JP6076719B2 - Cgrp応答性促進剤 - Google Patents
Cgrp応答性促進剤 Download PDFInfo
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- JP6076719B2 JP6076719B2 JP2012267170A JP2012267170A JP6076719B2 JP 6076719 B2 JP6076719 B2 JP 6076719B2 JP 2012267170 A JP2012267170 A JP 2012267170A JP 2012267170 A JP2012267170 A JP 2012267170A JP 6076719 B2 JP6076719 B2 JP 6076719B2
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Description
しかしながら、ジンセノシドRg3やRg5にCGRP応答促進作用があること、ニンジンエキスを特定のイオン交換樹脂を用いて加熱処理した処理物については、全く知られていない。
1)ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物を有効成分とするCGRP応答促進剤。
2)ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理するCGRP応答促進剤の製造方法。
3)ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物。
4)ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物を有効成分とする血流促進剤。
5)ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理する血流促進剤の製造方法。
またニンジンは、新鮮根をそのまま乾燥した生干ニンジン、周皮や細根を除いて乾燥した白参、蒸したのちに乾燥した紅参などの種類がある。特に紅参は、蒸す工程でマロニル化ジンセノシドの脱マロニル化が進行するとともに、ジンセノシドRg2の20位の糖が脱離したジンセノシドRg3を含むため好ましい。
上記部位は、ニンジンエキスの調製に際し、そのまま抽出工程に付されてもよく、又は粉砕、切断若しくは乾燥された後に抽出工程に付されて抽出物を得てもよい。該抽出物は天然成分由来であり安全性も高い。
上記ニンジンエキスの酸化を防止するため、煮沸脱気や窒素ガス等の不活性ガスを通気して溶存酸素を除去しつつ、いわゆる非酸化的雰囲気下で抽出する手段を併用してもよい。
また、上記加熱時間は、処理向上の観点から、0.5時間以上、好ましくは1時間以上、24時間以下、好ましくは5時間以下である。また0.5〜24時間、好ましくは1〜5時間の範囲である。
<1>ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物を有効成分とするCGRP応答促進剤。
<2>ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物を有効成分とする血流促進剤。
<3>CGRP応答促進剤を製造するための、ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物の使用。
<4>血流促進剤を製造するための、ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物の使用。
<5>CGRP応答促進に使用するための、ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物。
<6>血流促進に使用するための、ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物。
<7>CGRP応答促進のための、ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物の非治療的使用。
<8>血流促進のための、ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物の非治療的使用。
<9>ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物を、ヒト若しくは動物に有効量を投与又は摂取するCGRP応答促進方法。
<10>ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物を、ヒト若しくは動物に有効量を投与又は摂取する血流促進方法。
<11>非治療的方法である、<9>又は<10>に記載の方法。
<12>細胞のCGRP応答性を促進する方法であって、CGRP受容体を有し且つCGRP応答性を促進させたい細胞を、<1>に記載のCGRP応答性促進剤の存在下で培養する工程を含む方法。
<13><1>〜<12>に記載のH型陽イオン交換樹脂は、好適にはスルホン酸基を有する合成樹脂である。
<14><1>〜<13>に記載のニンジンは、好適には紅参である。
<15><1>、<3>、<5>、<7>、<9>、<11>〜<14>に記載のCGRP応答促進は、好適には血管平滑筋細胞のCGRP応答促進である。
<16>ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理するCGRP応答促進剤の製造方法。
<17>ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理する血流促進剤の製造方法。
<18>ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理して得られるニンジンエキス処理物。
<19>ジンセノシドRg3の固形分量が、好ましくは3〜20質量%、より好ましくは5〜10質量%である<18>に記載のニンジンエキス処理物。
<20>ジンセノシドRg3及びRg5が、ジンセノシドRb1、Rb2、Rc、Rd、Rg3及びRg5の合計に対し、好ましくは95〜100%、より好ましくは98〜100%である<18>又は<19>に記載のニンジンエキス処理物。
エキスの調製
紅参(新和物産より入手)80gを粉砕し、イオン交換水800mLを加え、漢方煎じ器(EK−SA10型)で2回熱水抽出した後、濾過し、溶媒を除き、軟エキス136gを得た。
上記軟エキス5gを水10mLで希釈し、アンバーリスト35WET(イオン交換樹脂)2.5gを加え、80度、20時間加熱,攪拌した。室温に冷却後、エタノール35mLを加え、ろ過し、ニンジンエキス処理物を得た(固形分3.2%)。
上記軟エキス5gを水45mLで希釈し、比較例エキス1を得た(固形分5.4%)。
上記軟エキス3.26gを10倍量の食酢((株)ミツカン社製:ミツカン 穀物酢)29.3g(pH2.90)を加えて100℃で3時間1回抽出した。濾液を減圧下で濃縮し、凍結乾燥して、褐色の抽出物を得た。水45mLで希釈し、比較例エキス2を得た(固形分7.0%)。
次に本発明のニンジンエキス処理物及び比較エキス1による細胞のCGRP応答性促進効果を調べた。
1.方法
(1)細胞培養
正常ヒト冠状動脈平滑筋細胞(HCASMC;クラボウ社、細胞lot# 01272)を増殖用培地(基礎培地HuMedia-SB2 500mLにFBS 25mL、hEGF 0.5mL、hFGF−B 0.5mL、インスリン0.5mL、抗菌剤0.5mLを添加したもの;クラボウ社)で培養した。継代には0.025%トリプシン/0.01%EDTAを用いた。
正常ヒト冠状動脈平滑筋細胞(HCASMC)を4000個/cm2の密度で増殖用培地を用いて48ウェルプレートに播種し、翌日分化用培地(基礎培地HuMedia-SB2 500mLにFBS 5mL、ヘパリン0.5mL、抗菌剤0.5mLを添加したもの;クラボウ社)に交換した。培地を1日おきに交換して7日間培養し、CGRP応答性の測定に供した。
細胞を、ホスホジエステラーゼ阻害剤(PDI)IBMX(3-Isobutyl-1-methylxanthine、500μM;シグマ社)及びRo-20-1724(100μM;和光純薬工業株式会社)を含む基礎培地(Humedia-SB2;クラボウ社)で2回洗浄し、更に同培地を200μL添加して37℃にて60分間培養し、細胞内に阻害剤を浸透させた。培地を除去して、実施例1で調製したニンジンエキス処理物又は比較エキス1をそれぞれ0.025%、及び0.5nM CGRP、ホスホジエステラーゼ阻害剤を含む基礎培地を添加し、15分間37℃にて培養した。反応の停止は、cAMP測定EIAキット(cAMP EIA (non-acetylation);GEヘルスケアバイオサイエンス株式会社)に付属の細胞溶解液を添加することにより行い、取扱説明書に記載の方法に従って細胞内cAMP濃度([cAMP]i)を測定し、その結果を図2に示す。なお、CGRP応答性促進能は、0.5nM CGRPのみで刺激したときの[cAMP]iを基準とし、これに対する百分率をImprove Indexとして表した。
Claims (2)
- ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理するCGRP応答促進剤の製造方法。
- ニンジンエキスを含む溶液を、H型陽イオン交換樹脂の存在下、60〜90℃で0.5〜24時間加熱処理する血流促進剤の製造方法。
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KR100750988B1 (ko) * | 2005-03-18 | 2007-08-22 | 주식회사 유니젠 | 천연물유래 진세노사이드를 포함하는 당뇨 또는혈당조절이상의 예방 또는 치료용 약학 조성물 |
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US7973014B2 (en) * | 2005-07-14 | 2011-07-05 | National Institute Of Pharmaceutical R&D Co., Ltd. | Medicinal composition containing ginseng secondary glycosides, its preparation method and application |
JP5730548B2 (ja) * | 2010-11-29 | 2015-06-10 | 花王株式会社 | Cgrp応答性促進剤 |
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