RU2317104C2 - Method for modifying alimentary behavior and application of pyy or its agonist as a preparation for modifying alimentary behavior - Google Patents

Method for modifying alimentary behavior and application of pyy or its agonist as a preparation for modifying alimentary behavior Download PDF

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RU2317104C2
RU2317104C2 RU2004113115/15A RU2004113115A RU2317104C2 RU 2317104 C2 RU2317104 C2 RU 2317104C2 RU 2004113115/15 A RU2004113115/15 A RU 2004113115/15A RU 2004113115 A RU2004113115 A RU 2004113115A RU 2317104 C2 RU2317104 C2 RU 2317104C2
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pyy
agonist
administered
dose
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RU2004113115/15A
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RU2004113115A (en
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Эндрю БАТЛЕР
Стивн Роберт БЛУМ
Речел Луиза БЭТТЕРХЭМ
Мохаммад Али ГАТЕЙ
Майкл КАУЛЕЙ
Роджер КОУН
Малкем ЛОУ
Кэролайн Джейн СМОЛЛ
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Импиэриэл Инноувейшнс Лимитид
Оригон Хелс энд Сайэнс Юнивесити
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Abstract

FIELD: medicine.
SUBSTANCE: the present innovation deals with decreasing the intake of calories, the intake of food and appetite in a subject. The method deals, also, with peripheral introduction of therapeutically efficient quantity of PYY3-36 or its agonist, thus, decreasing the intake of calories by a subject. The advantage of the present technique deals with increasing the efficiency in decreasing body weight in such persons.
EFFECT: higher efficiency.
48 cl, 9 dwg, 6 ex

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Claims (51)

1. Способ уменьшения потребления калорий, уменьшения потребления пищи или снижения аппетита, или увеличения энергозатрат у субъекта, отличающийся тем, что осуществляют периферическое введение субъекту PYY3-36 в количестве, эффективном для достижения физиологических уровней PYY3-36, определяемых после приема пищи, или осуществляют периферическое введение субъекту агониста PYY3-36 в количестве, эффективном для имитации физиологических уровней PYY3-36, определяемых после приема пищи, уменьшая таким образом потребление калорий, потребление пищи или снижая аппетит, или увеличивая энергозатраты у субъекта.1. The way to reduce calorie intake, reduce food intake or reduce appetite, or increase energy consumption in a subject, characterized in that the subject is administered peripherally PYY 3-36 in an amount effective to achieve physiological levels of PYY 3-36 , determined after eating, or carried peripherally administering to a subject agonist PYY 3-36 in an amount effective to mimic physiological levels of PYY 3-36, determined after a meal, thus reducing calorie intake, food intake, and and decreasing appetite or increasing energy expenditure in a subject. 2. Способ по п.1, отличающийся тем, что субъект имеет избыточную массу тела.2. The method according to claim 1, characterized in that the subject is overweight. 3. Способ по п.1, отличающийся тем, что субъект страдает ожирением.3. The method according to claim 1, characterized in that the subject is obese. 4. Способ по п.1, отличающийся тем, что субъект страдает диабетом.4. The method according to claim 1, characterized in that the subject suffers from diabetes. 5. Способ по п.1, отличающийся тем, что периферическое введение PYY3-36 или агониста PYY3-36 включает пероральное, подкожное, внутривенное, внутримышечное, интраназальное, чрескожное, интрацистернальное, внутривагинальное, интраперитонеальное, местное, чрезслизистое, буккальное, ректальное или подъязычное введение, или введение посредством легочной ингаляции.5. The method according to claim 1, characterized in that the peripheral administration of PYY 3-36 or an agonist of PYY 3-36 includes oral, subcutaneous, intravenous, intramuscular, intranasal, percutaneous, intracisternal, intravaginal, intraperitoneal, local, transmucosal, buccal, rectal or sublingual administration, or administration by pulmonary inhalation. 6. Способ по п.5, отличающийся тем, что доза PYY3-36 или его агониста составляет от приблизительно 45 до приблизительно 135 пмоль/кг массы тела субъекта.6. The method according to claim 5, characterized in that the dose of PYY 3-36 or its agonist is from about 45 to about 135 pmol / kg of body weight of the subject. 7. Способ по п.6, отличающийся тем, что доза PYY3-36 или его агониста составляет приблизительно 72 пмоль/кг массы тела субъекта.7. A method according to claim 6, characterized in that the dose of PYY 3-36 or agonist is approximately 72 pmol / kg, of subject body weight. 8. Способ по п.1, отличающийся тем, что PYY3-36 или его агонист вводят по меньшей мере за 30 мин до еды.8. The method of claim 1, wherein the PYY 3-36 or agonist is administered for at least 30 minutes before eating. 9. Способ по п.1, отличающийся тем, что периферическое введение PYY3-36 или его агониста осуществляют многократно, причем каждую дозу вводят в количестве от приблизительно 0,5 до приблизительно 135 пмоль/кг массы тела субъекта по меньшей мере приблизительно за 30 мин до приема пищи.9. The method according to claim 1, characterized in that the peripheral administration of PYY 3-36 or an agonist thereof is carried out repeatedly, each dose being administered in an amount of from about 0.5 to about 135 pmol / kg of subject body weight in at least about 30 min before eating. 10. Способ по п.1, отличающийся тем, что субъекту также вводят терапевтически эффективное количество дополнительного агента, подавляющего аппетит, который представляет собой амфепрамон (диэтилпропион), фентермин, мазиндол, фенилпропаноламин, фенфлурамин, дексфенфлурамин или флуоксетин.10. The method according to claim 1, characterized in that the subject is also administered a therapeutically effective amount of an additional appetite suppressing agent, which is ampepramone (diethylpropion), phentermine, mazindol, phenylpropanolamine, fenfluramine, dexfenfluramine or fluoxetine. 11. Способ по п.1, отличающийся тем, что PYY3-36 или его агонист вводят субъекту в количестве, эффективном для уменьшения потребления им калорий в течение по меньшей мере 2 ч.11. The method according to claim 1, characterized in that PYY 3-36 or its agonist is administered to the subject in an amount effective to reduce his calorie intake for at least 2 hours 12. Способ по п.11, отличающийся тем, что PYY3-36 или его агонист вводят субъекту в количестве, эффективном для уменьшения потребления им калорий в течение приблизительно от 2 до 24 ч.12. The method according to claim 11, characterized in that PYY 3-36 or its agonist is administered to the subject in an amount effective to reduce his calorie intake for about 2 to 24 hours. 13. Способ по п.1, отличающийся тем, что субъект является человеком.13. The method according to claim 1, characterized in that the subject is a human. 14. Способ по п.1, отличающийся тем, что агонист PYY3-36 содержит молекулу, которая специфически связывается с Y2 рецептором.14. The method according to claim 1, characterized in that the PYY 3-36 agonist contains a molecule that specifically binds to the Y2 receptor. 15. Способ по п.14, отличающийся тем, что агонист PYY3-36 увеличивает экспрессию c-fos в части дугообразного ядра, контактирующей с агонистом PYY3-36.15. The method according to 14, characterized in that the PYY 3-36 agonist increases the expression of c-fos in the part of the arcuate nucleus in contact with the PYY 3-36 agonist. 16. Способ по п.1, отличающийся тем, что агонист PYY3-36 специфически связывается с нейроном, содержащим нейропептид Y, и ингибирует активность нейрона, содержащего нейропептид Y.16. The method according to claim 1, characterized in that the PYY 3-36 agonist specifically binds to a neuron containing neuropeptide Y, and inhibits the activity of a neuron containing neuropeptide Y. 17. Способ по п.16, отличающийся тем, что агонист PYY3-36 уменьшает частоту следования импульсов потенциала действия нейрона, содержащего нейропептид Y.17. The method according to clause 16, wherein the PYY 3-36 agonist reduces the pulse rate of the action potential of the neuron containing the neuropeptide Y. 18. Способ по п.16, отличающийся тем, что нейрон, содержащий нейропептид Y, синаптически связан с проопиомеланокортиновым нейроном, при этом связывание агониста PYY3-36 с нейроном, содержащим нейропептид Y, приводит к увеличению активности проопиомеланокортинового нейрона.18. The method according to clause 16, wherein the neuron containing the neuropeptide Y is synaptically linked to the proopiomelanocortin neuron, and the binding of the PYY 3-36 agonist to the neuron containing the neuropeptide Y leads to an increase in the activity of the proopiomelanocortin neuron. 19. Способ по п.18, отличающийся тем, что агонист PYY3-36, связываясь с нейроном, содержащим нейропептид Y, снижает частоту следования импульсов потенциала действия нейрона, содержащего нейропептид Y, при этом уменьшение активности нейрона, содержащего нейропептид Y, приводит к усилению генерации потенциала действия проопиомеланокортинового нейрона.19. The method according to p. 18, characterized in that the PYY 3-36 agonist , binding to a neuron containing a neuropeptide Y, reduces the pulse rate of the action potential of a neuron containing a neuropeptide Y, while reducing the activity of a neuron containing a neuropeptide Y, leads to enhancing the generation of the action potential of the proopiomelanocortin neuron. 20. Способ по п.1, отличающийся тем, что достигают снижения аппетита у субъекта.20. The method according to claim 1, characterized in that they achieve a decrease in appetite in the subject. 21. Способ по п.20, отличающийся тем, что достигают уменьшения потребления пищи субъектом.21. The method according to claim 20, characterized in that achieve a reduction in food intake by the subject. 22. Способ по п.21, отличающийся тем, что достигают снижения потребления калорий субъектом.22. The method according to item 21, characterized in that they achieve a reduction in calorie intake by the subject. 23. Способ по п.1, отличающийся тем, что достигают профилактики или уменьшения набора массы тела субъекта.23. The method according to claim 1, characterized in that they achieve the prevention or reduction of weight gain of the subject. 24. Способ по п.1, отличающийся тем, что достигают индуцирования или поддержания потери массы тела субъекта.24. The method according to claim 1, characterized in that they achieve the induction or maintenance of weight loss of the subject. 25. Способ по п.1, отличающийся тем, что PYY3-36 или его агонист вводят в количестве от приблизительно 0,5 до приблизительно 135 пмоль/кг массы тела субъекта.25. The method according to claim 1, characterized in that PYY 3-36 or its agonist is administered in an amount of from about 0.5 to about 135 pmol / kg of body weight of the subject. 26. Способ по п.1, отличающийся тем, что достигают индуцирования или усиления насыщения и ощущения насыщения у субъекта.26. The method according to claim 1, characterized in that they achieve the induction or enhancement of saturation and the sensation of saturation in the subject. 27. Способ по п.1, отличающийся тем, что достигают подавления голода и ощущений голода у субъекта.27. The method according to claim 1, characterized in that the suppression of hunger and hunger sensations in a subject are achieved. 28. Способ по п.1, отличающийся тем, что периферическое введение субъекту РУУ3-36 или его агониста осуществляют многократно или в раздельных дозах.28. The method according to claim 1, characterized in that the peripheral administration to the subject of RUU 3-36 or its agonist is carried out repeatedly or in separate doses. 29. Способ по п.1, отличающийся тем, что периферическое введение субъекту PYY3-36 или его агониста осуществляют периферической инъекцией в пульсовой дозе.29. The method according to claim 1, characterized in that the peripheral administration to the subject of PYY 3-36 or its agonist is carried out by peripheral injection in a pulse dose. 30. Способ по п.1, отличающийся тем, что периферическое введение PYY3-36 или его агониста осуществляют в форме, обеспечивающей замедленное, длительное или контролируемое высвобождение лекарственного средства, или при помощи насоса, или имплантируемого устройства для введения лекарственного средства.30. The method according to claim 1, characterized in that the peripheral administration of PYY 3-36 or an agonist thereof is carried out in a form that provides sustained, prolonged or controlled release of the drug, or using a pump or implantable device for drug administration. 31. Способ по п.1, отличающийся тем, что осуществляют периферическое введение PYY3-36 или его агониста в дозе от приблизительно 5 до приблизительно 50 нмоль.31. The method according to claim 1, characterized in that carry out the peripheral administration of PYY 3-36 or its agonist in a dose of from about 5 to about 50 nmol. 32. Способ по п.1, отличающийся тем, что доза PYY3-36 или его агониста составляет от приблизительно 2 до приблизительно 20 нмоль.32. The method according to claim 1, characterized in that the dose of PYY 3-36 or its agonist is from about 2 to about 20 nmol. 33. Способ по п.32, отличающийся тем, что доза PYY3-36 или его агониста составляет приблизительно 10 нмоль.33. The method according to p, characterized in that the dose of PYY 3-36 or its agonist is approximately 10 nmol. 34. Способ по п.1, отличающийся тем, что субъекту вводят терапевтически эффективное количество дополнительного агента, подавляющего аппетит.34. The method according to claim 1, characterized in that the subject is administered a therapeutically effective amount of an additional agent that suppresses appetite. 35. Способ по п.1, отличающийся тем, что субъекту дополнительно вводят по меньшей мере один из агентов, снижающих уровень глюкозы в плазме крови, агентов, изменяющих содержание липидов в плазме крови или агентов, уменьшающих прием пищи.35. The method according to claim 1, characterized in that the subject is additionally administered at least one of the agents that reduce the level of glucose in blood plasma, agents that change the content of lipids in blood plasma or agents that reduce food intake. 36. Способ по п.1, отличающийся тем, что у субъекта достигают поддержания желаемой массы тела или поддержания желаемого индекса массы тела.36. The method according to claim 1, characterized in that the subject achieves maintaining the desired body mass or maintaining the desired body mass index. 37. Способ по п.1, отличающийся тем, что субъект страдает нарушением или входит в группу риска в отношении нарушения, фактором риска которого является ожирение или избыточная масса тела.37. The method according to claim 1, characterized in that the subject suffers from a disorder or is at risk for a disorder whose risk factor is obesity or overweight. 38. Способ по п.1, отличающийся тем, что субъект страдает нарушением, вызванным осложняющимся или обостряющимся в связи с относительно высокой доступностью питательных веществ.38. The method according to claim 1, characterized in that the subject suffers from a disorder caused by complicating or exacerbating due to the relatively high availability of nutrients. 39. Способ по п.1, отличающийся тем, что субъекту вводят агонист PYY3-36.39. The method according to claim 1, characterized in that the subject is administered a PYY 3-36 agonist. 40. Способ по п.1, отличающийся тем, что субъекту вводят PYY3-36.40. The method according to claim 1, characterized in that the subject is administered PYY 3-36 . 41. Способ по п.40, отличающийся тем, что PYY3-36 вводят субъекту в дозе от приблизительно 0,5 до приблизительно 135 пмоль/кг массы тела субъекта.41. The method of claim 40, wherein the PYY 3-36 is administered to a subject in a dose of from about 0.5 to about 135 pmol / kg body weight of the subject. 42. Способ по п.41, отличающийся тем, что PYY3-36 вводят субъекту в дозе от приблизительно 45 до приблизительно 135 пмоль/кг массы тела субъекта.42. The method according to paragraph 41, wherein PYY 3-36 is administered to the subject at a dose of from about 45 to about 135 pmol / kg of body weight of the subject. 43. Способ по п.41, отличающийся тем, что PYY3-36 вводят субъекту в дозе приблизительно 72 пмоль/кг массы тела субъекта.43. The method according to paragraph 41, wherein PYY 3-36 is administered to the subject at a dose of approximately 72 pmol / kg of body weight of the subject. 44. Способ по п.40, отличающийся тем, что PYY3-36 вводят в дозе от 1 до 100 нмоль.44. The method according to p, characterized in that PYY 3-36 is administered in a dose of from 1 to 100 nmol. 45. Способ по п.1, отличающийся тем, что физиологические уровни PYY3-36 после приема пищи составляют от 40 до 60 пМ.45. The method according to claim 1, characterized in that physiological levels of PYY 3-36 postprandial range from 40 to 60 pM. 46. Способ по п.45, отличающийся тем, что физиологические уровни PYY3-36 после приема пищи составляют от 40 до 50 пМ.46. The method according to item 45, wherein the physiological levels of PYY 3-36 after eating are from 40 to 50 PM. 47. Применение PYY3-36 или его агониста в качестве средства для уменьшения потребления калорий, уменьшения потребления пищи или снижения аппетита, или увеличения энергозатрат у субъекта.47. The use of PYY 3-36 or an agonist thereof as a means to reduce calorie intake, reduce food intake or reduce appetite, or increase energy consumption in a subject. 48. Применение PYY3-36 или его агониста в качестве активного ингредиента при производстве лекарственного средства для уменьшения потребления калорий, уменьшения потребления пищи или снижения аппетита, или увеличения энергозатрат у субъекта.48. The use of PYY 3-36 or an agonist thereof as an active ingredient in the manufacture of a medicament to reduce calorie intake, reduce food intake or reduce appetite, or increase energy consumption in a subject. Приоритет по пунктам:Priority on points: 24.09.2001 по пп.47 и 48;09/24/2001 according to claims 47 and 48; 10.01.2002 по пп.1-5, 10, 13-30, 34-40;01/10/2002 according to claims 1-5, 10, 13-30, 34-40; 28.06.2002 по пп.6-9, 11, 12, 31-33, 41-46.06/28/2002 according to claims 6-9, 11, 12, 31-33, 41-46.
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