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1. 发明申请

WO2021175740A1 FOLATE PREPARATIONS FOR THE TREATMENT OF OCULAR DISEASES 审中-公开
公开(公告)号：WO2021175740A1
公开(公告)日：2021-09-10
申请号：PCT/EP2021/054941
申请日：2021-02-26
申请人： APROFOL AG
发明人： ULMANN, Martin , WIESLER, Gerd , FLAMMER, Josef
IPC分类号： A61K31/519 , A61K31/047 , A61K31/065 , A61K31/197 , A61K31/355 , A61K31/375 , A61K31/51 , A61K31/525 , A61K31/593 , A61K31/675 , A61K31/714 , A61K33/04 , A61K33/30 , A61K33/34 , A61P27/02 , A61P27/06 , A61K31/07 , A61K31/191 , A61K31/198 , A61K31/205 , A61K31/221 , A61K31/4415 , A61K31/7008
摘要： A composition is described comprising at least one folate which is useful in the treatment of ocular diseases linked to elevated retinal venous pressure.

2. 发明申请

WO2020089443A1 FOLATE SALTS 审中-公开
公开(公告)号：WO2020089443A1
公开(公告)日：2020-05-07
申请号：PCT/EP2019/079941
申请日：2019-10-31
申请人： APROFOL AG
发明人： ULMANN, Martin , WIESLER, Gerd , BODENMÜLLER, Arthur
IPC分类号： A61K31/519 , C07D475/04 , A61P25/00 , A61P7/06 , A61P9/00 , A61P19/02
摘要： The invention relates to crystalline folate salts. The salt consists of a folate anion and an organic cation. The folate anion is 5-methyl-(6S)-tetrahydrofolic acid, and the cation is an organic compound which is an alkanolamine selected from the group consisting of choline, N-methylaminoethanol, 2-amino-2-methylpropanol and 2-dimethylaminoethanol.

3. 发明申请

WO2020043840A1 FOLATE PREPARATIONS 审中-公开
公开(公告)号：WO2020043840A1
公开(公告)日：2020-03-05
申请号：PCT/EP2019/073118
申请日：2019-08-29
申请人： APROFOL AG
发明人： ULMANN, Martin , WIESLER, Gerd , FLAMMER, Josef
IPC分类号： A61K31/519 , A61K31/047 , A61K31/065 , A61K31/197 , A61K31/198 , A61K31/355 , A61K31/375 , A61K31/51 , A61K31/525 , A61K31/593 , A61K31/675 , A61K31/714 , A61K33/04 , A61K33/30 , A61K33/34 , A61P27/06
摘要： The present invention relates to preparations of folate for use in the treatment of eye disorders in the presence of elevated intraocular pressure.

4. 发明申请

WO2020002714A1 FOLATE PREPARATIONS 审中-公开
公开(公告)号：WO2020002714A1
公开(公告)日：2020-01-02
申请号：PCT/EP2019/067644
申请日：2019-07-01
申请人： APROFOL AG
发明人： ULMANN, Martin , WIESLER, Gerd , DUTLER, Hans
IPC分类号： A61K31/519 , A61K9/00 , A61P17/14 , A61P17/02 , A61P17/06 , A61P17/00
摘要： The present invention relates to preparations of folate salts and their topical use for the treatment of epithelial tissue irritations and skin disorders.

5. 发明申请

WO2014177274A1 STABLE PHARMACEUTICAL COMPOSITION CONTAINING FOLATES 审中-公开
标题翻译：稳定的药物组合物
公开(公告)号：WO2014177274A1
公开(公告)日：2014-11-06
申请号：PCT/EP2014/001153
申请日：2014-04-30
申请人： APROFOL AG
发明人： ULMANN, Martin
IPC分类号： A61K9/00 , A61K9/08 , A61K31/505 , A61K47/12 , A61K47/24
CPC分类号： A61K31/519 , A61K9/0019 , A61K9/08 , A61K47/12 , A61K47/24
摘要： The administration of leucovorin as well as other active, reduced folates are useful as an antidote to drugs which act as folic acid antagonists and in combination chemotherapy with 5-FU. The most often used calcium salts of the folates have a low solubility in water and form almost insoluble degradation products. Therefore aqueous solutions are unstable and precipitates are resulting. Precipitates in injectable products present an unacceptable safety risk to patients. Stable high strength pharmaceutical aqueous compositions are formed containing calcium salts, magnesium or zinc salts of the reduced folates leucovorin, (6R,S)-tetrahydrofolic acid, (6S)-tetrahydrofolic acid, 5,10- methylene-(6R,S)-tetrahydrofolate, 5,10-methylene-(6R)-tetrahydrofolate, 5- methyl-(6R,S)-tetrahydrofolate or 5-methyl-(6S)-tetrahydrofolate and one or more of the compounds sodium gluconate, potassium gluconate, glycerophosphate disodium salt or glycerophosphate dipotassium salt.
摘要翻译：甲酰四氢叶酸和其他活性的还原叶酸的施用可用作作为叶酸拮抗剂和与5-FU联合化疗的药物的解毒剂。最常用的叶酸钙盐在水中的溶解度低，形成几乎不溶的降解产物。因此，水溶液不稳定，导致沉淀。注射用产品中的沉淀物对患者来说是不可接受的安全隐患。形成稳定的高强度药物含水组合物，其含有还原叶酸甲酰四氢叶酸（6R，S） - 四氢叶酸，（6S） - 四氢叶酸，5,10-亚甲基 - （6R，S） - 四氢叶酸的钙盐，镁或锌盐，四氢叶酸，5,10-亚甲基 - （6R） - 四氢叶酸，5-甲基 - （6R，S） - 四氢叶酸或5-甲基（6S） - 四氢叶酸和一种或多种化合物葡萄糖酸钠，葡萄糖酸钾，甘油磷酸二钠盐或甘油磷酸二钾盐。

6. 发明申请

WO2014177273A1 STABLE HIGH STRENGTH PHARMACEUTICAL COMPOSITION OF LEVOLEUCOVORIN 审中-公开
标题翻译： LEVOLEUCOVORIN稳定的高强度药物组合物
公开(公告)号：WO2014177273A1
公开(公告)日：2014-11-06
申请号：PCT/EP2014/001152
申请日：2014-04-30
申请人： APROFOL AG
发明人： ULMANN, Martin
IPC分类号： A61K9/00 , A61K31/505 , A61K9/08 , A61K47/12 , A61K47/24
CPC分类号： A61K9/08 , A61K9/0019 , A61K31/519 , A61K47/12 , A61K47/18 , A61K47/20 , A61K47/24
摘要： The administration of levoleucovorin is useful as an antidote to drugs which act as folic acid antagonists and in combination chemotherapy with 5-FU. The most often used calcium salt of levoleucovorin has a limited solubility in water and forms almost insoluble degradation products. Therefore aqueous solutions are unstable and precipitates are resulting. Precipitates in injectable products present an unacceptable safety risk to patients. Stable high strength pharmaceutical aqueous compositions containing calcium salts, magnesium or zinc salts of levoleucovorin and one or more of the compounds sodium gluconate, potassium gluconate, glycerophosphate disodium salt or glycerophosphate dipotassium salt are disclosed.
摘要翻译：左啡诺因的施用可用作作为叶酸拮抗剂和与5-FU联合化疗的药物的解毒剂。最常用的左旋溶蛋白钙盐在水中的溶解度有限，形成几乎不可溶的降解产物。因此，水溶液不稳定，导致沉淀。注射用产品中的沉淀物对患者来说是不可接受的安全隐患。公开了含有左旋硬脑组织钙盐，镁盐或锌盐和一种或多种化合物葡萄糖酸钠，葡萄糖酸钾，甘油磷酸二钠盐或甘油磷酸二钾盐的稳定的高强度药物含水组合物。

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