KR960703624A - 단백질 캡슐화 불용성 가스 마이크로스피어 및 그것의 제조 및 초음파 영상화제로서의 이용(protein encapsulated insoluble gas microspheres and their preparation and use as ultrasonic imaging agents) - Google Patents

단백질 캡슐화 불용성 가스 마이크로스피어 및 그것의 제조 및 초음파 영상화제로서의 이용(protein encapsulated insoluble gas microspheres and their preparation and use as ultrasonic imaging agents)

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Publication number
KR960703624A
KR960703624A KR1019960700002A KR19960700002A KR960703624A KR 960703624 A KR960703624 A KR 960703624A KR 1019960700002 A KR1019960700002 A KR 1019960700002A KR 19960700002 A KR19960700002 A KR 19960700002A KR 960703624 A KR960703624 A KR 960703624A
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South Korea
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gas
protein
encapsulated
composition
insoluble
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KR1019960700002A
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English (en)
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KR100218642B1 (ko
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제이. 램버트 카엘
베나이 포델 셰일라
지. 자블론스키 에드워드
헐 칼
해밀톤 케네스
로어만 롤프
Original Assignee
스티븐 로손
몰리쿨라 바이오시스템즈 인코퍼레이티드
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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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • B01J13/04—Making microcapsules or microballoons by physical processes, e.g. drying, spraying

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Radiology & Medical Imaging (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Acoustics & Sound (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Manufacturing Of Micro-Capsules (AREA)
  • Medicinal Preparation (AREA)

Abstract

개선된 압력내성 및 안정성을 갖는 캡슐화된 가스 마이크로스피어는 인간혈청알부민 같은 필모겐 단백질 수용액과 퍼플루오로프로판 같은 수불용성 가스와 혼합하고 대기에 대해 닫혀 있는 장치에서 산소부재하에서 혼합물을 초음파 또는 기계적 공동화시킴으로써 만들어진다.

Description

단백질 캡슐화 불용성 가스 마이크로스피어 및 그것의 제조 및 초음파 영상화제로서의 이용(PROTEIN ENCAPSULATED INSOLUBLE GAS MICROSPHERES AND THEIR PREPARATION AND USE AS ULTRASONIC IMAGING AGENTS)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (17)

  1. 열-불용성화된 팔모겐 단백질에 의해 캡슐화된 가스의 마이크로스피어의 수성현탁액을 함유하는 초음파 영상화제 조성물에서, 캡슐화된 가스는 완전히 약리학적으로 허용가능한 수 불용성 가스인 조성물.
  2. 제1항에 있어서, 25℃에서의 물에서의 가스의 용해도가 물 ㎖당 가스 0.01㎖ 이하인 것을 특징으로 하는 조성물.
  3. 제1항에 있어서, 단백질이 인간혈청 알부민인 것을 특징으로 하는 조성물.
  4. 제1항에 있어서, 단백질은 인간혈청 알부민이고 불용성 가스는 퍼플루오로프로판인 것을 특징으로 하는 조성물.
  5. 열-불용성화된 필모겐 단백질에 의해 캡슐화된 퍼플루오로 프로판 가스의 마이크로스피어의 수성현탁액을 함유하는 초음판 영상화제 조성물.
  6. 제3항에 있어서, 단백질의 인간혈청 알부민인 것을 특징으로 하는 조성물.
  7. 캡슐화된 가스의 존재하에서, 그리고 산소의 부재하에서 열-불용성화된 필모겐 단백질에 의해 캡슐화된 가스의 마이크로스피어의 수성현탁액을 함유하는 초음파 영상화제 조성물에서, 캡슐화된 가스는 완전히 약리학적으로 허용가능한 수 불용성 가스인 조성물.
  8. 제7항에 있어서, 25℃에서 물에서의 가스의 용해도가 물 ㎖당 가스 0,01㎖ 이하인 것을 특징으로 하는 조성물.
  9. 제7항에 있어서, 단백질은 인간혈청 알부민인 것을 특징으로 하는 조성물.
  10. 필모겐 단백질의 수용액과 약리학적으로 허용가능한 불용성 가스의 혼합물을 산소의 부재하에서 초음파 또는 기계적 공동화에 적용시키는 것으로 이루어지는, 초음파 영상화제로서 유용한 캡슐환된 가스마이크로스피어의 제조방법.
  11. 필모겐 단백질의 수용액과 약리학적으로 허용가능한 불용성 가스의 혼합물을 대기에 대해 닫혀있는 장치에서 초음파 또는 기계적 공동화에 적용시키는 것으로 이루어지는, 초음파 영상화제로서 유용한 캡슐화된 가스 마이크로스피어의 제조방법.
  12. 제5항 또는 제6항에 있어서, 단백질은 인간혈청 알부민이고, 가스는 퍼플루오로프로판인 것을 특징으로 하는 방법.
  13. 하기의 단계들로 이루어지는 초음파 영상화제로서 유용한 캡슐화된 가스 마이크로스피어의 제조방법; a) 후속되는 기계적 유화공정동안 초기변성온도를 달성하는데 필요한 온도에서 열-변성 가능 단백질의 수용액을 제공하는 단계; b) 이 용액을 가스와 조합하는 단계; c) 단백질 용액과 가스혼합물을 기계적 전단에 의해 유화시켜서 약 0.1 내지 10미크론의 범위의 평균직경을 갖는 가스 마이크로버블의 현탁액을 형성하는 단계; 및 d) 현탁액을 기계적으로 공동화시켜서 가스-용액계면에서 단백질이 변성되게 하고 그로써 침전되게 함으로써 가스 마이크로버블을 캡슐화하여 마이크로스피어를 형성하는 단계.
  14. 제8항에 있어서, 단백질은 인간혈청 알부민이고 가스는 퍼플루오로프로판인 것을 특징으로 하는 방법.
  15. 제8항 또는 제9항에 있어서, 단계(c) 및 (d)는 혼합물을 밀(mill)을 통과시킴으로서 이루어지는 것을 특징으로 하는 방법.
  16. 제10항, 11항, 12항, 13항, 14항 또는 15항의 방법에 의해 제조된 캡슐화된 가스 마이크로스피어.
  17. 하기의 단계로 이루어지는 환자의조직 및/또는 기관의 콘트라스트를 초음파 영상에서 강화시키는 방법; (a) 제1항, 2항, 3항, 4항, 5항, 6항, 7항, 8항, 9항 또는 16항의 조성물 또는 마이크로스피어를 환자에게 주사하는 단계, (b) 조직 및/또는 기판에 초음파에너지를 적용시키는 단계, (c) 조직 및/또는 기관으로부터 반사되는 초음파 에너지를 검출하는 단계, 및 (d) 반사된 에너지를 영상으로 변환시키는 단계.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019960700002A 1993-07-02 1994-07-01 열변성된 단백질로부터 캡슐화된 마이크로스피어의 제조방법 KR100218642B1 (ko)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US8671793A 1993-07-02 1993-07-02
US8/086,717 1993-07-02
US08/086,717 1993-07-02
US18765694A 1994-01-26 1994-01-26
US08/187,656 1994-01-26
US8/187,656 1994-01-26
PCT/US1994/007533 WO1995001187A1 (en) 1993-07-02 1994-07-01 Protein encapsulated insoluble gas microspheres and their preparation and use as ultrasonic imaging agents

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KR960703624A true KR960703624A (ko) 1996-08-31
KR100218642B1 KR100218642B1 (ko) 1999-09-01

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Country Status (20)

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US (1) US5552133A (ko)
EP (2) EP0885615B1 (ko)
JP (3) JP2905598B2 (ko)
KR (1) KR100218642B1 (ko)
CN (1) CN1129910A (ko)
AT (1) ATE179334T1 (ko)
AU (1) AU683485B2 (ko)
BR (1) BR9406993A (ko)
CA (1) CA2166459C (ko)
CZ (1) CZ350895A3 (ko)
DE (2) DE69418101T2 (ko)
ES (2) ES2195247T3 (ko)
FI (1) FI956312A (ko)
HU (1) HUT74827A (ko)
IL (1) IL110185A (ko)
NO (1) NO955351L (ko)
NZ (1) NZ268826A (ko)
PL (1) PL312387A1 (ko)
TW (1) TW283646B (ko)
WO (1) WO1995001187A1 (ko)

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