RU2317086C2 - Лечение неврологической дисфункции с применением сульфаматов фруктопиранозы и эритропоэтина - Google Patents
Лечение неврологической дисфункции с применением сульфаматов фруктопиранозы и эритропоэтина Download PDFInfo
- Publication number
- RU2317086C2 RU2317086C2 RU2003124059/14A RU2003124059A RU2317086C2 RU 2317086 C2 RU2317086 C2 RU 2317086C2 RU 2003124059/14 A RU2003124059/14 A RU 2003124059/14A RU 2003124059 A RU2003124059 A RU 2003124059A RU 2317086 C2 RU2317086 C2 RU 2317086C2
- Authority
- RU
- Russia
- Prior art keywords
- erythropoietin
- topiramate
- treatment
- disease
- fructopyranose
- Prior art date
Links
- 102000003951 Erythropoietin Human genes 0.000 title claims abstract description 108
- 108090000394 Erythropoietin Proteins 0.000 title claims abstract description 108
- 229940105423 erythropoietin Drugs 0.000 title claims abstract description 108
- 238000011282 treatment Methods 0.000 title description 50
- LKDRXBCSQODPBY-VRPWFDPXSA-N D-fructopyranose Chemical compound OCC1(O)OC[C@@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-VRPWFDPXSA-N 0.000 title description 38
- -1 erythropoietin sulfamates Chemical class 0.000 title description 31
- 230000009251 neurologic dysfunction Effects 0.000 title description 6
- 208000015015 neurological dysfunction Diseases 0.000 title description 6
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims abstract description 111
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 claims abstract description 66
- 229960004394 topiramate Drugs 0.000 claims abstract description 65
- 230000014511 neuron projection development Effects 0.000 claims abstract description 26
- 239000003937 drug carrier Substances 0.000 claims abstract description 10
- 230000000638 stimulation Effects 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 39
- 230000002195 synergetic effect Effects 0.000 claims description 22
- 238000004113 cell culture Methods 0.000 claims description 17
- 210000002569 neuron Anatomy 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 230000000694 effects Effects 0.000 abstract description 18
- 239000000203 mixture Substances 0.000 abstract description 18
- 239000003814 drug Substances 0.000 abstract description 17
- 239000000126 substance Substances 0.000 abstract description 3
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 50
- 150000001875 compounds Chemical class 0.000 description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 35
- 201000010099 disease Diseases 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 23
- 241000700159 Rattus Species 0.000 description 22
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 20
- 230000000926 neurological effect Effects 0.000 description 20
- 239000002953 phosphate buffered saline Substances 0.000 description 20
- 208000015122 neurodegenerative disease Diseases 0.000 description 19
- 230000006378 damage Effects 0.000 description 16
- 206010010904 Convulsion Diseases 0.000 description 14
- 206010012289 Dementia Diseases 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- 201000001119 neuropathy Diseases 0.000 description 14
- 230000007823 neuropathy Effects 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 230000001684 chronic effect Effects 0.000 description 12
- 239000003085 diluting agent Substances 0.000 description 12
- 230000001154 acute effect Effects 0.000 description 11
- 238000002648 combination therapy Methods 0.000 description 11
- 230000001054 cortical effect Effects 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 208000000044 Amnesia Diseases 0.000 description 9
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 description 9
- 208000026139 Memory disease Diseases 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 208000029028 brain injury Diseases 0.000 description 9
- 230000001037 epileptic effect Effects 0.000 description 9
- 102000044890 human EPO Human genes 0.000 description 9
- 230000002093 peripheral effect Effects 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 208000019901 Anxiety disease Diseases 0.000 description 8
- 101000920686 Homo sapiens Erythropoietin Proteins 0.000 description 8
- 206010021143 Hypoxia Diseases 0.000 description 8
- 208000008457 Neurologic Manifestations Diseases 0.000 description 8
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 8
- 230000036506 anxiety Effects 0.000 description 8
- 206010008118 cerebral infarction Diseases 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000000971 hippocampal effect Effects 0.000 description 8
- 230000001771 impaired effect Effects 0.000 description 8
- 230000006984 memory degeneration Effects 0.000 description 8
- 208000023060 memory loss Diseases 0.000 description 8
- 230000002265 prevention Effects 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 235000002639 sodium chloride Nutrition 0.000 description 8
- 208000024827 Alzheimer disease Diseases 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 108010074604 Epoetin Alfa Proteins 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- 208000026106 cerebrovascular disease Diseases 0.000 description 7
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
- 206010015037 epilepsy Diseases 0.000 description 7
- 230000012010 growth Effects 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 230000007954 hypoxia Effects 0.000 description 7
- 230000003340 mental effect Effects 0.000 description 7
- 210000002241 neurite Anatomy 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229940098773 bovine serum albumin Drugs 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 230000003923 mental ability Effects 0.000 description 6
- 230000000324 neuroprotective effect Effects 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 230000004936 stimulating effect Effects 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 102100036509 Erythropoietin receptor Human genes 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000012981 Hank's balanced salt solution Substances 0.000 description 5
- 208000028017 Psychotic disease Diseases 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 208000007502 anemia Diseases 0.000 description 5
- 230000006931 brain damage Effects 0.000 description 5
- 231100000874 brain damage Toxicity 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 210000003618 cortical neuron Anatomy 0.000 description 5
- 230000007850 degeneration Effects 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 208000028867 ischemia Diseases 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 210000000653 nervous system Anatomy 0.000 description 5
- 230000007604 neuronal communication Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 201000006474 Brain Ischemia Diseases 0.000 description 4
- 206010008120 Cerebral ischaemia Diseases 0.000 description 4
- 108010075944 Erythropoietin Receptors Proteins 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 208000027747 Kennedy disease Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 108090000192 Methionyl aminopeptidases Proteins 0.000 description 4
- 102100021118 Microtubule-associated protein 2 Human genes 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- 208000010877 cognitive disease Diseases 0.000 description 4
- 230000003920 cognitive function Effects 0.000 description 4
- 238000011262 co‐therapy Methods 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 239000012737 fresh medium Substances 0.000 description 4
- 230000002489 hematologic effect Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000007917 intracranial administration Methods 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
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 208000020431 spinal cord injury Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 206010058842 Cerebrovascular insufficiency Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
- 208000028698 Cognitive impairment Diseases 0.000 description 3
- 108010019673 Darbepoetin alfa Proteins 0.000 description 3
- 206010012218 Delirium Diseases 0.000 description 3
- 208000010496 Heart Arrest Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001413 amino acids Chemical group 0.000 description 3
- 239000001961 anticonvulsive agent Substances 0.000 description 3
- 210000001130 astrocyte Anatomy 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- XTHPWXDJESJLNJ-UHFFFAOYSA-M chlorosulfate Chemical compound [O-]S(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-M 0.000 description 3
- 230000003930 cognitive ability Effects 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 210000002257 embryonic structure Anatomy 0.000 description 3
- 230000002124 endocrine Effects 0.000 description 3
- 229960003388 epoetin alfa Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 206010022437 insomnia Diseases 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 210000003657 middle cerebral artery Anatomy 0.000 description 3
- 208000005264 motor neuron disease Diseases 0.000 description 3
- 210000000944 nerve tissue Anatomy 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 230000002685 pulmonary effect Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000000946 synaptic effect Effects 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 206010003062 Apraxia Diseases 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- 206010061666 Autonomic neuropathy Diseases 0.000 description 2
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 description 2
- 206010006542 Bulbar palsy Diseases 0.000 description 2
- 208000029402 Bulbospinal muscular atrophy Diseases 0.000 description 2
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 2
- 208000033647 Classic progressive supranuclear palsy syndrome Diseases 0.000 description 2
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 2
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 2
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 2
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 2
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 206010033885 Paraparesis Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 2
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 2
- 208000024777 Prion disease Diseases 0.000 description 2
- 206010037180 Psychiatric symptoms Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000021811 Sandhoff disease Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 208000002548 Spastic Paraparesis Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 2
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 2
- 208000032859 Synucleinopathies Diseases 0.000 description 2
- 208000022292 Tay-Sachs disease Diseases 0.000 description 2
- 208000000323 Tourette Syndrome Diseases 0.000 description 2
- 208000016620 Tourette disease Diseases 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 2
- 201000004810 Vascular dementia Diseases 0.000 description 2
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 210000003710 cerebral cortex Anatomy 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 201000005108 complex partial epilepsy Diseases 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 210000001787 dendrite Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000003073 embolic effect Effects 0.000 description 2
- 239000012055 enteric layer Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000003631 expected effect Effects 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000005021 gait Effects 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
- 230000035784 germination Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000001631 haemodialysis Methods 0.000 description 2
- 230000000322 hemodialysis Effects 0.000 description 2
- 208000008675 hereditary spastic paraplegia Diseases 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 210000004295 hippocampal neuron Anatomy 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000000185 intracerebroventricular administration Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 238000007914 intraventricular administration Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 201000010901 lateral sclerosis Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000007087 memory ability Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 230000000508 neurotrophic effect Effects 0.000 description 2
- 230000009984 peri-natal effect Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 208000001282 primary progressive aphasia Diseases 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 229940029359 procrit Drugs 0.000 description 2
- 208000032207 progressive 1 supranuclear palsy Diseases 0.000 description 2
- 201000002241 progressive bulbar palsy Diseases 0.000 description 2
- 201000000196 pseudobulbar palsy Diseases 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000010410 reperfusion Effects 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 230000001148 spastic effect Effects 0.000 description 2
- 208000002320 spinal muscular atrophy Diseases 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- WJXREUZUPGMAII-UHFFFAOYSA-N sulfurazidic acid Chemical compound OS(=O)(=O)N=[N+]=[N-] WJXREUZUPGMAII-UHFFFAOYSA-N 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000001732 thrombotic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 2
- 229960002555 zidovudine Drugs 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- CRYXXTXWUCPIMU-WNQIDUERSA-N (2s)-2-aminobutanediamide;phenol Chemical compound OC1=CC=CC=C1.NC(=O)[C@@H](N)CC(N)=O CRYXXTXWUCPIMU-WNQIDUERSA-N 0.000 description 1
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 1
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 201000011452 Adrenoleukodystrophy Diseases 0.000 description 1
- 208000018126 Adrenomyeloneuropathy Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 206010001488 Aggression Diseases 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002942 Apathy Diseases 0.000 description 1
- 206010003594 Ataxia telangiectasia Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 0 CC1C(*)C(*)(*)*CC1* Chemical compound CC1C(*)C(*)(*)*CC1* 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 206010057645 Chronic Inflammatory Demyelinating Polyradiculoneuropathy Diseases 0.000 description 1
- 208000004051 Chronic Traumatic Encephalopathy Diseases 0.000 description 1
- 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000019736 Cranial nerve disease Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 206010013954 Dysphoria Diseases 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 101710102442 Erythropoietin receptor Proteins 0.000 description 1
- 241001539473 Euphoria Species 0.000 description 1
- 206010015535 Euphoric mood Diseases 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 208000001730 Familial dysautonomia Diseases 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 208000024412 Friedreich ataxia Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102100032610 Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010018985 Haemorrhage intracranial Diseases 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 208000019897 Holoprosencephaly-craniosynostosis syndrome Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 208000008574 Intracranial Hemorrhages Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 208000034693 Laceration Diseases 0.000 description 1
- 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 1
- 208000010000 Lambert syndrome Diseases 0.000 description 1
- 208000034800 Leukoencephalopathies Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010027374 Mental impairment Diseases 0.000 description 1
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 206010034620 Peripheral sensory neuropathy Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 208000005587 Refsum Disease Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 201000001638 Riley-Day syndrome Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 208000018359 Systemic autoimmune disease Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 206010043395 Thalassaemia sickle cell Diseases 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 206010063661 Vascular encephalopathy Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- PSSHGMIAIUYOJF-XBWDGYHZSA-N [(3as,5ar,8ar,8bs)-2,2,7,7-tetramethyl-5,5a,8a,8b-tetrahydrodi[1,3]dioxolo[4,5-a:5',3'-d]pyran-3a-yl]methanol Chemical compound C1O[C@@]2(CO)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 PSSHGMIAIUYOJF-XBWDGYHZSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000011360 adjunctive therapy Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 208000030597 adult Refsum disease Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 125000002009 alkene group Chemical group 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229940115115 aranesp Drugs 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 229940090047 auto-injector Drugs 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- YUMNNMSNSLHINV-UHFFFAOYSA-N chloro sulfamate Chemical compound NS(=O)(=O)OCl YUMNNMSNSLHINV-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 208000014826 cranial nerve neuropathy Diseases 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 208000017004 dementia pugilistica Diseases 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000010102 embolization Effects 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 210000002375 erythropoietic cell Anatomy 0.000 description 1
- 230000000913 erythropoietic effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 210000000256 facial nerve Anatomy 0.000 description 1
- 201000006061 fatal familial insomnia Diseases 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012054 flavored emulsion Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000020375 flavoured syrup Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 229960002737 fructose Drugs 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000005337 ground glass Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 206010023497 kuru Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 230000037230 mobility Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000001611 motor endplate Anatomy 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 208000020469 nerve plexus disease Diseases 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004012 neuralation Effects 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 208000031237 olivopontocerebellar atrophy Diseases 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000005989 paraneoplastic polyneuropathy Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 238000011518 platinum-based chemotherapy Methods 0.000 description 1
- 201000006380 plexopathy Diseases 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000003236 psychic effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 201000005572 sensory peripheral neuropathy Diseases 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000003755 striatonigral degeneration Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1816—Erythropoietin [EPO]
-
- 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
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth 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)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Psychology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26619401P | 2001-02-02 | 2001-02-02 | |
| US60/266,194 | 2001-02-02 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2003124059A RU2003124059A (ru) | 2005-01-27 |
| RU2317086C2 true RU2317086C2 (ru) | 2008-02-20 |
Family
ID=23013568
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2003124059/14A RU2317086C2 (ru) | 2001-02-02 | 2002-01-24 | Лечение неврологической дисфункции с применением сульфаматов фруктопиранозы и эритропоэтина |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US6908902B2 (enExample) |
| EP (1) | EP1471871B1 (enExample) |
| JP (1) | JP2005501801A (enExample) |
| KR (1) | KR100896971B1 (enExample) |
| AT (1) | ATE361089T1 (enExample) |
| CA (1) | CA2437333A1 (enExample) |
| CY (1) | CY1106733T1 (enExample) |
| DE (1) | DE60219961T8 (enExample) |
| DK (1) | DK1471871T3 (enExample) |
| ES (1) | ES2284858T3 (enExample) |
| MX (1) | MXPA03006952A (enExample) |
| NO (1) | NO20033440L (enExample) |
| NZ (1) | NZ548578A (enExample) |
| PT (1) | PT1471871E (enExample) |
| RU (1) | RU2317086C2 (enExample) |
| WO (1) | WO2002064085A2 (enExample) |
| ZA (1) | ZA200306818B (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7674776B2 (en) | 1999-06-14 | 2010-03-09 | Vivus, Inc. | Combination therapy for effecting weight loss and treating obesity |
| US20080103179A1 (en) * | 2006-10-27 | 2008-05-01 | Tam Peter Y | Combination Therapy |
| US20080255093A1 (en) * | 1999-06-14 | 2008-10-16 | Tam Peter Y | Compositions and methods for treating obesity and related disorders |
| JP2005501801A (ja) * | 2001-02-02 | 2005-01-20 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | フラクトピラノーススルファメートとエリスロポイエチンを含んで成る神経学的機能不全治療 |
| CA2459146A1 (en) * | 2001-08-30 | 2003-03-13 | Ortho-Mcneil Pharmaceutical, Inc. | Treatment of dementia and memory disorders with anticonvulsants and acetylcholinesterase inhibitors |
| EP1535065A4 (en) * | 2002-06-11 | 2007-07-11 | Burnham Inst | NEUROPROTECTOR SYNERGY OF ERYTHROPOIETIN AND INSULIN-LIKE GROWTH FACTOR |
| DE10226814A1 (de) * | 2002-06-15 | 2004-01-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Arzneimittelkombinationen zur Behandlung ischämischer Zustände |
| US20030235576A1 (en) * | 2002-06-15 | 2003-12-25 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | New drug combinations for the treatment of ischaemic conditions |
| ES2286453T3 (es) * | 2002-09-17 | 2007-12-01 | Motac Neuroscience Limited | Tratamiento de la discinesia. |
| EP1815854A1 (en) * | 2002-09-17 | 2007-08-08 | Motac Neuroscience Limited | Treatment of dyskenesia |
| US7388079B2 (en) * | 2002-11-27 | 2008-06-17 | The Regents Of The University Of California | Delivery of pharmaceutical agents via the human insulin receptor |
| AT500929B1 (de) * | 2004-11-09 | 2007-03-15 | Medizinische Uni Wien Muw | Pharmazeutische zubereitung die erythropoietin enthält |
| JPWO2007020922A1 (ja) * | 2005-08-17 | 2009-02-26 | 創 戸苅 | 脳疾患の治療剤および予防剤 |
| US8124095B2 (en) * | 2005-10-07 | 2012-02-28 | Armagen Technologies, Inc. | Fusion proteins for delivery of erythropoietin to the CNS |
| US8741260B2 (en) * | 2005-10-07 | 2014-06-03 | Armagen Technologies, Inc. | Fusion proteins for delivery of GDNF to the CNS |
| WO2008022349A2 (en) * | 2006-08-18 | 2008-02-21 | Armagen Technologies, Inc. | Agents for blood-brain barrier delivery |
| CA2686816A1 (en) * | 2007-01-16 | 2008-07-24 | The Johns Hopkins University | Use of various glutamate receptor antagonists for delaying or preventing platelet activity or for treating or preventing a thrombotic disease or disorder |
| WO2008137066A1 (en) * | 2007-05-02 | 2008-11-13 | The Board Of Regents Of The University Of Oklahoma | Use of compacted nucleic acid nanoparticles in non-viral treatments of ocular diseases |
| RU2335296C1 (ru) * | 2007-06-26 | 2008-10-10 | Сергей Марович Дудкин | Фармацевтическая композиция для профилактики и лечения неврологических заболеваний |
| EP2997976A1 (en) * | 2007-07-27 | 2016-03-23 | Armagen Technologies, Inc. | Methods and compositions for increasing alpha-l-iduronidase activity in the cns |
| EP2303309A2 (en) * | 2008-05-22 | 2011-04-06 | Edison Pharmaceuticals, Inc. | Treatment of mitochondrial diseases with an erythropoietin mimetic |
| US8580298B2 (en) * | 2008-06-09 | 2013-11-12 | Vivus, Inc. | Low dose topiramate/phentermine composition and methods of use thereof |
| US20090304789A1 (en) | 2008-06-09 | 2009-12-10 | Thomas Najarian | Novel topiramate compositions and an escalating dosing strategy for treating obesity and related disorders |
| JP5873003B2 (ja) | 2009-03-18 | 2016-03-01 | アーメイゲン・テクノロジーズ・インコーポレイテッドArmagen Technologies, Inc. | IgGデコイ受容体融合タンパク質の血液脳関門送達のための組成物および方法 |
| EP2485761B1 (en) | 2009-10-09 | 2019-02-27 | Armagen, Inc. | Methods and compositions for increasing iduronate 2-sulfatase activity in the cns |
| EP2785378B1 (en) | 2011-12-02 | 2020-05-13 | Armagen, Inc. | Methods and compositions for increasing arylsulfatase a activity in the cns |
| CN103316026B (zh) | 2012-03-23 | 2016-05-11 | 中国人民解放军军事医学科学院毒物药物研究所 | 含芬特明和托吡酯的联合产品及其制备方法 |
| CN102579367B (zh) | 2012-03-23 | 2014-03-12 | 中国人民解放军军事医学科学院毒物药物研究所 | 托吡酯缓释药物组合物、其制备方法及用途 |
| CN104220064B (zh) | 2012-03-23 | 2017-10-10 | 中国人民解放军军事医学科学院毒物药物研究所 | 一种含辛弗林和托吡酯的联合产品 |
| US8652527B1 (en) | 2013-03-13 | 2014-02-18 | Upsher-Smith Laboratories, Inc | Extended-release topiramate capsules |
| US9101545B2 (en) | 2013-03-15 | 2015-08-11 | Upsher-Smith Laboratories, Inc. | Extended-release topiramate capsules |
| US10538589B2 (en) | 2015-01-14 | 2020-01-21 | Armagen Inc. | Methods and compositions for increasing N-acetylglucosaminidase (NAGLU) activity in the CNS using a fusion antibody comprising an anti-human insulin receptor antibody and NAGLU |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999051097A1 (en) * | 1998-04-02 | 1999-10-14 | Avicena Group, Inc. | Compositions containing a combination of a creatine compound and a second agent |
| RU2139875C1 (ru) * | 1993-12-23 | 1999-10-20 | Орто Фармасьютикал Корпорейшн | Сульфаматы псевдофруктопиранозы и фармацевтическая композиция на их основе |
| WO2000061164A1 (en) * | 1999-04-13 | 2000-10-19 | Kenneth S. Warren Laboratories | Modulation of excitable tissue function by peripherally administered erythropoietin |
| WO2000061138A1 (en) * | 1999-04-08 | 2000-10-19 | Ortho-Mcneil Pharmaceutical, Inc. | Anticonvulsant derivatives useful in treating chronic neurodegenerative disorders |
| WO2000067744A1 (en) * | 1999-05-05 | 2000-11-16 | Gestilab Inc. | Neuroprotective composition and uses thereof |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4513006A (en) | 1983-09-26 | 1985-04-23 | Mcneil Lab., Inc. | Anticonvulsant sulfamate derivatives |
| US4703008A (en) | 1983-12-13 | 1987-10-27 | Kiren-Amgen, Inc. | DNA sequences encoding erythropoietin |
| DK173067B1 (da) | 1986-06-27 | 1999-12-13 | Univ Washington | Humant erythropoietin-gen, fremgangsmåde til ekspression deraf i transficerede cellelinier, de transficerede cellelinier sa |
| US5242942A (en) | 1992-04-28 | 1993-09-07 | Mcneilab, Inc. | Anticonvulsant fructopyranose cyclic sulfites and sulfates |
| US6153407A (en) | 1992-07-28 | 2000-11-28 | Beth Israel Deaconess Medical Center | Erythropoietin DNA having modified 5' and 3' sequences and its use to prepare EPO therapeutics |
| TW402639B (en) | 1992-12-03 | 2000-08-21 | Transkaryotic Therapies Inc | Protein production and protein delivery |
| US5384327A (en) | 1992-12-22 | 1995-01-24 | Mcneilab, Inc. | Anticonvulsant sorbopyranose sulfamates |
| US5354934A (en) | 1993-02-04 | 1994-10-11 | Amgen Inc. | Pulmonary administration of erythropoietin |
| JPH09501418A (ja) | 1993-07-19 | 1997-02-10 | アムジエン・インコーポレーテツド | エアゾル化タンパク質の安定化 |
| US5571787A (en) | 1993-07-30 | 1996-11-05 | Myelos Corporation | Prosaposin as a neurotrophic factor |
| US5700909A (en) | 1993-07-30 | 1997-12-23 | The Regents Of The University Of California | Prosaposin and cytokine-derived peptides |
| ZA946122B (en) | 1993-08-17 | 1995-03-20 | Amgen Inc | Erythropoietin analogs |
| US5643575A (en) | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US5773569A (en) | 1993-11-19 | 1998-06-30 | Affymax Technologies N.V. | Compounds and peptides that bind to the erythropoietin receptor |
| IL116085A (en) | 1994-12-16 | 1999-12-31 | Ortho Pharma Corp | Spray dried erythropoietin |
| US5767078A (en) | 1995-06-07 | 1998-06-16 | Johnson; Dana L. | Agonist peptide dimers |
| WO1998000124A1 (en) | 1996-06-28 | 1998-01-08 | Ortho Pharmaceutical Corporation | Use of topiramate or derivatives thereof for the manufacture of a medicament for the treatment of postischemic neurodegeneration |
| US5753694A (en) | 1996-06-28 | 1998-05-19 | Ortho Pharmaceutical Corporation | Anticonvulsant derivatives useful in treating amyotrophic lateral sclerosis (ALS) |
| ES2273373T3 (es) | 1996-08-02 | 2007-05-01 | Ortho-Mcneil Pharmaceutical, Inc. | Polipeptidos que tienen unido a su extremo n un unico polimero soluble al agua. |
| JP4541539B2 (ja) | 1997-07-23 | 2010-09-08 | ロシュ ダイアグノスティックス ゲーエムベーハー | 内因性遺伝子活性化によるエリスロポエチンの製造 |
| EP0902085B1 (en) | 1997-09-01 | 2003-12-03 | Aventis Pharma Deutschland GmbH | Recombinant human erythropoietin with advantageous glycosylation profile |
| US6165783A (en) | 1997-10-24 | 2000-12-26 | Neuro Spheres Holdings Ltd. | Erythropoietin-mediated neurogenesis |
| WO1999066054A2 (en) | 1998-06-15 | 1999-12-23 | Genzyme Transgenics Corp. | Erythropoietin analog-human serum albumin fusion protein |
| JP2005501801A (ja) * | 2001-02-02 | 2005-01-20 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | フラクトピラノーススルファメートとエリスロポイエチンを含んで成る神経学的機能不全治療 |
-
2002
- 2002-01-24 JP JP2002563882A patent/JP2005501801A/ja not_active Ceased
- 2002-01-24 KR KR1020037010232A patent/KR100896971B1/ko not_active Expired - Fee Related
- 2002-01-24 EP EP02724904A patent/EP1471871B1/en not_active Expired - Lifetime
- 2002-01-24 US US10/056,828 patent/US6908902B2/en not_active Expired - Lifetime
- 2002-01-24 ES ES02724904T patent/ES2284858T3/es not_active Expired - Lifetime
- 2002-01-24 MX MXPA03006952A patent/MXPA03006952A/es active IP Right Grant
- 2002-01-24 PT PT02724904T patent/PT1471871E/pt unknown
- 2002-01-24 DE DE60219961T patent/DE60219961T8/de active Active
- 2002-01-24 RU RU2003124059/14A patent/RU2317086C2/ru not_active IP Right Cessation
- 2002-01-24 AT AT02724904T patent/ATE361089T1/de active
- 2002-01-24 NZ NZ548578A patent/NZ548578A/en not_active IP Right Cessation
- 2002-01-24 WO PCT/US2002/003096 patent/WO2002064085A2/en not_active Ceased
- 2002-01-24 DK DK02724904T patent/DK1471871T3/da active
- 2002-01-24 CA CA002437333A patent/CA2437333A1/en not_active Abandoned
-
2003
- 2003-08-01 NO NO20033440A patent/NO20033440L/no not_active Application Discontinuation
- 2003-09-01 ZA ZA2003/06818A patent/ZA200306818B/en unknown
-
2005
- 2005-01-31 US US11/047,420 patent/US20050261182A1/en not_active Abandoned
-
2007
- 2007-07-13 CY CY20071100943T patent/CY1106733T1/el unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2139875C1 (ru) * | 1993-12-23 | 1999-10-20 | Орто Фармасьютикал Корпорейшн | Сульфаматы псевдофруктопиранозы и фармацевтическая композиция на их основе |
| WO1999051097A1 (en) * | 1998-04-02 | 1999-10-14 | Avicena Group, Inc. | Compositions containing a combination of a creatine compound and a second agent |
| WO2000061138A1 (en) * | 1999-04-08 | 2000-10-19 | Ortho-Mcneil Pharmaceutical, Inc. | Anticonvulsant derivatives useful in treating chronic neurodegenerative disorders |
| WO2000061164A1 (en) * | 1999-04-13 | 2000-10-19 | Kenneth S. Warren Laboratories | Modulation of excitable tissue function by peripherally administered erythropoietin |
| WO2000067744A1 (en) * | 1999-05-05 | 2000-11-16 | Gestilab Inc. | Neuroprotective composition and uses thereof |
Non-Patent Citations (3)
| Title |
|---|
| описание - с.1-2. * |
| реферат, с.1-3 описания. Бертрам Г.Катцунг. Базисная и клиническая фармакология, в 2 тт., пер. с англ., 1998. - М.: Бином, СПб.: Невский Диалект, т.2, с.624, кол. 1. Приложение II. Важнейшие взаимодействия лекарственных средств. Фармакодинамические механизмы. * |
| реферат, с.1-8 описания. * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002064085A2 (en) | 2002-08-22 |
| ATE361089T1 (de) | 2007-05-15 |
| EP1471871A2 (en) | 2004-11-03 |
| DK1471871T3 (da) | 2007-09-17 |
| EP1471871B1 (en) | 2007-05-02 |
| WO2002064085A3 (en) | 2004-09-10 |
| NO20033440L (no) | 2003-09-29 |
| EP1471871A4 (en) | 2005-11-09 |
| DE60219961T2 (de) | 2008-01-17 |
| KR100896971B1 (ko) | 2009-05-14 |
| KR20040011458A (ko) | 2004-02-05 |
| JP2005501801A (ja) | 2005-01-20 |
| ES2284858T3 (es) | 2007-11-16 |
| US20020169109A1 (en) | 2002-11-14 |
| MXPA03006952A (es) | 2004-10-15 |
| US6908902B2 (en) | 2005-06-21 |
| US20050261182A1 (en) | 2005-11-24 |
| ZA200306818B (en) | 2005-02-23 |
| DE60219961D1 (de) | 2007-06-14 |
| DE60219961T8 (de) | 2008-04-17 |
| CA2437333A1 (en) | 2002-08-22 |
| CY1106733T1 (el) | 2012-05-23 |
| PT1471871E (pt) | 2007-06-05 |
| RU2003124059A (ru) | 2005-01-27 |
| NO20033440D0 (no) | 2003-08-01 |
| NZ548578A (en) | 2008-03-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2317086C2 (ru) | Лечение неврологической дисфункции с применением сульфаматов фруктопиранозы и эритропоэтина | |
| KR101802411B1 (ko) | Fam19a5 단백질을 포함하는 비만 예방 또는 치료용 조성물 및 이를 이용한 비만 치료제의 스크리닝 방법 | |
| EA015672B1 (ru) | Тканезащитные пептиды и их применения | |
| JP2003534384A (ja) | 神経保護性ペプチド | |
| EP2440225B1 (en) | Novel applications of hip/pap or derivatives thereof | |
| US20150087598A1 (en) | Treating muc1-expressing cancers with helicase inhibitors | |
| US20020198150A1 (en) | Methods of using colony stimulating factors in the treatment of tissue damage and ischemia | |
| US6638914B1 (en) | Pharmaceutical administration of adenosine agonists | |
| CA2408255A1 (en) | Methods for stimulating nervous system regeneration and repair by regulating arginase 1 and polyamine synthesis | |
| AU2001259453A1 (en) | Methods for stimulating nervous system regeneration and repair by regulating arginase 1 and polyamine synthesis | |
| EP2139510B1 (en) | Treating cerebrovascular diseases with erythropoietin and granulocyte-colony stimulating factor jointly | |
| CA2304956C (en) | Pharmaceutical composition for preventing or treating ischemic diseases | |
| Yoo et al. | Neuregulin-1 reverses anxiety-like behavior and social behavior deficits induced by unilateral micro-injection of CoCl2 into the ventral hippocampus (vHPC) | |
| AU2002255504B2 (en) | Treatment of neurological dysfunction comprising fructopyranose sulfamates and erythropoietin | |
| EA025027B1 (ru) | Способ лечения острого нарушения мозгового и спинального кровообращения ишемического и геморрагического характера | |
| EP1529533A1 (en) | Use of GH secretagogues in hypoxic-ischemic brain injury | |
| KR20220003652A (ko) | 에리스로포이에틴-유래된 펩타이드, 이의 제조 방법 및 이의 용도 | |
| AU2002255504A1 (en) | Treatment of neurological dysfunction comprising fructopyranose sulfamates and erythropoietin | |
| US8106009B2 (en) | Pharmaceutical composition for preventing or treating ischemic diseases | |
| AU2003200309B2 (en) | Pharmaceutical Composition for Preventing or Treating Ischaemic Diseases | |
| KR101844816B1 (ko) | 구아나벤즈를 포함하는 식욕부진증의 개선 또는 치료용 조성물 및 이를 이용한 방법 | |
| CN1278736C (zh) | 一个新的多巴胺能神经元保护因子及其应用 | |
| WO1994016721A1 (en) | Methods of treatment using ciliary neurotrophic factor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20180125 |