JP2015526459A5 - - Google Patents
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- Publication number
- JP2015526459A5 JP2015526459A5 JP2015527966A JP2015527966A JP2015526459A5 JP 2015526459 A5 JP2015526459 A5 JP 2015526459A5 JP 2015527966 A JP2015527966 A JP 2015527966A JP 2015527966 A JP2015527966 A JP 2015527966A JP 2015526459 A5 JP2015526459 A5 JP 2015526459A5
- Authority
- JP
- Japan
- Prior art keywords
- nhe
- alkyl
- small molecule
- optionally substituted
- pharmaceutically acceptable
- 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
- 150000001875 compounds Chemical class 0.000 claims 19
- 230000002401 inhibitory effect Effects 0.000 claims 15
- 150000003384 small molecules Chemical class 0.000 claims 14
- 238000000034 method Methods 0.000 claims 13
- 229910052739 hydrogen Inorganic materials 0.000 claims 12
- 125000000217 alkyl group Chemical group 0.000 claims 11
- 150000003839 salts Chemical class 0.000 claims 10
- 239000008194 pharmaceutical composition Substances 0.000 claims 8
- 125000001072 heteroaryl group Chemical group 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims 4
- 241000124008 Mammalia Species 0.000 claims 4
- 239000003795 chemical substances by application Substances 0.000 claims 4
- 125000005647 linker group Chemical group 0.000 claims 4
- 229920001515 polyalkylene glycol Polymers 0.000 claims 4
- 239000002202 Polyethylene glycol Substances 0.000 claims 3
- 239000013543 active substance Substances 0.000 claims 3
- 125000002947 alkylene group Chemical group 0.000 claims 3
- 208000020832 chronic kidney disease Diseases 0.000 claims 3
- 229910052736 halogen Inorganic materials 0.000 claims 3
- 150000002367 halogens Chemical class 0.000 claims 3
- 239000000203 mixture Substances 0.000 claims 3
- 229920001223 polyethylene glycol Polymers 0.000 claims 3
- 239000000651 prodrug Substances 0.000 claims 3
- 229940002612 prodrug Drugs 0.000 claims 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims 2
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims 2
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims 2
- 239000000556 agonist Substances 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- -1 diluents Chemical class 0.000 claims 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 239000008141 laxative Substances 0.000 claims 2
- 229940125722 laxative agent Drugs 0.000 claims 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims 2
- 235000019341 magnesium sulphate Nutrition 0.000 claims 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims 2
- 235000019799 monosodium phosphate Nutrition 0.000 claims 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 claims 1
- 239000005541 ACE inhibitor Substances 0.000 claims 1
- 229940123338 Aldosterone synthase inhibitor Drugs 0.000 claims 1
- 229940127291 Calcium channel antagonist Drugs 0.000 claims 1
- 206010057573 Chronic hepatic failure Diseases 0.000 claims 1
- 101500007657 Crotalus durissus terrificus Crotoxin chain gamma Proteins 0.000 claims 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims 1
- 229940097420 Diuretic Drugs 0.000 claims 1
- 208000010334 End Stage Liver Disease Diseases 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 241001499733 Plantago asiatica Species 0.000 claims 1
- 235000003421 Plantago ovata Nutrition 0.000 claims 1
- 229920000148 Polycarbophil calcium Polymers 0.000 claims 1
- 239000009223 Psyllium Substances 0.000 claims 1
- 239000002170 aldosterone antagonist Substances 0.000 claims 1
- 229940083712 aldosterone antagonist Drugs 0.000 claims 1
- 239000002160 alpha blocker Substances 0.000 claims 1
- 229940035676 analgesics Drugs 0.000 claims 1
- 239000000584 angiotensin II type 2 receptor blocker Substances 0.000 claims 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims 1
- 239000000730 antalgic agent Substances 0.000 claims 1
- 239000003146 anticoagulant agent Substances 0.000 claims 1
- 229940127219 anticoagulant drug Drugs 0.000 claims 1
- 239000003524 antilipemic agent Substances 0.000 claims 1
- 229940127218 antiplatelet drug Drugs 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 230000003796 beauty Effects 0.000 claims 1
- 239000002876 beta blocker Substances 0.000 claims 1
- 229940097320 beta blocking agent Drugs 0.000 claims 1
- 239000000480 calcium channel blocker Substances 0.000 claims 1
- 239000002368 cardiac glycoside Substances 0.000 claims 1
- 229940097217 cardiac glycoside Drugs 0.000 claims 1
- 208000011444 chronic liver failure Diseases 0.000 claims 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 claims 1
- 235000013325 dietary fiber Nutrition 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims 1
- 239000002934 diuretic Substances 0.000 claims 1
- 230000001882 diuretic effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000008144 emollient laxative Substances 0.000 claims 1
- 208000028208 end stage renal disease Diseases 0.000 claims 1
- 201000000523 end stage renal failure Diseases 0.000 claims 1
- 235000011187 glycerol Nutrition 0.000 claims 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 1
- 230000036571 hydration Effects 0.000 claims 1
- 238000006703 hydration reaction Methods 0.000 claims 1
- 208000002551 irritable bowel syndrome Diseases 0.000 claims 1
- JCQLYHFGKNRPGE-FCVZTGTOSA-N lactulose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 JCQLYHFGKNRPGE-FCVZTGTOSA-N 0.000 claims 1
- 229960000511 lactulose Drugs 0.000 claims 1
- PFCRQPBOOFTZGQ-UHFFFAOYSA-N lactulose keto form Natural products OCC(=O)C(O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1O PFCRQPBOOFTZGQ-UHFFFAOYSA-N 0.000 claims 1
- 229960005336 magnesium citrate Drugs 0.000 claims 1
- 235000002538 magnesium citrate Nutrition 0.000 claims 1
- 239000004337 magnesium citrate Substances 0.000 claims 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims 1
- 239000000347 magnesium hydroxide Substances 0.000 claims 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims 1
- 229960000816 magnesium hydroxide Drugs 0.000 claims 1
- 235000012254 magnesium hydroxide Nutrition 0.000 claims 1
- 239000000395 magnesium oxide Substances 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 229940042003 metamucil Drugs 0.000 claims 1
- 229920000609 methyl cellulose Polymers 0.000 claims 1
- 239000001923 methylcellulose Substances 0.000 claims 1
- 239000008267 milk Substances 0.000 claims 1
- 210000004080 milk Anatomy 0.000 claims 1
- 235000013336 milk Nutrition 0.000 claims 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 claims 1
- 239000002357 osmotic agent Substances 0.000 claims 1
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229950005134 polycarbophil Drugs 0.000 claims 1
- 229940070687 psyllium Drugs 0.000 claims 1
- 239000002461 renin inhibitor Substances 0.000 claims 1
- 229940086526 renin-inhibitors Drugs 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000000600 sorbitol Substances 0.000 claims 1
- 229930002534 steroid glycoside Natural products 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 1
- 239000000829 suppository Substances 0.000 claims 1
- 239000004094 surface-active agent Substances 0.000 claims 1
- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 claims 1
- 229940124549 vasodilator Drugs 0.000 claims 1
- 239000003071 vasodilator agent Substances 0.000 claims 1
- 0 C***(**C)**N(C)C Chemical compound C***(**C)**N(C)C 0.000 description 2
- BFHKHGFNQCTRGN-PKBZYTSCSA-N CN(CC[C@H](CC(CO)O)O)C(NC(CCC(NCCOCCOCCNS(c1cccc([C@H](CN(C)C2)c3c2c(Cl)cc(Cl)c3)c1)(=O)=O)=[NH+][O-])(CCC(NCCOCCOCCNS(c1cccc([C@H](CN(C)C2)c3c2c(Cl)cc(Cl)c3)c1)(=O)=O)=O)CCC(NCCOCCOCCNS(c1cccc([C@H](CN(C)C2)c3c2c(Cl)cc(Cl)c3)c1)(=O)=O)=O)=O Chemical compound CN(CC[C@H](CC(CO)O)O)C(NC(CCC(NCCOCCOCCNS(c1cccc([C@H](CN(C)C2)c3c2c(Cl)cc(Cl)c3)c1)(=O)=O)=[NH+][O-])(CCC(NCCOCCOCCNS(c1cccc([C@H](CN(C)C2)c3c2c(Cl)cc(Cl)c3)c1)(=O)=O)=O)CCC(NCCOCCOCCNS(c1cccc([C@H](CN(C)C2)c3c2c(Cl)cc(Cl)c3)c1)(=O)=O)=O)=O BFHKHGFNQCTRGN-PKBZYTSCSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261691637P | 2012-08-21 | 2012-08-21 | |
| US61/691,637 | 2012-08-21 | ||
| PCT/GB2013/052193 WO2014029984A1 (en) | 2012-08-21 | 2013-08-20 | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019151700A Division JP2019218376A (ja) | 2012-08-21 | 2019-08-22 | 体液貯留又は塩過負荷に関係する疾患及び消化管疾患の治療におけるｎｈｅ仲介の逆輸送を阻害するための化合物並びに方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015526459A JP2015526459A (ja) | 2015-09-10 |
| JP2015526459A5 true JP2015526459A5 (OSRAM) | 2016-10-06 |
| JP6726964B2 JP6726964B2 (ja) | 2020-07-22 |
Family
ID=49036603
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015527966A Active JP6726964B2 (ja) | 2012-08-21 | 2013-08-20 | 体液貯留又は塩過負荷に関係する疾患及び消化管疾患の治療におけるｎｈｅ仲介の逆輸送を阻害するための化合物並びに方法 |
| JP2019151700A Pending JP2019218376A (ja) | 2012-08-21 | 2019-08-22 | 体液貯留又は塩過負荷に関係する疾患及び消化管疾患の治療におけるｎｈｅ仲介の逆輸送を阻害するための化合物並びに方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019151700A Pending JP2019218376A (ja) | 2012-08-21 | 2019-08-22 | 体液貯留又は塩過負荷に関係する疾患及び消化管疾患の治療におけるｎｈｅ仲介の逆輸送を阻害するための化合物並びに方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US20150299131A1 (OSRAM) |
| EP (1) | EP2887963B1 (OSRAM) |
| JP (2) | JP6726964B2 (OSRAM) |
| KR (1) | KR102138391B1 (OSRAM) |
| CN (1) | CN104837503B (OSRAM) |
| AU (2) | AU2013304813B2 (OSRAM) |
| BR (1) | BR112015003516A2 (OSRAM) |
| CA (1) | CA2880432C (OSRAM) |
| ES (1) | ES2644309T3 (OSRAM) |
| MX (1) | MX363056B (OSRAM) |
| RU (1) | RU2684097C2 (OSRAM) |
| WO (1) | WO2014029984A1 (OSRAM) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10543207B2 (en) | 2008-12-31 | 2020-01-28 | Ardelyx, Inc. | Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| EP2590656B1 (en) | 2010-07-07 | 2017-11-15 | Ardelyx, Inc. | Compounds and methods for inhibiting phosphate transport |
| EP2590655B1 (en) | 2010-07-07 | 2015-06-24 | Ardelyx, Inc. | Compounds and methods for inhibiting phosphate transport |
| WO2012006477A1 (en) | 2010-07-07 | 2012-01-12 | Ardelyx, Inc. | Compounds and methods for inhibiting phosphate transport |
| EP2590965B1 (en) | 2010-07-07 | 2016-04-20 | Ardelyx, Inc. | Compounds and methods for inhibiting phosphate transport |
| RU2684097C2 (ru) * | 2012-08-21 | 2019-04-04 | Эрделикс, Инк. | Соединения и способы для ингибирования NHE-опосредованного антипорта в лечении расстройств, ассоциированных с задержкой жидкости или солевой перегрузкой, и заболеваний желудочно-кишечного тракта |
| NZ752535A (en) * | 2013-04-12 | 2022-08-26 | Ardelyx Inc | Nhe3-binding compounds and methods for inhibiting phosphate transport |
| PL3173408T3 (pl) * | 2014-07-25 | 2019-05-31 | Taisho Pharma Co Ltd | Związek fenylotetrahydroizochinolinowy podstawiony heteroarylem |
| US10531837B1 (en) * | 2015-09-25 | 2020-01-14 | Cerner Innovation, Inc. | Predicting chronic kidney disease progression |
| EP3436011A4 (en) * | 2016-03-29 | 2019-12-04 | Colonaryconcepts LLC | FORMULATIONS FOR TREATING CONSTIPATION |
| RU2745992C2 (ru) * | 2016-04-25 | 2021-04-05 | Джелесис ЭлЭлСи | Способ лечения запора |
| WO2018129557A1 (en) * | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Inhibitors of nhe-mediated antiport |
| WO2018129552A1 (en) * | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Compounds useful for treating gastrointestinal tract disorders |
| WO2019060051A1 (en) | 2017-08-04 | 2019-03-28 | Ardelyx, Inc. | GLYCYRRHETINIC ACID DERIVATIVES FOR THE TREATMENT OF HYPERKALIEMIA |
| GB2565823A (en) * | 2017-08-24 | 2019-02-27 | Xiros Ltd | Psyllium based moisture absorbent material |
| CN107782829A (zh) * | 2017-11-01 | 2018-03-09 | 上海莱士血液制品股份有限公司 | 一种利用离子色谱法检测生物制品中三羟甲基氨基甲烷（Tris）的方法 |
| CN109813897A (zh) * | 2017-11-18 | 2019-05-28 | 镇江亿特生物科技发展有限公司 | 盐酸可乐定快速时间分辨荧光免疫层析定量检测试纸条 |
| JP7164114B2 (ja) * | 2018-01-19 | 2022-11-01 | 学校法人 名古屋電気学園 | バナジウム錯体及びそれを用いた窒素固定方法 |
| PH12021551892A1 (en) | 2019-02-07 | 2022-08-01 | Ardelyx Inc | Glycyrrhetinic acid derivatives for use in treating hyperkalemia |
| WO2021213089A1 (en) * | 2020-04-24 | 2021-10-28 | The University Of Hong Kong | A controlled drug release system of photoresponsive nanocarriers, methods of making and using thereof |
| EP4265608A4 (en) * | 2020-12-18 | 2024-12-11 | Shanghai Jemincare Pharmaceuticals Co., Ltd. | Benzoheterocycle substituted tetrahydroisoquinoline compound |
| CN114805202A (zh) * | 2021-01-28 | 2022-07-29 | 江西济民可信集团有限公司 | 苯磺酰胺类化合物及其制备方法和应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19941764A1 (de) * | 1999-09-02 | 2001-03-15 | Aventis Pharma Gmbh | Substituierte Acylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikamente oder Diagnostika sowie sie enthaltende Medikamente |
| CO5271699A1 (es) * | 2000-01-24 | 2003-04-30 | Pfizer Prod Inc | Procedimiento para el tratamiento de cardiomiopatia utilizando inhibidores de la glucogeno fosforilasa |
| DK1453810T3 (da) * | 2001-12-05 | 2009-07-20 | Sanofi Aventis Deutschland | Substituerede 4-phenyltetrahydroisoquinoliner, fremgangsmåde til deres fremstilling, deres anvendelse som medikament indeholdende samme |
| EP2384318B1 (en) * | 2008-12-31 | 2017-11-15 | Ardelyx, Inc. | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| RU2684097C2 (ru) * | 2012-08-21 | 2019-04-04 | Эрделикс, Инк. | Соединения и способы для ингибирования NHE-опосредованного антипорта в лечении расстройств, ассоциированных с задержкой жидкости или солевой перегрузкой, и заболеваний желудочно-кишечного тракта |
-
2013
- 2013-08-20 RU RU2015107018A patent/RU2684097C2/ru active
- 2013-08-20 WO PCT/GB2013/052193 patent/WO2014029984A1/en not_active Ceased
- 2013-08-20 CA CA2880432A patent/CA2880432C/en active Active
- 2013-08-20 US US14/421,454 patent/US20150299131A1/en not_active Abandoned
- 2013-08-20 MX MX2015002284A patent/MX363056B/es unknown
- 2013-08-20 EP EP13753340.2A patent/EP2887963B1/en active Active
- 2013-08-20 AU AU2013304813A patent/AU2013304813B2/en active Active
- 2013-08-20 JP JP2015527966A patent/JP6726964B2/ja active Active
- 2013-08-20 BR BR112015003516A patent/BR112015003516A2/pt not_active Application Discontinuation
- 2013-08-20 KR KR1020157006560A patent/KR102138391B1/ko active Active
- 2013-08-20 ES ES13753340.2T patent/ES2644309T3/es active Active
- 2013-08-20 CN CN201380054632.XA patent/CN104837503B/zh active Active
-
2016
- 2016-08-24 AU AU2016219612A patent/AU2016219612A1/en not_active Abandoned
-
2018
- 2018-06-13 US US16/007,622 patent/US10385024B2/en active Active
-
2019
- 2019-08-22 JP JP2019151700A patent/JP2019218376A/ja active Pending
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