RU2015127834A - Способы лечения диабета путем введения антагониста рецептора глюкагона в сочетании с ингибитором поглощения холестерина - Google Patents

Способы лечения диабета путем введения антагониста рецептора глюкагона в сочетании с ингибитором поглощения холестерина Download PDF

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RU2015127834A
RU2015127834A RU2015127834A RU2015127834A RU2015127834A RU 2015127834 A RU2015127834 A RU 2015127834A RU 2015127834 A RU2015127834 A RU 2015127834A RU 2015127834 A RU2015127834 A RU 2015127834A RU 2015127834 A RU2015127834 A RU 2015127834A
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receptor antagonist
glucagon receptor
absorption inhibitor
cholesterol absorption
compound
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Хун-Пин ГУАНЬ
Хосе М. КАСТРО-ПЕРЕС
Гарри Р. ДЭВИС
Сэмюэль С. ЭНДЖЕЛ
Дуглас Г. ДЖОНС
Суннянь ЛИНЬ
Стивен Ф. ПРЕВИС
Томас П. РОДДИ
Лянсу ВАН
Шэн-Пин ВАН
Юйшэн Сюн
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Мерк Шарп И Доум Корп.
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    • A—HUMAN NECESSITIES
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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
    • A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
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    • 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
    • A61K31/40—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
    • A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
    • 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
    • A61K31/40—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
    • A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • 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
    • A61K31/415—1,2-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
    • A61K31/41—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
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Claims (28)

1. Способ лечения диабета у млекопитающего субъекта, включающий введение указанному млекопитающему субъекту:
(a) антагониста рецептора глюкагона и
(b) ингибитора поглощения холестерина;
при этом у млекопитающего субъекта уровень в плазме ЛПНП холестерина составляет менее 130 мг/дл.
2. Способ уменьшения гипергликемии у млекопитающего субъекта, включающий введение указанному млекопитающему субъекту:
(a) антагониста рецептора глюкагона и
(b) ингибитора поглощения холестерина;
при этом у млекопитающего субъекта уровень в плазме ЛПНП холестерина составляет менее 130 мг/дл.
3. Способ по п. 1 или 2, отличающийся тем, что у субъекта уровень в плазме ЛПНП холестерина составляет менее 100 мг/дл.
4. Способ по п. 1 или 2, отличающийся тем, что соединение антагониста рецептора глюкагона и соединение ингибитора поглощения холестерина содержатся в одной лекарственной форме.
5. Способ по п. 4, отличающийся тем, что соединение антагониста рецептора глюкагона и соединение ингибитора поглощения холестерина содержатся в двухслойной таблетке.
6. Способ по п. 1 или 2, отличающийся тем, что соединение антагониста рецептора глюкагона и соединение ингибитора поглощения холестерина содержатся каждое в отдельной лекарственной форме для одновременного или последовательного введения.
7. Способ по п. 1 или 2, предназначенный для лечения диабета 2 типа.
8. Способ по п. 1 или 2, отличающийся тем, что соединение ингибитора поглощения холестерина представляет собой:
Figure 00000001
или его фармацевтически приемлемую соль.
9. Способ по п. 1 или 2, отличающийся тем, что соединение антагониста рецептора глюкагона представляет собой соединение, выбранное из следующей таблицы соединений:
Figure 00000002
Figure 00000003
или его фармацевтически приемлемую соль.
10. Комбинация, включающая:
(a) антагонист рецептора глюкагона и
(b) ингибитор поглощения холестерина,
предназначенная для лечения диабета у млекопитающего субъекта, имеющего уровень в плазме ЛПНП холестерина менее 130 мг/дл.
11. Применение комбинации, включающей:
(a) антагонист рецептора глюкагона и
(b) ингибитор поглощения холестерина,
для производства лекарственного средства, предназначенного для лечения диабета у млекопитающего субъекта, имеющего уровень в плазме ЛПНП холестерина менее 130 мг/дл.
RU2015127834A 2012-12-10 2013-12-09 Способы лечения диабета путем введения антагониста рецептора глюкагона в сочетании с ингибитором поглощения холестерина RU2015127834A (ru)

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US201261735304P 2012-12-10 2012-12-10
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PCT/US2013/073780 WO2014093189A1 (en) 2012-12-10 2013-12-09 Methods of treating diabetes by administering a glucagon receptor antagonist in combination with a cholesterol absorption inhibitor

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