JP6461922B2 - アミロイド線維形成の抑制又は阻害剤 - Google Patents
アミロイド線維形成の抑制又は阻害剤 Download PDFInfo
- Publication number
- JP6461922B2 JP6461922B2 JP2016514694A JP2016514694A JP6461922B2 JP 6461922 B2 JP6461922 B2 JP 6461922B2 JP 2016514694 A JP2016514694 A JP 2016514694A JP 2016514694 A JP2016514694 A JP 2016514694A JP 6461922 B2 JP6461922 B2 JP 6461922B2
- Authority
- JP
- Japan
- Prior art keywords
- amyloid
- inhibitor
- amyloidosis
- tranilast
- dementia
- 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.)
- Active
Links
- 239000003112 inhibitor Substances 0.000 title description 36
- 230000003941 amyloidogenesis Effects 0.000 title description 31
- NZHGWWWHIYHZNX-CSKARUKUSA-N tranilast Chemical compound C1=C(OC)C(OC)=CC=C1\C=C\C(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-CSKARUKUSA-N 0.000 claims description 50
- 229960005342 tranilast Drugs 0.000 claims description 50
- 206010002022 amyloidosis Diseases 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 29
- 229940124597 therapeutic agent Drugs 0.000 claims description 26
- 230000003449 preventive effect Effects 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 14
- 208000015413 lichen amyloidosis Diseases 0.000 claims description 10
- 206010011659 Cutaneous amyloidosis Diseases 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 7
- 230000000069 prophylactic effect Effects 0.000 claims description 5
- 239000002674 ointment Substances 0.000 claims description 4
- HHJIUUAMYGBVSD-YTFFSALGSA-N Diflucortolone valerate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@H](C(=O)COC(=O)CCCC)[C@@]2(C)C[C@@H]1O HHJIUUAMYGBVSD-YTFFSALGSA-N 0.000 claims 1
- 102000001049 Amyloid Human genes 0.000 description 40
- 108010094108 Amyloid Proteins 0.000 description 40
- 206010012289 Dementia Diseases 0.000 description 24
- 201000010099 disease Diseases 0.000 description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- 208000037259 Amyloid Plaque Diseases 0.000 description 23
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 17
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 17
- 230000009471 action Effects 0.000 description 15
- 230000008021 deposition Effects 0.000 description 15
- 210000001519 tissue Anatomy 0.000 description 14
- 210000004556 brain Anatomy 0.000 description 13
- 239000000835 fiber Substances 0.000 description 9
- 230000006872 improvement Effects 0.000 description 9
- 239000002775 capsule Substances 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 210000000056 organ Anatomy 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 208000024827 Alzheimer disease Diseases 0.000 description 6
- 230000002776 aggregation Effects 0.000 description 6
- 238000004220 aggregation Methods 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000000314 lubricant Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 4
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 4
- 206010012438 Dermatitis atopic Diseases 0.000 description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 201000008937 atopic dermatitis Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000029142 excretion Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 206010037844 rash Diseases 0.000 description 4
- 208000010201 Exanthema Diseases 0.000 description 3
- 206010033733 Papule Diseases 0.000 description 3
- 208000012641 Pigmentation disease Diseases 0.000 description 3
- 208000003251 Pruritus Diseases 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000007599 discharging Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 201000005884 exanthem Diseases 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 210000000944 nerve tissue Anatomy 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 230000019612 pigmentation Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- ZQAQXZBSGZUUNL-BJUDXGSMSA-N 2-[4-(methylamino)phenyl]-1,3-benzothiazol-6-ol Chemical compound C1=CC(N[11CH3])=CC=C1C1=NC2=CC=C(O)C=C2S1 ZQAQXZBSGZUUNL-BJUDXGSMSA-N 0.000 description 2
- 208000023769 AA amyloidosis Diseases 0.000 description 2
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 2
- 201000010374 Down Syndrome Diseases 0.000 description 2
- 208000034846 Familial Amyloid Neuropathies Diseases 0.000 description 2
- 206010016207 Familial Mediterranean fever Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 108010076876 Keratins Proteins 0.000 description 2
- 102000011782 Keratins Human genes 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 201000002832 Lewy body dementia Diseases 0.000 description 2
- 208000001089 Multiple system atrophy Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 102000029797 Prion Human genes 0.000 description 2
- 108091000054 Prion Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 102000003802 alpha-Synuclein Human genes 0.000 description 2
- 108090000185 alpha-Synuclein Proteins 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 239000001058 brown pigment Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 2
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000000593 degrading effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- -1 huntingtin Proteins 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000004768 organ dysfunction Effects 0.000 description 2
- 239000006174 pH buffer Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001515 polyalkylene glycol Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000004215 skin function Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 229920002677 supramolecular polymer Polymers 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000009092 tissue dysfunction Effects 0.000 description 2
- 238000003325 tomography Methods 0.000 description 2
- 201000007905 transthyretin amyloidosis Diseases 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- BXVVYPVVDLGLPF-UHFFFAOYSA-N 1-hexadecyl-1-methylpiperidin-1-ium Chemical compound CCCCCCCCCCCCCCCC[N+]1(C)CCCCC1 BXVVYPVVDLGLPF-UHFFFAOYSA-N 0.000 description 1
- NZHGWWWHIYHZNX-UHFFFAOYSA-N 2-((3-(3,4-dimethoxyphenyl)-1-oxo-2-propenyl)amino)benzoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C=CC(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-UHFFFAOYSA-N 0.000 description 1
- AAALVYBICLMAMA-UHFFFAOYSA-N 4,5-dianilinophthalimide Chemical compound C=1C=CC=CC=1NC=1C=C2C(=O)NC(=O)C2=CC=1NC1=CC=CC=C1 AAALVYBICLMAMA-UHFFFAOYSA-N 0.000 description 1
- 208000020687 AH amyloidosis Diseases 0.000 description 1
- 208000023761 AL amyloidosis Diseases 0.000 description 1
- 102100022524 Alpha-1-antichymotrypsin Human genes 0.000 description 1
- 102000005666 Apolipoprotein A-I Human genes 0.000 description 1
- 108010059886 Apolipoprotein A-I Proteins 0.000 description 1
- 102000002723 Atrial Natriuretic Factor Human genes 0.000 description 1
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 1
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 102000012192 Cystatin C Human genes 0.000 description 1
- 108010061642 Cystatin C Proteins 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010064553 Dialysis amyloidosis Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 206010016202 Familial Amyloidosis Diseases 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 102000004878 Gelsolin Human genes 0.000 description 1
- 108090001064 Gelsolin Proteins 0.000 description 1
- 206010019889 Hereditary neuropathic amyloidosis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 208000005531 Immunoglobulin Light-chain Amyloidosis Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
- 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000009018 Medullary thyroid cancer Diseases 0.000 description 1
- 208000003351 Melanosis Diseases 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 201000002795 Muckle-Wells syndrome Diseases 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 101001034830 Mus musculus Interferon-induced transmembrane protein 5 Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 102100037591 Neuroserpin Human genes 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010071690 Prealbumin Proteins 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010039811 Secondary amyloidosis Diseases 0.000 description 1
- 108700028909 Serum Amyloid A Proteins 0.000 description 1
- 102000054727 Serum Amyloid A Human genes 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 102100029290 Transthyretin Human genes 0.000 description 1
- 206010044688 Trisomy 21 Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 108010091628 alpha 1-Antichymotrypsin Proteins 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 1
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 description 1
- 235000012754 curcumin Nutrition 0.000 description 1
- 229940109262 curcumin Drugs 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- BTIJJDXEELBZFS-QDUVMHSLSA-K hemin Chemical compound CC1=C(CCC(O)=O)C(C=C2C(CCC(O)=O)=C(C)\C(N2[Fe](Cl)N23)=C\4)=N\C1=C/C2=C(C)C(C=C)=C3\C=C/1C(C)=C(C=C)C/4=N\1 BTIJJDXEELBZFS-QDUVMHSLSA-K 0.000 description 1
- 229940025294 hemin Drugs 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 206010022498 insulinoma Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 108010080874 neuroserpin Proteins 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 208000021255 pancreatic insulinoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 208000008864 scrapie Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 102000013498 tau Proteins Human genes 0.000 description 1
- 108010026424 tau Proteins Proteins 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
1−1 症例1
上背部に皮膚アミロイドーシス特有の色素を伴う浸潤とそう痒の症状が認められる患者(N.Y、60歳、女性)は、当初トラニラストを含まない治療を4年間行っていたが、治療効果が全く認められなかった。このため、トラニラストによる治療に移行した。上記患者に対して、トラニラスト(商品名:リザベン、キッセイ薬品工業社製)100mgのカプセルを1日当たり3回経口投与したところ、経口投与を開始して約1カ月後から色素沈着が薄くなり始め、さらに1カ月後にかけて色素沈着レベルが段階的に減少するとともに、そう痒が減弱し、皮疹が大幅に改善することが示された。その後、少なくとも3年間皮疹の悪化又は再発は認められなかった。
上背部に典型的なアミロイド苔癬の症状が認められる患者(27歳、女性、幼少時にアトピー性皮膚炎発症)は、当初「Very Strong:II群」に分類されるステロイド外用剤であるジフルプレナート軟膏(マイザー軟膏)による治療を行っていたが、改善が認められなかった。このため、トラニラストによる治療に移行した。上記患者に対して、トラニラスト(商品名:リザベン、キッセイ薬品工業社製)100mgのカプセルを1日当たり3回経口投与したところ、2014年6月30日に経口投与を開始(図1A参照)して16日目(2014年7月16日)(図1B参照)からアミロイド沈着褐色丘疹は明らかに薄く小さくなり改善した。日を追うごとに皮疹の改善度合いは増し(図1C〜E参照)、経口投与を開始して151日目(2014年11月28日)(図1F参照)にアミロイド沈着褐色丘疹はほぼ消失し、少なくとも238日目(2015年2月23日)(図1H参照)までその状態は維持された。
数年来上背部に激しい掻痒(そうよう)を伴う発疹があり、慢性湿疹が認められる患者(23歳、女性)に対して、トラニラストによる治療を開始した。かかる患者に、トラニラスト(商品名:リザベン、キッセイ薬品工業社製)100mgのカプセルを1日当たり3回経口投与したところ、2014年7月29日に経口投与を開始したときはアミロイド沈着褐色丘疹が密に苔癬化していた(図2A参照)が、経口投与開始後15日目(2014年8月13日)(図2B参照)には症状の改善が認められた。さらに、経口投与開始後29日目(2014年8月27日)(図2C参照)には明らかな症状の改善が認められ、その後、少なくとも89日目(2014年10月26日)までは改善状態が維持された(図2D〜G参照)。
トラニラストが、皮膚におけるアミロイド線維形成を抑制する作用を有することが示されたので、脳におけるアミロイド線維の沈着に起因する認知症やアルツハイマー病についても改善できるかどうか検討した。
認知症患者(H.Y、79歳、男性)に対して、トラニラスト(商品名:リザベン、キッセイ薬品工業社製)100mgのカプセルを1日当たり3回経口投与した。2012年8月にトラニラストによる投与を開始してから1年4カ月後に、2種類の認知症の検査法(HDS−R[改訂長谷川式簡易知能評価スケール]及びMMSE[認知機能検査])により、明確な改善効果が認められた(表1参照)。
アルツハイマー病患者(88歳、男性)に対して、トラニラスト(商品名:リザベン、キッセイ薬品工業社製)100mgのカプセルを1日当たり3回経口投与した。2014年10月11日にトラニラストによる投与を開始してから約5カ月後に、2種類の認知症の検査法(HDS−R及びMMSE)により、アルツハイマー型認知症の症状の明確な改善効果が認められた(表2参照)。
ある組織に長期間持続的に消耗状態が存在する場合、例えばアトピー性皮膚炎のような消耗性疾患に長期間罹患するとアミロイド線維が皮膚に沈着し難治性の皮膚アミロイド苔癬となることは従来から知られている。従来治療により症状の改善が認められなかった皮膚アミロイド苔癬患者やアルツハイマー型認知症等の認知症患者に対して、トラニラストを全身投与すると、トラニラストが効果的に皮膚や海馬の脳組織に沈着したアミロイド線維を減少させるように作用したものと考えられる。すなわち、トラニラストによる治療は、脳組織でも有効であることから、トラニラストは脳血管関門を通過したと考えられる。
Claims (2)
- トラニラスト又はその薬理学的に許容される塩を有効成分として含有することを特徴とする皮膚アミロイドーシスの予防又は治療剤(但し、テクスメテン軟膏及びウレパール軟膏の混合薬と併用する場合を除く)。
- 皮膚アミロイドーシスが皮膚アミロイド苔癬であることを特徴とする請求項1に記載の予防又は治療剤。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2018215533A JP6907174B2 (ja) | 2014-04-24 | 2018-11-16 | アミロイド線維形成の抑制又は阻害剤 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2014090476 | 2014-04-24 | ||
JP2014090476 | 2014-04-24 | ||
PCT/JP2015/002067 WO2015162870A1 (ja) | 2014-04-24 | 2015-04-14 | アミロイド線維形成の抑制又は阻害剤 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018215533A Division JP6907174B2 (ja) | 2014-04-24 | 2018-11-16 | アミロイド線維形成の抑制又は阻害剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2015162870A1 JPWO2015162870A1 (ja) | 2017-04-13 |
JP6461922B2 true JP6461922B2 (ja) | 2019-01-30 |
Family
ID=54332051
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016514694A Active JP6461922B2 (ja) | 2014-04-24 | 2015-04-14 | アミロイド線維形成の抑制又は阻害剤 |
JP2018215533A Active JP6907174B2 (ja) | 2014-04-24 | 2018-11-16 | アミロイド線維形成の抑制又は阻害剤 |
JP2021072080A Pending JP2021105061A (ja) | 2014-04-24 | 2021-04-21 | アミロイド線維形成の抑制又は阻害剤 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018215533A Active JP6907174B2 (ja) | 2014-04-24 | 2018-11-16 | アミロイド線維形成の抑制又は阻害剤 |
JP2021072080A Pending JP2021105061A (ja) | 2014-04-24 | 2021-04-21 | アミロイド線維形成の抑制又は阻害剤 |
Country Status (4)
Country | Link |
---|---|
US (2) | US11844774B2 (ja) |
EP (2) | EP4039255A1 (ja) |
JP (3) | JP6461922B2 (ja) |
WO (1) | WO2015162870A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11844774B2 (en) * | 2014-04-24 | 2023-12-19 | Omoidesouzou Co., Ltd. | Amyloid fiber formation limiter or inhibitor |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2244679C (en) | 1996-02-07 | 2007-08-07 | Lead Chemical Co., Ltd. | Tranilast-containing preparation for external application and method of producing the same |
WO1998006403A1 (en) | 1996-08-13 | 1998-02-19 | P.N. Gerolymatos S.A. | Use of the chelating agent clioquinol for the manufacture of a pharmaceutical composition for the treatment of alzheimer's disease |
BRPI0113470B8 (pt) | 2000-08-24 | 2021-05-25 | Univ Pittsburgh | composto de ligação amilóide, composição farmacêutica e métodos de síntese de composto, de detecção in vivo de depósitos amilóides num indivíduo e em tecido humano ou animal, de quantificação de depósito amilóide em tecido de biópsia ou postmortem e de distinção de um cérebro de doença de alzheimer de um cérebro normal |
US7531575B2 (en) | 2002-10-31 | 2009-05-12 | Eberhard-Karls-Universität Tübingin | Method of modulating cellular activity and agents useful for same |
EP2030617A1 (en) | 2007-08-17 | 2009-03-04 | Sygnis Bioscience GmbH & Co. KG | Use of tranilast and derivatives thereof for the therapy of neurological conditions |
JP2009120607A (ja) | 2007-10-25 | 2009-06-04 | Kanazawa Univ | 新規な肝疾患の予防又は治療薬並びにインスリン抵抗性改善剤 |
US20100160351A1 (en) * | 2008-12-19 | 2010-06-24 | Nuon Therapeutics, Inc. | Pharmaceutical compositions and methods for treating hyperuricemia and related disorders |
US11844774B2 (en) * | 2014-04-24 | 2023-12-19 | Omoidesouzou Co., Ltd. | Amyloid fiber formation limiter or inhibitor |
-
2015
- 2015-04-14 US US15/305,114 patent/US11844774B2/en active Active
- 2015-04-14 JP JP2016514694A patent/JP6461922B2/ja active Active
- 2015-04-14 EP EP22163941.2A patent/EP4039255A1/en active Pending
- 2015-04-14 EP EP15782806.2A patent/EP3135280B1/en active Active
- 2015-04-14 WO PCT/JP2015/002067 patent/WO2015162870A1/ja active Application Filing
-
2018
- 2018-11-16 JP JP2018215533A patent/JP6907174B2/ja active Active
-
2021
- 2021-02-19 US US17/179,462 patent/US11723889B2/en active Active
- 2021-04-21 JP JP2021072080A patent/JP2021105061A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
US20210169834A1 (en) | 2021-06-10 |
JP2021105061A (ja) | 2021-07-26 |
JP2019023235A (ja) | 2019-02-14 |
US20170035717A1 (en) | 2017-02-09 |
EP4039255A1 (en) | 2022-08-10 |
EP3135280A4 (en) | 2017-10-04 |
US11723889B2 (en) | 2023-08-15 |
EP3135280B1 (en) | 2023-09-20 |
EP3135280A1 (en) | 2017-03-01 |
JP6907174B2 (ja) | 2021-07-21 |
WO2015162870A1 (ja) | 2015-10-29 |
US11844774B2 (en) | 2023-12-19 |
JPWO2015162870A1 (ja) | 2017-04-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11980616B2 (en) | Treating liver disease by selectively eliminating senescent cells | |
US20200338097A1 (en) | Use of a heterocyclic bcl-2 inhibitor for removing senescent cells and treating senescence-associated conditions | |
US10583125B2 (en) | Method for treating neurodegenerative diseases | |
KR20080043763A (ko) | 염증성 상태의 치료 | |
US10016409B2 (en) | Method for improving interstitial flow | |
Palhegyi et al. | Biomedical implications of autophagy in macromolecule storage disorders | |
KR20050042154A (ko) | 통증의 치료에 사용하기 위한 알파-2-델타 리간드와 pdev 억제제의 상승작용 조합물 | |
KR20190019171A (ko) | 섬유증 치료에서 사용하기 위한 wnt 억제제 | |
EP2444078B1 (en) | Use of amides of mono and dicarboxylic acids in the treatment of renal diseases | |
JP6907174B2 (ja) | アミロイド線維形成の抑制又は阻害剤 | |
KR102536917B1 (ko) | 메나퀴논-7을 유효성분으로 포함하는 퇴행성 신경질환 치료 또는 예방용 조성물 | |
EP3010532A1 (en) | Materials for positive cathepsin b modulation and methods of use for treating mild cognitive impairment (mci), early dementia, a-synucleinopathy, traumatic brain injury, cardiomyopathy, eye disease and skin damage |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180328 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180612 |
|
A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20180612 |
|
A975 | Report on accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A971005 Effective date: 20180620 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180705 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180822 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20180904 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181116 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20181116 |
|
C876 | Explanation why request for accelerated appeal examination is justified |
Free format text: JAPANESE INTERMEDIATE CODE: C876 Effective date: 20181116 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20181130 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20181203 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20181210 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20181226 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6461922 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |