CN116472044A - 包含可溶胀核芯的Tyk2抑制剂的剂型 - Google Patents
包含可溶胀核芯的Tyk2抑制剂的剂型 Download PDFInfo
- Publication number
- CN116472044A CN116472044A CN202180074961.5A CN202180074961A CN116472044A CN 116472044 A CN116472044 A CN 116472044A CN 202180074961 A CN202180074961 A CN 202180074961A CN 116472044 A CN116472044 A CN 116472044A
- Authority
- CN
- China
- Prior art keywords
- dosage form
- swellable core
- methyl
- subject
- bms
- 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
Links
- 239000002552 dosage form Substances 0.000 title claims abstract description 20
- 229940123371 Tyrosine kinase 2 inhibitor Drugs 0.000 title description 2
- -1 (2-methoxy-3- (1-methyl-1H-1, 2, 4-triazol-3-yl) phenyl) amino Chemical group 0.000 claims abstract description 15
- 239000006185 dispersion Substances 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 18
- BZZKEPGENYLQSC-FIBGUPNXSA-N 6-(cyclopropanecarbonylamino)-4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-N-(trideuteriomethyl)pyridazine-3-carboxamide Chemical compound C1(CC1)C(=O)NC1=CC(=C(N=N1)C(=O)NC([2H])([2H])[2H])NC1=C(C(=CC=C1)C1=NN(C=N1)C)OC BZZKEPGENYLQSC-FIBGUPNXSA-N 0.000 claims description 14
- 229940124282 BMS-986165 Drugs 0.000 claims description 14
- 201000004681 Psoriasis Diseases 0.000 claims description 13
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 9
- 208000011231 Crohn disease Diseases 0.000 claims description 6
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 208000011594 Autoinflammatory disease Diseases 0.000 claims description 5
- DMYLUKNFEYWGCH-UHFFFAOYSA-N pyridazine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=N1 DMYLUKNFEYWGCH-UHFFFAOYSA-N 0.000 claims description 5
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 239000011159 matrix material Substances 0.000 claims description 4
- 229920000642 polymer Polymers 0.000 claims description 4
- 239000000203 mixture Substances 0.000 description 9
- 238000009472 formulation Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000010922 spray-dried dispersion Methods 0.000 description 3
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 2
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 2
- ZUAAPNNKRHMPKG-UHFFFAOYSA-N acetic acid;butanedioic acid;methanol;propane-1,2-diol Chemical compound OC.CC(O)=O.CC(O)CO.OC(=O)CCC(O)=O ZUAAPNNKRHMPKG-UHFFFAOYSA-N 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 208000037979 autoimmune inflammatory disease Diseases 0.000 description 2
- 230000005784 autoimmunity Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000008199 coating composition Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000002227 Interferon Type I Human genes 0.000 description 1
- 108010014726 Interferon Type I Proteins 0.000 description 1
- 102000042838 JAK family Human genes 0.000 description 1
- 108010024121 Janus Kinases Proteins 0.000 description 1
- 102000015617 Janus Kinases Human genes 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 108010010057 TYK2 Kinase Proteins 0.000 description 1
- 102000015774 TYK2 Kinase Human genes 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000000887 Transcription factor STAT Human genes 0.000 description 1
- 108050007918 Transcription factor STAT Proteins 0.000 description 1
- 108700036252 Tyrosine Kinase 2 Deficiency Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000005553 drilling Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000017214 establishment of T cell polarity Effects 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 239000013022 formulation composition Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 208000018615 immunodeficiency 35 Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000010472 type I IFN response Effects 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
Classifications
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0004—Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
-
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
可溶胀核芯剂型包含无定形6‑(环丙烷酰胺基)‑4‑((2‑甲氧基‑3‑(1‑甲基‑1H‑1,2,4‑三唑‑3‑基)苯基)氨基)‑N‑(甲基‑d3)哒嗪‑3‑甲酰胺的分散体。
Description
技术领域
本文所述的无定形6-(环丙烷酰胺基)-4-((2-甲氧基-3-(1-甲基-1H-1,2,4-三唑-3-基)苯基)氨基)-N-(甲基-d3)哒嗪-3-甲酰胺(BMS-986165)的分散体可用于包含可溶胀核芯的控制释放剂型中。可以向患者施用所述剂型以治疗自身免疫性疾病和自身炎性疾病，诸如炎性肠病(IBD)和银屑病。
背景技术
酪氨酸激酶2(Tyk2)是非受体酪氨酸激酶两面神激酶(Janus kinase)(JAK)家族的成员，并且已显示在调节小鼠(Ishizaki,M.等人,“Involvement of tyrosine kinase-2in both the IL-12/Th1and IL-23/Th17axes in vivo,”J.Immunol.,187:181–189(2011)；Prchal-Murphy,M.等人,“TYK2kinase activity is required for functionaltype I interferon responses in vivo,”PLoS One,7:e39141(2012))和人(Minegishi,Y.等人,“Human tyrosine kinase 2deficiency reveals its requisite roles inmultiple cytokine signals involved in innate and acquired immunity,”Immunity,25:745-755(2006))两者中在IL-12、IL-23和I型干扰素的受体的下游的信号转导级联方面是至关重要的。Tyk2介导受体诱导的STAT转录因子家族成员的磷酸化，所述磷酸化是导致STAT蛋白二聚化和STAT依赖性促炎基因转录的重要信号。Tyk2缺陷型小鼠对结肠炎、银屑病和多发性硬化症的实验模型具有抗性，证明了Tyk2介导的信号传导在自身免疫和相关障碍中的重要性(Ishizaki,M.等人,“Involvement of tyrosine kinase-2in both the IL-12/Th1and IL-23/Th17axes in vivo,”J.Immunol.,187:181–189(2011)；Oyamada,A.等人,“Tyrosine kinase 2plays critical roles in the pathogenic CD4T cellresponses for the development of experimental autoimmune encephalomyelitis,”J.Immunol.,183:7539-7546(2009))。
在人类中，表达Tyk2的非活性变体的个体受到保护免于遭受多发性硬化症以及可能地其他自身免疫性障碍(Couturier,N.等人,“Tyrosine kinase 2variant influencesT lymphocyte polarization and multiple sclerosis susceptibility,”Brain,134:693-703(2011))。全基因组关联研究显示，Tyk2的其他变体与自身免疫性障碍诸如克罗恩病、银屑病、系统性红斑狼疮和类风湿关节炎相关，进一步证明了Tyk2在自身免疫中的重要性(Ellinghaus,D.等人,“Combined Analysis of Genome-wide Association Studiesfor Crohn Disease and Psoriasis Identifies Seven Shared Susceptibility Loci,”Am.J.Hum.Genet.,90:636-647(2012)；Graham,D.等人,“Association of polymorphismsacross the tyrosine kinase gene,TYK2in UK SLE families,”Rheumatology(Oxford),46:927-930(2007)；Eyre,S.等人,“High-density genetic mapping identifies newsusceptibility loci for rheumatoid arthritis,”Nat.Genet.,44:1336-1340(2012))。
BMS-986165是指具有下式(I)的化合物
它是6-(环丙烷酰胺基)-4-((2-甲氧基-3-(1-甲基-1H-1,2,4-三唑-3-基)苯基)氨基)-N-(甲基-d3)哒嗪-3-甲酰胺。正在研究的用于治疗自身免疫性疾病和自身炎性疾病诸如银屑病、银屑病性关节炎、狼疮、狼疮性肾炎、干燥综合征( syndrome)、炎性肠病(包括溃疡性结肠炎和克罗恩病)和强直性脊柱炎的BMS-986165是Tyk2介导的信号转导的高度选择性抑制剂。它选择性地结合至Tyk2假激酶(JH2)结构域，并且通过稳定调节性JH2结构域来阻断受体介导的Tyk2激活。
美国专利号9,505,748B2中披露了可用作IL-12、IL-23和/或IFNα应答的调节剂的BMS-986165和其他酰胺取代的杂环化合物、其制备方法以及其使用方法，将所述美国专利的内容特此通过引用以其整体并入本文。美国临时专利申请号62/478,789和PCT/US 2018/025100(公开为WO 2018/183649)中披露了合成BMS-986165的其他方法，将所述专利各自的内容特此通过引用以其整体并入本文。
例如，美国专利号6,706,283和美国专利号9,028,870中描述了具有可溶胀核芯的配制品和剂型。
发明内容
本发明提供了治疗患者的自身免疫性疾病和自身炎性疾病的方法，所述方法包括：每天一次给患者口服施用6-(环丙烷酰胺基)-4-((2-甲氧基-3-(1-甲基-1H-1,2,4-三唑-3-基)苯基)氨基)-N-(甲基-d3)哒嗪-3-甲酰胺(BMS-986165)的可溶胀核芯剂型，所述可溶胀核芯剂型包含无定形BMS-986165在聚合物基质中的喷雾干燥分散体。自身免疫性疾病或自身炎性疾病可以是例如炎性肠病(诸如溃疡性结肠炎或克罗恩病)或银屑病(诸如斑块状银屑病)。所述剂型优选是双层片剂。
本发明还提供了治疗患者的炎性肠病的方法，所述方法包括：每天一次给患者口服施用6-(环丙烷酰胺基)-4-((2-甲氧基-3-(1-甲基-1H-1,2,4-三唑-3-基)苯基)氨基)-N-(甲基-d3)哒嗪-3-甲酰胺(BMS-986165)的可溶胀核芯剂型，所述可溶胀核芯剂型包含无定形BMS-986165在聚合物基质中的喷雾干燥分散体。所述炎性肠病可以是溃疡性结肠炎或克罗恩病。所述剂型优选是双层片剂。
本发明进一步提供了治疗患者的银屑病的方法，所述方法包括：每天一次给患者口服施用6-(环丙烷酰胺基)-4-((2-甲氧基-3-(1-甲基-1H-1,2,4-三唑-3-基)苯基)氨基)-N-(甲基-d3)哒嗪-3-甲酰胺(BMS-986165)的可溶胀核芯剂型，所述可溶胀核芯剂型包含无定形BMS-986165在聚合物基质中的喷雾干燥分散体。所述银屑病可以是斑块状银屑病。所述剂型优选是双层片剂。
以下实施例仅用于说明本发明及其实践。所述实施例不应被解释为对本发明的范围或精神的限制。
实施例
包含BMS-986165SDD的可溶胀核芯配制品
在可溶胀核芯配制品和剂型中使用BMS-986165-01SDD(15％ BMS 986165-01:85％HPMCAS)。“BMS-986165-01”在此实施例中以及在整个公开内容中具体是指呈游离碱形式的6-(环丙烷酰胺基)-4-((2-甲氧基-3-(1-甲基-1H-1,2,4-三唑-3-基)苯基)氨基)-N-(甲基-d3)哒嗪-3-甲酰胺。HPMCAS是醋酸琥珀酸羟丙基甲基纤维素(也称为醋酸琥珀酸羟丙甲纤维素)。
在此可溶胀核芯剂型实施方案中，所述剂型是包含药物层和溶胀剂层的双层片剂；每个层包含渗透原(osmogen)。这两个层构成核芯，并且所述核芯包被有半透性包衣。通过在双层的药物层侧的激光钻孔释放药物。半透性包衣包含水不溶性聚合物。表A1-A3提供了可溶胀核芯配制品的组成。另外，可以在可溶胀核芯配制品中包含结晶抑制剂，以防止或减少BMS-986165的结晶。
可以通过改变核芯组成、包衣组成和/或包衣量来精调可溶胀核芯配制品的药物释放速率。例如，每天一次给药的可溶胀核芯片剂可以实现与通过每天两次给药常释片剂所实现的药物释放曲线相似的药物释放曲线。
表A-1.研究的可溶胀核芯配制品组成和范围
表A-2.用于BMS-986165可溶胀核芯片剂的药物层和溶胀剂层配制品
表A-3.包衣组成
Claims (8)
1.一种可溶胀核芯剂型，所述可溶胀核芯剂型包含无定形6-(环丙烷酰胺基)-4-((2-甲氧基-3-(1-甲基-1H-1,2,4-三唑-3-基)苯基)氨基)-N-(甲基-d3)哒嗪-3-甲酰胺(BMS-986165)分散在聚合物基质中的分散体。
2.一种治疗受试者的自身免疫性疾病或自身炎性疾病的方法，所述方法包括向所述受试者施用根据权利要求1所述的可溶胀核芯剂型。
3.一种治疗受试者的炎性肠病的方法，所述方法包括向所述受试者施用根据权利要求1所述的可溶胀核芯剂型。
4.根据权利要求3所述的方法，其中所述炎性肠病是溃疡性结肠炎。
5.根据权利要求3所述的方法，其中所述炎性肠病是克罗恩病。
6.一种治疗受试者的银屑病的方法，所述方法包括向所述受试者施用根据权利要求1所述的可溶胀核芯剂型。
7.根据权利要求6所述的方法，其中所述银屑病是斑块状银屑病。
8.根据权利要求2-7中任一项所述的方法，其中所述可溶胀核芯剂型是双层片剂。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063080030P | 2020-09-18 | 2020-09-18 | |
| US63/080,030 | 2020-09-18 | ||
| PCT/US2021/050928 WO2022061149A1 (en) | 2020-09-18 | 2021-09-17 | Dosage forms for tyk2 inhibitors comprising swellable cores |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116472044A true CN116472044A (zh) | 2023-07-21 |
Family
ID=78135169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202180074961.5A Pending CN116472044A (zh) | 2020-09-18 | 2021-09-17 | 包含可溶胀核芯的Tyk2抑制剂的剂型 |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP4213813A1 (zh) |
| JP (1) | JP2023541997A (zh) |
| KR (1) | KR20230069976A (zh) |
| CN (1) | CN116472044A (zh) |
| AU (1) | AU2021342517A1 (zh) |
| BR (1) | BR112023004824A2 (zh) |
| CA (1) | CA3192982A1 (zh) |
| IL (1) | IL301389A (zh) |
| MX (1) | MX2023003194A (zh) |
| WO (1) | WO2022061149A1 (zh) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6706283B1 (en) | 1999-02-10 | 2004-03-16 | Pfizer Inc | Controlled release by extrusion of solid amorphous dispersions of drugs |
| NZ518281A (en) | 1999-12-23 | 2005-01-28 | Pfizer Prod Inc | Controlled release drug dosage core comprising a drug-containing composition and a water-swellable composition |
| KR20040083493A (ko) * | 2002-02-01 | 2004-10-02 | 화이자 프로덕츠 인크. | 콜레스테릴 에스테르 전달 단백질 억제제의 제어 방출형제약상 제형 |
| MY175448A (en) | 2012-11-08 | 2020-06-29 | Bristol Myers Squibb Co | Amide-substituted heterocyclic compounds useful as modulators of il-12, il-23 and/or ifna responses |
| EP3601268B1 (en) | 2017-03-30 | 2021-03-17 | Bristol-Myers Squibb Company | Process for the preparation of 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1h-1,2,4-triazol-3-yl)phenyl)amino)-n-(methyl-d3)pyridazine-3-carboxamide |
| WO2019246273A1 (en) * | 2018-06-20 | 2019-12-26 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with a jak or other kinase inhibitor |
| EP4031109A1 (en) * | 2019-09-18 | 2022-07-27 | Bristol-Myers Squibb Company | Extended release dosage forms for tyk2 inhibitors |
-
2021
- 2021-09-17 MX MX2023003194A patent/MX2023003194A/es unknown
- 2021-09-17 IL IL301389A patent/IL301389A/en unknown
- 2021-09-17 WO PCT/US2021/050928 patent/WO2022061149A1/en active Application Filing
- 2021-09-17 JP JP2023517922A patent/JP2023541997A/ja active Pending
- 2021-09-17 KR KR1020237012594A patent/KR20230069976A/ko unknown
- 2021-09-17 BR BR112023004824A patent/BR112023004824A2/pt unknown
- 2021-09-17 CN CN202180074961.5A patent/CN116472044A/zh active Pending
- 2021-09-17 EP EP21791149.4A patent/EP4213813A1/en active Pending
- 2021-09-17 CA CA3192982A patent/CA3192982A1/en active Pending
- 2021-09-17 AU AU2021342517A patent/AU2021342517A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2023541997A (ja) | 2023-10-04 |
| MX2023003194A (es) | 2023-04-13 |
| IL301389A (en) | 2023-05-01 |
| AU2021342517A1 (en) | 2023-05-11 |
| CA3192982A1 (en) | 2022-03-24 |
| KR20230069976A (ko) | 2023-05-19 |
| BR112023004824A2 (pt) | 2023-04-18 |
| WO2022061149A1 (en) | 2022-03-24 |
| EP4213813A1 (en) | 2023-07-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | Selective inhibition of the p38α MAPK–MK2 axis inhibits inflammatory cues including inflammasome priming signals | |
| Kumar et al. | JNK pathway signaling: a novel and smarter therapeutic targets for various biological diseases | |
| Zhuang et al. | Small-molecule inhibitors of necroptosis: current status and perspectives | |
| Platanias | The p38 mitogen-activated protein kinase pathway and its role in interferon signaling | |
| Coskun et al. | Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease | |
| ES2670601T3 (es) | Derivados de benzamida para la inhibición de la actividad de ABL1, ABL2 y BCR-ABL1 | |
| Verstrepen et al. | Receptor proximal kinases in NF-κB signaling as potential therapeutic targets in cancer and inflammation | |
| McCormack et al. | Dasatinib: a review of its use in the treatment of chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaemia | |
| US20080032989A1 (en) | Method of treating inflammatory diseases using tyroskine kinase inhibitors | |
| Lees et al. | Pharmacokinetics, pharmacodynamics, toxicology and therapeutics of mavacoxib in the dog: a review | |
| WO2020011168A1 (zh) | PDE9A抑制剂在制备提升Treg含量的制品、防治炎性肠病的药物及保健品中的应用 | |
| Haselager et al. | The therapeutic potential of targeting NIK in b cell malignancies | |
| Yang et al. | Identification of a novel 2, 8-diazaspiro [4.5] decan-1-one derivative as a potent and selective dual TYK2/JAK1 inhibitor for the treatment of inflammatory bowel disease | |
| Gao et al. | Targeting STING: From antiviral immunity to treat osteoporosis | |
| CN116472044A (zh) | 包含可溶胀核芯的Tyk2抑制剂的剂型 | |
| Young | Pharmacological modulation of cytokine action and production through signaling pathways | |
| JP5903433B2 (ja) | 癌の治療に有用なｖｅｇｆｒ阻害剤およびｍｅｋ阻害剤の医薬的組み合わせ | |
| JP2013507382A (ja) | 組合せ | |
| Liu et al. | Gli2 mediated activation of hedgehog signaling attenuates acute pancreatitis via balancing inflammatory cytokines in mice | |
| Kim et al. | Tubulosine selectively inhibits JAK3 signalling by binding to the ATP‐binding site of the kinase of JAK3 | |
| Welage | Pharmacologic features of proton pump inhibitors and their potential relevance to clinical practice | |
| JP4776537B2 (ja) | 糖尿病処置のためのチロシンキナーゼ阻害剤の使用 | |
| Haefner | The transcription factor NF-κB as drug target | |
| Wang et al. | Discovery, Optimization, and Evaluation of Novel N-(Benzimidazol-5-yl)-1, 3, 4-thiadiazol-2-amine Analogues as Potent STAT3 Inhibitors for Cancer Treatment | |
| JP2016193903A (ja) | 組合せ |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |