IL274233B2 - Compounds, compositions and methods for treatment of eye disorders and skin diseases - Google Patents

Compounds, compositions and methods for treatment of eye disorders and skin diseases

Info

Publication number
IL274233B2
IL274233B2 IL274233A IL27423320A IL274233B2 IL 274233 B2 IL274233 B2 IL 274233B2 IL 274233 A IL274233 A IL 274233A IL 27423320 A IL27423320 A IL 27423320A IL 274233 B2 IL274233 B2 IL 274233B2
Authority
IL
Israel
Prior art keywords
pharmaceutical composition
compound
treatment
crystal
pharmaceutically acceptable
Prior art date
Application number
IL274233A
Other languages
English (en)
Hebrew (he)
Other versions
IL274233B1 (en
IL274233A (en
Inventor
Mahesh Kandula
Original Assignee
Cellix Bio Private Ltd
Mahesh Kandula
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
Application filed by Cellix Bio Private Ltd, Mahesh Kandula filed Critical Cellix Bio Private Ltd
Publication of IL274233A publication Critical patent/IL274233A/en
Publication of IL274233B1 publication Critical patent/IL274233B1/en
Publication of IL274233B2 publication Critical patent/IL274233B2/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D339/00Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
    • C07D339/02Five-membered rings
    • C07D339/04Five-membered rings having the hetero atoms in positions 1 and 2, e.g. lipoic acid
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/38Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/38Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/498Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/02Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/28Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36Radicals substituted by singly-bound nitrogen atoms
    • C07D213/40Acylated substituent nitrogen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56Benzopyrazoles; Hydrogenated benzopyrazoles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/06Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/06Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
    • C07D233/08Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms with alkyl radicals, containing more than four carbon atoms, directly attached to ring carbon atoms
    • C07D233/10Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms with alkyl radicals, containing more than four carbon atoms, directly attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring nitrogen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D285/00Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01Five-membered rings
    • C07D285/02Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/101,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D339/00Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
    • C07D339/02Five-membered rings
    • C07D339/06Five-membered rings having the hetero atoms in positions 1 and 3, e.g. cyclic dithiocarbonates
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D453/00Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13Crystalline forms, e.g. polymorphs

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Ophthalmology & Optometry (AREA)
  • Dermatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
IL274233A 2017-11-17 2018-11-10 Compounds, compositions and methods for treatment of eye disorders and skin diseases IL274233B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IN201741041231 2017-11-17
IN201841032406 2018-08-29
PCT/IB2018/058848 WO2019097381A1 (en) 2017-11-17 2018-11-10 Compounds, compositions and methods for treatment of eye disorders and skin diseases

Publications (3)

Publication Number Publication Date
IL274233A IL274233A (en) 2020-06-30
IL274233B1 IL274233B1 (en) 2023-12-01
IL274233B2 true IL274233B2 (en) 2024-04-01

Family

ID=66538944

Family Applications (1)

Application Number Title Priority Date Filing Date
IL274233A IL274233B2 (en) 2017-11-17 2018-11-10 Compounds, compositions and methods for treatment of eye disorders and skin diseases

Country Status (14)

Country Link
US (1) US11186561B2 (https=)
EP (1) EP3709982A4 (https=)
JP (1) JP7038437B2 (https=)
KR (1) KR102405239B1 (https=)
CN (1) CN111315369A (https=)
AU (1) AU2018369853B2 (https=)
BR (1) BR112020009364A2 (https=)
CA (1) CA3081482A1 (https=)
IL (1) IL274233B2 (https=)
MX (1) MX392359B (https=)
RU (1) RU2020119228A (https=)
SG (1) SG11202004078YA (https=)
WO (1) WO2019097381A1 (https=)
ZA (1) ZA202002075B (https=)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112021003452A2 (pt) * 2018-08-29 2021-05-18 Cellix Bio Private Limited composto e composição farmacêutica
WO2020144546A1 (en) * 2019-01-12 2020-07-16 Cellix Bio Private Limited Combination of selective alpha-adrenergic receptor agonist or an anticholinergic agent and lipoic acid and uses thereof
JP7795555B2 (ja) * 2021-04-30 2026-01-07 ▲遠▼大医▲薬▼(中国)有限公司 近視を治療するための方法及び薬物組成物
CN118634218A (zh) 2023-05-24 2024-09-13 温州医科大学附属眼视光医院 一种有效延缓及治疗近视的药物组合物

Citations (4)

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WO2007149313A1 (en) * 2006-06-16 2007-12-27 Indigene Pharmaceuticals Inc. Metformin r-(+) lipoate as an antidiabetic agent for control of diabetic hyperglycemia and diabetic complications
WO2010125416A1 (en) * 2009-04-27 2010-11-04 Raouf Rekik Drug delivery to the anterior and posterior segments of the eye
US20140221467A1 (en) * 2013-02-07 2014-08-07 Banavara L. Mylari Metformin derivatives for treating diabetes and diabetes complications
CN104387364A (zh) * 2014-12-15 2015-03-04 南京工业大学 L-鸟氨酸硫辛酸复合盐及其制备方法和应用

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US6239180B1 (en) 1995-11-08 2001-05-29 The Regents Of The University Of California Transdermal therapeutic device and method with capsaicin and capsaicin analogs
WO1999021537A1 (fr) 1997-10-28 1999-05-06 Bando Chemical Industries, Ltd. Feuille de timbre cutane et procede de production d'une feuille de base pour timbre
US6103275A (en) 1998-06-10 2000-08-15 Nitric Oxide Solutions Systems and methods for topical treatment with nitric oxide
DE19827732A1 (de) 1998-06-22 1999-12-23 Rottapharm Bv Transdermales System vom Matrix-Typ zur Abgabe von Wirkstoffen mit einer hohen Abgaberate von Steroid-Hormonen und die Verwendung eines derartigen Systems zur Hormonersatztherapie
US6312716B1 (en) 1999-05-10 2001-11-06 Peierce Management Llc Patch and method for transdermal delivery of bupropion base
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CA2936146A1 (en) * 2014-01-06 2015-07-09 Stealth Biotherapeutics Corp Methods and compositions for preventing or treating dominant optic atrophy
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WO2007149313A1 (en) * 2006-06-16 2007-12-27 Indigene Pharmaceuticals Inc. Metformin r-(+) lipoate as an antidiabetic agent for control of diabetic hyperglycemia and diabetic complications
WO2010125416A1 (en) * 2009-04-27 2010-11-04 Raouf Rekik Drug delivery to the anterior and posterior segments of the eye
US20140221467A1 (en) * 2013-02-07 2014-08-07 Banavara L. Mylari Metformin derivatives for treating diabetes and diabetes complications
CN104387364A (zh) * 2014-12-15 2015-03-04 南京工业大学 L-鸟氨酸硫辛酸复合盐及其制备方法和应用

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JP2021503451A (ja) 2021-02-12
EP3709982A4 (en) 2021-10-13
ZA202002075B (en) 2021-04-28
KR20200089700A (ko) 2020-07-27
IL274233B1 (en) 2023-12-01
AU2018369853B2 (en) 2022-07-14
NZ763699A (en) 2022-05-27
IL274233A (en) 2020-06-30
BR112020009364A2 (pt) 2020-10-27
US11186561B2 (en) 2021-11-30
CA3081482A1 (en) 2019-05-23
SG11202004078YA (en) 2020-05-28
JP7038437B2 (ja) 2022-03-18
EP3709982A1 (en) 2020-09-23
RU2020119228A3 (https=) 2022-02-08
WO2019097381A1 (en) 2019-05-23
AU2018369853A1 (en) 2020-05-07
CN111315369A (zh) 2020-06-19
KR102405239B1 (ko) 2022-06-08
MX2020004667A (es) 2022-05-16
RU2020119228A (ru) 2021-12-20
MX392359B (es) 2025-03-24
US20200262809A1 (en) 2020-08-20

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