JP6814891B2 - ベンズイミダゾール誘導体の酸付加塩 - Google Patents
ベンズイミダゾール誘導体の酸付加塩 Download PDFInfo
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- JP6814891B2 JP6814891B2 JP2019536803A JP2019536803A JP6814891B2 JP 6814891 B2 JP6814891 B2 JP 6814891B2 JP 2019536803 A JP2019536803 A JP 2019536803A JP 2019536803 A JP2019536803 A JP 2019536803A JP 6814891 B2 JP6814891 B2 JP 6814891B2
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- malate
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- 150000003839 salts Chemical class 0.000 title claims description 90
- 239000002253 acid Substances 0.000 title claims description 48
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title 1
- 239000000126 substance Substances 0.000 claims description 132
- 150000001875 compounds Chemical class 0.000 claims description 104
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 29
- 150000004701 malic acid derivatives Chemical class 0.000 claims description 26
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims description 23
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 22
- 238000004519 manufacturing process Methods 0.000 claims description 20
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 claims description 19
- 239000007787 solid Substances 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 235000011090 malic acid Nutrition 0.000 claims description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 239000006184 cosolvent Substances 0.000 claims description 12
- 239000001630 malic acid Substances 0.000 claims description 12
- 230000001404 mediated effect Effects 0.000 claims description 12
- 230000003042 antagnostic effect Effects 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 9
- 238000002347 injection Methods 0.000 claims description 8
- 239000007924 injection Substances 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 201000006549 dyspepsia Diseases 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000000843 powder Substances 0.000 claims description 7
- 229940049920 malate Drugs 0.000 claims description 6
- 206010019375 Helicobacter infections Diseases 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 4
- 206010028813 Nausea Diseases 0.000 claims description 3
- 206010030216 Oesophagitis Diseases 0.000 claims description 3
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 3
- 208000007107 Stomach Ulcer Diseases 0.000 claims description 3
- 208000025865 Ulcer Diseases 0.000 claims description 3
- 201000008629 Zollinger-Ellison syndrome Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 208000000718 duodenal ulcer Diseases 0.000 claims description 3
- 208000006881 esophagitis Diseases 0.000 claims description 3
- 201000005917 gastric ulcer Diseases 0.000 claims description 3
- 201000000052 gastrinoma Diseases 0.000 claims description 3
- 230000008693 nausea Effects 0.000 claims description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 3
- 208000011906 peptic ulcer disease Diseases 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 230000009747 swallowing Effects 0.000 claims description 3
- 231100000397 ulcer Toxicity 0.000 claims description 3
- 208000009935 visceral pain Diseases 0.000 claims description 3
- 208000007882 Gastritis Diseases 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 208000029493 gastroesophageal disease Diseases 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- JTZCTMAVMHRNTR-UHFFFAOYSA-N Pyridate Chemical class CCCCCCCCSC(=O)OC1=CC(Cl)=NN=C1C1=CC=CC=C1 JTZCTMAVMHRNTR-UHFFFAOYSA-N 0.000 claims 1
- 206010039424 Salivary hypersecretion Diseases 0.000 claims 1
- 208000026451 salivation Diseases 0.000 claims 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 26
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 22
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 239000013078 crystal Substances 0.000 description 15
- 238000000634 powder X-ray diffraction Methods 0.000 description 12
- 239000002994 raw material Substances 0.000 description 12
- 238000010586 diagram Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 229940099690 malic acid Drugs 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 10
- 238000000354 decomposition reaction Methods 0.000 description 9
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 8
- 239000012458 free base Substances 0.000 description 8
- 229940116298 l- malic acid Drugs 0.000 description 8
- 235000006408 oxalic acid Nutrition 0.000 description 8
- 238000001556 precipitation Methods 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 7
- 239000001530 fumaric acid Substances 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 239000007791 liquid phase Substances 0.000 description 7
- 230000002378 acidificating effect Effects 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 239000007853 buffer solution Substances 0.000 description 5
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- 239000008186 active pharmaceutical agent Substances 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 239000011975 tartaric acid Chemical class 0.000 description 4
- 235000002906 tartaric acid Nutrition 0.000 description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001556 benzimidazoles Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 235000008504 concentrate Nutrition 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- -1 L-tartaric acid salts Chemical class 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- CLIQCDHNPDMGSL-HNNXBMFYSA-N 7-[[(4s)-5,7-difluoro-3,4-dihydro-2h-chromen-4-yl]oxy]-n,n,2-trimethyl-3h-benzimidazole-5-carboxamide Chemical compound C1COC2=CC(F)=CC(F)=C2[C@H]1OC1=C(N=C(C)N2)C2=CC(C(=O)N(C)C)=C1 CLIQCDHNPDMGSL-HNNXBMFYSA-N 0.000 description 1
- 229940121819 ATPase inhibitor Drugs 0.000 description 1
- 208000000884 Airway Obstruction Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- 206010064147 Gastrointestinal inflammation Diseases 0.000 description 1
- 238000003109 Karl Fischer titration Methods 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229940121353 acid pump inhibitor Drugs 0.000 description 1
- 239000000362 adenosine triphosphatase inhibitor Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229940043131 pyroglutamate Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic 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
- C07D405/02—Heterocyclic 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
- C07D405/12—Heterocyclic 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 chain containing hetero atoms as chain links
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic 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
- A61K31/352—Heterocyclic 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
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
-
- 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
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
Claims (12)
- 下記化学式1で表される化合物のピドレート塩又はマレート塩(リンゴ酸塩)。
[化1]
- 前記ピドレート塩は、下記化学式2で表される、請求項1に記載の塩。
[化2]
- 前記マレート塩(リンゴ酸塩)は、下記化学式3で表される、請求項1に記載の塩。
[化3]
- 前記塩は非晶質である、請求項1に記載の塩。
- 請求項1ないし請求項4のいずれか1項に記載の塩を含む、アシッドポンプ拮抗活性により媒介される疾患の予防又は治療用薬学組成物。
- 前記アシッドポンプ拮抗活性により媒介される疾患は、胃食道疾患、胃食道逆流症(GERD)、消化性潰瘍、胃潰瘍、十二指膓潰瘍、NSAIDにより誘導される潰瘍、胃炎、ヘリコバクターピロリ感染症(Helicobacter pylori infection)、消化不良、機能性消化不良、ゾリンジャー−エリソン症侯群(Zollinger−Ellison syndrome)、非びらん性胃食道逆流症(NERD)、内臓痛、胸やけ、悪心、食道炎、嚥下困難、唾液分泌、気道障害、及び喘息を含む群より選択されるいずれか1つである、請求項5に記載の薬学組成物。
- 前記組成物の剤形は、散剤、顆粒剤、錠剤、カプセル剤、懸濁液、エマルジョン、シロップ、エアロゾル、軟膏、クリーム、坐剤、及び注射剤からなる群より選択されるいずれか1つである、請求項5に記載の薬学組成物。
- a)下記化学式1で表される化合物と、ピログルタミン酸又はリンゴ酸を有機溶媒に溶解させるステップ、
b)前記a)ステップで製造された溶液を減圧濃縮して固体を析出させた後、共溶媒(Co−solvent)を加えて撹拌するステップ、及び
c)析出された固体を濾過、乾燥するステップを含む、請求項1に記載の塩の製造方法。
[化1]
- 前記ステップa)の有機溶媒は、メタノールであり、前記化学式1で表される化合物に対して10(体積/重量)倍添加される、請求項8に記載の塩の製造方法。
- 前記ステップb)の共溶媒(Co−solvent)は、アセトンとエチルアセテートの混合溶媒であり、前記化学式1で表される化合物に対して5(体積/重量)倍添加される、請求項8に記載の塩の製造方法。
- 前記共溶媒の割合は、アセトン:エチルアセテート=1:4(v/v)である、請求項10に記載の塩の製造方法。
- アシッドポンプ拮抗活性により媒介される疾患の治療のための薬剤の製造において、請求項1ないし請求項4のいずれか一項に記載の化学式1で表される化合物のピドレート塩又はマレート塩(リンゴ酸塩)の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2016-0120996 | 2016-09-21 | ||
KR1020160120996A KR101829706B1 (ko) | 2016-09-21 | 2016-09-21 | 벤즈이미다졸 유도체의 산부가염 |
PCT/KR2017/010332 WO2018056697A1 (ko) | 2016-09-21 | 2017-09-20 | 벤즈이미다졸 유도체의 산부가염 |
Publications (2)
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EP (1) | EP3517528B1 (ja) |
JP (1) | JP6814891B2 (ja) |
KR (1) | KR101829706B1 (ja) |
CN (1) | CN109769392B (ja) |
AR (1) | AR109679A1 (ja) |
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JO (1) | JOP20170172B1 (ja) |
MX (1) | MX2019003171A (ja) |
MY (1) | MY197242A (ja) |
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KR20200024413A (ko) * | 2018-08-28 | 2020-03-09 | 에이치케이이노엔 주식회사 | 항혈소판제와 산 분비 억제제를 포함하는 약학 조성물 |
JOP20190201A1 (ar) * | 2018-08-29 | 2020-02-29 | Hk Inno N Corp | تركيبة لاستئصال الملوية البوابية |
EP3927340A4 (en) * | 2019-02-18 | 2022-11-02 | HK inno.N Corporation | PHARMACEUTICAL COMPOSITION WITH BENZIMIDAZOLE DERIVATIVE COMPOUND |
CA3182245A1 (en) * | 2020-06-12 | 2021-12-16 | Jae Hee Cheon | Pharmaceutical composition comprising benzimidazole derivative compound |
WO2022086238A1 (en) * | 2020-10-23 | 2022-04-28 | Hk Inno.N Corporation | Orally disintegrating tablet comprising benzimidazole derivative compound and preparation method thereof |
TWI822151B (zh) * | 2021-07-02 | 2023-11-11 | 南韓商Lg化學股份有限公司 | 製備黃嘌呤氧化酶抑制劑的方法 |
WO2023106842A1 (ko) * | 2021-12-08 | 2023-06-15 | (주) 팜젠사이언스 | 벤즈이미다졸 유도체 화합물 및 이의 용도 |
KR20230114163A (ko) | 2022-01-24 | 2023-08-01 | 엠에프씨 주식회사 | 칼륨 경쟁적 위산분비억제제 계열 약물의 신규한 무정형 고체분산체 및 그의 제조방법 |
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WO2005042485A1 (en) * | 2003-10-30 | 2005-05-12 | Sk Chemicals, Co., Ltd. | Acid added salts of amlodipine |
EP1695973A1 (en) * | 2005-02-24 | 2006-08-30 | Neuro3D | Ocaperidone salt and pharmaceutical compositions containing the same |
ATE442140T1 (de) | 2005-06-14 | 2009-09-15 | Raqualia Pharma Inc | Chroman-substituierte benzimidazolderivate als säurepumpenantagonisten |
EP1963311B1 (en) * | 2005-12-19 | 2010-06-16 | RaQualia Pharma Inc | Chromane substituted benzimidazoles and their use as acid pump inhibitors |
EP2318411A2 (en) | 2008-07-03 | 2011-05-11 | Ratiopharm GmbH | Crystalline salts of sitagliptin |
TW201920110A (zh) * | 2009-01-16 | 2019-06-01 | 美商艾克塞里克斯公司 | 包含n-(4-{[6,7-雙(甲氧基)喹啉-4-基]氧基}苯基)-n'-(4-氟苯基)環丙烷-1,1-二甲醯胺之蘋果酸鹽之醫藥組合物及其用途 |
KR101605063B1 (ko) | 2009-07-09 | 2016-03-21 | 라퀄리아 파마 인코포레이티드 | 소화관 운동이상이 관여하는 질환의 치료용 산 펌프 길항제 |
KR101684053B1 (ko) | 2015-01-20 | 2016-12-08 | 씨제이헬스케어 주식회사 | 벤즈이미다졸 유도체의 신규 결정형 및 이의 제조방법 |
KR102262743B1 (ko) | 2017-07-07 | 2021-06-09 | 에이치케이이노엔 주식회사 | 주사용 조성물 |
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KR101829706B1 (ko) | 2018-02-19 |
US11535610B2 (en) | 2022-12-27 |
CN109769392B (zh) | 2022-06-24 |
US20230192670A1 (en) | 2023-06-22 |
TWI659028B (zh) | 2019-05-11 |
JOP20170172B1 (ar) | 2022-03-14 |
EP3517528A1 (en) | 2019-07-31 |
MX2019003171A (es) | 2019-06-10 |
TW201815786A (zh) | 2018-05-01 |
BR112019005505A2 (pt) | 2019-06-04 |
ES2896802T3 (es) | 2022-02-25 |
US20240150331A1 (en) | 2024-05-09 |
MY197242A (en) | 2023-06-07 |
EP3517528A4 (en) | 2020-05-20 |
WO2018056697A1 (ko) | 2018-03-29 |
JOP20170172A1 (ar) | 2019-01-30 |
JP2019529557A (ja) | 2019-10-17 |
US20210292307A1 (en) | 2021-09-23 |
AR109679A1 (es) | 2019-01-09 |
CN109769392A (zh) | 2019-05-17 |
PH12019500602A1 (en) | 2019-11-11 |
US11912690B2 (en) | 2024-02-27 |
EP3517528B1 (en) | 2021-09-01 |
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