JP2008533131A - イソオリエンチンを含むヒスタミン抑制用組成物 - Google Patents
イソオリエンチンを含むヒスタミン抑制用組成物 Download PDFInfo
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- JP2008533131A JP2008533131A JP2008501819A JP2008501819A JP2008533131A JP 2008533131 A JP2008533131 A JP 2008533131A JP 2008501819 A JP2008501819 A JP 2008501819A JP 2008501819 A JP2008501819 A JP 2008501819A JP 2008533131 A JP2008533131 A JP 2008533131A
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- isoorientin
- histamine
- aloe
- disease
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Abstract
Description
主な経路は、イミダゾール環が、N−メチルトランスフェラーゼ(N-methyltransferase)によってN−メチルヒスタミンに転換された後、当該N−メチルヒスタミンがアモノアミンオキシダーゼ(amonoamine oxidase)によってN−メチルイミダゾール酢酸(N-methylimidazole acetic acid)に転換される。
他の経路は、ヒスタミンが、非特異性ジアミンオキシダーゼによって酸化的に脱アミン化され、ヒスタミンの代謝産物は活性がほとんどなく、尿で***される。
イソオリエンチンを含有するアロエ、タケまたはイネ抽出物は、これらに限定されないが、水、若しくはメタノール、エタノール、プロパノール、ブタノールなどのC1−4アルコール、又はこれらの混合溶媒での抽出物が好ましい。特に、イソオリエンチンを含有するアロエ抽出物は、30〜80%のメタノールまたはエタノールで抽出して得られるものが好ましい。イソオリエンチンを含有するタケ抽出物は、タケを水で抽出して得られた乾燥物をメタノールまたはエタノールで再抽出して得られるものが好ましい。上記抽出物は、総抽出物及びその画分物を含む。更に、上記イソオリエンチンを含有するアロエ抽出物は、これに限定されないが、アロエの外皮から得られるものが好ましい。
1.抗ヒスタミン活性成分の分離
本発明者らは、天然物の抽出物中から最高の収率及び活性を有する画分物を選択し、当該画分物から抗ヒスタミン活性成分を分離するべく試みた。天然物の抽出物を減圧下に濃縮した後、少量の水によく溶解した。その後、抽出物を同量のCH2Cl2溶媒で抽出分画を行い、非極性物質を除去し、更に同量のBuOH溶媒で抽出分画をした。所望のイソオリエンチンが、BuOH層にあるため、BuOH層を減圧下で濃縮した後、シリカカラムで処理した。この時、使用した溶媒は、CHCl3、MeOH及び水の混合溶媒(C:M:W=7:3:1〜6:4:1)を使用した。
黄色粉末のC21H22O11;1H−NMR(300MHz,d6−DMSO)及び13C−NMR(75MHz,d6−DMSO)のデータは、参考文献と比較した。「Biosci.Biotechnol.Biochem., 67(2), 410-414, 2003」を参照されたい。
上記実施例1で、イソオリエンチンが抗ヒスタミン活性を有することを確認し、出願人が保有する幾つかの植物の抽出物を対象にして分析を実施した結果、下記表2のような植物の抽出物及びそれらのイソオリエンチン含量の結果を得た。
アロエベラの外皮1kgを、15Lの95%、80%、70%、60%、50%、40%または30%のエタノール水溶液で抽出した後、減圧下で蒸発させて、水和した抽出物を確保した。これら抽出物のイソオリエンチン含量を、HPLCにより実施例2と同じ分析方法で分析した。比較した結果、イソオリエンチン含量は、50%のエタノール抽出物で最高の含量を示した。
タケ葉10kgを、水150Lで、80℃にて8時間抽出し、その後、減圧下で蒸発させて、抽出物680gを得た。水和した抽出物500gを、エタノール4Lで70℃にて2時間抽出し、室温に冷却した後、濾過し、そして濾過物を減圧下に蒸発させて、濃縮の抽出物127gを得た。濃縮抽出物100gに水800mLを加えて、80℃にて2時間抽出し、その後、濾過して得られた濾過物を凍結乾燥して、水和した抽出物61gを得た。
HPLCによって実施例2の分析方法で分析した結果、イソオリエンチン含量は3.2%であった。
1.テンジクネズミ肺の肥満細胞の精製
8匹のテンジクネズミ(雌性、200g)の肺組織(3g/1匹)を分離し、脂肪組織と気管支、血液を除去した後、Ca2+、Mg2+及び0.1%のゼラチンが含まれたタイロード緩衝液(TGCMバッファー)を使用し、15、15及び25分間の3回、酵素処理(5mg/mLコラゲナーゼ、1.8unit/27μLエラスターゼ)した。各酵素処理に、ナイロンメッシュと金属メッシュ(100μm)で濾過した後、遠心分離した(単分散肥満細胞という)。ペレットを、Ca2+、Mg2+フリー、0.1%のゼラチン含有緩衝液(TGバッファー)16mLに懸濁し、ラフパーコール(1.041mg/mL密度)で処理し、1,400rpmで25分間遠心分離してペレットを得た。また、TGバッファー8mLに細胞を懸濁し、不連続パーコール(1.06〜1.10mg/mL密度)で処理し、1,400rpmで25分間遠心分離して、様々な細胞層に分離した。その中、第3層又は第4層に、肥満細胞が主に存在するので、これらの層の細胞を得て、TGCMバッファーで2回洗浄した。全体の細胞及び肥満細胞は、それぞれトリパンブルー及びアルシアンブルー染色し、顕微鏡で細胞数を測定して、肥満細胞の純粋度(purity)を測定して約80〜90%を得た。
肥満細胞(4×105細胞)にテンジクネズミIgG1抗体(抗OVAの1mL/106細胞)を加え、37℃で45分間反応させ、その後、肥満細胞膜に結合しない抗OVA抗体を除去するために、TGCM緩衝液で洗浄した。細胞を1mLのTGCMに懸濁させた後、各々の濃度の薬剤(検索しようとする物質)で5分間処置した。1.0μg/mLのOVA(オボアルブミン)で感作し、10分間反応させた後、氷で冷却し、遠心分離し、その後、上清でヒスタミンを測定した。
*ヒスタミン量=(サンプルのヒスタミン遊離量−自然遊離量)/(全体ヒスタミン
遊離量−自然遊離量)×100
b:遊離されたヒスタミン量は、全体ヒスタミン量の百分率として示した。丸括弧の値は、UG4−92前処理で引き起こされた減少百分率として示した。
*:p<0.05;**:p<0.01;***:p<0.001、各々の値は、OVA単独と比較したときの値
( ):抑制率%
イソオリエンチン 1g
砂糖 10g
異性化糖 10g
レモン香 適量
精製水を加えた全体量 100mL
上記の成分を通常の液剤の製造方法に従い混合し、滅菌させて液剤を製造した。
イソオリエンチン 500mg
ラクトース 50mg
デンプン 50mg
タルク 2mg
ステアリン酸マグネシウム 適量
上記の成分を混合し、通常のカプセル剤の製造方法に従いゼラチンカプセルに充填してカプセル剤を製造した。
Claims (18)
- 有効成分として天然物由来のイソオリエンチン(isoorientin)を含有する、過剰のヒスタミンによる生理的変化または機能異常による疾患の予防または治療用薬学組成物。
- 過剰のヒスタミンによる生理的変化または機能異常による疾患が、アレルギー疾患、アトピー疾患、皮膚疾患、風邪、胃酸過多または神経系障害である、請求項1に記載の組成物。
- 天然物由来のイソオリエンチンを含有する組成物が、アロエ、タケまたはイネ抽出物である、請求項1に記載の組成物。
- イソオリエンチンを含有するアロエ抽出物が、30〜80%のメタノールまたはエタノールで抽出して得られるものである、請求項3に記載の組成物。
- イソオリエンチンを含有するタケ抽出物が、タケを水で抽出して得られた乾燥物を、メタノールまたはエタノールで再抽出して得られる乾燥した抽出物である、請求項3に記載の組成物。
- イソオリエンチンを含有するアロエ抽出物が、アロエの外皮から得られるものである、請求項3又は4に記載の組成物。
- 過剰のヒスタミンによる生理的変化または機能異常による疾患の、予防または治療用薬剤の製造のための、天然物由来のイソオリエンチンの使用。
- 過剰のヒスタミンによる生理的変化または機能異常による疾患が、アレルギー疾患、アトピー疾患、皮膚疾患、風邪、胃酸過多または神経系障害である、請求項7に記載の使用。
- 天然物由来のイソオリエンチンを含有する組成物が、アロエ、タケまたはイネ抽出物である、請求項7に記載の使用。
- イソオリエンチンを含有するアロエ抽出物が、30〜80%のメタノールまたはエタノールで抽出して得られるものである、請求項9に記載の使用。
- イソオリエンチンを含有するタケ抽出物が、タケを水で抽出して得られた乾燥物を、メタノールまたはエタノールで再抽出して得られる乾燥した抽出物である、請求項9に記載の使用。
- イソオリエンチンを含有するアロエ抽出物が、アロエの外皮から得られるものである、請求項9又は10に記載の使用。
- 治療有効量の天然物由来のイソオリエンチンを対象に投与し、対象において過剰のヒスタミンによる生理的変化または機能異常による疾患を予防または治療する方法。
- 過剰のヒスタミンによる生理的変化または機能異常による疾患が、アレルギー疾患、アトピー疾患、皮膚疾患、風邪、胃酸過多または神経系障害である、請求項13に記載の方法。
- 天然物由来のイソオリエンチンを含有する組成物が、アロエ、タケまたはイネ抽出物である、請求項13に記載の方法。
- イソオリエンチンを含有するアロエ抽出物が、30〜80%のメタノールまたはエタノールで抽出して得られるものである、請求項15に記載の方法。
- イソオリエンチンを含有するタケ抽出物が、タケを水で抽出して得られた乾燥物を、メタノールまたはエタノールで再抽出して得られる乾燥した抽出物である、請求項15に記載の方法。
- イソオリエンチンを含有するアロエ抽出物が、アロエの外皮から得られるものである、請求項15又は16に記載の方法。
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KR1020050022772A KR100720973B1 (ko) | 2005-03-18 | 2005-03-18 | 천연물 유래 아이소오리엔틴을 포함하는 히스타민 억제용약학 조성물 |
PCT/KR2006/000984 WO2006098603A2 (en) | 2005-03-18 | 2006-03-17 | Composition comprising isoorientin for suppressing histamine |
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US (1) | US20080214658A1 (ja) |
EP (1) | EP1863498A2 (ja) |
JP (1) | JP2008533131A (ja) |
KR (1) | KR100720973B1 (ja) |
CN (1) | CN101203228A (ja) |
AU (1) | AU2006223734B2 (ja) |
BR (1) | BRPI0608546A2 (ja) |
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US20060078632A1 (en) * | 2003-03-27 | 2006-04-13 | Unigen, Inc. | Composition comprising bamboo extract and the compounds isolated therefrom showing treating and preventing activity for inflammatory and blood circulation disease |
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KR100720971B1 (ko) * | 2004-06-11 | 2007-05-22 | 주식회사 유니젠 | 대나무 또는 대나무 추출물을 포함하는 안드로젠 효능성조성물 |
KR100761248B1 (ko) | 2006-10-12 | 2007-10-04 | 주식회사 유니젠 | 대나무 및 황금 추출물을 유효성분으로 함유하는 아토피성피부염 치료를 위한 조성물 |
KR101050129B1 (ko) * | 2008-06-18 | 2011-07-19 | 주식회사 한국인삼공사 | 알레르기 질환 예방 또는 치료용 조성물 |
KR101702056B1 (ko) * | 2009-11-16 | 2017-02-03 | 주식회사 유니베라 | 피부세포증식 촉진, 항산화 및 항알러지 효과가 우수한 알로에 베라 새순 농축물 또는 추출물 |
FR2956324A1 (fr) * | 2010-01-18 | 2011-08-19 | Valerie Baille | Complexe vegetal comprenant un extrait polyphenolique de bambou |
CN101843612B (zh) * | 2010-05-21 | 2012-01-11 | 暨南大学 | 异荭草苷作为制备抗呼吸道合胞病毒的药物的用途 |
CN102285976A (zh) * | 2011-09-27 | 2011-12-21 | 天津市尖峰天然产物研究开发有限公司 | 从竹叶黄酮中提取异荭草素的方法 |
CN102743375A (zh) * | 2012-04-28 | 2012-10-24 | 苏州凯祥生物科技有限公司 | 异荭草素的用途及其药物组合物 |
KR20150019505A (ko) | 2013-08-14 | 2015-02-25 | 대화제약 주식회사 | 플라본-6-c-글루코스 유도체를 유효성분으로 함유하는 신경정신질환의 치료 또는 예방용 약학적 조성물 |
KR102488562B1 (ko) * | 2020-11-02 | 2023-01-12 | 인천대학교 산학협력단 | 갯끈풀 추출물을 유효성분으로 포함하는 염증 또는 아토피 피부염의 개선, 예방 또는 치료용 조성물 |
KR102543123B1 (ko) * | 2021-05-27 | 2023-06-13 | 주식회사 유니베라 | 알로에 꽃 추출물을 유효성분으로 함유하는 피부 보습용 조성물 |
WO2022250313A1 (ko) * | 2021-05-27 | 2022-12-01 | 주식회사 유니베라 | 알로에 베라 꽃 추출물, 또는 알로에 베라 꽃 추출물 및 알로에 베라 다당체를 유효성분으로 함유하는 피부 보습, 재생 촉진 및 상처 치료용 조성물 |
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JP2007045755A (ja) * | 2005-08-10 | 2007-02-22 | Kameda Seika Co Ltd | 美白剤、抗アレルギー剤及び食料品 |
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EP1863498A2 (en) | 2007-12-12 |
AU2006223734B2 (en) | 2012-03-29 |
US20080214658A1 (en) | 2008-09-04 |
BRPI0608546A2 (pt) | 2010-11-16 |
KR20070039406A (ko) | 2007-04-12 |
CA2601046A1 (en) | 2006-09-21 |
AU2006223734A1 (en) | 2006-09-21 |
CN101203228A (zh) | 2008-06-18 |
KR100720973B1 (ko) | 2007-05-22 |
WO2006098603A3 (en) | 2006-11-30 |
WO2006098603A2 (en) | 2006-09-21 |
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