RU2761342C2 - Доставка терапевтических агентов в цнс - Google Patents

Доставка терапевтических агентов в цнс Download PDF

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RU2761342C2
RU2761342C2 RU2017125281A RU2017125281A RU2761342C2 RU 2761342 C2 RU2761342 C2 RU 2761342C2 RU 2017125281 A RU2017125281 A RU 2017125281A RU 2017125281 A RU2017125281 A RU 2017125281A RU 2761342 C2 RU2761342 C2 RU 2761342C2
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composition
enzyme
lysosomal
storage disease
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Периклс КАЛИАС
Цзинь ПАН
Джен ПАУВЕЛЛ
Лоуренс ЧАРНАС
Томас Макколи
Тереса Леах РАЙТ
Ричард ПФАЙФЕР
Захра ШАХРОКХ
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Шир Хьюман Дженетик Терапис, Инк.
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Abstract

Настоящая группа изобретений относится к фармацевтической промышленности, а именно к композиции для интравентрикулярного введения для лечения лизосомной болезни накопления, ассоциированной со сниженным уровнем или активностью лизосомального фермента и к применению композиции. Предложена фармацевтическая композиция для интравентрикулярного введения для лечения лизосомной болезни накопления, ассоциированной со сниженным уровнем или активностью лизосомального фермента, причем указанная композиция содержит замещающий фермент для лизосомального фермента в концентрации 5 мг/мл или выше, до 50 мМ фосфата и имеет pH 5,5-7,0. А также применение композиции, содержащей замещающий фермент, для приготовления лекарственного средства для лечения лизосомной болезни накопления, ассоциированной со сниженным уровнем или активностью лизосомального фермента, причем указанный замещающий фермент присутствует в композиции в концентрации 5 мг/мл или выше, композиция содержит до 50 мМ фосфата при pH 5,5-7,0, и лекарственное средство предназначено для интравентрикулярного введения субъекту. Вышеописанная композиция эффективна для интравентрикулярного введения для лечения лизосомной болезни накопления, ассоциированной со сниженным уровнем или активностью лизосомального фермента, способствует эффективному диффундированию замещающего лизосомального фермента через поверхность мозга и проникновению в различные слои или области мозга, включая глубокие области мозга для эффективной доставки активных агентов в центральную нервную систему. 2 н. и 8 з.п. ф-лы, 192 ил., 28 табл.

Claims (10)

1. Фармацевтическая композиция для интравентрикулярного введения для лечения лизосомной болезни накопления, ассоциированной со сниженным уровнем или активностью лизосомального фермента, причем указанная композиция содержит замещающий фермент для лизосомального фермента в концентрации 5 мг/мл или выше, до 50 мМ фосфата и имеет pH 5,5-7,0.
2. Композиция по п. 1, отличающаяся тем, что указанная композиция дополнительно содержит один или более из (i) поверхностно-активного вещества или (ii) регулятора тоничности.
3. Композиция по п. 1, отличающаяся тем, что указанную композицию вводят в объеме одной дозы менее 5 мл.
4. Композиция по любому из пп. 1-3, отличающаяся тем, что лизосомная болезнь накопления выбрана из группы, состоящей из синдрома Хантера, метахроматической лейкодистрофии (МЛ), синдрома Санфилиппо типа А и лейкодистрофии глобоидных клеток (ЛГК).
5. Композиция по любому из пп. 1-4, отличающаяся тем, что замещающий фермент необязательно выбран из группы, состоящей из рекомбинантной идуронат-2-сульфатазы (I2S), арилсульфатазы А (ASA), гепаран N-сульфатазы (HNS) или β-галактозидазы (GLC).
6. Применение композиции, содержащей замещающий фермент, для приготовления лекарственного средства для лечения лизосомной болезни накопления, ассоциированной со сниженным уровнем или активностью лизосомального фермента, причем указанный замещающий фермент присутствует в композиции в концентрации 5 мг/мл или выше, композиция содержит до 50 мМ фосфата при pH 5,5-7,0, и лекарственное средство предназначено для интравентрикулярного введения субъекту.
7. Применение по п. 6, отличающееся тем, что композиция дополнительно содержит один или более из (i) поверхностно-активного вещества или (ii) регулятора тоничности.
8. Применение по п. 6, отличающееся тем, что композицию вводят в объеме одной дозы менее 5 мл.
9. Применение по любому из пп. 6-8, отличающееся тем, что лизосомная болезнь накопления выбрана из группы, состоящей из синдрома Хантера, метахроматической лейкодистрофии (МЛ), синдрома Санфилиппо типа А и лейкодистрофии глобоидных клеток (ЛГК).
10. Применение по любому из пп. 6-9, отличающееся тем, что замещающий фермент необязательно выбран из группы, состоящей из рекомбинантной идуронат-2-сульфатазы (I2S), арилсульфатазы А (ASA), гепаран N-сульфатазы (HNS) или β-галактозидазы (GLC).
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