IL311303B1 - Medicinal resin components and methods for their production and use - Google Patents

Medicinal resin components and methods for their production and use

Info

Publication number
IL311303B1
IL311303B1 IL311303A IL31130324A IL311303B1 IL 311303 B1 IL311303 B1 IL 311303B1 IL 311303 A IL311303 A IL 311303A IL 31130324 A IL31130324 A IL 31130324A IL 311303 B1 IL311303 B1 IL 311303B1
Authority
IL
Israel
Prior art keywords
active agent
pharmaceutical composition
molecular weight
ion exchange
less
Prior art date
Application number
IL311303A
Other languages
English (en)
Hebrew (he)
Other versions
IL311303A (en
Inventor
Mohsen Sadatrezaei
Gerard P Frunzi
Original Assignee
Rhodes Pharmaceuticals Lp
Mohsen Sadatrezaei
Gerard P Frunzi
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 Rhodes Pharmaceuticals Lp, Mohsen Sadatrezaei, Gerard P Frunzi filed Critical Rhodes Pharmaceuticals Lp
Publication of IL311303A publication Critical patent/IL311303A/en
Publication of IL311303B1 publication Critical patent/IL311303B1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/135Amines having aromatic rings, e.g. ketamine, nortriptyline
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/135Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/3533,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • 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
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4458Non condensed piperidines, e.g. piperocaine only substituted in position 2, e.g. methylphenidate
    • 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
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4468Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
    • 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
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/485Morphinan derivatives, e.g. morphine, codeine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/658Medicinal preparations containing organic active ingredients o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34Macromolecular 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2009Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2013Organic compounds, e.g. phospholipids, fats
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2013Organic compounds, e.g. phospholipids, fats
    • A61K9/2018Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2027Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2031Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2063Proteins, e.g. gelatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841Filling excipients; Inactive ingredients
    • A61K9/485Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841Filling excipients; Inactive ingredients
    • A61K9/4858Organic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841Filling excipients; Inactive ingredients
    • A61K9/4866Organic macromolecular compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36Opioid-abuse
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Addiction (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Psychiatry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
IL311303A 2017-10-09 2018-10-08 Medicinal resin components and methods for their production and use IL311303B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762569813P 2017-10-09 2017-10-09
PCT/US2018/054830 WO2019074829A1 (en) 2017-10-09 2018-10-08 RESINATE-BASED PHARMACEUTICAL COMPOSITIONS, AND METHODS OF MAKING AND USING THEM

Publications (2)

Publication Number Publication Date
IL311303A IL311303A (en) 2024-05-01
IL311303B1 true IL311303B1 (en) 2026-01-01

Family

ID=66100936

Family Applications (2)

Application Number Title Priority Date Filing Date
IL311303A IL311303B1 (en) 2017-10-09 2018-10-08 Medicinal resin components and methods for their production and use
IL273904A IL273904B2 (en) 2017-10-09 2018-10-08 Medicinal resin components and methods for their production and use

Family Applications After (1)

Application Number Title Priority Date Filing Date
IL273904A IL273904B2 (en) 2017-10-09 2018-10-08 Medicinal resin components and methods for their production and use

Country Status (9)

Country Link
US (3) US11690840B2 (https=)
EP (1) EP3694555A4 (https=)
JP (2) JP2020536892A (https=)
KR (1) KR102901919B1 (https=)
CN (2) CN119524126A (https=)
AU (3) AU2018347991A1 (https=)
CA (1) CA3078844A1 (https=)
IL (2) IL311303B1 (https=)
WO (1) WO2019074829A1 (https=)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102881925B1 (ko) * 2022-02-22 2025-11-06 인제대학교 산학협력단 양이온교환수지를 사용한 약물의 방출 조절을 위한 조성물

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030118641A1 (en) * 2000-07-27 2003-06-26 Roxane Laboratories, Inc. Abuse-resistant sustained-release opioid formulation
US20140127306A1 (en) * 2006-03-16 2014-05-08 Tris Pharma, Inc. Modified Release Formulations Containing Drug-Ion Exchange Resin Complexes

Family Cites Families (20)

* Cited by examiner, † Cited by third party
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FI65910C (fi) * 1976-11-26 1984-08-10 Pennwalt Corp Foerfarande foer framstaellning av farmaceutiska preparat med laongtidsverkan
US6375957B1 (en) 1997-12-22 2002-04-23 Euro-Celtique, S.A. Opioid agonist/opioid antagonist/acetaminophen combinations
WO2001008661A2 (en) * 1999-07-29 2001-02-08 Roxane Laboratories, Inc. Opioid sustained-released formulation
AU764453B2 (en) * 1999-10-29 2003-08-21 Euro-Celtique S.A. Controlled release hydrocodone formulations
EP2092936B1 (en) * 2000-02-08 2013-03-20 Euro-Celtique S.A. Tamper-resistant oral opioid agonist formulations
AR039744A1 (es) * 2002-06-26 2005-03-09 Alza Corp Metodos y formas de dosificacion para aumentar la solubilidad de las composiciones de farmacos para la administracion controlada
US8343546B2 (en) 2005-09-13 2013-01-01 Coating Place, Inc. Ion exchange resin treated to control swelling
CA2689101C (en) * 2007-05-30 2013-01-22 Neos Therapeutics, Lp Modifying drug release in suspensions of ionic resin systems
JP5482012B2 (ja) * 2008-09-19 2014-04-23 セイコーエプソン株式会社 ターゲット支持装置、ターゲット搬送機構及び液体噴射装置
WO2011063164A2 (en) * 2009-11-18 2011-05-26 Steady Sleep Rx Co., Inc. Sustained release cannabinoid medicaments
WO2011107855A2 (en) 2010-03-04 2011-09-09 Torrent Pharmaceuticals Limited Sustained release oral liquid suspension dosage form
US8623409B1 (en) * 2010-10-20 2014-01-07 Tris Pharma Inc. Clonidine formulation
US20130230587A1 (en) * 2010-11-10 2013-09-05 Rubicon Research Private Limited Sustained release compositions
BR112013019431A2 (pt) * 2011-02-02 2020-10-27 Alpharma Pharmaceuticals, Llc composição farmacêutica compreendendo agonista opioide e antagonista sequestrado
US20140127300A1 (en) 2011-06-30 2014-05-08 Neos Therapeutics, Lp Abuse resistant drug forms
WO2013119231A1 (en) 2012-02-09 2013-08-15 Tris Pharma, Inc. Abuse resistant opioid drug - ion exchange resin complexes having hybrid coatings
MX354677B (es) 2012-03-02 2018-03-15 Rhodes Pharmaceuticals Lp Formulaciones de liberacion inmediata resistentes a la manipulacion.
CN105188677A (zh) * 2013-03-13 2015-12-23 特瑞斯制药股份有限公司 苯佐那酯调释固体片剂和胶囊剂
MA41152A (fr) 2014-12-12 2017-10-17 Johnson & Johnson Consumer Inc Procédé de fabrication de particules de résinate de phényléphrine ; particules de résinate de phényléphrine et utilisation des particules de résinate de phényléphrine dans des formulations pharmaceutiques
EP3522890A4 (en) * 2016-10-10 2020-06-03 Rhodes Pharmaceuticals L.P. PHARMACEUTICAL RESINATE COMPOSITIONS AND METHOD FOR THE PRODUCTION AND USE THEREOF

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030118641A1 (en) * 2000-07-27 2003-06-26 Roxane Laboratories, Inc. Abuse-resistant sustained-release opioid formulation
US20140127306A1 (en) * 2006-03-16 2014-05-08 Tris Pharma, Inc. Modified Release Formulations Containing Drug-Ion Exchange Resin Complexes

Also Published As

Publication number Publication date
US20230285388A1 (en) 2023-09-14
US20250375438A1 (en) 2025-12-11
IL273904B1 (en) 2024-04-01
EP3694555A4 (en) 2021-07-07
BR112020007061A2 (pt) 2020-10-06
AU2018347991A1 (en) 2020-05-07
KR20200097685A (ko) 2020-08-19
EP3694555A1 (en) 2020-08-19
KR102901919B1 (ko) 2025-12-17
US20200253956A1 (en) 2020-08-13
IL273904A (en) 2020-05-31
IL311303A (en) 2024-05-01
CN119524126A (zh) 2025-02-28
US11690840B2 (en) 2023-07-04
CN111629758A (zh) 2020-09-04
AU2022201848B2 (en) 2024-06-13
WO2019074829A1 (en) 2019-04-18
JP2023123471A (ja) 2023-09-05
JP2020536892A (ja) 2020-12-17
CA3078844A1 (en) 2019-04-18
AU2024219439A1 (en) 2024-09-26
IL273904B2 (en) 2024-08-01
AU2022201848A1 (en) 2022-04-14

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