Dimethicone PEG-8 Phthalate, Dimethicone PEG-8 Polyacrylate, Dimethicone PEG/PPG- 20/23 Benzoate, Dimethicone PEG/PPG-7/4 Phosphate, Dimethicone PEG/PPG-12/4 Phos phate, Dimethicone PEG-7 Succinate, Dimethicone PEG-8 Succinate, Dimethicone PEG-7 Sul fate, Dimethicone PEG-7 Undecylenate, Dimethicone PG-Diethylmonium Chloride, Dimethi- cone/Phenyl Vinyl Dimethicone Crosspolymer, Dimethicone/Polyglycerin-3 Crosspolymer, Dimethicone/PPG-20 Crosspolymer, Dimethicone Propylethylenediamine Behenate, Dimethi cone Propyl PG-Betaine, Dimethicone/Silsesquioxane Copolymer, Dimethicone Silylate, Dime- thicone?/inyl Dimethicone Crosspolymer, Dimethicone/Vinyltrimethylsiloxysilicate Crosspol ymer, Dimethiconol, Dimethiconol Arginine, Dimethiconol Beeswax, Dimethiconol Behenate, Dimethiconol Borageate, Dimethiconol Candelillate, Dimethiconol Carnaubate, Dimethiconol Cysteine, Dimethiconol Dhupa Butterate, Dimethiconol Fluoroalcohol Dilinoleic Acid, Dime thiconol Hydroxystearate, Dimethiconol lllipe Butterate, Dimethiconol/IPDI Copolymer, Dime thiconol Isostearate, Dimethiconol Kokum Butterate, Dimethiconol Lactate, Dimethiconol Meadowfoamate, Dimethiconol Methionine, Dimethiconol/Methylsilanol/Silicate Crosspoly mer, Dimethiconol Mohwa Butterate, Dimethiconol Panthenol, Dimethiconol Sal Butterate, Dimethiconol/Silica Crosspolymer, Dimethiconol/Silsesquioxane Copolymer, Dimethiconol Stearate, Dimethiconol/Stearyl, Methicone/Phenyl Trimethicone Copolymer, Dimethoxysilyl Ethylenediaminopropyl Dimethicone, Dimethylaminopropylamido PCA Dimethicone, Dime thyl Oxobenzo Dioxasilane, Dimethylsilanol Hyaluronate, Dioleyl Tocopheryl Methylsilanol, Diphenyl Amodimethicone, Diphenyl Dimethicone, Diphenyl Dimethicone Crosspolymer Di phenyl Dimethicone?/inyl Diphenyl Dimethicone/Silsesquioxane Crosspolymer, Diphenylethyl Benzyloxy Dilsiloxane, Diphenylisopropyl Dimethicone, Diphenylsiloxy Phenyl/Propyl Trime thicone, Diphenylsiloxy Phenyl Trimethicone Disiloxane, Disodium Amodimethicone Disuccin- amide, Disodium PEG-12 Dimethicone Sulfosuccinate, Disodium PEG-8 Lauryl Dimethicone Sulfosuccinate, Divinyldimethicone/Dimethicone Copolymer, Divinyldimethi- cone/Dimethicone Crosspolymer, Drometrizole Trisiloxane, Ethylhexyl Acry- late/VP/Dimethicone Methacrylate Copolymer, Ethyl Methicone, Ethyl Trisiloxane, Fluoro C2-8 Alkyldimethicone, Gluconamidopropyl Aminopropyl Dimethicone, 4-(2-Beta- Glucopyranosiloxy) Propoxy-2-Hydroxybenzophenone, Glyceryl Undecyl Dimethicone, Glycidoxy Dimethicone, Hexadecyl Methicone, Hexyl Dimethicone, Hexyl Methicone, Hex- yltrimethoxysilane, Hydrogen Dimethicone, Hydrogen Dimethicone/Octyl Silsesquioxane Co polymer, Hydrolyzed Collagen PG-Propyl Dimethiconol, Hydrolyzed Collagen PG-Propyl Me- thylsilanediol, Hydrolyzed Collagen PG-Propyl Silanetriol, Hydrolyzed Keratin PG-Propyl Me- thylsilanediol, Hydrolyzed Sesame Protein PG-Propyl Methylsilanediol, Hydrolyzed Silk PG- Propyl Methylsilanediol, Hydrolyzed Silk PG-Propyl Methylsilanediol Crosspolymer, Hydro lyzed Soy Protein/Dimethicone PEG-7 Acetate, Hydrolyzed Soy Protein PG-Propyl Me thylsilanediol, Hydrolyzed Vegetable Protein PG-Propyl Silanetriol, Hydrolyzed Wheat Pro tein/Cystine Bis-PG-Propyl Silanetriol Copolymer, Hydrolyzed Wheat Protein/Dimethicone PEG-7 Acetate, Hydrolyzed Wheat Protein/Dimethicone PEG-7 Phosphate Copolymer, Hydro lyzed Wheat Protein PG-Propyl Methylsilanediol, Hydrolyzed Wheat Protein PG-Propyl Silan-
etriol, Hydroxyethyl Acetomonium PG-Dimethicone, Hydroxypropyldimethicone, Hydroxy- propyl Dimethicone Behenate, Hydroxypropyl Dimethicone Isostearate, Hydroxypropyl Dime- thicone Stearate, Isobutylmethacrylate/Bis-Hydroxypropyl Dimethicone Acrylate Copolymer, Isobutylmethacrylate/T rifluoroethylmethacrylate/Bis-Hydroxypropyl Dimethicone Acrylate Copolymer, Isopentyl Trimethoxycinnamate Trisiloxane, lsopolyglyceryl-3 Dimethicone, lsopolyglyceryl-3 Dimethiconol, Isopropyl Titanium Triisostearate/Triethoxysilylethyl, Polydi- methylsiloxyethyl Dimethicone Crosspolymer, Isostearyl Carboxydecyl PEG-8 Dimethicone, Lactoyl Methylsilanol Elastinate, Lauryl Dimethicone, Lauryl Dimethicone PEG-15 Crosspoly mer, Lauryl Dimethicone PEG- 10 Phosphate, Lauryl Dimethicone/Polyglycerin-3 Crosspoly mer, Lauryl Methicone, Lauryl PEG-8 Dimethicone, Lauryl PEG-10 Methyl Ether Dimethicone, Lauryl PEG-9 Polydimethylsiloxyethyl Dimethicone, Lauryl PEG/PPG-18/18 Methicone, Lauryl Phenylisopropyl Methicone, Lauryl Phenylpropyl Methicone, Lauryl Polydimethylsiloxyethyl Dimethicone/Bis-Vinyldimethicone Crosspolymer, Lauryl Polyglyceryl-3 Polydimethylsiloxy ethyl Dimethicone, Lauryl Trimethicone, Linoleamidopropyl PG-Dimonium Chloride Phos phate Dimethicone, Methacryloyl Propyltrimethoxysilane, Methicone, Methoxy Amodimethi- cone/Silsesquioxane Copolymer, Methoxycinnamidopropyl Polysilsesquioxane, Methox- ycinnamoylpropyl Silsesquioxane Silicate, Methoxy PEG-13 Ethyl Polysilsesquioxane, Methoxy PEG/PPG-7/3 Aminopropyl Dimethicone, Methoxy PEG/PPG-25/4 Dimethicone, Methoxy PEG-10 Propyltrimethoxysilane, Methyleugenyl PEG- 8 Dimethicone, Methylpolysiloxane Emulsion, Methylsilanol Acetylmethionate, Methylsilanol Acetyltyrosine, Methylsilanol Ascor bate, Methylsilanol Carboxymethyl Theophylline, Methylsilanol Carboxymethyl Theophylline Alginate, Methylsilanol Elastinate, Methylsilanol Glycyrrhizinate, Methylsilanol Hydroxy pro line, Methylsilanol Hydroxyproline Aspartate, Methylsilanol Mannuronate, Methylsilanol PCA, Me thylsilanol PEG-7 Glyceryl Cocoate, Methylsilanol/Silicate Crosspolymer, Methylsilanol Spiruli- nate, Methylsilanol Tri-PEG-8 Glyceryl Cocoate, Methyl Trimethicone, Methyltrimethoxysilane, Myristylamidopropyl Dimethylamine Dimethicone PEG-7 Phosphate, Myristyl Methicone, Myristyl Trisiloxane, Nylon-611/Dimethicone Copolymer, PCA Dimethicone, PEG-7 Amodime- thicone, PEG-8 Amodimethicone, PEG-8 Cetyl Dimethicone, PEG-3 Dimethicone, PEG-6 Dime thicone, PEG-7 Dimethicone, PEG-8 Dimethicone, PEG-9 Dimethicone, PEG-10 Dimethicone, PEG-12 Dimethicone, PEG-14 Dimethicone, PEG-17 Dimethicone, PEG-10 Dimethicone Cross polymer, PEG-12 Dimethicone Crosspolymer, PEG-8 Dimethicone Dimer Dilinoleate, PEG-8 Dimethicone/Dimer Dilinoleic Acid Copolymer, PEG-10 Dimethicone/Vinyl Dimethicone Crosspolymer, PEG-8 Distearmonium Chloride PG-Dimethicone, PEG-10/Lauryl Dimethicone Crosspolymer, PEG- 15/Lauryl Dimethicone Crosspolymer, PEG-15/Lauryl Polydimethylsiloxy ethyl Dimethicone Crosspolymer, PEG-8 Methicone, PEG-6 Methicone Acetate, PEG-6 Methyl Ether Dimethicone, PEG- 7 Methyl Ether Dimethicone, PEG-8 Methyl Ether Dimethicone, PEG- 9 Methyl Ether Dimethicone, PEG-10 Methyl Ether Dimethicone, PEG-11 Methyl Ether Dime thicone, PEG-32 Methyl Ether Dimethicone, PEG-8 Methyl Ether Triethoxysilane, PEG-10 No- nafluorohexyl Dimethicone Copolymer, PEG-4 PEG-12 Dimethicone, PEG-8 PG-Coco- Glucoside Dimethicone, PEG-9 Polydimethylsiloxyethyl Dimethicone, PEG/PPG-20/22 Butyl Ether Dimethicone, PEG/PPG-22/22 Butyl Ether Dimethicone, PEG/PPG-23/23 Butyl Ether Di-
methicone, PEG/PPG-24/18 Butyl Ether Dimethicone, PEG/PPG-27/9 Butyl Ether Dimethicone, PEG/PPG-3/10 Dimethicone, PEG/PPG-4/12 Dimethicone, PEG/PPG-6/4 Dimethicone, PEG/PPG-6/11 Dimethicone, PEG/PPG-8/14 Dimethicone, PEG/PPG-8/26 Dimethicone,
PEG/PPG-10/2 Dimethicone, PEG/PPG-12/16 Dimethicone, PEG/PPG- 12/18 Dimethicone, PEG/PPG-14/4 Dimethicone, PEG/PPG-15/5 Dimethicone, PEG/PPG-15/15 Dimethicone,
PEG/PPG- 16/2 Dimethicone, PEG/PPG-16/8 Dimethicone, PEG/PPG-17/18 Dimethicone,
PEG/PPG-18/6 Dimethicone, PEG/PPG-18/12 Dimethicone, PEG/PPG-18/18 Dimethicone,
PEG/PPG-19/19 Dimethicone, PEG/PPG-20/6 Dimethicone, PEG/PPG-20/15 Dimethicone, PEG/PPG-20/20 Dimethicone, PEG/PPG-20/23 Dimethicone, PEG/PPG-20/29 Dimethicone, PEG/PPG-22/23 Dimethicone, PEG/PPG-22/24 Dimethicone, PEG/PPG-23/6 Dimethicone, PEG/PPG-25/25 Dimethicone, PEG/PPG-27/27 Dimethicone, PEG/PPG-30/10 Dimethicone, PEG/PPG-25/25 Dimethicone/ Acrylates Copolymer, PEG/PPG-20/22 Methyl Ether Dimethi cone, PEG/PPG-24/24 Methyl Ether Glycidoxy Dimethicone, PEG/PPG-10/3 Oleyl Ether Dime thicone, PEG/PPG-5/3 Trisiloxane, PEG-4 Trifluoropropyl Dimethicone Copolymer, PEG-8 Tri- fluoropropyl Dimethicone Copolymer, PEG-10 Trifluoropropyl Dimethicone Copolymer, PEG- 8 Trisiloxane, Perfluorocaprylyl riethoxysilylethyl Methicone, Perfluorononyl Dimethicone, Perfluorononyl Dimethicone/Methicone/Amodimethicone Crosspolymer, Perfluorononylethyl Carboxydecyl Behenyl Dimethicone, Perfluorononylethyl Carboxydecyl Hexacosyl Dimethi cone, Perfluorononylethyl Carboxydecyl Lauryl/Behenyl Dimethicone, Perfluorononylethyl Carboxydecyl Lauryl Dimethicone, Perfluorononylethyl Carboxydecyl PEG-8 Dimethicone, Perfluorononylethyl Carboxydecyl PEG- 10 Dimethicone, Perfluorononylethyl Dimethi- cone/Methicone Copolymer, Perfluorononylethyl PEG-8 Dimethicone, Perfluorononylethyl Stearyl Dimethicone, Perfluorooctylethyl/Diphenyl Dimethicone Copolymer, Perfluo- rooctylethyl Triethoxysilane, Perfluorooctylethyl Trimethoxysilane, Perfluorooctylethyl Trisiloxane, Perfluorooctyl Triethoxysilane, PG-Amodimethicone, Phenethyl Dimethicone, Phenethyl Disiloxane, Phenyl Dimethicone, Phenylisopropyl Dimethicone, Phenyl Methicone, Phenyl Methiconol, Phenylpropyldimethylsiloxysilicate, Phenylpropyl Ethyl Methicone, Phenyl Propyl Trimethicone, Phenyl Propyl Trimethicone/Diphenylmethicone, Phenyl Trimethicone, Platinum Divinyldisiloxane, Polyacrylate-6, Polydiethylsiloxane, Polydimethylsiloxyethyl Dime- thicone/Bis-Vinyldimethicone Crosspolymer, Polydimethylsiloxyethyl Dimethicone/Methicone Copolymer, Polydimethylsiloxy PEG/PPG-24/19 Butyl Ether Silsesquioxane, Polydimethylsiloxy PPG- 13 Butyl Ether Silsesquioxane, Polyglyceryl-3 Disiloxane Dimethicone, Polyglyceryl- 3/Lauryl Polydimethylsiloxyethyl Dimethicone Crosspolymer, Polyglyceryl-3 Polydime thylsiloxyethyl Dimethicone, Poly(Glycol Adipate)/Bis-Hydroxyethoxypropyl Dimethicone Co polymer, Polymethylsilsesquioxane, Polymethylsilsesquioxane/Trimethylsiloxysilicate, Poly- phenylsilsesquioxane, Polypropylsilsesquioxane, Polysilicone-1, Polysilicone-2, Polysilicone-3, Polysilicone-4, Polysilicone-5, Polysilicone-6, Polysilicone-7, Polysilicone-8, Polysilicone-9, Polysilicone-10, Polysilicone-11, Polysilicone-12, Polysilicone-13, Polysilicone-14, Polysilicone- 15, Polysilicone-16, Polysilicone-17, Polysilicone-18, Polysilicone-19, Polysilicone-20, Polysili- cone-21, Polysilicone-18 Cetyl Phosphate, Polysilicone-1 Crosspolymer, Polysilicone-18 Stea rate, Polyurethane-10, Potassium Dimethicone PEG-7 Panthenyl Phosphate, Potassium Dime-
thicone PEG- 7 Phosphate, PPG-12 Butyl Ether Dimethicone, PPG-2 Dimethicone, PPG-12 Dimethicone, PPG-27 Dimethicone, PPG-4 Oleth-10 Dimethicone, Propoxytetra methyl Piperi- dinyl Dimethicone, Propyl Trimethicone, Quaternium-80, Retinoxytrimethylsilane, Silanediol Salicylate, Silanetriol, Silanetriol Arginate, Silanetriol Glutamate, Silanetriol Lysinate, Silanetriol Melaninate, Silanetriol Trehalose Ether, Silica, Silica Dimethicone Silylate, Silica Dimethyl Si- lylate, Silica Silylate, Silicon Carbide, Silicone Quaternium-1, Silicone Quaternium-2, Silicone Quaternium-2 Panthenol Succinate, Silicone Quaternium-3, Silicone Quaternium-4, Silicone Quaternium-5, Silicone Quaternium-6, Silicone Quaternium-7, Silicone Quaternium-8, Silicone Quaternium-9, Silicone Quaternium-10, Silicone Quaternium-11, Silicone Quaternium-12, Silicone Quaternium-15, SiliconeQuaternium-16, Silicone Quaternium-16/Glycidoxy Dimethi cone Crosspolymer, Silicone Quaternium-17, Silicone Quaternium- 18, Silicone Quaternium- 19, Silicone Quaternium-20, Silicone Quaternium-21, Silicone Quaternium- 22, Silicone Qua- ternium-24, Silicone Quaternium-25, Siloxanetriol Alginate, Siloxanetriol Phytate, Simethi cone, Sodium Carboxydecyl PEG-8 Dimethicone, Sodium Dimethicone PEG-7 Acetyl Methyl- taurate, Sodium Hyaluronate Dimethylsilanol, Sodium Lactate Methylsilanol, Sodium Mannu- ronate Methylsilanol, Sodium PCA Methylsilanol, Sodium PG-Propyldimethicone Thiosulfate Copolymer, Sodium PG-Propyl Thiosulfate Dimethicone, Sodium Propoxyhydroxypropyl Thio sulfate Silica, Sorbityl Silanediol, Soy Triethoxysilylpropyldimonium Chloride, Stearalkonium Dimethicone PEG-8 Phthalate, Stearamidopropyl Dimethicone, Steardimonium Hydroxypro- pyl Panthenyl PEG-7 Dimethicone Phosphate Chloride, Steardimonium Hydroxypropyl PEG-7 Dimethicone Phosphate Chloride, Stearoxy Dimethicone, Stearoxymethicone/Dimethicone Copolymer, Stearoxytrimethylsilane, Stearyl Aminopropyl Methicone, Stearyl Dimethicone, Stearyl/Lauryl Methacrylate Crosspolymer, Stearyl Methicone, Stearyl Triethoxysilanek, Stearyl Trimethicone, Styrene/ Acrylates/Dimethicone Acrylate Crosspolymer, Sty- rene/Acrylates/Dimethicone Copolymer, TEA-Dimethicone PEG-7 Phosphate, Tetrabutoxy- propyl Trisiloxane, Tetramethyl Hexaphenyl Tetrasiloxane, Tetramethyl Tetraphenyl Trisilox- ane, Tocopheryloxypropyl Trisiloxane, Trideceth-9 PG-Amodimethicone, Triethoxycapry- lylsilane, Triethoxysilylethyl Dimethicone/Methicone Copolymer, Triethoxysilylethyl Polydime- thylsiloxyethyl Dimethicone, Triethoxysilylethyl Polydimethylsiloxyethyl Hexyl Dimethicone, Triethoxysilylpropylcarbamoyl Ethoxypropyl Butyl Dimethicone, Trifluoromethyl C1-4 Alkyl Dimethicone, Trifluoropropyl Cyclopentasiloxane, Trifluoropropyl Cyclotetrasiloxane, Tri- fluoropropyl Dimethicone, Trifluoropropyl Dimethicone/PEG-10 Crosspolymer, Trifluoropro pyl Dimethicone/Trifluoropropyl Divinyldimethicone Crosspolymer, Trifluoropropyl Dimethi- cone/Vinyl Trifluoropropyl, Dimethicone/Silsesquioxane Crosspolymer, Trifluoropropyl Dime- thiconol, Trifluoropropyldimethyl/trimethylsiloxysilicate, Trifluoropropyl Methicone, Tri- methoxycaprylylsilane, Trimethoxysilyl Dimethicone, Trimethyl Pentaphenyl Trisiloxane, Tri- methylsiloxyamodimethicone, Trimethylsiloxyphenyl Dimethicone, Trimethylsiloxysilicate, Trimethylsiloxysilicate/Dimethicone Crosspolymer, Trimethylsiloxysilicate/Dimethiconol Crosspolymer, Trimethylsiloxysilylcarbamoyl Pullulan, Trimethylsilyl Hydrolyzed Conchiolin Protein PG-Propyl Methylsilanediol Crosspolymer, Trimethylsilyl Hydrolyzed Silk PG-Propyl Methylsilanediol Crosspolymer, Trimethylsilyl Hydrolyzed Wheat Protein PG-Propyl Me-
thylsilanediol Crosspolymer, Trimethylsilyl Pullulan, Trimethylsilyl Trimethylsiloxy Glycolate, Trimethylsilyl Trimethylsiloxy Lactate, Trimethylsilyl Trimethylsiloxy Salicylate, Triphenyl Trime- thicone, Trisiloxane, Tris-Tributoxysiloxymethylsilane, Undecylcrylene Dimethicone, Vinyl Di- methicone, Vinyl Dimethicone/Lauryl Dimethicone Crosspolymer, Vinyl Dimethi- cone/Methicone Silsesquioxane Crosspolymer, Vinyldimethyl/Trimethylsiloxysilicate Stearyl Dimethicone Crosspolymer, VP/Dimethiconylacrylate/Polycarbamyl/Polyglycol Ester, Zinc Carboxydecyl Trisiloxane and Zinc Dimethicone PEG-8 Succinate and mixtures thereof.
[0043] More preferably the silicones to be contained in the mixture according to the inven tions are Dimethicone, Cyclomethicone, Phenyl Trimethicone, Cyclohexasiloxane and Cyclo- pentasiloxane. A detailed overview of suitable volatile silicones can be found in Todd et al. in Cosm. Toil. 91, 27 (1976).
Waxes and stabilizers
[0044] Besides natural oils used, waxes may also be present in the preparations, more espe cially natural waxes such as, for example, candelilla wax, carnauba wax, Japan wax, espar- tograss wax, cork wax, guaruma wax, rice oil wax, sugar cane wax, ouricury wax, montan wax, beeswax, shellac wax, spermaceti, lanolin (wool wax), uropygial fat, ceresine, ozocerite (earth wax), petrolatum, paraffin waxes and microwaxes; chemically modified waxes (hard waxes) such as, for example, montan ester waxes, sasol waxes, hydrogenated jojoba waxes and syn thetic waxes such as, for example, polyalkylene waxes and polyethylene glycol waxes.
[0045] Metal salts of fatty acids such as, for example, magnesium, aluminium and/or zinc stearate or ricinoleate may be used as stabilizers.
Primary sun protection filters
[0046] Primary sun protection filters in the context of the invention are, for example, organic substances (light filters) which are liquid or crystalline at room temperature and which are capable of absorbing ultraviolet radiation and of releasing the energy absorbed in the form of longer-wave radiation, for example heat.
[0047] The formulations according to the invention advantageously contain at least one UV- A filter and/or at least one UV-B filter and/or a broadband filter and/or at least one inorganic pigment. Formulations according to the invention preferably contain at least one UV-B filter or a broadband filter, more particularly preferably at least one UV-A filter and at least one UV-B filter.
[0048] The UV filters cited below which can be used within the context of the present inven tion are preferred but naturally are not limiting. UV filters which are preferably used are se lected from the group consisting of one, two, three, four, five or more of the following spe cies:
[0049] In a preferred embodiment the sun protection filter forming component (ii) repre sents a blend of UV-A- and UV-B-filters selected from the group consisting of homosalate, octocrylene, bis-ethylhexyloxyphenol methoxyphenyl triazine, butyl methoxydibenzoylme- thane, ethylhexyl salicylate and mixtures thereof. Particular preferred is a blend of all these filters which is commercially available in the market under the trademark NeoHeliopan® Flat (SYMRISE), which also subject to WO 2020 088778 A1.
[0050] Suitable pigments encompass oxides of titanium (T1O2), zinc (ZnO), iron (Fe20s), zirco nium (Zr02), silicon (S1O2), manganese (e.g. MnO), aluminium (AI2O3), cerium (e.g. Ce20s) and/or mixtures thereof.
[0051] In a further preferred embodiment a formulation according to the invention contains a total amount of sunscreen agents, i.e. in particular UV filters and/or inorganic pigments (UV
filtering pigments) so that the formulation according to the invention has a light protection factor of greater than or equal to 5 and up to 50. Such formulations according to the inven tion are particularly suitable for protecting the skin and hair.
Secondary sun protection filters
[0052] Besides the groups of primary sun protection factors mentioned above, secondary sun protection factors of the antioxidant type may also be used. Secondary sun protection factors of the antioxidant type interrupt the photochemical reaction chain which is initiated when UV rays penetrate into the skin. Typical examples are amino acids (for example glycine, histidine, tyrosine, tryptophane) and derivatives thereof, imidazoles (for example urocanic acid) and derivatives thereof, peptides, such as D,L-carnosine, D-carnosine, L-carnosine and derivatives thereof (for example anserine), carotinoids, carotenes (for example alpha- carotene, beta-carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, liponic acid and derivatives thereof (for example dihydroliponic acid), aurothioglu- cose, propylthiouracil and other thiols (for example thioredoxine, glutathione, cysteine, cys tine, cystamine and glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, alpha-linoleyl, cholesteryl and glyceryl esters thereof) and their salts, dilaurylthiodi- propionate, distearylthiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (for example butionine sulfoximines, homocysteine sulfoximine, butionine sulfones, penta-, hexa- and hepta-thionine sulfoximine) in very small compatible dosages, also (metal) chelators (for example alpha-hydroxyfatty acids, palmitic acid, phytic acid, lactoferrine), alpha-hydroxy acids (for example citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and derivatives thereof, unsaturated fatty acids and derivatives thereof (for example linoleic acid, oleic acid), folic acid and derivatives thereof, ubiquinone and ubiq- uinol and derivatives thereof, vitamin C and derivatives thereof (for example ascorbyl palmi- tate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (for example vit amin E acetate), vitamin A and derivatives (vitamin A palmitate) and coniferyl benzoate of benzoin resin, rutinic acid and derivatives thereof, glycosyl rutin, ferulic acid, furfurylidene glucitol, carnosine, butyl hydroxytoluene, butyl hydroxyanisole, nordihydroguaiac resin acid, nordihydroguaiaretic acid, trihydroxybutyrophenone, uric acid and derivatives thereof, man nose and derivatives thereof, superoxide dismutase, titanium dioxide (for example disper sions in ethanol), zinc and derivatives thereof (for example ZnO, ZnSC ), selenium and deriva tives thereof (for example selenium methionine), stilbenes and derivatives thereof (for exam ple stilbene oxide, trans-stilbene oxide) and derivatives of these active substances suitable for the purposes of the invention (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids).
[0053] Advantageous inorganic secondary light protection pigments are finely dispersed metal oxides and metal salts which are also mentioned in WO 2005 123101 A1. The total
quantity of inorganic pigments, in particular hydrophobic inorganic micro-pigments in the finished cosmetic preparation according to the present invention is advantageously from 0.1 to 30% by weight, preferably 0.5 to 10.0% by weight, in each case based on the total weight of the preparation.
[0054] Also preferred are particulate UV filters or inorganic pigments, which can optionally be hydrophobed, can be used, such as the oxides of titanium (T1O2), zinc (ZnO), iron (Fe20s), zirconium (Zr02), silicon (S1O2), manganese (e.g. MnO), aluminium (AI2O3), cerium (e.g. Ce20s) and/or mixtures thereof.
Biogenic agents and antioxidants
[0055] Biogenic active substances include, for example, tocopherol, tocopherol acetate, to copherol palmitate, ascorbic acid, (deoxy)ribonucleic acid and its fragmentation products, b- glucans, retinol, Bisabolol, allantoin, phytantriol, panthenol, AHA acids, amino acids, ceramides, pseudoceramides, essential oils, plant extracts, such as such as prunus extract, bambaranus extract and vitamin complexes.
[0056] Antioxidants interrupt the photochemical reaction chain which is triggered when UV radiation penetrates the skin. Typical examples are amino acids (e.g. glycine, histidine, tyro sine, tryptophan) and their derivatives, imidazoles (e.g. urocanic acid) and their derivatives, peptides like D,L-carnosine, D-carnosine, L-carnosine and their derivatives (e.g. anserine), carotenoids, carotenes (e.g. -carotene, lycopene) and their derivates, chlorogenic acid and its derivatives, lipoic acid and its derivatives (e.g. dihydrolic acid), aurothioglucose, propylthiou racil and other thiols (e.g. thioredoxin, glutathione, cysteine, cystine, cystamin and their gly- cosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, linoleyl, choles- teryl and glyceryl esters) and their salts Dilaurylthiodipropionate, ditearylthiodipropionate, thiodipropionic acid and its derivatives (esters, ethers, peptides, lipids, nucleotides, nucleo sides and salts) as well as sulfoximine compounds (e.g. (e.g. buthionine sulfoximines, homo cysteine sulfoximines, butionine sulfones, penta-, hexa-, heptathionine sulfoximines) in very low tolerated dosages (e.g. pmol to mol/kg), furthermore (metal) chelators (e.g. hydroxy fatty acids, palmitic acid, phytinic acid, lactoferrin), hydroxy acids (e.g. (e.g. citric acid, lactic acid, malic acid), humic acid, gallic acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives (e.g. linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and its derivatives (e.g. ascorbyl palmitate, Mg-ascorbyl phosphate, ascorbylacetate), tocoph- erols and derivatives (e.g. vitamin E acetate), vitamin A and derivates (vitamin A palmitate) as well as conifer aryl benzoate of benzoic resin, rutinic acid and its derivatives, glycosyl rutin, ferulic acid, furfurylidene glucitol, carnosine, butyl hydroxytoluene, butylhydroxyanisole, nor- dihydroguaiac resin acid, nordihydroguajaretic acid, trihydroxybutyrophenone, uric acid and its derivatives, mannose and its derivatives, superoxide dismutase, zinc and its derivatives (e.g. e.g. ZnO, ZnS04) selenium and its derivatives (e.g. selenium-methionine), stilbenes and
their derivatives (e.g. styrene oxide, trans-stilbene oxide) and the derivatives suitable for the invention (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these named active substances.
Actives modulating hair pigmentation
[0057] Preferred active ingredients for hair lightening are selected from the group consisting of: kojic acid (5-hydroxy-2-hydroxymethyl-4-pyranone), kojic acid derivatives, preferably kojic acid dipalmitate, arbutin, ascorbic acid, ascorbic acid derivatives, preferably magnesium ascorbyl phosphate, hydroquinone, hydroquinone derivatives, resorcinol, resorcinol deriva tives, preferably 4-alkylresorcinols and 4-(1-phenylethyl)1,3-dihydroxybenzene (phenylethyl resorcinol), cyclohexylcarbamates (preferably one or more cyclohexyl carbamates disclosed in WO 2010/122178 and WO 2010/097480), sulfur-containing molecules, preferably glutathione or cysteine, alpha-hydroxy acids (preferably citric acid, lactic acid, malic acid), salts and esters thereof, N-acetyl tyrosine and derivatives, undecenoyl phenylalanine, gluconic acid, chro- mone derivatives, preferably aloesin, flavonoids, 1-aminoethyl phosphinic acid, thiourea de rivatives, ellagic acid, nicotinamide (niacinamide), zinc salts, preferably zinc chloride or zinc gluconate, thujaplicin and derivatives, triterpenes, preferably maslinic acid, sterols, preferably ergosterol, benzofuranones, preferably senkyunolide, vinyl guiacol, ethyl guiacol, dionic acids, preferably octodecene dionic acid and/or azelaic acid, inhibitors of nitrogen oxide synthesis, preferably L-nitroarginine and derivatives thereof, 2,7-dinitroindazole or thiocitrulline, metal chelators (preferably alpha-hydroxy fatty acids, phytic acid, humic acid, bile acid, bile extracts, EDTA, EGTA and derivatives thereof), retinoids, soy milk and extract, serine protease inhibitors or lipoic acid or other synthetic or natural active ingredients for skin and hair lightening, the latter preferably used in the form of an extract from plants, preferably bearberry extract, rice extract, papaya extract, turmeric extract, mulberry extract, bengkoang extract, nutgrass ex tract, liquorice root extract or constituents concentrated or isolated therefrom, preferably glabridin or licochalcone A, artocarpus extract, extract of rumex and ramulus species, extracts of pine species (pinus), extracts of vitis species or stilbene derivatives isolated or concentrat ed therefrom, saxifrage extract, scutelleria extract, grape extract and/or microalgae extract, in particular Tetraselmis suecica Extract.
[0058] Advantageous skin and hair tanning active ingredients in this respect are substrates or substrate analogues of tyrosinase such as L-tyrosine, N-acetyl tyrosine, L-DOPA or L- dihydroxyphenylalanine, xanthine alkaloids such as caffeine, theobromine and theophyl-line and derivatives thereof, proopiomelanocortin peptides such as ACTH, alpha-MSH, peptide analogues thereof and other substances which bind to the melanocortin receptor, peptides such as Val-Gly-Val-Ala-Pro-Gly, Lys-lle- Gly-Arg-Lys or Leu-lle-Gly-Lys, purines, pyrimidines, folic acid, copper salts such as copper gluconate, chloride or pyrrolidonate, 1,3,4-oxadiazole- 2-thiols such as 5-pyrazin-2-yl-1,3,4-oxadiazole-2-thiol, curcumin, zinc diglycinate (Zn(Gly)2), manganese(ll) bicarbonate complexes ("pseudocat-alases") as described for example in EP 0
584 178, tetrasubstituted cyclohexene deriva-tives as described for example in WO 2005/032501 , isoprenoids as described in WO 2005/102252 and in WO 2006/010661 , mela nin derivatives such as Melasyn-100 and MelanZe, diacyl glycerols, aliphatic or cyclic diols, psoralens, prostaglandins and ana-logues thereof, activators of adenylate cyclase and com pounds which activate the transfer of melanosomes to keratinocytes such as serine proteases or agonists of the PAR-2 receptor, extracts of plants and plant parts of the chrysanthemum species, san-guisorba species, walnut extracts, urucum extracts, rhubarb extracts, microalgae extracts, in particular Isochrysis galbana, trehalose, erythru-lose and dihydroxyacetone. Flavo- noids which bring about skin and hair tinting or brown-ing (e.g. quercetin, rhamnetin, kaempferol, fisetin, genistein, daidzein, chrysin and api-genin, epicatechin, diosmin and di- osmetin, morin, quercitrin, naringenin, hesperidin, phloridzin and phloretin) can also be used.
[0059] The amount of the aforementioned examples of additional active ingredients for the modulation of skin and hair pigmentation (one or more compounds) in the products accord ing to the invention is then preferably 0.00001 to 30 wt.%, preferably 0.0001 to 20 wt.%, par ticularly preferably 0.001 to 5 wt.%, based on the total weight of the preparation.
Hair growth activators or inhibitors
[0060] Formulations and products according to the present invention may also comprise one or more hair growth activators, i.e. agents to stimulate hair growth. Hair growth activators are preferably selected from the group consisting of pyrimidine derivatives such as 2,4- diaminopyrimidine-3-oxide (Aminexil), 2,4-diamino-6-piperidinopyrimidine-3-oxide (Minox idil) and derivatives thereof, 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine and its derivatives, xanthine alkaloids such as caffeine, theobromine and theophylline and derivatives thereof, quercetin and derivatives, dihydroquercetin (taxifolin) and derivatives, potassium channel openers, antiandrogenic agents, synthetic or natural 5-reductase inhibi tors, nicotinic acid esters such as tocopheryl nicotinate, benzyl nicotinate and C1-C6 alkyl nicotinate, proteins such as for example the tripeptide Lys-Pro-Val, diphencypren, hormons, finasteride, dutasteride, flutamide, bicalutamide, pregnane derivatives, progesterone and its derivatives, cyproterone acetate, spironolactone and other diuretics, calcineurin inhibitors such as FK506 (Tacrolimus, Fujimycin) and its derivatives, Cyclosporin A and derivatives thereof, zinc and zinc salts, polyphenols, procyanidins, proanthocyanidins, phytosterols such as for example beta-sitosterol, biotin, eugenol, (±)-beta-citronellol, panthenol, glycogen for example from mussels, extracts from microorganisms, algae, plants and plant parts of for example the genera dandelion (Leontodon or Taraxacum), Orthosiphon, Vitex, Coffea, Paullinia, Theobroma, Asiasarum, Cucurbita or Styphnolobium, Serenoa repens (saw palmet to), Sophora flavescens, Pygeum africanum, Panicum miliaceum, Cimicifuga racemosa, Gly cine max, Eugenia caryophyllata, Cotinus coggygria, Hibiscus rosa-sinensis, Camellia sinensis, Ilex paraguariensis, Isochrysis galbana, licorice, grape, apple, barley or hops or/nd hydroly sates from rice or wheat.
[0061] Alternatively, formulations and products according to the present invention may comprise one or more hair growth inhibitors (as described above), i.e. agents to reduce or prevent hair growth. Hair growth inhibitors are preferably selected from the group consisting of activin, activin derivatives or activin agonists, ornithine decarboxylase inhibitors such as alpha-difluoromethylornithine or pentacyclic triterpenes like for example ursolic acid, betulin, betulinic acid, oleanolic acid and derivatives thereof, 5alpha-reductase inhibitors, androgen receptor antagonists, S-adenosylmethionine decarboxylase inhibitors, gamma-glutamyl transpeptidase inhibitors, transglutaminase inhibitors, soybean-derived serine protease inhib itors, extracts from microorganisms, algae, different microalgae or plants and plant parts of for example the families Leguminosae, Solanaceae, Graminae, Asclepiadaceae or Cucurbita- ceae, the genera Chondrus, Gloiopeltis, Ceramium, Durvillea, Glycine max, Sanguisorba offici nalis, Calendula officinalis, Hamamelis virginiana, Arnica montana, Salix alba, Hypericum per foratum or Gymnema sylvestre.
Physiological cooling and warming agents
[0062] Physiological cooling agents are preferably selected from the following list: menthol and menthol derivatives (for example L-menthol, D-menthol, racemic menthol, isomenthol, neoisomenthol, neomenthol) menthylethers (for example (l-menthoxy)-1,2-propandiol, (I- menthoxy)-2-methyl-1,2-propandiol), menthone glyceryl acetal, menthone glyceryl ketal or mixtures of both, menthylesters (for example menthylformiate, menthyhydroxyisobutyrat, menthyllactates, L-menthyl-L-lactate, L-menthyl-D-lactate, menthyl-(2-methoxy)acetate, menthyl-(2-methoxyethoxy)acetate, menthylpyroglutamate), menthylcarbonates (for example menthylpropyleneglycolcarbonate, menthylethyleneglycolcarbonate, menthylglycerolcar- bonate or mixtures thereof), the semi-esters of menthols with a dicarboxylic acid or deriva tives thereof (for example mono-menthylsuccinate, mono-menthylglutarate, mono- menthylmalonate, O-menthyl succinic acid ester-N,N-(dimethyl)amide, O-menthyl succinic acid ester amide), menthanecarboxylic acid amides (in this case preferably menthanecarbox- ylic acid-N-ethylamide [WS3] or Na-(menthanecarbonyl)glycinethylester [WS5], as described in US 4,150,052, menthanecarboxylic acid-N-(4-cyanophenyl)amide or menthanecarboxylic acid-N-(4-cyanomethylphenyl)amide as described in WO 2005 049553 A1, menthanecar boxylic acid-N-(alkoxyalkyl)amides), menthone and menthone derivatives (for example L- menthone glycerol ketal), 2,3-dimethyl-2-(2-propyl)-butyric acid derivatives (for example 2,3- dimethyl-2-(2-propyl)-butyric acid-N-methylamide [WS23]), isopulegol or its esters (l-(-)- isopulegol, l-(-)-isopulegolacetate), menthane derivatives (for example p-menthane-3,8-diol), cubebol or synthetic or natural mixtures, containing cubebol, pyrrolidone derivatives of cy- cloalkyldione derivatives (for example 3-methyl-2(1-pyrrolidinyl)-2-cyclopentene-1-one) or tetrahydropyrimidine-2-one (for example iciline or related compounds, as described in WO 2004 026840 A1), further carboxamides (for example N-(2-(pyridin-2-yl)ethyl)-3-p- menthanecarboxamide or related compounds), (1R,2S,5R)-N-(4-Methoxyphenyl)-5-methyl-2- (l-isopropyl)cyclohexane-carboxamide [WS12], oxamates (preferably those described in EP
2033688 A2) and [(1 R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl] 2-(ethylamino)-2-oxo-acetate
(X Cool).
[0063] Physiological warming agents can be selected from the group consisting of capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin, homodihydrocapsaicin nonivamid, and chili extracts.
Anti-inflammatory agents
[0064] Suitable anti-inflammatory agents may be selected from the group formed by:
(i) steroidal anti-inflammatory substances of the corticosteroid type, in particular hydro cortisone, hydrocortisone derivatives such as hydrocortisone 17-butyrate, dexame- thasone, dexamethasone phosphate, methylprednisolone or cortisone,
(ii) non-steroidal anti-inflammatory substances, in particular oxicams such as piroxicam or tenoxicam, salicylates such as aspirin, disalcid, solprin or fendosal, acetic acid deriv atives such as diclofenac, fenclofenac, indomethacin, sulindac, tolmetin or clindanac, fenamates such as mefenamic, meclofenamic, flufenamic or niflumic, propionic acid derivatives such as ibuprofen, naproxen or benoxaprofen, pyrazoles such as phenyl butazone, oxyphenylbutazone, febrazone or azapropazone,
(iii) natural or naturally occuring anti-inflammatory substances or substances that alleviate reddening and/or itching, in particular extracts or fractions from camomile, Aloe vera, Commiphora species, Rubia species, willow, willow-herb, oats, calendula, arnica, St John's wort, honeysuckle, rosemary, Passiflora incarnata, witch hazel, ginger or Echina cea, or single active compounds thereof,
(iv) histamine receptor antagonists, serine protease inhibitors (e.g. of Soy extracts), TRPV1 antagonists (e.g. 4-t-Butylcyclohexanol), NK1 antagonists (e.g. Aprepitant, Hydroxy- phenyl Propamidobenzoic Acid), cannabinoid receptor agonists (e.g. Palmitoyl Etha- nolamine) and TRPV3 antagonists.
Anti-microbial agents
[0065] Suitable anti-microbial agents are, in principle, all substances effective against Gram positive bacteria, such as, for example, 4- hydroxybenzoic acid and its salts and esters, N-(4- chlorophenyl)-N'-(3,4- dichlorophenyl)urea, 2,4,4'-trichloro-2'-hydroxy-diphenyl ether (triclo- san), 4-chloro-3, 5-dimethyl-phenol, 2,2'-methylenebis(6-bromo-4- chlorophenol), 3-methyl- 4-(1-methylethyl)phenol, 2-benzyl-4-chloro-phenol, 3-(4-chlorophenoxy)-1, 2-propanediol, 3- iodo-2-propynyl butylcarbamate, chlorhexidine, 3,4,4'-trichlorocarbanilide (TTC), antibacterial fragrances, thymol, thyme oil, eugenol, oil of cloves, menthol, mint oil, farnesol, phenoxy- ethanol, glycerol monocaprate, glycerol monocaprylate, glycerol monolaurate (GML), diglyc-
erol monocaprate (DMC), salicylic acid N-alkylamides, such as, for example, n- octylsalicylamide or n- decylsalicylamide.
Enzyme inhibitors
[0066] Suitable enzyme inhibitors are, for example, esterase inhibitors. These are preferably trialkyl citrates, such as trimethyl citrate, tripropyl citrate, triisopropyl citrate, tributyl citrate and, in particular, triethyl citrate (Hydagen CAT). The substances inhibit enzyme activity, thereby reducing the formation of odour. Other substances which are suitable esterase inhib itors are sterol sulfates or phosphates, such as, for example, lanosterol, cholesterol, campes- terol, stigmasterol and sitosterol sulfate or phosphate, dicarboxylic acids and esters thereof, such as, for example, glutaric acid, monoethyl glutarate, diethyl glutarate, adipic acid, mo noethyl adipate, diethyl adipate, malonic acid and diethyl malonate, hydroxycarboxylic acids and esters thereof, such as, for example, citric acid, malic acid, tartaric acid or diethyl tartrate, and zinc glycinate.
Odour absorbers and antiperspirant active agents
[0067] Suitable odour absorbers are substances which are able to absorb and largely retain odour-forming compounds. They lower the partial pressure of the individual components, thus also reducing their rate of diffusion. It is important that perfumes must remain unim paired in this process. Odour absorbers are not effective against bacteria. They comprise, for example, as main constituent, a complex zinc salt of ricinoleic acid or specific, largely odour- neutral fragrances which are known to the person skilled in the art as "fixatives", such as, for example, extracts of labdanum or styrax or certain abietic acid derivatives. The odour masking agents are fragrances or perfume oils, which, in addition to their function as odour masking agents, give the deodorants their respective fragrance note. Perfume oils which may be men tioned are, for example, mixtures of natural and synthetic fragrances. Natural fragrances are extracts from flowers, stems and leaves, fruits, fruit peels, roots, woods, herbs and grasses, needles and branches, and resins and balsams. Also suitable are animal products, such as, for example, civet and castoreum. Typical synthetic fragrance compounds are products of the ester, ether, aldehyde, ketone, alcohol, and hydrocarbon type. Fragrance compounds of the ester type are, for example, benzyl acetate, p-tert-butylcyclohexyl acetate, linalyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, allyl cyclohexylpropionate, styrallyl pro pionate and benzyl salicylate. The ethers include, for example, benzyl ethyl ether, and the aldehydes include, for example, the linear alkanals having 8 to 18 carbon atoms, citral, citron- ellal, citronellyloxyacetaldehyde, cyclamen aldehyde, hydroxycitronellal, lilial and bourgeonal, the ketones include, for example, the ionones and methyl cedryl ketone, the alcohols include anethole, citronellol, eugenol, isoeugenol, geraniol, linaool, phenylethyl alcohol and terpineol, and the hydrocarbons include mainly the terpenes and balsams. Preference is, however, given to using mixtures of different fragrances which together produce a pleasing fragrance note.
Essential oils of relatively low volatility, which are mostly used as aroma components, are also suitable as perfume oils, e.g. sage oil, camomile oil, oil of cloves, melissa oil, mint oil, cinna mon leaf oil, linden flower oil, juniperberry oil, vetiver oil, olibanum oil, galbanum oil, labda- num oil and lavandin oil. Preference is given to using bergamot oil, dihydromyrcenol, lilial, lyral, citronellol, phenylethyl alcohol, a-hexylcinnamaldehyde, geraniol, benzylacetone, cyc lamen aldehyde, linalool, boisambrene forte, ambroxan, indole, hedione, sandelice, lemon oil, mandarin oil, orange oil, allyl amyl glycolate, cyclovertal, lavandin oil, clary sage oil, b- damascone, geranium oil bourbon, cyclohexyl salicylate, Vertofix coeur, iso-E-super, Fixolide NP, evernyl, iraldein gamma, phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide, romilat, irotyl and floramat alone or in mixtures.
[0068] Suitable astringent antiperspirant active ingredients are primarily salts of aluminium, zirconium or of zinc. Such suitable antihydrotic active ingredients are, for example, aluminium chloride, aluminium chlorohydrate, aluminium dichlorohydrate, aluminium sesquichlorohy- drate and complex compounds thereof, e.g. with 1,2- propylene glycol, aluminium hydroxy- allantoinate, aluminium chloride tartrate, aluminium zirconium trichlorohydrate, aluminium zirconium tetrachlorohydrate, aluminium zirconium pentachlorohydrate and complex com pounds thereof, e.g. with amino acids, such as glycine.
Film formers and anti-dandruff agents
[0069] Standard film formers are, for example, chitosan, microcrystalline chitosan, quater- nized chitosan, polyvinyl pyrrolidone, vinyl pyrrolidone/vinyl acetate copolymers, polymers of the acrylic acid series, quaternary cellulose derivatives, collagen, hyaluronic acid and salts thereof and similar compounds.
[0070] Suitable antidandruff agents are Pirocton Olamin (1-hydroxy-4-methyl-6-(2,4,4- trimethylpentyl)-2-(1 H)-pyridinone monoethanolamine salt), Baypival® (Climbazole), Keto- conazol® (4-acetyl-1-{4-[2-(2,4-dichlorophenyl) r-2-(1 H-imidazol-1-ylmethyl)-1,3-dioxylan-c- 4-ylmethoxyphenyl}-piperazine, ketoconazole, elubiol, selenium disulfide, colloidal sulfur, sulfur polyethylene glycol sorbitan monooleate, sulfur ricinol polyethoxylate, sulfur tar distil late, salicylic acid (or in combination with hexachlorophene), undecylenic acid, monoethano- lamide sulfosuccinate Na salt, Lamepon® UD (protein/undecylenic acid condensate), zinc py- rithione, aluminium pyrithione and magnesium pyrithione/dipyrithione magnesium sulfate.
Carriers and hydrotropes
[0071] Preferred cosmetics carrier materials are solid or liquid at 25°C and 1013 mbar (in cluding highly viscous substances) as for example glycerol, 1,2-propylene glycol, 1,2-butylene glycol, 1,3-propylene glycol, 1,3-butylene glycol, ethanol, water and mixtures of two or more of said liquid carrier materials with water. Optionally, these preparations according to the invention may be produced using preservatives or solubilizers. Other preferred liquid carrier
substances, which may be a component of a preparation according to the invention are se lected from the group consisting of oils such as vegetable oil, neutral oil and mineral oil.
[0072] Preferred solid carrier materials, which may be a component of a preparation accord ing to the invention are hydrocolloids, such as starches, degraded starches, chemically or physically modified starches, dextrins, (powdery) maltodextrins (preferably with a dextrose equivalent value of 5 to 25, preferably of 10 - 20), lactose, silicon dioxide, glucose, modified celluloses, gum arabic, ghatti gum, traganth, karaya, carrageenan, pullulan, curdlan, xanthan gum, gellan gum, guar flour, carob bean flour, alginates, agar, pectin and inulin and mixtures of two or more of these solids, in particular maltodextrins (preferably with a dextrose equiva lent value of 15 - 20), lactose, silicon dioxide and/or glucose.
[0073] In addition, hydrotropes, for example ethanol, isopropyl alcohol or polyols, may be used to improve flow behaviour. Suitable polyols preferably contain 2 to 15 carbon atoms and at least two hydroxyl groups. The polyols may contain other functional groups, more especially amino groups, or may be modified with nitrogen. Typical examples are
• glycerol;
• alkylene glycols such as, for example, ethylene glycol, diethylene glycol, propylene gly col, butylene glycol, hexylene glycol and polyethylene glycols with an average molecu lar weight of 100 to 1000 Dalton;
• technical oligoglycerol mixtures with a degree of self-condensation of 1.5 to 10, such as for example technical diglycerol mixtures with a diglycerol content of 40 to 50% by weight;
• methylol compounds such as, in particular, trimethylol ethane, trimethylol propane, trimethylol butane, pentaerythritol and dipentaerythritol;
• lower alkyl glucosides, particularly those containing 1 to 8 carbon atoms in the alkyl group, for example methyl and butyl glucoside;
• sugar alcohols containing 5 to 12 carbon atoms, for example sorbitol or mannitol,
• sugars containing 5 to 12 carbon atoms, for example glucose or sucrose;
• amino sugars, for example glucamine;
• dialcoholamines, such as diethanolamine or 2-aminopropane-1,3-diol.
Preservatives and/or product protection agents
[0074] Suitable preservatives are, for example, phenoxyethanol, sodium benzoate or sorbic acid, blends of the mentioned ingredients and the other classes of compounds listed in Ap pendix 6, Parts A and B of the Kosmetikverordnung ("Cosmetics Directive"). Alternative prod ucts which could improve the product protection are for example 1,2-alkanediols such as for
example 1,2-penatnediol, 1,2-hexanediol, 1,2-octanediol, 1,2-decanediol, 1,2-dodecanediol and mixtures thereof, 4-hydroxy acetophenone.
Perfume oils [0075] Suitable perfume oils are mixtures of natural and synthetic perfumes. Natural per fumes include the extracts of blossoms (lily, lavender, rose, jasmine, neroli, ylang-ylang), stems and leaves (geranium, patchouli, petitgrain), fruits (anise, coriander, caraway, juniper), fruit peel (bergamot, lemon, orange), roots (nutmeg, angelica, celery, cardamom, costus, iris, calmus), woods (pinewood, sandalwood, guaiac wood, cedarwood, rosewood), herbs and grasses (tarragon, lemon grass, sage, thyme), needles and branches (spruce, fir, pine, dwarf pine), resins and balsams (galbanum, elemi, benzoin, myrrh, olibanum, opoponax). Animal raw materials, for example civet and beaver, may also be used.
Fragrances with woody odor [0076] Suitable fragrances with woody odor are selected from the group consisting of:
(Ethoxymethoxy)cyclododecane AMBERWOOD® Symrise b-2, 2, 3-Tetramethylcyclopent-3-ene-1 -butanol BRAHMANOL® Symrise alpha-Ethyl-2,2,6- MADRANOL® Symrise trimethylcyclohexanepropanol
Octahydro-4,7-methano-1 H-indenemethyl MYROSE® ACETATE Symrise acetate
1,1 -Dimethoxy-cyclododecane PALISANDAL® Symrise
Methoxycyclododecane PALISANDIN® Symrise
(2E)-2-Ethyl-4-(2,2,3)-trimethylcyclopent-3-en- SANDRANOL® Symrise 1 -yl) but-2-en-1 -ol
2H-2,4a-Methanonaphthalene, 1, 3, 4, 5,6,7- SYMROXANE® Symrise hexahydro-7-methoxy-1,1,5,5-tetramethyl-
4-Methyl-4-phenylpentan-2-one VETIKON® Symrise
4-Cyclohexyl -4-methylpentan-2-one VETIRAL® Symrise
1 ',1 ',5',5'-Tetramethylhexahydro-spiro[1,3- YSAMBER® K Symrise dioxolane-2,8'(5'H)-2H-2,4a- methanonaphthalene]
Fragrances with amber odor
[0077] Suitable fragrances with amber odor are selected from the group consisting of:
(4aR,5R,7aS,9R)-Octahydro-2,2,5,8,8,9a- AMBROCENIDE® Symrise hexamethyl-4H-4a,9-methanoazuleno[5,6-d]-
1,3-dioxole
3a, 6, 6, 9a- AMBROXIDE® Symrise
Tetra m ethyl d od eca hyd rona phtho [2, 1 - b]f u ra n
Fragrances with fruity odor [0078] Suitable fragrances with fruity odor are selected from the group consisting of:
Acetophenone Symrise
2-tert.-butyl cyclohexyl acetate AGRUMEX® HC Symrise
Octadecanal ALDEHYDE C18 Symrise
Allyl caproate Symrise
Allyl cyclohexyl propionate Symrise
Allyl heptoate Symrise
Allyl phenoxy acetal Symrise
5-Hexyldihydro-4-methylfuran-2(3H)-one APRIFLOREN® Symrise
Benzaldehyde Symrise
Benzyl alcohol Symrise
1,5-Dimethyl-bicyclo[3.2.1]octan-8-one oxime BUCCOXIME® Symrise
1 -Cyclohexylethyl-2-butenoate DATILAT® Symrise
3, 7-Dimethyloct-1, 6-diene DIHYDROMYRCENE Symrise
Ethyl acetoacetate Symrise
Ethyl butyrate Symrise
Ethyl caproate Symrise
Ethyl heptoate Symrise
Ethyl isovalerate Symrise
Ethyl methyl butyrate-2 Symrise
Ethyl propionate Symrise
(2E)-5-Methylhept-2-en-4-one FILBERTONE® Symrise
2,4,6-Trimethyl-4-phenyl-1,3-dioxane FLOROPAL® Symrise
Ethyl 2,4-dimethyl-1 ,3-dioxolane-2-acetate FRAGOLANE® Symrise 4-(4-Methoxyphenyl)butan-2-one FRAMBION METHL ETHER Symrise
1.3-Dimethylbutyl 2-butenoate FRUTINAT® Symrise Hexyl acetate Symrise
Isoamyl butyrate Symrise Isoamyl isovalerate Symrise
(2 E) - 1 -(2,4,4-Trimethylcyclohex-2-en-1 -y|) but- ISODAMASCONE Symrise 2-en-1 -one
Ethyl (2-methyl-1,3-dioxolan-2-yl)acetate JASMAPRUNAT® Symrise
Methyl phenyl acetate Symrise
6-Butyl-tetrahydro-pyran-2-one NONALACTONE DELTA Symrise
2-Methyl-4-propyl-[1,3]-oxathiane OXANTHIA® Symrise
1,1 '-Bi(cyclopentyl)-2-yl (2E)-but-2-enoate PYROPRUNAT® Symrise
2-Cyclopentene-1 -acetic acid, ethyl ester SULTAN ENE® Symrise rel-(2R,4S,6R)-2,4,6-Trimethyl-4-phenyl-1,3- VERTACETAL® COEUR Symrise dioxane
1.3-Dimethyl-3-phenylbutylacetate VERTICOLACETAT® Symrise
Fragrances with musk odor
[0079] Suitable fragrances with musk odor are selected from the group consisting of:
Oxacycloheptadec-10-en-2-one AMBRETTOLIDE® Symrise Cyclohexadec-8(7)-en-1 -one AURELIONE® Symrise Oxacyclohexadecen-2-one GLOBALIDE® Symrise Cyclohexadec-8-en-1 -one GLOBANONE® Symrise Cyclohexadecanone ISOMUSCONE Symrise Oxacyclohexadecan-2-one MACROLIDE® Symrise Pentadecan-15-olide MACROLIDE® SUPRA Symrise 1 ,4-Dioxacycloheptadecan-5,17-dion ETHYLENE BRASSYLATE Merck
Dyes
[0080] Suitable dyes are any of the substances suitable and approved for cosmetic purposes as listed, for example, in the publication "Kosmetische Farbemittel" of the Farbstoff- kommission der Deutschen Forschungsgemeinschaft, Verlag Chemie, Weinheim, 1984, pages 81 to 106. Examples include cochineal red A (C.l. 16255), patent blue V (C.l. 42051), indigotin (C.l. 73015), chlorophyllin (C.l. 75810), quinoline yellow (C.l. 47005), titanium dioxide (C.l. 77891), indanthrene blue RS (C.l. 69800) and madder lake (C.l. 58000). Luminol may also be present as a luminescent dye. Advantageous coloured pigments are for example titanium dioxide, mica, iron oxides (e.g. Fe2C>3 FesC , FeO(OH)) and/or tin oxide. Advantageous dyes are for example carmine, Berlin blue, chromium oxide green, ultramarine blue and/or manga nese violet.
Preparations
[0081] Preferred compositions according to the present inventions are selected from the group of products for treatment, protecting, care and cleansing of the skin and/or hair or as a make-up product, preferably as a leave-on product (meaning that the one or more com pounds stay on the skin and/or hair for a longer period of time, compared to rinse-off prod ucts).
[0082] The formulations according to the invention are preferably in the form of an emulsion, e.g. W/O (water-in-oil), O/W (oil-in-water), W/O/W (water-in-oil-in-water), O/W/O (oil-in- water-in-oil) emulsion, PIT emulsion, Pickering emulsion, emulsion with a low oil content, micro- or nanoemulsion, a solution, e.g. in oil (fatty oils or fatty acid esters, in particular C&- C32 fatty acid C2-C30 esters) or silicone oil, dispersion, suspension, creme, lotion or milk, de pending on the production method and ingredients, a gel (including hydrogel, hydrodisper sion gel, oleogel), spray (e.g. pump spray or spray with propellant) or a foam or an impreg nating solution for cosmetic wipes, a detergent, e.g. soap, synthetic detergent, liquid wash ing, shower and bath preparation, bath product (capsule, oil, tablet, salt, bath salt, soap, etc.), effervescent preparation, a skin care product such as e.g. an emulsion (as described above), ointment, paste, gel (as described above), oil, balsam, serum, powder (e.g. face powder, body powder), eau de perfume, eau de toilette, after-shave, a mask, a pencil, stick, roll-on, pump, aerosol (foaming, non-foaming or post-foaming), a deodorant and/or antiperspirant, mouth wash and mouth rinse, a foot care product (including keratolytic, deodorant), an insect repel lent, a sunscreen, aftersun preparation, a shaving product, aftershave balm, pre- and after shave lotion, a depilatory agent, a hair care product such as e.g. shampoo (including 2-in- 1 shampoo, anti-dandruff shampoo, baby shampoo, shampoo for dry scalps, concentrated shampoo), conditioner, hair tonic, hair water, hair rinse, styling creme, pomade, perm and setting lotion, hair spray, styling aid (e.g. gel or wax), hair smoothing agent (detangling agent, relaxer), hair dye such as e.g. temporary direct-dyeing hair dye, semi-permanent hair dye,
permanent hair dye, hair conditioner, hair mousse, eye care product, make-up, make-up re mover or baby product.
[0083] Auxiliary substances and additives can be included in quantities of 5 to 99 % b.w., preferably 10 to 80 % b.w., based on the total weight of the formulation. The amounts of cosmetic or dermatological auxiliary agents and additives and perfume to be used in each case can easily be determined by the person skilled in the art by simple trial and error, de pending on the nature of the particular product.
[0084] The preparations can also contain water in a quantity of up to 99 wt. -percent., prefer ably from about 5 to about 80 wt. -percent and more preferably either from about 10 to about 50 or from about 60 to about 80 wt. -percent based on the total weight of the prepara tion.
CAPSULES AND ENCAPSULATION
[0085] The compositions are typically encapsulated by means of a solid covering material, which is preferably selected from starches, degraded or chemically or physically modified starches (in particular dextrins and maltodextrins), gelatines, gum arabic, agar-agar, ghatti gum, gellan gum, modified and non-modified celluloses, pullulan, curdlan, carrageenans, alginic acid, alginates, pectin, inulin, xanthan gum and mixtures of two or more of said substances.
[0086] The solid covering material is preferably selected from gelatine (preferred are pork, beef, chicken and/or fish gelatines and mixtures thereof, preferably comprising at least one gelatine with a bloom value of greater than or equal to 200, preferably with a bloom value of greater than or equal to 240), maltodextrin (preferably obtained from maize (corn), wheat, tapioca or potato, preferred maltodextrins have a DE value of 10 - 20), modified cellulose (for example cellulose ether), alginates (for example Na-alginate), carrageenan (beta-, iota-, lambda- and/or kappa carrageenan), gum arabic, curdlan and/or agar-agar. Gelatine is pref erably used, in particular, because of its good availability in different bloom values. Particular ly preferred, especially for oral use are seamless gelatine or alginate capsules, the covering of which dissolves very rapidly in the mouth or bursts when chewing. Production may take place, for example, as described in EP 0389700 A1, US 4,251,195, US 6,214,376, WO 2003 055587 or WO 2004 050069 A1.
[0087] The capsules, however, may also represent micro-capsules. "Microcapsules" are un derstood to be spherical aggregates with a diameter of about 0.1 to about 5 mm which con tain at least one solid or liquid core surrounded by at least one continuous membrane. More precisely, they are finely dispersed liquid or solid phases coated with film-forming polymers, in the production of which the polymers are deposited onto the material to be encapsulated after emulsification and coazervation or interfacial polymerization. In another process, liquid active principles are absorbed in a matrix ("micro-sponge") and, as micro-particles, may be
additionally coated with film-forming polymers. The microscopically small capsules, also known as nano-capsules, can be dried in the same way as powders. Besides single-core mi crocapsules, there are also multiple-core aggregates, also known as microspheres, which con tain two or more cores distributed in the continuous membrane material. In addition, single core or multiple-core microcapsules may be surrounded by an additional second, third etc. membrane. The membrane may consist of natural, semisynthetic or synthetic materials. Natu ral membrane materials are, for example, gum arabic, agar agar, agarose, maltodextrins, al- ginic acid and salts thereof, for example sodium or calcium alginate, fats and fatty acids, cetyl alcohol, collagen, chitosan, lecithins, gelatine, albumin, shellac, polysaccharides, such as starch or dextran, polypeptides, protein hydrolysates, sucrose and waxes. Semisynthetic membrane materials are inter alia chemically modified celluloses, more particularly cellulose esters and ethers, for example cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, hy- droxypropyl methyl cellulose and carboxymethyl cellulose, and starch derivatives, more par ticularly starch ethers and esters. Synthetic membrane materials are, for example, polymers, such as polyacrylates, polyamides, polyvinyl alcohol or polyvinyl pyrrolidone.
[0088] Examples of known microcapsules are the following commercial products (the mem brane material is shown in brackets) Hallcrest Microcapsules (gelatin, gum arabic), Coletica Thalaspheres (maritime collagen), Lipotec Millicapseln (alginic acid, agar agar), Induchem Unispheres (lactose, microcrystalline cellulose, hydroxypropylmethyl cellulose), Unicetin C30 (lactose, microcrystalline cellulose, hydroxypropylmethyl cellulose), Kobo Glycospheres (modified starch, fatty acid esters, phospholipids), Softspheres (modified agar agar) and Kuhs Probiol Nanospheres (phospholipids).
[0089] The active principles are released from the microcapsules by mechanical, thermal, chemical or enzymatic destruction of the membrane, normally during the use of the prepara tions containing the microcapsules. Despite the fact that the state of the art a huge range of possibilities for the encapsulation of actives, methods according to which a shell is obtained by coazervation, precipitation or polycondensation of anionic and cationic polymers has been quite suitable for the formation of stable capsules. Particularly, a preferred process for the encapsulation of active principles according to the present invention is characterised in that it comprises the steps of
• preparing a matrix from gel formers, cationic polymers and active principles;
• optionally dispersing said matrix in an oil phase; and
• treating said dispersed matrix with aqueous solutions of anionic polymers and option ally removing the in phase in the process.
[0090] Of course, anionic and cationic polymers in steps (a) and (c) can be exchanged.
Gel formers
[0091] In the context of the invention, preferred gel formers are substances which are capa ble of forming gels in aqueous solution at temperatures above 40° C. Typical examples of such gel formers are heteropolysaccharides and proteins. Preferred thermogelling heteropol ysaccharides are agaroses which may be present in the form of the agar agar obtainable from red algae, even together with up to 30% by weight of non-gel-forming agaropectins. The principal constituent of agaroses are linear polysaccharides of Galactose and 3,6-anhydro-L- galactose with alternate 1,3- and 1,4-glycosidic bonds. The heteropolysaccharides preferably have a molecular weight of 110,000 to 160,000 and are both odourless and tasteless. Suitable alternatives are pectins, xanthans (including xanthan gum) and mixtures thereof. Other pre ferred types are those which in 1% by weight aqueous solution still form gels that do not melt below 80° C. and solidify again above 40° C. Examples from the group of thermogelling proteins are the various gelatines.
Anionic polymers
[0092] Salts of alginic acid are preferred for this purpose. The alginic acid is a mixture of car boxyl-containing polysaccharides with the following idealized monomer unit:
[0093] The average molecular weight of the alginic acid or the alginates is in the range from 150,000 to 250,000. Salts of alginic acid and complete and partial neutralization products thereof are understood In particular to be the alkali metal salts, preferably sodium alginate ("algin") and the ammonium and alkaline earth metal salts. Mixed alginates, for example so dium/magnesium or sodium/calcium alginates, are particularly preferred. In an alternative embodiment of the invention, however, carboxymethyl celluloses and anionic chitosan deriv atives, for example the carboxylation and above all succinylation products are also suitable for this purpose.
Cationic polymers
[0094] Chitosans are biopolymers which belong to the group of hydrocolloids. Chemically, they are partly de-acetylated chitins differing in their molecular weights which contain the following - idealized - monomer unit:
[0095] In contrast to most hydrocolloids, which are negatively charged at biological pH val ues, chitosans are cationic biopolymers under these conditions. The positively charged chi- tosans are capable of interacting with oppositely charged surfaces and are therefore used in cosmetic hair-care and body-care products and pharmaceutical preparations.
[0096] In a preferred embodiment of the invention a 1 to 10 and preferably 2 to 5% by weight aqueous solution of the gel former, preferably agar agar, is normally prepared and heated under reflux. A second aqueous solution containing the cationic polymer, preferably chitosan, in quantities of 0.1 to 2 and preferably 0.25 to 0.5% by weight and the active princi ple in quantities of 0.1 to 25 and preferably 0.25 to 10% by weight is added in the boiling heat, preferably at 80 to 100 ° C; this mixture is called the matrix. Accordingly, the charging of the microcapsules with active principles may also comprise 0.1 to 25% by weight, based on the weight of the capsules. If desired, water-insoluble constituents, for example inorganic pigments, may also be added at this stage to adjust viscosity, generally in the form of aque ous or aqueous/alcoholic dispersions. In addition, to emulsify or disperse the active princi ples, it can be useful to add emulsifiers and/or solubilisers to the matrix. After its preparation from gel former, cationic polymer and active principle, the matrix optionally is very finely dis persed in an oil phase with intensive shearing in order to produce small particles in the sub sequent encapsulation process. It has proved to be particularly advantageous in this regard to heat the matrix to temperatures in the range from 40 to 60° C while the oil phase is cooled to 10 to 20° C. The actual encapsulation, i.e. formation of the membrane by contacting the cationic polymer in the matrix with the anionic polymers, takes place in the third step. To this end, it is advisable to wash the matrix - dispersed in the oil phase - with an aqueous ca. 0.1 to 3 and preferably 0.25 to 0.5% by weight aqueous solution of the anionic polymer, preferably the alginate, at a temperature in the range from 40 to 100 and preferably 50 to 60° C. and, at the same time, to remove the oil phase if present. The resulting aqueous preparations gener ally have a microcapsule content of 1 to 10% by weight. In some cases, it can be of ad vantage for the solution of the polymers to contain other ingredients, for example emulsifiers or preservatives. After filtration, microcapsules with a mean diameter of preferably 1 to 3 mm are obtained. It is advisable to sieve the capsules to ensure a uniform size distribution. The microcapsules thus obtained may have any shape within production-related limits, but are preferably substantially spherical.
INDUSTRIAL APPLICATION
[0097] Another object of the present invention refers to a non-therapeutic method for modulation of the endocannabinoid system of a human being, and/or enhancing the mood of a human being - protecting endogenous cells of a human being against oxidative stress and/or oxidative damages prophylaxis and treatment of a human being against skin redness prophylaxis and treatment of a disturbed skin barrier and/or dry skin of a human being prophylaxis and treatment of excessive sebum production of a human being comprising or consisting of the following steps:
(i) providing a composition comprising or consisting of Cannabidiol and optionally Bisabolol; and
(ii) administering said composition to said individual.
[0098] The administration of the composition according to the methods as described above can be effected either by topical application or oral uptake.
[0099] Another object of the present invention refers to the non-therapeutic use of composi tion comprising or consisting of
(a) Cannabidiol and optionally
(b) Bisabolol for
(i) modulating CB-2 receptors;
(ii) increasing the expression of beta-endorphins;
(iii) modulating the expression cortisol;
(iv) protecting endogenous cells against oxidative stress and damage; (v) modulating the expression of IL8 and PGE-2
(vi) increasing biosynthesis of hyaluronic acid
(vii) modulating sebum production in sebum glands.
[00100] A final object of the present invention is directed to the use of a composition comprising or consisting of (a) Cannabidiol and optionally
(b) Bisabolol
as
(i) mood enhancers;
(ii) antioxidants;
(iii) soothing agents; (iv) moisturizers;
(v) sebum modulators.
[00101] As far as the methods and uses as described above are concerned, the compositions can be administered to the human body for example topically as a component of a cosmetic formulation such as for example a cream, lotion, emulsion, mousse and the like. In case of oral uptake, capsules comprising the compositions are the preferred embodiment.
[00102] For the sake of good order, it is emphasized that all the above-mentioned preferred embodiments, in particular with respect to mixtures and mixing ratios as well as indications, apply to the methods and uses according to the present invention. Therefore, repetition is not necessary at this point.
EXAMPLES
Examples 1 and 2, Comparative Example C1
CB2 activity
[00103] The cannabinoid receptor types 1 and 2, abbreviated as CBi and CB2, are G protein- coupled receptor from the cannabinoid receptor family that in humans are encoded by the CNR2 gene. Both receptors inhibit the activity of adenylyl cyclase through their Gi/Goa subunits. CB2 can also couple to stimulatory Gccs subunits leading to an increase of intracellular cAMP, as has been shown for human leukocytes. Through their GpY subunits, CB2 receptors are also known to be coupled to the MAPK-ERK pathway, a complex and highly conserved signal transduction pathway, which regulates a number of cellular processes in mature and developing tissue. The CB2 receptors are mainly found on white blood cells, in the tonsils and in the spleen. The immune cells also express CB1, although there are fewer of them than CB2. In the immune system, one important function of the cannabinoid receptors is the regulation of cytokine release. CB2 activation is considered having positive effects on the course of Alzheimer's disease through various mechanisms, including the reduction of local, microglia-mediated inflammation and an increased rate of beta-amyloid removal.
[00104] For determining CB activity 293T-CB2 cells (stably transfected with CB2 cDNAs) are incubated in 24-well plates (5x104 cell/ml) and transiently transfected with 0,1 pg/ml of the plasmid CRE-luc that contains six consensus cAMP responsive elements (CRE) linked to firefly luciferase. Transient transfections are performed with Rotifect (Carl Roth GmbH, Karlsruhe, Germany) according to the manufacturer's instructions and harvested 24 h after transfection
[00105] To measure CB2 antagonistic activity the ability of the test substances was measured to prevent WIN-55, 212-2-mediated inhibition of CRE-Luc activity in the same cellular system. As a positive control for CB2 antagonism we used AM630 and SR144528. After six hours of stimulation the cells were lysed in 25 mM Tris-phosphate pH 7.8, 8 mM MgCh, 1 mM DTT, 1% Triton X-100, and 7% glycerol and luciferase activity measured using a plate reader TriStar2 Berthold/LB942 multimode reader (Berthold Technologies) following the instructions of the luciferase assay kit (Promega, Madison, Wl). The background obtained with the lysis buffer will be subtracted in each experimental value, and the specific transactivation expressed as fold induction over basal levels (CRE-Luc). The results are compiled in Table 1 and show an increased antagonistic CB2 activity for the inventive compositions
Table 1
Effect of the compounds on CB2 antagonistic activity
293T-CB2 cells were transient transfect with CRE-luc plasmid. After 24 h the cells were treated with Forskolin and WIN55, 212-2 (ImM) and the test compounds. After 6 h luciferase activity was measured in the cell lysates. CB2 antagonist is reflected by reversing WIN-induced inhibition of Forskolin-mediated CRE-Luc activation
0 Control 10+0 100
0 Control 10+1 60
Cl Bisabolol 10 10+1 15
1 Cannabidiol* 10 10+1 125
2 Cannabidiol + Bisabolol (1:1)** 10 10+1 145
* SymDStress ** SymDStress 100
Examples 3 to 6
Moisturisation
[00106] Moisturisation is a key property of cosmetic skin care formulations and strengthens its barrier function to protect it from intruding pathogenic bacteria and other noxes. Hyalu ronic acid contributes in moisturisation as it has high water capturing activity.
[00107] Gene expression is the process by which information from a gene is used in the syn thesis of a functional gene product. These products are often proteins. Stressors or Signals acting on cells are transferred and processed resulting in gene expression. Based on the spe cific gene expression alterations, conclusions about intracellular processes can be drawn.
[00108] Hyaluronic acid (HA), is a glycosaminoglycan (GAG) and is a major contributor in moisturisation in the skin synthesized by fibroblasts in the dermis and epidermis. It exhibits high water binding capacity and thus captures ambient water on the skin surface subse quently moisturizing it. In the following, moisturisation was determined by Gene Expression Analysis using quantitative Real Time Polymerase Chain Reaction (qPCR)
[00109] Gene expression analysis was performed by measuring the concentration of mRNA using quantitative real-time qPCR. The purified RNA from cells was reversely transcribed and the resulting cDNA used as a template in the qPCR reaction to detect and quantitate gene expression products. Subsequently, human dermal skin fibroblasts were seeded on cell cul ture tissue plastic and treated with 2mM SymDStress™. After 24h cells were harvested, RNA was isolated and subjected to reverse transcription and qPCR. In the following experiments Cannabidiol was used at a concentration of 0.0000628 %, equivalent to 0.002 mM. Genes and resulting fold induction in response to Cannabidiol treatment are shown in Table 2:
Table 2
Genes and resulting fold induction in response to Cannabidiol treatment
3 Aggrecan ACAN 2,59398431 2.5
4 Cell migration inducing hya CEMIP 4,01237255 4.0 luronan binding protein
5 Hyaluronic acid binding pro HABP1 2,34835008 2.3 tein 1
6 Hyaluronan mediated motili HMMR 2,78249926 2.7 ty receptor
* relative to untreated control
[00110] The results clearly demonstrate that Cannabidiol also at low concentrations induces gene expression of Aggrecan, CEMIP Cell migration inducing hyaluronan binding protein, HABP1 Hyaluronic acid binding protein 1 and HMMR Hyaluronan mediated motility receptor being involved in Hyaluronic acid synthesis and binding.
Examples 7 and 8, Comparative Example C2
Stimulation of hyaluronic acid biosynthesis
[00111] Hyaluronic acid (HA), also known as hyaluronan or hyaluronate is a large linear non- sulfated glycosaminoglycan (GAG) with a molecular weight between 106 and 107 Da. It is a major component of connective tissues and thus distributed ubiquitously in the organism.
[00112] About one-half of the body's entire hyaluronan is found in the skin and about one fourth in the skeleton and the supporting structures like ligaments and joints. Hyaluronan is synthesized by fibroblasts and other specialized connective tissue cells. [00113] Hyaluronan is especially important for the structure and organization of extracellular matrices. The hyaluronan network acts as an osmotic buffer and is responsible for water ho meostasis as well as it regulates protein distribution via the formation of flow and diffusion barriers. Additionally, hyaluronan interacts with proteins and cell surfaces and thus has a strong influence on cell proliferation, differentiation and tissue repair. [00114] Hyaluronic acid concentration produced in response to a specific compound was determined using the ELISA technique. Human dermal skin fibroblasts were seeded on cell culture plastic for 96 h. Subsequently cells were treated with test compound for 72h. Then, cells were lysed and subjected to the ELISA assay. Here, a specific antibody was immobilized on plastic dishes and captured the HA from the cell lysate. After removing the supernatant
and several washing steps the bound HA was detected by an enzyme linked detection anti body specifically binding HA. By addition of the enzyme substrate the amount of immobilized HA was made visible by a color reaction. Table 3 shows HA stimulation in response to Can nabidiol and Bisabolol treatment.
Table 3
HA stimulation in response to Cannabidiol/Bisabolol treatment
C2 Bisabolol 0.25 +26.5
7 Cannabidiol 0.25 +44.3
8 Cannabidiol/Bisabolol (1:1) 0.25 +46.5
Examples 9 to 17, Comparison Example C3to C5
Inhibition of IL8 and PEG2
[00115] Inflammation in the skin occurs after UV or chemical exposure, microbial infection or wounding to form a defence against pathogens. However, inflammation in response to UV is associated with degenerative processes in the skin resulting in photoaging, wrinkle and age spot formation. In order to identify the Anti-inflammatory (Al) potential of Cannabidiol, we quantified the inflammatory mediator interleukin 8 (IL8) and prostaglandin E2 (PGE2), which initiates and mediates inflammation through recruitment of inflammatory cells from the vas culature.
[00116] Interleukin 8 (IL8) or CXCL8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. IL8 is initially produced as a precursor which undergoes cleavage to create several active IL8 isoforms. In- terleukin-8 plays a key role as inflammation mediator to recruit and activate neutrophils, for example, in association with gingivitis, psoriasis and other diseases. IL8 secretion is increased by various kinds of stress including UV & oxidant stress, which thereby cause the recruitment of inflammatory cells and induces a further increase in oxidant stress mediators, making it a key parameter in localized inflammation.
[00117] Prostaglandin E2 (PGE2) is a principal mediator of inflammation and is produced in response to NFkB signalling activated by IL1 alpha/beta and IL8 stimulation. In cells, arachi- donic acid is transformed into PGE2 via cyclooxygenase (COX) enzymes and terminal prosta glandin E synthases (PGES). Selective COX-2 and NFkB/IL8 inhibitors reduce PGE2 production to diminish inflammation. Therefore, inhibition of PGE2 is an important target for the screen ing of anti-inflammatory substances.
[00118] The ELISA assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of a protein in a liquid sample using antibodies directed against the protein to be measured.
[00119] Therefore, the protein of interest is immobilized on a solid surface, e.g. a microtiter plate. This protein is then detected by a specific antibody, forming a complex with the pro tein. This antibody is conjugated covalently to an enzyme or to a secondary antibody that is linked to an enzyme. The excess proteins and antibodies that are non-specifically bound are removed by washing steps. The amount of bound antibody is quantified by adding an enzy matic substrate to produce a visible signal, which indicates the quantity of the protein of in terest in the sample.
IL8 ELISA
[00120] According to the following test approach, IL8 produced and secreted by cells was determined in an enzyme linked immunosorbance assay (ELISA) from cell supernatants utiliz ing antibodies detecting the IL8. The assay was performed on HaCaT cells by addition of test substances and their incubation for 6h (37°C). Afterwards, inflammation was triggered with IL1 alpha for 24h or 2h, respectively, and IL8 was measured. For this purpose the quantitative sandwich enzyme immunoassay technique was employed. A monoclonal antibody specific for human IL8 was pre-coated onto a microplate. Standards and samples/supernatants were pi petted into the wells and any IL8 present was bound by the immobilized antibody. After re moving any unbound substances, an enzyme-linked polyclonal antibody specific for human IL8 was added to the wells. After removing any unbound antibody-enzyme reagent, a sub strate solution was added. A colour develops in proportion to the amount of IL8 bound in the initial step. Results were calculated as IL8 inhibition [%]. Therefore, the IL8 concentrations for unknown samples were interpolated from the standard curve. Finally, the IL8 concentration of the non-stimulated control was subtracted of each determined IL8 concentration. Afterwards the inhibition was determined in relation to the stimulated control. The results are shown in Tables 4 and 5:
Table 4
Inhibition of IL8 secretion versus control = 0
9 Cannabidiol 0.000343 0.011 35.31
10 Cannabidiol 0.000159 0.0050 19.47
11 Cannabidiol 0.000074 0.0023 6.68
[00121] The results indicate that Cannabidiol exhibits good anti-inflammatory potential. In flammation was triggered with IL1 alpha for 24h. * indicates a statistically significant differ ence (Multiple Comparisons versus Control Group (One Way ANOVA with repeated measures, Bonferroni t-test) p < 0,05).
Table 5
Inhibition of IL8 secretion versus control = 0
C3 Bisabolol 0.002847 4316 61 8.02 39 12 Cannabidiol 0.000150 5576 79 8.68 21 [00122] The results show that Cannabidiol exhibits higher anti-inflammatory potential than
Bisabolol. Inflammation was triggered with IL1 alpha for 24h
PGE2 ELISA
[00123] To evaluate PGE2 amount secreted by cells in response to IL1 alpha stimulation, again ELISA technique was used. An antibody has been pre-coated onto 96-well plates. Standards or test samples were added to the wells, along with an enzyme-conjugated-PGE2 antigen and a monoclonal antibody specific to PGE2. In several washing steps excess rea gents were removed. Then, a substrate was added and after a short incubation the enzyme reaction was stopped and the yellow colour generated was read at 405 nm. The intensity of the yellow coloration was inversely proportional to the amount of PGE2 captured in the plate. The results are shown in Table 6:
Table 6
Inhibition of PEG2 secretion versus control = 0
C4 Bisabolol 0.003 0.1 17.71
13 Cannabidiol 0.000015 0.005 47.8
14 Cannabidiol 0.000013 0.004 42.55
15 Cannabidiol 0.000010 0.003 26.77
16 Cannabidiol 0.00006 0.002 28.26
[00124] The results show a strong anti-inflammatory potential of Cannabidiol and Bisabolol on PGE2 release. Inflammation was triggered with IL1 alpha for 24h.
Ex vivo IL8 ELISA
[00125] Human skin from abdominal plastic surgery was used (donor: female, born in 1976). Informed consent has been obtained. The skin samples were cut in pieces of approx. 8x3 mm (0 x thickness) and cultured up to the planned endpoint (i.e. day 2). Four skin specimens were used for each treatment. Skin samples were cultured in an air-liquid interface in a perforated ring of stainless steel in contact with culture medium (modified Williams' E medium). At day 2 the culture medium was collected to perform the IL8 assay. The skin samples were cultured without any treatment for 24 hours, for acclimation. After this time, the culture medium was renewed and replaced by fresh medium containing IL1 alpha. The test samples were applied topically. For topical application skin biopsies were gently cleaned with a sterile cohon pad and 4mI of treatment for each tested sample were applied on top of each piece and covered with a 6 0 mm delivery membrane. At day 2 the organ culture medium was withdrawn from the wells and analysed for IL8. The media coming from 2 wells were assayed separately, 3 readings for each well have been made. The IL8 secreted was quantified using ELISA tech- nique. The results are shown in Table 7:
Table 7
IL8 inhibition on ex vivo explants versus control = 0
C5 Bisabolol 0.5 7.1
17 Cannabidiol 0.025 12.0
Claims
1. A composition comprising or consisting of
(a) Cannabidiol and optionally
(b) Bisabolol for use as a medicament for prophylaxis and treatment of inflammation, preferably of microglia-mediated inflammation of mature and developing tissue.
2. A composition comprising or consisting of
(a) Cannabidiol and optionally
(b) Bisabolol for use as a medicament for prophylaxis and/or treatment of depressions, stress and anxiety states.
3. A composition comprising or consisting of
(a) Cannabidiol and optionally
(b) Bisabolol for use as a medicament for protection of endogenous cells against oxidative stress and/or oxidative damages.
4. A composition comprising or consisting of
(a) Cannabidiol and optionally
(b) Bisabolol for use as a medicament for prophylaxis and/or treatment of skin redness.
5. A composition comprising or consisting of
(a) Cannabidiol and optionally
(b) Bisabolol for use as a medicament for prophylaxis and/or treatment of disturbed skin barriers and/or dry skin.
6. A composition comprising or consisting of
(a) Cannabidiol and optionally
(b) Bisabolol for use as a medicament for prophylaxis and/or treatment of excessive sebum produc tion.
7. The compositions of any of the proceeding Claims 1 to 6, comprising components (a) and (b) in a ratio by weight of from about 0,1:99.09 to about 20:80.
8. The compositions of any of the proceeding Claims 1 to 6, wherein said Cannabidiol is obtained synthetically from up-cycled D-limonene.
9. The compositions of any of the proceeding Claims 1 to 6, wherein said Bisabolol con tains ginger root extract or tocopherol to an amount of at most 5 wt. -percent.
10. A non-therapeutic method for modulation of the endocannabinoid system of a human being, comprising or consisting of the following steps:
(i) providing a composition comprising or consisting of Cannabidiol and optionally Bisabolol; and
(ii) administering said composition to said individual.
11. A non-therapeutic method for enhancing the mood of a human being, comprising or consisting of the following steps:
(i) providing a composition comprising or consisting of Cannabidiol and optionally Bisabolol; and
(ii) administering said composition to said individual.
12. A non-therapeutic method for protecting endogenous cells of a human being against oxidative stress and/or oxidative damages, comprising or consisting of the following steps:
(i) providing a composition comprising or consisting of Cannabidiol and optionally Bisabolol; and
(ii) administering said composition to said individual.
13. A non-therapeutic method for prophylaxis and treatment of a human being against skin redness, comprising or consisting of the following steps:
(i) providing a composition comprising or consisting of Cannabidiol and optionally Bisabolol; and
(ii) administering said composition to said individual.
14. A non-therapeutic method for prophylaxis and treatment of a disturbed skin barrier and/or dry skin of a human being, comprising or consisting of the following steps:
(i) providing a composition comprising or consisting of Cannabidiol and optionally Bisabolol; and
(ii) administering said composition to said individual.
15. A non-therapeutic method for prophylaxis and treatment of excessive sebum produc tion of a human being, comprising or consisting of the following steps:
(i) providing a composition comprising or consisting of Cannabidiol and optionally Bisabolol; and
(ii) administering said composition to said individual.
16. The method according to any of the preceding Claims 10 to 15 wherein the administra tion is effected either by topical application or oral uptake.
17. The non-therapeutic use of composition comprising or consisting of (a) Cannabidiol and optionally
(b) Bisabolol for
(i) modulating CB-2 receptors;
(ii) increasing the expression of beta-endorphins;
(iii) modulating the expression cortisol;
(iv) protecting endogenous cells against oxidative stress and damage;
(v) modulating the expression of IL8 and PGE-2
(vi) increasing biosynthesis of hyaluronic acid
(vii) modulating sebum production in sebum glands.
18. Use of a composition comprising or consisting of
(a) Cannabidiol and optionally
(b) Bisabolol as
(i) mood enhancers;
(ii) antioxidants;
(iii) soothing agents;
(iv) moisturizers;
(v) sebum modulators.
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CN113164792A (en) | 2018-11-02 | 2021-07-23 | 西姆莱斯股份公司 | Liquid transparent mixtures of UV filters |
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2021
- 2021-04-19 EP EP21724198.3A patent/EP4326251A1/en active Pending
- 2021-04-19 WO PCT/EP2021/060135 patent/WO2022223099A1/en active Application Filing
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2022
- 2022-04-19 EP EP22168732.0A patent/EP4079301A3/en active Pending
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WO2022223099A1 (en) | 2022-10-27 |
EP4079301A3 (en) | 2023-01-18 |
EP4079301A2 (en) | 2022-10-26 |
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