JP5728085B2 - マクロラクチンa及びその誘導体を有効成分として含有する抗血管新生組成物 - Google Patents
マクロラクチンa及びその誘導体を有効成分として含有する抗血管新生組成物 Download PDFInfo
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- JP5728085B2 JP5728085B2 JP2013519563A JP2013519563A JP5728085B2 JP 5728085 B2 JP5728085 B2 JP 5728085B2 JP 2013519563 A JP2013519563 A JP 2013519563A JP 2013519563 A JP2013519563 A JP 2013519563A JP 5728085 B2 JP5728085 B2 JP 5728085B2
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Description
本発明に係る化合物は、本発明者らが所有している特許出願(特許文献1)に記載された方法で製造して得ることができる。
受精卵は、Baekja Korean native chicken(青松(Cheongsong)、韓国)から得た。2−ピリジンカルボキサルデヒド、2−アセチルフラン及び酢酸コルチゾンはAldrich Chemical Co. (St. Louis, MO, USA)から、血管内皮成長因子(VEGF)とインターロイキン−8(IL−8)はR&D Systems (Minneapolis, MN, USA)から、腫瘍壊死因子−α(TNF−α)はInvitrogen Life Tech.から、ワットマンフィルタディスクはWhatman (UK)から、そしてバチマスタット(batimastat)はTocris Bioscience (Ballwin, MO, USA)から購入した。
MA、MMA及びSMAは、本発明者らの特許出願(特許文献1)に開示記載された製造方法に従って得た。
インビボ試験で、マクロラクチン化合物の抗血管新生効果を確認するために、絨毛尿膜(CAM)分析を実施した(Nguyen M. et al., Microvascular Res., 47, pp. 31-40, 1994)。各群当たり6±1個の受精卵を使用した。
図1、図2及び図3は、各実験群で観察された新生血管の写真及び各実験群の血管枝個数測定結果を示すグラフである。
−細胞培養
ヒト繊維肉腫細胞(HT−1080)を、10%ウシ胎仔血清(FBS)及び1%ペニシリン/ストレプトマイシン(PS)を含有するDMEM培地で、37℃及び5%CO2の条件下で培養した。細胞が培養フラスコの80%またはそれ以上に成長したときに、これらを1:3の割合で継代して、本実験に用いた。
インビトロ試験で、マクロラクチン化合物の癌転移抑制効果を確認するために、8mmの細孔径を有するポリカーボネートフィルタを取り付けた24−ウェルのトランスウェル(transwell)を利用して繊維肉腫細胞の浸潤性実験を遂行した。まず、フィルタの底部をI型コラーゲン(0.5mg/mL)でコーティングし、次いで、フィルタの上部をマトリゲル(Matrigel、1.5mg/mL)でコーティングした。コーティング終了後、挿入部分の下部に5%FBS含有培地を充填し、上部に細胞培養器で18時間培養したヒト繊維肉腫細胞HT−1080を含有している無血清培地を充填した。フィルタの底部に浸潤したヒト繊維肉腫細胞をメタノールで固定した後、ヘマトキシリンとエオシンで染色した。浸潤した細胞を顕微鏡で観察し、各フィルタから無作為に三つの部分を選択して写真を撮影した後、細胞数を測定した(Kim, M.S. et al., Cancer Res., 63, pp. 5454-5461, 2003; Park, B.C. et al., Eur. J. Pharm., 567, pp. 193-197, 2007)。
図4(a)及び(b)に示されるように、マクロラクチン化合物の癌転移抑制効果を比較するための対照群として、癌転移に必須のマトリックスメタロプロテイナーゼ(以下、‘MMP’という)の抑制剤である、バチマスタット(batimastat)を使用した。5%FBSによって誘導された繊維肉腫細胞の浸潤は増加したが、MMP抑制剤であるバチマスタット5μmで処理した対照群では浸潤は有意に抑制された。MAとSMAは、5%FBSで誘導された浸潤を伴う繊維肉腫細胞の転移を濃度依存的に抑制した。特に、SMA 1μmは転移に対する有意な抑制効果を示し、SMA 5μmはバチマスタットに匹敵する優れた転移抑制効果を示した。
Claims (4)
- マクロラクチンA(macrolactin A)及び7−O−スクシニルマクロラクチンA(7−O−succinyl macrolactin A)の少なくとも1つを有効成分として含む、繊維肉腫の血管新生を抑制する方法に使用するための医薬組成物。
- 有効成分がマクロラクチンAである、請求項1に記載の医薬組成物。
- 有効成分が7−O−スクシニルマクロラクチンAである、請求項1に記載の医薬組成物。
- マクロラクチンA(macrolactin A)及び7−O−スクシニルマクロラクチンA(7−O−succinyl macrolactin A)の少なくとも一つを有効成分として含む、新生血管形成及び繊維肉腫の転移を阻害する方法に使用するための医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2010-0068886 | 2010-07-16 | ||
KR20100068886 | 2010-07-16 | ||
PCT/KR2011/001228 WO2012008674A1 (ko) | 2010-07-16 | 2011-02-23 | 마크로락틴 에이 및 그 유도체를 유효성분으로 함유하는 항혈관신생효과를 갖는 조성물 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013531032A JP2013531032A (ja) | 2013-08-01 |
JP5728085B2 true JP5728085B2 (ja) | 2015-06-03 |
Family
ID=45469646
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013519563A Expired - Fee Related JP5728085B2 (ja) | 2010-07-16 | 2011-02-23 | マクロラクチンa及びその誘導体を有効成分として含有する抗血管新生組成物 |
Country Status (7)
Country | Link |
---|---|
US (2) | US20130109745A1 (ja) |
EP (1) | EP2594268B1 (ja) |
JP (1) | JP5728085B2 (ja) |
KR (1) | KR101271593B1 (ja) |
CN (1) | CN103002892B (ja) |
CA (1) | CA2803999C (ja) |
WO (1) | WO2012008674A1 (ja) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102256185B1 (ko) * | 2014-09-09 | 2021-05-26 | 아르투로 솔리스 헤레라 | 멜라닌 및 멜라닌 유사체, 전구체, 및 유도체로 안과 질병, 질환, 및 증상의 치료 및 예방을 위한 방법 |
KR102094255B1 (ko) | 2017-09-27 | 2020-03-30 | 한양대학교 산학협력단 | 종양 표적 치료용 락토페린-글리시리진 컨쥬게이트 |
CN110051680B (zh) * | 2018-01-19 | 2022-02-18 | 沈阳福洋医药科技有限公司 | 一种用于预防和/或治疗阿尔茨海默病的药物、组合产品及其应用 |
JP7152052B2 (ja) | 2018-01-19 | 2022-10-12 | 沈陽福洋医薬科技有限公司 | カリマイシン又はその活性成分の用途 |
Family Cites Families (5)
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DE102004046024A1 (de) * | 2004-09-21 | 2006-03-30 | GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) | Antibiotikum und Verfahren zur Herstellung |
KR100764667B1 (ko) * | 2006-05-03 | 2007-10-08 | 한국생명공학연구원 | 펩타이드 디포밀레이즈 저해 및 항균활성을 갖는 신규이소마크로락틴 화합물 |
KR100895908B1 (ko) * | 2007-03-16 | 2009-05-04 | 일동제약주식회사 | 바실러스 폴리퍼멘티쿠스 케이제이에스-2 균주가 생산하는항균물질 마크로락틴 에이 |
JP2010011429A (ja) | 2008-06-30 | 2010-01-14 | Canon Inc | 画像処理装置及び画像処理装置の制御方法 |
KR101070324B1 (ko) * | 2009-05-22 | 2011-10-06 | 대우제약 주식회사 | 마크로락틴 에이 및 그 유도체를 유효성분으로 함유하는 항염제 조성물 |
-
2011
- 2011-02-14 KR KR1020110012707A patent/KR101271593B1/ko active IP Right Grant
- 2011-02-23 JP JP2013519563A patent/JP5728085B2/ja not_active Expired - Fee Related
- 2011-02-23 US US13/809,752 patent/US20130109745A1/en not_active Abandoned
- 2011-02-23 CN CN201180035102.1A patent/CN103002892B/zh not_active Expired - Fee Related
- 2011-02-23 WO PCT/KR2011/001228 patent/WO2012008674A1/ko active Application Filing
- 2011-02-23 EP EP11806959.0A patent/EP2594268B1/en not_active Not-in-force
- 2011-02-23 CA CA2803999A patent/CA2803999C/en not_active Expired - Fee Related
-
2013
- 2013-07-15 US US13/941,932 patent/US8940788B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
US20130303600A1 (en) | 2013-11-14 |
EP2594268A1 (en) | 2013-05-22 |
CN103002892B (zh) | 2016-03-30 |
US20130109745A1 (en) | 2013-05-02 |
EP2594268B1 (en) | 2016-10-19 |
KR101271593B1 (ko) | 2013-06-11 |
WO2012008674A1 (ko) | 2012-01-19 |
CA2803999A1 (en) | 2012-01-19 |
CA2803999C (en) | 2015-11-24 |
KR20120008429A (ko) | 2012-01-30 |
JP2013531032A (ja) | 2013-08-01 |
CN103002892A (zh) | 2013-03-27 |
EP2594268A4 (en) | 2013-12-18 |
US8940788B2 (en) | 2015-01-27 |
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