CA3059539A1 - Pharmaceutical composition comprising pde9 inhibitor - Google Patents

Pharmaceutical composition comprising pde9 inhibitor Download PDF

Info

Publication number
CA3059539A1
CA3059539A1 CA3059539A CA3059539A CA3059539A1 CA 3059539 A1 CA3059539 A1 CA 3059539A1 CA 3059539 A CA3059539 A CA 3059539A CA 3059539 A CA3059539 A CA 3059539A CA 3059539 A1 CA3059539 A1 CA 3059539A1
Authority
CA
Canada
Prior art keywords
compound
subjects
mean
auc
day
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
CA3059539A
Other languages
English (en)
French (fr)
Inventor
Edgar Schuck
Robert Lai
Ishani Savant Landry
Bhaskar Rege
Mai Miyamoto
Sadaharu Kotani
Kanta HORIE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eisai R&D Management Co Ltd
Original Assignee
Eisai R&D Management Co Ltd
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 Eisai R&D Management Co Ltd filed Critical Eisai R&D Management Co Ltd
Publication of CA3059539A1 publication Critical patent/CA3059539A1/en
Pending legal-status Critical Current

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
    • A61K31/435—Heterocyclic 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • 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
    • A61K31/435—Heterocyclic 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • 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
    • A61K31/435—Heterocyclic 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
    • A61K31/4353—Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • 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
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Hospice & Palliative Care (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CA3059539A 2017-06-01 2018-05-30 Pharmaceutical composition comprising pde9 inhibitor Pending CA3059539A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201762513690P 2017-06-01 2017-06-01
US62/513,690 2017-06-01
PCT/JP2018/020643 WO2018221546A1 (en) 2017-06-01 2018-05-30 Pharmaceutical composition comprising pde9 inhibitor

Publications (1)

Publication Number Publication Date
CA3059539A1 true CA3059539A1 (en) 2018-12-06

Family

ID=64455959

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3059539A Pending CA3059539A1 (en) 2017-06-01 2018-05-30 Pharmaceutical composition comprising pde9 inhibitor

Country Status (12)

Country Link
US (2) US11484502B2 (https=)
EP (1) EP3630113A4 (https=)
JP (1) JP7293129B2 (https=)
KR (1) KR20200010211A (https=)
CN (2) CN116585316A (https=)
AU (1) AU2018276566A1 (https=)
BR (1) BR112019023557A2 (https=)
CA (1) CA3059539A1 (https=)
MX (1) MX2019013198A (https=)
RU (1) RU2019135261A (https=)
SG (1) SG11201909359YA (https=)
WO (1) WO2018221546A1 (https=)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018221550A1 (ja) 2017-06-01 2018-12-06 エーザイ・アール・アンド・ディー・マネジメント株式会社 ピラゾロキノリン誘導体とメマンチンの併用による認知症治療剤
RU2019135834A (ru) 2017-06-01 2021-07-13 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Терапевтическое средство для лечения деменции, представляющее собой комбинацию производного пиразолохинолина и донепезила
BR112019023552A2 (pt) 2017-06-01 2020-06-02 Eisai R&D Management Co., Ltd. Agente terapêutico para a demência com corpos de lewy contendo derivado de pirazoloquinolina
WO2023064857A1 (en) 2021-10-14 2023-04-20 Incyte Corporation Quinoline compounds as inhibitors of kras
CN120897742A (zh) * 2022-11-15 2025-11-04 福睿德姆生物科学公司 通过抑制9型磷酸二酯酶增强血清素能致幻药物在治疗或预防某些神经精神障碍中的功效
CN119302958B (zh) * 2023-12-01 2025-10-21 郑州大学第一附属医院 含有bay 73-6691或其衍生物的药物制剂在制备治疗脑损伤疾病药物中的应用

Family Cites Families (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5318759A (en) 1976-08-02 1978-02-21 Nisshin Oil Mills Ltd Method of making fried beancurd
JPH05132484A (ja) 1991-04-26 1993-05-28 Otsuka Pharmaceut Factory Inc ピラゾロキノリン及びピラゾロナフチリジン誘導体
DK0760819T3 (da) 1994-05-24 2000-10-09 Hoffmann La Roche Tricykliske dicarbonylderivater
DE19642591A1 (de) 1996-10-15 1998-04-16 Basf Ag Neue Piperidin-Ketocarbonsäure-Derivate, deren Herstellung und Anwendung
HN2002000317A (es) 2001-11-02 2003-05-21 Pfizer Inhibidores de pde9 para tratamiento de trastornos cardiovasculares
BR0313262A (pt) 2002-08-07 2005-07-12 Mitsubishi Pharma Corp Compostos de dihidropirazolpiridina
DE10238722A1 (de) * 2002-08-23 2004-03-11 Bayer Ag Selektive Phosphodiesterase 9A-Inhibitoren als Arzneimittel zur Verbesserung kognitiver Prozesse
DE102004004142A1 (de) 2003-05-09 2004-11-25 Bayer Healthcare Ag 6-Cyclylmethyl- und 6-Alkylmethyl-substituierte Pyrazolopyrimidine
RU2426734C2 (ru) 2003-10-03 2011-08-20 Зм Инновейтив Пропертиз Компани Пиразолопиридины и их аналоги
WO2005118583A1 (en) 2004-05-28 2005-12-15 Millennium Pharmaceuticals, Inc. 2, 5-dihydro-pyrazolo`4, 3-c!quinolin-4-ones as chk-1 inhibitors
JP2006045118A (ja) 2004-08-04 2006-02-16 Mochida Pharmaceut Co Ltd 新規ピラゾロキノロン誘導体
CA2622605A1 (en) 2005-09-15 2007-03-22 Aska Pharmaceutical Co., Ltd. Heterocycle compound, and production process and application thereof
CN101466365A (zh) 2006-06-09 2009-06-24 惠氏公司 增强认知功能的方法
TW200808741A (en) 2006-06-09 2008-02-16 Wyeth Corp 6-methoxy-8-[4-(1-(5-fluoro)-quinolin-8-yl-piperidin-4-yl)-piperazin-1-yl]-quinoline hydrochloric acid salts
WO2008072778A1 (ja) 2006-12-13 2008-06-19 Aska Pharmaceutical Co., Ltd. 尿路系疾患の処置剤
CA2671980C (en) 2006-12-13 2015-05-05 Aska Pharmaceutical Co., Ltd. Quinoxaline derivatives
PT2152712E (pt) 2007-05-11 2012-02-29 Pfizer Compostos amino-heterocíclicos
UA105362C2 (en) 2008-04-02 2014-05-12 Бьорингер Ингельхайм Интернациональ Гмбх 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators
JP5453431B2 (ja) 2008-09-08 2014-03-26 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング ピラゾロピリミジン及びｃｎｓ障害の治療のためのそれらの使用
TWI404721B (zh) 2009-01-26 2013-08-11 Pfizer 胺基－雜環化合物
WO2010101230A1 (ja) 2009-03-05 2010-09-10 アステラス製薬株式会社 キノキサリン化合物
PE20120505A1 (es) 2009-03-31 2012-05-09 Boehringer Ingelheim Int Derivados de 1-heterociclil-1,5-dihidro-pirazolo[3,4-d]pirimidin-4-ona como moduladores de pde9a
SMT201800036T1 (it) 2009-04-13 2018-03-08 Theravance Biopharma R&D Ip Llc Combinazioni di agonisti di recettore 5-ht4 e inibitori di acetilcolinesterasi per il trattamento di disturbi cognitivi
US8880976B2 (en) 2009-09-25 2014-11-04 Stmicroelectronics, Inc. Method and apparatus for encoding LBA information into the parity of a LDPC system
AP2012006631A0 (en) 2010-08-12 2012-12-31 Boehringer Ingelheim Int 6-Cycloalkyl-1, 5-dihydro-pyrazolo[3,4-D] pyrimidin-4-one derivatives and their use as PDE9A inhibitors
RS54834B1 (sr) 2010-09-07 2016-10-31 Astellas Pharma Inc Jedinjenja pirazolokvinolina
US20130040971A1 (en) 2011-02-14 2013-02-14 Boehringer Ingelheim International Gmbh 6-cycloalkyl-pyrazolopyrimidinones for the treatment of cns disorders
PT2573073E (pt) 2011-09-26 2015-02-05 Sanofi Sa Derivados de pirazoloquinolinona, sua preparação e sua utilização terapêutica
JP6042060B2 (ja) 2011-09-26 2016-12-14 サノフイ ピラゾロキノリノン誘導体、その調製および治療上の使用
JP5938299B2 (ja) 2011-10-05 2016-06-22 ダイセルポリマー株式会社 繊維強化樹脂組成物
WO2013051639A1 (ja) 2011-10-07 2013-04-11 エーザイ・アール・アンド・ディー・マネジメント株式会社 ピラゾロキノリン誘導体
EP2982675B1 (en) 2013-04-05 2017-08-16 Eisai R&D Management Co., Ltd. Salt of pyrazoloquinoline derivative, and crystal thereof
CN107847499A (zh) 2015-05-07 2018-03-27 阿速万科学有限责任公司 治疗神经退行性疾病的方法
BR112019023552A2 (pt) 2017-06-01 2020-06-02 Eisai R&D Management Co., Ltd. Agente terapêutico para a demência com corpos de lewy contendo derivado de pirazoloquinolina
RU2019135834A (ru) 2017-06-01 2021-07-13 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Терапевтическое средство для лечения деменции, представляющее собой комбинацию производного пиразолохинолина и донепезила
WO2018221550A1 (ja) 2017-06-01 2018-12-06 エーザイ・アール・アンド・ディー・マネジメント株式会社 ピラゾロキノリン誘導体とメマンチンの併用による認知症治療剤

Also Published As

Publication number Publication date
WO2018221546A1 (en) 2018-12-06
CN116585316A (zh) 2023-08-15
SG11201909359YA (en) 2019-11-28
KR20200010211A (ko) 2020-01-30
RU2019135261A (ru) 2021-07-09
JP7293129B2 (ja) 2023-06-19
EP3630113A4 (en) 2021-02-24
JP2020521726A (ja) 2020-07-27
RU2019135261A3 (https=) 2021-09-08
CN110545812A (zh) 2019-12-06
US11484502B2 (en) 2022-11-01
AU2018276566A1 (en) 2019-11-07
BR112019023557A2 (pt) 2020-06-02
US20220378706A1 (en) 2022-12-01
MX2019013198A (es) 2020-01-20
US20200078306A1 (en) 2020-03-12
EP3630113A1 (en) 2020-04-08

Similar Documents

Publication Publication Date Title
US11484502B2 (en) Pharmaceutical composition comprising PDE9 inhibitor
EP1741446B1 (en) Combinations comprising dipeptidylpeptidase-IV inhibitors and antidiabetic agents
EP2278972B1 (en) Treatment for neurological and mental disorders
Gerra et al. Intravenous flumazenil versus oxazepam tapering in the treatment of benzodiazepine withdrawal: a randomized, placebo‐controlled study
US20130345202A1 (en) Flumazenil Complexes, Compositions Comprising Same And Uses Thereof
JP2012229261A (ja) 神経刺激性ステロイドの医薬組成物及びその使用
EP4054620B1 (en) Semaglutide in the treatment of alzheimer's dementia
KR20140054129A (ko) 라퀴니모드와 인터페론-베타의 병용에 의한 다발성 경화증의 치료
JP2008074852A (ja) 肝機能が低下した精神医学上の患者をパリペリドンで治療
WO2008047340A1 (en) Combined therapies of antipsychotic drugs and tetracyclines in the treatment of psychiatric disorders
CN104582793A (zh) 用拉喹莫德和氨吡啶的组合治疗多发性硬化症
TW200843741A (en) Pharmaceutical composition
US20040006072A1 (en) Sustained-release alprazolam composition
TW202038955A (zh) 用於治療多巴胺性cns病症之ly3154207劑量療法
CN117715641A (zh) 用神经活性类固醇进行治疗的方法
WO2015153263A1 (en) Compositions and methods to treat addiction
EP4665333A1 (en) Regimens and compositions useful for alleviating pain
RU2258506C2 (ru) Лекарственные средства для предупреждения и лечения нейродегенеративных заболеваний
DE602004005000T2 (de) Methode zur behandlung von niereninsuffizienz
Valsecchi et al. Paliperidone extended-release in the short-and long-term treatment of schizophrenia
KR20230041006A (ko) 오피오이드 사용 감소 치료에 사용하기 위한 mglur5 길항제 마보글루란트
US20230123140A1 (en) Dose treatments of tauopathies
WO2025264845A1 (en) Use of anavex3-71 for medical treatments
WO2022240612A1 (en) Use of complement factor d inhibitor for treatment of generalized myasthenia gravis
CN121511089A (zh) 伊博格碱治疗

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20230505

B12 Application deemed to be withdrawn, abandoned or lapsed

Free format text: ST27 STATUS EVENT CODE: N-6-6-B10-B12-B303 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: DEEMED ABANDONED - FAILURE TO RESPOND TO AN EXAMINER'S REQUISITION

Effective date: 20241015

U13 Renewal or maintenance fee not paid

Free format text: ST27 STATUS EVENT CODE: N-2-6-U10-U13-U300 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: DEEMED ABANDONED - FAILURE TO RESPOND TO MAINTENANCE FEE NOTICE

Effective date: 20260206