US20130004445A1 - Organosiloxanes containing ester derivatives of ascorbic acid - Google Patents
Organosiloxanes containing ester derivatives of ascorbic acid Download PDFInfo
- Publication number
- US20130004445A1 US20130004445A1 US13/590,736 US201213590736A US2013004445A1 US 20130004445 A1 US20130004445 A1 US 20130004445A1 US 201213590736 A US201213590736 A US 201213590736A US 2013004445 A1 US2013004445 A1 US 2013004445A1
- Authority
- US
- United States
- Prior art keywords
- ascorbic acid
- carboxy
- functional
- group
- organosiloxane
- 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.)
- Abandoned
Links
- -1 ester derivatives of ascorbic acid Chemical class 0.000 title claims abstract description 63
- 125000005375 organosiloxane group Chemical group 0.000 title claims abstract description 49
- 239000000203 mixture Substances 0.000 claims abstract description 75
- 238000000034 method Methods 0.000 claims abstract description 40
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
- 125000005647 linker group Chemical group 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 110
- 229960005070 ascorbic acid Drugs 0.000 claims description 55
- 239000011668 ascorbic acid Substances 0.000 claims description 52
- 235000010323 ascorbic acid Nutrition 0.000 claims description 51
- 238000002156 mixing Methods 0.000 claims description 25
- 102000004190 Enzymes Human genes 0.000 claims description 20
- 108090000790 Enzymes Proteins 0.000 claims description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 125000006239 protecting group Chemical group 0.000 claims description 15
- 108090001060 Lipase Proteins 0.000 claims description 10
- 102000004882 Lipase Human genes 0.000 claims description 10
- 102000004157 Hydrolases Human genes 0.000 claims description 8
- 108090000604 Hydrolases Proteins 0.000 claims description 8
- 239000011942 biocatalyst Substances 0.000 claims description 8
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 claims description 8
- 239000004367 Lipase Substances 0.000 claims description 7
- 235000019421 lipase Nutrition 0.000 claims description 7
- 238000006664 bond formation reaction Methods 0.000 claims description 6
- 125000000524 functional group Chemical group 0.000 claims description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 6
- 239000000839 emulsion Substances 0.000 claims description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 108090000371 Esterases Proteins 0.000 claims description 3
- 108091005804 Peptidases Proteins 0.000 claims description 3
- 239000004365 Protease Substances 0.000 claims description 3
- 108010005400 cutinase Proteins 0.000 claims description 3
- 108050008598 Phosphoesterases Proteins 0.000 claims description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 15
- 239000000047 product Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000012530 fluid Substances 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 150000002148 esters Chemical class 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 18
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 17
- 238000009472 formulation Methods 0.000 description 17
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 17
- XMSXQFUHVRWGNA-UHFFFAOYSA-N Decamethylcyclopentasiloxane Chemical compound C[Si]1(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O1 XMSXQFUHVRWGNA-UHFFFAOYSA-N 0.000 description 16
- 239000004205 dimethyl polysiloxane Substances 0.000 description 16
- KISVAASFGZJBCY-UHFFFAOYSA-N methyl undecenate Chemical compound COC(=O)CCCCCCCCC=C KISVAASFGZJBCY-UHFFFAOYSA-N 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
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- 239000004615 ingredient Substances 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 206010040829 Skin discolouration Diseases 0.000 description 11
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- OEWBEINAQKIQLZ-CMRBMDBWSA-N [(2s)-2-[(2r)-3,4-bis(2-hexyldecanoyloxy)-5-oxo-2h-furan-2-yl]-2-(2-hexyldecanoyloxy)ethyl] 2-hexyldecanoate Chemical compound CCCCCCCCC(CCCCCC)C(=O)OC[C@H](OC(=O)C(CCCCCC)CCCCCCCC)[C@H]1OC(=O)C(OC(=O)C(CCCCCC)CCCCCCCC)=C1OC(=O)C(CCCCCC)CCCCCCCC OEWBEINAQKIQLZ-CMRBMDBWSA-N 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000004408 titanium dioxide Substances 0.000 description 9
- BANXPJUEBPWEOT-UHFFFAOYSA-N 2-methyl-Pentadecane Chemical compound CCCCCCCCCCCCCC(C)C BANXPJUEBPWEOT-UHFFFAOYSA-N 0.000 description 8
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 8
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 8
- 229960004705 kojic acid Drugs 0.000 description 8
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 125000003289 ascorbyl group Chemical group [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 150000002170 ethers Chemical class 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 229920001296 polysiloxane Polymers 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- OSCJHTSDLYVCQC-UHFFFAOYSA-N 2-ethylhexyl 4-[[4-[4-(tert-butylcarbamoyl)anilino]-6-[4-(2-ethylhexoxycarbonyl)anilino]-1,3,5-triazin-2-yl]amino]benzoate Chemical compound C1=CC(C(=O)OCC(CC)CCCC)=CC=C1NC1=NC(NC=2C=CC(=CC=2)C(=O)NC(C)(C)C)=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=N1 OSCJHTSDLYVCQC-UHFFFAOYSA-N 0.000 description 5
- CIWBSHSKHKDKBQ-DUZGATOHSA-N D-isoascorbic acid Chemical compound OC[C@@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-DUZGATOHSA-N 0.000 description 5
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 5
- YBGZDTIWKVFICR-JLHYYAGUSA-N Octyl 4-methoxycinnamic acid Chemical compound CCCCC(CC)COC(=O)\C=C\C1=CC=C(OC)C=C1 YBGZDTIWKVFICR-JLHYYAGUSA-N 0.000 description 5
- 125000001931 aliphatic group Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000003833 cell viability Effects 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- ARXJGSRGQADJSQ-UHFFFAOYSA-N 1-methoxypropan-2-ol Chemical compound COCC(C)O ARXJGSRGQADJSQ-UHFFFAOYSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 229940043268 2,2,4,4,6,8,8-heptamethylnonane Drugs 0.000 description 4
- 238000005133 29Si NMR spectroscopy Methods 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 238000013270 controlled release Methods 0.000 description 4
- 239000002537 cosmetic Substances 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
- KUVMKLCGXIYSNH-UHFFFAOYSA-N isopentadecane Natural products CCCCCCCCCCCCC(C)C KUVMKLCGXIYSNH-UHFFFAOYSA-N 0.000 description 4
- SWGZAKPJNWCPRY-UHFFFAOYSA-N methyl-bis(trimethylsilyloxy)silicon Chemical compound C[Si](C)(C)O[Si](C)O[Si](C)(C)C SWGZAKPJNWCPRY-UHFFFAOYSA-N 0.000 description 4
- 229960001679 octinoxate Drugs 0.000 description 4
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- 238000003756 stirring Methods 0.000 description 4
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- 239000010409 thin film Substances 0.000 description 4
- ZQTYRTSKQFQYPQ-UHFFFAOYSA-N trisiloxane Chemical compound [SiH3]O[SiH2]O[SiH3] ZQTYRTSKQFQYPQ-UHFFFAOYSA-N 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 3
- HPGGRRWTQXPMHJ-UHFFFAOYSA-N 3-iodoprop-1-ynyl carbamate Chemical compound NC(=O)OC#CCI HPGGRRWTQXPMHJ-UHFFFAOYSA-N 0.000 description 3
- 239000004925 Acrylic resin Substances 0.000 description 3
- 229920004511 Dow Corning® 200 Fluid Polymers 0.000 description 3
- FXNFFCMITPHEIT-UHFFFAOYSA-N Ethyl 10-undecenoate Chemical compound CCOC(=O)CCCCCCCCC=C FXNFFCMITPHEIT-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000002211 L-ascorbic acid Substances 0.000 description 3
- 235000000069 L-ascorbic acid Nutrition 0.000 description 3
- 239000004909 Moisturizer Substances 0.000 description 3
- 102000004316 Oxidoreductases Human genes 0.000 description 3
- 108090000854 Oxidoreductases Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000004809 Teflon Substances 0.000 description 3
- 229920006362 Teflon® Polymers 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
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- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
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- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 3
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- WMNULTDOANGXRT-UHFFFAOYSA-N bis(2-ethylhexyl) butanedioate Chemical compound CCCCC(CC)COC(=O)CCC(=O)OCC(CC)CCCC WMNULTDOANGXRT-UHFFFAOYSA-N 0.000 description 2
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
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- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- HTDJPCNNEPUOOQ-UHFFFAOYSA-N hexamethylcyclotrisiloxane Chemical compound C[Si]1(C)O[Si](C)(C)O[Si](C)(C)O1 HTDJPCNNEPUOOQ-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- VKPSKYDESGTTFR-UHFFFAOYSA-N isododecane Natural products CC(C)(C)CC(C)CC(C)(C)C VKPSKYDESGTTFR-UHFFFAOYSA-N 0.000 description 1
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- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical group CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
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- 229920001921 poly-methyl-phenyl-siloxane Polymers 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
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- 229940068977 polysorbate 20 Drugs 0.000 description 1
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- 229940008424 tetradecamethylhexasiloxane Drugs 0.000 description 1
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 description 1
- 229940093609 tricaprylin Drugs 0.000 description 1
- DHWLRNPWPABRBG-UHFFFAOYSA-N tridecyl 2,2-dimethylpropanoate Chemical compound CCCCCCCCCCCCCOC(=O)C(C)(C)C DHWLRNPWPABRBG-UHFFFAOYSA-N 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- UHUUYVZLXJHWDV-UHFFFAOYSA-N trimethyl(methylsilyloxy)silane Chemical compound C[SiH2]O[Si](C)(C)C UHUUYVZLXJHWDV-UHFFFAOYSA-N 0.000 description 1
- OTOIBUHBRMYFLY-UHFFFAOYSA-N trimethyl-[(2,4,4,6,6-pentamethyl-1,3,5,2,4,6-trioxatrisilinan-2-yl)oxy]silane Chemical compound C[Si](C)(C)O[Si]1(C)O[Si](C)(C)O[Si](C)(C)O1 OTOIBUHBRMYFLY-UHFFFAOYSA-N 0.000 description 1
- UUJLHYCIMQOUKC-UHFFFAOYSA-N trimethyl-[oxo(trimethylsilylperoxy)silyl]peroxysilane Chemical compound C[Si](C)(C)OO[Si](=O)OO[Si](C)(C)C UUJLHYCIMQOUKC-UHFFFAOYSA-N 0.000 description 1
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0834—Compounds having one or more O-Si linkage
- C07F7/0838—Compounds with one or more Si-O-Si sequences
Definitions
- This disclosure relates to organosiloxanes having the formula (R 3 SiO) n R (3-n) Si—X-A wherein R is an alkyl group containing 1 to 6 carbon atoms, n is 1 to 3 inclusive, X is a divalent organic linking group, and A is an ester derivative of ascorbic acid.
- This disclosure further relates to a method of making an organosiloxane containing ester derivatives of ascorbic acid and the products prepared according to the method.
- the compounds and compositions of the present disclosure are useful to affect tissue lightening when applied topically to keratinaceous tissue.
- Ascorbic acid and related compounds are of known utility in skin-lightening and other technologies related to hyper-pigmentation. Ascorbic acid formulations, however, are prone to oxidation and are easily destabilized. In addition, cosmetic or pharmacological compositions comprising these acids may damage tissue or irritate human skin on repeated topical applications due to lower pH of the formulations. Hence, ascorbic acid and other related compounds have been compounded with other hydrophobic materials to improve their stability and performance.
- ester derivatives of ascorbic acid and 2-keto-acid saccharides have been disclosed in WO 2006/066227 wherein the ester is introduced by ester bond formation between at least one hydroxy-functionality on the ascorbic acid or 2-keto-acid saccharide and a carboxy-functional organosiloxane.
- the organosiloxane structures suggested in WO 2006/066227 are numerous.
- the working examples in WO 2006/066227 emphasized A-B-A structures based on a linear polydimethylsiloxane having end groups containing an ester linkage to ascorbic acid.
- WO 2006/066227 demonstrated skin lightening effects and good formulation stabilities, they did not provide skin lightening effects equivalent or better than kojic acid.
- Kojic acid is known for its skin lightening capabilities and is often used as a benchmark for determining skin lightening performance.
- kojic acid's water solubility can limit its delivery and formulation latitude.
- the use of kojic acid in skin care formulation is questioned in some countries for safety reasons.
- the present inventors have unexpectedly discovered certain short chain organosiloxanes containing ester derivatives of ascorbic acid provide enhanced skin lightening performance.
- these ascorbyl containing short chain organosiloxanes have skin lightening performance comparable to or better than kojic acid.
- the present ascorbyl containing short chain organosiloxanes are useful in many personal care formulations because of their compatibility with many organic oils and silicones.
- This disclosure relates to compounds having the formula
- This disclosure further provides a method of making an organosiloxane containing ester derivatives of ascorbic acid and the products prepared according to the method, the method comprising:
- compositions comprising the present organosiloxane compounds and a carrier fluid.
- tissue lightening effects are effected.
- This disclosure yet further relates to keratinaceous tissue lightening agent compositions comprising the compound and compositions described herein.
- This disclosure yet further relates to personal care compositions containing the compounds and compositions described herein.
- This disclosure relates to organosiloxane compounds having the formula
- X is a divalent organic linking group. While X may be any organic linking group, typically X contains 1 to 30 carbon atoms. X may be a linear or branched C 1 -C 30 alkylene chain. Thus X may be a divalent, aliphatic hydrocarbon group having 1-30 carbons, alternatively having 3-12 carbons, or alternatively having 10 carbons such as —(CH 2 ) 10 —.
- A is an ester derivative of ascorbic acid.
- the scope of the inventive compounds includes all ester derivatives of ascorbic acid and isoascorbic acid wherein the organosiloxane is covalently bound to the ascorbic, or isoascorbic via an ester bond.
- the term “ascorbic acid” includes ascorbic acid and its diastereoisomer, isoascorbic acid, unless specifically referred to as L-ascorbic acid or D-eiythorbic acid, and salts thereof.
- the fourth and fifth carbon atoms of an ascorbic acid molecule are chiral, leading to the existence of two enantiomeric isomers at each chiral center for a total of 4 diasteroisomers.
- D-erythorbic acid One of the enantiomers of isoascorbic acid is also known as D-erythorbic acid. Due to its strong reducing properties, D-erythorbic acid has similar technological applications to L-ascorbic acid as a water-soluble antioxidant. “Ascorbic acid” also includes the derivatives of all distereoisomers, including those wherein one or more of the free hydroxy functional groups thereof are formed as esters, ethers, ketones, and so forth, and including those comprising groups intended to be protecting and/or functional groups.
- A may have the following structure
- each P is independently any protecting or functional group, a proton or a cation chosen from the alkali or alkaline earth metals.
- protecting group includes groups formed involving one or more of the free hydroxy functional groups of the ascorbic acid, and includes esters, ethers, ketones and so forth.
- the process to form the ester derivative comprises “protecting” at least one of the hydroxyl groups of the ascorbic acid or derivatives thereof as esters (for example, as acetate esters) or ethers (for example, methyl ethers or), epoxys, or cyclic ketals.
- the ascorbic acid is protected at one or more hydroxyl sites by initial conversion to the cyclic ketal by the formation of 2,3-isopropylidene-ascorbic acid.
- protecting group may include a functional group, or added functionality may not relate to “protecting” at all.
- the ascorbic acid comprises at least one hydroxy group which is functionalized or protected or both.
- the ascorbic acid is protected at one or more hydroxyl sites as esters (for example as O-carbonates, O-acetates, O-phosphates and the like).
- esters for example as O-carbonates, O-acetates, O-phosphates and the like.
- the latter may then be derivatized using biocatalyzed esterification methods described below ultimately to produce the structures of the present disclosure.
- mono and diphosphates of ascorbic acid are described thoroughly in the literature. For example, U.S. Pat. No. 4,939,128 to Kato et al., the contents of which are incorporated herein by reference, teaches the formation of phosphoric acid esters of ascorbic acid. Similarly, U.S. Pat. No.
- the organosiloxane compound has the formula
- AUTS referred herein as “AUTS”.
- organosiloxanes containing ester derivatives of ascorbic acid may vary. Alternatively, they may be prepared by methods as described herein. Thus, the present disclosure further provides a method of making organosiloxanes containing ester derivatives of ascorbic acid comprising:
- Step I) of the method provides a protected ascorbic acid by forming a protecting group from at least one hydroxy-functional group thereon.
- the protecting groups are the same as described above.
- the hydroxyls are protected in the form of a trimethylsilyl (TMS) ether, and in a very specific embodiment the protected ascorbic acid comprises a tetra-O-trimethylsilyl ascorbic acid. Protection as a tetra-O-trimethylsilyl derivative allows enhanced miscibility of the ascorbic acid with the carboxy-functional organosiloxane.
- Protection as a tetra-O-trimethylsilyl derivative also allows the removal of the 6-O-TMS ether in situ through the action of the carboxy-functional siloxane, an additive such as a tertiary alcohol or water generated as a result of the esterification reaction. The latter also prevents the accumulation of water during the course of the reaction. Removal of the 6-O-TMS ether allows subsequent esterification of the 6-OH group of the otherwise protected ascorbic acid.
- ascorbic acid is reacted with 1,1,1,3,3,3-hexamethyldisilazane, typically in a suitable solvent like acetonitrile, as represented below.
- Step II) of the method involves mixing the protected ascorbic acid with a carboxy-functional organosiloxane having the formula (R 3 SiO) n R (3-n) Si—X—C(O)OR 1 where R, n and X are the same as described above, and R 1 is a hydrocarbyl containing 1 to 20 carbon atoms or hydrogen, to form a solution.
- the carboxy-functional organosiloxane having the formula (R 3 SiO) n R (3-n) Si—X—C(O)OR 1 may be prepared by any method known in the art.
- the carboxy-function organosiloxanes having the formula (R 3 SiO) n R (3-n) Si—X—C(O)OR 1 are prepared by a hydrosilylation reaction between an organohydrogensiloxane of the average formula (R 3 SiO) n R (3-n) Si—H, where R and n is as defined above, and a terminally aliphatic unsaturated carboxylic acid or ester.
- Techniques and catalysts for effecting hydrosilylation reactions are known in the art and any may be used to prepare the carboxy-functional organosiloxane useful in step II) of the present method.
- the terminally aliphatic unsaturated carboxylic acid or ester may have the formula R 2 —Y—R 1 where R 2 is an monovalent unsaturated aliphatic hydrocarbon group, Y is a divalent hydrocarbon group, and R 1 is as defined above.
- R 2 is CH 2 ⁇ CH—, CH 2 ⁇ CHCH 2 —, or CH ⁇ C—, and similar substituted unsaturated groups such as H 2 C ⁇ C(CH 3 )—, and HC ⁇ C(CH 3 )—.
- the terminally aliphatic unsaturated carboxylic acid or ester is an undeconate ester, such as methyl 10-undecenoate or ethyl 10-undecenoate.
- a representative reaction scheme is shown below for producing a carboxy-functional organosiloxane useful in step II) of the method.
- Step III) of the method involves contacting the solution with a biocatalyst which is capable of catalyzing ester bond formation.
- biocatalyst includes: 1) natural, semi-synthetic, or metabolically engineered catalytic substances that are isolated from biological sources; and 2) synthetic catalytic molecules that mimic biological pathways.
- enzyme includes proteins that are capable of catalyzing chemical changes in other substances. The enzymes can be wild-type enzymes or variant enzymes.
- Enzymes within the scope of the present invention include, but are not limited to, pullulanases, proteases, cellulases, amylases, isomerases, lipases, oxidases, oxidoreductases, hydrolases, aldolases, ketolases, glycosidases, oxidoreductases, hydrolases, aldolases, ketolases, glycosidases, lyases, ligases, transferases, and ligases.
- lipolytic enzyme refers to a polypeptide, protein or enzyme exhibiting a lipid degrading capability such as a capability of degrading a triglyceride or a phospholipid.
- a lipolytic enzyme may be, for example, a lipase, a phospholipase, an esterase or a cutinase.
- lipolytic activity may be determined according to any procedure known in the art. See, for example, Gupta et al, Biotechnol. Appl. Biochem. (2003) 37:63-71; Andre, Christophe, et al, U.S. Pat. No. 5,990,069 (International Publication WO 96/1 8729A1).
- protein refers to polymers of large molecular mass composed of one or more polypeptide chains and whose monomers are amino acids joined together by peptide bonds.
- protein and polypeptide are sometimes used interchangeably herein.
- the conventional one-letter or three-letter code for amino acid residues is used herein.
- the biocatalyst comprises an enzyme, and in a more specific embodiment the biocatalyst comprises a hydrolase enzyme.
- the hydrolase enzyme is selected from the group consisting of a lipase, a protease, a phosphoesterase, an esterase, an amidase, a cutinase, and combinations thereof.
- the hydrolase enzyme comprises a lipase, and in a further specific embodiment the lipase comprises an immobilized form of Candida antarctica lipase B (CALB) marketed as N435 and available from Novozymes (Denmark).
- CAB Candida antarctica lipase B
- Step III is typically performed under those conditions that favor the formation of ester bonds such as the removal or sequestration of water or low molecular weight alcohols to prevent the hydrolysis of the ester functionalities.
- the linker group could be attached to ascorbic acid through ester bond formation, and subsequently the modified linker may be attached to an organosiloxane polymer comprising an appropriate chemistry.
- an ascorbic acid-modified linker bearing a terminal olefinic function could be attached to a hydride-functional organosiloxane via hydrosilylation.
- the ester linkage may result from the reaction of an organosiloxane containing an acid chloride, such as 10-undecenoyl chloride, with ascorbic acid.
- the present disclosure further provides compositions containing the organosiloxane compounds as described above and a carrier fluid.
- the carrier fluid may be either an organic or silicone fluid.
- Suitable carrier fluids include silicones, both linear and cyclic, organic oils, organic solvents and mixtures of these. Specific examples of solvents may be found in U.S. Pat. No. 6,200,581, which is hereby incorporated by reference for this purpose.
- the carrier fluid is a low viscosity silicone or a volatile methyl siloxane or a volatile ethyl siloxane or a volatile methyl ethyl siloxane having a viscosity at 25° C.
- Organic solvents may be exemplified by, but not limited to, aromatic hydrocarbons, aliphatic hydrocarbons, alcohols, aldehydes, ketones, amines, esters, ethers, glycols, glycol ethers, alkyl halides and aromatic halides.
- Hydrocarbons including isododecane, isohexadecane, Isopar L (C11-C13), Isopar H (C11-C12), hydrogentated polydecene.
- Ethers and esters including isodecyl neopentanoate, neopentylglycol heptanoate, glycol distearate, dicaprylyl carbonate, diethylhexyl carbonate, propylene glycol n butyl ether, ethyl-3 ethoxypropionate, propylene glycol methyl ether acetate, tridecyl neopentanoate, propylene glycol methylether acetate (PGMEA), propylene glycol methylether (PGME), octyldodecyl neopentanoate, diisobutyl adipate, diisopropyl adipate, propylene glycol dicaprylate/dicaprate, and octyl palmitate.
- Additional organic carrier fluids suitable as a stand alone compound or as an ingredient to the carrier fluid include fats, oils, fatty acids, and fatty alcohols.
- the amount of organosiloxane compounds combined with the carrier fluid may vary, such as from 0.1 wt % to 99 wt % percent of the organosiloxane in the carrier fluid.
- Formulations containing organosiloxanes containing ester derivatives of ascorbic acid are contemplated for use in skin-lightening products.
- an emulsion of an organosiloxane containing ester derivatives of ascorbic acid and water containing 0.1 to 50% active ascorbic acid is applied to skin over a period of time to lighten the tone of the skin and remove blemishes and other discolorations.
- the active ascorbic acid in the said formulations can be that either covalently bound to carboxy-functional polysiloxanes, as well as free unconjugated ascorbic acid and mixtures thereof.
- Such formulations may optionally contain additional active compounds including vitamins, fragrances, anti-oxidants, herbal extracts, surfactants, humectants and the like.
- One particular embodiment is directed to a keratinaceous tissue lightening agent comprising the inventive ester derivatives of either ascorbic acid.
- the keratinaceous tissue comprises human skin.
- a further embodiment provides a composition comprising a safe and effective amount of the keratinaceous tissue lightening agent and a suitable vehicle or base.
- the composition is in the form of an emulsion.
- the novel compound comprises the inventive organosiloxanes containing ester derivatives of ascorbic acid and is contemplated as a controlled release keratinaceous tissue lightening agent.
- a further embodiment provides a method of lightening keratinaceous tissue comprising topical application of the compositions comprising the inventive ester derivatives of ascorbic acid.
- One particular embodiment provides a method of lightening keratinaceous tissue comprising topical application of a controlled release composition which comprises the organosiloxanes containing ester derivatives of ascorbic acid.
- a controlled release composition which comprises the organosiloxanes containing ester derivatives of ascorbic acid.
- Such “controlled release,” for example may be achieved by delivery of a precursor which allows sustained release of ascorbic acid or undergoes subsequent conversion to free ascorbic acid.
- the controlled release composition comprises inventive organosiloxanes containing ester derivatives of ascorbic acid.
- inventive organosiloxanes containing ester derivatives of ascorbic acid exhibit a relatively-higher permeability to the skin and mucosa, they are desirable for cosmetic applications which generally include skin, hair, and orally-usable products.
- inventive ester derivatives may also be mixed with other cosmetically suitable ingredients such as oily bases, water-soluble bases, flavors, colors, dyes, refrigerants, humectants, emollients, emulsifiers, gelation agents, viscosity enhancers, surfactants, stabilizers for foaming, clearances, antioxidants, germicides, putrefactive agents, coating-forming agents, and injection agents.
- the cosmetics according to the present invention contain at least 0.1 w/w %, and preferably at least 1.0 w/w % of the present inventive ester derivatives. It is also contemplated that the inventive ester derivatives may provide skin absorption enhancing effects to other benefit agents intended to provide benefit via absorption through the skin when administered in conjunction with those benefit agents.
- the inventive ester derivatives may also be desirably mixed with one or more pharmaceutical or nutritive agents such as vitamins, amino acids, peptides, hormones, extracts, vasodilators, blood circulation-promoting agents, cell-activating agents, anti-inflammatory drugs, urtication-preventing agents, skin-function-promoting agents, enzymes, and keratolytics.
- the mixtures may be in the form of liquid, emulsion, cream, paste, powder, granule, or solid products.
- the personal care compositions according to the present invention contain at least 0.1 w/w %, and preferably at least 1.0 w/w % of the present inventive ester derivatives.
- formulations with minimal water content where an organosiloxane containing ester derivative of ascorbic acid is formulated with additional polysiloxane materials including polydimethylsiloxane, polydimethylsiloxane polyethers, siloxane resins and other organosiloxane compounds.
- additional polysiloxane materials including polydimethylsiloxane, polydimethylsiloxane polyethers, siloxane resins and other organosiloxane compounds.
- Such formulations may also contain additional active compounds including vitamins, fragrances, anti-oxidants, herbal extracts and the like.
- 1,1,1,3,5,5,5-Heptamethyltrisiloxane (1,208.2 g, 5.4 moles) was placed in a 5000 mL three neck flask.
- An addition funnel was charged with methyl 10-undecenoate (1,291.9 g, 6.5 moles). The content of the pot was heated to 75° C. and a small amount of methyl 10-undecenoate was introduced just prior to adding 0.45 mL of a 2.67 weight percent Pt IV solution (final Pt content of 4 ppm).
- the methyl 10-undecenoate was added from the addition funnel at a rate so the temperature of the reaction did not exceed 100° C. After the addition of the methyl 10-undecenoate was complete the mixture was maintained at 90° C.
- 1,1,1,3,5,5,5-Heptamethyltrisiloxane (1,691.5 g, 7.6 moles) was placed in a 5000 mL three neck flask.
- An addition funnel was charged with methyl 10-undecenoate (1,000.1 g, 5.0 moles) which had been distilled at 71-74° C./1 mmHg prior to use.
- the content of the pot was heated to 70° C. and a small amount of methyl 10-undecenoate was introduced just prior to adding 0.60 mL of a 2.67 weight percent Pt IV solution (final Pt content of 4 ppm).
- the methyl 10-undecenoate was added from the addition funnel at a rate so the temperature of the reaction did not exceed 90° C.
- Acetonitrile (1883.5 grams) was added into a 5000 mL three neck round bottom-jacketed flask.
- the flask was connected to a circulating water bath, containing an antifreeze/water solution, with a set point temperature of 0° C.
- a small vent was placed in the side neck of the flask.
- the flask was purged and then a Nitrogen sweep was applied throughout the reaction to remove any ammonia generated during the capping process.
- L-Ascorbic Acid (536.0 grams, 1.11 moles) was slowly added to the acetonitrile with rapid mixing using a mechanical stirrer with a Teflon stir rod and paddle.
- 1,1,1,3,3,3-Hexamethyldisilazane (1109.3 grams, 2.54 moles) was added to this mixture with rapid mixing. Mixing at 0° C. was maintained overnight. The mixture was then allowed to equilibrate to room temperature with mixing for two additional hours. The reaction mixture was transferred into single neck round bottom recovery flasks and concentrated under vacuum at 35-50° C. using a Rotavapor. A clear solution formed, which was poured into amber bottles, purged with nitrogen and placed into a 4° C. refrigerator for storage.
- the trimethylsilyl-functional ascorbic acid of Example 3 (201.4 grams, 0.43 moles) and distilled-trisiloxane undecyl methyl ester of Example 1 (190.5 grams, 0.43 moles) were added into a 600 mL water-jacketed reaction flask that was connected to a circulating water bath with a set point temperature of 70° C. A nitrogen sweep was applied to the flask and a small vent was placed in one of the flask necks to remove any methanol formed during the reaction. A lipase enzyme immobilized on a polyacrylic resin bead (39.22 grams) and t-amyl alcohol (47.84 grams) were added to the flask with rapid mixing.
- the reaction mixture was mixed for 87.5 hours and then drained from the reactor into a 2000-milliliter single-neck round-bottom flask.
- Methanol (407.7 grams) was added to the flask, capped flask and mixed at room temperature for two hours on a Rotavapor without the use of vacuum. Filtered solid particles from the flask using a number five Whatman filter paper in a Buchner funnel with vacuum. Methanol was than stripped from the product under vacuum using a Rotavapor set to 65° C. until a viscous straw-colored fluid was remaining.
- Acetone (230.2 grams) was added to the reaction product and was mixed on a Rotavapor without the use of vacuum until the entire product was in a solution with the acetone.
- the trimethylsilyl-functional ascorbic acid of Example 3 (15.0 grams, 0.32 moles) and trisiloxane undecyl ethyl ester of Example 2 (13.6 grams, 0.32 moles) were added into a 50 mL water-jacketed reaction flask that was connected to a circulating water bath with a set point temperature of 70° C.
- a Nitrogen sweep was applied to the flask and a small vent was placed in one of the flask necks to remove any methanol formed during the reaction.
- a lipase enzyme immobilized on a polyacrylic resin bead (3.2 grams) and t-Amyl Alcohol (3.9 grams) was added to the flask with rapid mixing.
- the reaction mixture was mixed for 72 hours and then drained from the reactor into a 50-milliliter centrifuge tube.
- the tube was centrifuged at 4000 rpm to separate any un-reacted ascorbic acid from the product.
- the liquid phase was recovered and centrifuged again. This process was repeated until there was no visually apparent residue present in the solution.
- the capped product was a viscous, amber/straw-colored fluid.
- Example 3 The trimethylsilyl-functional ascorbic acid of Example 3 (354.5 grams, 0.73 moles), trisiloxane undecyl methyl ester of Example 1 (320.9 grams, 0.73 moles) and cyclopentasiloxane (386.8 grams) were added into a 2000 mL water-jacketed reaction flask that was connected to a circulating water bath with a set point temperature of 70° C. A Nitrogen sweep was applied to the flask and a small vent was placed in one of the flask necks to remove any methanol formed during the reaction. The flask drain was plumbed using a glass adapter to attach 1 ⁇ 8 inch inside diameter Teflon tubing using compression fittings.
- the tubing was attached to the top of a one-inch diameter, water-jacketed column with a total length of 300 mL.
- the column was packed, from bottom to top, with a coarse disk filter, glass beads (35.0 grams) and a lipase enzyme immobilized on a polyacrylic resin bead (65.1 grams).
- Tubing was attached to the column outlet and run back to the original reaction flask.
- the reaction mixture was stirred slowly using a mechanical stirrer with a Teflon stir rod and paddle. This mixture was pumped from the flask bottom through tubing, pressure relief valve, pressure gauge, into the top of the column, through the bottom of the column and then pumped back into the flask.
- the reaction mixture was mixed/pumped for 124.5 hours and then drained from the reactor into a 3000-milliliter single-neck round-bottom flask.
- Methanol (684.7 grams) was added to the flask, capped flask and mixed at room temperature for two hours on a Rotavapor without the use of vacuum. Methanol was than stripped from the product under vacuum using a Rotavapor set to 65° C. until a viscous straw-colored fluid was remaining.
- Acetone 700.0 grams was added to the reaction product and was mixed on a Rotavapor without the use of vacuum until the entire product was in a solution with the acetone. Solution was centrifuged at 3500 rpm to separate any unreacted ascorbic acid from the product. The liquid phase was recovered and centrifuged again. This process was repeated until there was no visually apparent residue present in the solution. The acetone was then removed by a vacuum strip on a Rotavapor at 68° C. Product was a clear, viscous, amber/straw-colored fluid.
- a reaction product mixture containing trimethylsilyl-functional ascorbic acid (such as from Example 3) was placed in the reservoir of a thin film stripping apparatus.
- the external jacket of the apparatus was heated to and maintained at 175 ⁇ 5° C.
- the vacuum was introduced to the system and allowed to run until the pressure in the system is below 1.5 mmHg.
- the product mixture is introduced to the top of the thin film stripper wiper blades and the motor is now turned on to start the wiper assembly spinning.
- the material is introduced from the reservoir at such a rate as to not overwhelm the wiper blades ( ⁇ 1 ml/min).
- the trimethyl silyl ether capped ascorbic acid and the methyl 10-undecanoate trisiloxane are volatilized and condense on the internal cold finger while the purified trimethyl silyl ether capped ascorbyl 10-undecanoate trisiloxane remains in the non-volatile portion of the thin film stripper. Both the non-volatile and volatile portions of the process are collected. Using this method, it is possible to obtain trimethyl silyl ether capped ascorbyl undecanoate trisiloxane that contains less than 1% of the trimethyl silyl ether capped ascorbic acid and less than 1% of the methyl 10-undecanoate trisiloxane.
- the filtrate was diluted with toluene, placed in a separatory funnel and washed with 2 ⁇ 100 ml portions of water, 2 ⁇ 100 ml portions of saturated sodium bicarbonate, 2 ⁇ 100 ml portions of water and then 1 ⁇ 100 ml portion of saturated sodium chloride.
- the organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent removed on a rotary evaporator to yield a slightly yellow oil.
- This example illustrates cell viability properties and efficacy of skin lightening formulations according to the present invention.
- two formulations according to the present invention containing AUTS as prepared according to Example 4
- water a negative control
- 1% kojic acid Sigma, WI
- ascorbyl tetraisopalmitate in D5 decamethylcyclopentasiloxane
- MELANODERMTM cell viability was tested by MTT assay after exposure to test and reference preparations.
- the assays were carried out using Melanoderm tissue model MEL 300 A cell line (MELANODERM tissue model available from MatTek, Ashland, Mass.).
- MTT data showed that viability of MelanoDerm skin model was not affected by the treatment. (Cell viability with both materials in D5 at 10 and 25 ⁇ L dose was >90%).
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Abstract
Organosiloxanes containing ester derivatives of ascorbic acid are disclosed having the formula (R3SiO)nR(3-n)Si—X-A wherein R is an alkyl group containing 1 to 6 carbon atoms, n is 1 to 3 inclusive, X is a divalent organic linking group, A is an ester derivative of ascorbic acid. A method of making an organosiloxane containing ester derivatives of ascorbic acid and the products prepared according to the method are also taught. The compounds and compositions of the present disclosure are useful to affect tissue lightening when applied topically to keratinaceous tissue.
Description
- This application is a divisional application of U.S. application Ser. No. 12/680,407 which was a national stage filing under 35 U.S.C. §371 of PCT Application No. PCT/US08/76494 filed on Sep. 1, 2008 which claimed the benefit of U.S. Provisional Patent Application No. 60/975,863 filed Sep. 28, 2007 under 35 U.S.C. §119(e). U.S. application Ser. No. 12/680,407, PCT Application No. PCT/US08/76494 and U.S. Provisional Patent Application No. 60/975,863 are hereby incorporated by reference.
- This disclosure relates to organosiloxanes having the formula (R3SiO)nR(3-n)Si—X-A wherein R is an alkyl group containing 1 to 6 carbon atoms, n is 1 to 3 inclusive, X is a divalent organic linking group, and A is an ester derivative of ascorbic acid. This disclosure further relates to a method of making an organosiloxane containing ester derivatives of ascorbic acid and the products prepared according to the method. The compounds and compositions of the present disclosure are useful to affect tissue lightening when applied topically to keratinaceous tissue.
- Ascorbic acid and related compounds are of known utility in skin-lightening and other technologies related to hyper-pigmentation. Ascorbic acid formulations, however, are prone to oxidation and are easily destabilized. In addition, cosmetic or pharmacological compositions comprising these acids may damage tissue or irritate human skin on repeated topical applications due to lower pH of the formulations. Hence, ascorbic acid and other related compounds have been compounded with other hydrophobic materials to improve their stability and performance. Most recently, ester derivatives of ascorbic acid and 2-keto-acid saccharides have been disclosed in WO 2006/066227 wherein the ester is introduced by ester bond formation between at least one hydroxy-functionality on the ascorbic acid or 2-keto-acid saccharide and a carboxy-functional organosiloxane. The organosiloxane structures suggested in WO 2006/066227 are numerous. However, the working examples in WO 2006/066227 emphasized A-B-A structures based on a linear polydimethylsiloxane having end groups containing an ester linkage to ascorbic acid. While the examples in WO 2006/066227 demonstrated skin lightening effects and good formulation stabilities, they did not provide skin lightening effects equivalent or better than kojic acid. Kojic acid is known for its skin lightening capabilities and is often used as a benchmark for determining skin lightening performance. However, kojic acid's water solubility can limit its delivery and formulation latitude. Furthermore, the use of kojic acid in skin care formulation is questioned in some countries for safety reasons.
- The present inventors have unexpectedly discovered certain short chain organosiloxanes containing ester derivatives of ascorbic acid provide enhanced skin lightening performance. In particular, these ascorbyl containing short chain organosiloxanes have skin lightening performance comparable to or better than kojic acid. Furthermore, the present ascorbyl containing short chain organosiloxanes are useful in many personal care formulations because of their compatibility with many organic oils and silicones.
- This disclosure relates to compounds having the formula
-
(R3SiO)nR(3-n)Si—X-A wherein -
- R is an alkyl group containing 1 to 6 carbon atoms,
- n is 1 to 3 inclusive,
- X is a divalent organic linking group,
- A is an ester derivative of ascorbic acid.
- This disclosure further provides a method of making an organosiloxane containing ester derivatives of ascorbic acid and the products prepared according to the method, the method comprising:
-
- I) providing a protected ascorbic acid by forming a protecting group from at least one hydroxy-functional group thereon;
- II) mixing the protected ascorbic acid with a carboxy-functional organosiloxane having the formula (R3SiO)nR(3-n)Si—X—C(O)OR1
- where R is an alkyl group containing 1 to 6 carbon atoms,
- n is 1 to 3 inclusive, X is a divalent organic linking group,
- R1 is a hydrocarbyl containing 1 to 20 carbon atoms or hydrogen, to form a solution;
- where R is an alkyl group containing 1 to 6 carbon atoms,
- III) contacting the solution with a biocatalyst which is capable of catalyzing ester bond formation;
- IV) optionally, removing the protecting group, and wherein the protecting group may comprise a functional group.
- This disclosure further relates to compositions comprising the present organosiloxane compounds and a carrier fluid.
- When the compounds and compositions of the present disclosure are applied topically to keratinaceous tissue, and in particular human skin, tissue lightening effects are effected.
- This disclosure yet further relates to keratinaceous tissue lightening agent compositions comprising the compound and compositions described herein.
- This disclosure yet further relates to personal care compositions containing the compounds and compositions described herein.
- This disclosure relates to organosiloxane compounds having the formula
-
(R3SiO)nR(3-n)Si—X-A wherein -
- R is an alkyl group containing 1 to 6 carbon atoms,
- n is 1 to 3 inclusive, alternatively n is 2.
- X is a divalent organic linking group, and
- A is an ester derivative of ascorbic acid.
R may be any alkyl group containing 1 to 6 carbons such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, or hexyl. Alternatively, R is methyl.
- X is a divalent organic linking group. While X may be any organic linking group, typically X contains 1 to 30 carbon atoms. X may be a linear or branched C1-C30 alkylene chain. Thus X may be a divalent, aliphatic hydrocarbon group having 1-30 carbons, alternatively having 3-12 carbons, or alternatively having 10 carbons such as —(CH2)10—.
- A is an ester derivative of ascorbic acid. The scope of the inventive compounds includes all ester derivatives of ascorbic acid and isoascorbic acid wherein the organosiloxane is covalently bound to the ascorbic, or isoascorbic via an ester bond. As used herein the term “ascorbic acid” includes ascorbic acid and its diastereoisomer, isoascorbic acid, unless specifically referred to as L-ascorbic acid or D-eiythorbic acid, and salts thereof. The fourth and fifth carbon atoms of an ascorbic acid molecule are chiral, leading to the existence of two enantiomeric isomers at each chiral center for a total of 4 diasteroisomers. One of the enantiomers of isoascorbic acid is also known as D-erythorbic acid. Due to its strong reducing properties, D-erythorbic acid has similar technological applications to L-ascorbic acid as a water-soluble antioxidant. “Ascorbic acid” also includes the derivatives of all distereoisomers, including those wherein one or more of the free hydroxy functional groups thereof are formed as esters, ethers, ketones, and so forth, and including those comprising groups intended to be protecting and/or functional groups.
- In the (R3SiO)nR(3-n)Si—X-A formula, A may have the following structure;
- where each P is independently any protecting or functional group, a proton or a cation chosen from the alkali or alkaline earth metals. As used herein the term “protecting group” includes groups formed involving one or more of the free hydroxy functional groups of the ascorbic acid, and includes esters, ethers, ketones and so forth. In one embodiment, the process to form the ester derivative comprises “protecting” at least one of the hydroxyl groups of the ascorbic acid or derivatives thereof as esters (for example, as acetate esters) or ethers (for example, methyl ethers or), epoxys, or cyclic ketals. In a specific embodiment the ascorbic acid is protected at one or more hydroxyl sites by initial conversion to the cyclic ketal by the formation of 2,3-isopropylidene-ascorbic acid. Also as used herein the term “protecting” group may include a functional group, or added functionality may not relate to “protecting” at all. In one embodiment, the ascorbic acid comprises at least one hydroxy group which is functionalized or protected or both.
- In another specific embodiment, the ascorbic acid is protected at one or more hydroxyl sites as esters (for example as O-carbonates, O-acetates, O-phosphates and the like). The latter may then be derivatized using biocatalyzed esterification methods described below ultimately to produce the structures of the present disclosure. In addition, the formation of mono and diphosphates of ascorbic acid are described thoroughly in the literature. For example, U.S. Pat. No. 4,939,128 to Kato et al., the contents of which are incorporated herein by reference, teaches the formation of phosphoric acid esters of ascorbic acid. Similarly, U.S. Pat. No. 4,999,437 to Dobler et al., the contents of which are also fully incorporated herein by reference, describes the preparation of ascorbic acid 2-phosphate. In another specific embodiment the ascorbic acid is protected at the hydroxyls by formation of ethers, and in a very specific embodiment the protecting moiety is a trimethylsilyl ether. Any of these known ascorbic acid derivatives can be used within the scope of the present invention.
- In one very specific embodiment, the organosiloxane compound has the formula;
- referred herein as “AUTS”.
- The process or method of making the organosiloxanes containing ester derivatives of ascorbic acid as described above may vary. Alternatively, they may be prepared by methods as described herein. Thus, the present disclosure further provides a method of making organosiloxanes containing ester derivatives of ascorbic acid comprising:
-
- I) providing a protected ascorbic acid by forming a protecting group from at least one hydroxy-functional group thereon;
- II) mixing the protected ascorbic acid with a carboxy-functional organosiloxane having the formula (R3SiO)nR(3-n)Si—X—C(O)OR1
- where R, n and X are the same as described above, and
- R1 is a hydrocarbyl containing 1 to 20 carbon atoms or hydrogen, to form a solution;
- where R, n and X are the same as described above, and
- III) contacting the solution with a biocatalyst which is capable of catalyzing ester bond formation;
- IV) optionally, removing the protecting group, and wherein the protecting group may comprise a functional group.
- Step I) of the method provides a protected ascorbic acid by forming a protecting group from at least one hydroxy-functional group thereon. The protecting groups are the same as described above. In a specific embodiment the hydroxyls are protected in the form of a trimethylsilyl (TMS) ether, and in a very specific embodiment the protected ascorbic acid comprises a tetra-O-trimethylsilyl ascorbic acid. Protection as a tetra-O-trimethylsilyl derivative allows enhanced miscibility of the ascorbic acid with the carboxy-functional organosiloxane. Protection as a tetra-O-trimethylsilyl derivative also allows the removal of the 6-O-TMS ether in situ through the action of the carboxy-functional siloxane, an additive such as a tertiary alcohol or water generated as a result of the esterification reaction. The latter also prevents the accumulation of water during the course of the reaction. Removal of the 6-O-TMS ether allows subsequent esterification of the 6-OH group of the otherwise protected ascorbic acid.
- In this embodiment, ascorbic acid is reacted with 1,1,1,3,3,3-hexamethyldisilazane, typically in a suitable solvent like acetonitrile, as represented below.
- Step II) of the method involves mixing the protected ascorbic acid with a carboxy-functional organosiloxane having the formula (R3SiO)nR(3-n)Si—X—C(O)OR1 where R, n and X are the same as described above, and R1 is a hydrocarbyl containing 1 to 20 carbon atoms or hydrogen, to form a solution. The carboxy-functional organosiloxane having the formula (R3SiO)nR(3-n)Si—X—C(O)OR1 may be prepared by any method known in the art. Typically, the carboxy-function organosiloxanes having the formula (R3SiO)nR(3-n)Si—X—C(O)OR1 are prepared by a hydrosilylation reaction between an organohydrogensiloxane of the average formula (R3SiO)nR(3-n)Si—H, where R and n is as defined above, and a terminally aliphatic unsaturated carboxylic acid or ester. Techniques and catalysts for effecting hydrosilylation reactions are known in the art and any may be used to prepare the carboxy-functional organosiloxane useful in step II) of the present method. The terminally aliphatic unsaturated carboxylic acid or ester may have the formula R2—Y—R1 where R2 is an monovalent unsaturated aliphatic hydrocarbon group, Y is a divalent hydrocarbon group, and R1 is as defined above. Typically R2 is CH2═CH—, CH2═CHCH2—, or CH≡C—, and similar substituted unsaturated groups such as H2C═C(CH3)—, and HC≡C(CH3)—. In one embodiment, the terminally aliphatic unsaturated carboxylic acid or ester is an undeconate ester, such as methyl 10-undecenoate or ethyl 10-undecenoate. A representative reaction scheme is shown below for producing a carboxy-functional organosiloxane useful in step II) of the method.
- Step III) of the method involves contacting the solution with a biocatalyst which is capable of catalyzing ester bond formation. As used herein, the term “biocatalyst” includes: 1) natural, semi-synthetic, or metabolically engineered catalytic substances that are isolated from biological sources; and 2) synthetic catalytic molecules that mimic biological pathways. As used herein, the term “enzyme” includes proteins that are capable of catalyzing chemical changes in other substances. The enzymes can be wild-type enzymes or variant enzymes. Enzymes within the scope of the present invention include, but are not limited to, pullulanases, proteases, cellulases, amylases, isomerases, lipases, oxidases, oxidoreductases, hydrolases, aldolases, ketolases, glycosidases, oxidoreductases, hydrolases, aldolases, ketolases, glycosidases, lyases, ligases, transferases, and ligases.
- As used herein, the term “lipolytic enzyme” refers to a polypeptide, protein or enzyme exhibiting a lipid degrading capability such as a capability of degrading a triglyceride or a phospholipid. A lipolytic enzyme may be, for example, a lipase, a phospholipase, an esterase or a cutinase. For the present invention, lipolytic activity may be determined according to any procedure known in the art. See, for example, Gupta et al, Biotechnol. Appl. Biochem. (2003) 37:63-71; Andre, Christophe, et al, U.S. Pat. No. 5,990,069 (International Publication WO 96/1 8729A1). As used herein, the term “protein” refers to polymers of large molecular mass composed of one or more polypeptide chains and whose monomers are amino acids joined together by peptide bonds. The terms “protein” and “polypeptide” are sometimes used interchangeably herein. The conventional one-letter or three-letter code for amino acid residues is used herein.
- In a specific embodiment the biocatalyst comprises an enzyme, and in a more specific embodiment the biocatalyst comprises a hydrolase enzyme. In very specific embodiments the hydrolase enzyme is selected from the group consisting of a lipase, a protease, a phosphoesterase, an esterase, an amidase, a cutinase, and combinations thereof. In an even more specific embodiment the hydrolase enzyme comprises a lipase, and in a further specific embodiment the lipase comprises an immobilized form of Candida antarctica lipase B (CALB) marketed as N435 and available from Novozymes (Denmark).
- Step III is typically performed under those conditions that favor the formation of ester bonds such as the removal or sequestration of water or low molecular weight alcohols to prevent the hydrolysis of the ester functionalities.
- One of ordinary skill in the art will appreciate that additional synthetic methods could be used to produce the aforementioned compounds. For example, the linker group could be attached to ascorbic acid through ester bond formation, and subsequently the modified linker may be attached to an organosiloxane polymer comprising an appropriate chemistry. In one specific example, an ascorbic acid-modified linker bearing a terminal olefinic function could be attached to a hydride-functional organosiloxane via hydrosilylation. Alternatively, the ester linkage may result from the reaction of an organosiloxane containing an acid chloride, such as 10-undecenoyl chloride, with ascorbic acid.
- The present disclosure further provides compositions containing the organosiloxane compounds as described above and a carrier fluid. The carrier fluid may be either an organic or silicone fluid. Suitable carrier fluids include silicones, both linear and cyclic, organic oils, organic solvents and mixtures of these. Specific examples of solvents may be found in U.S. Pat. No. 6,200,581, which is hereby incorporated by reference for this purpose.
- Typically, the carrier fluid is a low viscosity silicone or a volatile methyl siloxane or a volatile ethyl siloxane or a volatile methyl ethyl siloxane having a viscosity at 25° C. in the range of 1 to 1,000 mm2/sec such as hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, octamethyltrisiloxane, decamethyltetrasiloxane, dodecamethylpentasiloxane, tetradecamethylhexasiloxane, hexadeamethylheptasiloxane, heptamethyl-3-{(trimethylsilyl)oxy)}trisiloxane, hexamethyl-3,3,bis{(trimethylsilyl)oxy}trisiloxane pentamethyl{(trimethylsilyl)oxy}cyclotrisiloxane as well as polydimethylsiloxanes, polyethylsiloxanes, polymethylethylsiloxanes, polymethylphenylsiloxanes, polydiphenylsiloxanes.
- Organic solvents may be exemplified by, but not limited to, aromatic hydrocarbons, aliphatic hydrocarbons, alcohols, aldehydes, ketones, amines, esters, ethers, glycols, glycol ethers, alkyl halides and aromatic halides. Hydrocarbons including isododecane, isohexadecane, Isopar L (C11-C13), Isopar H (C11-C12), hydrogentated polydecene. Ethers and esters including isodecyl neopentanoate, neopentylglycol heptanoate, glycol distearate, dicaprylyl carbonate, diethylhexyl carbonate, propylene glycol n butyl ether, ethyl-3 ethoxypropionate, propylene glycol methyl ether acetate, tridecyl neopentanoate, propylene glycol methylether acetate (PGMEA), propylene glycol methylether (PGME), octyldodecyl neopentanoate, diisobutyl adipate, diisopropyl adipate, propylene glycol dicaprylate/dicaprate, and octyl palmitate. Additional organic carrier fluids suitable as a stand alone compound or as an ingredient to the carrier fluid include fats, oils, fatty acids, and fatty alcohols.
- The amount of organosiloxane compounds combined with the carrier fluid may vary, such as from 0.1 wt % to 99 wt % percent of the organosiloxane in the carrier fluid.
- Formulations containing organosiloxanes containing ester derivatives of ascorbic acid are contemplated for use in skin-lightening products. For example an emulsion of an organosiloxane containing ester derivatives of ascorbic acid and water containing 0.1 to 50% active ascorbic acid is applied to skin over a period of time to lighten the tone of the skin and remove blemishes and other discolorations. The active ascorbic acid in the said formulations can be that either covalently bound to carboxy-functional polysiloxanes, as well as free unconjugated ascorbic acid and mixtures thereof. Such formulations may optionally contain additional active compounds including vitamins, fragrances, anti-oxidants, herbal extracts, surfactants, humectants and the like.
- One particular embodiment is directed to a keratinaceous tissue lightening agent comprising the inventive ester derivatives of either ascorbic acid. In a specific embodiment the keratinaceous tissue comprises human skin. A further embodiment provides a composition comprising a safe and effective amount of the keratinaceous tissue lightening agent and a suitable vehicle or base. In a more specific embodiment the composition is in the form of an emulsion. In one aspect of these embodiments, the novel compound comprises the inventive organosiloxanes containing ester derivatives of ascorbic acid and is contemplated as a controlled release keratinaceous tissue lightening agent.
- A further embodiment provides a method of lightening keratinaceous tissue comprising topical application of the compositions comprising the inventive ester derivatives of ascorbic acid. One particular embodiment provides a method of lightening keratinaceous tissue comprising topical application of a controlled release composition which comprises the organosiloxanes containing ester derivatives of ascorbic acid. Such “controlled release,” for example, may be achieved by delivery of a precursor which allows sustained release of ascorbic acid or undergoes subsequent conversion to free ascorbic acid. In a very specific embodiment the controlled release composition comprises inventive organosiloxanes containing ester derivatives of ascorbic acid.
- Other embodiments are directed to personal care formulations comprising cosmetic or personal care compositions. Since the inventive organosiloxanes containing ester derivatives of ascorbic acid exhibit a relatively-higher permeability to the skin and mucosa, they are desirable for cosmetic applications which generally include skin, hair, and orally-usable products. The inventive ester derivatives may also be mixed with other cosmetically suitable ingredients such as oily bases, water-soluble bases, flavors, colors, dyes, refrigerants, humectants, emollients, emulsifiers, gelation agents, viscosity enhancers, surfactants, stabilizers for foaming, clearances, antioxidants, germicides, putrefactive agents, coating-forming agents, and injection agents. The cosmetics according to the present invention contain at least 0.1 w/w %, and preferably at least 1.0 w/w % of the present inventive ester derivatives. It is also contemplated that the inventive ester derivatives may provide skin absorption enhancing effects to other benefit agents intended to provide benefit via absorption through the skin when administered in conjunction with those benefit agents. The inventive ester derivatives may also be desirably mixed with one or more pharmaceutical or nutritive agents such as vitamins, amino acids, peptides, hormones, extracts, vasodilators, blood circulation-promoting agents, cell-activating agents, anti-inflammatory drugs, urtication-preventing agents, skin-function-promoting agents, enzymes, and keratolytics. The mixtures may be in the form of liquid, emulsion, cream, paste, powder, granule, or solid products. The personal care compositions according to the present invention contain at least 0.1 w/w %, and preferably at least 1.0 w/w % of the present inventive ester derivatives.
- Also contemplated are formulations with minimal water content where an organosiloxane containing ester derivative of ascorbic acid is formulated with additional polysiloxane materials including polydimethylsiloxane, polydimethylsiloxane polyethers, siloxane resins and other organosiloxane compounds. Such formulations may also contain additional active compounds including vitamins, fragrances, anti-oxidants, herbal extracts and the like.
- These examples are intended to illustrate the invention to one of ordinary skill in the art and should not be interpreted as limiting the scope of the invention set forth in the claims. All measurements and experiments were conducted at 23° C., unless indicated otherwise.
- 1,1,1,3,5,5,5-Heptamethyltrisiloxane (1,329 g, 6.0 moles) and methyl 10-undecenoate (1,421.0 g, 7.2 moles) were placed in a 5000 mL three neck flask. The mixture was heated to 80° C. and 1.4 mL of a 1.0 weight percent chloroplatinic acid solution in 2-propanol was added (final platinum content is 4 ppm). The temperature of the mixture was then maintained at 100° C. for 24 hours. Measurement of the SiH content indicated that the reaction had proceeded to 98% completion. The excess methyl 10-undecenoate and other volatiles were removed by heating the mixture to 105° C./1 mmHg. Characterization of the product by FTIR, GC, 13C NMR and 29Si NMR indicated that the desired material was obtained as a slightly tan liquid.
- 1,1,1,3,5,5,5-Heptamethyltrisiloxane (1,208.2 g, 5.4 moles) was placed in a 5000 mL three neck flask. An addition funnel was charged with methyl 10-undecenoate (1,291.9 g, 6.5 moles). The content of the pot was heated to 75° C. and a small amount of methyl 10-undecenoate was introduced just prior to adding 0.45 mL of a 2.67 weight percent Pt IV solution (final Pt content of 4 ppm). The methyl 10-undecenoate was added from the addition funnel at a rate so the temperature of the reaction did not exceed 100° C. After the addition of the methyl 10-undecenoate was complete the mixture was maintained at 90° C. for 12 hours. The reaction was determined to be 98% complete based on the consumption of SiH. The crude reaction mixture was heated to 95° C./1 mmHg to remove volatiles and excess methyl 10-undecenoate from the product. Characterization of the product (GC, FTIR, 13C NMR and 29Si NMR) confirmed that the desired product had been obtained as a slightly tan liquid.
- 1,1,1,3,5,5,5-Heptamethyltrisiloxane (1,691.5 g, 7.6 moles) was placed in a 5000 mL three neck flask. An addition funnel was charged with methyl 10-undecenoate (1,000.1 g, 5.0 moles) which had been distilled at 71-74° C./1 mmHg prior to use. The content of the pot was heated to 70° C. and a small amount of methyl 10-undecenoate was introduced just prior to adding 0.60 mL of a 2.67 weight percent Pt IV solution (final Pt content of 4 ppm). The methyl 10-undecenoate was added from the addition funnel at a rate so the temperature of the reaction did not exceed 90° C. After the first amount of methyl 10-undecenoate had been added and additional 808.5 g (4.1 moles) was added via the addition funnel. After all the methyl 10-undecenoate had been added the mixture was maintained at 75° C. for 1 hour at which point FTIR indicated that 99.5% conversion had been achieved based on SiH consumption. Volatiles and excess methyl 10-undecenoate were removed from the crude product mixture by to 90° C./1 mmHg. The pressure in the reaction flask was brought to atmospheric and 50 g of activated carbon was introduced. The mixture was maintained at 90° C. for 6 hours. Next, the mixture was filtered through Celite to obtain the product as a colorless liquid. Characterization (GC, FTIR, 13C NMR and 29Si NMR) indicated that the desired product had been obtained. Additionally, ICP analysis indicated that the level of platinum in this product was <1 ppm.
- 1,1,1,3,5,5,5-Heptamethyltrisiloxane (116.6 g, 0.52 moles) and ethyl 10-undecenoate (133.5 g, 0.63 moles) were placed in a 500 mL three neck flask. The mixture was heated to 80° C. and 60 μl of a 2.67 weight percent Pt IV solution (final Pt content of 5 ppm) was added. The temperature of the mixture was then maintained at 100° C. for 6 hours. Measurement of the SiH content indicated that the reaction had proceeded to 98.5% completion. The excess ethyl 10-undecenoate and other volatiles were removed by heating the mixture to 105° C./1 mmHg. Characterization of the product by FTIR, GC, 13C NMR and 29Si NMR indicated that the desired material was obtained as a slightly tan liquid.
- Acetonitrile (1883.5 grams) was added into a 5000 mL three neck round bottom-jacketed flask. The flask was connected to a circulating water bath, containing an antifreeze/water solution, with a set point temperature of 0° C. A small vent was placed in the side neck of the flask. The flask was purged and then a Nitrogen sweep was applied throughout the reaction to remove any ammonia generated during the capping process. L-Ascorbic Acid (536.0 grams, 1.11 moles) was slowly added to the acetonitrile with rapid mixing using a mechanical stirrer with a Teflon stir rod and paddle. 1,1,1,3,3,3-Hexamethyldisilazane (1109.3 grams, 2.54 moles) was added to this mixture with rapid mixing. Mixing at 0° C. was maintained overnight. The mixture was then allowed to equilibrate to room temperature with mixing for two additional hours. The reaction mixture was transferred into single neck round bottom recovery flasks and concentrated under vacuum at 35-50° C. using a Rotavapor. A clear solution formed, which was poured into amber bottles, purged with nitrogen and placed into a 4° C. refrigerator for storage.
- The trimethylsilyl-functional ascorbic acid of Example 3 (201.4 grams, 0.43 moles) and distilled-trisiloxane undecyl methyl ester of Example 1 (190.5 grams, 0.43 moles) were added into a 600 mL water-jacketed reaction flask that was connected to a circulating water bath with a set point temperature of 70° C. A nitrogen sweep was applied to the flask and a small vent was placed in one of the flask necks to remove any methanol formed during the reaction. A lipase enzyme immobilized on a polyacrylic resin bead (39.22 grams) and t-amyl alcohol (47.84 grams) were added to the flask with rapid mixing. The reaction mixture was mixed for 87.5 hours and then drained from the reactor into a 2000-milliliter single-neck round-bottom flask. Methanol (407.7 grams) was added to the flask, capped flask and mixed at room temperature for two hours on a Rotavapor without the use of vacuum. Filtered solid particles from the flask using a number five Whatman filter paper in a Buchner funnel with vacuum. Methanol was than stripped from the product under vacuum using a Rotavapor set to 65° C. until a viscous straw-colored fluid was remaining. Acetone (230.2 grams) was added to the reaction product and was mixed on a Rotavapor without the use of vacuum until the entire product was in a solution with the acetone. Solution was centrifuged at 3500 rpm to separate any unreacted ascorbic acid from the product. The liquid phase was recovered and centrifuged again. This process was repeated until there was no visually apparent residue present in the solution. The acetone was then removed by a vacuum strip on a Rotavapor at 68° C. Product was a clear, viscous, amber/straw-colored fluid.
- Preparation of Ascorbyl Undecyl Trisiloxane (from Ethyl Ester)
- The trimethylsilyl-functional ascorbic acid of Example 3 (15.0 grams, 0.32 moles) and trisiloxane undecyl ethyl ester of Example 2 (13.6 grams, 0.32 moles) were added into a 50 mL water-jacketed reaction flask that was connected to a circulating water bath with a set point temperature of 70° C. A Nitrogen sweep was applied to the flask and a small vent was placed in one of the flask necks to remove any methanol formed during the reaction. A lipase enzyme immobilized on a polyacrylic resin bead (3.2 grams) and t-Amyl Alcohol (3.9 grams) was added to the flask with rapid mixing. The reaction mixture was mixed for 72 hours and then drained from the reactor into a 50-milliliter centrifuge tube. The tube was centrifuged at 4000 rpm to separate any un-reacted ascorbic acid from the product. The liquid phase was recovered and centrifuged again. This process was repeated until there was no visually apparent residue present in the solution. The capped product was a viscous, amber/straw-colored fluid.
- Preparation of Ascorbyl Undecyl Trisiloxane (AUTS) using a Recycle Process
- The trimethylsilyl-functional ascorbic acid of Example 3 (354.5 grams, 0.73 moles), trisiloxane undecyl methyl ester of Example 1 (320.9 grams, 0.73 moles) and cyclopentasiloxane (386.8 grams) were added into a 2000 mL water-jacketed reaction flask that was connected to a circulating water bath with a set point temperature of 70° C. A Nitrogen sweep was applied to the flask and a small vent was placed in one of the flask necks to remove any methanol formed during the reaction. The flask drain was plumbed using a glass adapter to attach ⅛ inch inside diameter Teflon tubing using compression fittings. The tubing was attached to the top of a one-inch diameter, water-jacketed column with a total length of 300 mL. The column was packed, from bottom to top, with a coarse disk filter, glass beads (35.0 grams) and a lipase enzyme immobilized on a polyacrylic resin bead (65.1 grams). Tubing was attached to the column outlet and run back to the original reaction flask. The reaction mixture was stirred slowly using a mechanical stirrer with a Teflon stir rod and paddle. This mixture was pumped from the flask bottom through tubing, pressure relief valve, pressure gauge, into the top of the column, through the bottom of the column and then pumped back into the flask. The reaction mixture was mixed/pumped for 124.5 hours and then drained from the reactor into a 3000-milliliter single-neck round-bottom flask. Methanol (684.7 grams) was added to the flask, capped flask and mixed at room temperature for two hours on a Rotavapor without the use of vacuum. Methanol was than stripped from the product under vacuum using a Rotavapor set to 65° C. until a viscous straw-colored fluid was remaining. Acetone (700.0 grams) was added to the reaction product and was mixed on a Rotavapor without the use of vacuum until the entire product was in a solution with the acetone. Solution was centrifuged at 3500 rpm to separate any unreacted ascorbic acid from the product. The liquid phase was recovered and centrifuged again. This process was repeated until there was no visually apparent residue present in the solution. The acetone was then removed by a vacuum strip on a Rotavapor at 68° C. Product was a clear, viscous, amber/straw-colored fluid.
- A reaction product mixture containing trimethylsilyl-functional ascorbic acid (such as from Example 3) was placed in the reservoir of a thin film stripping apparatus. The external jacket of the apparatus was heated to and maintained at 175±5° C. The vacuum was introduced to the system and allowed to run until the pressure in the system is below 1.5 mmHg. Once the temperature and pressure have reached the set values, the product mixture is introduced to the top of the thin film stripper wiper blades and the motor is now turned on to start the wiper assembly spinning. The material is introduced from the reservoir at such a rate as to not overwhelm the wiper blades (˜1 ml/min). The volatile components under these conditions, the trimethyl silyl ether capped ascorbic acid and the methyl 10-undecanoate trisiloxane are volatilized and condense on the internal cold finger while the purified trimethyl silyl ether capped ascorbyl 10-undecanoate trisiloxane remains in the non-volatile portion of the thin film stripper. Both the non-volatile and volatile portions of the process are collected. Using this method, it is possible to obtain trimethyl silyl ether capped ascorbyl undecanoate trisiloxane that contains less than 1% of the trimethyl silyl ether capped ascorbic acid and less than 1% of the methyl 10-undecanoate trisiloxane.
- To a 50 ml three neck round bottom flask was added 5.0 g (28.4 mmoles) of ascorbic acid, 4.7 ml (3.4 g, 34.0 mmoles) of triethylamine and 30 ml of N,N,-dimethylformamide. To this mixture was slowly added, with stirring, 7.0 g (34.5 mmoles) of 10-undecenoyl chloride. During the addition, a slight exotherm was observed. The mixture was allowed to stir for 2.5 h and then filtered to remove the precipitate that had formed. The filtrate was diluted with toluene, placed in a separatory funnel and washed with 2×100 ml portions of water, 2×100 ml portions of saturated sodium bicarbonate, 2×100 ml portions of water and then 1×100 ml portion of saturated sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent removed on a rotary evaporator to yield a slightly yellow oil.
- Skin Lightening with Ascorbyl Undecyl Trisiloxane (AUTS)
- This example illustrates cell viability properties and efficacy of skin lightening formulations according to the present invention. In particular, two formulations according to the present invention (containing AUTS as prepared according to Example 4), water (a negative control), 1% kojic acid (Sigma, WI) in water (positive control), and ascorbyl tetraisopalmitate in D5 (decamethylcyclopentasiloxane) were assayed and compared for cell viability and skin lightening efficacy (see Table 1)
-
TABLE 1 Preparations assayed and cell viability by MTT Viability by Compound Carrier Concentration1 Dosed MTT AUTS D5 3.2% 10 μL 95.5% AUTS D5 3.2% 25 μL 96.5% VC-IP D5 6.4% 10 μL 94.1% VC-IP D5 6.4% 25 μL 98.2% Negative control: 25 μL water Positive control: 25 μL kojic acid, 1% - Test Preparation: 3.2 wt % AUTS in decamethylcyclopentasiloxane (D5).
- Reference Preparation: 6.4% Nikkol VC-IP (ascorbyl tetraisopalmitate supplied by Nikko Chemicals Co, Ltd. Of Japan) in D5
- 1The concentrations of the test material and the reference material were set to provide the equivalent of 1% ascorbic acid in the test solutions.
- MELANODERM™ cell viability was tested by MTT assay after exposure to test and reference preparations. The assays were carried out using Melanoderm tissue model MEL 300 A cell line (MELANODERM tissue model available from MatTek, Ashland, Mass.). This melanoderm model consists of normal, human-derived epidermal keratinocytes and melanocytes that have been co-cultured to form a multilayer, highly differentiated model of human epidermis. MTT data showed that viability of MelanoDerm skin model was not affected by the treatment. (Cell viability with both materials in D5 at 10 and 25 μL dose was >90%).
- Skin whitening effect was evaluated by measuring melanin concentration (μg/ml) after six applications of each preparation. The results are summarized in Table 2.
-
TABLE 2 Melanin concentration at Day 10 Test Preparation vs Reference Preparation AUTS, VC-IP, AUTS, VC-IP, Kojic Acid*** 10 μl 10 μl 25 μl 25 μl 25 μL Average 37.4* 57.8* 26.6** 55.2** 41.9 (μg/ml) SD 7.5 3.8 4.4 5.9 P value 1.1E−03 7.3E−05 *Significantly lower melanin concentration (p < 0.05) in cell culture dosed with AUTS, 10 μl in comparison with VC-IP, 10 μl. **Significantly lower melanin concentration (p < 0.05) in cell culture dosed with AUTS, 25 μl in comparison with VC-IP, 25 μl. ***1 wt % in water - The solubility characteristics of the organosiloxanes containing ester derivatives of ascorbic acid of the present disclosure vs the organosiloxanes as taught in WO2006/066227 is shown in this representative comparative example.
- A 36 wt % mixture of the referenced sample and listed solvents were prepared in a glass vial. The sealed glass vials containing the mixtures were then placed in a 60° C. water bath and periodically shaken and observed. The results, as summarized in Table 3, show the representative organosiloxanes of the present disclosure had improved solubility characteristics.
- Comparative sample #1 is the same average formula as the ascorbyl containing organosiloxane of Example 4 in WO2006/066227.
- Comparative sample #2 is the same average formula as the ascorbyl containing organosiloxane of Example 6 in WO2006/066227.
- AUTS is representative of Example 4 as described above.
-
TABLE 3 Reference A B C D E Water Bis-Ascorbyl Undecyl Comparative No No No No na Yes* Tetramethyldisiloxane sample #1 Bis-Ascorbyl Undecyl Comparative Yes No No Yes Yes No Polydimethylsiloxane sample #2 Ascorbyl Undecyl AUTS Yes** Yes** Yes** na Yes** No A = C12-15 Alkyl Benzoate (FINSOLV TN) B = Cyclopentasiloxane (Dow Corning 245 Fluid) C = Squalane (Uniqema PRIPURE 3759) D = Tricaprylin (TRIVENT OC-G) E = Caprylic/Capric Triglyceride *forms a translucent mixture that thickens to a viscous hazy liquid when cooled **dissolves to form a solution that ranges from nearly clear to hazy, depending on the solvent; solutions gel when cooled to room temperature - Representative ascorbyl undecyl trisiloxanes were incorporated into various personal care formulations as illustrated below to demonstrate.
-
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Weight % INCI name Trade Name (Supplier) Part A 5.0% Hydroxyethylacrylate/Sodium Simulgel FL (SEPPIC) Acryloyldimethyl Taurate Copolymer (and) Isohexadecane (and) Polysorbate 80 6.8% Cyclopentasiloxane Dow Corning ® 245 Fluid (DOW CORNING) 3.2% Ascorbyl Undecyl Trisiloxane (AUTS) 4.0% Diethylhexyl Succinate Crodamol OSU (CRODA) Part B 2.0% Glycerin 78.8% Deionized Water 0.2% Propylene Glycol (and) Diazolidinyl Liquid Germall Plus Urea (and) Iodopropynyl Carbamate (SUTTON LABS) 100.0%
PROCEDURE: Combine the AUTS, cyclopentasiloxane, and diethylhexyl succinate in a vessel that is large enough to hold the entire batch. Heat these ingredients with gently mixing to about 60° C. until the AUTS disperses completely. Add the Simulgel FL and mix until uniform while maintaining the temperature at about 55° C. Mix the ingredients for Part B in a separate vessel until a homogenous solution is obtained and heat to about 55° C. Slowly add Part B to Part A with continuous mixing. The batch will thicken as more of Part B is added. After all of Part B has been added, mix the batch with sufficient agitation to achieve good turnover and allow the batch to cool to room temperature.
Facial Moisturizer with Inorganic Sunscreen -
Weight % INCI name Trade Name (Supplier) Part A 5.0% Hydroxyethylacrylate/Sodium Simulgel FL (SEPPIC) Acryloyldimethyl Taurate Copolymer (and) Isohexadecane (and) Polysorbate 80 6.8% Cyclopentasiloxane Dow Corning ® 245 Fluid (DOW CORNING) 3.2% Ascorbyl Undecyl Trisiloxane (AUTS) 4.0% Titanium Dioxide (and) Alumina UV-TITAN M262 (and) Dimethicone (Kemira) 6.0% Dimethicone Dow Corning ® 200 Fluid/100 cSt (DOW CORNING) Part B 2.0% Glycerin 72.8% Deionized Water 0.2% Propylene Glycol (and) Diazolidinyl Liquid Germall Plus Urea (and) Iodopropynyl Carbamate (SUTTON LABS) 100.0%
PROCEDURE: Disperse the UV-TITAN M262 in the dimethicone using high shear mixing equipment to fully disperse the titanium dioxide. Set this dispersion aside. Combine the AUTS and cyclopentasiloxane in a vessel that is large enough to hold the entire batch. Heat these ingredients with gently mixing to about 60° C. until the AUTS disperses completely. Add the Simulgel FL and the titanium dioxide dispersion, then mix until uniform while maintaining the temperature at about 55° C. Mix the ingredients for Part B in a separate vessel until a homogenous solution is obtained and heat to about 55° C. Slowly add Part B to Part A with continuous mixing. The batch will thicken as more of Part B is added. After all of Part B has been added, mix the batch with sufficient agitation to achieve good turnover and allow the batch to cool to room temperature.
Facial Moisturizer with Organic Sunscreen -
Weight % INCI name Trade Name (Supplier) Part A 7.5% Hydroxyethylacrylate/Sodium Simulgel FL (SEPPIC) Acryloyldimethyl Taurate Copolymer (and) Isohexadecane (and) Polysorbate 80 6.8% Cyclopentasiloxane Dow Corning ® 245 Fluid (DOW CORNING) 3.2% Ascorbyl Undecyl Trisiloxane (AUTS) 7.5% Ethylhexyl Methoxycinnamate Escalol 557 (Octinoxate) (International Specialty Porducts) Part B 2.0% Glycerin 72.8% Deionized Water 0.2% Propylene Glycol (and) Diazolidinyl Liquid Germall Plus Urea (and) Iodopropynyl Carbamate (SUTTON LABS) 100.0%
PROCEDURE: Combine the AUTS, cyclopentasiloxane, and ethylhexyl methoxycinnamate in a vessel that is large enough to hold the entire batch. Heat these ingredients with gently mixing to about 60° C. until the AUTS disperses completely. Add the Simulgel FL and mix until uniform while maintaining the temperature at about 55° C. Mix the ingredients for Part B in a separate vessel until a homogenous solution is obtained and heat to about 55° C. Slowly add Part B to Part A with continuous mixing. The batch will thicken as more of Part B is added. After all of Part B has been added, mix the batch with sufficient agitation to achieve good turnover and allow the batch to cool to room temperature. -
-
Wt. % INCI name Trade Name (Supplier) 2.0% Titanium Dioxide (and) Alumina UV-TITAN M262 (Kemira) (and) Dimethicone 3.0% Dimethicone Dow Corning ® 200 Fluid/ 100 cSt (DOW CORNING) 21.8% Cyclopentasiloxane Dow Corning ® 245 Fluid (DOW CORNING) 65.0% Cyclopentasiloxane (and) Dow Corning ® 9045 Dimethicone Crosspolymer Silicone Elastomer Blend (DOW CORNING) 3.2% Ascorbyl Undecyl Trisiloxane (AUTS) 5.0% Ethylhexyl Methoxycinnamate (Octoxinate) 100.0%
PROCEDURE: Disperse the UV-TITAN M262 in the dimethicone using high shear mixing equipment to fully disperse the titanium dioxide. Combine the remaining ingredients in a suitable mixing vessel. Heat these ingredients to about 60° C. and then mix until the AUTS is melted and uniformly dispersed. Begin cooling the batch and add the titanium dioxide/dimethicone dispersion to the batch. Mix until uniform and continue mixing until the batch cools to room temperature. -
-
Weight % INCI name Trade Name (Supplier) Part A 3.4% Titanium Dioxide (and) Alumina UV-TITAN M262 (and) Dimethicone (Kemira) 6.6% Dimethicone Dow Corning ® 200 Fluid/100 cSt (DOW CORNING) 7.5% Cyclopentasiloxane (and) PEG/PPG- Dow Corning ® 5225C 18/18 Dimethicone Formulation Aid (DOW CORNING) 3.2% Ascorbyl Undecyl Trisiloxane (AUTS) 6.8% Cyclopentasiloxane Dow Corning ® 245 Fluid (DOW CORNING) 5.0% Aluminum Starch Octenyl Succinate Dry Flo PC/National Starch and Chemical 4.0% Cyclopentasiloxane (and) Dow Corning ® 749 Trimethylsiloxysilicate Fluid (DOW CORNING) Part B 62.3% Water 1.0% Sodium Chloride 0.2% Polysorbate 20 Tween 20 (CRODA) 100.0%
PROCEDURE: Disperse the UV-TITAN M262 in the dimethicone using high shear mixing equipment to fully disperse the titanium dioxide. Combine the titanium dioxide dispersion with the remaining ingredients for Part A in a mixing vessel that is large enough to contain the entire batch. Heat Part A to about 60° C. and mix until the AUTS is melted and uniformly dispersed. Combine the ingredients for Part B in a separate vessel and mix until a homogeneous solution is obtained, then heat to about 60° C. Slowly add Part B to Part A while mixing vigorously to produce a turbulent mixing action such that Part B is quickly incorporated into the batch as it is added. When all of Part B has been added, begin cooling and continue mixing for another 10-15 minutes.
Claims (17)
1. A method of making an organosiloxane containing ester derivative of ascorbic acid comprising:
I) providing a protected ascorbic acid by forming a protecting group from at least one hydroxy-functional group thereon;
II) mixing the protected ascorbic acid with a carboxy-functional organosiloxane having the formula (R3SiO)nR(3-n)Si—X—C(O)OR1
where R is an alkyl group containing 1 to 6 carbon atoms,
n is 1 to 3 inclusive, X is a divalent organic linking group,
R1 is a hydrocarbyl containing 1 to 20 carbon atoms or hydrogen, to form a solution;
III) contacting the solution with a biocatalyst which is capable of catalyzing ester bond formation;
IV) optionally, removing the protecting group, and wherein the protecting group may comprise a functional group.
2. The method of claim 1 wherein the protecting group comprises a trimethylsilyl ether.
3. The method of claim 1 wherein the carboxy-functional organosiloxane formula R is methyl and n=2.
4. The method of claim 1 wherein the carboxy-functional organosiloxane formula X is a linear or branched C1-C30 alkylene chain.
5. The method of claim 1 wherein the carboxy-functional organosiloxane formula X is —(CH2)10—.
6. The method of claim 1 wherein the carboxy-functional organosiloxane formula R1 is methyl or ethyl.
7. The method of claim 1 wherein the biocatalyst comprises an enzyme.
8. The method of claim 7 wherein the enzyme comprises a hydrolase enzyme.
9. The method of claim 8 wherein the hydrolase enzyme exits in either free or immobilized form and is selected from the group consisting of a lipase, a protease, a phosphoesterase, an esterase, a cutinase, and combinations thereof.
10. The method of claim 8 wherein the hydrolase enzyme comprises a lipase.
11. The product produced by the method of claim 1 .
12. A keratinaceous tissue lightening agent composition comprising the product as claimed in claim 11 .
13. The keratinaceous tissue lightening agent composition of claim 12 wherein the keratinaceous tissue comprises human skin.
14. The keratinaceous tissue lightening agent composition of claim 13 further comprising a suitable vehicle or base.
15. The keratinaceous tissue lightening agent composition of claim 14 further comprising free ascorbic acid.
16. The keratinaceous tissue lightening agent composition of claim 14 wherein the composition is in the form of an emulsion.
17. A personal care composition comprising the product of claim 11 .
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/590,736 US20130004445A1 (en) | 2007-09-28 | 2012-08-21 | Organosiloxanes containing ester derivatives of ascorbic acid |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US97586307P | 2007-09-28 | 2007-09-28 | |
PCT/US2008/076494 WO2009045709A1 (en) | 2007-09-28 | 2008-09-16 | Organosiloxanes containing ester derivatives of ascorbic acid |
US68040710A | 2010-03-26 | 2010-03-26 | |
US13/590,736 US20130004445A1 (en) | 2007-09-28 | 2012-08-21 | Organosiloxanes containing ester derivatives of ascorbic acid |
Related Parent Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2008/076494 Division WO2009045709A1 (en) | 2007-09-28 | 2008-09-16 | Organosiloxanes containing ester derivatives of ascorbic acid |
US68040710A Division | 2007-09-28 | 2010-03-26 |
Publications (1)
Publication Number | Publication Date |
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US20130004445A1 true US20130004445A1 (en) | 2013-01-03 |
Family
ID=39940622
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/680,407 Expired - Fee Related US8278288B2 (en) | 2007-09-28 | 2008-09-16 | Organosiloxanes containing ester derivatives of ascorbic acid |
US13/590,736 Abandoned US20130004445A1 (en) | 2007-09-28 | 2012-08-21 | Organosiloxanes containing ester derivatives of ascorbic acid |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
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US12/680,407 Expired - Fee Related US8278288B2 (en) | 2007-09-28 | 2008-09-16 | Organosiloxanes containing ester derivatives of ascorbic acid |
Country Status (6)
Country | Link |
---|---|
US (2) | US8278288B2 (en) |
EP (1) | EP2197887A1 (en) |
JP (1) | JP5468006B2 (en) |
KR (1) | KR20100075870A (en) |
CN (1) | CN101809023A (en) |
WO (1) | WO2009045709A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8906351B2 (en) | 2010-09-17 | 2014-12-09 | Merck Patent Gmbh | 2,2′-furoin derivatives and use thereof to light skin |
US20150343944A1 (en) * | 2013-11-21 | 2015-12-03 | Ford Global Technologies, Llc | Printed led trim panel lamp |
US20150378217A1 (en) * | 2014-06-25 | 2015-12-31 | Samsung Display Co., Ltd. | Fluorescent sheet and light unit and liquid crystal display including the same |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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US7214364B2 (en) | 2000-12-27 | 2007-05-08 | Corus Pharma, Inc. | Inhalable aztreonam lysinate formulation for treatment and prevention of pulmonary bacterial infections |
WO2012150891A1 (en) * | 2011-05-02 | 2012-11-08 | Lipidor Ab | Composition for administration of a pharmacologically or cosmetically active agent onto a surface of a living organism |
KR102043605B1 (en) | 2012-01-18 | 2019-11-12 | 다우 실리콘즈 코포레이션 | Methods of making saccharide siloxane copolymers |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
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IL89850A0 (en) | 1988-04-25 | 1989-12-15 | Takeda Chemical Industries Ltd | Ester of ascorbic acid 2-phosphate |
US4870191A (en) * | 1988-07-22 | 1989-09-26 | Ethyl Corporation | Silicon containing reaction product |
DE3909198A1 (en) | 1989-03-21 | 1990-09-27 | Basf Ag | METHOD FOR THE PRODUCTION OF ASCORBIN ACID-2-PHOSPHATE AND 5,6-ISORPROPYLIDENE-ASCORBIN ACID AS A BASE PRODUCT |
GB2296011B (en) | 1994-12-13 | 1999-06-16 | Solvay | Novel fusarium isolate and lipases, cutinases and enzyme compositions derived therefrom |
US5986122A (en) * | 1996-11-18 | 1999-11-16 | Witco Corporation | Treatment of polyethers prior to hydrosilylation |
US6200581B1 (en) | 1999-04-28 | 2001-03-13 | Dow Corning Corporation | Elastomeric silicone terpolymer |
FR2800073B1 (en) * | 1999-10-26 | 2001-11-23 | Oreal | NOVEL SILICATED COMPOUNDS DERIVED FROM ASCORBIC ACID, PROCESS FOR THEIR PREPARATION, COMPOSITIONS COMPRISING SAME AND USES THEREOF |
EP1546159B1 (en) | 2002-08-16 | 2014-06-18 | Dow Corning Corporation | Enzyme catalyzed method of forming organosilicon esters |
US20050112158A1 (en) * | 2003-11-17 | 2005-05-26 | Clariant Internatinonal, Ltd. | Method for synthesis of silylated ascorbic acid derivatives |
US7132558B1 (en) | 2004-02-12 | 2006-11-07 | Surfatech Corporation | Silicone vitamin esters |
US7871987B2 (en) | 2004-12-16 | 2011-01-18 | Dow Corning Corporation | Ester derivatives of ascorbic and 2-keto acid saccharides |
-
2008
- 2008-09-16 EP EP08836351A patent/EP2197887A1/en not_active Withdrawn
- 2008-09-16 JP JP2010527022A patent/JP5468006B2/en not_active Expired - Fee Related
- 2008-09-16 CN CN200880108951A patent/CN101809023A/en active Pending
- 2008-09-16 KR KR1020107006777A patent/KR20100075870A/en not_active Application Discontinuation
- 2008-09-16 US US12/680,407 patent/US8278288B2/en not_active Expired - Fee Related
- 2008-09-16 WO PCT/US2008/076494 patent/WO2009045709A1/en active Application Filing
-
2012
- 2012-08-21 US US13/590,736 patent/US20130004445A1/en not_active Abandoned
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8906351B2 (en) | 2010-09-17 | 2014-12-09 | Merck Patent Gmbh | 2,2′-furoin derivatives and use thereof to light skin |
US20150343944A1 (en) * | 2013-11-21 | 2015-12-03 | Ford Global Technologies, Llc | Printed led trim panel lamp |
US20150378217A1 (en) * | 2014-06-25 | 2015-12-31 | Samsung Display Co., Ltd. | Fluorescent sheet and light unit and liquid crystal display including the same |
Also Published As
Publication number | Publication date |
---|---|
CN101809023A (en) | 2010-08-18 |
JP5468006B2 (en) | 2014-04-09 |
US20100221201A1 (en) | 2010-09-02 |
WO2009045709A1 (en) | 2009-04-09 |
KR20100075870A (en) | 2010-07-05 |
EP2197887A1 (en) | 2010-06-23 |
US8278288B2 (en) | 2012-10-02 |
JP2010540540A (en) | 2010-12-24 |
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Free format text: EXPRESSLY ABANDONED -- DURING EXAMINATION |