KR920702232A - 효과적인 안정한 무-임뮤노겐형 적혈구 대용물인 화학적 변형 헤모글로빈 - Google Patents

효과적인 안정한 무-임뮤노겐형 적혈구 대용물인 화학적 변형 헤모글로빈

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KR920702232A
KR920702232A KR1019920701208A KR920701208A KR920702232A KR 920702232 A KR920702232 A KR 920702232A KR 1019920701208 A KR1019920701208 A KR 1019920701208A KR 920701208 A KR920701208 A KR 920701208A KR 920702232 A KR920702232 A KR 920702232A
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South Korea
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poly
hemoglobin
process according
polyalkylene oxide
ethylene glycol
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KR1019920701208A
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English (en)
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노(Nho)쾅
새뮤얼 짤리프스키
프랭크 데이빗
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엔존, 인코퍼레이티드
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Publication of KR920702232A publication Critical patent/KR920702232A/ko

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C07K17/02—Peptides being immobilised on, or in, an organic carrier
    • C07K17/06—Peptides being immobilised on, or in, an organic carrier attached to the carrier via a bridging agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6445—Haemoglobin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/795—Porphyrin- or corrin-ring-containing peptides
    • C07K14/805—Haemoglobins; Myoglobins

Abstract

내용 없음

Description

효과적인 안정한 무-임뮤노겐형 적혈구 대용물인 화학적 변형 헤모글로빈
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 헤모글로빈 변형을 위한 SC-PEG와 BSC-PEG의 이용관계를 보여준다.

Claims (58)

  1. (ⅰ)헤모글로빈을 환원하고 (ⅱ)(ⅰ)단계의 환원된 헤모글로빈을 헴(heme)산소 결합위치의 구조적 집 체를 유지하는 조건하에서 활성화 폴리알킬렌 산화물에 결합시키는 것을 특징으로 하는 화학적 변형 헤모글로빈 제조방법.
  2. 제1항에 있어서, 헤로글로빈을 시스테인을 써서 환원하는 것을 특징으로 하는 제조방법.
  3. 제2항에 있어서, 시스테인 농도가 약 300mM인 것을 특징으로 하는 제조방법.
  4. 제1항에 있어서, 고음이온 농도를 이용하여 헴 산소결합위치의 구조적 집체를 유지하는 조건을 만드는 것을 특징으로 하는 제조방법.
  5. 제4항에 있어서, 음이온이 염화물 이온인 것을 특징으로 하는 제조방법.
  6. 제1항에 있어서, 폴리알킬렌 산화물이 폴리(에틸렌 글리콜)인 것을 특징으로 하는 제조방법.
  7. 제2항에 있어서, 폴리알킬렌 산화물이 폴리(에틸렌 글리콜)인 것을 특징으로 하는 제조방법.
  8. 제3항에 있어서, 폴리알킬렌 산화물이 폴리(에틸렌 글리콜)인 것을 특징으로 하는 제조방법.
  9. 제4항에 있어서, 폴리알킬렌 산화물이 폴리(에틸렌 글리콜)인 것을 특징으로 하는 제조방법.
  10. 제5항에 있어서, 폴리알킬렌 산화물이 폴리(에틸렌 글리콜)인 것을 특징으로 하는 제조방법.
  11. 제1항에 있어서, 폴리알킬렌 산화물을 우레탄 결합으로 헤모글로빈에 결합시키는 것을 특징으로 하는 제조방법.
  12. 제2항에 있어서, 폴리알킬렌 산화물을 우레탄 결합으로 헤모글로빈에 결합시키는 것을 특징으로 하는 제조방법.
  13. 제3항에 있어서, 폴리알킬렌 산화물을 우레탄 결합으로 헤모글로빈에 결합시키는 것을 특징으로 하는 제조방법.
  14. 제4항에 있어서, 폴리알킬렌 산화물을 우레탄 결합으로 헤모글로빈에 결합시키는 것을 특징으로 하는 제조방법.
  15. 제5항에 있어서, 폴리알킬렌 산화물을 우레탄 결합으로 헤모글로빈에 결합시키는 것을 특징으로 하는 제조방법.
  16. 제6항에 있어서, 폴리(에틸렌 글리콜)이 우레탄 결합에 의해 헤모글로빈에 결합하는 것을 특징으로 하는 제조방법.
  17. 제7항에 있어서, 폴리(에틸렌 글리콜)이 우레탄 결합에 의해 헤모글로빈에 결합하는 것을 특징으로 하는 제조방법.
  18. 제8항에 있어서, 폴리(에틸렌 글리콜)이 우레탄 결합에 의해 헤모글로빈에 결합하는 것을 특징으로 하는 제조방법.
  19. 제9항에 있어서, 폴리(에틸렌 글리콜)이 우레탄 결합에 의해 헤모글로빈에 결합하는 것을 특징으로 하는 제조방법.
  20. 제10항에 있어서, 폴리(에틸렌 글리콜)이 우레탄 결합에 의해 헤모글로빈에 결합하는 것을 특징으로 하는 제조방법.
  21. 제1항에 있어서, 활성화 폴리(에틸렌 글리콜)이 폴리(에틸렌-글리콜)-N-숙신이미드 카보네이트인 것을 특징으로 하는 제조방법.
  22. 제2항에 있어서, 활성화 폴리(에틸렌 글리콜)이 폴리(에틸렌-글리콜)-N-숙신이미드 카보네이트인 것을 특징으로 하는 제조방법.
  23. 제3항에 있어서, 활성화 폴리(에틸렌 글리콜)이 폴리(에틸렌-글리콜)-N-숙신이미드 카보네이트인 것을 특징으로 하는 제조방법.
  24. 제4항에 있어서, 활성화 폴리(에틸렌 글리콜)이 폴리(에틸렌-글리콜)-N-숙신이미드 카보네이트인 것을 특징으로 하는 제조방법.
  25. 제5항에 있어서, 활성화 폴리(에틸렌 글리콜)이 폴리(에틸렌-글리콜)-N-숙신이미드 카보네이트인 것을 특징으로 하는 제조방법.
  26. 제1항에 있어서, 활성화 폴리(에틸렌 글리콜)이 폴리(에틸렌-글리콜)-비스-N-숙신이미드 카보네이트인 것을 특징으로 하는 제조방법.
  27. 제2항에 있어서, 활성화 폴리(에틸렌 글리콜)이 폴리(에틸렌-글리콜)-비스-N-숙신이미드 카보네이트인 것을 특징으로 하는 제조방법.
  28. 제3항에 있어서, 활성화 폴리(에틸렌 글리콜)이 폴리(에틸렌-글리콜)-비스-N-숙신이미드 카보네이트인 것을 특징으로 하는 제조방법.
  29. 제4항에 있어서, 활성화 폴리(에틸렌 글리콜)이 폴리(에틸렌-글리콜)-비스-N-숙신이미드 카보네이트인 것을 특징으로 하는 제조방법.
  30. 제5항에 있어서, 활성화 폴리(에틸렌 글리콜)이 폴리(에틸렌-글리콜)-비스-N-숙신이미드 카보네이트인 것을 특징으로 하는 제조방법.
  31. 제1항에 있어서, 활성 폴리알킬렌 산화물이 폴리알킬렌 산화물의 활성 카보네이트 유도체인 것을 특징으로 하는 제조방법.
  32. 제2항에 있어서, 활성 폴리알킬렌 산화물이 폴리알킬렌 산화물의 활성 카보네이트 유도체인 것을 특징으로 하는 제조방법.
  33. 제3항에 있어서, 활성 폴리알킬렌 산화물이 폴리알킬렌 산화물의 활성 카보네이트 유도체인 것을 특징으로 하는 제조방법.
  34. 제4항에 있어서, 활성 폴리알킬렌 산화물이 폴리알킬렌 산화물의 활성 카보네이트 유도체인 것을 특징으로 하는 제조방법.
  35. 제5항에 있어서, 활성 폴리알킬렌 산화물이 폴리알킬렌 산화물의 활성 카보네이트 유도체인 것을 특징으로 하는 제조방법.
  36. 제1항에 있어서, 헤모글로빈을 (ⅰ)단계에서 부분환원시 데옥시헤모글로빈의 백분율이 50%이상이고 80%는 초과하지 않는 것을 특징으로 하는 제조방법.
  37. 제1항에 있어서, 헤모글로빈을 (ⅰ)단계에서 30nM농도의 시스테인으로 환원시키고 다시 (ⅱ)단계에서 약 1M의 염화물 농도로 폴리(에틸렌 글리콜)-N-숙신이미드 카보네이트에 결합시키는 것을 특징으로 하는 제조방법.
  38. 제1항에 있어서, 헤모글로빈을 기체-투과막을 통과하는 기체 교환법에 따라 (ⅰ)단계에서 환원하는 것을 특징으로 하는 제조방법.
  39. 제38항에 있어서, 헤모글로빈을 (ⅱ)단계에서 약 30:1의 몰비율로 폴리(에틸렌 글리콜)-N-숙신이드 카보네이트에 결합시키는 것을 특징으로 하는 제조방법.
  40. 제38항에 있어서, 헤모글로빈을 (ⅱ)단계에서 약 40:1의 몰비율로 폴리(에틸렌 글리콜)-N-숙신이미드 카보네이트에 결합시키는 것을 특징으로 하는 제조방법.
  41. 제1항에 있어서, 헤모글로빈을 (ⅰ)단계에서 30nM농도의 시스테인으로 환원시키고 다시 (ⅱ)단계에서 약 1M의 염화물 이온 농도로 폴리(에틸렌 글리콜)버스-N-숙신이미드 카보네이트에 결합시키는 것을 특징으로 하는 제조방법.
  42. 헤모글로빈을 환원하여 데옥시헤모글로빈의 백분율이 50%이상 80%이하가 되게하는 것을 특징으로 하는 화학적 변형에 앞선 헤모글로빈 예비처리 방법.
  43. 산화 헤모글로빈을 불활성 기체에 노출하여 (ⅰ)산소를 헤모글로빈에서 제거하고 (ⅱ)데옥시헤모글로빈의 백분율이 50%이상 80%이하가 되게 하는 것을 특징으로 하는 화학적 변형에 앞선 헤모글로빈 예비처리 방법.
  44. 제43항에 있어서, 산화 헤모글로빈을 기체 투과막을 통해 불활성 기체에 노출시키는 것을 특징으로 하는 제조방법.
  45. 제44항에 있어서, 기체 투과막이 폴리프로필렌막인 것을 특징으로 하는 제조방법.
  46. 제44항에 있어서, 기체 투과막이 셀룰로오스막인 것을 특징으로 하는 제조방법.
  47. 산화 헤모글로빈을 효과적인 농도의 화학적 환원제에 노출시켜 (ⅰ)산소를 헤모글로빈에서 제거하고 (ⅱ)최종데옥시헤모글로빈의 농도가 약 50%이상 80%이하가 되게 하는 것을 특징으로 하는 화학적 변형에 앞선 헤모글로빈 예비처리 방법.
  48. 제47항에 있어서, 화학적 환원제가 아스코르빈산 나트륨인 것을 특징으로 하는 제조방법.
  49. 제47항에 있어서, 화학적 환원제가 디티온산 나트륨인 것을 특징으로 하는 제조방법.
  50. 제47항에 있어서, 화학적 환원제가 이황화나트륨인 것을 특징으로 하는 제조방법.
  51. 제50항에 있어서, 효과적인 아황화나트륨의 농도가 약 100mH인 것을 특징으로 하는 제조방법.
  52. 폴리알킬렌 산화물에 결합되고 P50값이 20mmHg 이상인 것을 특징으로 하는 화학적 변형 헤로글로빈.
  53. 제52항에 있어서, 폴리알킬렌 산화물이 폴리(에틸렌 글리콜)인 것을 특징으로 하는 제조방법.
  54. 제52항에 있어서, 헤모글로빈이 분자내 교차 결합된 것을 특징으로 하는 제조방법.
  55. 제52항에 있어서, 헤모글로빈이 분자내 분자상호 교차결합된 것을 특징으로 하는 제조방법.
  56. 제52항에 있어서, 헤모글로빈이 우레탄 결합에 의해 폴리알킬렌 산화물에 결합된 것을 특징으로 하는 제조방법.
  57. 제53항에 있어서, 헤모글로빈이 우레탄 결합에 의해 폴리알킬렌 산화물에 결합된 것을 특징으로 하는 제조방법.
  58. 적절한 약제학적 담체속에 제52항의 화학적 변형 헤모글로빈이 들어있는 것으로된 약제학적 조성물.
    ※ 참고사항 : 최초출원 내용에 의하여 공개되는 것임.
KR1019920701208A 1989-11-22 1990-11-21 효과적인 안정한 무-임뮤노겐형 적혈구 대용물인 화학적 변형 헤모글로빈 KR920702232A (ko)

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US44055389A 1989-11-22 1989-11-22
US440553 1989-11-22
US07/616,129 US5234903A (en) 1989-11-22 1990-11-20 Chemically modified hemoglobin as an effective, stable non-immunogenic red blood cell substitute
US616129 1990-11-20
PCT/US1990/006843 WO1991007190A1 (en) 1989-11-22 1990-11-21 Chemically modified hemoglobin as an effective, stable, non-immunogenic red blood cell substitute

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HUT61031A (en) 1992-11-30
WO1991007190A1 (en) 1991-05-30
EP0502113A1 (en) 1992-09-09
CA2069402A1 (en) 1991-05-23
AU6957691A (en) 1991-06-13
JPH05504133A (ja) 1993-07-01
US5234903A (en) 1993-08-10
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AU642692B2 (en) 1993-10-28
JP2907300B2 (ja) 1999-06-21

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