RU2018105494A - Улучшенные системы доставки наночастиц - Google Patents
Улучшенные системы доставки наночастиц Download PDFInfo
- Publication number
- RU2018105494A RU2018105494A RU2018105494A RU2018105494A RU2018105494A RU 2018105494 A RU2018105494 A RU 2018105494A RU 2018105494 A RU2018105494 A RU 2018105494A RU 2018105494 A RU2018105494 A RU 2018105494A RU 2018105494 A RU2018105494 A RU 2018105494A
- Authority
- RU
- Russia
- Prior art keywords
- composition according
- therapeutic agent
- nanoparticles
- composition
- prodrug
- Prior art date
Links
- 239000002105 nanoparticle Substances 0.000 title claims 7
- 239000000203 mixture Substances 0.000 claims 12
- 239000003814 drug Substances 0.000 claims 10
- 229940124597 therapeutic agent Drugs 0.000 claims 10
- 230000002209 hydrophobic effect Effects 0.000 claims 6
- 238000000034 method Methods 0.000 claims 6
- 239000000651 prodrug Substances 0.000 claims 5
- 229940002612 prodrug Drugs 0.000 claims 5
- 239000012074 organic phase Substances 0.000 claims 4
- 239000008346 aqueous phase Substances 0.000 claims 3
- 229920001577 copolymer Polymers 0.000 claims 3
- 239000003381 stabilizer Substances 0.000 claims 3
- 239000002202 Polyethylene glycol Substances 0.000 claims 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 229920001223 polyethylene glycol Polymers 0.000 claims 2
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 claims 1
- 229940126638 Akt inhibitor Drugs 0.000 claims 1
- QEVGZEDELICMKH-UHFFFAOYSA-N Diglycolic acid Chemical group OC(=O)COCC(O)=O QEVGZEDELICMKH-UHFFFAOYSA-N 0.000 claims 1
- 239000012824 ERK inhibitor Substances 0.000 claims 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims 1
- 108091007960 PI3Ks Proteins 0.000 claims 1
- 229940123237 Taxane Drugs 0.000 claims 1
- 235000012000 cholesterol Nutrition 0.000 claims 1
- 229920000359 diblock copolymer Polymers 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 229940124302 mTOR inhibitor Drugs 0.000 claims 1
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims 1
- 239000004626 polylactic acid Substances 0.000 claims 1
- 239000003197 protein kinase B inhibitor Substances 0.000 claims 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
- A61K9/5153—Polyesters, e.g. poly(lactide-co-glycolide)
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/554—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5192—Processes
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Botany (AREA)
- Dermatology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (17)
1. Фармацевтический состав, включающий набор фармацевтических составов, содержащих наночастицы, где указанные наночастицы имеют средний диаметр менее 80 нм, и содержат:
а) по меньшей мере два терапевтических агента, каждый терапевтический агент соединен через линкер с гидрофобной частью для формирования пролекарства, и
b) амфифильный стабилизатор, содержащий гидрофобную часть и гидрофильную часть, в котором массовое соотношение гидрофобной части к гидрофильной части находится в диапазоне 8:5-12:5 и в котором гидрофобная часть имеет молекулярную массу 8 кДа - 15 кДа.
2. Состав по п. 1, в котором указанный амфифильный стабилизатор представляет собой диблок-сополимер.
3. Состав по п. 1, в котором в указанном амфифильном стабилизаторе гидрофобная часть содержит полимолочную кислоту (PLA) или сополимер молочной и гликолевой кислот (PLGA), и гидрофильная часть содержит полиэтиленгликоль (PEG).
4. Состав по п. 1, в котором по меньшей мере два терапевтических агента включены в одну и ту же наночастицу.
5. Состав по п. 1, в котором один терапевтический агент представляет собой таксан, и другой терапевтический агент представляет собой HSP ингибитор, или где один терапевтический агент представляет собой PI3K/AKT/mTOR ингибитор, и другой терапевтический агент представляет собой RAS/RAF/MEK/ERK ингибитор.
6. Состав по п. 1, в котором в каждом из указанных пролекарств, гидрофобная часть представляет собой холестерин и/или линкер представляет собой дигликолевую кислоту.
7. Состав по п. 1, в котором указанные наночастицы формируются путем смешивания водной фазы и органической фазы, указанная органическая фаза содержит указанный сополимер и указанное пролекарство.
8. Состав по п. 7, в котором указанное смешивание проводится путем быстрого смешивания струйных потоков, один из которых содержит водную фазу и другой содержит органическую фазу.
9. Состав по п. 1, в котором указнные наночастицы имеют средний диаметр 20-80 нм.
10. Состав по п. 1, который дополнительно содержит третий терапевтический агент.
11. Состав по п. 10, в котором указанный третий терапевтический агент поставляется как пролекарство и инкапсулирован в указанные наночастицы.
12. Способ введения комбинации двух или больше терапевтических агентов, способ, который содержит введение к субьекту состава по п. 1.
13. Способ по п. 12, в котором указанное введение осуществляется путем парентерального введения.
14. Способ по п. 13, в котором субъект является человеком или не принадлежащим к человеческому роду млекопитающим или птицей.
15. Способ получения состава по п. 1, способ, который содержит быстрое смешивание водной фазы с органической фазой, содержащей указанный сополимер и указанное пролекарство.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562192973P | 2015-07-15 | 2015-07-15 | |
| US62/192,973 | 2015-07-15 | ||
| US201562252396P | 2015-11-06 | 2015-11-06 | |
| US62/252,396 | 2015-11-06 | ||
| PCT/US2016/042330 WO2017011685A1 (en) | 2015-07-15 | 2016-07-14 | Improved nanoparticle delivery systems |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2018105494A true RU2018105494A (ru) | 2019-08-15 |
| RU2018105494A3 RU2018105494A3 (ru) | 2019-12-17 |
Family
ID=57757767
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018105494A RU2018105494A (ru) | 2015-07-15 | 2016-07-14 | Улучшенные системы доставки наночастиц |
Country Status (17)
| Country | Link |
|---|---|
| US (4) | US10285951B2 (ru) |
| EP (1) | EP3322404A4 (ru) |
| JP (2) | JP2018521068A (ru) |
| KR (1) | KR20180029242A (ru) |
| CN (1) | CN107920985B (ru) |
| AU (2) | AU2016294617B2 (ru) |
| BR (1) | BR112018000217A2 (ru) |
| CA (1) | CA2991062C (ru) |
| CO (1) | CO2018000146A2 (ru) |
| HK (1) | HK1251159A1 (ru) |
| IL (1) | IL256797B (ru) |
| MA (1) | MA42458A (ru) |
| MX (1) | MX2018000611A (ru) |
| RU (1) | RU2018105494A (ru) |
| SG (1) | SG10201912394VA (ru) |
| WO (1) | WO2017011685A1 (ru) |
| ZA (1) | ZA201800130B (ru) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109640959B (zh) | 2016-04-29 | 2023-03-17 | 西奈山伊坎医学院 | 靶向先天免疫系统以诱导长期耐受性及解决动脉粥样硬化中的巨噬细胞累积 |
| EP3713547A4 (en) * | 2017-11-20 | 2023-07-19 | Icahn School of Medicine at Mount Sinai | INHIBITION OF TRAINED IMMUNITY WITH A THERAPEUTIC NANOBIOLOGICAL COMPOSITION |
| WO2019178443A1 (en) * | 2018-03-16 | 2019-09-19 | University Of Massachusetts | Yeast cell wall particle encapsulation of biodegradable pro-payloads |
| KR102088663B1 (ko) * | 2018-03-20 | 2020-03-13 | 한국세라믹기술원 | 친수성 및 소수성 약물의 동시 전달을 위한 온도민감성 나노스펀지 플랫폼 및 이의 용도 |
| WO2020123481A1 (en) * | 2018-12-10 | 2020-06-18 | Celator Pharmaceuticals Inc. | Combination formulations of taxanes and mtor inhibitors |
| US20240189230A1 (en) * | 2019-08-13 | 2024-06-13 | Peptinovo Biopharma Inc. | Palm for the treatment of chemotherapy-induced peripheral neuropathy incidental to the treatment of cancer |
| JP2023541389A (ja) * | 2020-09-11 | 2023-10-02 | ナミ セラピューティクス， インコーポレイテッド | がんの処置において有用なｐｄ－１アンタゴニストプロドラッグを含有する製剤化および／または共製剤化リポソーム組成物ならびにその方法 |
| KR20230171435A (ko) | 2021-03-19 | 2023-12-20 | 트레인드 테라퓨틱스 디스커버리, 아이엔씨. | 훈련된 면역을 조절하기 위한 화합물 및 이의 사용 방법 |
| WO2025199353A1 (en) * | 2024-03-21 | 2025-09-25 | Purdue Research Foundation | Nanoparticulate formulations and foliar administration thereof in the treatment and prevention of citrus greening disease |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2462369C (en) | 2001-10-03 | 2009-12-22 | Celator Technologies Inc. | Compositions for delivery of drug combinations |
| CA2467559A1 (en) * | 2001-11-19 | 2003-05-30 | Control Delivery Systems, Inc. | Topical delivery of codrugs |
| WO2004075636A1 (en) * | 2003-02-20 | 2004-09-10 | University Of Connecticut Health Center | Methods for using compositions comprising heat shock proteins or alpha-2-macroglobulin in the treatment of cancer and infectious disease |
| AU2005269800B8 (en) | 2004-07-19 | 2011-12-01 | Celator Pharmaceuticals, Inc. | Particulate constructs for release of active agents |
| AU2006235538A1 (en) * | 2005-04-12 | 2006-10-19 | Wisconsin Alumni Research Foundation | Micelle composition of polymer and passenger drug |
| WO2009070761A1 (en) * | 2007-11-28 | 2009-06-04 | Celator Pharmaceuticals, Inc | Improved taxane delivery system |
| EA201171195A8 (ru) * | 2009-03-30 | 2014-08-29 | Серулин Фарма Инк. | Конъюгаты, частицы, композиции "полимер-агент" и способы их применения |
| JP2013510585A (ja) * | 2009-11-13 | 2013-03-28 | インフィニティー ファーマシューティカルズ， インコーポレイテッド | 癌の同定、評価、予防および治療のための組成物、キットおよび方法 |
| EA201390144A1 (ru) * | 2010-08-20 | 2013-06-28 | Серулин Фарма Инк. | Конъюгаты терапевтический пептид-полимер, частицы, композиции и связанные с ними способы |
| CN104689318A (zh) | 2010-11-19 | 2015-06-10 | 葛兰素史密斯克莱知识产权（第2号）有限公司 | 使用braf抑制剂的治疗方法 |
| CN117205331A (zh) * | 2011-04-29 | 2023-12-12 | 西莱克塔生物科技公司 | 用于降低抗体应答的致耐受性合成纳米载体 |
| WO2012166923A2 (en) * | 2011-05-31 | 2012-12-06 | Bind Biosciences | Drug loaded polymeric nanoparticles and methods of making and using same |
| DE102011109374A1 (de) * | 2011-08-04 | 2013-02-07 | Bock 1 Gmbh & Co. Kg | Stuhl mit Wippmechanik |
| KR102062025B1 (ko) * | 2014-06-30 | 2020-01-03 | 타베다 세라퓨틱스, 인코포레이티드 | 표적화된 콘주게이트 및 입자 및 그것의 제형 |
-
2016
- 2016-07-14 JP JP2018500438A patent/JP2018521068A/ja not_active Withdrawn
- 2016-07-14 EP EP16825199.9A patent/EP3322404A4/en not_active Withdrawn
- 2016-07-14 MX MX2018000611A patent/MX2018000611A/es unknown
- 2016-07-14 SG SG10201912394VA patent/SG10201912394VA/en unknown
- 2016-07-14 CA CA2991062A patent/CA2991062C/en active Active
- 2016-07-14 CN CN201680041368.XA patent/CN107920985B/zh active Active
- 2016-07-14 WO PCT/US2016/042330 patent/WO2017011685A1/en not_active Ceased
- 2016-07-14 KR KR1020187004307A patent/KR20180029242A/ko not_active Ceased
- 2016-07-14 BR BR112018000217A patent/BR112018000217A2/pt not_active Application Discontinuation
- 2016-07-14 HK HK18110619.0A patent/HK1251159A1/zh unknown
- 2016-07-14 MA MA042458A patent/MA42458A/fr unknown
- 2016-07-14 RU RU2018105494A patent/RU2018105494A/ru not_active Application Discontinuation
- 2016-07-14 US US15/744,723 patent/US10285951B2/en active Active
- 2016-07-14 AU AU2016294617A patent/AU2016294617B2/en not_active Ceased
-
2018
- 2018-01-08 IL IL256797A patent/IL256797B/en active IP Right Grant
- 2018-01-08 ZA ZA2018/00130A patent/ZA201800130B/en unknown
- 2018-01-09 CO CONC2018/0000146A patent/CO2018000146A2/es unknown
-
2019
- 2019-03-15 US US16/355,594 patent/US20190209484A1/en not_active Abandoned
-
2020
- 2020-09-04 US US17/013,101 patent/US11413253B2/en active Active
-
2021
- 2021-11-08 JP JP2021181961A patent/JP2022033751A/ja active Pending
- 2021-12-16 AU AU2021286353A patent/AU2021286353A1/en not_active Abandoned
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2022
- 2022-07-15 US US17/812,832 patent/US20240366519A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| MA42458A (fr) | 2018-05-23 |
| CO2018000146A2 (es) | 2018-04-19 |
| US20190209484A1 (en) | 2019-07-11 |
| SG10201912394VA (en) | 2020-02-27 |
| EP3322404A1 (en) | 2018-05-23 |
| ZA201800130B (en) | 2018-12-19 |
| JP2022033751A (ja) | 2022-03-02 |
| AU2016294617B2 (en) | 2021-09-16 |
| WO2017011685A1 (en) | 2017-01-19 |
| AU2021286353A1 (en) | 2022-01-20 |
| CA2991062C (en) | 2023-06-20 |
| US20240366519A1 (en) | 2024-11-07 |
| US20180207104A1 (en) | 2018-07-26 |
| AU2016294617A1 (en) | 2018-01-25 |
| CA2991062A1 (en) | 2017-01-19 |
| CN107920985A (zh) | 2018-04-17 |
| IL256797A (en) | 2018-06-28 |
| JP2018521068A (ja) | 2018-08-02 |
| IL256797B (en) | 2021-05-31 |
| RU2018105494A3 (ru) | 2019-12-17 |
| HK1251159A1 (zh) | 2019-01-25 |
| MX2018000611A (es) | 2018-09-06 |
| EP3322404A4 (en) | 2019-03-20 |
| US10285951B2 (en) | 2019-05-14 |
| US20210052508A1 (en) | 2021-02-25 |
| US11413253B2 (en) | 2022-08-16 |
| BR112018000217A2 (pt) | 2018-09-04 |
| KR20180029242A (ko) | 2018-03-20 |
| CN107920985B (zh) | 2022-03-01 |
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