JP5737888B2 - アトピー性皮膚炎治療剤 - Google Patents
アトピー性皮膚炎治療剤 Download PDFInfo
- Publication number
- JP5737888B2 JP5737888B2 JP2010198475A JP2010198475A JP5737888B2 JP 5737888 B2 JP5737888 B2 JP 5737888B2 JP 2010198475 A JP2010198475 A JP 2010198475A JP 2010198475 A JP2010198475 A JP 2010198475A JP 5737888 B2 JP5737888 B2 JP 5737888B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- atopic dermatitis
- phosphatidic acid
- cyclic phosphatidic
- therapeutic agent
- 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.)
- Active
Links
- 206010012438 Dermatitis atopic Diseases 0.000 title claims description 49
- 201000008937 atopic dermatitis Diseases 0.000 title claims description 49
- 238000011282 treatment Methods 0.000 title description 9
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 claims description 31
- 125000004122 cyclic group Chemical group 0.000 claims description 31
- 239000003814 drug Substances 0.000 claims description 26
- 229940124597 therapeutic agent Drugs 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 208000003251 Pruritus Diseases 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- 230000000699 topical effect Effects 0.000 claims description 7
- 150000001768 cations Chemical class 0.000 claims description 5
- 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 claims description 5
- 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 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 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 claims description 4
- 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 claims description 4
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 claims description 3
- -1 cyclic phospholipid Chemical class 0.000 description 36
- 208000024891 symptom Diseases 0.000 description 18
- 230000000694 effects Effects 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- LOTKRQAVGJMPNV-UHFFFAOYSA-N 1-fluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C([N+]([O-])=O)=C1 LOTKRQAVGJMPNV-UHFFFAOYSA-N 0.000 description 8
- 201000004624 Dermatitis Diseases 0.000 description 8
- 208000010668 atopic eczema Diseases 0.000 description 8
- 150000003431 steroids Chemical class 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 206010030113 Oedema Diseases 0.000 description 6
- 229920002674 hyaluronan Polymers 0.000 description 6
- 229960003160 hyaluronic acid Drugs 0.000 description 6
- 230000007803 itching Effects 0.000 description 6
- 150000003904 phospholipids Chemical class 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 102000011420 Phospholipase D Human genes 0.000 description 4
- 108090000553 Phospholipase D Proteins 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 230000002354 daily effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 230000003020 moisturizing effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010003645 Atopy Diseases 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 235000019271 petrolatum Nutrition 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229960005323 phenoxyethanol Drugs 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- 229940043375 1,5-pentanediol Drugs 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical group 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical group 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical compound CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
- 229940075529 glyceryl stearate Drugs 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- WCVRQHFDJLLWFE-UHFFFAOYSA-N pentane-1,2-diol Chemical compound CCCC(O)CO WCVRQHFDJLLWFE-UHFFFAOYSA-N 0.000 description 2
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- PQUXFUBNSYCQAL-UHFFFAOYSA-N 1-(2,3-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1F PQUXFUBNSYCQAL-UHFFFAOYSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-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
- 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 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
- 206010061218 Inflammation Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 240000001307 Myosotis scorpioides Species 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 206010040799 Skin atrophy Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000147083 Streptomyces chromofuscus Species 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000003788 bath preparation Substances 0.000 description 1
- IWWCATWBROCMCW-UHFFFAOYSA-N batyl alcohol Natural products CCCCCCCCCCCCCCCCCCOC(O)CO IWWCATWBROCMCW-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit 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
- 239000011230 binding agent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical group CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000003493 decenyl group Chemical group [H]C([*])=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
- 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
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229960000735 docosanol Drugs 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
- 239000002552 dosage form Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- 230000005722 itchiness Effects 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
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000010172 mouse model Methods 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
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 231100000957 no side effect Toxicity 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
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 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 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229940067631 phospholipid Drugs 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000036573 scar formation Effects 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940047670 sodium acrylate Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 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
- 230000003637 steroidlike Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical group C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000013519 translation Methods 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
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
好ましくは、本発明のアトピー性皮膚炎治療剤は、局所適用製剤である。
好ましくは、局所適用製剤は皮膚外用剤である。
好ましくは、本発明のアトピー性皮膚炎治療剤は、環状ホスファチジン酸を0.001〜1重量%含有する。
好ましくは、本発明のアトピー性皮膚炎治療剤は、アトピー性皮膚炎における掻痒感の改善剤として使用する。
式(I)で示される環状ホスファチジン酸(cPA)中のMは、水素原子又は対カチオンである。Mが対カチオンである場合の例としては、例えば、アルカリ金属原子、アルカリ土類金属原子、置換若しくは無置換アンモニウム基が挙げられる。アルカリ金属原子としては、例えば、リチウム、ナトリウム、カリウムなどが挙げられ、アルカリ土類金属原子としては、例えば、マグネシウム、カルシウムなどが挙げられる。置換アンモニウム基としては、例えば、ブチルアンモニウム基、トリエチルアンモニウム基、テトラメチルアンモニウム基などが挙げられる。
cPAの抗アレルギー効果について、DNFB誘発耳介浮腫およびダニ誘発によるアトピー性皮膚炎モデルを用いた評価(非特許文献1、2)を行った(実施例5、6)。ステロイド剤が効果を示すDNFB誘発耳介浮腫モデルに対しては濃度依存傾向はあるが有意の効果は認められなかった。一方、図2に示すように、ダニ誘発によるアトピー性皮膚炎モデルcPA投与群(0.004%濃度)は基剤群に対し明確な効果が認められたので、アトピー性皮膚炎の症状を呈するボランティア(7名)に、製造例1又は製造例2の処方からなる外用剤を、1日2〜3回、1ヶ月間、毎日塗布してもらったところ、全例に症状の軽快、改善が認められた(実施例1〜4)。
成分 含有割合(重量%)
水 71.85
エタノール 3
ミリスチン酸オクチルドデシル 5
ペンチレングリコール 5
PEG−32 5
ステアリン酸グリセリル 5
グリセリン 5
環状フォスファチジン酸 0.05
フェノキシエタノール 0.1
成分 含有割合(重量%)
水 48.85
エタノール 3
ミリスチン酸オクチルドデシル 7
ペンチレングリコール 7
PEG−32 7
ステアリン酸グリセリル 7
グリセリン 5
環状フォスファチジン酸 0.05
フェノキシエタノール 0.1
白色ワセリン 15
女性61歳、毎年春に目の周りに痒みと湿疹のアトピー性皮膚炎を惹起する成人女性について、本剤(製造例2のクリーム剤で、環状ホスファチジン酸を含有)を毎日、朝、昼、夜と塗布し1ヶ月間観察した。本剤を使用していなかった過去には、毎年上記症状のアレギー症状が出現していた。1ヶ月の観察後に、症状は徐々に軽快し、ほぼ正常な皮膚層に回復していた。
女性45歳、暖かい季節において首のまわりにアトピー性の湿疹が出るため、本剤(製造例1の乳化剤で、環状ホスファチジン酸を含有)を毎日、朝と晩に塗布して約1ヶ月観察した。ほぼ観察期間終了時に、劇的に症状は消えてまた不日における湿疹や痒みも症状は治まり、そう痒感はの改善が認められた。
女性30歳、手のアレルギー性湿疹があり、製造例1の乳化剤を朝、昼、夜と毎日塗布した。塗布後2週間で症状は軽減した。更に1ヵ月後には回復した。
女性28歳、アトピー性皮膚炎で、製造例2のクリーム剤を朝、昼、夜と毎日塗布した。塗布後2週間で痒みの低減が認められた。また、症状は極めて良好状態に回復し、1ヶ月後にほぼ全快した。
エーテルにてマウスを麻酔し、剪毛した背部に0.5%DNFB/アセトン:オリーブ油(4:1)の100μl塗布を2日間連続行った(感作)。最初の感作から5日後と6日後に、0.2%DNFB/アセトン:オリーブ油(4:1)を右耳に20μl塗布した。被験物質としては、ビヒクル(50%エタノール)、0.004%cPA(式(I)においてRがペンタデシル基であるパルミトイルcPAと、 Rがヘプタデシル基であるステアロイルcPAとの混合物からなる、リゾホスファチジルコリンから誘導されるcPA)、0.04%cPA(上記)、又は0.025%デキサメタゾン(DEX)(陽性対照)を使用した。被験物質の投与は、惹起直後に、右耳介の両面に20μl(片耳10μl)塗布した。DNFB塗布前と惹起の3,24時間に耳介厚をマイクロメーター(ミツトヨ)を用いて測定した。この処理を3週間繰り返し行った。惹起後、経時的に耳の厚さを測り、惹起前の厚さと比較して浮腫率を算出した。
シェーバーで除毛した後、4%SDS水溶液150μlをマイクロピペットでBalb/c系雄性マウスの背部に滴下しながら、マイクロピペットのチップ裏部で均一に塗布した。約2〜3時間自然乾燥させ、アトピー性皮膚炎誘発試薬ビオスタAD(コナヒョウダニ由来)(100mg)をマイクロピペット裏部で、マウス背部に均一に塗布した。この処理を1週間に2〜3回のペースで行った。3週間、計9回の処理でアトピー性皮膚炎マウスを作製し、適時、水分蒸発量を測定した。
Claims (5)
- パルミトイル基を有する環状ホスファチジン酸又はその塩と、ステアロイル基を有する環状ホスファチジン酸又はその塩との混合物を有効成分とするアトピー性皮膚炎治療剤であって、環状ホスファチジン酸を0.001%〜0.004%含有し、アトピー性皮膚炎における掻痒感の改善剤として使用するアトピー性皮膚炎治療剤。
- 環状ホスファチジン酸が、リゾホスファチジルコリンから誘導される環状ホスファチジン酸である、請求項1又は2に記載のアトピー性皮膚炎治療剤。
- 局所適用製剤である、請求項1から3の何れかに記載のアトピー性皮膚炎治療剤。
- 局所適用製剤が皮膚外用剤である請求項4に記載のアトピー性皮膚炎治療剤。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010198475A JP5737888B2 (ja) | 2010-09-06 | 2010-09-06 | アトピー性皮膚炎治療剤 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010198475A JP5737888B2 (ja) | 2010-09-06 | 2010-09-06 | アトピー性皮膚炎治療剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012056853A JP2012056853A (ja) | 2012-03-22 |
JP5737888B2 true JP5737888B2 (ja) | 2015-06-17 |
Family
ID=46054382
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010198475A Active JP5737888B2 (ja) | 2010-09-06 | 2010-09-06 | アトピー性皮膚炎治療剤 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP5737888B2 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11452681B2 (en) | 2019-07-29 | 2022-09-27 | Orient Europharma Co., Ltd. | Cosmetic compositions to prevent and/or ameliorate skin aging and methods of applications |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10413559B2 (en) | 2013-01-28 | 2019-09-17 | Ochanomizu University | Method for treating demyelinating disease |
JP6189709B2 (ja) * | 2013-10-22 | 2017-08-30 | 株式会社ファンケル | 痒み抑制剤 |
JP6727596B1 (ja) | 2019-11-22 | 2020-07-22 | 国立大学法人お茶の水女子大学 | カルバリゾホスファチジン酸 |
JPWO2022114058A1 (ja) | 2020-11-26 | 2022-06-02 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5238965A (en) * | 1991-05-31 | 1993-08-24 | The Procter & Gamble Company | Methods of using lysophosphatidic acids for regulating skin wrinkles |
JPH11158057A (ja) * | 1997-12-03 | 1999-06-15 | Nof Corp | 浴用剤および浴用剤組成物 |
JP4876334B2 (ja) * | 2001-06-06 | 2012-02-15 | 日油株式会社 | ヒアルロン酸産生能増強剤およびその用途 |
CA2588183A1 (en) * | 2004-11-23 | 2006-08-10 | Wendy Bollinger Bollag | Methods and compositions for modulating keratinocyte function |
JP2009234931A (ja) * | 2008-03-26 | 2009-10-15 | Nof Corp | トランスグルタミナーゼ遺伝子発現促進剤および、その用途 |
JP2010202585A (ja) * | 2009-03-04 | 2010-09-16 | Sansho Kk | アトピー性皮膚炎治療剤 |
-
2010
- 2010-09-06 JP JP2010198475A patent/JP5737888B2/ja active Active
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11452681B2 (en) | 2019-07-29 | 2022-09-27 | Orient Europharma Co., Ltd. | Cosmetic compositions to prevent and/or ameliorate skin aging and methods of applications |
Also Published As
Publication number | Publication date |
---|---|
JP2012056853A (ja) | 2012-03-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7008988B2 (ja) | ソフト抗コリン作用性エステルの投与の方法および使用 | |
JP5737888B2 (ja) | アトピー性皮膚炎治療剤 | |
CA2919258C (en) | Formulations for epidermal repair | |
US20020010128A1 (en) | Treatment of hyperproliferative, inflammatory and related mucocutaneous disorders using inhibitors of mevalonate synthesis and metabolism | |
KR101514970B1 (ko) | 피토스핑고신-1-포스페이트 또는 그 유도체를 포함하는 아토피 또는 피부상처 치료 또는 예방용 조성물 | |
JP2010184903A (ja) | 外用医薬組成物 | |
JP2010202585A (ja) | アトピー性皮膚炎治療剤 | |
EP2135622B1 (en) | Compositions for providing an analgesic effect to the skin | |
JP4934304B2 (ja) | 鎮痒剤組成物 | |
EP3125865B1 (en) | Association of active ingredients for topical use in restructuring altered cutaneous barrier following to cutaneous diseases | |
EP2838509A1 (en) | Formulations and methods for treatment of inflammatory skin diseases | |
CA3223022A1 (en) | Use of mangosteen fruit shell extract in the preparation of a medicament for treating psoriasis | |
KR20180092256A (ko) | 민감성 피부용 보습 화장료 조성물 | |
US20110237593A1 (en) | Topical anti-pruritic compositions and methods of action of same | |
WO1999016435A1 (en) | Pharmaceutical compositions containing ricinoleic acid and their use in anti-inflammatory and analgesic therapy | |
JPWO2019221114A1 (ja) | ベタニンまたはその類似化合物を含む皮膚組織修復剤 | |
KR102691959B1 (ko) | 파모인산을 유효성분으로 포함하는 가려움증 억제용 조성물 | |
EP1747782A1 (en) | Products for topical application comprising lysophospholipids and fatty acids | |
WO2022153309A1 (en) | Topical composition | |
KR20150057014A (ko) | 강황 잎 추출물을 함유하는 여드름 개선용 화장료 조성물 | |
JP2024127663A (ja) | 皮膚の短鎖脂肪酸生成促進剤 | |
CN113272020A (zh) | 具有抗真菌特性的指甲组合物 | |
US8716294B2 (en) | Methods for treating inflammatory conditions | |
JP2000327571A (ja) | 抗かゆみ組成物 | |
WO2016061328A1 (en) | Topical composition |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130610 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140701 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140901 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20141007 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150106 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150217 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150204 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20150226 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150414 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150421 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5737888 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |