JP2010037204A - セラミド産生促進剤 - Google Patents
セラミド産生促進剤 Download PDFInfo
- Publication number
- JP2010037204A JP2010037204A JP2008197959A JP2008197959A JP2010037204A JP 2010037204 A JP2010037204 A JP 2010037204A JP 2008197959 A JP2008197959 A JP 2008197959A JP 2008197959 A JP2008197959 A JP 2008197959A JP 2010037204 A JP2010037204 A JP 2010037204A
- Authority
- JP
- Japan
- Prior art keywords
- group
- salt
- ceramide
- ceramide production
- compound
- 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
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 title claims abstract description 37
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 title claims abstract description 37
- 229940106189 ceramide Drugs 0.000 title claims abstract description 37
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 title claims abstract description 37
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 27
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 125000002252 acyl group Chemical group 0.000 claims abstract description 5
- 239000004480 active ingredient Substances 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 239000002537 cosmetic Substances 0.000 abstract description 11
- 230000001737 promoting effect Effects 0.000 abstract description 8
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- -1 2-heptylundecyl group Chemical group 0.000 description 32
- 239000003814 drug Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 229940125904 compound 1 Drugs 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- BLTCBVOJNNKFKC-QUDYQQOWSA-N N-acetylsphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@H](CO)NC(C)=O BLTCBVOJNNKFKC-QUDYQQOWSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 201000008482 osteoarthritis Diseases 0.000 description 3
- 208000028169 periodontal disease Diseases 0.000 description 3
- 229920000137 polyphosphoric acid Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- AHMMVDCKGMWVDM-VWMHFEHESA-N (2s)-2-amino-5-(diaminomethylideneamino)pentanoic acid;[2-hydroxy-3-(2-octyldodecoxy)propyl] dihydrogen phosphate Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.CCCCCCCCCCC(CCCCCCCC)COCC(O)COP(O)(O)=O AHMMVDCKGMWVDM-VWMHFEHESA-N 0.000 description 2
- VJVVVUYVGDRZCU-VWMHFEHESA-N (2s)-2-amino-5-(diaminomethylideneamino)pentanoic acid;[3-(2-heptylundecoxy)-2-hydroxypropyl] dihydrogen phosphate Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.CCCCCCCCCC(CCCCCCC)COCC(O)COP(O)(O)=O VJVVVUYVGDRZCU-VWMHFEHESA-N 0.000 description 2
- GBXRUYNQDDTQQS-UHFFFAOYSA-N 1-O-dodecylglycerol Chemical compound CCCCCCCCCCCCOCC(O)CO GBXRUYNQDDTQQS-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000008035 Back Pain Diseases 0.000 description 2
- 208000010392 Bone Fractures Diseases 0.000 description 2
- 208000008930 Low Back Pain Diseases 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 150000001483 arginine derivatives Chemical class 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical class OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 2
- OKNQUFCJURSTBR-UHFFFAOYSA-L dipotassium;[2-hydroxy-3-(12-methylheptadecoxy)propyl] phosphate Chemical compound [K+].[K+].CCCCCC(C)CCCCCCCCCCCOCC(O)COP([O-])([O-])=O OKNQUFCJURSTBR-UHFFFAOYSA-L 0.000 description 2
- WDVPBYJAMGJZBV-UHFFFAOYSA-L disodium;(3-dodecoxy-2-hydroxypropyl) phosphate Chemical compound [Na+].[Na+].CCCCCCCCCCCCOCC(O)COP([O-])([O-])=O WDVPBYJAMGJZBV-UHFFFAOYSA-L 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000006882 induction of apoptosis Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000002674 ointment Substances 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
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- NWOPIWLNGYLZCJ-GMUIIQOCSA-M sodium [(2R)-3-hexadecanoyloxy-2-hydroxypropyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)COP(O)([O-])=O NWOPIWLNGYLZCJ-GMUIIQOCSA-M 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- GGUNZNKVFQSXNE-VWMHFEHESA-N (2s)-2-amino-5-(diaminomethylideneamino)pentanoic acid;(2-hydroxy-3-tetradecoxypropyl) dihydrogen phosphate Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.CCCCCCCCCCCCCCOCC(O)COP(O)(O)=O GGUNZNKVFQSXNE-VWMHFEHESA-N 0.000 description 1
- JWFWSOKSCFQZAY-VWMHFEHESA-N (2s)-2-amino-5-(diaminomethylideneamino)pentanoic acid;[2-hydroxy-3-(16-methylheptadecoxy)propyl] dihydrogen phosphate Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N.CC(C)CCCCCCCCCCCCCCCOCC(O)COP(O)(O)=O JWFWSOKSCFQZAY-VWMHFEHESA-N 0.000 description 1
- 208000002679 Alveolar Bone Loss Diseases 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Chemical group CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 102000011971 Sphingomyelin Phosphodiesterase Human genes 0.000 description 1
- 108010061312 Sphingomyelin Phosphodiesterase Proteins 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 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 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000003788 bath preparation Substances 0.000 description 1
- 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 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001783 ceramides Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000003074 decanoyl 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(*)=O 0.000 description 1
- 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 1
- 238000006731 degradation reaction Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- PRJCIONZFSNYAE-UHFFFAOYSA-L disodium;(2-hydroxy-3-octadecoxypropyl) phosphate Chemical compound [Na+].[Na+].CCCCCCCCCCCCCCCCCCOCC(O)COP([O-])([O-])=O PRJCIONZFSNYAE-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 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 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
- 150000002169 ethanolamines Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 230000003752 improving hair Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
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- 125000000400 lauroyl group Chemical group O=C([*])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 1
- 239000010410 layer Substances 0.000 description 1
- 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 1
- 239000007788 liquid Substances 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 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 1
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- 230000003020 moisturizing effect Effects 0.000 description 1
- 125000001419 myristoyl group Chemical group O=C([*])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 1
- 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 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 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 1
- 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 1
- 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 1
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- 125000001312 palmitoyl group Chemical group O=C([*])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 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 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 1
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- 150000003904 phospholipids Chemical class 0.000 description 1
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- 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
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- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
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- 230000037394 skin elasticity Effects 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
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- 125000003696 stearoyl group Chemical group O=C([*])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 1
- 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 1
- 238000003756 stirring Methods 0.000 description 1
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- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
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- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- 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 1
- 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 1
- 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 1
- 229910001868 water Inorganic materials 0.000 description 1
Abstract
Description
従って、セラミドの産生を促進する物質には、動物細胞の増殖抑制、分化誘導、アポトーシスを誘導するなどの効果が期待でき、ひいては炎症性疾患、悪性腫瘍など、細胞の増殖あるいは分化の異常に起因する疾患に対する治療効果が期待できると考えられている(非特許文献1)。
更に、セラミドには、毛髪のハリ、コシの付与及び感触改善作用があることも報告され(特許文献3)、セラミド産生促進物質には、斯かる効果も期待できる。
で表される化合物又はその塩を有効成分とするセラミド産生促進剤に係るものである。
R1の具体例としては、オクチル基、ノニル基、デシル基、ウンデシル基、ドデシル基、トリデシル基、テトラデシル基、ペンタデシル基、ヘキサデシル基、ヘプタデシル基、オクタデシル基、ノナデシル基、イコシル基、ドコシル基、トリコシル基、テトラコシル基、2−ヘプチルウンデシル基、イソステアリル基、12−メチルヘプタデシル基、2−オクチルドデシル基、3,7−ジメチルオクチル基、3,7−ジメチルオクタン−3−イル基、2−ヘキシルデシル基、3,7,11−トリメチルドデシル基、1,1,3,3−テトラメチルブチル基、3,7,11,15−テトラメチルヘキサデシル基、3,5,5−トリメチルヘキシル基、1−イソプロピル−1,2−ジメチルプロピル基、1−イソプロピル−1,2,4,4−テトラメチルペンチル基等が挙げられ、
このうち、n−ドデシル基、n−テトラデシル基、n−オクタデシル基、i-オクタデシル基、2−ヘプチルウンデシル基、イソステアリル基、12−メチルヘプタデシル基、2−オクチルドデシル基等が好ましく、n−ドデシル基、n−テトラデシル基、n−オクタデシル基、2−ヘプチルウンデシル基、イソステアリル基、12−メチルヘプタデシル基、2−オクチルドデシル基、ヘキサデシル基がより好ましい。
例えば1−ドデシ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が(実験化学講座1,有機化合物の合成I,p206−210,化学同人社)、ポリリン酸が好ましい。
得られた化合物は、適宜公知の方法により分離精製を行うことができる。
従って、本発明の式(1)で表される化合物又はその塩は、セラミド産生促進剤として使用でき、またセラミド産生促進剤を製造するために使用できる。当該セラミド産生促進剤は、動物細胞の増殖抑制、分化誘導、アポトーシスの誘導等の効果が期待できることから、炎症性疾患、悪性腫瘍など、細胞の増殖あるいは分化の異常に起因する疾患を予防又は治療するための医薬品、医薬部外品等として使用でき(前記非特許文献1)、また、骨粗鬆症、骨折、腰痛、リウマチなどの骨関節疾患の予防又は改善、歯周病の予防又は改善のための医薬品、医薬部外品等として使用できる(前記特許文献1及び2)。また更に、毛髪にハリ、コシを付与したり毛髪の感触を改善するための医薬部外品、化粧品として使用できる(前記特許文献3)。当該セラミド産生促進剤は、セラミド産生促進をコンセプトとし、必要に応じてその旨を表示した医薬部外品、化粧品として使用することもできる。
該製剤中の本発明の式(1)で表される化合物又はその塩の含有量は、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。
また、本発明のセラミド産生促進剤を医薬品として使用する場合、成人1人当たりの1日の投与量は、本発明の式(1)で表される化合物又はその塩として、例えば0.1〜2000mgとすればよく、1〜500mgとするのが好ましい。
当該医薬部外品、化粧料中の本発明の式(1)で表される化合物又はその塩の含有量は、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。
(1)1−ドデシルグリセロール−3−リン酸ジナトリウム塩(化合物1)
(2)1−テトラデシルグリセロール−3−リン酸モノアルギニン塩(化合物2)
(8)1−パルミトイル−sn−グリセロ−3−リン酸ナトリウム塩(化合物8)
ALEXIS社から購入したものを使用
<培養条件>
正常ヒト表皮角化細胞(NHEK(F))をEpiLife-KG2(KURABO社)6well Plate に播種し、コンフルエントの状態になるまで培養した。その後、EpiLife-KG2(増殖添加因子無し)に換え、上記化合物1〜8及び比較化合物1の各溶液(化合物8は1mM、それ以外は5mM)、control溶液(化合物3、9は50%エタノール、化合物8は80%エタノール、それ以外は10%エタノール)を1%量添加した。3日間培養した後、各々の細胞を1wellごとに回収した。
回収した細胞からBligh and Dyer法によって脂質を抽出した。抽出液を窒素乾固した後、クロロホルム、メタノール、に再溶解したものを脂質サンプルとした。なお、タンパク量はBCA法により定量した。
抽出した脂質中を薄膜クロマトグラフィー(TLC)でクロロホルム:メタノール:酢酸=190:9:1で2回水平展開した。硫酸銅液をスプレーで噴霧した後、ホットプレートで焼き付けセラミドを検出した。その後、各々の蛋白量で割り、セラミド量とした。結果を表1に示す。表の数値はControlのセラミド量を1とした時の相対値を示す。
Claims (2)
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US13/001,701 US8440645B2 (en) | 2008-07-31 | 2009-07-30 | Ceramide production promoter |
CN2009801205557A CN102438629A (zh) | 2008-07-31 | 2009-07-30 | 神经酰胺产生促进剂 |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013053109A (ja) * | 2011-09-05 | 2013-03-21 | Teikyo Univ | リン脂質結合型dha増加剤 |
JP2013053110A (ja) * | 2011-09-05 | 2013-03-21 | Teikyo Univ | 経口投与剤 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992021323A1 (en) * | 1991-05-31 | 1992-12-10 | The Procter & Gamble Company | Use of lysophosphate acids for the treatment of skin wrinkles |
JPH0867621A (ja) * | 1994-06-21 | 1996-03-12 | Advanced Sukin Res Kenkyusho:Kk | グリコサミノグリカン産生促進作用を有する皮膚活性化剤 |
JPH11139957A (ja) * | 1997-11-06 | 1999-05-25 | Nof Corp | 浴用剤及び浴用剤組成物 |
JP2001192315A (ja) * | 2000-01-07 | 2001-07-17 | Kao Corp | 皮膚弾力性改善剤 |
JP2002187817A (ja) * | 2000-10-12 | 2002-07-05 | Kao Corp | 毛穴収縮剤 |
JP2007119361A (ja) * | 2005-10-25 | 2007-05-17 | Nagase Chemtex Corp | ホスホリパーゼa2阻害剤 |
JP2008105975A (ja) * | 2006-10-24 | 2008-05-08 | Kao Corp | ケラチノサイト収縮剤 |
-
2008
- 2008-07-31 JP JP2008197959A patent/JP5527952B2/ja active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992021323A1 (en) * | 1991-05-31 | 1992-12-10 | The Procter & Gamble Company | Use of lysophosphate acids for the treatment of skin wrinkles |
JPH0867621A (ja) * | 1994-06-21 | 1996-03-12 | Advanced Sukin Res Kenkyusho:Kk | グリコサミノグリカン産生促進作用を有する皮膚活性化剤 |
JPH11139957A (ja) * | 1997-11-06 | 1999-05-25 | Nof Corp | 浴用剤及び浴用剤組成物 |
JP2001192315A (ja) * | 2000-01-07 | 2001-07-17 | Kao Corp | 皮膚弾力性改善剤 |
JP2002187817A (ja) * | 2000-10-12 | 2002-07-05 | Kao Corp | 毛穴収縮剤 |
JP2007119361A (ja) * | 2005-10-25 | 2007-05-17 | Nagase Chemtex Corp | ホスホリパーゼa2阻害剤 |
JP2008105975A (ja) * | 2006-10-24 | 2008-05-08 | Kao Corp | ケラチノサイト収縮剤 |
Non-Patent Citations (1)
Title |
---|
JPN7013002763; 新化粧品ハンドブック , 20061030, 512頁〜513頁, 日光ケミカルズ株式会社 外4社 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013053109A (ja) * | 2011-09-05 | 2013-03-21 | Teikyo Univ | リン脂質結合型dha増加剤 |
JP2013053110A (ja) * | 2011-09-05 | 2013-03-21 | Teikyo Univ | 経口投与剤 |
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