KR20100003306A - 미토콘드리아 표적화 산화방지제로서 사용되는 미토퀴논 유도체를 포함하는 약제학적 조성물 - Google Patents
미토콘드리아 표적화 산화방지제로서 사용되는 미토퀴논 유도체를 포함하는 약제학적 조성물 Download PDFInfo
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- KR20100003306A KR20100003306A KR1020097024866A KR20097024866A KR20100003306A KR 20100003306 A KR20100003306 A KR 20100003306A KR 1020097024866 A KR1020097024866 A KR 1020097024866A KR 20097024866 A KR20097024866 A KR 20097024866A KR 20100003306 A KR20100003306 A KR 20100003306A
- Authority
- KR
- South Korea
- Prior art keywords
- compound
- mitoquinone
- antioxidant
- cyclodextrin
- formula
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 45
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 43
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Abstract
Description
Claims (27)
- 결합 잔기에 의해 산화방지성 잔기에 결합된 친유성 양이온성 잔기와, 당해 양이온성 잔기를 위한 음이온성 보충물을 포함하고, 양이온성 잔기가 산화방지성 잔기를 미토콘드리아에 표적화할 수 있으며, 음이온성 보충물이 브로마이드 이온 또는 니트레이트 음이온이 아니고 산화방지성 잔기, 양이온성 잔기 또는 결합 잔기에 대해 반응성을 나타내지 않는 약제학적으로 허용되는 음이온인 화학적으로 안정한 산화방지성 화합물.
- 제1항에 있어서, 친유성 양이온성 잔기가 치환되거나 치환되지 않은 트리페닐포스포늄 양이온인 화합물.
- 제1항에 있어서, 약제학적으로 허용되는 음이온이 (i) 알킬 설포네이트, (ii) 할로겐 이온이 아닌 약제학적으로 허용되는 음이온 및 (iii) 친핵성이 아닌 약제학적으로 허용되는 음이온으로 이루어진 그룹으로부터 선택되는 화합물.
- 제1항에 있어서, 약제학적으로 허용되는 음이온이 메탄설포네이트, p-톨루엔설포네이트, 에탄설포네이트, 벤젠설포네이트 및 2-나프탈렌설포네이트로 이루어진 그룹으로부터 선택되는 화합물.
- 제1항에 있어서, 약제학적으로 허용되는 음이온이 메탄설포네이트인 화합물.
- 제1항에 있어서, 산화방지성 잔기가 (i) 퀴논 또는 퀴놀, (ii) 비타민 E 또는 비타민 E 유도체, (iii) 쇄 절단형 산화방지제, (iv) 유도체화 플러린 및 (v) 스핀 트랩으로 이루어진 그룹으로부터 선택되는 화합물.
- 제1항에 있어서, 산화방지성 잔기가 부틸화 하이드록시아니솔, 부틸화 하이드록시톨루엔, 5,5-디메틸피롤린-N-옥사이드, 3급-부틸니트로소벤젠, 3급-니트로소벤젠 및 α-페닐-3급-부틸니트론으로 이루어진 그룹으로부터 선택되는 화합물.
- 제8항에 있어서, Z가 알킬 설포네이트, 아릴 설포네이트, 알킬 니트레이트 및 아릴 니트레이트로 이루어진 그룹으로부터 선택되는 화합물.
- 제8항에 있어서, (C)n의 C가 포화된 화합물.
- 제1항 내지 제12항 중의 어느 한 항에 따른 화학적으로 안정한 산화방지성 화합물, 및 담체 또는 부형제를 포함하는, 노화와 관련된 퇴행성 질환, 뇌졸중, 심장 마비, 수술 또는 장기 이식에서의 염증 및/또는 허혈-재관류 조직 손상 치료용 약제학적 조성물.
- 제13항에 있어서, 담체 또는 부형체가 사이클로덱스트린을 포함하는 약제학적 조성물.
- 제14항에 있어서, 산화방지성 화합물 대 사이클로덱스트린의 몰 비가 약 10:1 내지 약 1:10으로 존재하는 약제학적 조성물.
- 제14항에 있어서, 산화방지성 화합물 대 사이클로덱스트린의 몰 비가 (i) 약 5:1 내지 약 1:5, (ii) 약 4:1 내지 약 1:4, (iii) 약 2:1 내지 약 1:2, (iv) 약 1:1 및 (v) 약 1:2로 이루어진 그룹으로부터 선택되는 약제학적 조성물.
- 제14항에 있어서, 사이클로덱스트린이 β-사이클로덱스트린인 약제학적 조성물.
- 제13항에 있어서, 산화방지성 화합물이 제12항에 따르는 화합물을 포함하고, 담체 또는 부형제가 사이클로덱스트린을 포함하고, 산화방지성 화합물 대 사이클로덱스트린의 몰 비가 약 1:2인 약제학적 조성물.
- 제13항에 있어서, 경구 투여용으로 제형화된 약제학적 조성물 및 비경구 투여용으로 제형화된 약제학적 조성물로 이루어진 그룹으로부터 선택되는 약제학적 조성물.
- 제18항에 있어서, 경구 투여용으로 제형화된 약제학적 조성물 및 비경구 투여용으로 제형화된 약제학적 조성물로 이루어진 그룹으로부터 선택되는 약제학적 조성물.
- 제1항 내지 제12항 중의 어느 한 항에 따르는 화학적으로 안정한 산화방지성 화합물을 포함하는, 파킨슨병(Parkinson's disease), 알츠하이머병(Alzheimer's disease), 헌팅턴 무도병(Huntington's Chorea) 또는 프리드라이히 보행 실조(Friedreich's Ataxia) 치료용 약제학적 조성물.
- 사이클로덱스트린 또는 사이클로덱스트린 유도체를 (a) 화학식 1의 화합물 및/또는 이의 퀴놀 형태 및 (b) 화학식 3의 화합물 및/또는 이의 퀴놀 형태로부터 선택된 화합물과 혼합하는 단계를 포함하는, 세포 내의 산화성 스트레스를 감소시킬 수 있는 산화방지성 화합물의 제조방법.화학식 1화학식 3위의 화학식 1에서,R1, R2 및 R3은 동일하거나 상이하며, C1 내지 C5 알킬, 치환된 C1 내지 C5 알킬 및 H로부터 선택되고,n은 2 내지 20의 정수이고,Z는 브로마이드 이온 또는 니트레이트 음이온이 아니고 화학식 1의 화합물의 모든 잔기에 대해 반응성을 나타내지 않는 약제학적으로 허용되는 음이온이다.
- 제23항에 있어서, 이데베놀 메실레이트가 트리페닐포스핀과의 반응 전에 이데베논 메실레이트를 화학적으로 환원시킴으로써 수득되는 방법.
- 제23항에 있어서, 이데베놀 메실레이트와 트리페닐포스핀의 반응 전에,(a) 이데베논 용액에 트리에틸아민을 첨가하여 이데베논 트리에틸아민 혼합물을 수득하는 단계;(b) 단계 (a)의 이데베논 트리에틸아민 혼합물을 냉각시키는 단계 및(c) 이데베논 트리에틸아민 혼합물을 메탄설포닐 클로라이드 용액와 반응시켜 이데베논 메실레이트를 수득하는 단계를 추가로 포함하는 방법.
- 제25항에 있어서,(i) 트리에틸아민을 이데베논에 비해 몰 과량으로 첨가함을 포함하는 단계(a),(ii) 10±3℃로 냉각시킴을 포함하는 단계(b) 및(iii) 약 10 내지 15℃에서 반응시킴을 포함하는 단계(c) 중의 하나 이상을 포함하는 방법.
- 제21항에 있어서, 제1항 내지 제12항 중의 어느 한 항에 따르는 화학적으로 안정한 산화방지성 화합물을 포함하는, 프리드라이히 보행실조 치료용 약제학적 조성물.
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- 2006-03-20 ZA ZA2006/02304A patent/ZA200602304B/en unknown
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-
2011
- 2011-01-05 US US12/985,205 patent/US20110288055A1/en not_active Abandoned
- 2011-04-28 AU AU2011201909A patent/AU2011201909A1/en not_active Abandoned
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2016
- 2016-10-14 US US15/294,519 patent/US20170246195A1/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2021125800A1 (ko) * | 2019-12-16 | 2021-06-24 | 울산과학기술원 | 신생혈관형성인자의 억제를 위한 화합물 및 그 용도 |
Also Published As
Publication number | Publication date |
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IL173807A0 (en) | 2006-07-05 |
US20080161267A1 (en) | 2008-07-03 |
JP2007503387A (ja) | 2007-02-22 |
NZ546070A (en) | 2010-01-29 |
SG145715A1 (en) | 2008-09-29 |
JP4648319B2 (ja) | 2011-03-09 |
ES2541769T3 (es) | 2015-07-24 |
IL173807A (en) | 2014-02-27 |
KR101003960B1 (ko) | 2010-12-30 |
CN1839142B (zh) | 2010-06-16 |
ZA200602304B (en) | 2012-06-27 |
CN1839142A (zh) | 2006-09-27 |
AU2011201909A1 (en) | 2011-05-19 |
US7888335B2 (en) | 2011-02-15 |
US20110288055A1 (en) | 2011-11-24 |
US20170246195A1 (en) | 2017-08-31 |
HK1093988A1 (en) | 2007-03-16 |
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