AR110270A1 - Preparación de complejos sólidos de ciclodextrina para la administración de ingredientes farmacéuticos activos oftálmicos - Google Patents

Preparación de complejos sólidos de ciclodextrina para la administración de ingredientes farmacéuticos activos oftálmicos

Info

Publication number
AR110270A1
AR110270A1 ARP170103328A ARP170103328A AR110270A1 AR 110270 A1 AR110270 A1 AR 110270A1 AR P170103328 A ARP170103328 A AR P170103328A AR P170103328 A ARP170103328 A AR P170103328A AR 110270 A1 AR110270 A1 AR 110270A1
Authority
AR
Argentina
Prior art keywords
cyclodextrin
active pharmaceutical
pharmaceutical ingredient
ophthalmic composition
acceptable medium
Prior art date
Application number
ARP170103328A
Other languages
English (en)
Inventor
Zoltn Flp
Thorsteinn Loftsson
Original Assignee
Oculis Ehf
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=61656066&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR110270(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Oculis Ehf filed Critical Oculis Ehf
Publication of AR110270A1 publication Critical patent/AR110270A1/es

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Classifications

    • 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
    • A61K9/0048—Eye, e.g. artificial tears
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • 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
    • A61K9/08—Solutions
    • 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
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Ophthalmology & Optometry (AREA)
  • Inorganic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Dispersion Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Nanotechnology (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • Optics & Photonics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Composiciones oftálmicas que contienen complejos sólidos de ingrediente farmacéutico activo y ciclodextrina, a su método de preparación y a sus usos. Reivindicación 1: Una composición oftálmica que comprende, en un medio oftálmicamente aceptable: un complejo sólido que comprende un ingrediente farmacéutico activo y una ciclodextrina, caracterizada porque la composición comprende menos de 2%, en particular menos de 1%, más particularmente menos de 0,8%, en peso de impurezas en base al peso del ingrediente farmacéutico activo. Reivindicación 5: Una composición oftálmica según cualquiera de las reivindicaciones 1 a 3, caracterizada porque el ingrediente farmacéutico activo se selecciona del grupo que consiste en dexametasona, axitinib, cediranib, dovitinib, motesanib, pazopanib, regorafenib, losartán, olmesartán, dorzolamida, diclofenac, nepafenac, y combinaciones de los mismos. Reivindicación 39: Una composición oftálmica según cualquiera de las reivindicaciones 14 a 38, caracterizada porque la composición comprende: 1 a 2% de dexametasona, por ejemplo, 1,5% de dexametasona; 12 a 16% de g-ciclodextrina, por ejemplo, 14% de g-ciclodextrina; 2,2 a 2,8% de polímero, por ejemplo, 2,5% de poloxámero; 0 a 0,2% de agente estabilizante, por ejemplo, 0,1% de edetato disódico; 0 a 1% de electrolito, por ejemplo, 0,57% de cloruro de sodio; y agua; caracterizada porque el % es % en peso en base al volumen de la composición. Reivindicación 42: Un método para preparar una composición oftálmica, que comprende los pasos de: a) suspender un ingrediente farmacéutico activo en un medio oftálmicamente aceptable para formar una suspensión y calentar dicha suspensión hasta que el ingrediente farmacéutico activo se disuelva sustancialmente en el medio oftálmicamente aceptable; b) suspender una ciclodextrina en un medio oftálmicamente aceptable para formar una suspensión y calentar dicha suspensión hasta que la ciclodextrina se disuelva sustancialmente en el medio oftálmicamente aceptable; c) mezclar las composiciones de los pasos a) y b) a una temperatura T1 inferior a 120ºC y calentar la mezcla a una temperatura T1 inferior a 120 ºC durante un tiempo t; y d) enfriar la solución resultante a una temperatura T2 para obtener una composición oftálmica que comprenda un complejo sólido de un ingrediente farmacéutico activo y una ciclodextrina.
ARP170103328A 2016-11-29 2017-11-29 Preparación de complejos sólidos de ciclodextrina para la administración de ingredientes farmacéuticos activos oftálmicos AR110270A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201662427737P 2016-11-29 2016-11-29

Publications (1)

Publication Number Publication Date
AR110270A1 true AR110270A1 (es) 2019-03-13

Family

ID=61656066

Family Applications (2)

Application Number Title Priority Date Filing Date
ARP170103328A AR110270A1 (es) 2016-11-29 2017-11-29 Preparación de complejos sólidos de ciclodextrina para la administración de ingredientes farmacéuticos activos oftálmicos
ARP170103327A AR110269A1 (es) 2016-11-29 2017-11-29 Preparación de nanopartículas de ciclodextrina para la administración de fármacos oftálmicos

Family Applications After (1)

Application Number Title Priority Date Filing Date
ARP170103327A AR110269A1 (es) 2016-11-29 2017-11-29 Preparación de nanopartículas de ciclodextrina para la administración de fármacos oftálmicos

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US (6) US11135311B2 (es)
EP (2) EP3548091B1 (es)
JP (2) JP7138103B2 (es)
KR (3) KR102525438B1 (es)
CN (2) CN117018220A (es)
AR (2) AR110270A1 (es)
AU (1) AU2017369971B2 (es)
CA (1) CA3045226A1 (es)
CL (1) CL2019001447A1 (es)
CO (1) CO2019005729A2 (es)
CY (1) CY1124917T1 (es)
DK (1) DK3548091T3 (es)
EA (1) EA201991299A1 (es)
ES (1) ES2903383T3 (es)
HR (1) HRP20220046T1 (es)
HU (1) HUE057221T2 (es)
IL (2) IL310360A (es)
LT (1) LT3548091T (es)
MA (1) MA46997B1 (es)
MD (1) MD3548091T2 (es)
MX (1) MX2019006221A (es)
PH (1) PH12019550088A1 (es)
PL (1) PL3548091T3 (es)
PT (1) PT3548091T (es)
RS (1) RS62845B1 (es)
SI (1) SI3548091T1 (es)
TW (2) TWI773706B (es)
UA (1) UA124774C2 (es)
WO (1) WO2018100434A1 (es)
ZA (1) ZA201903307B (es)

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WO2022003037A1 (en) * 2020-06-30 2022-01-06 Oculis SA Preparation of solid cyclodextrin complexes for ophthalmic active pharmaceutical ingredient delivery
CN111728953B (zh) * 2020-07-29 2023-08-08 中国科学院上海药物研究所 一种托法替布或其盐的缓释制剂及其制备方法
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IL266964B1 (en) 2024-02-01
KR20230025939A (ko) 2023-02-23
AU2017369971A1 (en) 2019-06-13
CY1124917T1 (el) 2023-01-05
DK3548091T3 (da) 2022-01-17
PT3548091T (pt) 2022-01-21
US20190343846A1 (en) 2019-11-14
CN110177576A (zh) 2019-08-27
TWI773706B (zh) 2022-08-11
CN110177576B (zh) 2023-08-11
EA201991299A1 (ru) 2019-11-29
US11491240B2 (en) 2022-11-08
TW201825100A (zh) 2018-07-16
MX2019006221A (es) 2019-10-07
JP2022172291A (ja) 2022-11-15
MA46997A (fr) 2019-10-09
KR20240036731A (ko) 2024-03-20
EP3548091A1 (en) 2019-10-09
HRP20220046T1 (hr) 2022-04-15
CL2019001447A1 (es) 2019-08-09
AR110269A1 (es) 2019-03-13
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US20230042785A1 (en) 2023-02-09
KR20190091308A (ko) 2019-08-05
CA3045226A1 (en) 2018-06-07
US11135311B2 (en) 2021-10-05
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JP2019535798A (ja) 2019-12-12
IL266964B2 (en) 2024-06-01
PL3548091T3 (pl) 2022-03-28
PH12019550088A1 (en) 2020-06-15
JP7455917B2 (ja) 2024-03-26
ZA201903307B (en) 2020-09-30
US20180147297A1 (en) 2018-05-31
IL266964A (en) 2019-07-31
MA46997B1 (fr) 2022-01-31
SI3548091T1 (sl) 2022-04-29
TWI810167B (zh) 2023-08-01
JP7138103B2 (ja) 2022-09-15
KR102525438B1 (ko) 2023-04-26
MD3548091T2 (ro) 2022-03-31
CO2019005729A2 (es) 2019-08-30
US20230037486A1 (en) 2023-02-09
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BR112019011067A2 (pt) 2019-12-17
UA124774C2 (uk) 2021-11-17
IL310360A (en) 2024-03-01
WO2018100434A1 (en) 2018-06-07
ES2903383T3 (es) 2022-04-01
LT3548091T (lt) 2022-02-10
US20220008555A1 (en) 2022-01-13
TW201818943A (zh) 2018-06-01
EP3548091B1 (en) 2021-12-01
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AU2017369971B2 (en) 2023-06-01
RS62845B1 (sr) 2022-02-28

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