JP5066356B2 - Keratinocyte contractor - Google Patents
Keratinocyte contractor Download PDFInfo
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- JP5066356B2 JP5066356B2 JP2006288880A JP2006288880A JP5066356B2 JP 5066356 B2 JP5066356 B2 JP 5066356B2 JP 2006288880 A JP2006288880 A JP 2006288880A JP 2006288880 A JP2006288880 A JP 2006288880A JP 5066356 B2 JP5066356 B2 JP 5066356B2
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- Prior art keywords
- salt
- keratinocyte
- octadecyl
- compound
- carbon atoms
- Prior art date
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- 210000002510 keratinocyte Anatomy 0.000 title claims description 18
- 239000011148 porous material Substances 0.000 claims description 27
- 150000001875 compounds Chemical class 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- -1 alkali metal salts Chemical class 0.000 description 41
- 239000003795 chemical substances by application Substances 0.000 description 18
- 238000004519 manufacturing process Methods 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- 230000008602 contraction Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 229910019142 PO4 Inorganic materials 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 239000002537 cosmetic Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- 210000003491 skin Anatomy 0.000 description 6
- QIAUWGCLDFMEML-UHFFFAOYSA-N 1-butoxy-3-octadecoxypropan-2-ol Chemical compound C(CCCCCCCCCCCCCCCCC)OCC(O)COCCCC QIAUWGCLDFMEML-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- KLSNOCPGVDDUFV-UHFFFAOYSA-N 1-ethoxy-3-tetradecoxypropan-2-ol Chemical compound CCCCCCCCCCCCCCOCC(O)COCC KLSNOCPGVDDUFV-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 229940125904 compound 1 Drugs 0.000 description 4
- 230000001595 contractor effect Effects 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- 229910001868 water Inorganic materials 0.000 description 4
- OVIOARMPCBARQQ-UHFFFAOYSA-N 1-ethoxy-3-octadecoxypropan-2-ol Chemical compound C(CCCCCCCCCCCCCCCCC)OCC(O)COCC OVIOARMPCBARQQ-UHFFFAOYSA-N 0.000 description 3
- BCTYQSRQYAFNHG-UHFFFAOYSA-N C(CCCCCCCCCCCCCCC)OCC(O)COCC Chemical compound C(CCCCCCCCCCCCCCC)OCC(O)COCC BCTYQSRQYAFNHG-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 239000000512 collagen gel Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- NVKSMKFBUGBIGE-UHFFFAOYSA-N 2-(tetradecoxymethyl)oxirane Chemical compound CCCCCCCCCCCCCCOCC1CO1 NVKSMKFBUGBIGE-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 125000001204 arachidyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([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 description 2
- 125000002511 behenyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([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 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 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 2
- 125000002463 lignoceryl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([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 description 2
- 125000002960 margaryl 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])C([H])([H])C([H])([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 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 125000001421 myristyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000001196 nonadecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([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 description 2
- 125000001400 nonyl 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])C([H])([H])[H] 0.000 description 2
- 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 description 2
- 125000000913 palmityl 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])C([H])([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 description 2
- 125000002958 pentadecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000004079 stearyl 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])C([H])([H])C([H])([H])C([H])([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 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000002469 tricosyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([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 description 2
- 125000002889 tridecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 125000002948 undecyl 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])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- YZUMRMCHAJVDRT-UHFFFAOYSA-N 2-(hexadecoxymethyl)oxirane Chemical compound CCCCCCCCCCCCCCCCOCC1CO1 YZUMRMCHAJVDRT-UHFFFAOYSA-N 0.000 description 1
- ZXJBWUAALADCRI-UHFFFAOYSA-N 2-(octadecoxymethyl)oxirane Chemical compound CCCCCCCCCCCCCCCCCCOCC1CO1 ZXJBWUAALADCRI-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 244000061408 Eugenia caryophyllata Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 235000016639 Syzygium aromaticum Nutrition 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical class OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 229910052757 nitrogen Inorganic materials 0.000 description 1
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- 239000002674 ointment Substances 0.000 description 1
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- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
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- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 238000005406 washing Methods 0.000 description 1
Landscapes
- Cosmetics (AREA)
Description
本発明は、ケラチノサイト収縮剤及び毛穴収縮剤に関する。 The present invention relates to a keratinocyte shrinkage agent and a pore shrinkage agent.
スキンケアは老若男女を問わず高い関心を持たれている。このスキンケアの際に改善したい肌のトラブルとして毛穴の目立ちが上位を占めている。
この毛穴の目立ちの原因としては、毛穴に形成された角栓、色素沈着、毛穴開口部の広がり等が挙げられる。このうち角栓については、種々の角栓除去剤が開発され、広く用いられている。しかし、単に角栓を除去しただけでは毛穴が開いたままであり、毛穴が目立ったままの状態であるという欠点がある。
Skin care has a high interest regardless of gender. The conspicuous pores occupy the top as skin troubles to be improved during this skin care.
Causes of the conspicuous pores include square plugs formed in the pores, pigmentation, and spread of pore openings. Among these, for horn plugs, various horn plug removers have been developed and widely used. However, there is a disadvantage that the pores remain open when the square plug is simply removed, and the pores remain conspicuous.
毛穴を目立たなくさせるために、ヒバマタ等天然由来の多糖（特許文献１参照。）や炭素数８〜３２のアルキル基を有するリン酸化グリセリルエーテル誘導体（特許文献２参照。）等種々の毛穴収縮剤が提案されている。しかしながら、効果の点から必ずしも十分であるとはいえず、根本的に毛穴目立ちを改善するための毛穴収縮剤の探索が望まれている。 In order to make pores inconspicuous, various pore-contracting agents such as natural polysaccharides such as Hibamata (see Patent Document 1) and phosphorylated glyceryl ether derivatives having an alkyl group having 8 to 32 carbon atoms (see Patent Document 2) Has been proposed. However, it is not necessarily sufficient from the viewpoint of the effect, and a search for a pore contractor for fundamentally improving pore conspicuousness is desired.
一方、１，３−ジアルキルグリセル２−リン酸のアルカノールアミン塩又はアルカリ金属塩には皮膚洗浄効果があることが知られているが（特許文献３参照。）、ケラチノサイト収縮作用や毛穴収縮作用があることは知られていない。
本発明は、毛穴を目立たなくさせることができるケラチノサイト収縮剤及び毛穴収縮剤を提供することに関する。 The present invention relates to providing a keratinocyte shrinkage agent and a pore shrinkage agent that can make pores inconspicuous.
本発明者らは、表皮細胞の収縮と毛穴の収縮関係について検討してきたところ、下記式（１）で表わされる１，３−ジアルキルグリセル２−リン酸又はその塩がケラチノサイト収縮作用に優れ、ケラチノサイト収縮剤及び毛穴収縮剤として有用であることを見出した。 The inventors of the present invention have examined the contraction of epidermal cells and the contraction of pores. It was found useful as a keratinocyte contractor and a pore contractor.
すなわち、本発明は、下記式（１）で表わされる化合物又はその塩を含有するケラチノサイト収縮剤及び毛穴収縮剤を提供するものである。 That is, the present invention provides a keratinocyte shrinkage agent and a pore shrinkage agent containing a compound represented by the following formula (1) or a salt thereof.
〔Ｒ1は炭素数８〜２４のアルキル基、Ｒ2は炭素数１〜２４のアルキル基〕 [R 1 is an alkyl group having 8 to 24 carbon atoms, R 2 is an alkyl group having 1 to 24 carbon atoms]
本発明のケラチノサイト収縮剤及び毛穴収縮剤によれば、ケラチノサイトを収縮して毛穴を収縮し、毛穴を目立たなくすることができる。 According to the keratinocyte contraction agent and pore contraction agent of the present invention, the keratinocytes can be contracted to contract the pores, and the pores can be made inconspicuous.
式（１）中、Ｒ1で示される炭素数８〜２４のアルキル基としては、炭素数１０〜２４のものが好ましく、炭素数１２〜２０のものがより好ましい。また、炭素鎖は、直鎖又は分岐の何れでもよいが、好ましくは直鎖である。
当該Ｒ1で表されるアルキル基の好適な具体例としては、例えば、オクチル、ノニル、デシル、ウンデシル、ドデシル、トリデシル、テトラデシル、ペンタデシル、ヘキサデシル、ヘプタデシル、オクタデシル、i-オクタデシル、ノナデシル、イコシル、ヘンイコシル、ドコシル、トリコシル、テトラコシル、２−エチルヘキシル、１，１，３，３−テトラメチルブチル、３，７−ジメチルオクチル、３，７−ジメチルオクタン−３−イル、２−ヘキシルデシル、２−ヘプチルウンデシル、２−オクチルドデシル、３，７，１１−トリメチルドデシル、３，７，１１，１５−テトラメチルヘキサデシル、３，５，５−トリメチルへキシル、２，３，４−トリメチルペンタン−３−イル、２，３，４，６−ペンタメチルヘプタン−３−イル、イソステアリル等が挙げられる。
In the formula (1), the alkyl group having 8 to 24 carbon atoms represented by R 1 is preferably one having 10 to 24 carbon atoms, more preferably 12 to 20 carbon atoms. The carbon chain may be linear or branched, but is preferably linear.
Preferable specific examples of the alkyl group represented by R 1 include, for example, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, i-octadecyl, nonadecyl, icosyl, heicosyl. , Docosyl, tricosyl, tetracosyl, 2-ethylhexyl, 1,1,3,3-tetramethylbutyl, 3,7-dimethyloctyl, 3,7-dimethyloctane-3-yl, 2-hexyldecyl, 2-heptylun Decyl, 2-octyldodecyl, 3,7,11-trimethyldodecyl, 3,7,11,15-tetramethylhexadecyl, 3,5,5-trimethylhexyl, 2,3,4-trimethylpentane-3- Yl, 2,3,4,6-pentamethylheptan-3-yl, iso Stearyl etc. are mentioned.
式（１）中、Ｒ2で示される炭素数１〜２４のアルキル基としては、炭素数１〜１０のものがより好ましく、炭素数１〜６のものが特に好ましい。また、炭素鎖は、直鎖又は分岐の何れでもよいが、好ましくは直鎖である。
当該Ｒ2のアルキル基の好適な具体的としては、例えば、例えば、メチル、エチル、ｎ−プロピル、i-プロピル、ｎ−ブチル、i-ブチル、ｔ−ブチル、ペンチル、ネオペンチル、ヘキシル、ヘプチル、オクチル、ノニル、デシル、ウンデシル、ドデシル、トリデシル、テトラデシル、ペンタデシル、ヘキサデシル、ヘプタデシル、オクタデシル、i-オクタデシル、ノナデシル、イコシル、ヘンイコシル、ドコシル、トリコシル、テトラコシル、２−エチルヘキシル、３，３−ジメチルブチル、１，１，３，３−テトラメチルブチル、３，７−ジメチルオクチル、３，７−ジメチルオクタン−３−イル、２−ヘキシルデシル、２−ヘプチルウンデシル、２−オクチルドデシル、３，７，１１−トリメチルドデシル、３，７，１１，１５−テトラメチルヘキサデシル、３，５，５−トリメチルへキシル、２，３，４−トリメチルペンタン−３−イル、２，３，４，６−ペンタメチルヘプタン−３−イル、イソステアリル等が挙げられる。
In the formula (1), the alkyl group having 1 to 24 carbon atoms represented by R 2, and more preferably has 1 to 10 carbon atoms, particularly preferably from 1 to 6 carbon atoms. The carbon chain may be linear or branched, but is preferably linear.
Preferable specific examples of the alkyl group for R 2 include, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, pentyl, neopentyl, hexyl, heptyl, Octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, i-octadecyl, nonadecyl, icosyl, heicosyl, docosyl, tricosyl, tetracosyl, 2-ethylhexyl, 3,3-dimethylbutyl, 1 , 1,3,3-tetramethylbutyl, 3,7-dimethyloctyl, 3,7-dimethyloctane-3-yl, 2-hexyldecyl, 2-heptylundecyl, 2-octyldodecyl, 3,7,11 -Trimethyldodecyl, 3,7,11,15-tetrame Ruhekisadeshiru, hexyl 3,5,5-trimethyl, 2,3,4-trimethylpentane-3-yl, 2,3,4,6-pentamethylheptane-3-yl, isostearyl and the like.
また、式（１）で表わされる化合物の塩は、薬学上許容しうる塩であればよく、例えば、リチウム塩、ナトリウム塩、カリウム塩等のアルカリ金属塩、カルシウム塩、マグネシウム塩等のアルカリ土類金属塩、トリメチルアミン、トリエチルアミン等のアルキルアミン塩及び4級アンモニウム塩、トリエタノールアミン、ジエタノールアミン、モノエタノールアミン等のアルカノールアミン塩又は、リジン、ヒスチジン、アルギニン等アミノ酸塩が挙げられる。 The salt of the compound represented by the formula (1) may be any salt that is pharmaceutically acceptable. For example, an alkali metal salt such as a lithium salt, a sodium salt, or a potassium salt, an alkaline earth such as a calcium salt, or a magnesium salt. Metal salt, alkylamine salts such as trimethylamine and triethylamine and quaternary ammonium salts, alkanolamine salts such as triethanolamine, diethanolamine and monoethanolamine, or amino acid salts such as lysine, histidine and arginine.
本発明における式（１）で表わされる化合物は、何れも公知化合物であり、公知の方法により製造することができる。例えば１，３−ジアルキルグリセロールをリン酸エステル化し、必要に応じて適宜上記の塩を形成するようなアルカリで中和することにより得ることができる。リン酸エステル化試薬としては、例えばオキシ塩化リン、三塩化リン、五塩化リン、ポリリン酸、水と無水リン酸、リン酸と無水リン酸等を用いることができる（実験化学講座１，有機化合物の合成I，ｐ２０６−２１０，化学同人社）。得られた化合物は、適宜公知の方法により分離精製を行ってもよい。尚、１，３−ジアルキルグリセロールは、公知化合物であり、その原料であるアルキルグリシジルエーテルは公知の方法により製造することができ（特開昭56-63974号公報）、例えば、アルキルグリシジルエーテルとアルコールとの適当な酸又は塩基の存在下の反応により得ることができる。 The compounds represented by the formula (1) in the present invention are all known compounds and can be produced by a known method. For example, it can be obtained by converting 1,3-dialkylglycerol into a phosphoric ester and neutralizing with an alkali that appropriately forms the above-mentioned salt if necessary. Examples of the phosphoric acid esterifying reagent include phosphorus oxychloride, phosphorus trichloride, phosphorus pentachloride, polyphosphoric acid, water and phosphoric anhydride, phosphoric acid and phosphoric anhydride (Experimental Chemistry Course 1, Organic Compounds) Synthesis I, p206-210, Chemical Dojinsha). The obtained compound may be appropriately separated and purified by a known method. 1,3-dialkylglycerol is a known compound, and alkyl glycidyl ether as a raw material thereof can be produced by a known method (Japanese Patent Laid-Open No. 56-63974). For example, alkyl glycidyl ether and alcohol In the presence of a suitable acid or base.
後記実施例のように、本発明の式（１）で表わされる化合物又はその塩は、ヒト表皮ケラチノサイトを接着させたコラーゲンゲルに対して収縮作用を示すことから、ケラチノサイト収縮作用があるといえる。
従って、式（１）で表わされる化合物又はその塩は、ケラチノサイト収縮剤を収縮させて毛穴を収縮させる毛穴収縮剤として使用することができ、ケラチノサイト収縮剤又は毛穴収縮剤を製造するために使用できる。そして、ケラチノサイト収縮剤及び毛穴収縮剤は、毛穴を目立たなくさせる効果を発揮する医薬部外品、化粧品として使用可能である。
Since the compound represented by the formula (1) of the present invention or a salt thereof exhibits a contracting action on a collagen gel to which human epidermal keratinocytes are adhered as in Examples described later, it can be said that it has a keratinocyte contracting action.
Therefore, the compound represented by the formula (1) or a salt thereof can be used as a pore shrinkage agent that shrinks pores by shrinking a keratinocyte shrinkage agent, and can be used to produce a keratinocyte shrinkage agent or a pore shrinkage agent. . The keratinocyte shrinkage agent and pore shrinkage agent can be used as quasi-drugs and cosmetics that exhibit the effect of making pores inconspicuous.
本発明のケラチノサイト収縮剤又は毛穴収縮剤を医薬部外品や化粧料として用いる場合は、皮膚外用剤、洗浄剤、メイクアップ化粧料等とすることができ、使用方法に応じて、ローション、乳液、ゲル、クリーム、軟膏剤、粉末、顆粒等の種々の剤型で提供することができる。このような種々の剤型の医薬部外品や化粧料は、本発明の式（１）で表わされる化合物又はその塩を単独で、又は医薬部外品、皮膚化粧料及び洗浄料に配合される、油性成分、保湿剤、粉体、色素、乳化剤、可溶化剤、洗浄剤、紫外線吸収剤、増粘剤、薬剤（例えば、抗炎症剤、殺菌剤、酸化防止剤、ビタミン類等）、香料、樹脂、防腐剤、植物抽出物、アルコール類等を適宜組み合わせることにより調製することができる。
当該医薬部外品、化粧料中の本発明の式（１）で表わされる化合物又はその塩の含有量は、一般的に０．００１〜２０質量％とするのが好ましく、０．０１〜５質量％とするのがより好ましい
When the keratinocyte shrinkage agent or pore shrinkage agent of the present invention is used as a quasi-drug or cosmetic, it can be used as an external preparation for skin, a cleaning agent, a makeup cosmetic, or the like. Depending on the method of use, lotion, emulsion , Gels, creams, ointments, powders, granules and the like. Such quasi-drugs and cosmetics in various dosage forms are blended with the compound represented by the formula (1) of the present invention or a salt thereof alone or in quasi-drugs, skin cosmetics and cleansing agents. Oil components, moisturizers, powders, pigments, emulsifiers, solubilizers, detergents, UV absorbers, thickeners, drugs (eg anti-inflammatory agents, bactericides, antioxidants, vitamins, etc.), It can be prepared by appropriately combining flavors, resins, preservatives, plant extracts, alcohols and the like.
The content of the compound represented by the formula (1) of the present invention or a salt thereof in the quasi drug or cosmetic is generally preferably 0.001 to 20% by mass, and preferably 0.01 to 5%. It is more preferable to set it as the mass%.
製造例１：１−ｎ−テトラデシル−３−エチルグリセリル−２−リン酸アルギニン塩（化合物１）の製造
1-n-テトラデシルグリシジルエーテルを、特開昭56-63974号公報記載の方法に準じて得た。
エタノール851.8g(18.5mol)中に、窒素気流下、ナトリウムエトキシド30gを投入し、80℃に昇温した後、テトラデシルグリシジルエーテル500g(1.85mol)を滴下した。同温度にて18時間攪拌した。その後、エタノールを留去し、85％リン酸10.8gを投入し、3回水洗した。水洗後、減圧蒸留して、1-n-テトラデシル-3-エチルグリセロール446g（収率76.2%）を得た。
トルエン200mlにオキシ塩化リン232g（1.51mol）を溶解し、窒素雰囲気下、10℃以下に冷却したのち、1-n-テトラデシル-3-エチルグリセロール400.0g（1.26mol）及びトルエン400mlの混合溶液を滴下し、更に、トルエチルアミン140.6g（1.39mol）及びトルエン100mlの混合溶液を30分間かけて滴下した。同温度にて4時間攪拌後、水800gを徐々に投入し、50℃にて1時間攪拌した。トルエン、イソプロピルアルコールを加え、水層を分離後、上層を洗浄し、溶媒留去して、無色透明油状物511gを得た。このうち、200gをエタノール-ヘキサン混合溶媒に溶解し、L-アルギニン86.5g(0.496mol)を加え、60℃にて均一になるまで攪拌後、冷却して、アセトン中に投入し、析出した結晶をろ過後、減圧乾燥して1-n-テトラデシル-3-エチルグリセリル-2-リン酸アルギニン塩266g（収率94%）（化合物１）を得た。
Production Example 1: Production of 1-n-tetradecyl-3-ethylglyceryl-2-phosphate arginine salt (Compound 1)
1-n-Tetradecylglycidyl ether was obtained according to the method described in JP-A-56-63974.
In 851.8 g (18.5 mol) of ethanol, 30 g of sodium ethoxide was added under a nitrogen stream and the temperature was raised to 80 ° C., and then 500 g (1.85 mol) of tetradecyl glycidyl ether was added dropwise. Stir at the same temperature for 18 hours. Thereafter, ethanol was distilled off, 10.8 g of 85% phosphoric acid was added, and the mixture was washed with water three times. After washing with water and distillation under reduced pressure, 446 g (yield 76.2%) of 1-n-tetradecyl-3-ethylglycerol was obtained.
Dissolve 232 g (1.51 mol) of phosphorus oxychloride in 200 ml of toluene, cool to 10 ° C or less under a nitrogen atmosphere, and then add 400.0 g (1.26 mol) of 1-n-tetradecyl-3-ethylglycerol and 400 ml of toluene to a mixed solution. Further, a mixed solution of 140.6 g (1.39 mol) of toluethylamine and 100 ml of toluene was dropped over 30 minutes. After stirring at the same temperature for 4 hours, 800 g of water was gradually added and stirred at 50 ° C. for 1 hour. Toluene and isopropyl alcohol were added and the aqueous layer was separated. The upper layer was washed and the solvent was distilled off to obtain 511 g of a colorless transparent oil. Of these, 200 g was dissolved in an ethanol-hexane mixed solvent, 86.5 g (0.496 mol) of L-arginine was added, stirred at 60 ° C. until uniform, cooled, poured into acetone, and precipitated crystals After filtration, the residue was dried under reduced pressure to obtain 266 g of 1-n-tetradecyl-3-ethylglyceryl-2-phosphate arginine salt (yield 94%) (Compound 1).
IR（cm-1,ATR法）：3159,2922,2853,1632, 1110,1053,919
1H-NMR(D2O,ppm)：0.67-1.73(m,32H),3.03(t,J=6Hz,2H),3.28-3.59(m,11H),4.11(m,1H)
IR (cm −1 , ATR method): 3159,2922,2853,1632, 1110,1053,919
1 H-NMR (D 2 O, ppm): 0.67-1.73 (m, 32H), 3.03 (t, J = 6Hz, 2H), 3.28-3.59 (m, 11H), 4.11 (m, 1H)
製造例２：１−ｎ−ヘキサデシル−３−エチルグリセリル−２−リン酸アルギニン塩（化合物２）の製造
1-n-テトラデシル-3-エチルグリセロールに代えて1-n-ヘキサデシル-3-エチルグリセロール1g（2.68mmol）を用い、製造例１と同様に製造を行い、1-n-ヘキサデシル-3-エチルグリセリル-2-リン酸アルギニン塩0.80g（収率63%）（化合物２）を得た。尚、1-n-ヘキサデシル-3-エチルグリセロールは、1-n-ヘキサデシルグリシジルエーテル及びエタノールを用いて製造例１と同様に合成した。
Production Example 2: Production of 1-n-hexadecyl-3-ethylglyceryl-2-phosphate arginine salt (Compound 2)
1-n-hexadecyl-3-ethylglycerol was used instead of 1-n-hexadecyl-3-ethylglycerol 1 g (2.68 mmol), and the same production as in Production Example 1 was carried out. 0.80 g (yield 63%) of glyceryl-2-phosphate arginine salt (Compound 2) was obtained. 1-n-hexadecyl-3-ethylglycerol was synthesized in the same manner as in Production Example 1 using 1-n-hexadecylglycidyl ether and ethanol.
IR（cm-1,ATR法）：3160,2922,2853,1632, 1110,1053,919
1H-NMR(D2O,ppm)：0.66-1.73(m,40H),3.03(t,J=6Hz,2H),3.28-3.59(m,11H),4.10(m,1H)
IR (cm −1 , ATR method): 3160,2922,2853,1632, 1110,1053,919
1 H-NMR (D 2 O, ppm): 0.66-1.73 (m, 40H), 3.03 (t, J = 6Hz, 2H), 3.28-3.59 (m, 11H), 4.10 (m, 1H)
製造例３：１−ｉ−オクタデシル−３−ブチルグリセリル−２−リン酸アルギニン塩（化合物３）の製造
1-n-テトラデシル-3-エチルグリセロールに代えて1-i-オクタデシル-3-ブチルグリセロール5g（12.5mmol）を用い、製造例１と同様に製造を行い、1-i-オクタデシル-3-ブチルグリセリル-2-リン酸アルギニン塩3.49g（収率56%）（化合物３）を得た。尚、1-i-オクタデシル-3-ブチルグリセロールは、1-i-オクタデシルグリシジルエーテル及びブタノールを用いて製造例１と同様に合成した。
Production Example 3: Production of 1-i-octadecyl-3-butylglyceryl-2-phosphate arginine salt (Compound 3)
Using 1-i-octadecyl-3-butylglycerol 5 g (12.5 mmol) instead of 1-n-tetradecyl-3-ethylglycerol, production was carried out in the same manner as in Production Example 1, and 1-i-octadecyl-3-butyl was produced. 3.49 g (56% yield) of glyceryl-2-phosphate arginine salt (Compound 3) was obtained. 1-i-octadecyl-3-butylglycerol was synthesized in the same manner as in Production Example 1 using 1-i-octadecylglycidyl ether and butanol.
IR（cm-1,ATR法）：3160,2922,2853,1632, 1110,1053,919
1H-NMR(D2O,ppm)：0.65-1.73(m,42H),3.02(t,J=6Hz,2H),3.28-3.59(m,11H),4.10(m,1H)
IR (cm −1 , ATR method): 3160,2922,2853,1632, 1110,1053,919
1 H-NMR (D 2 O, ppm): 0.65-1.73 (m, 42H), 3.02 (t, J = 6Hz, 2H), 3.28-3.59 (m, 11H), 4.10 (m, 1H)
製造例４：１−ｉ−オクタデシル−３−エチルグリセリル−２−リン酸アルギニン塩（化合物４）の製造
1-n-テトラデシル-3-エチルグリセロールに代えて1-i-オクタデシル-3-エチルグリセロール2g（5.37mmol）を用い、製造例１と同様に製造を行い、1-i-オクタデシル-3-エチルグリセリル-2-リン酸アルギニン塩2.0g（収率60%）（化合物４）を得た。尚、１-i-オクタデシル-3-エチルグリセロールは、1-i-オクタデシルグリシジルエーテル及びエタノールを用いて得た。
Production Example 4: Production of 1-i-octadecyl-3-ethylglyceryl-2-phosphate arginine salt (Compound 4)
1-i-octadecyl-3-ethylglycerol was used instead of 1-n-tetradecyl-3-ethylglycerol, and 2 g (5.37 mmol) of 1-i-octadecyl-3-ethylglycerol was used. 2.0 g (yield 60%) of glyceryl-2-phosphate arginine salt (Compound 4) was obtained. 1-i-octadecyl-3-ethylglycerol was obtained using 1-i-octadecylglycidyl ether and ethanol.
IR（cm-1,ATR法）：3160,2922,2853,1632, 1110,1053,919
1H-NMR(D2O,ppm)：0.67-1.73(m,40H),3.03(t,J=6Hz,2H),3.28-3.60(m,11H),4.11(m,1H)
IR (cm −1 , ATR method): 3160,2922,2853,1632, 1110,1053,919
1 H-NMR (D 2 O, ppm): 0.67-1.73 (m, 40H), 3.03 (t, J = 6Hz, 2H), 3.28-3.60 (m, 11H), 4.11 (m, 1H)
製造例５：１−ｎ−オクタデシル−３−ブチルグリセリル−２−リン酸アルギニン塩（化合物５）の製造
1-n-テトラデシル-3-エチルグリセロールに代えて1-n-オクタデシル-3-ブチルグリセロール5g（12.5mmol）を用い、製造例１と同様に製造を行い、1-n-オクタデシル-3-ブチルグリセリル-2-リン酸アルギニン塩3.8g（収率61%）（化合物５）を得た。尚、1-n-オクタデシル-3-ブチルグリセロールは、1-n-オクタデシルグリシジルエーテル及びブタノールを用いて製造例１と同様に合成した。
Production Example 5: Production of 1-n-octadecyl-3-butylglyceryl-2-phosphate arginine salt (Compound 5)
1-n-octadecyl-3-butylglycerol was used instead of 1-n-octadecyl-3-butylglycerol, and 5 g (12.5 mmol) was used. 3.8 g (61% yield) of glyceryl-2-phosphate arginine salt (Compound 5) was obtained. 1-n-octadecyl-3-butylglycerol was synthesized in the same manner as in Production Example 1 using 1-n-octadecylglycidyl ether and butanol.
IR（cm-1,ATR法）：3159,2922,2853,1632, 1110,1053,919
1H-NMR(D2O,ppm)：0.65-1.73(m,42H),3.03(t,J=6Hz,2H),3.28-3.59(m,11H),4.09(m,1H)
IR (cm −1 , ATR method): 3159,2922,2853,1632, 1110,1053,919
1 H-NMR (D 2 O, ppm): 0.65-1.73 (m, 42H), 3.03 (t, J = 6Hz, 2H), 3.28-3.59 (m, 11H), 4.09 (m, 1H)
実施例１：ケラチノサイト収縮能
Ｉ型コラーゲン（セルマトリックスType-IA：新田ゼラチン）、MCDB153
培地（SIGMA：5倍濃度）、20mM HEPES（DOJINDO）及び精製水を氷冷しながらよく混合した後、24穴プレート（ファルコン）に各ウェル500μＬずつ注入し、インキュベーターで37℃に加温しゲル化させた。得られたコラーゲンゲルにケラチノサイト用培地（Epi Life：クラボウ）を用いてケラチノサイト（HEKn：Cascade Biologics）を2×104 cells/cm2で1mＬずつ播種し、24時間培養した後、スクレーパーを用いてコラーゲンゲルを培養皿から剥離した。
その直後、１０ｍＭ水溶液に調製した各被験物質（化合物１〜５）を１μＬずつ添加した。添加１時間後、ミノルタ707-siカメラ、50Macroレンズを用い、収縮の様子を撮影した。写真現像後、収縮環をＯＨＰ用紙に写し取り、画像解析ソフトImage-Pro PLUS（Media Cybanetics社）により収縮環内の面積を求め、コントロール（ゲル剥離のみ）を１００として収縮率（％）を求めた。
Example 1: Keratinocyte contractility I type collagen (cell matrix Type-IA: Nitta Gelatin), MCDB153
Medium (SIGMA: 5 times concentration), 20 mM HEPES (DOJINDO) and purified water are mixed well while cooling with ice, and then 500 μL of each well is injected into a 24-well plate (Falcon) and heated to 37 ° C. in an incubator. Made it. Keratinocytes (HEKn: Cascade Biologics) are seeded at 2 × 10 4 cells / cm 2 at 1 × L using the keratinocyte medium (Epi Life: Kurabo Industries) on the obtained collagen gel, cultured for 24 hours, and then scrapered. The collagen gel was peeled from the culture dish.
Immediately thereafter, 1 μL of each test substance (compounds 1 to 5) prepared in a 10 mM aqueous solution was added. One hour after the addition, the contraction was photographed using a Minolta 707-si camera and a 50 Macro lens. After photo-development, copy the shrink ring onto OHP paper, determine the area inside the shrink ring using image analysis software Image-Pro PLUS (Media Cybanetics), and obtain the shrinkage rate (%) with control (only gel peeling) as 100. It was.
表１から明らかなように化合物１〜５は優れたケラチノサイト収縮作用を有し、優れた毛穴収縮作用を有していると考えられる。 As is apparent from Table 1, compounds 1 to 5 have an excellent keratinocyte contracting action and are considered to have an excellent pore contracting action.
式（１）で表わされる化合物のうち化合物１を用いて常法により調製した処方例１を下記に示す。
処方例１
化合物１ ２．０％
グリセリン ５．０％
ジプロピレングリコール ４．０％
ポリオキシエチレンイソセチルエーテル
（２０ＥＯ） １．０％
チョウジエキス １．０％
エタノール ８．０％
防腐剤 適量
香料 適量
緩衝剤 適量
精製水 バランス
Formulation Example 1 prepared by a conventional method using Compound 1 among the compounds represented by Formula (1) is shown below.
Formulation Example 1
Compound 1 2.0%
Glycerin 5.0%
Dipropylene glycol 4.0%
Polyoxyethylene isocetyl ether
(20EO) 1.0%
Clove extract 1.0%
Ethanol 8.0%
Preservative Appropriate amount Perfume Appropriate amount Buffer agent Appropriate amount Purified water Balance
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