KR940002301A - 5,10-메틸렌테트라히드로폴산-시클로덱스트린 포접 화합물 - Google Patents

5,10-메틸렌테트라히드로폴산-시클로덱스트린 포접 화합물 Download PDF

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KR940002301A
KR940002301A KR1019930012965A KR930012965A KR940002301A KR 940002301 A KR940002301 A KR 940002301A KR 1019930012965 A KR1019930012965 A KR 1019930012965A KR 930012965 A KR930012965 A KR 930012965A KR 940002301 A KR940002301 A KR 940002301A
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cyclodextrin
methylenetetrahydrofolic acid
salt
acid
derivatives
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루돌프 뮐러 한스
울만 마틴
콘티 요세프
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에이치. 알. 뮐러.에이. 피거
에프로바 아크티엔 게젤샤프트
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    • 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
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • 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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

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Abstract

본 발명은 신규한 5,10-메틸렌테트라히드로폴산의 시클로렉스트린 포접 화합물에 관한 것으로, 하기 성분,ⅰ) (6R)-, (6S)-또는 (6R,S)-5,10-메틸렌테트라히드로폴산, 또는(6R)-, (6S)-또는 (6R,S)-5.10-메틸렌테트라히드로폴산의 염과, ⅱa) α-, β- 또는 γ-시클로덱스트린, 또는 α-, β- 또는 γ-시클로덱스트린 유도체 또는 ⅱb)α-, β- 또는 γ-시클로덱스트린 혼합물 또는α-, β- 또는 γ-시클로덱스트린 유도체의 혼합물, 또는 α-, β- 또는 γ-시클로덱스트린과 α-, β- 또는 γ-시클로덱스트린 유도체의 혼합물로 이루어지는 안정한 수용성 조성물을 제공한다.
본 발명의 포접화합물은 안정도가 매우 양호하기 때문에 약제학적 용도로 사용할 수 있다.
또한, 본 발명은 상기 물질의 제조방법 및 이들의 약물을 제조하기 위한 용도도 제공한다.

Description

5,10-메틸렌테트리히드로폴산-시클로덱스트린 포접 화합물
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (11)

  1. 하기 성분 ⅱa) 또는 ⅱb)와 성분 ⅰ)로 이루어지는 안정한 수용성 조성물:
    ⅰ)(6R)-, (6S)- 또는 (6R,S)-5,10-메틸렌테트라히드로폴산, 또는 (6R)-, (6S)- 또는 (6R,S)-5,10-메틸렌테트라히드로폴산의 염, ⅱa)α-, β- 또는 γ-시클로덱스트린, 또는α-, β- 또는 γ-시클로덱스트린 유도체, ⅱb)α-, β- 또는 γ-시클로덱스트린 혼합물 또는α-, β- 또는 γ-시클로덱스트린 유도체의 혼합물, 또는α-, β- 또는 γ-시클로덱스트린과 α-, β- 또는 γ-시클로덱스트린 유도체의 혼합물.
  2. 제1항에 있어서, (6R)-5,10-메틸렌테트라히드로폴산 또는 이의 약제학적으로 허용가능한 염 및 β- 또는 γ-시클로덱스트린 또는 이의 약제학적으로 허용가능한 유도체가 사용되는 것을 특징으로 하는 조성물.
  3. 제1항 또는 제2항에 있어서, 사용되는 5,10-메틸렌테트라히드로폴산의 약제학적으로 허용가능한 염은 알칼리금속 또는 알칼리토금속염으로서, 나트륨, 마그네슘 또는 칼슘염이 사용되고, 사용되는 시클로덱스트린의 약제학적으로 허용가능한 유도체는 히드록시알킬화 또는 알킬화된 β- 또는 γ-시클로텍스트린으로서, 히드록시 프로필-β-, 히드록시프로필-γ- 또는 디메틸-β-시클로덱스트린이 사용되는 것을 특징으로 하는 조성물.
  4. (6R)- 또는 (6S)-5,10-메딜렌테트라히드로폴산 또는 이의 염과α-, β- 또는 γ-시클로덱스트린의 포접 화합물.
  5. (6R)- 또는 (6S)-5,10-메틸렌테트라히드로폴산 또는 이의 염과 히드록시알킬-β- 또는 히드록시알킬 -γ-시클로덱스트린의 포접 화합물.
  6. (6R)- 또는 (6S)-5,10-메틸렌테트라히드로폴산 또는 이의 염과 히드록시프로필-β- 또는 히드록시프로필-γ-시클로덱스트린의 포접 화합물.
  7. (6R) - 또는 (6S)-5,10-메틸렌테트라히드로폴산 또는 이의 염과 알킬-β- 또는 알킬-γ-시클로덱스트린의 포접 화합물.
  8. (6R) - 또는 (6S)-5.10-메틸렌테트라히드로폴산 또는 이의 염과 디메틸-β- 또는 디메틸-γ-시클로덱스트린의 포접 화합물.
  9. α-, β- 또는 γ-시클로덱스트린 또는 이의 유도체를 첨가하여 (6R)-, (6S)-또는 (6R,S)-5,10-메틸렌테트라히드로폴산 및 이의 염의 수용성용액의 안정화 방법.
  10. (6R)-, (6S)- 또는 (6R,S)-5,10-메틸렌테트라히드로폴산 또는 이의 염의 안정한 용액의 제조방법에 있어서, (6S)-. (6R)- 또는 (6R,S)-5,10-메틸렌테트라히드로폴산 또는 상응하는 테트라히드로폴산염을 α-, β- 또는 γ-시클로덱스트린, 또는 이의 유도체의 존재하에 포름알데리드와 반응시키고, 필요시, 다른 염으로 전환하고 필요시 얻어진 5,10-메틸렌테트라히드로폴산-시클로덱스트린 포접 화합물을 분리하는 것을 특징으로 하는 (6R)-. (6S)- 또는 (6R.S)-5,10-메틸렌테트라히드로폴산 또는 이의 염의 안정한 용액의 제조방법.
  11. 약물 제조용 출발물질 또는 성분으로서 α-, β- 또는 γ-시클로덱스트린 또는 이의 유도체중의 포접화합물로서의 (6R)-, (6S)- 또는 (6R,S)-5,10-메틸렌테트라히드로폴산 또는 이의 염의 용도.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019930012965A 1992-07-09 1993-07-10 5,10-메틸렌테트라히드로폴산-시클로덱스트린 포접 화합물 KR100217788B1 (ko)

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ES9201417 1992-07-09
JP92-207304 1992-07-10
ES02192/92-0 1992-07-13
CH02192/92-0 1992-07-13
CH2192/92A CH684644A5 (de) 1992-07-13 1992-07-13 5,10-Methylentetrahydrofolsäure-Cyclodextrin-Einschlussverbindungen.
JP93-57484 1993-03-17

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EP (1) EP0579996B1 (ko)
JP (1) JP2667354B2 (ko)
KR (1) KR100217788B1 (ko)
CN (1) CN1032901C (ko)
AT (1) ATE121949T1 (ko)
AU (1) AU661591B2 (ko)
CA (1) CA2100126C (ko)
CH (1) CH684644A5 (ko)
DE (1) DE59300176D1 (ko)
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HU211484A9 (en) 1995-11-28
NO932517D0 (no) 1993-07-09
US5455236A (en) 1995-10-03
NO303715B1 (no) 1998-08-24
FI933151A0 (fi) 1993-07-09
DE59300176D1 (de) 1995-06-08
AU661591B2 (en) 1995-07-27
HUT65714A (en) 1994-07-28
DK0579996T3 (da) 1995-07-10
CA2100126A1 (en) 1994-01-14
CN1081688A (zh) 1994-02-09
HU9301990D0 (en) 1993-09-28
FI933151A (fi) 1994-01-14
KR100217788B1 (ko) 1999-09-01
EP0579996A1 (de) 1994-01-26
JP2667354B2 (ja) 1997-10-27
EP0579996B1 (de) 1995-05-03
ES2072163T3 (es) 1995-07-01
CN1032901C (zh) 1996-10-02
CA2100126C (en) 1998-05-05
NO932517L (no) 1994-01-14
HU212665B (en) 1996-09-30
JPH0718084A (ja) 1995-01-20
RU2135519C1 (ru) 1999-08-27
CH684644A5 (de) 1994-11-15
TW379142B (en) 2000-01-11
ZA934907B (en) 1994-02-09
ATE121949T1 (de) 1995-05-15

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