RU2008126198A - Индукция толерантности к антигенам через слизистую - Google Patents
Индукция толерантности к антигенам через слизистую Download PDFInfo
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Abstract
1. Применение микроорганизма, экспрессирующего иммуномодулирующее соединение, в комбинации с антигеном в изготовлении лекарственного средства, медицинского пищевого продукта или нутрицевтика для индукции иммуннотолерантности или для лечения заболевания, связанного с иммунным ответом, у млекопитающего. ! 2. Применение композиции для изготовления лекарственного средства, медицинского пищевого продукта или нутрицевтика для лечения, профилактики и/или облегчения заболевания или расстройства, связанного с иммунным ответом, или для индукции иммуннотолерантности у млекопитающего, отличающееся тем, что указанная композиция включает в себя по меньшей мере микроорганизм, экспрессирующий иммуномодулирующее соединение, и антиген. ! 3. Применение по п.1 или 2, где указанную индукцию иммуннотолерантности определяют по повышению уровня цитокина, где указанный цитокин выбран из группы, состоящей из IL-10, TGF-β, IL-4 и IFNα. ! 4. Применение по п.1 или 2, где указанную индукцию иммунотолерантности определяют по снижению уровня цитокина, при этом указанный цитокин выбран из группы, состоящей из IFN-γ, IL-2, IL-5, IL-6, IL-12, IL-13 и TNF-α, MCP-1. ! 5. Применение по п.1 или 2, при котором указанный антиген вызывает опосредованный T-клетками и/или опосредованный B-клетками иммунный ответ, где указанный опосредованный T-клетками иммунный ответ представляет собой иммунный ответ Th1 или иммунный ответ Th2. ! 6. Применение по п.1 или 2, где указанный антиген вовлечен в индукцию аллергической астмы, рассеянного склероза, диабета I типа, аутоиммунного увеита, аутоиммунного тиреоидита, аутоиммунной миастении gravis, ревматоидного артрита, пищевой аллергии или целиакии. ! 7. Пр�
Claims (25)
1. Применение микроорганизма, экспрессирующего иммуномодулирующее соединение, в комбинации с антигеном в изготовлении лекарственного средства, медицинского пищевого продукта или нутрицевтика для индукции иммуннотолерантности или для лечения заболевания, связанного с иммунным ответом, у млекопитающего.
2. Применение композиции для изготовления лекарственного средства, медицинского пищевого продукта или нутрицевтика для лечения, профилактики и/или облегчения заболевания или расстройства, связанного с иммунным ответом, или для индукции иммуннотолерантности у млекопитающего, отличающееся тем, что указанная композиция включает в себя по меньшей мере микроорганизм, экспрессирующий иммуномодулирующее соединение, и антиген.
3. Применение по п.1 или 2, где указанную индукцию иммуннотолерантности определяют по повышению уровня цитокина, где указанный цитокин выбран из группы, состоящей из IL-10, TGF-β, IL-4 и IFNα.
4. Применение по п.1 или 2, где указанную индукцию иммунотолерантности определяют по снижению уровня цитокина, при этом указанный цитокин выбран из группы, состоящей из IFN-γ, IL-2, IL-5, IL-6, IL-12, IL-13 и TNF-α, MCP-1.
5. Применение по п.1 или 2, при котором указанный антиген вызывает опосредованный T-клетками и/или опосредованный B-клетками иммунный ответ, где указанный опосредованный T-клетками иммунный ответ представляет собой иммунный ответ Th1 или иммунный ответ Th2.
6. Применение по п.1 или 2, где указанный антиген вовлечен в индукцию аллергической астмы, рассеянного склероза, диабета I типа, аутоиммунного увеита, аутоиммунного тиреоидита, аутоиммунной миастении gravis, ревматоидного артрита, пищевой аллергии или целиакии.
7. Применение по п.1 или 2, где указанный антиген доставляется экспрессирующим антиген микроорганизмом.
8. Применение по п.7, где указанный антиген представлен на поверхности указанного экспрессирующего антиген микроорганизма и/или где указанное иммуномодулирующее соединение представлено на поверхности указанного экспрессирующего антиген микроорганизма.
9. Применение по п.7, где указанный антиген и/или указанное иммуномодулирующее соединение являются секретируемыми.
10. Применение по п.1 или 2, где указанный способ является терапевтическим или профилактическим.
11. Применение по п.1 или 2 для доставки на слизистую оболочку, где указанная доставка на слизистую выбрана из группы, состоящей из ректальной доставки, буккальной доставки, пульмональной доставки, доставки в глаза, назальной доставки, вагинальной доставки и оральной доставки.
12. Применение по п.1 или 2, при котором доставку микроорганизма, экспрессирующего указанный антиген и/или указанное иммуномодулирующее соединение, осуществляют с помощью спрея, капсул, аэрозоля, лепешек, болюса, таблеток, пакетиков, жидкости, суспензии, эмульсии или пастилок.
13. Применение по п.1 или 2, где указанное иммуномодулирующее соединение представляет собой иммуносупрессорное соединение, выбранное из усиливающего толерантность цитокина или усиливающего толерантность антитела, иммуносупрессорного цитокина или антитела, при этом указанный иммуносупрессорный цитокин выбран из группы, состоящей из IL-4, IL-10, IFN-α, Flt3L, TGFβ и RANK-L, а указанное иммуносупрессорное антитело выбрано из группы, состоящей из антитела против IL-2, антитела против IL-12 и антитела против IFN-γ.
14. Применение по п.1 или 2, где указанным микроорганизмом является бактерия или дрожжи.
15. Применение по п.14, где указанная бактерия является молочнокислой бактерией.
16. Применение по п.15, где указанная молочнокислая бактерия выбрана из группы, состоящей из Lactobacillus, Leuconostoc, Pediococcus, Lactococcus, Streptococcus, Aerococcus, Carnobacterium, Enterococcus, Oenococcus, Teragenococcus, Vagococcus и Weisella.
17. Применение по п.14, где указанные дрожжи представляют собой Saccharomyces cerevisiae.
18. Применение по п.1 или 2, где микроорганизм, экспрессирующий указанный антиген и/или указанное иммуномодулирующее соединение, дополнительно содержит адъювант, фармацевтически приемлемый носитель и/или наполнитель.
19. Применение по п.1 или 2, где микроорганизм, экспрессирующий указанный антиген и/или указанное иммуномодулирующее соединение, дополнительно содержит соединение, стимулирующее выработку иммуносупрессорных цитокинов.
20. Применение по п.1 или 2, при котором доставку микроорганизма, экспрессирующего указанный антиген и/или указанное иммуномодулирующее соединение, осуществляют по меньшей мере в течение 1 дня, предпочтительнее, по меньшей мере в течение 1 недели, еще предпочтительнее, по меньшей мере в течение 1 месяца или 1 года.
21. Применение по п.1 или 2, при котором доставку микроорганизма, экспрессирующего указанный антиген и/или указанное иммуномодулирующее соединение, осуществляют в дозе, составляющей по меньшей мере от 10 фемтограммов до 100 мг в день.
22. Композиция, содержащая микроорганизм, экспрессирующий иммуномодулирующее соединение, в комбинации с антигеном, где указанное иммуномодулирующее соединение, указанный микроорганизм и/или указанный антиген являются таковыми, определяемыми в пп.1-21.
23. Способ индукции у животного иммуннотолерантности к антигену, включающий в себя доставку на слизистую оболочку указанного антигена в комбинации с доставкой на слизистую оболочку микроорганизма, экспрессирующего иммуномодулирующую молекулу.
24. Способ лечения заболевания, связанного с иммунным ответом, у млекопитающего, нуждающегося в таком лечении, включающий в себя доставку на слизистую антигена в комбинации с доставкой на слизистую микроорганизма, секретирующего иммуномодулирующее соединение.
25. Лекарственное средство, нутрицевтик или медицинский пищевой продукт для лечения, профилактики и/или облегчения заболевания или расстройства, связанного с иммунным ответом, или для индукции иммуннотолерантности, содержащие по меньшей мере антиген в комбинации с микроорганизмом, секретирующим иммуномодулирующее соединение.
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