http://support.spring8.or.jp/Report_JSR/PDF_IAe_ALL/IAe_11B1793.pdf

2011B1793                          BL40B2ࣄࢺ⓶⭵࡜㢮ఝ࡞ゅᒙ⣽⬊㛫⬡㉁ᵓ㐀ࢆ᭷ࡍࡿ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝࡢ㛤Ⓨ
Development of Three-dimensional Cultured Human Skin Model with theIntercellular Lipid Structure of Stratum Corneum Similar to Human Skinᆏ ㈆ᚫ, ୰㛫 ‶㞝, ᒣୗ ┿⏤
Sadanori Ban, Mitsuo Nakama, Mayu Yamashita᪥ᮏ࣓ࢼ࣮ࢻ໬⢝ရ㻔ᰴ㻕⥲ྜ◊✲ᡤ Research Laboratories, Nippon Menard Cosmetic Co. Ltd.
ࣄࢺ⓶⭵࡜㢮ఝ࡞ゅᒙ⣽⬊㛫⬡㉁ᵓ㐀ࢆ᭷ࡍࡿ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝࡢ㛤Ⓨࡢ୍⎔࡜ࡋ࡚ࠊゅᒙ⣽⬊㛫⬡㉁ࡢ⤌⧊໬࡟ཬࡰࡍࣜࣥ⬡㉁⭷ᵓ㐀ࡢ㐪࠸࡟ࡘ࠸᳨࡚ウࡍࡿࡓࡵ࡟ࠊࣜࣥ⬡㉁ࡢ஧
ศᏊ⭷⢏Ꮚ࠿ࡽ࡞ࡿ࣏ࣜࢯ࣮࣒ࡲࡓࡣ༢ศᏊ⭷⢏Ꮚ࠿ࡽ࡞ࡿ⬡㉁࢚࣐ࣝࢩࣙࣥࢆ㐺⏝ࡋࠊᑠゅ㺃ᗈゅ X ⥺ᅇᢡᐇ㦂ࢆ⾜ࡗࡓࠋࡑࡢ⤖ᯝࠊ࣏ࣜࢯ࣮࣒ࡢ㐺⏝࡟࠾࠸࡚ࠊ⬡㉁࢚࣐ࣝࢩࣙࣥࡢ㐺⏝࡜ẚ࡭࡚ゅᒙ⣽⬊㛫⬡㉁ࡢ⤌⧊໬ࡀඃ఩࡟㉳ࡇࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋ࣮࣮࢟࣡ࢻ㸸 ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝࠊ⣽⬊㛫⬡㉁ࠊ࣏ࣜࢯ࣮࣒ࠊ࢚࣐ࣝࢩࣙࣥ
⫼ᬒ࡜◊✲┠ⓗ㸸⓶⭵ゅᒙ୰ࡢ⣽⬊㛫⬡㉁ࡣࠊࢭ࣑ࣛࢻࠊ⬡⫫㓟ࠊࢥࣞࢫࢸ࣮ࣟࣝࢆ୺࡞ᵓᡂᡂศ࡜ࡋ࡚࠾ࡾࠊእ⏺࠿ࡽࡢ่⃭࡟ᑐࡍࡿࣂࣜ࢔ᶵ⬟ࡢ⥔ᣢ࡟࠾࠸࡚㔜せ࡞ᙺ๭ࢆᯝࡓࡋ࡚࠸ࡿࠋ໬⢝ရ㛤Ⓨ࡟࠾࠸࡚ࡣࠊゅᒙ⣽⬊㛫⬡㉁ᵓ㐀ࡀࠊ໬⢝ရࡢᾐ㏱࡟ࡼࡾ࡝ࡢࡼ࠺࡞ᙳ㡪ࢆཷࡅࡿ࠿ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࡀ㔜せ࡛࠶ࡿࠋ⌧ᅾࠊື≀ࡢ௦᭰࡜ࡋ࡚ࠊ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝࢆ⏝࠸ࡓ⓶⭵ᾐ㏱ᛶヨ㦂ࡀᐇ᪋ࡉࢀ࡚࠸ࡿࡀࠊ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝ࡟࠾ࡅࡿ≀㉁ࡢ㏱㐣ᛶࡀࣄࢺ⓶⭵ࡼࡾࡶ࠾ࡼ
ࡑ 10 ಸ㧗࠸ࡇ࡜[1]ࠊࡑࡢ⌮⏤ࡢ୍ࡘ࡜ࡋ࡚ࠊ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝࡢゅᒙ⣽⬊㛫⬡㉁ࡢ࣓ࣛ
ࣛᵓ㐀ࡀ୙᏶඲࡛ࠊ⬡⁐ᛶࡢ≀㉁ࡀ⤖ᬗ໬ࡋ࡚࠸ࡿྍ⬟ᛶࡀ࠶ࡿࡇ࡜[2]➼ࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋᡃࠎ
ࡣࠊࡇࢀࡲ࡛ࡢㄢ㢟[3][4][5]࡟࠾࠸࡚ࠊ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝ࡬ࡢ༸㯤⏤᮶ࣇ࢛ࢫࣇ࢓ࢳࢪࣝࢥࣜࣥ㻔༸㯤 PC㻕࠶ࡿ࠸ࡣ኱㇋ PC ࣏ࣜࢯ࣮࣒ࡢ㐺⏝࡟ࡼࡗ࡚ࠊゅᒙ⣽⬊㛫⬡㉁ࡢ࣓ࣛࣛᵓ㐀ࡀࣄࢺ⓶⭵࡟㏆࡙ࡃࡇ࡜ࢆぢฟࡋ࡚࠸ࡿࠋ௒ᚋࡣࠊࣄࢺ⓶⭵࡟㏆࡙ࡅࡓ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝࢆᕷሙ࡟ᥦ౪ࡍࡿࡇ࡜ࢆ┠ᣦࡋࠊ࣏ࣜࢯ࣮࣒ࡢ㐺⏝࡟ࡼࡿゅᒙ⣽⬊㛫⬡㉁ᵓ㐀ࡢ⤌⧊໬࡟ࡘ࠸࡚ࡢ
ヲ⣽࡞᳨ウࢆ㐍ࡵ࡚࠸ࡃᚲせࡀ࠶ࡿ࡜⪃࠼ࡿࠋࡇࢀࡲ࡛ࡢㄢ㢟࡟࠾࠸࡚ࡣࠊࣜࣥ⬡㉁ࡢ஧ศᏊ⭷⢏Ꮚ࠿ࡽ࡞ࡿ࣏ࣜࢯ࣮࣒ࢆㄪ〇ࡋ࡚୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝ࡬㐺⏝ࡋࠊゅᒙ⣽⬊㛫⬡㉁ᵓ㐀ࡢ⤌⧊໬࡟ࡘ࠸᳨࡚ウࡋࡓࠋ୍⯡࡟࣏ࣜࢯ࣮࣒ࡣ⏕య⭷ࣔࢹࣝ࡜ࡋ࡚▱ࡽࢀ࡚࠸ࡿࠋ୍᪉ࠊࣜࣥ⬡㉁ࡢ༢ศᏊ⭷⢏Ꮚ࡛࠶ࡿ⬡㉁࢚࣐ࣝࢩࣙࣥࡣ
⾑₢࣏ࣜࢱࣥࣃࢡ㉁ࡢࢱࣥࣃࢡ㉁ࣇ࣮ࣜࣔࢹࣝ࡜ࡋ࡚ᗈࡃ◊✲ࡉࢀ࡚࠸ࡿࠋࡑࡇ࡛ᮏㄢ㢟࡟࠾࠸࡚ࡣࠊゅᒙ⣽⬊㛫⬡㉁ᵓ㐀ࡢ⤌⧊໬࡟ཬࡰࡍࣜࣥ⬡㉁⭷ᵓ㐀ࡢᙳ㡪࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡋࠊゅᒙ⣽⬊㛫⬡㉁ᵓ㐀ࡢ⤌⧊໬࡟ࡘ࠸࡚ࡢヲ⣽࡞᳨ウࢆ㐍ࡵ࡚࠸ࡃࡓࡵࡢ⛉Ꮫⓗ᰿ᣐ࡜࡞ࡿࢹ࣮ࢱࢆᚓࡿࡇ࡜ࢆ┠ⓗ࡜ࡋࡓࠋᐇ㦂㸸࣏ࣜࢯ࣮࣒ࡣ༸㯤 PC㻔COATSOME NC-50ࠊ᪥Ἔ㻕ࢆ⏝࠸࡚ࠊࣜࣥ⬡㉁⃰ᗘࡀ 0.5%࡜࡞ࡿࡼ࠺࡟
Bangham ἲ࡟࡚ㄪ〇ࡋࠊ࣓ࣥࣈࣛࣥࣇ࢕ࣝࢱ࣮㻔࣑࣏ࣜ࢔㻕ࢆ㏻ࡋ࡚⢏Ꮚᚄࢆㄪᩚࡋࡓࠋ⬡㉁࢚࣐
ࣝࢩࣙࣥࡣ༸㯤 PC㻔COATSOME NC-50ࠊ᪥Ἔ㻕5%ࠊ኱㇋Ἔ㻔኱㇋Ἔ YMࠊ᪥Ύ࢜࢖ࣜ࢜㻕5%ࠊMilli-Q
90%ࢆ㧗ᅽங໬ฎ⌮ࡋ࡚ㄪ〇ࡋࠊࣜࣥ⬡㉁⃰ᗘࡀ 0.5%࡜࡞ࡿࡼ࠺࡟ Milli-Q ࡛ᕼ㔘ࡋ࡚㐺⏝ࢧࣥࣉࣝ࡜ࡋࡓࠋ⢏Ꮚᚄࡣ࡜ࡶ࡟ 100nm ๓ᚋ࡜࡞ࡿࡼ࠺࡟ࡋࡓࠋ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝ㻔ᮾὒ⣳㻕ࢆࣇࣛࣥࢶᆺᣑᩓࢭࣝ㻔ࣃ࣮࣓ࢠ࢔㻕࡟ᣳࡳ㎸ࡳࠊゅᒙഃ࠿ࡽ࣏ࣜࢯ࣮࣒ࡲࡓࡣ⬡㉁࢚࣐ࣝࢩࣙࣥࢆ㐺⏝ࡋࠊ24 ᫬㛫ᚋ࡟ゅᒙࢆ᥇ྲྀࡋࡓࠋ0.1%ࢺࣜࣉࢩࣥ⁐ᾮ࡟ᾐࡋ࡚ゅᒙࡢࡳࢆ๤㞳ࡋࠊ⬺Ỉᚋ࡟Ỉࢆຍ࠼࡚❅⣲࢞ࢫ୰࡟࡚ゅᒙỈศ㔞ࢆ 20%࡟ㄪ〇ࡋࠊ࢟ࣕࣆ࣮ࣛࣜࢳ࣮ࣗࣈ㻔ȭ1 mm; W. Muller 〇㻕࡟ワࡵ ᐃヨᩱ࡜ࡋࡓࠋ⬡㉁⣔ࡢ࣓ࣛࣛᵓ㐀࡜⬡㉁ࡢ
඘ሸᵓ㐀ࢆྠ᫬࡟ ᐃࡍࡿࡓࡵ࡟ࠊᑠゅ࣭ᗈゅ X ⥺ᅇᢡྠ᫬ ᐃࠊࡉࡽ࡟♧ᕪ㉮ᰝ⇕㔞ィ࡟ࡼࡿྠ᫬ ᐃࡢྍ⬟࡞ࣅ࣮࣒ࣛ࢖ࣥ BL40B2 ࢆ౑⏝ࡋࡓࠋ ᐃ᮲௳ࡣࠊX ⥺ࡢἼ㛗 0.1 nmࠊ࣓࢝ࣛ㛗500 mmࠊ࣓࢝ࣛ࡟ࡣ RAXIS㻔ࣜ࢞ࢡ〇㻕ࢆ⏝࠸ࠊIP ࡣ 300300 mm ࢆ౑⏝ࡋࡓࠋࡲࡓࠊᩓ஘࣋ࢡࢺ
ࣝ㹑㸻q/2Sq S sinș/Ȝ㻌㻔nm-1㻕㻔Ȝ㸸X ⥺ࡢἼ㛗㸪2ș㸸ᩓ஘ゅ㻕࡜ᐃ⩏ࡋࡓࠋ⤖ᯝ࠾ࡼࡧ⪃ᐹ㸸
ᅗ 1 ࡣࠊ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝ࡬࣏ࣜࢯ࣮࣒ࢆ㐺⏝ࡋࡓゅᒙヨᩱ࡟࠾ࡅࡿ X ⥺ᅇᢡࣉࣟࣇ
࢓࢖ࣝࢆ♧ࡍࠋ㠀㐺⏝ヨᩱ࡟࠾࠸࡚ࡣࠊᑠゅ㡿ᇦࡢ S=0.170 nm-1㻔5.6 nm㻕ࠊS=0.275 nm-1㻔3.6 nm㻕ࠊ
S=0.294 nm-1㻔3.4 nm㻕࡟ࠊᗈゅ㡿ᇦࡢ S=2.41 nm-1㻔0.41 nm㻕ࠊS=2.61 nm-1㻔0.38 nm㻕࡟ࡑࢀࡒࢀᅇᢡࣆ࣮ࢡࡀぢࡽࢀࡓࠋS=0.170 nm-1 ࡣ▷࿘ᮇ࣓ࣛࣛᵓ㐀ࡢ୍ḟࠊS=0.294 nm-1 ࡣࢥࣞࢫࢸ࣮ࣟࣝ[6]ࠊS=2.41nm-1 ࡜ S=2.61 nm-1 ࡣ⣽⬊㛫⬡㉁ࡢ඘ሸᵓ㐀࡜ࡑࢀࡒࢀ୍⮴ࡋࡓࠋࡲࡓࠊS=0.275 nm-1 ࡣࢥࣞࢫࢸ࣮ࣟࣝ㸭⬡⫫㓟࡞࠸ࡋࢭ࣑ࣛࢻ㸭⬡⫫㓟࡜ᛮࢃࢀࡿᅇᢡࣆ࣮ࢡࡀࡳࡽࢀࡓ[7]ࠋ࣏ࣜࢯ࣮࣒ࢆ㐺⏝ࡋࡓヨᩱ࡟࠾࠸࡚ࡣࠊࡇࢀࡽࡢᅇᢡࣆ࣮ࢡࡀᙉࡲࡿ⌧㇟ࡀぢࡽࢀࡓࠋ㻔a㻕㻔b㻕

ᅗ 1㸬୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝ࡬࣏ࣜࢯ࣮࣒ࢆ㐺⏝ࡋࡓ
ゅᒙヨᩱ࡟࠾ࡅࡿ X ⥺ᅇᢡࣉࣟࣇ࢓࢖ࣝ
㻔a㻕ᑠゅ X ⥺ᅇᢡࣉࣟࣇ࢓࢖ࣝࠊ㻔b㻕 ᗈゅ X ⥺ᅇᢡࣉࣟࣇ࢓࢖ࣝ
ᅗ 2 ࡣࠊ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝ࡬⬡㉁࢚࣐ࣝࢩࣙࣥࢆ㐺⏝ࡋࡓゅᒙヨᩱ࡟࠾ࡅࡿ X ⥺ᅇᢡࣉࣟࣇ࢓࢖ࣝࢆ♧ࡍࠋ㠀㐺⏝ヨᩱ࡟࠾࠸࡚ࡣࠊᅗ 1 ࡜ྠᵝ࡞ᅇᢡࣆ࣮ࢡࡀぢࡽࢀࡓࠋ⬡㉁࢚࣐ࣝ
ࢩࣙࣥࢆ㐺⏝ࡋࡓヨᩱ࡟࠾࠸࡚ࡣࠊࡇࢀࡽࡢᅇᢡࣆ࣮ࢡࡀᙉࡲࡿ⌧㇟ࡣぢࡽࢀ࡞࠿ࡗࡓࠋ
㻔a㻕㻔b㻕

ᅗ 2㸬୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝ࡬⬡㉁࢚࣐ࣝࢩࣙࣥࢆ㐺⏝ࡋࡓ
ゅᒙヨᩱ࡟࠾ࡅࡿ X ⥺ᅇᢡࣉࣟࣇ࢓࢖ࣝ
㻔a㻕 ᑠゅ X ⥺ᅇᢡࣉࣟࣇ࢓࢖ࣝࠊ㻔b㻕 ᗈゅ X ⥺ᅇᢡࣉࣟࣇ࢓࢖ࣝ ᮏㄢ㢟࡟࠾࠸࡚ࡣࠊࣄࢺ⓶⭵࡟㏆࡙ࡅࡓ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝࢆᕷሙ࡟ᥦ౪ࡍࡿࡇ࡜ࢆ┠ᣦࡋࠊゅᒙ⣽⬊㛫⬡㉁ᵓ㐀ࡢ⤌⧊໬࡟ཬࡰࡍࣜࣥ⬡㉁⭷ᵓ㐀ࡢᙳ㡪࡟ࡘ࠸᳨࡚ウࡋࡓࠋࡑࡢ⤖ᯝࠊࣜࣥ⬡㉁ࡢ஧ศᏊ⭷⢏Ꮚ࠿ࡽ࡞ࡿ࣏ࣜࢯ࣮࣒ࡢ㐺⏝࡟࠾࠸࡚ࠊ༢ศᏊ⭷⢏Ꮚ࠿ࡽ࡞ࡿ⬡㉁࢚࣐ࣝ
ࢩࣙࣥࡢ㐺⏝࡜ẚ࡭࡚⣽⬊㛫⬡㉁ࡢ⮬ᕫ⤌⧊໬ࡀඃ఩࡟㉳ࡇࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋ௒ᚋࡢㄢ㢟㸸ᮏㄢ㢟࡟࠾࠸࡚ࡣࠊࣜࣥ⬡㉁ࡢ஧ศᏊ⭷⢏Ꮚ࠿ࡽ࡞ࡿ࣏ࣜࢯ࣮࣒ࡢ㐺⏝࡟࠾࠸࡚ࠊゅᒙ⣽⬊㛫⬡㉁ࡢ⤌⧊໬ࡀඃ఩࡟㉳ࡇࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋࡋ࠿ࡋ࡞ࡀࡽࠊࣜࣥ⬡㉁ࡀ஧ศᏊ⭷ᵓ㐀ࡢ࡜ࡁ࡟ゅᒙ⣽⬊㛫⬡㉁ࡢ⤌⧊໬ࡀ㉳ࡇࡿ⌮⏤ࡣᮍࡔ୙࡛᫂࠶ࡿࠋ௒ᚋࡣࠊࣜࣥ⬡㉁࡜ྠᵝ࡟௚ࡢ୧ぶ፹ᛶ≀㉁࡟࠾࠸࡚ࡶゅᒙ⣽⬊㛫⬡㉁ࡢ⤌⧊໬ࡀ㉳ࡇࡿࡢ࠿ࢆ᳨ウࡋࠊࣄࢺ⓶⭵࡟㏆࡙ࡅࡓ୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝࡢ㛤Ⓨ࡟ྥࡅ࡚ࠊゅᒙ⣽⬊㛫⬡㉁ᵓ㐀ࡢ⤌⧊໬࡟ࡘ࠸࡚ࡉࡽ࡟ヲ⣽࡞᳨ウࢆ㐍ࡵ࡚࠸ࡃᚲせࡀ࠶ࡿ࡜⪃࠼ࡿࠋཧ⪃ᩥ⊩㸸
[1] Watanabe, T., et al., “Utility of the three-dimensional cultured human skin model as a tool to evaluate
skin penetration of drugs.” Altern. Animal Test. Experiment., 8, 1-14, 㻔2001㻕.
[2] ᅧ⃝┤⨾, ᖹᡂ 18 ᖺᗘୗ༙ᮇඛ➃኱ᆺ◊✲᪋タᡓ␎ά⏝ࣉࣟࢢ࣒ࣛᡂᯝሗ࿌᭩, 㻔2006B㻕㻚
[3] ᆏ㈆ᚫ, 㺀୕ḟඖᇵ㣴ࣄࢺ⓶⭵ࣔࢹࣝࢆ⏝࠸ࡓ⤒⓶྾཰ヨ㦂㺁, 㻔2008B㻕㻚
[4] ᆏ㈆ᚫ, 㺀᦬ฟࣄࢺ⓶⭵ࢆ⏝࠸ࡓ໬⢝ရ〇๣ࡢ⓶⭵ᾐ㏱ᛶ࡟㛵ࡍࡿ◊✲㺁, 㻔2009B㻕㻚
[5] ᆏ㈆ᚫ, 㺀࣏ࣜࢯ࣮࣒〇๣ࡢ⓶⭵ᾐ㏱ᛶ࡟㛵ࡍࡿ◊✲㺁, 㻔2010B㻕㻚
[6] ᆏ㈆ᚫ, ᖹᡂ 17 ᖺᗘඛ➃኱ᆺ◊✲᪋タᡓ␎ά⏝ࣉࣟࢢ࣒ࣛᡂᯝሗ࿌᭩, 㻔2005B㻕㻚
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