KR940703691A - 초음파반향검사용 증진제로서의 안정한 미기포 현탁액(stable mi-crobubble suspensions as enhancement agents for ultrasound echography) - Google Patents

초음파반향검사용 증진제로서의 안정한 미기포 현탁액(stable mi-crobubble suspensions as enhancement agents for ultrasound echography)

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KR940703691A
KR940703691A KR1019940702306A KR19940702306A KR940703691A KR 940703691 A KR940703691 A KR 940703691A KR 1019940702306 A KR1019940702306 A KR 1019940702306A KR 19940702306 A KR19940702306 A KR 19940702306A KR 940703691 A KR940703691 A KR 940703691A
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phospholipid
suspension
microbubbles
gas
surfactant
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슈네이더 미셀
브로쇼 쟝
퓌기니에 제롬
얀 펑
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네나드 토모브-그리소고노
브라코 인터내셔날 비. 브이.
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
    • A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
    • A61K49/225—Microparticles, microcapsules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
    • A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
    • A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres

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Abstract

본 명세서에는 초음파반향검사에서 콘트라스트제로 사용가능한 수성 담체액체내에서의 가스충전 미기포의 주사용 현탁액이 기재되어 있다. 이 현탁액은 양친매성 화합물들로 이루어지는데 양친매성 화합물 중 적어도 하나는 시간경과 및 압력으로 인한 미기포의 터짐을 방지하는 안정제로서의 박층화된 인지질일 수 있다. 담체액체에서의 인지질 농도는 0.01중량％ 이하이나 인지질 분자가 가스미기포-액체 계면에 단독으로 존재할 때의 것과 동일하거나 그보다 높다. 또한 공기 또는 가스충전 미기포의 한정한 현탁액 제조방법도 기재되어 있다.

Description

초음파반향검사용 증진제로서의 안정한 미기포 현탁액(STABLE MICROBUBBLE SUSPE-NSIONS AS ENHANCEMENT AGENTS FOR ULTRASOUND ECHOGRAPHY)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (22)

  1. 밀리리터당 적어도 107개의 미기포와 양친매성 화합물을 포함하며 상기 양친매성 화합물중 적어도 하나가 미기포의 터짐을 방지하는 인지질 안정제인 초음파반향검사에서 콘트라스트제로 사용가능한 수성 담체 액체내에서의 가스충전 미기포의 주사용 현탁액에 있어서, 담체약체에서의 인지질 농도는 0.01중량％ 이하임과 동시에 인지질 분자가 가스미기포-액체 계면에 단독으로 존재할 때의 것과 동일하거나 그보다 높은 것을 특징으로 하는 주사용 현탁액.
  2. 제 1 항에 있어서, 밀리리터당 미기포의 농도가 108내지 1014인 것을 특징으로 하는 주사용 현탁액.
  3. 제 1 항에 있어서, 인지질의 농도가 0.00013중량％ 이상인 것을 특징으로 하는 주사용 현탁액.
  4. 제 1 항 내지 제 3항 중 어느 한 항 에 있어서, 액체담체가 수용성 다당류, 올리고당류, 및 폴리에틸렌 글리콜과 같은 친수성 중합체를 안정제로서 더 함유하는 것을 특징으로 하는 주사용 현탁액.
  5. 제 1 항 내지 제 4항 중 어느 한 항에 있어서, 인지질이 적어도 부분적으로 박막 또는 박층상으로 되어 있고, 포스파티드산, 포스파티딜콜린, 포스파티딜에탄올아민, 포스파티딜세린, 포스파티딜글리세롤 포스파티딜노시톨, 카르디올리핀 및 스핀고미에린과 같은 레시틴 중에서 선택되는 것을 특징으로 하는 주사용 현탁액.
  6. 제 4 항 또는 제 5항에 있어서, 포스파티딜글리세롤, 포스파티드산, 디세틸인산염, 콜레스테롤, 에르고스테롤, 피토스테롤, 시토스테롤, 라노스테롤, 토코페놀, 갈산프로필, 팔미트산 아스코르빌 및 부틸화 히드록시톨루엔 중에서 선택된 인지질의 성질에 양향을 미치는 물질을 더 함유하는 것을 특징으로 하는 주사용 현탁액.
  7. 제 1 항 내지 제 3항 중 어느 한 항에 있어서, 인지지질이 동결건조 또는 분무건조에 의해 얻어진 분말상인 것을 특징으로 하는 주사용 현탁액.
  8. 제 1 항에 있어서, 밀리리터당 약 108-109개의 미기포를 함유함과 동시에 미기포 크기가 저장 중에 거의 또는 전혀 변화를 보이지 않는 0.5 내지 10㎛인 것을 특징으로 하는 주사용 현탁액.
  9. 제 1 항에 있어서, 액체담체가 지방산, 지방산 및 알코올의 폴리알킬렌 글리콜, 폴리알킬렌화 당 및 기타 탄수화물과 같은 폴리올과의 에스테르 및 에테르 및 폴리알킬렌화 글리세롤 중에서 선택된 비박층상의 계면화성제를 50중량％까지 더 포함하는 것을 특징으로 하는 주사용 현탁액.
  10. 제 1 항 내지 제 9항 중 어느 한 항에 있어서, 미기포가 SF6, CF4, 프레온 또는 공기로 충전되어 있는 것을 특징으로 하는 주사용 현탁액.
  11. 공기 또는 가스충전 미기포의 현탁액 제조방법으로, 적어도 하나의 피막형성성 계면활성제를 선택하고, 이 계면활성제를 분말로 전환하고, 이 분말을 공기 또는 또다른 가스와 접촉시키고, 분말 계면활성제를 수성 담체액체와 혼합하여 상기 현탁액을 생성하는 방법에 있어서, 현탁액을 용기에 넣고, 용기 상부에 가스충전 미기포의 층을 형성하고, 형성된 미기포의 층을 분리하고, 미기포를 미기포가스로 포화된 수용액으로 세정하는 것을 특징으로 하는 방법.
  12. 제11항에 있어서, 분말로 전환하기 전에 피막형성성 계면활성제를 적어도 부분적으로 박막화하는 것을 특징으로하는 방법.
  13. 제12항에 있어서, 공기 또는 또다른 가스와 접속시키기 전에 부분적으로 박막화된 계면활성제를 수성액체담체와 혼합하는 것을 특징으로 하는 방법.
  14. 제12항 또는 제13항에 있어서, 액체담체가 수용성 단백질, 폴리펩티드, 당, 다당류, 올리고당류 및 친수성 중합체 중에서 선택된 안정제 화합물을 더 함유하는 것을 특징으로 하는 방법.
  15. 제12항에 있어서, 전환은 계면활성제를 가용성 또는 불용성 물질의 입자상에 피복하여 이 피복입자를 공기 또는 가스중에 잠시 방치하고, 이 피복입자를 수성 액체 담체와 혼합함으로써 행하는 것을 특징으로 하는 방법.
  16. 제12항에 있어서, 전환은 필름 형성성 지질의 수용액을 고압하에 초음파처리 또는 균질화함으로써 행하고, 이 조작은 적어도 부분적으로 리포솜을 생성하는 것을 특징으로 하는 방법.
  17. 제16항에 있어서, 적어도 부분적으로 박막화된 계면활성제를 공기 또는 또다른 가스와 접촉시키기 전에 리포솜함유 용액을 동결건조하는 것을 특징으로 하는 방법.
  18. 제16항 또는 제17항에 있어서, 피막형성성 지질의 수용액이 또한 친수성 중합체 및 탄수화물 중에서 선택된 점성강화제 또는 안정제를 포함된 지질에 대하여 10 : 1 내지 1000: 1의 중량비로 함유하는 것을 특징으로 하는 방법.
  19. 피막형성성 계면활성제, 친수성 안정제 및 수성 액체담체로 이루어진 공기 또는 가스충전 미기포의 현탁액 제조방법에 있어서, 피막형성성 계면활성제 및 친수성 안정제를 유기용매에 용해하고, 이 용액을 동결건조하여 건조분말을 생성하고, 이 분말을 공기 또는 또다른 가스와 접촉시키고, 상기 분말을 수성 담체와 혼합하는 것을 특징으로 하는 방법.
  20. 제19항에 있어서, 친수성 안정제가 폴리에틸렌 글리콜, 폴리비닐 피롤리돈, 폴리비닐 알코올, 글리콜산, 말산 또는 말톨인 것을 특징으로 하는 방법.
  21. 제19항 또는 제20항에 있어서, 유기용매가 4차 부탄올, 2-메틸-2-부탄올 또는 C2Cl4F2인 것을 특징으로 하는 방법.
  22. 박층화 인지질과 임의로 기타 첨가제를 수성 담체액체에 현탁하고, 상기 인지질을 반향검사응답을 제공하기에 충분한 농도의 미기포가 현탁액에 생성될 정도의 조건하에서, 현탁하기 전 또는 후에 가스와 접촉시키고, 상기 인지질 부분이 상기 기포 둘레에 안정화층을 형성하도록 하고, 그후 미기포 안정화에 관련되지 않은 과잉 인지질의 담체액체를 제거하는 것으로 이루어지는 것을 특징으로 하는 특허청구의 범위 제1항에 따른 가스충전 미기포의 주사용 현탁액 제조방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019940702306A 1992-11-02 1993-10-21 초음파반향검사용 증진제로서의 안정한 미기포 현탁액 KR100216138B1 (ko)

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EP92810837.2 1992-11-02
EP92810837 1992-11-02
PCT/EP1993/002915 WO1994009829A1 (en) 1992-11-02 1993-10-21 Stable microbubble suspensions as enhancement agents for ultrasound echography

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KR940703691A true KR940703691A (ko) 1994-12-12
KR100216138B1 KR100216138B1 (ko) 1999-08-16

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FI943167A0 (fi) 1994-07-01
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DE10199055I2 (de) 2005-09-29
DE69307124D1 (de) 1997-02-13
AU704954B2 (en) 1999-05-13
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FI943167A (fi) 1994-07-01
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US5908610A (en) 1999-06-01
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