JP2016512527A5 - - Google Patents
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- JP2016512527A5 JP2016512527A5 JP2016501330A JP2016501330A JP2016512527A5 JP 2016512527 A5 JP2016512527 A5 JP 2016512527A5 JP 2016501330 A JP2016501330 A JP 2016501330A JP 2016501330 A JP2016501330 A JP 2016501330A JP 2016512527 A5 JP2016512527 A5 JP 2016512527A5
- Authority
- JP
- Japan
- Prior art keywords
- therapeutic agent
- particle
- cerebral
- cerebral artery
- calcium channel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 239000003814 drug Substances 0.000 claims description 82
- 229940124597 therapeutic agent Drugs 0.000 claims description 80
- 239000002245 particle Substances 0.000 claims description 69
- 239000000203 mixture Substances 0.000 claims description 40
- 210000001627 cerebral artery Anatomy 0.000 claims description 38
- 239000003937 drug carrier Substances 0.000 claims description 34
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 25
- 239000011859 microparticle Substances 0.000 claims description 21
- 206010008118 cerebral infarction Diseases 0.000 claims description 20
- 230000003111 delayed effect Effects 0.000 claims description 20
- 239000012530 fluid Substances 0.000 claims description 20
- 239000002105 nanoparticle Substances 0.000 claims description 20
- 230000001225 therapeutic effect Effects 0.000 claims description 20
- 229940125400 channel inhibitor Drugs 0.000 claims description 19
- 230000009969 flowable effect Effects 0.000 claims description 18
- 201000006474 Brain Ischemia Diseases 0.000 claims description 16
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 16
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 238000013268 sustained release Methods 0.000 claims description 14
- 239000012730 sustained-release form Substances 0.000 claims description 14
- 238000002347 injection Methods 0.000 claims description 12
- 239000007924 injection Substances 0.000 claims description 12
- 239000011159 matrix material Substances 0.000 claims description 12
- 231100000682 maximum tolerated dose Toxicity 0.000 claims description 12
- 230000036470 plasma concentration Effects 0.000 claims description 12
- 238000009472 formulation Methods 0.000 claims description 9
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 8
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 claims description 8
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 8
- 229920002988 biodegradable polymer Polymers 0.000 claims description 8
- 239000004621 biodegradable polymer Substances 0.000 claims description 8
- 239000000480 calcium channel blocker Substances 0.000 claims description 8
- 239000011248 coating agent Substances 0.000 claims description 8
- 238000000576 coating method Methods 0.000 claims description 8
- 239000006185 dispersion Substances 0.000 claims description 8
- 238000009826 distribution Methods 0.000 claims description 8
- 229920002674 hyaluronan Polymers 0.000 claims description 8
- 229960003160 hyaluronic acid Drugs 0.000 claims description 8
- 229960000715 nimodipine Drugs 0.000 claims description 8
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims description 8
- 210000002330 subarachnoid space Anatomy 0.000 claims description 8
- 102000004016 L-Type Calcium Channels Human genes 0.000 claims description 6
- 108090000420 L-Type Calcium Channels Proteins 0.000 claims description 6
- -1 bamidipine Chemical compound 0.000 claims description 6
- 208000024891 symptom Diseases 0.000 claims description 6
- 239000010419 fine particle Substances 0.000 claims description 5
- PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 claims description 4
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 4
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 claims description 4
- XTFPDGZNWTZCMF-DHZHZOJOSA-N 3-o-methyl 5-o-[(e)-3-phenylprop-2-enyl] 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC\C=C\C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 XTFPDGZNWTZCMF-DHZHZOJOSA-N 0.000 claims description 4
- 108091006146 Channels Proteins 0.000 claims description 4
- 206010010071 Coma Diseases 0.000 claims description 4
- 108090000699 N-Type Calcium Channels Proteins 0.000 claims description 4
- 102000004129 N-Type Calcium Channels Human genes 0.000 claims description 4
- 108010027023 Q-Type Calcium Channels Proteins 0.000 claims description 4
- 108090000583 R-Type Calcium Channels Proteins 0.000 claims description 4
- 102000004059 R-Type Calcium Channels Human genes 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 206010047163 Vasospasm Diseases 0.000 claims description 4
- 210000002551 anterior cerebral artery Anatomy 0.000 claims description 4
- 230000002051 biphasic effect Effects 0.000 claims description 4
- 208000029028 brain injury Diseases 0.000 claims description 4
- 210000004004 carotid artery internal Anatomy 0.000 claims description 4
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 4
- 230000001054 cortical effect Effects 0.000 claims description 4
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 4
- 210000004055 fourth ventricle Anatomy 0.000 claims description 4
- 230000036541 health Effects 0.000 claims description 4
- 208000028867 ischemia Diseases 0.000 claims description 4
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims description 4
- 210000003140 lateral ventricle Anatomy 0.000 claims description 4
- 230000007774 longterm Effects 0.000 claims description 4
- 229960003963 manidipine Drugs 0.000 claims description 4
- ANEBWFXPVPTEET-UHFFFAOYSA-N manidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ANEBWFXPVPTEET-UHFFFAOYSA-N 0.000 claims description 4
- 210000003657 middle cerebral artery Anatomy 0.000 claims description 4
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 claims description 4
- 229960001597 nifedipine Drugs 0.000 claims description 4
- 229960005425 nitrendipine Drugs 0.000 claims description 4
- 229920000642 polymer Polymers 0.000 claims description 4
- 229950004891 pranidipine Drugs 0.000 claims description 4
- 238000001179 sorption measurement Methods 0.000 claims description 4
- 238000003892 spreading Methods 0.000 claims description 4
- 230000007480 spreading Effects 0.000 claims description 4
- 230000001839 systemic circulation Effects 0.000 claims description 4
- 210000000211 third ventricle Anatomy 0.000 claims description 4
- 230000001052 transient effect Effects 0.000 claims description 4
- 210000000689 upper leg Anatomy 0.000 claims description 4
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 claims description 3
- NSVFSAJIGAJDMR-UHFFFAOYSA-N 2-[benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound CC=1NC(C)=C(C(=O)OCCN(CC=2C=CC=CC=2)C=2C=CC=CC=2)C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1P1(=O)OCC(C)(C)CO1 NSVFSAJIGAJDMR-UHFFFAOYSA-N 0.000 claims description 3
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 claims description 3
- ZKFQEACEUNWPMT-UHFFFAOYSA-N Azelnidipine Chemical compound CC(C)OC(=O)C1=C(C)NC(N)=C(C(=O)OC2CN(C2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZKFQEACEUNWPMT-UHFFFAOYSA-N 0.000 claims description 3
- FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 claims description 3
- 229940125968 Voltage-Gated Calcium Channel inhibitor Drugs 0.000 claims description 3
- 229960000528 amlodipine Drugs 0.000 claims description 3
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 claims description 3
- 229950004646 azelnidipine Drugs 0.000 claims description 3
- 229960004916 benidipine Drugs 0.000 claims description 3
- QZVNQOLPLYWLHQ-ZEQKJWHPSA-N benidipine Chemical compound C1([C@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)O[C@H]2CN(CC=3C=CC=CC=3)CCC2)=CC=CC([N+]([O-])=O)=C1 QZVNQOLPLYWLHQ-ZEQKJWHPSA-N 0.000 claims description 3
- 230000002490 cerebral effect Effects 0.000 claims description 3
- 210000004720 cerebrum Anatomy 0.000 claims description 3
- 229950003102 efonidipine Drugs 0.000 claims description 3
- 229960003580 felodipine Drugs 0.000 claims description 3
- 229960004427 isradipine Drugs 0.000 claims description 3
- 229960004294 lercanidipine Drugs 0.000 claims description 3
- ZDXUKAKRHYTAKV-UHFFFAOYSA-N lercanidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZDXUKAKRHYTAKV-UHFFFAOYSA-N 0.000 claims description 3
- 229960005366 nilvadipine Drugs 0.000 claims description 3
- 229940076372 protein antagonist Drugs 0.000 claims description 3
- 210000001367 artery Anatomy 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 claims 2
- 230000000903 blocking effect Effects 0.000 claims 2
- 210000003414 extremity Anatomy 0.000 claims 2
- 239000003112 inhibitor Substances 0.000 claims 2
- 229960001783 nicardipine Drugs 0.000 claims 2
- 108090000312 Calcium Channels Proteins 0.000 claims 1
- 102000003922 Calcium Channels Human genes 0.000 claims 1
- 238000007913 intrathecal administration Methods 0.000 claims 1
- 108091023044 voltage-gated calcium channel activity Proteins 0.000 claims 1
- 102000038650 voltage-gated calcium channel activity Human genes 0.000 claims 1
- 238000000034 method Methods 0.000 description 47
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000002414 leg Anatomy 0.000 description 2
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 2
- 229960000227 nisoldipine Drugs 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 102000003691 T-Type Calcium Channels Human genes 0.000 description 1
- 108090000030 T-Type Calcium Channels Proteins 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/793,767 | 2013-03-11 | ||
| US13/793,767 US10092524B2 (en) | 2008-06-11 | 2013-03-11 | Compositions and their use to treat complications of aneurysmal subarachnoid hemorrhage |
| PCT/US2014/023748 WO2014164904A1 (en) | 2013-03-11 | 2014-03-11 | Compositions and their use to treat complications of aneurysmal subarachnoid hemorrhage |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2016512527A JP2016512527A (ja) | 2016-04-28 |
| JP2016512527A5 true JP2016512527A5 (enExample) | 2017-02-16 |
Family
ID=49157870
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016501330A Pending JP2016512527A (ja) | 2013-03-11 | 2014-03-11 | 動脈瘤性くも膜下出血の合併症を治療するための組成物およびそれらの使用 |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US10092524B2 (enExample) |
| EP (1) | EP2968166A4 (enExample) |
| JP (1) | JP2016512527A (enExample) |
| KR (1) | KR101902319B1 (enExample) |
| CN (1) | CN105324108A (enExample) |
| AU (1) | AU2014248877A1 (enExample) |
| BR (1) | BR112015022218A2 (enExample) |
| CA (1) | CA2905327A1 (enExample) |
| GB (1) | GB2528801A (enExample) |
| HK (1) | HK1216002A1 (enExample) |
| NZ (1) | NZ629730A (enExample) |
| RU (1) | RU2015143206A (enExample) |
| SG (1) | SG11201507398XA (enExample) |
| WO (1) | WO2014164904A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10092524B2 (en) | 2008-06-11 | 2018-10-09 | Edge Therapeutics, Inc. | Compositions and their use to treat complications of aneurysmal subarachnoid hemorrhage |
| EP2694133B1 (en) | 2011-04-05 | 2018-05-23 | Edge Therapeutics, Inc. | Intraventricular drug delivery system for improving outcome after a brain injury affecting cerebral blood flow |
| CA2986692A1 (en) * | 2015-05-29 | 2016-12-08 | Edge Therapeutics, Inc. | Compositions and methods for reducing visual loss |
| WO2017176914A1 (en) * | 2016-04-07 | 2017-10-12 | Edge Therapeutics, Inc. | Formulations of site-specific, microparticulate compositions and their use to improve outcome after aneurysmal subarachnoid hemorrhage |
| CN108403629B (zh) * | 2018-04-26 | 2019-11-05 | 徐州医科大学 | 一种尼莫地平口服长效悬浮液及其制备方法 |
| JP2022533564A (ja) * | 2019-05-07 | 2022-07-25 | イェール ユニバーシティー | 骨内の注入物の分布を最大化すること及び流出を最小化すること並びに増強した吸引抽出のための方法 |
| WO2020235947A1 (ko) * | 2019-05-22 | 2020-11-26 | 경북대학교 산학협력단 | Cacb1 유래 펩타이드, Cacb1 유래 펩타이드의 변이체 및 이의 용도 |
| WO2021168351A1 (en) * | 2020-02-20 | 2021-08-26 | Postsurgical Therapeutics, Inc. | Brain drug delivery system and method |
| WO2021262725A1 (en) * | 2020-06-22 | 2021-12-30 | Curelator, Inc. | Systems and methods for segmentation of a user population based on time-based variations in biomarker levels |
| US11452690B1 (en) | 2021-01-27 | 2022-09-27 | ECI Pharmaceuticals, LLC | Oral liquid compositions comprising amlodipine besylate and methods of using the same |
| EP4301425B1 (en) * | 2021-03-03 | 2025-01-22 | Crannmed Limited | Alginate based particles as a temporary embolic agent |
| WO2025151741A1 (en) * | 2024-01-10 | 2025-07-17 | Brown David Donaldson | Methods of treating migraine headache or tension headache with hyaluronic acid |
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-
2013
- 2013-03-11 US US13/793,767 patent/US10092524B2/en not_active Expired - Fee Related
-
2014
- 2014-03-11 KR KR1020157028454A patent/KR101902319B1/ko not_active Expired - Fee Related
- 2014-03-11 HK HK16103935.4A patent/HK1216002A1/zh unknown
- 2014-03-11 RU RU2015143206A patent/RU2015143206A/ru not_active Application Discontinuation
- 2014-03-11 WO PCT/US2014/023748 patent/WO2014164904A1/en not_active Ceased
- 2014-03-11 NZ NZ629730A patent/NZ629730A/en not_active IP Right Cessation
- 2014-03-11 BR BR112015022218A patent/BR112015022218A2/pt not_active IP Right Cessation
- 2014-03-11 EP EP14780318.3A patent/EP2968166A4/en not_active Withdrawn
- 2014-03-11 CA CA2905327A patent/CA2905327A1/en not_active Abandoned
- 2014-03-11 GB GB1516997.2A patent/GB2528801A/en not_active Withdrawn
- 2014-03-11 JP JP2016501330A patent/JP2016512527A/ja active Pending
- 2014-03-11 SG SG11201507398XA patent/SG11201507398XA/en unknown
- 2014-03-11 CN CN201480026815.5A patent/CN105324108A/zh active Pending
- 2014-03-11 AU AU2014248877A patent/AU2014248877A1/en not_active Abandoned
-
2016
- 2016-05-16 US US15/156,152 patent/US20160324796A1/en not_active Abandoned
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