KR950701819A - 안티트롬빈-iii 액상 제제 및 그 안정화 방법(liquid antithrombin iii preparation and method of stabilizing the same) - Google Patents

안티트롬빈-iii 액상 제제 및 그 안정화 방법(liquid antithrombin iii preparation and method of stabilizing the same)

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Publication number
KR950701819A
KR950701819A KR1019940704443A KR19940704443A KR950701819A KR 950701819 A KR950701819 A KR 950701819A KR 1019940704443 A KR1019940704443 A KR 1019940704443A KR 19940704443 A KR19940704443 A KR 19940704443A KR 950701819 A KR950701819 A KR 950701819A
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antithrombin
formulation
iii
liquid formulation
concentration
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KR1019940704443A
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KR100330540B1 (ko
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가쯔히로 우리유
아키마사 오미즈
하지메 후쿠야마
가즈오 다케치
가즈마사 요코야마
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가와노 다케히코
가부시키가이샤 미도리 쥬지
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • A61K38/57—Protease inhibitors from animals; from humans
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Inorganic Chemistry (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)

Abstract

본 발명은 안티트롬빈-Ⅲ(AT-Ⅲ), 유기산 또는 이것의 염, 당의 황산염 또는 계면활성제를 안정제로서 포함하는 AT-Ⅲ 액상 제제 및 pH가 9 내지 10인 AT-Ⅲ 액상 제제에 관한 것이다, 본 발명의 제제는 장기 보존후에 안정하며, 약리학적 효과 및 안정성의 견지에서 임상적인 문제점이 없다. 상기 제제는 주사용 증류수에 용해시킬 필요가 없고 용이하게 사용할 수 있다는 점에서 동결건조 제제보다 더 유리하다. 따라서, 상기제제는 임상적으로 매우 유용하다.

Description

안티트롬빈 -Ⅲ 액상 제제 및 그 안정화 방법 (LIQUID ANTITHROMBIN Ⅲ PREPARATION AND METHOD OF STABILIZING THE SAME)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 AT-Ⅲ의 동결 건조 제제를 용해시켜 제조된 수용액에서의 AT-Ⅲ의안정성과, 본 발명의 액상제제에서의 AT-Ⅲ의 안정성을 비교한 실험 실시예 3의 결과를 도시한 그래프이다.

Claims (32)

  1. 안티트롬빈-Ⅲ, 및 유기산 또는 이것의 염을 함유하는 안티트롬빈-Ⅲ 액상제제.
  2. 제1항에 있어서, 유기산이 이염기산인 제제.
  3. 제1항에 있어서, 유기산이 시트르산인 제제.
  4. 제1항에 있어서, 안티트롬빈-Ⅲ, 이염기산 또는 이것의 염, 및 시트르산 또는 이것의 염을 함유 하는 제제.
  5. 제1항 또는 제4항에 있어서, 추가로 당을 함유하는 제제.
  6. 제1항 또는 제4항에 있어서, 추가로 계면활성제를 함유하는 제제.
  7. 제1항, 제4항 내지 제6항중 어느 한 항에 있어서, pH가 7내지 8인 제제.
  8. 제1항, 제4항 내지 제7항중 어느 한 항에 있어서, 유기산 또는 이것의 염을 총 0.1 내지 10 w/v% 의 농도롤 함유하는 제제.
  9. 안티트롬빈-Ⅲ 및 당의 황산염을 함유하고, pH가 7내지 10인 안티트롬빈-Ⅲ 액상 제제.
  10. 제9항에 있어서, 당의황산염이 헤파린인 제제.
  11. 제9항에 있어서, pH가 8내지 10인 제제.
  12. 제10항에 있어서, 안티트롬빈-Ⅲ 이 1내지 1000단위/ml의 농도로 존재하고, 헤파린이 1 내지 1000단위/ml의 농도로 존재하는 제제.
  13. 제12항에 있어서, 안티트롬빈-Ⅲ의농도가 10 내지 100단/ml인제제.
  14. pH가 9내지 10인 안티트롬빈-Ⅲ 액상 제제.
  15. 제4항에 있어서, pH가 9.3내지 9.8인 제제.
  16. 안티트롬빈-Ⅲ 및 계면활성제를 함유하는 안티트롬빈-Ⅲ 액상 제제.
  17. 안정제로서 유기산 또는 이것의 염을 안티트롬빈-Ⅲ 액상 제제에 첨가하는 것을 포함하는, 보관중의 안티트롬빈-Ⅲ 액상 제제의 안정화 방법.
  18. 제17항에 있어서, 유기산이 이염기산인 방법.
  19. 제17항에 있어서, 유기산이 시트르산인 방법.
  20. 제17항에 있어서, 안정제가 이염기산 또는 이것의 염, 및 시트르산 또는 이것의 염을 함유하는 방법.
  21. 제17항 또는 제20항에 있어서, 당을 보조 안정제로서 추가로 첨가하는 것을 포함하는 방법.
  22. 제17항 또는 제20항에 있어서, 계면활성제를 보조 안정제로서 추가로 첨가하는 것을 포함하는 방법.
  23. 제17항, 제20항 내지 제22항중 어느 한 항에 있어서, 안티트롬빈-Ⅲ 액상 제제의 pH를 7내지 8로 조정하는 것을 포함하는 방법.
  24. 제17항, 제20항 내지 제23항중 어느 한 항에 있어서, 유기산 또는 이것의 염을 총 0.1 내지 10w/v%의 농도로 첨가하는 것을 포함하는 방법.
  25. 당의 황산염을 안정제로 첨가하고, 제제의 pH를 7 내지 10으로 조정하는 것을 포함하는 보관중의 안티트롬빈-Ⅲ 액상 제제의 안정화 방법.
  26. 제25항에 있어서, 당의 황산염이 헤파린인 방법.
  27. 제25항에 있어서, 안티트롬빈-Ⅲ 액상 제제의 pH를 8내지 10로 조정하는 것을 포함하는 방법.
  28. 제26항에 있어서, 안티트롬빈-Ⅲ이 제제내에 1 내지 1000단위/ml의 농도로 존재하고 헤파린을 1 내지 1000단위/ml의 농도로 첨가하는 방법.
  29. 제28항에 있어서, 안티트롬빈-Ⅲ이 제제내에 10내지 100단위/ml의 농도로 존재하는 방법.
  30. 제제의 pH를 9내지 10으로 조정하는 것을 포함하는, 보관중의 안티트롬빈-Ⅲ 액상 제제의 안정화 방법.
  31. 제30항에 있어서, 안티트롬빈-Ⅲ 액상 제제 pH를 9.3 내지 9.8로 조정하는 것을 포함하는 방법.
  32. 계면활성제를 안티트롬빈-Ⅲ 액상 제제에 첨가하는 것을 포함하는, 보관중의 안티트롬빈-Ⅲ 액상제제 안정화 방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019940704443A 1993-04-05 1994-04-05 안티트롬빈-iii액상제제및그안정화방법 KR100330540B1 (ko)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
JP10011793 1993-04-05
JP93-100117 1993-04-05
JP93-328205 1993-12-24
JP32820593 1993-12-24
JP94-5073 1994-01-21
JP507394 1994-01-21
PCT/JP1994/000563 WO1994022471A1 (en) 1993-04-05 1994-04-05 Liquid antithrombin iii preparation and method of stabilizing the same

Publications (2)

Publication Number Publication Date
KR950701819A true KR950701819A (ko) 1995-05-17
KR100330540B1 KR100330540B1 (ko) 2002-09-04

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Country Link
US (1) US5589516A (ko)
JP (1) JP3711561B2 (ko)
KR (1) KR100330540B1 (ko)
CA (1) CA2137258A1 (ko)
WO (1) WO1994022471A1 (ko)

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JP3711561B2 (ja) 2005-11-02
KR100330540B1 (ko) 2002-09-04
CA2137258A1 (en) 1994-10-13
WO1994022471A1 (en) 1994-10-13
US5589516A (en) 1996-12-31

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