BR112018016346A2 - processo - Google Patents
processoInfo
- Publication number
- BR112018016346A2 BR112018016346A2 BR112018016346A BR112018016346A BR112018016346A2 BR 112018016346 A2 BR112018016346 A2 BR 112018016346A2 BR 112018016346 A BR112018016346 A BR 112018016346A BR 112018016346 A BR112018016346 A BR 112018016346A BR 112018016346 A2 BR112018016346 A2 BR 112018016346A2
- Authority
- BR
- Brazil
- Prior art keywords
- neosaxitoxin
- analogs
- variants
- production
- intermediates
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
- C12P17/182—Heterocyclic compounds containing nitrogen atoms as the only ring heteroatoms in the condensed system
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/10—Nitrogen as only ring hetero atom
- C12P17/12—Nitrogen as only ring hetero atom containing a six-membered hetero ring
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- C12N9/1288—Transferases for other substituted phosphate groups (2.7.8)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/32—Amino acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/42—Organic phosphate, e.g. beta glycerophosphate
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/185—Escherichia
- C12R2001/19—Escherichia coli
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/08—Transferases for other substituted phosphate groups (2.7.8)
- C12Y207/08007—Holo-[acyl-carrier-protein] synthase (2.7.8.7)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
a presente invenção refere-se a processos para fabricar neosaxitoxina, e análogos e variantes da mesma, e intermediários na produção de neosaxitoxina em células hospedeiras recombinantes. neosaxitoxina e os análogos e variantes da mesma podem ser usados na produção de composições farmacêuticas.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB1602576.9A GB201602576D0 (en) | 2016-02-12 | 2016-02-12 | Process |
PCT/EP2017/053077 WO2017137606A1 (en) | 2016-02-12 | 2017-02-10 | Process |
Publications (1)
Publication Number | Publication Date |
---|---|
BR112018016346A2 true BR112018016346A2 (pt) | 2019-01-22 |
Family
ID=55697646
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BR112018016346A BR112018016346A2 (pt) | 2016-02-12 | 2017-02-10 | processo |
Country Status (14)
Country | Link |
---|---|
US (2) | US10920256B2 (pt) |
EP (2) | EP3414334B1 (pt) |
JP (1) | JP2019504650A (pt) |
KR (1) | KR20190006478A (pt) |
CN (1) | CN109790558A (pt) |
AU (2) | AU2017218598B2 (pt) |
BR (1) | BR112018016346A2 (pt) |
CA (1) | CA3014109A1 (pt) |
CL (1) | CL2018002149A1 (pt) |
EA (1) | EA201891805A1 (pt) |
GB (3) | GB201602576D0 (pt) |
IL (1) | IL261106A (pt) |
MX (1) | MX2018009676A (pt) |
WO (1) | WO2017137606A1 (pt) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109097415A (zh) * | 2018-08-08 | 2018-12-28 | 浙江海洋大学 | 一种利用产毒海洋亚硫酸杆菌发酵制备石房蛤毒素的方法 |
US20230145895A1 (en) * | 2020-03-26 | 2023-05-11 | The Cawthron Institute Trust Board | Preparation of neosaxitoxin |
CN115466219B (zh) * | 2022-07-28 | 2023-09-08 | 中国科学院天津工业生物技术研究所 | 一种1-[3-(2-氨基-4-乙基-1h-咪唑-5-基)丙基]胍的制备方法 |
Family Cites Families (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0693072B9 (en) | 1993-04-08 | 2004-09-15 | The Trustees of Columbia University in the City of New York | Method for the synthesis of 4- and/or 5-(di)substituted 2-aminoimidazoles from 2-aminoimidazoles and aldehydes |
AU7389098A (en) | 1997-05-16 | 1998-12-08 | Brigham And Women's Hospital | Local anesthetic formulations |
JP4289694B2 (ja) | 1998-04-03 | 2009-07-01 | 正昭 児玉 | 新規のサキシトキシン誘導体およびその製造方法 |
CN1559007A (zh) | 2000-12-12 | 2004-12-29 | 澳大利亚海洋科学研究院 | 致瘫痪水生有壳类动物毒素的分析 |
JP2003012699A (ja) | 2001-07-04 | 2003-01-15 | Japan Science & Technology Corp | 抗麻酔性貝毒抗体の製法、新規抗体、該抗体を用いるelisa測定キット、該製法による系標識毒標品 |
CA2466697C (en) | 2001-11-15 | 2013-09-24 | Micro Algae Corporation | Pharmaceutical compositions containing 3,4-propinoperhydropurines and uses thereof for blocking neuronal transmission |
US20030148359A1 (en) | 2002-01-11 | 2003-08-07 | Yale University | Saxitoxin detection and assay method |
AU2003901897A0 (en) | 2003-02-12 | 2003-05-08 | Australian Institute Of Marine Science | Conjugate |
WO2006032481A1 (en) | 2004-09-21 | 2006-03-30 | Laboratorios Del Dr. Esteve S.A. | Tetrodotoxin and its derivatives for the treatment of central-nervously derived neuropathic pain |
AU2005287580A1 (en) | 2004-09-22 | 2006-03-30 | Wex Medical Limited | Tetrodotoxin and its derivatives for the treatment of peripheral-nervously derived neuropathic pain |
RU2277097C1 (ru) | 2004-12-27 | 2006-05-27 | Институт Молекулярной Генетики Российской Академии Наук (Имг Ран) | Высокомеченный тритием дигидрохлорид [3h]сакситоксина |
EP1853268A1 (en) * | 2005-02-11 | 2007-11-14 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers and their analogues for the treatment of nicotine dependency |
WO2007025212A2 (en) | 2005-08-25 | 2007-03-01 | Wex Pharmaceuticals, Inc. | Use of sodium channel blockers for the treatment of visceral pain or pain caused by cancer treatment |
US20100048592A1 (en) | 2005-08-25 | 2010-02-25 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers for the management of musculoskeletal pain |
EP1844781A1 (en) | 2006-02-22 | 2007-10-17 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers for the treatment of preterm labor |
EP1844782A1 (en) | 2006-03-27 | 2007-10-17 | Wex Pharmaceuticals, Inc | Use of 4,9-anhydro-tetrodotoxin for the treatment of diseases related to the voltage-gated sodium channel subunit Nav1.6 |
CA2647235C (en) | 2006-03-27 | 2019-03-12 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers for the treatment of neuropathic pain developing as a consequence of chemotherapy |
CN101903530A (zh) * | 2007-10-12 | 2010-12-01 | 加利福尼亚大学董事会 | 被改造以产生异丙醇的微生物 |
DK2279265T3 (da) | 2008-04-24 | 2014-12-08 | Newsouth Innovations Pty Ltd | Cyanobakterie-saxitoxin-gencluster og detektering af cyanotoksiske organismer |
US8957207B2 (en) * | 2009-03-24 | 2015-02-17 | Proteus S.A. | Methods for producing phycotoxins |
CL2009000723A1 (es) | 2009-03-24 | 2009-06-19 | Proteus Sa | Metodo de purificacion industrial de ficotoxinas biologicamente activas que comprende proporcionar una cantidad adecuada de una fuente de ficotoxinas como por ejemplo el cultivo de un clon de cianobacterias. |
CN102459273A (zh) | 2009-05-07 | 2012-05-16 | 里兰斯坦福初级大学理事会 | 用于研究、成像以及治疗疼痛的方法和组合物 |
WO2011094367A1 (en) | 2010-01-26 | 2011-08-04 | Evans Michael A | Methods, devices, and agents for denervation |
WO2011098539A1 (en) | 2010-02-10 | 2011-08-18 | Phytotox Limited | Treatment of loss of sense of touch with saxitoxin derivatives |
SG194948A1 (en) | 2011-05-16 | 2013-12-30 | Newsouth Innovations Pty Ltd | Detection of saxitoxin-producing dinoflagellates |
EP2638908A1 (en) | 2012-03-16 | 2013-09-18 | Phytotox SpA | Paralytic Shellfish Poison |
US9408846B2 (en) | 2012-04-23 | 2016-08-09 | The Children's Medical Center Corporation | Formulations and methods for delaying onset of chronic neuropathic pain |
WO2014168721A2 (en) | 2013-04-12 | 2014-10-16 | Tufts Medical Center | Methods and systems for designing and/or characterizing soluble lipidated ligand agents |
EP3129381B1 (en) | 2014-04-09 | 2020-11-04 | Siteone Therapeutics Inc. | 10',11'-modified saxitoxins useful for the treatment of pain |
-
2016
- 2016-02-12 GB GBGB1602576.9A patent/GB201602576D0/en not_active Ceased
-
2017
- 2017-02-10 WO PCT/EP2017/053077 patent/WO2017137606A1/en active Application Filing
- 2017-02-10 KR KR1020187025912A patent/KR20190006478A/ko unknown
- 2017-02-10 EP EP17706173.6A patent/EP3414334B1/en active Active
- 2017-02-10 AU AU2017218598A patent/AU2017218598B2/en active Active
- 2017-02-10 EA EA201891805A patent/EA201891805A1/ru unknown
- 2017-02-10 GB GB1903649.0A patent/GB2569907B/en active Active
- 2017-02-10 GB GB1702275.7A patent/GB2552859B/en active Active
- 2017-02-10 JP JP2018561309A patent/JP2019504650A/ja active Pending
- 2017-02-10 BR BR112018016346A patent/BR112018016346A2/pt not_active Application Discontinuation
- 2017-02-10 CN CN201780023087.6A patent/CN109790558A/zh active Pending
- 2017-02-10 CA CA3014109A patent/CA3014109A1/en active Pending
- 2017-02-10 MX MX2018009676A patent/MX2018009676A/es unknown
- 2017-02-10 US US16/077,281 patent/US10920256B2/en active Active
- 2017-02-10 EP EP23192625.4A patent/EP4279577A3/en active Pending
-
2018
- 2018-08-08 CL CL2018002149A patent/CL2018002149A1/es unknown
- 2018-08-12 IL IL261106A patent/IL261106A/en unknown
-
2020
- 2020-10-19 US US17/074,607 patent/US11566271B2/en active Active
-
2021
- 2021-03-30 AU AU2021201969A patent/AU2021201969B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
GB201903649D0 (en) | 2019-05-01 |
MX2018009676A (es) | 2019-06-06 |
EP3414334C0 (en) | 2023-10-11 |
US20210108239A1 (en) | 2021-04-15 |
KR20190006478A (ko) | 2019-01-18 |
WO2017137606A1 (en) | 2017-08-17 |
EP4279577A3 (en) | 2024-01-24 |
CA3014109A1 (en) | 2017-08-17 |
EP3414334B1 (en) | 2023-10-11 |
AU2017218598B2 (en) | 2021-05-06 |
EA201891805A1 (ru) | 2019-02-28 |
GB2569907A (en) | 2019-07-03 |
CL2018002149A1 (es) | 2019-02-15 |
JP2019504650A (ja) | 2019-02-21 |
GB201702275D0 (en) | 2017-03-29 |
GB2552859A (en) | 2018-02-14 |
AU2021201969A1 (en) | 2021-04-29 |
GB2552859B (en) | 2019-09-18 |
GB2569907B (en) | 2020-04-08 |
AU2021201969B2 (en) | 2023-02-02 |
US10920256B2 (en) | 2021-02-16 |
EP3414334A1 (en) | 2018-12-19 |
AU2017218598A1 (en) | 2018-10-04 |
US20190048375A1 (en) | 2019-02-14 |
EP4279577A2 (en) | 2023-11-22 |
IL261106A (en) | 2018-10-31 |
US11566271B2 (en) | 2023-01-31 |
CN109790558A (zh) | 2019-05-21 |
GB201602576D0 (en) | 2016-03-30 |
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