食物アレルゲンの消化管吸収と経口感作におよぼす非ステロイド性抗炎症薬の影響解析

概要

༤ኈㄽᩥ

㣗≀࢔ࣞࣝࢤࣥࡢᾘ໬⟶྾཰࡜⤒ཱྀឤస࡟࠾ࡼࡰࡍ
㠀ࢫࢸࣟ࢖ࢻᛶᢠ⅖⑕⸆ࡢᙳ㡪ゎᯒ

ᗈᓥ኱Ꮫ኱Ꮫ㝔་ṑ⸆ಖ೺Ꮫ◊✲⛉ ་ṑ⸆Ꮫᑓᨷ
        ⑓㝔⸆๣Ꮫ◊✲ᐊ
ᖹᡂ 27 ᖺᗘධᏛ  ⚟ᓥ 㝯ᏹ
୺ᣦᑟᩍဨ  ᯇᑿ ⿱ᙲ

┠ḟ
ᗎㄽ ........................................................................................................................................................................... 1
ᮏㄽ ........................................................................................................................................................................... 6
➨  ❶ ᑠ㯏ࢢࣜ࢔ࢪࣥࡢᾘ໬⟶྾཰ᶵᵓ࡜࢔ࢫࣆࣜࣥࡢᙳ㡪ゎᯒ ........................................................... 6
➨ 1 ⠇ ࢢࣜ࢔ࢪࣥࡢᾘ໬⟶྾཰࡜࢔ࢫࣆࣜࣥࡢᙳ㡪 ........................................................................ 9
1-1. ⥴ゝ ............................................................................................................................................. 9
1-2. ⤖ᯝ ............................................................................................................................................. 9
1-3. ⪃ᐹ ........................................................................................................................................... 11
➨ 2 ⠇ ᑠ⭠㐃⥆℺ὶἲ࡟ࡼࡿࢢࣜ࢔ࢪࣥࡢ྾཰࡟୚࠼ࡿ࢔ࢫࣆࣜࣥࡢᙳ㡪ゎᯒ ........................... 13
2-1. ⥴ゝ ........................................................................................................................................... 13
2-2. ⤖ᯝ ............................................................................................................................................... 13
2.3. ⪃ᐹ ........................................................................................................................................... 17
➨ 3 ⠇ ⤒ཱྀ྾཰ࡉࢀࡓࢢࣜ࢔ࢪࣥࡢศᏊ㔞࡜࢔ࣞࣝࢤࣥάᛶࡢゎᯒ ............................................. 20
3.1. ⥴ゝ ........................................................................................................................................... 20
3.2. ⤖ᯝ ........................................................................................................................................... 20
3-3. ⪃ᐹ ........................................................................................................................................... 22
➨ 4 ⠇ ᑠᣓ ........................................................................................................................................ 24
➨ 2 ❶ OVA ࡢᾘ໬⟶྾཰࡜ឤస࡟࠾ࡼࡰࡍ NSAIDs ࡢᙳ㡪ゎᯒ ............................................................ 25
➨ 1 ⠇ OVA ࡢᾘ໬⟶྾཰࡟࠾ࡼࡰࡍ࢔ࢫࣆࣜࣥࡢᙳ㡪 ................................................................. 26
1-1. ⥴ゝ ........................................................................................................................................... 26
1-2. ⤖ᯝ ........................................................................................................................................... 26
1-3. ⪃ᐹ ........................................................................................................................................... 28
➨ 2 ⠇ OVA ࡢ⤒ཱྀឤస࡟࠾ࡼࡰࡍ NSAIDs ࡢᙳ㡪 ........................................................................ 30
2-1. ⥴ゝ ........................................................................................................................................... 30
2-2. ⤖ᯝ ........................................................................................................................................... 30
2-3. ⪃ᐹ ........................................................................................................................................... 35
➨ 3 ⠇ OVA ࡢ⤒⓶ឤస࡟࠾ࡼࡰࡍ NSAIDs ࡢᙳ㡪 ........................................................................ 37
3-1. ⥴ゝ ........................................................................................................................................... 37
3-2. ⤖ᯝ ........................................................................................................................................... 37
3-3. ⪃ᐹ ........................................................................................................................................... 40
➨ 4 ⠇ ᑠᣓ ........................................................................................................................................ 41
⤖ㄽ ......................................................................................................................................................................... 42
ᐇ㦂᪉ἲ ................................................................................................................................................................. 44
ㄽᩥ┠㘓 ................................................................................................................................................................. 53
ཧ⪃ᩥ⊩ ................................................................................................................................................................. 54

␎ㄒ୍ぴ
COX

Cyclooxygenase

Da

Dalton

EBD 

Evans blue dye

ELISA

Enzyme-linked immunosorbent assay

EtOH

Ethanol

FD

Fluorescein isothiocyanate–dextran

FDEIA

Food-dependent exercise-induced anaphylaxis

FITC

Fluorescein isothiocyanate

IL

Interleukin

IAP

Intestinal alkaline phosphatase

NSAIDs

Non-steroidal anti-inflammatory drugs

OVA

Ovalbumin

PBS

Phosphate buffered saline

PGs

Prostaglandins

Th

Helper T cell

TSLP

Thymic stromal lymphopoietin

Tween-20

Polyoxyethylene sorbitan monolaurate

WDEIA

Wheat-dependent exercise-induced anaphylaxis










ᗎㄽ

㣗≀࢔ࣞࣝࢠ࣮ࡣࠕ㣗≀࡟ࡼࡗ࡚ᘬࡁ㉳ࡇࡉࢀࡿ࢔ࣞࣝࢤࣥ≉␗ⓗ࡞ච␿Ꮫⓗᶵᗎࢆ௓ࡋ࡚⏕
య࡟࡜ࡗ࡚୙฼┈࡞⑕≧ࡀច㉳ࡉࢀࡿ⌧㇟ࠖ࡜ᐃ⩏ࡉࢀ࡚࠸ࡿ [1]ࠋ㏆ᖺࠊ㣗≀࢔ࣞࣝࢠ࣮ࡢᝈ⪅
ᩘࡣቑຍഴྥ࡟࠶ࡾࠊ㣗≀࢔ࣞࣝࢠ࣮ࢆ⨯ᝈࡋࡓᏛ❺ࡀㄗ㣗࡟ࡼࡾ࢔ࢼࣇ࢕ࣛ࢟ࢩ࣮ࢆ⏕ࡌࠊṚஸ
ࡋࡓ౛ࡀሗ࿌ࡉࢀࡿ࡞࡝㔜኱࡞♫఍ၥ㢟࡜࡞ࡗ࡚࠸ࡿࠋSampson ࡟ࡼࡿ࢔࣓࡛ࣜ࢝ࡢ␿Ꮫㄪᰝࡸ
Venter ࡽ࡟ࡼࡿ࢖ࢠࣜࢫ࡛ࡢ␿Ꮫㄪᰝࡢ⤖ᯝࠊᑠඣࡢ 5~6%ࠊᡂேࡢ 3~4%ࡀఱࡽ࠿ࡢ㣗≀࢔ࣞࣝࢠ
࣮࡟⨯ᝈࡋ࡚࠸ࡿ࡜ሗ࿌ࡉࢀ࡚࠸ࡿ [2,3]ࠋࡲࡓࠊUrisu ࡽࡢ␿Ꮫㄪᰝ࡟ࡼࡿ࡜ࠊᡃࡀᅜ࡟࠾ࡅࡿ㣗
≀࢔ࣞࣝࢠ࣮ࡢ⨯ᝈ⋡ࡣஙඣ࡛ 5㹼10%ࠊᗂඣ࡛ 5%ࠊᏛ❺࡛ 4.5%࡛࠶ࡾ௚ᅜ࡜ྠ⛬ᗘࡢ⨯ᝈ⋡࡛
࠶ࡗࡓࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸ࡿ [1]ࠋ
 㣗≀࢔ࣞࣝࢠ࣮ࡢ⑓ែࡣࠊⓎ⑕࡟㛵୚ࡍࡿච␿Ꮫⓗᶵᗎ࡟ࡼࡗ࡚ immunoglobulin-E ᢠయ㸦IgE㸧
౫Ꮡᛶ཯ᛂ࡜㠀 IgE ౫Ꮡᛶ㸦⣽⬊౫Ꮡᛶ㸧཯ᛂࡢ 2 ࡘ࡟኱ูࡉࢀࡿࠋ㠀 IgE ౫Ꮡᛶ㣗≀࢔ࣞࣝࢠ࣮
࡟ࡣࠊ᪂⏕ඣᮇࡸஙඣᮇ࡟჎ྤࡸୗ⑩ࢆᘬࡁ㉳ࡇࡍ᪂⏕ඣ࣭ஙඣᾘ໬⟶࢔ࣞࣝࢠ࣮ࡀ࠶ࡿࠋ㠀 IgE
౫Ꮡᛶ㣗≀࢔ࣞࣝࢠ࣮ࡢⓎ⑕ᶵᗎ࡟ࡣ T ⣽⬊ࡢ㛵୚ࡀ᥎ ࡉࢀ࡚࠸ࡿࡀࠊࡑࡢヲ⣽ࡣ᫂ࡽ࠿࡛࡞
࠸ࠋ୍᪉ࠊIgE ౫Ꮡᛶ㣗≀࢔ࣞࣝࢠ࣮࡟ࡣࠊཎᅉ㣗≀ࡢᦤྲྀᚋ 2 ᫬㛫௨ෆ࡟࢔ࣞࣝࢠ࣮⑕≧ࡀច㉳
ࡉࢀࡿ༶᫬ᆺ㣗≀࢔ࣞࣝࢠ࣮ࡸⰼ⢊⑕ࡸ㐠ືㄏⓎࡀ㛵୚ࡍࡿ≉Ṧᆺࡀ࠶ࡿࠋࡲࡓࠊஙඣ࢔ࢺࣆ࣮ᛶ
⓶⭵⅖࡟ࡶ㣗≀࢔ࣞࣝࢠ࣮ࡀ㛵୚ࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿࠋࡇࢀࡽࡢ࠺ࡕࠊ᭱ࡶⓎ⑕㢖ᗘࡢ㧗࠸༶
᫬ᆺ㣗≀࢔ࣞࣝࢠ࣮ࡢ⑕≧ࡣከᒱ࡟ࢃࡓࡾࠊⶼ㯞⑈ࡸ⣚ᩬ࡞࡝ࡢ⓶⭵⑕≧ࡸ⢓⭷⑕≧ࡀከࡃࡢ⑕౛
࡛ㄆࡵࡽࢀࡿࡀࠊ࿧྾ჾ⑕≧ࡸࢩࣙࢵࢡ⑕≧࡞࡝⮴Ṛⓗ࡞⑕≧ࢆ࿊ࡍࡿࡇ࡜ࡶᑡ࡞ࡃ࡞࠸ࠋᡃࡀᅜ
࡟࠾ࡅࡿ༶᫬ᆺ㣗≀࢔ࣞࣝࢠ࣮ࡢ୺せཎᅉ㣗≀࡟ࡣ㭜༸ࡸ∵ஙࠊᑠ㯏ࠊ⏥Ẇ㢮ࠊࡑࡤࠊࣆ࣮ࢼࢵࢶ
࡞࡝ࡀ࠶ࡿࠋ≉࡟ࠊ㭜༸ࡸ∵ஙࠊᑠ㯏ࡣ඲యࡢ⣙ 70%ࢆ༨ࡵ࡚࠾ࡾࠊ㣗≀࢔ࣞࣝࢠ࣮ࡢ୕኱ཎᅉ㣗
≀࡜⛠ࡉࢀ࡚࠸ࡿ [1]ࠋࡲࡓࠊ≉Ṧᆺ࡟ࡣⰼ⢊࢔ࣞࣝࢤࣥ࡟ᑐࡍࡿ IgE ࡀᯝ≀ࡸ㔝⳯୰ࡢ࢔ࣞࣝࢤ
ࣥ࡜஺ᕪ཯ᛂࢆ♧ࡍࡇ࡜ཱྀ࡛၁ཱྀ࣭⭍⢓⭷⑕≧ࢆ♧ࡍཱྀ⭍࢔ࣞࣝࢠ࣮⑕ೃ⩌㸦OAS㸧ࡸཎᅉ㣗≀ࢆ
ᦤྲྀࡋࡓᚋ࡟ࠊ㐠ື㈇Ⲵࡀຍࢃࡿࡇ࡜࡛࢔ࢼࣇ࢕ࣛ࢟ࢩ࣮ࡀច㉳ࡉࢀࡿ㣗≀౫Ꮡᛶ㐠ືㄏⓎ࢔ࢼࣇ
࢕ࣛ࢟ࢩ࣮㸦FDEIA㸧࡞࡝ࡀᏑᅾࡍࡿ [1]ࠋFDEIA ࡢึⓎᖺ㱋ࡣ 10 ṓ௦ࡀ᭱ࡶ㢖ᗘࡀ㧗࠸ࡇ࡜࠿
1

ࡽࠊ㐠ືࢆࡍࡿᶵ఍ࡀከ࠸ᖺ㱋ᒙ࡟೫ࡗ࡚࠸ࡿࡇ࡜ࡀ≉ᚩ࡛࠶ࡿࠋከࡃࡣ㣗ᚋ 2 ᫬㛫௨ෆࡢ㐠ື࡛
Ⓨ⑕ࡋࠊཎᅉ㣗≀ࡢᦤྲྀ࡜㐠ື㈇Ⲵ࡟ຍ࠼࡚ࠊ」ᩘࡢㄏⓎせᅉࡀ㛵୚ࡍࡿࠋ౛࠼ࡤࠊ⑂ປࡸࢫࢺࣞ
ࢫ࡞࡝ࡢ඲㌟≧ែࡸప ࡞࡝ࡢ⎔ቃࠊ㠀ࢫࢸࣟ࢖ࢻᛶᢠ⅖⑕⸆㸦NSAIDs㸧࡞࡝ࡢ⸆๣ࡢ᭹⏝ࡀⓎ⑕
࡟ᙳ㡪ࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿࠋFDEIA ࡢཎᅉ㣗≀ࡣࣃࣥࡸ࠺࡝ࢇ࡞࡝ࡢᑠ㯏〇ရࡢ㢖ᗘࡀ 57%
࡜᭱ࡶከࡃࠊḟ࠸࡛࢚ࣅࡸ࢝ࢽ࡞࡝ࡢ⏥Ẇ㢮࡛࠶ࡿࠋ୍᪉ࠊ༶᫬ᆺ㣗≀࢔ࣞࣝࢠ࣮ࡢཎᅉ㣗≀࡜ࡋ
࡚㧗࠸㢖ᗘࢆ♧ࡍ㭜༸ࡸ∵ஙࡣࠊFDEIA ࡢཎᅉ㣗≀࡜ࡋ࡚ࡣ㢖ᗘࡀప࠸ [4]ࠋ
IgE ౫Ꮡᛶ㣗≀࢔ࣞࣝࢠ࣮ࡢⓎ⑕ᶵᗎࡣࠊ௚ࡢⅠᆺ࢔ࣞࣝࢠ࣮࡜ྠᵝ࡟ࠊ“ឤసࡢᡂ❧”࡜“⑕≧ࡢ
ច㉳”࡜࠸࠺ 2 ࡘࡢ㐣⛬ࢆ⤒ࡿࠋ㏻ᖖࠊ⤒ཱྀࡸ⤒Ẽ㐨ࠊ⤒⓶࡟ࡼࡗ࡚యෆ࡟౵ධࡋࡓ㣗≀࢔ࣞࣝࢤ
ࣥࡢ୍㒊ࡣࠊ␗≀࡜ࡋ࡚࣐ࢡࣟࣇ࢓࣮ࢪࡸ⓶⭵ࡢᶞ≧⣽⬊࡛࠶ࡿࣛࣥࢤࣝࣁࣥࢫ⣽⬊࡞࡝ࡢᢠཎᥦ
♧⣽⬊࡟ࡼࡾ㈎㣗ࡉࢀࡿࠋ࢔ࣞࣝࢤࣥࢆྲྀࡾ㎸ࢇࡔᢠཎᥦ♧⣽⬊ࡣࠊࡑࡢ୍㒊ࢆࢼ࢖࣮ࣈ T ⣽⬊࡟
ᥦ♧ࡍࡿࠋᥦ♧ࢆཷࡅࡓࢼ࢖࣮ࣈ T ⣽⬊ࡣ 2 ᆺ࣊ࣝࣃ࣮T㸦Th2㸧⣽⬊࡟ศ໬ࡋࠊ࢖ࣥࢱ࣮ࣟ࢖࢟ࣥ
(IL)-4 ࡸ IL-5ࠊIL-13 ࡞࡝ࡢࢧ࢖ࢺ࢝࢖ࣥࢆᨺฟࡍࡿࠋࡇࢀࡽࡢࢧ࢖ࢺ࢝࢖ࣥࡣࠊB ⣽⬊ࢆ࢔ࣞࣝࢤ
ࣥ࡟ᑐࡍࡿ≉␗ IgE ᢠయࢆ⏘⏕ࡍࡿࡇ࡜ࡢ࡛ࡁࡿᙧ㉁⣽⬊࡬࡜ศ໬ࡉࡏࡿࠋᙧ㉁⣽⬊ࡼࡾ⏘⏕ࡉࢀ
ࡓ࢔ࣞࣝࢤࣥ≉␗ IgE ᢠయࡣ⫧‶⣽⬊ࡸዲሷᇶ⌫⾲㠃ୖ࡟Ⓨ⌧ࡍࡿ㧗ぶ࿴ᛶ IgE ཷᐜయ㸦FcεRI㸧
࡜㧗࠸ぶ࿴ᛶࢆᣢࡗ࡚⤖ྜࡍࡿࡇ࡜࡛ឤసࡀᡂ❧ࡍࡿ㸦Fig. 1㸧
ࠋឤసࡀᡂ❧ࡋࡓᚋࠊ෌ࡧయෆ࡟౵
ධࡋࡓ࢔ࣞࣝࢤࣥࡣ⫧‶⣽⬊ࡸዲሷᇶ⌫ୖ࡟⤖ྜࡋࡓ 2 ศᏊ௨ୖࡢ࢔ࣞࣝࢤࣥ≉␗ IgE ᢠయ࡜ᯫᶫ
⤖ྜࢆᙧᡂࡍࡿࠋᯫᶫ⤖ྜࡢᙧᡂ࡟ࡼࡾࠊ⫧‶⣽⬊ࡸዲሷᇶ⌫࡞࡝ࡢ⣽⬊ࡀάᛶ໬ࡉࢀࠊ⬺㢛⢏ࡀ
ច㉳ࡉࢀࡿࠋ⬺㢛⢏᫬࡟ࡣࣄࢫࢱ࣑ࣥࡸࢭࣟࢺࢽࣥ࡞࡝ࡢࢣ࣑࣓࢝ࣝࢹ࢕࢚࣮ࢱ࣮ࡀᨺฟࡉࢀࠊࡑ
ࡢ⏕⌮άᛶ࡟ᇶ࡙ࡁࠊ⾑⟶ࡢ㏱㐣ᛶࡸ⢓ᾮศἪࠊዲ㓟⌫㐟㉮ࢆஹ㐍ࡍࡿࠋࡑࡢ⤖ᯝࠊⶼ㯞⑈ࡸႍᜥࠊ
⾑ᅽࡢపୗ࡞࡝ࡢ༶᫬ᆺ࢔ࣞࣝࢠ࣮཯ᛂࡀច㉳ࡉࢀࡿࠋ୍᪉ࠊ⫧‶⣽⬊ୖࡢ IgE ࡜࢔ࣞࣝࢤࣥ࡜ࡀ
ᯫᶫ⤖ྜࢆᙧᡂࡋࡓ㝿࡟ࡣࠊ⬺㢛⢏཯ᛂ࡟ຍ࠼࡚ࠊࣟ࢖ࢥࢺ࢚ࣜࣥࡸࣉࣟࢫࢱࢢࣛࣥࢪࣥ࡞࡝ࡢ⬡
㉁࣓ࢹ࢕࢚࣮ࢱ࣮ࡢྜᡂࡀஹ㐍ࡍࡿࠋࡇࢀࡽࡢ≀㉁ࡣ⾑⟶㏱㐣ᛶஹ㐍స⏝ࡸẼ⟶ᨭᖹ⁥➽཰⦰స⏝
ࢆ᭷ࡋ࡚࠸ࡿࠋࡲࡓࠊ⬡㉁࣓ࢹ࢕࢚࣮ࢱ࣮ࡢᨺฟࡣ⬺㢛⢏ࡼࡾࡶ᫬㛫ࢆせࡍࡿࡓࡵࠊ༶᫬ᆺ཯ᛂࡢ
ᾘኻ࠿ࡽᩘ᫬㛫ᚋ࡟෌ࡧ⅖⑕཯ᛂࡸႍᜥᵝ⑕≧ࡀ㐜Ⓨ཯ᛂ࡜ࡋ࡚ច㉳ࡉࢀࡿ [1]ࠋ

2

sensitization phase

elicitation phase

allergen
intestinal
tract

APC

allergic
reactions

Plasma
cell

T
B

class switch

APC: antigen presenting cell
T: T cell B: B cell

degranulation

Mast cell
: IgE
: FcεRⅠ

Fig. 1. Pathogenesis of IgE-mediated type I allergic reaction
NSAIDs ࡣࣉࣟࢫࢱࢢࣛࣥࢪࣥ㢮㸦PGs㸧ࡢྜᡂ㓝⣲࡛࠶ࡿࢩࢡࣟ࢜࢟ࢩࢤࢼ࣮ࢮ (COX) ࡢάᛶࢆ
㜼ᐖࡍࡿࡇ࡜࡛ࠊゎ⇕࣭㙠③స⏝ࡸᢠ⅖⑕స⏝ࢆ♧ࡍ⸆๣࡛࠶ࡿࠋCOX ࡟ࡣ COX-1 ࡜ COX-2 ࡢ 2
✀㢮ࡢ࢔࢖ࢯࢨ࢖࣒ࡀᏑᅾࡍࡿࠋCOX-1 ࡣ⫶ࡸ⭈⮚ࠊ⾑ᑠᯈ࡞࡝࠶ࡽࡺࡿ⤌⧊࡟ᜏᖖⓗ࡟Ⓨ⌧ࡋ࡚
࠾ࡾࠊ⫶⢓⭷ࡢಖㆤࡸ⾑ᑠᯈࡢจ㞟ࠊ⭈ᶵ⬟ࡢㄪ⠇࡞࡝⏕యࡢᜏᖖไࢆ⥔ᣢࡍࡿୖ࡛㔜せ࡞ᙺ๭ࢆ
ᯝࡓࡋ࡚࠸ࡿ [5,6]ࠋ୍᪉ࠊCOX-2 ࡣ⅖⑕཯ᛂ࡟ࡼࡾㄏᑟࡉࢀࡿ㓝⣲࡛࠶ࡾࠊ⅖⑕཯ᛂࡢୖ᪼࡟క
࠸Ⓨ⌧ࡀಁ㐍ࡉࢀࡿࠋྂ඾ⓗ࡞ NSAIDs ࡢከࡃࡣ COX-1ࠊCOX-2 ࡢ࡝ࡕࡽࡢ࢔࢖ࢯࢨ࢖࣒ࡢάᛶ
ࡶ㜼ᐖࡍࡿ㸦Table 1㸧
ࠋࡋࡓࡀࡗ࡚ࠊࡑࢀࡽࡢ NSAIDs ࡣ COX-2 ࡢ㜼ᐖ࡟㉳ᅉࡍࡿᾘ⅖࣭㙠③ຠᯝ
ࡔࡅ࡛࡞ࡃࠊCOX-1 ࡢ㜼ᐖ࡟㉳ᅉࡍࡿᾘ໬⟶യᐖ࡞࡝ࡢ๪స⏝ࢆច㉳ࡍࡿ [7]ࠋ
NSAIDs ࡢ 1 ࡘ࡛࠶ࡿ࢔ࢫࣆࣜࣥࡣ⫶⭠㞀ᐖࡀཎᅉ࡛ᚸᐜᛶࡢప࠿ࡗࡓࢧࣜࢳࣝ㓟ࡢ࢔ࢭࢳࣝ
໬ㄏᑟయ࡜ࡋ࡚㛤Ⓨࡉࢀࡓࠋ࢔ࢫࣆࣜࣥࡣ⏝㔞࡟ࡼࡗ࡚⮫ᗋ࡛ࡢ⏝㏵ࡀ␗࡞ࡾࠊప⏝㔞 (ᡂே࡛ 1
᪥ 100 mg) ࡛⏝࠸ࡿሙྜ࡟ࡣᢠ⾑ᑠᯈ⸆࡜ࡋ࡚ࠊ㧗⏝㔞 (ᡂே࡛ 1 ᪥ 1000 mg) ࡛⏝࠸ࡿሙྜ࡟ࡣ
ゎ⇕࣭㙠③⸆࡜ࡋ࡚⏝࠸ࡽࢀࡿࠋࡇࢀࡲ࡛ࡢ◊✲࡛ࠊ࢔ࢫࣆࣜࣥࡢ᭹⏝ࡀ㐠ື㈇Ⲵ࡜ྠᵝ࡟ᑠ㯏౫
Ꮡᛶ㐠ືㄏⓎ࢔ࢼࣇ࢕ࣛ࢟ࢩ࣮ (WDEIA) ᝈ⪅ࡢ࢔ࣞࣝࢠ࣮⑕≧ࢆច㉳ࡍࡿࡇ࡜ࡀሗ࿌ࡉࢀ࡚࠸
ࡿ [8]ࠋ࢔ࢫࣆࣜࣥ࡟ࡼࡿ WDEIA ࡢㄏⓎᶵᗎ࡟ࡘ࠸࡚ࡣࠊ」ᩘࡢሗ࿌ࡀ࠶ࡿࠋAihara ࡽࡣࠊ࢔ࢫ
ࣆࣜࣥࡀ WDEIA ᝈ⪅࡟ᑐࡍࡿ⓶⭵ࣉࣜࢵࢡࢸࢫࢺࡢ཯ᛂᛶࢆஹ㐍ࡉࡏࡓࡇ࡜ࢆሗ࿌ࡋ࡚࠸ࡿ [9]ࠋ
3

Table 1. ...

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