RU2012104816A - Стандартные лекарственные препараты и способы лечения тромбоза пероральным введением ингибитора фактора ха - Google Patents

Стандартные лекарственные препараты и способы лечения тромбоза пероральным введением ингибитора фактора ха Download PDF

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RU2012104816A
RU2012104816A RU2012104816/15A RU2012104816A RU2012104816A RU 2012104816 A RU2012104816 A RU 2012104816A RU 2012104816/15 A RU2012104816/15 A RU 2012104816/15A RU 2012104816 A RU2012104816 A RU 2012104816A RU 2012104816 A RU2012104816 A RU 2012104816A
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thrombin
sample
test sample
whole blood
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RU2012104816/15A
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Ума Синха
Стенли Дж. Холленбах
Кит ЭЙБ
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Милленниум Фармасьютикалз, Инк.
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    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

1. Способ определения in vitro антитромботической активности соединения in vivo, включающийа) введение испытуемого соединения в образец in vitro цельной крови или плазмы, содержащей тканевый фактор (TF) и обнаружимо меченный тромбиновый субстрат для формирования испытуемого образца;(b) определение степени активности тромбина в испытуемом образце путем отслеживания расщепления обнаружения меченного для тромбинового субстрата в испытуемом образце как функцию времени;с) определение степени активности тромбина в контрольном образце путем мониторинга расщепления меченного для обнаружения тромбинового субстрата в контрольном образце как функцию времени, где контрольный образец содержит цельную кровь или плазму, содержащую тканевый фактор (TF) и меченный для обнаружения тромбиновый субстрат;d) сравнение степени активности тромбина в испытуемом образце и в контрольном образце, где степень активности тромбина в испытуемом образце является показателем того, что испытуемое соединение имеет in vivo антитромботическую активность.2. Способ по п.1, где испытуемый образец и контрольный образец содержат цельную кровь.3. Способ по п.2, где цельную кровь предохраняют от коагуляции.4. Способ по п.2, где цельную кровь не предохраняют от коагуляции.5. Способ по п.1, где испытуемый образец и контрольный образец содержат плазму.6. Способ по п.5, где плазму предохраняют от коагуляции.7. Способ по п.5, где плазму не предохраняют от коагуляции.8. Способ по п.1, где меченным для обнаружения тромбиновым субстратом является Z-Gly-Gly-Arg-AMC.

Claims (8)

1. Способ определения in vitro антитромботической активности соединения in vivo, включающий
а) введение испытуемого соединения в образец in vitro цельной крови или плазмы, содержащей тканевый фактор (TF) и обнаружимо меченный тромбиновый субстрат для формирования испытуемого образца;
(b) определение степени активности тромбина в испытуемом образце путем отслеживания расщепления обнаружения меченного для тромбинового субстрата в испытуемом образце как функцию времени;
с) определение степени активности тромбина в контрольном образце путем мониторинга расщепления меченного для обнаружения тромбинового субстрата в контрольном образце как функцию времени, где контрольный образец содержит цельную кровь или плазму, содержащую тканевый фактор (TF) и меченный для обнаружения тромбиновый субстрат;
d) сравнение степени активности тромбина в испытуемом образце и в контрольном образце, где степень активности тромбина в испытуемом образце является показателем того, что испытуемое соединение имеет in vivo антитромботическую активность.
2. Способ по п.1, где испытуемый образец и контрольный образец содержат цельную кровь.
3. Способ по п.2, где цельную кровь предохраняют от коагуляции.
4. Способ по п.2, где цельную кровь не предохраняют от коагуляции.
5. Способ по п.1, где испытуемый образец и контрольный образец содержат плазму.
6. Способ по п.5, где плазму предохраняют от коагуляции.
7. Способ по п.5, где плазму не предохраняют от коагуляции.
8. Способ по п.1, где меченным для обнаружения тромбиновым субстратом является Z-Gly-Gly-Arg-AMC.
RU2012104816/15A 2006-12-08 2012-02-10 Стандартные лекарственные препараты и способы лечения тромбоза пероральным введением ингибитора фактора ха RU2012104816A (ru)

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US87379206P 2006-12-08 2006-12-08
US60/873,792 2006-12-08
US94762907P 2007-07-02 2007-07-02
US60/947,629 2007-07-02

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