US20020071816A1 - Skin whiteners containing hydroxytetronic acid - Google Patents
Skin whiteners containing hydroxytetronic acid Download PDFInfo
- Publication number
- US20020071816A1 US20020071816A1 US09/735,144 US73514400A US2002071816A1 US 20020071816 A1 US20020071816 A1 US 20020071816A1 US 73514400 A US73514400 A US 73514400A US 2002071816 A1 US2002071816 A1 US 2002071816A1
- Authority
- US
- United States
- Prior art keywords
- acid
- weight
- hydroxytetronic
- hydroquinone
- composition
- 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.)
- Granted
Links
- 239000002253 acid Substances 0.000 title claims abstract description 37
- 239000000203 mixture Substances 0.000 claims abstract description 52
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims abstract description 51
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims abstract description 26
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 16
- -1 glycolic acid Chemical class 0.000 claims abstract description 15
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 claims abstract description 12
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 claims abstract description 12
- 235000010385 ascorbyl palmitate Nutrition 0.000 claims abstract description 12
- 230000002087 whitening effect Effects 0.000 claims abstract description 11
- 229940061720 alpha hydroxy acid Drugs 0.000 claims abstract description 10
- 150000001280 alpha hydroxy acids Chemical class 0.000 claims abstract description 10
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 8
- 229930195729 fatty acid Natural products 0.000 claims abstract description 8
- 239000000194 fatty acid Substances 0.000 claims abstract description 8
- 235000010323 ascorbic acid Nutrition 0.000 claims abstract description 6
- 229960005070 ascorbic acid Drugs 0.000 claims abstract description 6
- 239000011668 ascorbic acid Substances 0.000 claims abstract description 6
- 239000004615 ingredient Substances 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 12
- 230000000699 topical effect Effects 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000005907 alkyl ester group Chemical group 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 3
- 125000004188 dichlorophenyl group Chemical group 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 125000000687 hydroquinonyl group Chemical group C1(O)=C(C=C(O)C=C1)* 0.000 claims 3
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 210000003491 skin Anatomy 0.000 description 23
- 229960004337 hydroquinone Drugs 0.000 description 16
- 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 10
- 230000000694 effects Effects 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 6
- 238000004061 bleaching Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 4
- 239000000542 fatty acid esters of ascorbic acid Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 239000006210 lotion Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000004261 Ascorbyl stearate Substances 0.000 description 3
- LITUBCVUXPBCGA-WMZHIEFXSA-N Ascorbyl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O LITUBCVUXPBCGA-WMZHIEFXSA-N 0.000 description 3
- 208000012641 Pigmentation disease Diseases 0.000 description 3
- 102000003425 Tyrosinase Human genes 0.000 description 3
- 108060008724 Tyrosinase Proteins 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 235000019276 ascorbyl stearate Nutrition 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000003974 emollient agent Substances 0.000 description 3
- 208000000069 hyperpigmentation Diseases 0.000 description 3
- 230000003810 hyperpigmentation Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QGLKIVPNOUPWOW-UHFFFAOYSA-N 3,4-dihydroxy-2h-furan-5-one Chemical compound OC1=C(O)C(=O)OC1 QGLKIVPNOUPWOW-UHFFFAOYSA-N 0.000 description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
- 208000003351 Melanosis Diseases 0.000 description 2
- 206010040829 Skin discolouration Diseases 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 229930003268 Vitamin C Natural products 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000007854 depigmenting agent Substances 0.000 description 2
- 210000001339 epidermal cell Anatomy 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- BJRNKVDFDLYUGJ-RMPHRYRLSA-N hydroquinone O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-RMPHRYRLSA-N 0.000 description 2
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 2
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 2
- 229960004705 kojic acid Drugs 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000002752 melanocyte Anatomy 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000019612 pigmentation Effects 0.000 description 2
- 230000036555 skin type Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000000475 sunscreen effect Effects 0.000 description 2
- 239000000516 sunscreening agent Substances 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- WVXRAFOPTSTNLL-NKWVEPMBSA-N 2',3'-dideoxyadenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1CC[C@@H](CO)O1 WVXRAFOPTSTNLL-NKWVEPMBSA-N 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 235000012871 Arctostaphylos uva ursi Nutrition 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 235000014698 Brassica juncea var multisecta Nutrition 0.000 description 1
- 235000006008 Brassica napus var napus Nutrition 0.000 description 1
- 240000000385 Brassica napus var. napus Species 0.000 description 1
- 235000006618 Brassica rapa subsp oleifera Nutrition 0.000 description 1
- 235000004977 Brassica sinapistrum Nutrition 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 240000008886 Ceratonia siliqua Species 0.000 description 1
- 235000013912 Ceratonia siliqua Nutrition 0.000 description 1
- 206010008570 Chloasma Diseases 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 240000008067 Cucumis sativus Species 0.000 description 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010014970 Ephelides Diseases 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 240000004670 Glycyrrhiza echinata Species 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 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 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 240000003394 Malpighia glabra Species 0.000 description 1
- 235000014837 Malpighia glabra Nutrition 0.000 description 1
- 240000000249 Morus alba Species 0.000 description 1
- 235000008708 Morus alba Nutrition 0.000 description 1
- 240000000783 Origanum majorana Species 0.000 description 1
- 235000006297 Origanum majorana Nutrition 0.000 description 1
- 201000011252 Phenylketonuria Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 244000178231 Rosmarinus officinalis Species 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 206010064127 Solar lentigo Diseases 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 235000016639 Syzygium aromaticum Nutrition 0.000 description 1
- 244000223014 Syzygium aromaticum Species 0.000 description 1
- 244000003892 Vaccinium erythrocarpum Species 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- 239000004164 Wax ester Substances 0.000 description 1
- DWKSHXDVQRZSII-SUMWQHHRSA-N [(2s)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O DWKSHXDVQRZSII-SUMWQHHRSA-N 0.000 description 1
- MSKSZMDNKAEBSG-HNAYVOBHSA-N [(2s)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethyl] tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O MSKSZMDNKAEBSG-HNAYVOBHSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 229960000271 arbutin Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229940116224 behenate Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 239000007844 bleaching agent Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002085 enols Chemical group 0.000 description 1
- 229940052303 ethers for general anesthesia Drugs 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229940043075 fluocinolone Drugs 0.000 description 1
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 230000002065 hypopigmenting effect Effects 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 238000013532 laser treatment Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000001780 majorana hortensis moench (origanum majorana l.) Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 201000009442 piebaldism Diseases 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 230000037307 sensitive skin Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- NJRXVEJTAYWCQJ-UHFFFAOYSA-N thiomalic acid Chemical compound OC(=O)CC(S)C(O)=O NJRXVEJTAYWCQJ-UHFFFAOYSA-N 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 235000019386 wax ester Nutrition 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- This invention relates to the use of hydroxytetronic acid and/or hydroxytetronic acid derivatives alone, or in combination with other ingredients such as hydroquinone, glycolic acid, and/or ascorbyl palmitate, in compositions that whiten skin, and methods for using the compositions.
- a variety of dermatological compositions have been suggested for skin whitening to improve the appearance of hyperpigmentary skin conditions such as that observed as freckles, melasma, café au lait and liver spots spots, and lesions observed in Addison's disease, hemochromatosis, vitiligo, piebald-ism, phenylketonuria, and the like, and/or for cosmetic purposes.
- Skin color is primarily determined by the amount of melanin present in epidermal cells, so many modern skin bleaching compositions either destroy melanin (typically by destroying or disrupting melanin granules) or inhibit its formation (often by inhibiting tyrosinase, a melanin biosynthetic enzyme, or melanocyte activity), or both. Many of these contain harsh chemicals such as peroxides, acids or formaldehyde, or thiolated materials such as glutathione, cysteine, mercaptosuccinic acid, mercaptodextran, and mercapto-ethanol, which have an objectionable odor that makes products containing them undesirable to a consumer (discussed in U.S. Pat. No.
- Topical retinoids and topical corticosteroids have been suggested as hypopigmenting agents, as have laser treatment and chemical peels, but these fall short of desirable responses.
- a new combination therapy recently suggested combines tretinoin and fluocinolone with hydroquinone (Willis, I., Skin & Aging Supp., Nov. 2000, 17-21).
- Kojic acid and arbutin have also been suggested, but these are marginal tyrosinase inhibitors and are not very bioavailable and thus have disappointing efficacy.
- compositions for whitening skin and methods for their use It is a further objective to provide compositions that can be used to enhance known skin whitening compositions and treatments.
- the present invention provides methods and compositions for whitening skin through the topical application of ⁇ -hydroxytetronic acid and/or 60 -hydroxytetronic derivatives, in a preparation that typically includes a dermatologically acceptable carrier.
- the ⁇ -hydroxytetronic active ingredient is applied to skin in combination with at least one adjunct ingredient such as hydroquinone, an ⁇ -hydroxy acid such as glycolic acid, and a fatty acid ester of ascorbic acid such as ascorbyl palmitate.
- Some preferred embodiments contain from about 0.5% to about 25% by weight ⁇ -hydroxytetronic acid and/or hydroxytetronic acid derivatives alone, or in combination with hydroquinone, glycolic acid and/or ascorbyl palmitate.
- This invention is based upon the finding that ⁇ -hydroxytetronic acid, alone or in combination with hydroquinone, provides significant bleaching when applied to the skin, without undesirable side effects.
- a composition containing an effective amount of ⁇ -hydroxytetronic acid active ingredient i.e., ⁇ -hydroxytetronic acid, a derivative, or mixtures thereof, is applied to skin to whiten it.
- whitening is meant the visually apparent reduction in skin pigmentation observed qualitatively and sometimes measured using an assay such as Melanoderm in vitro assays that quantify changes in melanin formation in cultured mammalian epidermal cells.
- Alpha-hydroxytetronic acid (sometimes called 2-hydroxytetronic acid) may be thought of as ascorbic acid without a side chain; the enol form, 3,4-dihydroxy-2-(5H) furnanone, has the formula
- Alpha-hydroxytetronic acid derivatives include, but are not limited to, acylated ⁇ -hydroxytetronic acid derivatives, particularly C 1 to C 6 (hereinafter referred to as “lower”) straight- or branched-chain alkyl esters; hyroxytetronic acid salts, particularly sodium, potassium, and magnesium salts (hereinafter collectively referred to as “physiologically acceptable salts”); alkyl derivatives, particularly lower, or C 1 to C 8 , alkyls, i.e., derivatives having a methyl-, ethyl-, and propyl- group in the ⁇ - (4-) position (sometimes called, respectively, tetrinic, pentinic, and hexinic acid), and their esters and salts, particularly lower alkyl esters and their physiologically acceptable salts); cycloaliphatic derivatives, i.e., derivatives having alkyl hydrocarbon side chains which are closed to form a ring structure, particularly those having
- hydroxytetronic acid includes ⁇ -hydroxytetronic acid itself, alone or in combination with known derivatives, esters, salts, and the like. Specifically encompassed are optical isomers and racemic mixtures, and natural vitamin C mixtures enriched with ⁇ -hydroxytetronic acid and/or its derivatives.
- compositions of the invention contain from about 0.5% to about 25% by weight, more narrowly from about 2% to about 15% by weight, and even more narrowly from about 3% to about 10% by weight, ⁇ -hydroxytetronic acid and/or a derivative thereof.
- Lower concentrations may be employed for less pronounced hyperpigmentation conditions and in sunscreens and sunblocks used after skin whitening treatment (more fully discussed below), and higher concentrations may be employed with more acute pigmentation conditions. Suggested ranges also depend upon any adjunct ingredients employed in the compositions (more fully discussed below) and the user's coloring and skin type as well as the extent of severity of the hyperpigmentation problem.
- Some embodiments contain from about 1% to 10%, more narrowly from about 2% to about 5%, even more narrowly from about 3% to about 4% by weight hydroxytetronic acid; others contain from about 7% to about 25%, more narrowly from about 10% to about 15%, by weight hydroxytetronic acid.
- the topically applied composition be formulated to contain at least about 3 to 5% by weight hydroxytetronic acid, and many embodiments contain about 10% or higher.
- some whitening compositions of the invention contain at least one other adjunct ingredient in addition to hydroxytetronic acid.
- Adjunct ingredients include, but are not limited to, hydroquinone, ⁇ -hydroxy acids, and fatty acid esters of ascorbic acid. Many embodiments employ more than one adjunct ingredient.
- Especially preferred bleaching compositions contain hydroquinone (sometimes also called p-dihydroxybenzene or 1,4 benzenediol) in addition to the hydroxytetronic active ingredient. Typical hydroquinone concentrations range from about 0.25% to about 25% by weight, more narrowly from about 1% to about 5%, and even more narrowly from about 2% to about 4% by weight.
- ⁇ -hydroxy acid has reference to and encompasses the general class of organic compounds containing at least one hydroxy group and at least one carboxyl group, and wherein at least one hydroxyl group is located on the ⁇ -carbon atom.
- the compounds are organic acids having at least one carboxylic acid group and at least one hydroxyl group on the ⁇ -carbon atom, and may contain other functional groups including additional hydroxyl and carboxylic acid moieties.
- Preferred ⁇ -hydroxy acids and/or ⁇ -hydroxy acid derivatives are those which are less bulky structurally, typically having a one- to three-carbon backbone, so that they penetrate the skin well such as those set out in U.S. Pat. No.
- glycolic and/or lactic acid or their derivatives are preferred; glycolic acid is especially efficacious.
- Lactic acid was suggested as a skin-whitening agent in U.S. Pat. No. 5,262,153 to Mashima, et al.
- Typical hydroxy acid concentrations range from about 1% to about 25% by weight, more narrowly from about 2% to about 15%, and even more narrowly from about 3% to 10% by weight.
- higher concentrations may be employed for more acute conditions. In some embodiments, for example, from about 8% to 12% may be employed; in others, ranges of from about 3% to about 7% by weight are sufficient.
- One efficacious composition of the invention contains about 10% hydroxytetronic acid, about 10% glycolic acid, and about 4% hydroquinone.
- Fat-soluble fatty acid esters of ascorbic acid are employed as alternate or additional adjunct ingredients in other embodiments, alone or in combination with hydroquinone or ⁇ -hydroxy acids.
- the more oxidation-resistant saturated fatty acid esters of ascorbic acid are preferred, including, but not limited to, ascorbyl laurate, ascorbyl myristate, ascorbyl palmitate, ascorbyl stearate, and ascorbyl behenate.
- Ascorbyl palmitate is used in one embodiment.
- fatty acid esters are described, e.g., ascorbyl stearate
- compositions having predominantly that ester, e.g., predominantly stearate are included.
- the esters may be prepared using hydrogenated oils or fats, or fractions thereof, and contain small amounts of another ester.
- Ascorbyl stearate prepared using canola for example, commonly contain about 4% ascorbyl palmitate. It is an advantage of the invention that where fatty acid esters of ascorbic acid are employed as an adjunct ingredient, they help provide emollient properties to the composition.
- Typical concentration ranges of ascorbyl palmitate vary from about 0.25% to about 10%, more narrowly from about 2% to about 8%, and even more narrowly from about 3% to about 5% by weight.
- the carrier is inert in the sense of not bringing about a deactivation or oxidation of active or adjunct ingredient(s), and in the sense of not bringing about any adverse effect on the skin areas to which it is applied.
- hydroxytetronic acids are applied in admixture with a dermatologically acceptable carrier or vehicle (e.g., as a lotion, cream, ointment, soap, stick, or the like) so as to facilitate topical application and, in some cases, provide additional beneficial effects as might be brought about, e.g., by moisturizing of the affected skin or mucosal areas.
- a dermatologically acceptable carrier or vehicle e.g., as a lotion, cream, ointment, soap, stick, or the like
- the carrier for dermatological compositions can consist of a relatively simple solvent or dispersant such as water
- the carrier comprise a composition more conducive to topical application, and particularly one which will form a film or layer on the skin to which it is applied so as to localize the application and provide some resistance to washing off by immersion in water or by perspiration and/or aid in the percutaneous delivery of the active agent.
- oils and/or alcohols and emollients such as olive oil, hydrocarbon oils and waxes, silicone oils, other vegetable, animal or marine fats or oils, glyceride derivatives, fatty acids or fatty acid esters or alcohols or alcohol ethers, lecithin, lanolin and derivatives, polyhydric alcohols or esters, wax esters, sterols, phospholipids and the like, and generally also emulsifiers (nonionic, cationic or anionic), although some of the emollients inherently possess emulsifying properties.
- oils and/or alcohols and emollients such as olive oil, hydrocarbon oils and waxes, silicone oils, other vegetable, animal or marine fats or oils, glyceride derivatives, fatty acids or fatty acid esters or alcohols or alcohol ethers, lecithin, lanolin and derivatives, polyhydric alcohols or esters, wax esters, sterols, phospholipids and the like, and generally
- compositions are referred to herein as dermally, dermatologically, or pharmaceutically acceptable carriers.
- Suitable carriers include water, alcohols, oils and the like, chosen for their ability to dissolve or disperse ingredients used in the treatment.
- active and/or adjunct ingredients are added to a sunscreen or sunblock formulations so that topical application has the further advantage of preventing repigmentation during and/or after treatment.
- Preferred formulae of this type are SPF 15 or higher.
- Many of these preferred embodiments contain titanium dioxide or zinc oxide which additionally soothe and lubricate the skin and help minimize side effects in sensitive skin and with formulations containing high concentrations of bleaching ingredients.
- the composition is topically applied to darkened skin areas in a predetermined or as-needed regimen either at intervals by application of a lotion or the like, it generally being the case that gradual lightening is noted with each successive application. Insofar as has been determined based upon clinical studies to date, no adverse side effects are encountered. It is an advantage of the invention that it can be used to augment other skin lightening treatments including, but not limited to, those discussed above such as topical administration of hydroquinone, hydroquinone and glycolic acid, and kojic acid.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- Birds (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Electrophonic Musical Instruments (AREA)
- Surgical Instruments (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Preventing Corrosion Or Incrustation Of Metals (AREA)
Abstract
Description
- Not Applicable
- 1. Field of the Invention
- This invention relates to the use of hydroxytetronic acid and/or hydroxytetronic acid derivatives alone, or in combination with other ingredients such as hydroquinone, glycolic acid, and/or ascorbyl palmitate, in compositions that whiten skin, and methods for using the compositions.
- 2. Description of Related Art
- A variety of dermatological compositions have been suggested for skin whitening to improve the appearance of hyperpigmentary skin conditions such as that observed as freckles, melasma, café au lait and liver spots spots, and lesions observed in Addison's disease, hemochromatosis, vitiligo, piebald-ism, phenylketonuria, and the like, and/or for cosmetic purposes. Skin color is primarily determined by the amount of melanin present in epidermal cells, so many modern skin bleaching compositions either destroy melanin (typically by destroying or disrupting melanin granules) or inhibit its formation (often by inhibiting tyrosinase, a melanin biosynthetic enzyme, or melanocyte activity), or both. Many of these contain harsh chemicals such as peroxides, acids or formaldehyde, or thiolated materials such as glutathione, cysteine, mercaptosuccinic acid, mercaptodextran, and mercapto-ethanol, which have an objectionable odor that makes products containing them undesirable to a consumer (discussed in U.S. Pat. No. 5,980,904 to Leverett and Dornoff, 5,747,006 to Dornoff, et al., and 6,077,503 to Dornoff; these and subsequent references are hereby incorporated herein in their entireties by reference).
- Less stringent therapies have other disadvantages. The only treatment for hyperpigmentation that is approved in the United States for use by consumers without a prescription, for example, is the topical application of hydroquinone, which acts by suppressing melanocyte activity. Hydroquinone is oxidized by air, light, and tyrosinase itself, however, which adversely effects the shelf life of preparations containing it and its bioavailability upon application. Hydroquinone can cause burning, redness, sensitization and irritation in some persons, particularly after application of quantities sufficient to cause skin bleaching as it requires prolonged treatment before results are noticeable, and its oxidized products have been implicated in skin irritation and pigmentation rebound (U.S. Pat. No. 6,068,834 to Kvalnes, et al.). Topical retinoids and topical corticosteroids have been suggested as hypopigmenting agents, as have laser treatment and chemical peels, but these fall short of desirable responses. A new combination therapy recently suggested combines tretinoin and fluocinolone with hydroquinone (Willis, I.,Skin & Aging Supp., Nov. 2000, 17-21). Kojic acid and arbutin have also been suggested, but these are marginal tyrosinase inhibitors and are not very bioavailable and thus have disappointing efficacy.
- Other pleasanter compositions recently suggested employ natural materials, which have in some cases been used for centuries in Asia or Europe to bleach skin and skin areas, or enhance the appearance of fair skin. These include the use of lemon, orange, cucumber, ginko, carob, rose fruit, geraniuim herb, cinnamon, sweet marjoram, rosemary, clove, mulberry, licorice, bearberry, and acerola cherry extracts (ibid.). The variability of active ingredients in these natural products sometimes limits their usefulness, particularly as skin type, color, age, and condition of vary greatly in different subjects, and make suggested dosages and regimens difficult to fashion. And other ingredients in the mixtures can cause allergic reactions in sensitive persons.
- It would be desirable to have alternative preparations, and/or ones that improve the efficacy of presently known skin whitening agents.
- It is an objective of the invention to provide new compositions for whitening skin and methods for their use. It is a further objective to provide compositions that can be used to enhance known skin whitening compositions and treatments.
- These objectives are achieved by the present invention, which provides methods and compositions for whitening skin through the topical application of α-hydroxytetronic acid and/or60 -hydroxytetronic derivatives, in a preparation that typically includes a dermatologically acceptable carrier. In many embodiments, the α-hydroxytetronic active ingredient is applied to skin in combination with at least one adjunct ingredient such as hydroquinone, an α-hydroxy acid such as glycolic acid, and a fatty acid ester of ascorbic acid such as ascorbyl palmitate. Some preferred embodiments contain from about 0.5% to about 25% by weight α-hydroxytetronic acid and/or hydroxytetronic acid derivatives alone, or in combination with hydroquinone, glycolic acid and/or ascorbyl palmitate.
- This invention is based upon the finding that α-hydroxytetronic acid, alone or in combination with hydroquinone, provides significant bleaching when applied to the skin, without undesirable side effects.
- In the practice of the invention, a composition containing an effective amount of α-hydroxytetronic acid active ingredient, i.e., α-hydroxytetronic acid, a derivative, or mixtures thereof, is applied to skin to whiten it. By “whitening” is meant the visually apparent reduction in skin pigmentation observed qualitatively and sometimes measured using an assay such as Melanoderm in vitro assays that quantify changes in melanin formation in cultured mammalian epidermal cells. Alpha-hydroxytetronic acid (sometimes called 2-hydroxytetronic acid) may be thought of as ascorbic acid without a side chain; the enol form, 3,4-dihydroxy-2-(5H) furnanone, has the formula
- Alpha-hydroxytetronic acid derivatives include, but are not limited to, acylated α-hydroxytetronic acid derivatives, particularly C1 to C6 (hereinafter referred to as “lower”) straight- or branched-chain alkyl esters; hyroxytetronic acid salts, particularly sodium, potassium, and magnesium salts (hereinafter collectively referred to as “physiologically acceptable salts”); alkyl derivatives, particularly lower, or C1 to C8, alkyls, i.e., derivatives having a methyl-, ethyl-, and propyl- group in the γ- (4-) position (sometimes called, respectively, tetrinic, pentinic, and hexinic acid), and their esters and salts, particularly lower alkyl esters and their physiologically acceptable salts); cycloaliphatic derivatives, i.e., derivatives having alkyl hydrocarbon side chains which are closed to form a ring structure, particularly those having a hydrocarbon ring structure containing from 3 to 6 carbon atoms attached to the γ- (4-) position; alkoxy derivatives, particularly those having a lower alkyl group attached to the molecule in the α-(2-), β- 3-), or γ-(4-) position by oxygen such as methoxy-, ethoxy-, propoxy-, and isopropoxy- derivatives, and the like; aryl derivatives, particularly those having a phenyl, benzyl, tolyl, or phenethyl group in the γ-(4-) position, and substituted aryls, notably halogenated derivatives such as those having a chlorophenyl or dichlorophenyl group attached to the γ-(4-) position; their lower alkyl essters and physiologically acceptable salts; and mixtures thereof. For convenience, as used herein, the term “hydroxytetronic acid” includes α-hydroxytetronic acid itself, alone or in combination with known derivatives, esters, salts, and the like. Specifically encompassed are optical isomers and racemic mixtures, and natural vitamin C mixtures enriched with α-hydroxytetronic acid and/or its derivatives.
- Typical compositions of the invention contain from about 0.5% to about 25% by weight, more narrowly from about 2% to about 15% by weight, and even more narrowly from about 3% to about 10% by weight, α-hydroxytetronic acid and/or a derivative thereof. Lower concentrations may be employed for less pronounced hyperpigmentation conditions and in sunscreens and sunblocks used after skin whitening treatment (more fully discussed below), and higher concentrations may be employed with more acute pigmentation conditions. Suggested ranges also depend upon any adjunct ingredients employed in the compositions (more fully discussed below) and the user's coloring and skin type as well as the extent of severity of the hyperpigmentation problem. Some embodiments contain from about 1% to 10%, more narrowly from about 2% to about 5%, even more narrowly from about 3% to about 4% by weight hydroxytetronic acid; others contain from about 7% to about 25%, more narrowly from about 10% to about 15%, by weight hydroxytetronic acid. As a practical matter, however, to avoid the need for repeated application, it is desirable that the topically applied composition be formulated to contain at least about 3 to 5% by weight hydroxytetronic acid, and many embodiments contain about 10% or higher.
- As summarized above, some whitening compositions of the invention contain at least one other adjunct ingredient in addition to hydroxytetronic acid. Adjunct ingredients include, but are not limited to, hydroquinone, α-hydroxy acids, and fatty acid esters of ascorbic acid. Many embodiments employ more than one adjunct ingredient. Especially preferred bleaching compositions contain hydroquinone (sometimes also called p-dihydroxybenzene or 1,4 benzenediol) in addition to the hydroxytetronic active ingredient. Typical hydroquinone concentrations range from about 0.25% to about 25% by weight, more narrowly from about 1% to about 5%, and even more narrowly from about 2% to about 4% by weight.
- As used herein, the term “α-hydroxy acid” has reference to and encompasses the general class of organic compounds containing at least one hydroxy group and at least one carboxyl group, and wherein at least one hydroxyl group is located on the α-carbon atom. Typically, the compounds are organic acids having at least one carboxylic acid group and at least one hydroxyl group on the α-carbon atom, and may contain other functional groups including additional hydroxyl and carboxylic acid moieties. Preferred α-hydroxy acids and/or α-hydroxy acid derivatives are those which are less bulky structurally, typically having a one- to three-carbon backbone, so that they penetrate the skin well such as those set out in U.S. Pat. No. 5,965,618 at column 6 lines 4 to 29. Where employed, glycolic and/or lactic acid or their derivatives are preferred; glycolic acid is especially efficacious. Lactic acid was suggested as a skin-whitening agent in U.S. Pat. No. 5,262,153 to Mashima, et al. Typical hydroxy acid concentrations range from about 1% to about 25% by weight, more narrowly from about 2% to about 15%, and even more narrowly from about 3% to 10% by weight. As with the hydroxytetronic acid ingredient, higher concentrations may be employed for more acute conditions. In some embodiments, for example, from about 8% to 12% may be employed; in others, ranges of from about 3% to about 7% by weight are sufficient. One efficacious composition of the invention contains about 10% hydroxytetronic acid, about 10% glycolic acid, and about 4% hydroquinone.
- Fat-soluble fatty acid esters of ascorbic acid (vitamin C) are employed as alternate or additional adjunct ingredients in other embodiments, alone or in combination with hydroquinone or α-hydroxy acids. The more oxidation-resistant saturated fatty acid esters of ascorbic acid are preferred, including, but not limited to, ascorbyl laurate, ascorbyl myristate, ascorbyl palmitate, ascorbyl stearate, and ascorbyl behenate. Ascorbyl palmitate is used in one embodiment. As denoted herein, where fatty acid esters are described, e.g., ascorbyl stearate, compositions having predominantly that ester, e.g., predominantly stearate, are included. The esters may be prepared using hydrogenated oils or fats, or fractions thereof, and contain small amounts of another ester. Ascorbyl stearate prepared using canola, for example, commonly contain about 4% ascorbyl palmitate. It is an advantage of the invention that where fatty acid esters of ascorbic acid are employed as an adjunct ingredient, they help provide emollient properties to the composition. Typical concentration ranges of ascorbyl palmitate vary from about 0.25% to about 10%, more narrowly from about 2% to about 8%, and even more narrowly from about 3% to about 5% by weight.
- However, only effective amounts of active ingredient(s) are needed to whiten skin, so generally topical application to skin sites is accomplished in association with a carrier, and particularly one in which the active ingredient is soluble per se or is effectively solubilized (e.g., as an emulsion or microemulsion). Where employed, the carrier is inert in the sense of not bringing about a deactivation or oxidation of active or adjunct ingredient(s), and in the sense of not bringing about any adverse effect on the skin areas to which it is applied. In one preferred practice of the invention, hydroxytetronic acids are applied in admixture with a dermatologically acceptable carrier or vehicle (e.g., as a lotion, cream, ointment, soap, stick, or the like) so as to facilitate topical application and, in some cases, provide additional beneficial effects as might be brought about, e.g., by moisturizing of the affected skin or mucosal areas. While the carrier for dermatological compositions can consist of a relatively simple solvent or dispersant such as water, it is generally preferred that the carrier comprise a composition more conducive to topical application, and particularly one which will form a film or layer on the skin to which it is applied so as to localize the application and provide some resistance to washing off by immersion in water or by perspiration and/or aid in the percutaneous delivery of the active agent. Many preparations are known in the art, and include lotions containing oils and/or alcohols and emollients such as olive oil, hydrocarbon oils and waxes, silicone oils, other vegetable, animal or marine fats or oils, glyceride derivatives, fatty acids or fatty acid esters or alcohols or alcohol ethers, lecithin, lanolin and derivatives, polyhydric alcohols or esters, wax esters, sterols, phospholipids and the like, and generally also emulsifiers (nonionic, cationic or anionic), although some of the emollients inherently possess emulsifying properties. These same general ingredients can be formulated into a cream rather than a lotion, or into gels, or into solid sticks by utilization of different proportions of the ingredients and/or by inclusion of thickening agents such as gums or other forms of hydrophilic colloids. One preferred embodiment is an oil-in-water cream. Such compositions are referred to herein as dermally, dermatologically, or pharmaceutically acceptable carriers.
- Suitable carriers include water, alcohols, oils and the like, chosen for their ability to dissolve or disperse ingredients used in the treatment. In some embodiments, active and/or adjunct ingredients are added to a sunscreen or sunblock formulations so that topical application has the further advantage of preventing repigmentation during and/or after treatment. Preferred formulae of this type are SPF 15 or higher. Many of these preferred embodiments contain titanium dioxide or zinc oxide which additionally soothe and lubricate the skin and help minimize side effects in sensitive skin and with formulations containing high concentrations of bleaching ingredients.
- Generally in the practice of methods of the invention, the composition is topically applied to darkened skin areas in a predetermined or as-needed regimen either at intervals by application of a lotion or the like, it generally being the case that gradual lightening is noted with each successive application. Insofar as has been determined based upon clinical studies to date, no adverse side effects are encountered. It is an advantage of the invention that it can be used to augment other skin lightening treatments including, but not limited to, those discussed above such as topical administration of hydroquinone, hydroquinone and glycolic acid, and kojic acid.
- The above description is for the purpose of teaching the person of ordinary skill in the art how to practice the present invention, and it is not intended to detail all those obvious modifications and variations of it which will become apparent to the skilled worker upon reading the description. It is intended, however, that all such obvious modifications and variations be included within the scope of the present invention, which is defined by the following claims. The claims are intended to cover the claimed components and steps in any sequence which is effective to meet the objectives there intended, unless the context specifically indicates the contrary.
Claims (20)
Priority Applications (12)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/735,144 US6417226B1 (en) | 2000-12-12 | 2000-12-12 | Skin whiteners containing hydroxytetronic acid |
JP2002572947A JP2004519494A (en) | 2000-12-12 | 2001-12-12 | Skin whitening agent containing oxytetronic acid |
ES01273547T ES2315260T3 (en) | 2000-12-12 | 2001-12-12 | EMBLANQUECADORES FOR THE SKIN CONTAINING HYDROXYTHETRONIC ACID. |
CN01804685A CN1416343A (en) | 2000-12-12 | 2001-12-12 | Skin Lighteners Containing Hydroxytetronic Acid |
CA002406783A CA2406783C (en) | 2000-12-12 | 2001-12-12 | Skin whiteners containing hydroxytetronic acid |
AT01273547T ATE409034T1 (en) | 2000-12-12 | 2001-12-12 | SKIN LIGHTENING AGENTS CONTAINING HYDROXYTETRONIC ACID |
PCT/US2001/051607 WO2002074236A2 (en) | 2000-12-12 | 2001-12-12 | Skin whiteners containing hydroxytetronic acid |
KR1020027009835A KR20030005174A (en) | 2000-12-12 | 2001-12-12 | Skin whiteners containing hydroxytetronic acid |
EP01273547A EP1341535B1 (en) | 2000-12-12 | 2001-12-12 | Skin whiteners containing hydroxytetronic acid |
AU2001297730A AU2001297730B2 (en) | 2000-12-12 | 2001-12-12 | Skin whiteners containing hydroxytetronic acid |
DE60135927T DE60135927D1 (en) | 2000-12-12 | 2001-12-12 | Nd |
US10/159,368 US7019029B2 (en) | 2000-12-12 | 2002-05-31 | Skin whiteners containing hydroxytetronic acid derivatives |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/735,144 US6417226B1 (en) | 2000-12-12 | 2000-12-12 | Skin whiteners containing hydroxytetronic acid |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/159,368 Continuation-In-Part US7019029B2 (en) | 2000-12-12 | 2002-05-31 | Skin whiteners containing hydroxytetronic acid derivatives |
Publications (2)
Publication Number | Publication Date |
---|---|
US20020071816A1 true US20020071816A1 (en) | 2002-06-13 |
US6417226B1 US6417226B1 (en) | 2002-07-09 |
Family
ID=24954554
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/735,144 Expired - Lifetime US6417226B1 (en) | 2000-12-12 | 2000-12-12 | Skin whiteners containing hydroxytetronic acid |
US10/159,368 Expired - Lifetime US7019029B2 (en) | 2000-12-12 | 2002-05-31 | Skin whiteners containing hydroxytetronic acid derivatives |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/159,368 Expired - Lifetime US7019029B2 (en) | 2000-12-12 | 2002-05-31 | Skin whiteners containing hydroxytetronic acid derivatives |
Country Status (11)
Country | Link |
---|---|
US (2) | US6417226B1 (en) |
EP (1) | EP1341535B1 (en) |
JP (1) | JP2004519494A (en) |
KR (1) | KR20030005174A (en) |
CN (1) | CN1416343A (en) |
AT (1) | ATE409034T1 (en) |
AU (1) | AU2001297730B2 (en) |
CA (1) | CA2406783C (en) |
DE (1) | DE60135927D1 (en) |
ES (1) | ES2315260T3 (en) |
WO (1) | WO2002074236A2 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060083697A1 (en) * | 2004-10-15 | 2006-04-20 | Huynh Anthony V | Topical skin lightening cream |
WO2007077259A1 (en) * | 2006-01-05 | 2007-07-12 | Symrise Gmbh & Co. Kg | Synergistic active preparations comprising diphenylmethane derivatives and further skin and/or hair lightening and/or senile keratosis reducing compounds |
ES2361350A1 (en) * | 2009-12-04 | 2011-06-16 | Julio Monje Diaz | Eliminating cream of hyperpigmentary spots for the skin of the face and its utilization. (Machine-translation by Google Translate, not legally binding) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5874463A (en) * | 1994-10-24 | 1999-02-23 | Ancira; Margaret | Hydroxy-kojic acid skin peel |
US6417226B1 (en) * | 2000-12-12 | 2002-07-09 | Nicholas V. Perricone | Skin whiteners containing hydroxytetronic acid |
US7189759B2 (en) * | 2001-05-23 | 2007-03-13 | Medicis Pharmaceutical Corporation | Compositions for the treatment of pigmentation disorders and methods for their manufacture |
US7025957B2 (en) | 2002-09-06 | 2006-04-11 | Desert Whale Jojoba Company | Composition and method to whiten skin |
US9453219B2 (en) * | 2003-05-15 | 2016-09-27 | Mello Biotech Taiwan Co., Ltd. | Cosmetic designs and products using intronic RNA |
US8016810B2 (en) * | 2003-06-23 | 2011-09-13 | Transpharma Medical Ltd. | Transdermal delivery system for cosmetic agents |
US7504385B2 (en) * | 2003-12-17 | 2009-03-17 | Avon Products, Inc. | si-RNA-mediated gene silencing technology to inhibit tyrosinase and reduce pigmentation |
US8119791B2 (en) * | 2003-12-17 | 2012-02-21 | Avon Products, Inc. | si-RNA-mediated gene silencing technology to inhibit tyrosinase and reduce pigmentation |
US7429391B2 (en) * | 2004-01-30 | 2008-09-30 | Access Business Group International Llc | Holistic composition and method for reducing skin pigmentation |
GB2465432A (en) * | 2008-11-25 | 2010-05-26 | Pornthip Lattmann | Novel skin brightening agents |
WO2011010306A1 (en) | 2009-07-21 | 2011-01-27 | Ramot At Tel-Aviv University Ltd. | A3 adenosine receptor ligands for modulation of pigmentation |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE946327C (en) * | 1953-03-29 | 1956-07-26 | Agfa Ag Fuer Photofabrikation | Process for improving the whiteness of photographic images produced by the silver salt diffusion process |
CH508899A (en) * | 1968-06-25 | 1971-06-15 | Ciba Geigy Ag | Color bleaching preparation for the photographic silver color bleaching process |
US5385938B1 (en) * | 1986-12-23 | 1997-07-15 | Tristrata Inc | Method of using glycolic acid for treating wrinkles |
US5091171B2 (en) * | 1986-12-23 | 1997-07-15 | Tristrata Inc | Amphoteric compositions and polymeric forms of alpha hydroxyacids and their therapeutic use |
JP2593714B2 (en) | 1989-09-20 | 1997-03-26 | 株式会社 林原生物化学研究所 | Whitening agent |
EP0561305B1 (en) * | 1992-03-17 | 1999-08-11 | Eisai Co., Ltd. | Skin whitening composition containing teprenone |
ES2160102T3 (en) * | 1992-09-11 | 2001-11-01 | Nicholas V Dr Perricone | TREATMENT OF ERITEMA CAUSED BY UV. |
JP2690672B2 (en) | 1993-03-30 | 1997-12-10 | 株式会社タウ技研 | Soap manufacturing equipment |
US5602259A (en) * | 1993-12-17 | 1997-02-11 | Pacific Corporation | Method for producing 4-hydroxy-5-methyl-3[2H]-furanone and uses of same |
US6068834A (en) | 1994-03-04 | 2000-05-30 | The Procter & Gamble Company | Skin lightening compositions |
EP0713139B1 (en) * | 1994-10-20 | 1998-06-03 | Fuji Photo Film Co., Ltd. | Novel, iron complex, process for producing the same, photographic processing composition and processing process using the same |
AU728163B2 (en) | 1996-08-21 | 2001-01-04 | Children's Hospital Medical Center | Skin lightening compositions |
US6005000A (en) * | 1996-08-22 | 1999-12-21 | Oxis International, Inc. | 5,5-Disubstituted-3, 4-dihydroxy-2(5H)-furanones and methods of use therefor |
US6162419A (en) * | 1996-11-26 | 2000-12-19 | Nicholas V. Perricone | Stabilized ascorbyl compositions |
US5776473A (en) * | 1997-01-17 | 1998-07-07 | Warner-Lambert Company | Razor comfort strip with alpha-hydroxy acid additive |
US5747006A (en) | 1997-05-14 | 1998-05-05 | Amway Corporation | Skin whitener composition containing acerola cherry fermentate |
US6077503A (en) | 1997-07-30 | 2000-06-20 | Amway Corporation | Skin whitener composition containing mercaptodextran |
US5932612A (en) | 1997-08-05 | 1999-08-03 | Medicis Pharmaceutical Corp. | Compositions and systems for the treatment of hyperpigmentation |
US6057360A (en) | 1997-08-05 | 2000-05-02 | Gordon; Benjamin D. | Compositions and systems for the treatment of hyperpigmentation |
US5980904A (en) | 1998-11-18 | 1999-11-09 | Amway Corporation | Skin whitening composition containing bearberry extract and a reducing agent |
US6010685A (en) | 1999-03-08 | 2000-01-04 | Oxis International, Inc. | Skin protectant comprising 5-substituted and 5,5-disubstituted 3,4-dihydroxy-2(5H)-furanones |
US6417226B1 (en) * | 2000-12-12 | 2002-07-09 | Nicholas V. Perricone | Skin whiteners containing hydroxytetronic acid |
-
2000
- 2000-12-12 US US09/735,144 patent/US6417226B1/en not_active Expired - Lifetime
-
2001
- 2001-12-12 WO PCT/US2001/051607 patent/WO2002074236A2/en not_active Application Discontinuation
- 2001-12-12 CN CN01804685A patent/CN1416343A/en active Pending
- 2001-12-12 AU AU2001297730A patent/AU2001297730B2/en not_active Ceased
- 2001-12-12 AT AT01273547T patent/ATE409034T1/en not_active IP Right Cessation
- 2001-12-12 EP EP01273547A patent/EP1341535B1/en not_active Expired - Lifetime
- 2001-12-12 DE DE60135927T patent/DE60135927D1/en not_active Expired - Lifetime
- 2001-12-12 KR KR1020027009835A patent/KR20030005174A/en not_active Ceased
- 2001-12-12 ES ES01273547T patent/ES2315260T3/en not_active Expired - Lifetime
- 2001-12-12 CA CA002406783A patent/CA2406783C/en not_active Expired - Fee Related
- 2001-12-12 JP JP2002572947A patent/JP2004519494A/en active Pending
-
2002
- 2002-05-31 US US10/159,368 patent/US7019029B2/en not_active Expired - Lifetime
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060083697A1 (en) * | 2004-10-15 | 2006-04-20 | Huynh Anthony V | Topical skin lightening cream |
WO2007077259A1 (en) * | 2006-01-05 | 2007-07-12 | Symrise Gmbh & Co. Kg | Synergistic active preparations comprising diphenylmethane derivatives and further skin and/or hair lightening and/or senile keratosis reducing compounds |
US20090148391A1 (en) * | 2006-01-05 | 2009-06-11 | Symrise Gmbh & Co. Kg | Synergistic active preparations comprising diphenylmethane derivatives and further skin and/or hair lightening and/or senile keratosis reducing compounds |
ES2361350A1 (en) * | 2009-12-04 | 2011-06-16 | Julio Monje Diaz | Eliminating cream of hyperpigmentary spots for the skin of the face and its utilization. (Machine-translation by Google Translate, not legally binding) |
Also Published As
Publication number | Publication date |
---|---|
CN1416343A (en) | 2003-05-07 |
US6417226B1 (en) | 2002-07-09 |
JP2004519494A (en) | 2004-07-02 |
AU2001297730B2 (en) | 2004-05-13 |
DE60135927D1 (en) | 2008-11-06 |
KR20030005174A (en) | 2003-01-17 |
ATE409034T1 (en) | 2008-10-15 |
US7019029B2 (en) | 2006-03-28 |
EP1341535A4 (en) | 2004-01-14 |
US20020141956A1 (en) | 2002-10-03 |
CA2406783A1 (en) | 2002-09-26 |
EP1341535B1 (en) | 2008-09-24 |
WO2002074236A2 (en) | 2002-09-26 |
ES2315260T3 (en) | 2009-04-01 |
WO2002074236A3 (en) | 2002-12-19 |
EP1341535A2 (en) | 2003-09-10 |
CA2406783C (en) | 2007-04-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR100928211B1 (en) | Compositions for the treatment of sun damage and compositions for reducing acne lesions | |
US6417226B1 (en) | Skin whiteners containing hydroxytetronic acid | |
KR100315502B1 (en) | Skin whitening agent containing acerola cherry fermentation material | |
KR101496373B1 (en) | Arginine heteromer for topical administration | |
ES2198662T3 (en) | USE OF RETINOIDS AS AN INDUCTIVE AGENT OF SKIN PIGMENTATION. | |
WO2018142033A1 (en) | Depigmenting dermatological and cosmetic compositions | |
US20110250157A1 (en) | Skin Hyperpigmentation Acyl Glutathione Treatments | |
US20020155075A1 (en) | Resorcinol composition | |
JP3803540B2 (en) | Use of DHEA or its precursors or metabolic derivatives as depigmenting agents | |
FR2723316A1 (en) | Compsn. for skin de-pigmentation caused by hyper:activation melanocytes | |
JP3451184B2 (en) | Cosmetic composition or pharmaceutical composition | |
JPH1067615A (en) | Pigment eliminator consisting of n,n'-dibenzylethylenediamine-n,n'-diacetic acid derivative | |
EP1874410B1 (en) | Depigmenting or brightening cosmetic composition comprising at least one oxazolin as an active ingredient | |
JP4754178B2 (en) | Promotion of melanin production by lignans | |
CN1121850C (en) | Use of unfermented honey as decolouring agent | |
JPH11180854A (en) | Skin preparation for external use | |
JPH0551312A (en) | Cosmetics mixed with multiple vitamin | |
US11213473B1 (en) | Skin brightening composition | |
Care et al. | Skin Lightening Challenges | |
JP2001302494A (en) | Composition including retinoid for skin care and caffeine | |
JPH06321767A (en) | Make-up goods or composition for dermatology with decoloring action |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCF | Information on status: patent grant |
Free format text: PATENTED CASE |
|
FPAY | Fee payment |
Year of fee payment: 4 |
|
AS | Assignment |
Owner name: UNION BANK OF CALIFORNIA, N.A., AS AGENT FOR THE L Free format text: SECURITY AGREEMENT;ASSIGNOR:N.V. PERRICONE LLC;REEL/FRAME:017251/0780 Effective date: 20060303 |
|
AS | Assignment |
Owner name: N. V. PERRICONE LLC, CONNECTICUT Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:PERRICONE, NICHOLAS V.;REEL/FRAME:018837/0240 Effective date: 20061025 |
|
FPAY | Fee payment |
Year of fee payment: 8 |
|
FEPP | Fee payment procedure |
Free format text: PAT HOLDER NO LONGER CLAIMS SMALL ENTITY STATUS, ENTITY STATUS SET TO UNDISCOUNTED (ORIGINAL EVENT CODE: STOL); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
FPAY | Fee payment |
Year of fee payment: 12 |
|
AS | Assignment |
Owner name: THE NORTHWESTERN MUTUAL LIFE INSURANCE COMPANY, AS Free format text: SECURITY INTEREST;ASSIGNOR:N.V. PERRICONE LLC;REEL/FRAME:035833/0948 Effective date: 20150605 Owner name: N.V. PERRICONE LLC, CONNECTICUT Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:MUFG UNION BANK, N.A., AS AGENT FORMERLY KNOWN AS UNION BANK OF CALIFORNIA, N.A., AS AGENT;REEL/FRAME:035835/0564 Effective date: 20150605 |