HRP20221100T1 - Stabilna parenteralna formulacija nimopidina - Google Patents
Stabilna parenteralna formulacija nimopidina Download PDFInfo
- Publication number
- HRP20221100T1 HRP20221100T1 HRP20221100TT HRP20221100T HRP20221100T1 HR P20221100 T1 HRP20221100 T1 HR P20221100T1 HR P20221100T T HRP20221100T T HR P20221100TT HR P20221100 T HRP20221100 T HR P20221100T HR P20221100 T1 HRP20221100 T1 HR P20221100T1
- Authority
- HR
- Croatia
- Prior art keywords
- nimodipine
- formulation
- pharmaceutically acceptable
- stable
- angina
- Prior art date
Links
- 238000009472 formulation Methods 0.000 title claims 7
- 239000000203 mixture Substances 0.000 title claims 7
- 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 11
- 229960000715 nimodipine Drugs 0.000 claims 11
- 238000001802 infusion Methods 0.000 claims 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- 201000001068 Prinzmetal angina Diseases 0.000 claims 2
- 238000001990 intravenous administration Methods 0.000 claims 2
- 206010002329 Aneurysm Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 241000282412 Homo Species 0.000 claims 1
- 208000007718 Stable Angina Diseases 0.000 claims 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims 1
- 208000009325 Variant Angina Pectoris Diseases 0.000 claims 1
- 206010000891 acute myocardial infarction Diseases 0.000 claims 1
- 239000008365 aqueous carrier Substances 0.000 claims 1
- 206010003119 arrhythmia Diseases 0.000 claims 1
- 230000006793 arrhythmia Effects 0.000 claims 1
- 210000004351 coronary vessel Anatomy 0.000 claims 1
- 206010020871 hypertrophic cardiomyopathy Diseases 0.000 claims 1
- 239000000693 micelle Substances 0.000 claims 1
- 230000002107 myocardial effect Effects 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims 1
- 229920000053 polysorbate 80 Polymers 0.000 claims 1
- 229940068968 polysorbate 80 Drugs 0.000 claims 1
- 238000001556 precipitation Methods 0.000 claims 1
- 208000002815 pulmonary hypertension Diseases 0.000 claims 1
- 239000004094 surface-active agent Substances 0.000 claims 1
- 238000001356 surgical procedure Methods 0.000 claims 1
- 208000037905 systemic hypertension Diseases 0.000 claims 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Claims (3)
1. Formulacija nimodipina za izravnu infuziju pogodna za parenteralnu primjenu kod ljudi, koja sadrži nimodipin u koncentraciji od 0.01 mg/ml do 1.0 mg/ml, farmaceutski prihvatljivo organsko otapalo koje se sastoji od etanola koji sadrži manje od 2% w/v formulacije, farmaceutski prihvatljivog vodenog nosača, i 0.01% - 2.5% w/v hidrofilnog surfaktanta koji se sastoji od polisorbata 80, tako da je nimodipin uglavnom sadržan u micelama, formulacija obuhvaća volumen od 50 ml do 1000 ml i sadržana je u farmaceutski prihvatljivom spremniku, formulacija je stabilna bistra micelarna otopina i ne pokazuje taloženje nimodipina.
2. Formulacija nimodipina prema zahtjevu 1, za uporabu u liječenju ljudskih pacijenata koji imaju stanje odabrano između aneurizme, subarahnoidnog krvarenja, vazospastične angine, Prinzmetalove angine, stabilne angine, akutnog infarkta miokarda, zastoja miokarda, aritmije, sistemske hipertenzije, plućne hipertenzije, kongestivnog zatajenja srca, operacije koronarne arterije i hipertrofične kardiomiopatije, koji se sastoji od kontinuirane infuzije intravenske otopine nimodipina u skladu sa zahtjevom 1 tijekom perioda od tri tjedna.
3. Formulacija nimodipina prema zahtjevu 1 ili 2, za uporabu u liječenju ljudskih pacijenata, gdje je brzina infuzije nimodipina od 0.05 mg nimodipina po satu do 5 mg nimodipina po satu, i intravenska doza nimodipina je od 2 do 10 mg primjenjenih svakih pet sati.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662322008P | 2016-04-13 | 2016-04-13 | |
| PCT/US2017/027164 WO2017180718A1 (en) | 2016-04-13 | 2017-04-12 | Stable nimopidine parenteral formulation |
| EP17783039.5A EP3442586B1 (en) | 2016-04-13 | 2017-04-12 | Stable nimopidine parenteral formulation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20221100T1 true HRP20221100T1 (hr) | 2022-11-25 |
Family
ID=60039305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20221100TT HRP20221100T1 (hr) | 2016-04-13 | 2017-04-12 | Stabilna parenteralna formulacija nimopidina |
Country Status (18)
| Country | Link |
|---|---|
| US (3) | US10092557B2 (hr) |
| EP (2) | EP4032527A1 (hr) |
| JP (3) | JP2019511522A (hr) |
| KR (1) | KR20190005871A (hr) |
| CN (2) | CN114886850A (hr) |
| AU (2) | AU2017249396A1 (hr) |
| BR (1) | BR112018070960A2 (hr) |
| CA (1) | CA3021237A1 (hr) |
| DK (1) | DK3442586T3 (hr) |
| EA (1) | EA201891977A1 (hr) |
| ES (1) | ES2927490T3 (hr) |
| HR (1) | HRP20221100T1 (hr) |
| HU (1) | HUE059921T2 (hr) |
| IL (1) | IL262335A (hr) |
| PL (1) | PL3442586T3 (hr) |
| PT (1) | PT3442586T (hr) |
| SI (1) | SI3442586T1 (hr) |
| WO (1) | WO2017180718A1 (hr) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110573167A (zh) * | 2017-01-12 | 2019-12-13 | 杜克大学 | 用于治疗脱髓鞘疾病的组合物和方法 |
| US10342787B1 (en) * | 2018-01-25 | 2019-07-09 | Arbor Pharmaceuticals, Llc | Non-aqueous liquid nimodipine compositions |
| US11517563B2 (en) | 2018-01-25 | 2022-12-06 | Azurity Pharmaceuticals, Inc. | Liquid nimodipine compositions |
| EP3755326A4 (en) * | 2018-02-22 | 2021-11-03 | Nortic Holdings Inc. | STABLE PARENTERAL NIMOPIDIN FORMULATION |
| US11278575B2 (en) | 2018-07-12 | 2022-03-22 | Duke University | Compositions and methods for the treatment of demyelinating conditions |
| JP2021535932A (ja) * | 2018-09-08 | 2021-12-23 | 江蘇九旭海天薬業有限公司 | ニモジピン注射用組成物及びその調製方法 |
| US20200163947A1 (en) * | 2018-11-02 | 2020-05-28 | Nortic Holdings Inc. | Methods of treatment using nimodipine parenteral formulations |
| CN114727955B (zh) * | 2019-11-25 | 2024-03-26 | 福多兹制药公司 | 包含降脂和降血压药物的制剂 |
| CN112137956A (zh) * | 2020-10-26 | 2020-12-29 | 辰欣药业股份有限公司 | 一种尼莫地平缓释乳注射液的制备方法 |
| CN113509434A (zh) * | 2021-04-26 | 2021-10-19 | 广东金城金素制药有限公司 | 尼莫地平口服溶液、其制备方法和应用 |
| WO2023140582A1 (ko) * | 2022-01-24 | 2023-07-27 | 주식회사 엘지화학 | 이소옥사졸린 유도체를 포함하는 주사용 제제 |
| US20230364068A1 (en) * | 2022-05-16 | 2023-11-16 | Acasti Pharma U.S., Inc. | Nimodipine Parenteral Administration |
| CN115990262A (zh) * | 2022-06-27 | 2023-04-21 | 北京德立福瑞医药科技有限公司 | 不含乙醇和磷脂的湿热灭菌的尼莫地平组合物及其制备方法 |
| CN116350586B (zh) * | 2023-04-19 | 2024-02-20 | 山东泰合医药科技有限公司 | 一种尼莫地平胶束注射液及其制备方法 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3316510A1 (de) | 1983-05-06 | 1984-11-08 | Bayer Ag | Parenterale formulierung von nimodipin, ein verfahren zu ihrer herstellung sowie ihre verwendung bei der bekaempfung von erkrankungen |
| US4879308A (en) | 1987-08-11 | 1989-11-07 | Lyphomed, Inc. | Aqueous nitroglycerin injection and manufacturing process |
| DE4440337A1 (de) * | 1994-11-11 | 1996-05-15 | Dds Drug Delivery Services Ges | Pharmazeutische Nanosuspensionen zur Arzneistoffapplikation als Systeme mit erhöhter Sättigungslöslichkeit und Lösungsgeschwindigkeit |
| US6363471B1 (en) | 2000-01-03 | 2002-03-26 | Advanced Micro Devices, Inc. | Mechanism for handling 16-bit addressing in a processor |
| WO2002055562A2 (en) | 2001-01-11 | 2002-07-18 | Eastman Chem Co | Cyclodextrin sulfonates, guest inclusion complexes, methods of making the same and related materials |
| DE10124952A1 (de) * | 2001-05-21 | 2002-12-12 | Bayer Ag | Verfahren zur Herstellung von Nanodispersionen |
| US6566347B1 (en) | 2001-08-22 | 2003-05-20 | Duquesne University Of The Holy Ghost | Controlled release pharmaceutical |
| US20040247624A1 (en) * | 2003-06-05 | 2004-12-09 | Unger Evan Charles | Methods of making pharmaceutical formulations for the delivery of drugs having low aqueous solubility |
| CN1183908C (zh) * | 2003-08-08 | 2005-01-12 | 北京四环科宝制药有限公司 | 一种尼莫地平的注射用药物组合物及其制备方法 |
| CN1589795A (zh) * | 2003-09-04 | 2005-03-09 | 范敏华 | 尼莫地平冻干组合物及其制备方法 |
| US20070117851A1 (en) * | 2005-10-14 | 2007-05-24 | Transform Pharmaceuticals, Inc. | Liquid pharmaceutical compositions of nimodipine |
| CN101129366A (zh) * | 2007-08-23 | 2008-02-27 | 沈阳万爱普利德医药科技有限公司 | 一种尼莫地平药物组合物及其制备方法 |
| US7947293B2 (en) | 2008-04-08 | 2011-05-24 | Arpida Ag | Aqueous pharmaceutical formulation |
| CN101904814A (zh) * | 2009-06-04 | 2010-12-08 | 上海恒瑞医药有限公司 | 制备载药乳剂的方法 |
| CN101926757B (zh) * | 2010-09-01 | 2013-01-02 | 北京大学 | 一种难溶性药物的液体组合物及其制备方法 |
| CN102525917B (zh) * | 2012-01-04 | 2014-06-18 | 四川百利药业有限责任公司 | 一种尼莫地平胶束注射剂及其制备方法 |
| UA119324C2 (uk) * | 2013-04-02 | 2019-06-10 | Теміс Медікер Лімітед | Композиції фармацевтично активних речовин, що містять моноетиловий ефір діетиленгліколю або інші алкільні похідні |
-
2017
- 2017-04-12 JP JP2018553182A patent/JP2019511522A/ja active Pending
- 2017-04-12 PT PT177830395T patent/PT3442586T/pt unknown
- 2017-04-12 ES ES17783039T patent/ES2927490T3/es active Active
- 2017-04-12 CN CN202210625514.0A patent/CN114886850A/zh active Pending
- 2017-04-12 HR HRP20221100TT patent/HRP20221100T1/hr unknown
- 2017-04-12 PL PL17783039.5T patent/PL3442586T3/pl unknown
- 2017-04-12 EA EA201891977A patent/EA201891977A1/ru unknown
- 2017-04-12 KR KR1020187032646A patent/KR20190005871A/ko not_active IP Right Cessation
- 2017-04-12 CA CA3021237A patent/CA3021237A1/en active Pending
- 2017-04-12 CN CN201780027632.9A patent/CN109069651A/zh active Pending
- 2017-04-12 BR BR112018070960A patent/BR112018070960A2/pt not_active IP Right Cessation
- 2017-04-12 WO PCT/US2017/027164 patent/WO2017180718A1/en active Application Filing
- 2017-04-12 AU AU2017249396A patent/AU2017249396A1/en not_active Abandoned
- 2017-04-12 EP EP22161459.7A patent/EP4032527A1/en active Pending
- 2017-04-12 HU HUE17783039A patent/HUE059921T2/hu unknown
- 2017-04-12 DK DK17783039.5T patent/DK3442586T3/da active
- 2017-04-12 EP EP17783039.5A patent/EP3442586B1/en active Active
- 2017-04-12 US US15/485,813 patent/US10092557B2/en active Active
- 2017-04-12 SI SI201731222T patent/SI3442586T1/sl unknown
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2018
- 2018-07-26 US US16/046,476 patent/US10765671B2/en active Active
- 2018-10-14 IL IL262335A patent/IL262335A/en unknown
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2020
- 2020-03-13 AU AU2020201863A patent/AU2020201863B2/en active Active
- 2020-09-03 US US17/011,345 patent/US11433062B2/en active Active
- 2020-09-25 JP JP2020160951A patent/JP7196373B2/ja active Active
-
2021
- 2021-10-11 JP JP2021166979A patent/JP2022009013A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| US20180325886A1 (en) | 2018-11-15 |
| IL262335A (en) | 2018-11-29 |
| AU2020201863B2 (en) | 2022-04-28 |
| AU2020201863A1 (en) | 2020-04-02 |
| US10092557B2 (en) | 2018-10-09 |
| CN109069651A (zh) | 2018-12-21 |
| US10765671B2 (en) | 2020-09-08 |
| AU2017249396A1 (en) | 2018-10-18 |
| EP3442586B1 (en) | 2022-06-08 |
| US20200397773A1 (en) | 2020-12-24 |
| US11433062B2 (en) | 2022-09-06 |
| CA3021237A1 (en) | 2017-10-19 |
| EA201891977A1 (ru) | 2019-09-30 |
| PL3442586T3 (pl) | 2023-01-30 |
| DK3442586T3 (da) | 2022-09-12 |
| ES2927490T3 (es) | 2022-11-07 |
| US20170296527A1 (en) | 2017-10-19 |
| CN114886850A (zh) | 2022-08-12 |
| JP2019511522A (ja) | 2019-04-25 |
| BR112018070960A2 (pt) | 2019-01-29 |
| EP3442586A4 (en) | 2019-11-20 |
| KR20190005871A (ko) | 2019-01-16 |
| EP3442586A1 (en) | 2019-02-20 |
| EP4032527A1 (en) | 2022-07-27 |
| JP2021011488A (ja) | 2021-02-04 |
| JP7196373B2 (ja) | 2022-12-27 |
| JP2022009013A (ja) | 2022-01-14 |
| SI3442586T1 (sl) | 2023-01-31 |
| WO2017180718A1 (en) | 2017-10-19 |
| HUE059921T2 (hu) | 2023-01-28 |
| PT3442586T (pt) | 2022-09-28 |
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