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RU2016121929A - Способы и композиции для устойчивой иммунотерапии - Google Patents

Способы и композиции для устойчивой иммунотерапии Download PDF

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RU2016121929A
RU2016121929A RU2016121929A RU2016121929A RU2016121929A RU 2016121929 A RU2016121929 A RU 2016121929A RU 2016121929 A RU2016121929 A RU 2016121929A RU 2016121929 A RU2016121929 A RU 2016121929A RU 2016121929 A RU2016121929 A RU 2016121929A
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disease
nanoparticle
antigen
mhcii
use according
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RU2016121929A
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RU2696876C2 (ru
RU2016121929A3 (ru
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Педро САНТАМАРИЯ
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Ютиай Лимитед Партнершип
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Claims (21)

1. Применение комплекса, включающего ядро наночастицы и комплексы причастного к заболеванию антигена с MHCII, функционально связанные с ядром наночастицы через линкерное покрытие, при экспансии и/или созревании популяций регуляторных В-клеток у субъекта, причем покрытая наночастица имеет плотность антиген-MHCII от около 0,05 рМНС/100 нм2 площади поверхности покрытой наночастицы до около 25 рМНС/100 нм2 площади поверхности покрытой наночастицы.
2. Применение комплекса, включающего ядро наночастицы и комплексы причастного к заболеванию антигена с MHCII, функционально связанные с ядром наночастицы через линкерное покрытие, при превращении когнатных В-клеток в регуляторные В-клетки у субъекта, причем покрытая наночастица имеет плотность антиген-MHCII от около 0,05 рМНС/100 нм2 площади поверхности покрытой наночастицы до около 25 рМНС/100 нм2 площади поверхности покрытой наночастицы.
3. Применение комплекса, включающего ядро наночастицы и комплексы причастного к заболеванию антигена с MHCII, функционально связанные с ядром наночастицы через линкерное покрытие, в лечении или профилактики аутоимунного растройства у субъекта, нуждающегося в этом, причем покрытая наночастица имеет плотность антиген-MHCII от около 0,05 рМНС/100 нм2 площади поверхности покрытой наночастицы до около 25 рМНС/100 нм2 площади поверхности покрытой наночастицы.
4. Применение по п. 3, где аутоиммунное расстройство выбрано из группы, включающей сахарный диабет, преддиабет, отторжение при трансплантации, рассеянный склероз, родственные рассеянному склерозу заболевания, преждевременное угасание функции яичников, склеродерма, болезнь Шегрена, волчанка, витилиго, алопеция (облысение), полигландулярная недостаточность, болезнь Грейвса, гипотиреоз, полимиозит, пузырчатка, болезнь Крона, колит, аутоиммунный гепатит, гипопитуитаризм, миокардит, болезнь Аддисона, аутоиммунные заболевания кожи, увеит, пернициозная анемия, гипопаратиреоз и/или ревматоидный артрит.
5. Применение по п. 1, при этом причастный к заболеванию антиген из комплекса антигена - MHCII происходит из аутоантигена, участвующего в аутоиммунной реакции или является его имитатором, причем необязательно аутоантиген вовлечен в аутоимунное расстройство, выбранное из сахарного диабета, преддиабета, отторжения при трансплантации, рассеянного склероза, родственного рассеянному склерозу заболевания, преждевременного угасания функции яичников, склеродермы, болезни Шегрена, волчанки, витилиго, алопеции (облысения), полигландулярной недостаточности, болезни Грейвса, гипотиреоза, полимиозита, пузырчатки, болезни Крона, колита, аутоиммунного гепатита, гипопитуитаризма, миокардита, болезни Аддисона, аутоиммунного заболевания кожи, увеита, пернициозной анемии, гипопаратиреоза и/или ревматоидного артрита.
6. Применение по п. 2, при этом причастный к заболеванию антиген из комплекса антигена - MHCII происходит из аутоантигена, участвующего в аутоиммунной реакции или является его имитатором, причем необязательно аутоантиген вовлечен в аутоимунное расстройство, выбранное из сахарного диабета, преддиабета, отторжения при трансплантации, рассеянного склероза, родственного рассеянному склерозу заболевания, преждевременного угасания функции яичников, склеродермы, болезни Шегрена, волчанки, витилиго, алопеции (облысения), полигландулярной недостаточности, болезни Грейвса, гипотиреоза, полимиозита, пузырчатки, болезни Крона, колита, аутоиммунного гепатита, гипопитуитаризма, миокардита, болезни Аддисона, аутоиммунного заболевания кожи, увеита, пернициозной анемии, гипопаратиреоза и/или ревматоидного артрита.
7. Применение по любому из пп. 1-6, при этом ядро наночастицы не является липосомой и/или является твердым ядром, предпочтительно ядром из золота или оксида железа.
8. Применение по любому из пп. 1-6, при этом линкерное покрытие содержит полиэтиленгликоль.
9. Применение по любому из пп. 1-6, при этом линкер из линкерного покрытия имеет размер менее 5 кДа.
10. Применение по любому из пп. 1-6, при этом ядро наночастицы являются биоабсорбируемыми и/или биоразлагаемыми.
11. Применение комплекса по любому из пп. 1-6, при этом диаметр ядра наночастицы составляет от примерное 1 нм до примерное 100 нм.
12. Применение по любому из пп. 1-6, при этом комплексы антиген-MHCII являются идентичными или разными.
13. Применение по п. 12, при этом линкеры из линкерного покрытия являются идентичными или разными.
14. Применение по любому из пп. 1-6, при этом субъект относится к млекопитающим.
15. Способ получения наночастиц из оксида железа, включающий термическое разложение ацетилацетоната железа в присутствии функционализированных молекул ПЭГ и/или бензилового эфира в диапазоне температур, выбранного из от примерно 80 до примерно 300°C, от примерно 80 до примерно 200°C, от примерно 80 до примерно 150°C, от примерно 100 до примерно 250°C, от примерно 100 до примерно 200°C, от примерно 150 до примерно 250°C, или от примерно 150 до примерно 250°C.
16. Способ по п. 15, при этом наночастицы из оксида железа растворимы в воде.
17. Способ по п. 15 или п. 16, при этом термическое разложение проводится в течение от 1 до 2 ч.
18. Способ по п. 15 или п. 16, при этом наночастицы являются стабильными при 4°C в PBS без заметной деградации или агрегации.
19. Способ по п. 18, при этом наночастицы стабильны в течение по крайней мере 6 месяцев.
20. Способ по п. 15 или 16, при этом способ дополнительно включает очистку наночастиц с помощью метода магнитного разделения.
21. Способ по п. 20, где метод магнитного разделения включает использование магнитной колонки.
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