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KR970704889A - 핵산-함유 조성물, 이의 제조 방법 및 용도 - Google Patents

핵산-함유 조성물, 이의 제조 방법 및 용도 Download PDF

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KR970704889A
KR970704889A KR1019970700200A KR19970700200A KR970704889A KR 970704889 A KR970704889 A KR 970704889A KR 1019970700200 A KR1019970700200 A KR 1019970700200A KR 19970700200 A KR19970700200 A KR 19970700200A KR 970704889 A KR970704889 A KR 970704889A
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장-폴 베르
오뜨망 부시프
바바라 데멘익스
프락 레주알츠
모간 머그니
다니엘 쉐르망
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필립프 베커
롱프랑 로라 소시에테 아노님
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Abstract

하나 이상의 핵산 및 양이온 중합체를 함유하는 조성물, 및 특히 생체내 헥산 전달을 위한 유전자 치료에서의 이의 용도.

Description

핵산-함유 조성물, 이의 제조 방법 및 용도
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
도 1: (중합체 아민/핵산 포스페이트) 비 R로 나타낸 pH7에서 PEI800K의 형질감염 효율.
도 2: DNA의 양으로 나타낸 pH6에서 PEI800K의 형질감염 효율.
도 3: 비 R로 나타낸 pH6에서 PEI800K의 형질감염 효율.
도 5: PEI800K와 폴리리신간의 비교.
도 7: 보조제의 존채하에 PEI50K의 형질감염 효율.

Claims (30)

  1. 적어도 하나의 핵산 및 화학식(I)의 양이온 중합체를 포함하는 조성물:
    [화학식 I]
    상기식에서,
    R은 수소 원자 또는 화학식의 그룹일 수 있고, n은 2 내지 10의 정수이며 p 및 q는 정수이며,
    p와 q의 합은 중합체의 평균 분자량이 100 내지 107이 되게 하는 값이다.
  2. 제 1 항에 있어서, 화학식 (I)에서 n이 2 내지 5인 것을 특징으로 하는 조성물.
  3. 제 1 또는 2 항에 있어서, 중합체가 103 내지 5×106의 평균 분자량을 갖는 것을 특징으로 하는 조성물.
  4. 제 1 내지 3 항중 어느 한 항에 있어서, 중합체가 폴리에틸렌이민(PEI) 및 폴리프로필렌이민(PPI)으로부터 선택되는 것을 특징으로 하는 조성물.
  5. 제 4 항에 있어서, 중합체가 평균 분자량 50,000의 폴리에틸렌이민(PEI50K) 및 평균 분자량 800,000의 폴리에틸렌이민(PEI800K)으로부터 선택되는 것을 특징으로 하는 조성물.
  6. 제 1 내지 5 항중 어느 한 항에 있어서, 중합체 및 핵산의 각각의 부분이 중합체 아민/핵산 포스페이트비 R이 0.5 내지 50 사이인 방식으로 선택되는 것을 특징으로 하는 조성물.
  7. 제 6 항에 있어서, 비 R이 2 내지 50인 것을 특징으로 하는 조성물.
  8. 제 7 항에 있어서, 비 R이 5 내지 30인 것을 특징으로 하는 조성물.
  9. 제 1 내지 8 항중 어느 한 항에 있어서, 중합체/핵산 복합물과 배합될 수 있고 형질감염력을 개선시킬수 있는 하나 이상의 보조제를 추가로 포함하는 것을 특징으로 하는 조성물.
  10. 제 9 항에 있어서, 보조제가 지질, 단백질, 리포폴리아민 및 합성 중합체로부터 선택되는 것을 특징으로하는 조성물.
  11. 제 10 항에 있어서, 보조제가 양이온 지질인 것을 특징으로 하는 조성물.
  12. 제 11 항에 있어서, 양이온 지질이 하나 이상의 리포폴리아민인 것을 특징으로 하는 조성물.
  13. 제 12 항에 있어서, 리포폴리아민이 m이 2 이상의 정수로서 두개의 아민사이에 놓인 상이한 탄소 그룹간에 변화가능하고, l이 1 이상의 정수인 화학식 H2N-(-(CH)m-NH-)l-H에 상응하는 것을 특징으로 하는 조성물.
  14. 제 13 항에 있어서, 리포폴리아민이 디옥타데실아미도글리실스퍼민(DOGS) 또는 팔미토일포스파티딜에탄올아민 5-카복시스퍼밀아미드(DPPES)로부터 선택되는 것을 특징으로 하는 조성물.
  15. 제 10 항에 있어서, 보조제가 하나 이상의 중성 지질인 것을 특징으로 하는 조성물.
  16. 제 15 항에 있어서, 중성 지질(들)이 양쪽성이거나 생리학적 조건하에 이온 전하가 부족한 합성 또는 천연 지질중에서 선택되는 것을 특징으로 하는 조성물.
  17. 제 16 항에 있어서, 중성 지질(들)이 2개의 지방 사슬을 포함하는 지질인 것을 특징으로 하는 조성물.
  18. 제 16 항에 있어서, 중성 지질(들)이 디올레오일포스파티딜에탄올아민(DOPE), 올레오일팔미토일포스파티딜에탄올아민(POPE), 디스테아로일-, 팔미토일- 및 미리스토일포스파티딜에탄올아민 및 이들의 1- 내지 3-중 N-메틸화된 유도체; 포스파티딜글리세롤, 디아실글리세롤, 글리코실디아실글리세롤, 세레브로시드(예를 들면, 특히 갈락토세레브로시드), 스핑고리피드(예를 들면, 특히 스핑고미엘린) 또는 아시알로강글리오시드(예를 들면, 특히 아시알로GM1 및 -GM2)로부터 선택되는 것을 특징으로 하는 조성물.
  19. 제 1 항에 있어서, 핵산이 DNA인 것을 특징으로 하는 조성물.
  20. 제 1 항에 있어서, 핵산이 RNA인 것을 특징으로 하는 조성물.
  21. 제 19 또는 20 항에 있어서, 핵산이 화학적으로 변형되는 것을 특징으로 하는 조성물.
  22. 제 19 내지 21 항중 어느 한 항에 있어서, 핵산이 안티센스 서열인 것을 특징으로 하는 조성물.
  23. 제 19 내지 22 항중 어느 한 항에 있어서, 핵산이 치료 유전자를 함유하는 것을 특징으로 하는 조성물.
  24. 제 9 항에 있어서, 핵산 포스페이트의 몰당량 당 O.1 내지 20 몰당량, 보다 바람직하게는 1 내지 5 몰당량의 보조제를 포함하는 것을 특징으로 하는 조성물.
  25. 제 1 내지 24 항중 어느 한 항에 있어서, 표적화 요소를 포함하는 것을 특징으로 하는 조성물.
  26. 제 25 항에 있어서, 표적화 요소가 당 및/또는 항체 또는 항체 단편, 세포 수용체 리간드 또는 이의 단편, 또는 수용체 또는 수용체 단편같은 펩티드로 이루어지는 것을 특징으로 하는 조성물.
  27. 제 25 또는 26 항에 있어서, 표적화 요소가 화학식 (I)의 중합체와 공유 결합하는 것을 특징으로 하는 조성물.
  28. 제 1 내지 27 항중 어느 한 항에 있어서, 주사제용으로 약학적으로 허용되는 담체를 포함하는 것을 특징으로 하는 조성물.
  29. 제 1 내지 28 항중 어느 한 항에 있어서, 피부 및/또는 점막에 적용하가 위해 약학적으로 허용되는 담체를 포함하는 것을 특징으로 하는 조성물.
  30. 핵산을 세포내로 전달하기 위한 제 1 항에 따른 양이온 중합체의 용도.
KR1019970700200A 1994-07-13 1995-07-07 핵산-함유조성물,이의제조방법및용도 Expired - Lifetime KR100424802B1 (ko)

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FR9408735A FR2722506B1 (fr) 1994-07-13 1994-07-13 Composition contenant des acides nucleiques, preparation et utilisations
FR94/08735 1994-07-13

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KR100424802B1 KR100424802B1 (ko) 2004-06-23

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EP (1) EP0770140B1 (ko)
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AT (1) ATE367448T1 (ko)
AU (1) AU2930795A (ko)
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DE (1) DE69535540T9 (ko)
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