JPWO2019213245A5 - - Google Patents

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JPWO2019213245A5
JPWO2019213245A5 JP2020561795A JP2020561795A JPWO2019213245A5 JP WO2019213245 A5 JPWO2019213245 A5 JP WO2019213245A5 JP 2020561795 A JP2020561795 A JP 2020561795A JP 2020561795 A JP2020561795 A JP 2020561795A JP WO2019213245 A5 JPWO2019213245 A5 JP WO2019213245A5
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JP2020561795A
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JP2021523126A (en
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Priority claimed from PCT/US2019/030184 external-priority patent/WO2019213245A1/en
Publication of JP2021523126A publication Critical patent/JP2021523126A/en
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対象において蓄積した病理学的Tauタンパク質を低減するための組成物であって、薬学的に有効な量の、2,4-ジスルホニルα-フェニルターシャリーブチルニトロン(2,4-DSPBN)またはその薬学的に許容される塩およびN-アセチルシステイン(NAC)またはその薬学的に許容される塩を含む組成物。 A composition for reducing pathological Tau protein accumulated in a subject, in a pharmaceutically effective amount, 2,4-disulfonylα-phenyltertiary butylnitron (2,4-DSPBN). Or a composition comprising a pharmaceutically acceptable salt thereof and N-acetylcysteine (NAC) or a pharmaceutically acceptable salt thereof. らに薬学的に許容される担体を含む、請求項1に記載の組成物The composition of claim 1, further comprising a pharmaceutically acceptable carrier. 象に経口で、静脈内に、皮下に、舌下に、真皮下に、髄腔内に、吸入により、または耳内局所に投与される、請求項1に記載の組成物The composition according to claim 1, which is orally administered to a subject , intravenously, subcutaneously, sublingually, subdermally, intrathecally, by inhalation, or topically in the ear. 蓄積した病理学的Tauタンパク質が加齢に起因する、請求項1に記載の組成物The composition according to claim 1, wherein the accumulated pathological Tau protein is due to aging. 蓄積した病理学的Tauタンパク質が中枢神経系疾患に起因する、請求項1に記載の組成物The composition according to claim 1, wherein the accumulated pathological Tau protein is caused by a central nervous system disease. 枢神経系疾患の発症後少なくとも2ヶ月、少なくとも3ヶ月、少なくとも6ヶ月、少なくとも9ヶ月、少なくとも12ヶ月、または1~60ヶ月対象に投与される、請求項5に記載の組成物The composition according to claim 5, which is administered to a subject at least 2 months, at least 3 months, at least 6 months, at least 9 months, at least 12 months, or 1 to 60 months after the onset of a central nervous system disease. 蓄積した病理学的Tauタンパク質が騒音への曝露に起因する、請求項1に記載の組成物The composition of claim 1, wherein the accumulated pathological Tau protein results from exposure to noise. 音への曝露後少なくとも2ヶ月、少なくとも3ヶ月、少なくとも6ヶ月、少なくとも9ヶ月、少なくとも12ヶ月、または1~60ヶ月対象に投与される、請求項7に記載の組成物The composition according to claim 7, which is administered to a subject at least 2 months, at least 3 months, at least 6 months, at least 9 months, at least 12 months, or 1-60 months after exposure to noise . 蓄積した病理学的Tauが爆風への曝露に起因する、請求項1に記載の組成物The composition according to claim 1, wherein the accumulated pathological Tau results from exposure to a blast. 風への曝露後少なくとも2ヶ月、少なくとも3ヶ月、少なくとも6ヶ月、少なくとも9ヶ月、少なくとも12ヶ月、または1~60ヶ月対象に投与される、請求項9に記載の組成物The composition of claim 9, which is administered to the subject at least 2 months, at least 3 months, at least 6 months, at least 9 months, at least 12 months, or 1-60 months after exposure to the blast . 蓄積した病理学的Tauが感染に起因する、請求項1に記載の組成物The composition according to claim 1, wherein the accumulated pathological Tau is caused by an infection. 染後少なくとも2ヶ月、少なくとも3ヶ月、少なくとも6ヶ月、少なくとも9ヶ月、少なくとも12ヶ月、または1~60ヶ月対象に投与される、請求項11に記載の組成物11. The composition of claim 11, which is administered to a subject at least 2 months, at least 3 months, at least 6 months, at least 9 months, at least 12 months, or 1-60 months after infection . 蓄積した病理学的Tauが毒素への曝露に起因する、請求項1に記載の組成物The composition according to claim 1, wherein the accumulated pathological Tau results from exposure to a toxin. 素への曝露後少なくとも2ヶ月、少なくとも3ヶ月、少なくとも6ヶ月、少なくとも9ヶ月、少なくとも12ヶ月、または1~60ヶ月対象に投与される、請求項13に記載の組成物13. The composition of claim 13, which is administered to the subject at least 2 months, at least 3 months, at least 6 months, at least 9 months, at least 12 months, or 1-60 months after exposure to the toxin . 対象の脳脊髄液が少なくとも0.07ng/mlの蓄積した病理学的Tauタンパク質を含む、請求項1に記載の組成物The composition of claim 1, wherein the subject cerebrospinal fluid comprises at least 0.07 ng / ml of accumulated pathological Tau protein. 対象が中枢神経系疾患を患っており、組成物の投与が中枢神経系における蓄積した病理学的Tauタンパク質を少なくとも5%低減する、請求項1に記載の組成物The composition according to claim 1, wherein the subject suffers from a central nervous system disease and administration of the composition reduces the pathological Tau protein accumulated in the central nervous system by at least 5%. 対象が慢性の騒音誘発性もしくは爆風誘発性難聴もしくは耳鳴り、または老人性難聴もしくは老人性難聴に随伴する耳鳴りを患っており、組成物の投与が蝸牛または前庭部における蓄積した病理学的Tauタンパク質を少なくとも5%低減する、請求項1に記載の組成物Subject suffers from chronic noise-induced or blast-induced tinnitus or tinnitus, or tinnitus associated with presbycusis or presbycusis, and administration of the composition to the accumulated pathological Tau protein in the cochlea or vestibule. The composition according to claim 1, which is reduced by at least 5%. さらにTau凝集阻害剤を含む、請求項1に記載の組成物The composition according to claim 1, further comprising a Tau aggregation inhibitor. 蓄積した病理学的Tauタンパク質が高リン酸化型である、請求項1に記載の組成物The composition according to claim 1, wherein the accumulated pathological Tau protein is a highly phosphorylated form. 対象において蓄積した病理学的Tauタンパク質を低減するための組成物であって、薬学的に有効な量の、2,4-ジスルホニルα-フェニルターシャリーブチルニトロン(2,4-DSPBN)またはその薬学的に許容される塩を含む組成物。 A composition for reducing pathological Tau protein accumulated in a subject, in a pharmaceutically effective amount, 2,4-disulfonylα-phenyltertiary butylnitron (2,4-DSPBN) or A composition comprising the pharmaceutically acceptable salt thereof. 蓄積した病理学的Tauが爆風または騒音への曝露に起因し、爆風または騒音への曝露後少なくとも2ヶ月、少なくとも3ヶ月、少なくとも6ヶ月、少なくとも9ヶ月、少なくとも12ヶ月、または1~60ヶ月対象に投与される、請求項20に記載の組成物Accumulated pathological Tau is due to exposure to blast or noise and is at least 2 months, at least 3 months, at least 6 months, at least 9 months, at least 12 months, or 1-60 months after exposure to blast or noise. The composition according to claim 20, which is administered to a subject. 蓄積した病理学的Tauタンパク質が高リン酸化型である、請求項20に記載の組成物The composition according to claim 20, wherein the accumulated pathological Tau protein is a highly phosphorylated form.
JP2020561795A 2018-05-03 2019-05-01 How to reduce accumulated pathological Tau protein Pending JP2021523126A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862666459P 2018-05-03 2018-05-03
US62/666,459 2018-05-03
PCT/US2019/030184 WO2019213245A1 (en) 2018-05-03 2019-05-01 Methods for reducing accumulated pathologic tau protein

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JP2021523126A JP2021523126A (en) 2021-09-02
JPWO2019213245A5 true JPWO2019213245A5 (en) 2022-05-10

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US (1) US20210137861A1 (en)
EP (1) EP3787750A1 (en)
JP (1) JP2021523126A (en)
WO (1) WO2019213245A1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2178212C (en) * 1993-12-21 2011-06-14 Marc Vandermeeren Monoclonal antibodies specific for phf-tau, hybridomas secreting them, antigen recognition by these antibodies and their applications
US5488145A (en) 1993-12-23 1996-01-30 Oklahoma Medical Research Foundation 2,4-disulfonyl phenyl butyl nitrone, its salts, and their use as pharmaceutical free radical traps
CA2505355A1 (en) * 2002-11-07 2004-05-27 Applied Neurosolutions Methods for predicting whether subjects with mild cognitive impairment (mci) will develop alzheimer's disease
AU2010289838C1 (en) * 2009-08-24 2014-03-06 Hough Ear Institute Methods for treating acute acoustic trauma
US9289404B2 (en) * 2011-02-04 2016-03-22 Hough Ear Institute Methods for treating brain injury
JP6126531B2 (en) * 2011-10-03 2017-05-10 国立研究開発法人国立長寿医療研究センター Tau aggregation inhibitor
US20180256756A1 (en) * 2015-09-18 2018-09-13 Oklahoma Medical Research Foundation Method of transporting an agent across blood-brain, blood-cochlear or blood-cerebrospinal fluid barrier

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