MD3548091T2 - Prepararea complexelor solide de ciclodextrină pentru livrarea ingredientelor farmaceutice active oftalmice - Google Patents

Prepararea complexelor solide de ciclodextrină pentru livrarea ingredientelor farmaceutice active oftalmice

Info

Publication number
MD3548091T2
MD3548091T2 MDE20191148T MDE20191148T MD3548091T2 MD 3548091 T2 MD3548091 T2 MD 3548091T2 MD E20191148 T MDE20191148 T MD E20191148T MD E20191148 T MDE20191148 T MD E20191148T MD 3548091 T2 MD3548091 T2 MD 3548091T2
Authority
MD
Moldova
Prior art keywords
preparation
active pharmaceutical
pharmaceutical ingredient
cyclodextrin complexes
ingredient delivery
Prior art date
Application number
MDE20191148T
Other languages
English (en)
Inventor
Thorsteinn Loftsson
Zoltan Fulop
Original Assignee
Oculis SA
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=MD3548091(T2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Oculis SA filed Critical Oculis SA
Publication of MD3548091T2 publication Critical patent/MD3548091T2/ro

Links

Classifications

    • 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
    • A61K9/0012—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
    • 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

Prezenta descriere se referă la compoziţii oftalmice care conţin complexe solide de ingredient farmaceutic activ şi ciclodextrină, la metoda lor de preparare şi la utilizările lor. Compoziţiile pot include un agent activ medicament/complex de ciclodextrină substanţial dizolvat într-un vehicul apos de picături pentru ochi. Compoziţia oftalmică este în general sub forma unei microsuspensii care include un complex de agent activ având un diametru mai mic de aproximativ 100 µm.
MDE20191148T 2016-11-29 2017-11-29 Prepararea complexelor solide de ciclodextrină pentru livrarea ingredientelor farmaceutice active oftalmice MD3548091T2 (ro)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662427737P 2016-11-29 2016-11-29
PCT/IB2017/001659 WO2018100434A1 (en) 2016-11-29 2017-11-29 Preparation of solid cyclodextrin complexes for ophthalmic active pharmaceutical ingredient delivery

Publications (1)

Publication Number Publication Date
MD3548091T2 true MD3548091T2 (ro) 2022-03-31

Family

ID=61656066

Family Applications (1)

Application Number Title Priority Date Filing Date
MDE20191148T MD3548091T2 (ro) 2016-11-29 2017-11-29 Prepararea complexelor solide de ciclodextrină pentru livrarea ingredientelor farmaceutice active oftalmice

Country Status (30)

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

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI773706B (zh) * 2016-11-29 2022-08-11 瑞士商歐庫利斯公司 用於眼用活性藥物成分輸送的固體環糊精複合物之製備
IT201900000561A1 (it) * 2019-01-14 2020-07-14 Medivis S R L Formulazioni topiche oftalmiche chimicamente e fisicamente stabili a base di Nepafenac
CN110051859B (zh) * 2019-06-06 2020-06-12 鲁南制药集团股份有限公司 一种阿昔替尼环糊精包合物
EP3993807A1 (en) 2019-07-01 2022-05-11 Oculis SA Method for stabilizing the ph of an aqueous composition comprising a drug
TWI756547B (zh) * 2019-07-15 2022-03-01 高雄榮民總醫院 奈米眼藥水及其製造方法
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
EP4282403A2 (en) * 2021-01-21 2023-11-29 Taejoon Pharmaceutical Co., Ltd. Ophthalmic composition
US11998562B2 (en) * 2021-01-25 2024-06-04 University Of South Florida Ophthalmological formulations for the prevention of a coronavirus infection
WO2023132947A1 (en) * 2022-01-05 2023-07-13 The Regents Of The University Of California Closo-dodecaiododecaborate complexes and methods of use for same
AU2023214622A1 (en) 2022-02-02 2024-08-08 Oculis Operations Sarl Multidose ophthalmic compositions

Family Cites Families (11)

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Publication number Priority date Publication date Assignee Title
US5472954A (en) * 1992-07-14 1995-12-05 Cyclops H.F. Cyclodextrin complexation
EP0938896A1 (en) 1998-01-15 1999-09-01 Novartis AG Autoclavable pharmaceutical compositions containing a chelating agent
US20020198174A1 (en) * 2001-05-07 2002-12-26 Allergan Sales, Inc. Disinfecting and solubilizing steroid compositions
WO2002039993A2 (en) * 2000-11-15 2002-05-23 Chandavarkar Mohan A Pharmaceutival preparations comprising corticosteroids and antiinfective agents
WO2004069280A1 (en) 2003-02-06 2004-08-19 Cipla Ltd Pharmaceutical inclusion complexes containing a steroid and optionally an antibacterial agent
CA2516429A1 (en) * 2003-02-21 2004-10-14 Sun Pharmaceutical Industries Limited Stable ophthalmic formulation containing an antibiotic and a corticosteroid
US7893040B2 (en) 2005-07-22 2011-02-22 Oculis Ehf Cyclodextrin nanotechnology for ophthalmic drug delivery
US20140163080A1 (en) * 2011-02-03 2014-06-12 Gnt, Llc Compositions and Methods for Treatment of Glaucoma
CN104411334A (zh) 2012-05-08 2015-03-11 欧尼斯治疗公司 用于配制肽蛋白酶体抑制剂的环糊精络合法
CA3050298A1 (en) * 2012-08-24 2014-02-27 Sun Pharma Global Fze Ophthalmic formulation of polyoxyl lipid or polyoxyl fatty acid and polyalkoxylated alcohol for use in the treatment of ocular conditions
TWI773706B (zh) * 2016-11-29 2022-08-11 瑞士商歐庫利斯公司 用於眼用活性藥物成分輸送的固體環糊精複合物之製備

Also Published As

Publication number Publication date
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
AR110270A1 (es) 2019-03-13
CL2019001447A1 (es) 2019-08-09
AR110269A1 (es) 2019-03-13
US20240091377A1 (en) 2024-03-21
US20230042785A1 (en) 2023-02-09
KR20190091308A (ko) 2019-08-05
CA3045226A1 (en) 2018-06-07
US11135311B2 (en) 2021-10-05
CN117018220A (zh) 2023-11-10
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
CO2019005729A2 (es) 2019-08-30
US20230037486A1 (en) 2023-02-09
EP4194011A1 (en) 2023-06-14
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
HUE057221T2 (hu) 2022-04-28
AU2017369971B2 (en) 2023-06-01
RS62845B1 (sr) 2022-02-28

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