IL227768A - Use of 2-, 4-disulfonyl-α-phenyl butyl tertiary nitron in the preparation of brain injury preparations - Google Patents
Use of 2-, 4-disulfonyl-α-phenyl butyl tertiary nitron in the preparation of brain injury preparationsInfo
- Publication number
- IL227768A IL227768A IL227768A IL22776813A IL227768A IL 227768 A IL227768 A IL 227768A IL 227768 A IL227768 A IL 227768A IL 22776813 A IL22776813 A IL 22776813A IL 227768 A IL227768 A IL 227768A
- Authority
- IL
- Israel
- Prior art keywords
- noise
- brain injury
- exposure
- nac
- composition
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims description 47
- 208000029028 brain injury Diseases 0.000 title claims description 20
- 238000002360 preparation method Methods 0.000 title claims description 4
- SRHWORQGHZESJE-UHFFFAOYSA-N N-[1-(4,6-disulfonylcyclohex-2-en-1-yl)-2,2-dimethylpropylidene]hydroxylamine Chemical compound CC(C)(C)C(=NO)C1C=CC(CC1=S(=O)=O)=S(=O)=O SRHWORQGHZESJE-UHFFFAOYSA-N 0.000 title 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical group CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims description 60
- 229960004308 acetylcysteine Drugs 0.000 claims description 60
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 29
- 230000009529 traumatic brain injury Effects 0.000 claims description 29
- RDHQFKQIGNGIED-MRVPVSSYSA-N O-acetyl-L-carnitine Chemical compound CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C RDHQFKQIGNGIED-MRVPVSSYSA-N 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 14
- YUKIAUPQUWVLBK-UHFFFAOYSA-N n-pentylidenehydroxylamine Chemical group CCCCC=NO YUKIAUPQUWVLBK-UHFFFAOYSA-N 0.000 claims description 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 3
- JKRODHBGNBKZLE-YUMQZZPRSA-N (2s)-2-amino-5-[[(2r)-1-[(2-ethoxy-2-oxoethyl)amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CCOC(=O)CNC(=O)[C@H](CS)NC(=O)CC[C@H](N)C(O)=O JKRODHBGNBKZLE-YUMQZZPRSA-N 0.000 claims description 2
- FFEARJCKVFRZRR-SCSAIBSYSA-N D-methionine Chemical compound CSCC[C@@H](N)C(O)=O FFEARJCKVFRZRR-SCSAIBSYSA-N 0.000 claims description 2
- 229930182818 D-methionine Natural products 0.000 claims description 2
- DYEFUKCXAQOFHX-UHFFFAOYSA-N Ebselen Chemical compound [se]1C2=CC=CC=C2C(=O)N1C1=CC=CC=C1 DYEFUKCXAQOFHX-UHFFFAOYSA-N 0.000 claims description 2
- 206010063602 Exposure to noise Diseases 0.000 claims description 2
- 108700024319 S-ethyl glutathione Proteins 0.000 claims description 2
- 229950010033 ebselen Drugs 0.000 claims description 2
- 230000000472 traumatic effect Effects 0.000 claims description 2
- WZXBYDBYBIGAQN-UWVGGRQHSA-N (2s)-2-amino-5-[[(2r)-1-(carboxymethylamino)-3-(diethylcarbamoylsulfanyl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CCN(CC)C(=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O WZXBYDBYBIGAQN-UWVGGRQHSA-N 0.000 claims 1
- 108700006011 carbamathione Proteins 0.000 claims 1
- 238000011282 treatment Methods 0.000 description 50
- 210000004027 cell Anatomy 0.000 description 34
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 27
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 27
- XLZOVRYBVCMCGL-BPNVQINPSA-L disodium;4-[(z)-[tert-butyl(oxido)azaniumylidene]methyl]benzene-1,3-disulfonate Chemical compound [Na+].[Na+].CC(C)(C)[N+](\[O-])=C\C1=CC=C(S([O-])(=O)=O)C=C1S([O-])(=O)=O XLZOVRYBVCMCGL-BPNVQINPSA-L 0.000 description 26
- 208000009205 Tinnitus Diseases 0.000 description 23
- 238000000034 method Methods 0.000 description 16
- 210000003952 cochlear nucleus Anatomy 0.000 description 14
- 241000700112 Chinchilla Species 0.000 description 13
- 210000004556 brain Anatomy 0.000 description 13
- 210000005056 cell body Anatomy 0.000 description 13
- 230000006378 damage Effects 0.000 description 13
- 208000014674 injury Diseases 0.000 description 12
- 231100000886 tinnitus Toxicity 0.000 description 12
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 10
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 10
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 10
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 10
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- 230000008499 blood brain barrier function Effects 0.000 description 10
- 210000001218 blood-brain barrier Anatomy 0.000 description 10
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 10
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 9
- 210000001320 hippocampus Anatomy 0.000 description 9
- 101000720704 Homo sapiens Neuronal migration protein doublecortin Proteins 0.000 description 8
- 102100025929 Neuronal migration protein doublecortin Human genes 0.000 description 8
- 208000027418 Wounds and injury Diseases 0.000 description 8
- 238000010186 staining Methods 0.000 description 8
- 238000000386 microscopy Methods 0.000 description 7
- 230000035699 permeability Effects 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000012744 immunostaining Methods 0.000 description 6
- 210000005036 nerve Anatomy 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 210000000133 brain stem Anatomy 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 210000001787 dendrite Anatomy 0.000 description 5
- 102100029184 Calmodulin regulator protein PCP4 Human genes 0.000 description 4
- 102100035244 Cerebellin-1 Human genes 0.000 description 4
- 101710135505 Cerebellin-1 Proteins 0.000 description 4
- 101000988362 Homo sapiens Calmodulin regulator protein PCP4 Proteins 0.000 description 4
- 101001092197 Homo sapiens RNA binding protein fox-1 homolog 3 Proteins 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- 102100035530 RNA binding protein fox-1 homolog 3 Human genes 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- 239000002872 contrast media Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 230000004792 oxidative damage Effects 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000008733 trauma Effects 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 210000003926 auditory cortex Anatomy 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 210000001353 entorhinal cortex Anatomy 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 238000002595 magnetic resonance imaging Methods 0.000 description 3
- 210000003470 mitochondria Anatomy 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 150000003839 salts Chemical group 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000007470 synaptic degeneration Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- WJJGAKCAAJOICV-JTQLQIEISA-N (2s)-2-(dimethylamino)-3-(4-hydroxyphenyl)propanoic acid Chemical compound CN(C)[C@H](C(O)=O)CC1=CC=C(O)C=C1 WJJGAKCAAJOICV-JTQLQIEISA-N 0.000 description 2
- 101800000068 Antioxidant peptide Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 206010011878 Deafness Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 206010061218 Inflammation Diseases 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 238000010162 Tukey test Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 230000006721 cell death pathway Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000033077 cellular process Effects 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- LGMLJQFQKXPRGA-VPVMAENOSA-K gadopentetate dimeglumine Chemical compound [Gd+3].CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O LGMLJQFQKXPRGA-VPVMAENOSA-K 0.000 description 2
- 230000010370 hearing loss Effects 0.000 description 2
- 231100000888 hearing loss Toxicity 0.000 description 2
- 208000016354 hearing loss disease Diseases 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000005291 magnetic effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 238000000879 optical micrograph Methods 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- 210000002182 synaptic membrane Anatomy 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000000202 Diffuse Axonal Injury Diseases 0.000 description 1
- OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 108700002232 Immediate-Early Genes Proteins 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- -1 PBN compound Chemical class 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- PSYHRZCRICXGJJ-WQLSENKSSA-N alpha-(4-hydroxyphenyl)-N-tert-butylnitrone Chemical compound CC(C)(C)[N+](\[O-])=C\C1=CC=C(O)C=C1 PSYHRZCRICXGJJ-WQLSENKSSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000007177 brain activity Effects 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 238000001739 density measurement Methods 0.000 description 1
- 230000009521 diffuse axonal injury Effects 0.000 description 1
- XLZOVRYBVCMCGL-UHFFFAOYSA-L disodium;4-[[tert-butyl(oxido)azaniumylidene]methyl]benzene-1,3-disulfonate Chemical compound [Na+].[Na+].CC(C)(C)[N+]([O-])=CC1=CC=C(S([O-])(=O)=O)C=C1S([O-])(=O)=O XLZOVRYBVCMCGL-UHFFFAOYSA-L 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 229940124274 edetate disodium Drugs 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 210000000320 geniculate body Anatomy 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 210000003552 inferior colliculi Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000002052 molecular layer Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000004693 neuron damage Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000009518 penetrating injury Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- HJHVQCXHVMGZNC-JCJNLNMISA-M sodium;(2z)-2-[(3r,4s,5s,8s,9s,10s,11r,13r,14s,16s)-16-acetyloxy-3,11-dihydroxy-4,8,10,14-tetramethyl-2,3,4,5,6,7,9,11,12,13,15,16-dodecahydro-1h-cyclopenta[a]phenanthren-17-ylidene]-6-methylhept-5-enoate Chemical compound [Na+].O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C([O-])=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C HJHVQCXHVMGZNC-JCJNLNMISA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000008925 spontaneous activity Effects 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 210000003478 temporal lobe Anatomy 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
-
- 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
- A61K31/13—Amines
- A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
-
- 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
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/221—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
-
- 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
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
- A61K38/063—Glutathione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/07—Tetrapeptides
-
- 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
- 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
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161439671P | 2011-02-04 | 2011-02-04 | |
| PCT/US2012/023855 WO2012106654A1 (en) | 2011-02-04 | 2012-02-03 | Methods for treating brain injury |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL227768A0 IL227768A0 (en) | 2013-09-30 |
| IL227768A true IL227768A (en) | 2016-10-31 |
Family
ID=46603106
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL227768A IL227768A (en) | 2011-02-04 | 2013-08-01 | Use of 2-, 4-disulfonyl-α-phenyl butyl tertiary nitron in the preparation of brain injury preparations |
| IL247911A IL247911B (en) | 2011-02-04 | 2016-09-19 | The use of 4,2-disulfonyl α-phenyl butyl tertiary nitrone in the preparation of preparations for the treatment of tinnitus |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL247911A IL247911B (en) | 2011-02-04 | 2016-09-19 | The use of 4,2-disulfonyl α-phenyl butyl tertiary nitrone in the preparation of preparations for the treatment of tinnitus |
Country Status (8)
| Country | Link |
|---|---|
| US (4) | US9289404B2 (enExample) |
| EP (1) | EP2670403B1 (enExample) |
| JP (2) | JP6099574B2 (enExample) |
| AU (1) | AU2012211989B2 (enExample) |
| CA (1) | CA2826602C (enExample) |
| ES (1) | ES2893825T3 (enExample) |
| IL (2) | IL227768A (enExample) |
| WO (1) | WO2012106654A1 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9050305B2 (en) | 2012-03-29 | 2015-06-09 | Chs Pharma, Inc. | Treatment for ischemic stroke |
| WO2014172583A2 (en) * | 2013-04-18 | 2014-10-23 | Jinsheng Zhang | Compositions and methods utilizing phosphodiesterase inhibitors to treat blast-induced tinnitus and/or hearing loss |
| WO2017048778A1 (en) * | 2015-09-18 | 2017-03-23 | Oklahoma Medical Research Foundation | Method of transporting an agent across blood-brain, blood-cochlear or blood-cerebrospinal fluid barrier |
| SMT202400469T1 (it) | 2016-05-18 | 2025-01-14 | Sound Pharmaceuticals Incorporated | Ebselen per l'uso nel trattamento della malattia di ménière |
| US10576125B2 (en) * | 2016-10-31 | 2020-03-03 | Hough Ear Institute | Methods for enhancing synaptogenesis and neuritogenesis |
| EP3570826A4 (en) * | 2017-01-19 | 2020-09-23 | Otologic Pharmaceutics, Inc. | N-ACETYLCYSTEIN FORMULATIONS AND THEIR USES |
| WO2018201024A1 (en) | 2017-04-28 | 2018-11-01 | Axcella Health Inc. | Amino acid compositions and their use for the treatment of traumatic brain injury |
| US20190046486A1 (en) * | 2017-08-14 | 2019-02-14 | Axcella Health Inc. | Compositions and methods for the treatment of neuronal injury |
| CN111132672A (zh) | 2017-09-20 | 2020-05-08 | 俄克拉荷马医学研究基金会 | 抗药性胶质瘤的治疗 |
| EP3700525A4 (en) | 2017-10-27 | 2021-08-25 | Beyond Barriers Therapeutics, Inc. | IMPROVED PROVISION OF ANTIOXIDANTS FOR TREATMENT OF CENTRAL NERVOUS SYSTEM DISEASES WITH OXIDATIVE STRESS |
| WO2019213245A1 (en) * | 2018-05-03 | 2019-11-07 | Hough Ear Institute | Methods for reducing accumulated pathologic tau protein |
| US20210369147A1 (en) * | 2018-07-18 | 2021-12-02 | The Regents Of The University Of California | Multimodal Neuroimaging-Based Diagnostic Systems and Methods for Detecting Tinnitus |
| WO2020023755A1 (en) | 2018-07-26 | 2020-01-30 | CHS Pharma Inc. | Treatment for ischemic stroke |
| EP3849530A4 (en) * | 2018-09-12 | 2022-06-22 | Hough Ear Institute | METHODS OF TREATMENT OF HEARING LOSS AFTER COCHLEAR IMPLANT SURGERY |
| WO2026039548A1 (en) * | 2024-08-13 | 2026-02-19 | Mcleay Matthew | Perfluorocarbon compositions, systems, and methods for ischemic, inflammatory, infectious, transplant, and other medical conditions |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5488145A (en) * | 1993-12-23 | 1996-01-30 | Oklahoma Medical Research Foundation | 2,4-disulfonyl phenyl butyl nitrone, its salts, and their use as pharmaceutical free radical traps |
| WO2000027376A2 (de) * | 1998-10-26 | 2000-05-18 | Michael Schedler | Verwendung von thiolverbindungen, oxidoreduktasen und/oder hydrolasen zur behandlung des tinnitus, insbesondere des chronischen tinnitus |
| AU1574701A (en) * | 1999-10-22 | 2001-04-30 | Wrair Walter Reed Army Institute Of Research | A pharmaceutical composition containing pglu-glu-pro-nh2 and method for treating diseases and injuries to the brain, spinal cord and retina using same |
| SE0001916D0 (sv) * | 2000-05-23 | 2000-05-23 | Astrazeneca Ab | Novel formulation |
| US6428474B1 (en) | 2000-05-24 | 2002-08-06 | Sol Weiss | Surgical instrument |
| US7115666B2 (en) * | 2002-10-15 | 2006-10-03 | Renovis, Inc. | Nitrone compounds, pharmaceutical compositions containing the same and methods for treating inflammation and neuropathic pain |
| CA3024434A1 (en) | 2004-01-23 | 2005-08-11 | Cornell Research Foundation, Inc. | Methods for reducing oxidative damage |
| CA2606053A1 (en) | 2005-04-21 | 2006-11-02 | Glenn Goldstein | N-acetylcysteine amide (nac amide) for the treatment of diseases and conditions associated with oxidative stress |
| US8231629B2 (en) | 2006-06-29 | 2012-07-31 | L.R.S. Ortho Ltd. | System and method for locating of distal holes of an intramedullary nail |
| JP5236641B2 (ja) * | 2006-07-25 | 2013-07-17 | ハフ イヤ インスティテュート | 急性音響外傷の治療方法 |
| US8784870B2 (en) | 2008-07-21 | 2014-07-22 | Otonomy, Inc. | Controlled release compositions for modulating free-radical induced damage and methods of use thereof |
| US9289462B2 (en) | 2008-09-17 | 2016-03-22 | Terry Gage | Method for medical treatment utilizing glutathione |
-
2012
- 2012-02-03 WO PCT/US2012/023855 patent/WO2012106654A1/en not_active Ceased
- 2012-02-03 AU AU2012211989A patent/AU2012211989B2/en active Active
- 2012-02-03 EP EP12742491.9A patent/EP2670403B1/en active Active
- 2012-02-03 ES ES12742491T patent/ES2893825T3/es active Active
- 2012-02-03 CA CA2826602A patent/CA2826602C/en active Active
- 2012-02-03 JP JP2013552693A patent/JP6099574B2/ja active Active
- 2012-02-03 US US13/983,515 patent/US9289404B2/en active Active
-
2013
- 2013-08-01 IL IL227768A patent/IL227768A/en active IP Right Grant
-
2016
- 2016-02-18 US US15/046,676 patent/US9642823B2/en active Active
- 2016-09-19 IL IL247911A patent/IL247911B/en active IP Right Grant
-
2017
- 2017-01-27 US US15/418,406 patent/US10022346B2/en active Active
- 2017-02-21 JP JP2017029662A patent/JP6286589B2/ja active Active
- 2017-06-23 US US15/632,230 patent/US10111843B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| IL227768A0 (en) | 2013-09-30 |
| JP2017137321A (ja) | 2017-08-10 |
| US20140187631A1 (en) | 2014-07-03 |
| US9289404B2 (en) | 2016-03-22 |
| IL247911B (en) | 2021-05-31 |
| AU2012211989B2 (en) | 2017-03-02 |
| US10111843B2 (en) | 2018-10-30 |
| JP6286589B2 (ja) | 2018-02-28 |
| JP2014511374A (ja) | 2014-05-15 |
| ES2893825T3 (es) | 2022-02-10 |
| WO2012106654A1 (en) | 2012-08-09 |
| EP2670403A4 (en) | 2014-07-09 |
| JP6099574B2 (ja) | 2017-03-22 |
| US10022346B2 (en) | 2018-07-17 |
| US9642823B2 (en) | 2017-05-09 |
| AU2012211989A1 (en) | 2013-08-22 |
| CA2826602C (en) | 2019-06-11 |
| CA2826602A1 (en) | 2012-08-09 |
| US20170202797A1 (en) | 2017-07-20 |
| EP2670403A1 (en) | 2013-12-11 |
| US20170281583A1 (en) | 2017-10-05 |
| EP2670403B1 (en) | 2021-08-18 |
| IL247911A0 (en) | 2016-11-30 |
| US20160158173A1 (en) | 2016-06-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2012211989B2 (en) | Methods for treating brain injury | |
| Godoy et al. | Quercetin exerts differential neuroprotective effects against H2O2 and Aβ aggregates in hippocampal neurons: the role of mitochondria | |
| EP1562566B1 (en) | Analgesic compositions comprising nmda receptor antagonists and benzalkonium chloride | |
| CN102256596B (zh) | 用于增强对流递送到中枢神经中心的脂质体组合物 | |
| US20050159364A1 (en) | Copper antagonist compounds | |
| JP7003045B2 (ja) | 神経変性の治療のための方法及び医薬組成物 | |
| WO2018081614A1 (en) | Methods for enhancing synaptogenesis and neuritogenesis | |
| US20090263507A1 (en) | Biological markers and response to treatment for pain, inflammation, neuronal or vascular injury and methods of use | |
| Fan et al. | Delivering the acetylcholine neurotransmitter by nanodrugs as an effective treatment for Alzheimer's disease | |
| CA3077036A1 (en) | Compositions and methods for treating septic cardiomyopathy | |
| WO2009029678A1 (en) | PROTEIN KINASE C-δ INHIBITORS THAT PROTECT AGAINST CELLULAR INJURY AND INFLAMMATION AND PROMOTE ASTROCYTE PROLIFERATION | |
| US20230390232A1 (en) | N-propargylglycine: a unique inhibitor of proline dehydrogenase with brain-enhancing mitohormesis properties capable of mitigating the pathogenesis of neurodegenerative disorders | |
| RU2777871C1 (ru) | Способ лечения нейродегенеративных заболеваний | |
| JP2002503209A (ja) | 著しく改善された抗腫瘍活性によるリポソーム抗腫瘍療法 | |
| CN115023222A (zh) | 神经系统病症的治疗 | |
| US20260130848A1 (en) | Methods and compositions for central nervous system (cns) drug delivery and treatment | |
| US20230132378A9 (en) | Compositions and methods for treating hemorrhagic stroke | |
| CA2926747A1 (en) | Use of mtor inhibitors to treat vascular cognitive impairment | |
| Deidda | Retinal neurodegeneration and an innovative nanostructured approach in an iron overload in vivo model | |
| EP3692042A1 (en) | Treatment of obesity-related conditions | |
| EA046226B1 (ru) | Применение фармацевтической композиции в качестве лекарственного средства для защиты и/или репарации/восстановления гематоэнцефалического барьера | |
| HK1261266A1 (en) | Method and pharmaceutical composition for treatment of neurodegeneration | |
| AU2015213386A1 (en) | Biological markers and response to treatment for pain, inflammation, neuronal or vascular injury and methods of use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed |