JP2019514935A5 - - Google Patents
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- Publication number
- JP2019514935A5 JP2019514935A5 JP2018556834A JP2018556834A JP2019514935A5 JP 2019514935 A5 JP2019514935 A5 JP 2019514935A5 JP 2018556834 A JP2018556834 A JP 2018556834A JP 2018556834 A JP2018556834 A JP 2018556834A JP 2019514935 A5 JP2019514935 A5 JP 2019514935A5
- Authority
- JP
- Japan
- Prior art keywords
- medicament
- pla2
- treatment
- combination
- inhibitors
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 claims description 42
- 239000003358 phospholipase A2 inhibitor Substances 0.000 claims description 35
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 27
- 238000002347 injection Methods 0.000 claims description 14
- 239000007924 injection Substances 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 12
- 206010048962 Brain oedema Diseases 0.000 claims description 11
- 208000006752 brain edema Diseases 0.000 claims description 11
- 206010018910 Haemolysis Diseases 0.000 claims description 10
- 230000008588 hemolysis Effects 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 8
- 238000001802 infusion Methods 0.000 claims description 7
- PXRCDPVYRPKGGI-MRXNPFEDSA-N (2R)-3-[3-(5-benzyl-2-carbamoylphenyl)phenyl]-2-methylpropanoic acid Chemical compound C[C@H](Cc1cccc(c1)-c1cc(Cc2ccccc2)ccc1C(N)=O)C(O)=O PXRCDPVYRPKGGI-MRXNPFEDSA-N 0.000 claims description 6
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims description 6
- UHEGDWIZAOPGIY-UHFFFAOYSA-N 3-[3-(5-benzyl-2-carbamoylphenyl)phenyl]propanoic acid Chemical compound C(C1=CC=CC=C1)C=1C=CC(=C(C=1)C1=CC(=CC=C1)CCC(=O)O)C(N)=O UHEGDWIZAOPGIY-UHFFFAOYSA-N 0.000 claims description 6
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 6
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 6
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 6
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 6
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 6
- AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 claims description 6
- 229960005370 atorvastatin Drugs 0.000 claims description 6
- 229960005110 cerivastatin Drugs 0.000 claims description 6
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 229960003765 fluvastatin Drugs 0.000 claims description 6
- 229960004844 lovastatin Drugs 0.000 claims description 6
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 6
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 6
- 229950009116 mevastatin Drugs 0.000 claims description 6
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 claims description 6
- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 claims description 6
- 229930185723 monacolin Natural products 0.000 claims description 6
- 229960002797 pitavastatin Drugs 0.000 claims description 6
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims description 6
- 229960002965 pravastatin Drugs 0.000 claims description 6
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 6
- 229960000672 rosuvastatin Drugs 0.000 claims description 6
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 6
- 229960002855 simvastatin Drugs 0.000 claims description 6
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 6
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 5
- 208000008585 mastocytosis Diseases 0.000 claims description 5
- 239000003783 hymenoptera venom Substances 0.000 claims description 4
- 239000002435 venom Substances 0.000 claims description 4
- 231100000611 venom Toxicity 0.000 claims description 4
- 210000001048 venom Anatomy 0.000 claims description 4
- 230000037396 body weight Effects 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 239000003998 snake venom Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims 22
- 102100037611 Lysophospholipase Human genes 0.000 claims 11
- 108010058864 Phospholipases A2 Proteins 0.000 claims 11
- 229940000425 combination drug Drugs 0.000 claims 6
- 229940079593 drug Drugs 0.000 claims 6
- 231100000614 poison Toxicity 0.000 claims 3
- 239000002574 poison Substances 0.000 claims 3
- 241000257303 Hymenoptera Species 0.000 claims 2
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 claims 1
- 241000256844 Apis mellifera Species 0.000 claims 1
- 206010030113 Oedema Diseases 0.000 claims 1
- 102000015439 Phospholipases Human genes 0.000 claims 1
- 108010064785 Phospholipases Proteins 0.000 claims 1
- 208000033626 Renal failure acute Diseases 0.000 claims 1
- 201000011040 acute kidney failure Diseases 0.000 claims 1
- 208000012998 acute renal failure Diseases 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 208000017169 kidney disease Diseases 0.000 claims 1
- 231100000636 lethal dose Toxicity 0.000 claims 1
- 230000000926 neurological effect Effects 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 230000008085 renal dysfunction Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 12
- UWYANTZRSJRLJO-UHFFFAOYSA-N 2-[2-ethyl-1-oxamoyl-3-[(2-phenylphenyl)methyl]indolizin-8-yl]oxyacetic acid Chemical compound N12C=CC=C(OCC(O)=O)C2=C(C(=O)C(N)=O)C(CC)=C1CC1=CC=CC=C1C1=CC=CC=C1 UWYANTZRSJRLJO-UHFFFAOYSA-N 0.000 description 4
- -1 methylindoxam Chemical compound 0.000 description 4
- 238000009472 formulation Methods 0.000 description 3
- 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 description 2
- 102100036050 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A Human genes 0.000 description 2
- 229940122055 Serine protease inhibitor Drugs 0.000 description 2
- 101710102218 Serine protease inhibitor Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 101000998548 Yersinia ruckeri Alkaline proteinase inhibitor Proteins 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000001062 anti-nausea Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 2
- 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 description 2
- 239000003001 serine protease inhibitor Substances 0.000 description 2
- 125000002345 steroid group Chemical group 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010063094 Cerebral malaria Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 206010014498 Embolic stroke Diseases 0.000 description 1
- 208000025499 G6PD deficiency Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- 206010062622 Pigment nephropathy Diseases 0.000 description 1
- 241000606701 Rickettsia Species 0.000 description 1
- 206010041509 Spherocytic anaemia Diseases 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 208000002903 Thalassemia Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000003659 bee venom Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 208000008605 glucosephosphate dehydrogenase deficiency Diseases 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 208000009601 hereditary spherocytosis Diseases 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000024241 parasitism Effects 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022135335A JP2022177020A (ja) | 2016-04-29 | 2022-08-26 | 溶血、脳浮腫および急性腎障害を引き起こす病態の治療のためのｐｌａ２およびｈｍｇ－ｃｏａ阻害剤 |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662329611P | 2016-04-29 | 2016-04-29 | |
| US62/329,611 | 2016-04-29 | ||
| US201662340075P | 2016-05-23 | 2016-05-23 | |
| US62/340,075 | 2016-05-23 | ||
| US201662423693P | 2016-11-17 | 2016-11-17 | |
| US62/423,693 | 2016-11-17 | ||
| PCT/US2017/030436 WO2017190141A1 (en) | 2016-04-29 | 2017-05-01 | Pla2 and hmg-coa inhibitors for treatment of pathological conditions causing hemolysis, cerebral edema, and acute kidney injury |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022135335A Division JP2022177020A (ja) | 2016-04-29 | 2022-08-26 | 溶血、脳浮腫および急性腎障害を引き起こす病態の治療のためのｐｌａ２およびｈｍｇ－ｃｏａ阻害剤 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019514935A JP2019514935A (ja) | 2019-06-06 |
| JP2019514935A5 true JP2019514935A5 (enExample) | 2020-06-18 |
| JP7542935B2 JP7542935B2 (ja) | 2024-09-02 |
Family
ID=60161200
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018556834A Active JP7542935B2 (ja) | 2016-04-29 | 2017-05-01 | 溶血、脳浮腫および急性腎障害を引き起こす病態の治療のためのｐｌａ２およびｈｍｇ－ｃｏａ阻害剤 |
| JP2022135335A Pending JP2022177020A (ja) | 2016-04-29 | 2022-08-26 | 溶血、脳浮腫および急性腎障害を引き起こす病態の治療のためのｐｌａ２およびｈｍｇ－ｃｏａ阻害剤 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022135335A Pending JP2022177020A (ja) | 2016-04-29 | 2022-08-26 | 溶血、脳浮腫および急性腎障害を引き起こす病態の治療のためのｐｌａ２およびｈｍｇ－ｃｏａ阻害剤 |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US12383531B2 (enExample) |
| EP (1) | EP3448378B1 (enExample) |
| JP (2) | JP7542935B2 (enExample) |
| KR (2) | KR102723249B1 (enExample) |
| CN (2) | CN109562098B (enExample) |
| AU (2) | AU2017257185B9 (enExample) |
| IL (2) | IL262620B2 (enExample) |
| MX (2) | MX391165B (enExample) |
| WO (1) | WO2017190141A1 (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102723249B1 (ko) | 2016-04-29 | 2024-10-28 | 오피렉스, 인크. | 벌목 유독동물독소중독으로 인한 용혈, 뇌부종, 및 급성 신손상의 치료를 위한 pla2 및 hmg-coa 억제제 |
| US20240382452A1 (en) * | 2021-11-09 | 2024-11-21 | Ophirex, Inc. | Compositions and dosage forms for topical and transdermal delivery of actives and methods of use |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL84252A (en) | 1987-10-23 | 1994-02-27 | Yissum Res Dev Co | Phospholipase inhibiting compositions |
| DE69527322T2 (de) * | 1994-04-01 | 2003-02-27 | Eli Lilly And Co., Indianapolis | 1H-Indol-3-Glyoxylamid sPLA2 Inhibitoren |
| CA2264254C (en) * | 1996-08-28 | 2003-03-11 | Yetunde Olabisi Taiwo | Phosphinic acid amides as matrix metalloprotease inhibitors |
| AUPP076797A0 (en) | 1997-12-05 | 1998-01-08 | Active (Pla) R&D Pty Ltd | Phospholipase inhibitor |
| GB2365769A (en) | 2000-08-18 | 2002-02-27 | Secr Defence | Skin preparations containing silicon |
| US8106019B2 (en) * | 2002-11-15 | 2012-01-31 | Philadelphia Health & Education Corporation | CHEC-7 a novel sPLA2 inhibitor |
| ATE400300T1 (de) * | 2003-09-09 | 2008-07-15 | Univ Florida | Polyamin-metallchelatbildner-konjugate |
| FR2873293B1 (fr) * | 2004-07-21 | 2006-11-17 | Cerep Sa | Utilisation d'un acide gras pour la preparation d'une composition topique destinee a l'apaisement des reactions inflammatoires dues aux piqures d'hymenopteres a venin |
| US20090234011A1 (en) | 2005-04-21 | 2009-09-17 | Goldstein Glenn A | N-acetylcysteine amide (nac amide) for the treatment of diseases and conditions associated with oxidative stress |
| CN102271507A (zh) | 2009-01-08 | 2011-12-07 | 安塞拉制药有限公司 | 分泌型磷脂酶a2(spla2)抑制剂和烟酸药物组合物以及治疗心血管疾病和血脂异常的方法 |
| WO2011137390A1 (en) | 2010-04-30 | 2011-11-03 | Anthera Pharmaceuticals, Inc. | Treatment of major adverse cardiac events and acute coronary syndrome in diabetic patients using secretory phospholipase a2 (spla2) inhibitor or spla2 inhibitor combination therapies |
| US20150224094A1 (en) | 2012-09-10 | 2015-08-13 | Ophirex, Inc. | Administration of acetylcholinesterase inhibitors to mitigate neurotoxin-induced paralysis and residual neuromuscular blockade |
| US20140087003A1 (en) * | 2012-09-21 | 2014-03-27 | Ignacio Cisneros | Method for treating venomous bites and stings |
| MA40998A (fr) | 2014-11-21 | 2017-09-26 | Ophirex Inc | Thérapies contre une envenimation, ainsi que compositions, systèmes et kits pharmaceutiques associés |
| US10786483B2 (en) * | 2016-03-04 | 2020-09-29 | Hk Pharma | Tumescent contravenom drug delivery |
| KR102723249B1 (ko) * | 2016-04-29 | 2024-10-28 | 오피렉스, 인크. | 벌목 유독동물독소중독으로 인한 용혈, 뇌부종, 및 급성 신손상의 치료를 위한 pla2 및 hmg-coa 억제제 |
-
2017
- 2017-05-01 KR KR1020237011040A patent/KR102723249B1/ko active Active
- 2017-05-01 JP JP2018556834A patent/JP7542935B2/ja active Active
- 2017-05-01 WO PCT/US2017/030436 patent/WO2017190141A1/en not_active Ceased
- 2017-05-01 EP EP17790643.5A patent/EP3448378B1/en active Active
- 2017-05-01 IL IL262620A patent/IL262620B2/en unknown
- 2017-05-01 US US16/097,160 patent/US12383531B2/en active Active
- 2017-05-01 AU AU2017257185A patent/AU2017257185B9/en active Active
- 2017-05-01 CN CN201780040801.2A patent/CN109562098B/zh active Active
- 2017-05-01 MX MX2018013084A patent/MX391165B/es unknown
- 2017-05-01 CN CN202310330976.4A patent/CN116585306B/zh active Active
- 2017-05-01 KR KR1020187034573A patent/KR20190005898A/ko not_active Ceased
-
2018
- 2018-10-25 MX MX2022003739A patent/MX2022003739A/es unknown
-
2022
- 2022-08-26 JP JP2022135335A patent/JP2022177020A/ja active Pending
-
2023
- 2023-09-22 AU AU2023233187A patent/AU2023233187A1/en active Pending
- 2023-09-26 IL IL307232A patent/IL307232B1/en unknown
-
2024
- 2024-12-23 US US19/000,226 patent/US20250120949A1/en active Pending
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