JP2011530585A - 難聴の治療法 - Google Patents
難聴の治療法 Download PDFInfo
- Publication number
- JP2011530585A JP2011530585A JP2011522927A JP2011522927A JP2011530585A JP 2011530585 A JP2011530585 A JP 2011530585A JP 2011522927 A JP2011522927 A JP 2011522927A JP 2011522927 A JP2011522927 A JP 2011522927A JP 2011530585 A JP2011530585 A JP 2011530585A
- Authority
- JP
- Japan
- Prior art keywords
- noise
- adenosine receptor
- receptor agonist
- exposure
- adenosine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 68
- 208000016354 hearing loss disease Diseases 0.000 title claims description 22
- 206010011878 Deafness Diseases 0.000 title claims description 21
- 230000010370 hearing loss Effects 0.000 title description 17
- 231100000888 hearing loss Toxicity 0.000 title description 17
- 239000003379 purinergic P1 receptor agonist Substances 0.000 claims abstract description 183
- 229940122614 Adenosine receptor agonist Drugs 0.000 claims abstract description 130
- 238000000034 method Methods 0.000 claims abstract description 43
- 206010011903 Deafness traumatic Diseases 0.000 claims abstract description 24
- 208000002946 Noise-Induced Hearing Loss Diseases 0.000 claims abstract description 24
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 106
- 210000003477 cochlea Anatomy 0.000 claims description 71
- 239000003814 drug Substances 0.000 claims description 55
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 53
- 229960005305 adenosine Drugs 0.000 claims description 53
- XSMYYYQVWPZWIZ-IDTAVKCVSA-N (2r,3r,4s,5r)-2-[2-chloro-6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(Cl)=NC(NC3CCCC3)=C2N=C1 XSMYYYQVWPZWIZ-IDTAVKCVSA-N 0.000 claims description 46
- 239000000126 substance Substances 0.000 claims description 20
- 230000006378 damage Effects 0.000 claims description 19
- 229940079593 drug Drugs 0.000 claims description 18
- -1 3-chloro-2-thienyl Chemical group 0.000 claims description 15
- 239000012528 membrane Substances 0.000 claims description 15
- GYWXTRVEUURNEW-TVDBPQCTSA-N (2R,3R,4S,5R)-2-[6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9-purinyl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@@H]3[C@H](CCC3)O)=C2N=C1 GYWXTRVEUURNEW-TVDBPQCTSA-N 0.000 claims description 14
- 230000001154 acute effect Effects 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 206010063602 Exposure to noise Diseases 0.000 claims description 13
- 150000003254 radicals Chemical class 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000012453 solvate Substances 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- FPHJJCBLRAPJQJ-CRKDRTNXSA-N (2s,3r,4s,5r)-2-amino-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@]1(N)O[C@H](CO)[C@@H](O)[C@H]1O FPHJJCBLRAPJQJ-CRKDRTNXSA-N 0.000 claims description 9
- VFEGXMIJIICQBD-SRNJXLPISA-N (2r,3r,4s,5r)-2-[6-[[(2r)-1-(1,3-benzothiazol-2-ylsulfanyl)propan-2-yl]amino]-2-chloropurin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N([C@@H](CSC=1SC2=CC=CC=C2N=1)C)C(C=1N=C2)=NC(Cl)=NC=1N2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VFEGXMIJIICQBD-SRNJXLPISA-N 0.000 claims description 7
- OESBDSFYJMDRJY-BAYCTPFLSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-[[(3r)-oxolan-3-yl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@H]3COCC3)=C2N=C1 OESBDSFYJMDRJY-BAYCTPFLSA-N 0.000 claims description 7
- 239000000039 congener Substances 0.000 claims description 7
- XRLDSWLMHUQECH-UHFFFAOYSA-N cyclopentanecarboxamide Chemical compound NC(=O)C1CCCC1 XRLDSWLMHUQECH-UHFFFAOYSA-N 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- JAKAFSGZUXCHLF-LSCFUAHRSA-N (2r,3r,4r,5r)-5-[6-(cyclohexylamino)purin-9-yl]-2-(hydroxymethyl)-4-methoxyoxolan-3-ol Chemical compound CO[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(NC3CCCCC3)=C2N=C1 JAKAFSGZUXCHLF-LSCFUAHRSA-N 0.000 claims description 6
- SQMWSBKSHWARHU-SDBHATRESA-N n6-cyclopentyladenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(NC3CCCC3)=C2N=C1 SQMWSBKSHWARHU-SDBHATRESA-N 0.000 claims description 6
- 208000037816 tissue injury Diseases 0.000 claims description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 5
- 229930195712 glutamate Natural products 0.000 claims description 5
- 230000002035 prolonged effect Effects 0.000 claims description 5
- 231100000895 deafness Toxicity 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 230000017531 blood circulation Effects 0.000 claims description 3
- 230000003492 excitotoxic effect Effects 0.000 claims description 3
- 231100000063 excitotoxicity Toxicity 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- JFRJCQJVFMHZOO-QZHHGCDDSA-N n-(2-aminoethyl)-2-[4-[[2-[4-[[9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]amino]phenyl]acetyl]amino]phenyl]acetamide Chemical group C1=CC(CC(=O)NCCN)=CC=C1NC(=O)CC(C=C1)=CC=C1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 JFRJCQJVFMHZOO-QZHHGCDDSA-N 0.000 description 132
- 238000002347 injection Methods 0.000 description 76
- 239000007924 injection Substances 0.000 description 76
- 241001465754 Metazoa Species 0.000 description 68
- 230000004044 response Effects 0.000 description 58
- 241000700159 Rattus Species 0.000 description 55
- 238000011084 recovery Methods 0.000 description 44
- GIANIJCPTPUNBA-QMMMGPOBSA-N (2s)-3-(4-hydroxyphenyl)-2-nitramidopropanoic acid Chemical compound [O-][N+](=O)N[C@H](C(=O)O)CC1=CC=C(O)C=C1 GIANIJCPTPUNBA-QMMMGPOBSA-N 0.000 description 37
- 239000000243 solution Substances 0.000 description 36
- 230000000694 effects Effects 0.000 description 31
- 210000002768 hair cell Anatomy 0.000 description 30
- 210000000133 brain stem Anatomy 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 24
- 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 22
- 239000002953 phosphate buffered saline Substances 0.000 description 22
- 239000003981 vehicle Substances 0.000 description 22
- 238000012744 immunostaining Methods 0.000 description 18
- 238000002474 experimental method Methods 0.000 description 17
- 210000000067 inner hair cell Anatomy 0.000 description 17
- 238000011866 long-term treatment Methods 0.000 description 16
- 210000002985 organ of corti Anatomy 0.000 description 15
- 238000011870 unpaired t-test Methods 0.000 description 15
- 238000000540 analysis of variance Methods 0.000 description 14
- PAOANWZGLPPROA-RQXXJAGISA-N CGS-21680 Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(NCCC=3C=CC(CCC(O)=O)=CC=3)=NC(N)=C2N=C1 PAOANWZGLPPROA-RQXXJAGISA-N 0.000 description 13
- 210000004379 membrane Anatomy 0.000 description 13
- 238000001543 one-way ANOVA Methods 0.000 description 13
- KPKZJLCSROULON-QKGLWVMZSA-N Phalloidin Chemical compound N1C(=O)[C@@H]([C@@H](O)C)NC(=O)[C@H](C)NC(=O)[C@H](C[C@@](C)(O)CO)NC(=O)[C@H](C2)NC(=O)[C@H](C)NC(=O)[C@@H]3C[C@H](O)CN3C(=O)[C@@H]1CSC1=C2C2=CC=CC=C2N1 KPKZJLCSROULON-QKGLWVMZSA-N 0.000 description 12
- 239000003937 drug carrier Substances 0.000 description 12
- 230000010412 perfusion Effects 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 230000013707 sensory perception of sound Effects 0.000 description 12
- 238000010162 Tukey test Methods 0.000 description 11
- 210000004049 perilymph Anatomy 0.000 description 11
- 108050000203 Adenosine receptors Proteins 0.000 description 10
- 102000009346 Adenosine receptors Human genes 0.000 description 10
- 230000036760 body temperature Effects 0.000 description 9
- 230000037396 body weight Effects 0.000 description 9
- 210000001323 spiral ganglion Anatomy 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 210000003027 ear inner Anatomy 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 230000036542 oxidative stress Effects 0.000 description 8
- 229940044601 receptor agonist Drugs 0.000 description 8
- 239000000018 receptor agonist Substances 0.000 description 8
- UTLPKQYUXOEJIL-UHFFFAOYSA-N LSM-3822 Chemical compound N1=CC=2C3=NC(C=4OC=CC=4)=NN3C(N)=NC=2N1CCC1=CC=CC=C1 UTLPKQYUXOEJIL-UHFFFAOYSA-N 0.000 description 7
- 210000000238 cell of claudius Anatomy 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 241000283707 Capra Species 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 108010009711 Phalloidine Proteins 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 210000001595 mastoid Anatomy 0.000 description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 6
- 0 CCC(*(C)C[C@]1(C)OC=CC(C)=C1)[O+]C*#*CC Chemical compound CCC(*(C)C[C@]1(C)OC=CC(C)=C1)[O+]C*#*CC 0.000 description 5
- 241000700157 Rattus norvegicus Species 0.000 description 5
- 229940121359 adenosine receptor antagonist Drugs 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 210000000354 cell of hensen Anatomy 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000002131 composite material Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 5
- 238000007619 statistical method Methods 0.000 description 5
- 101150007969 ADORA1 gene Proteins 0.000 description 4
- 101150051188 Adora2a gene Proteins 0.000 description 4
- 201000004384 Alopecia Diseases 0.000 description 4
- 241001546602 Horismenus Species 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 4
- 229930040373 Paraformaldehyde Natural products 0.000 description 4
- 238000000692 Student's t-test Methods 0.000 description 4
- 230000006727 cell loss Effects 0.000 description 4
- 230000003676 hair loss Effects 0.000 description 4
- 229960003299 ketamine Drugs 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 229920002866 paraformaldehyde Polymers 0.000 description 4
- 230000001953 sensory effect Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000012353 t test Methods 0.000 description 4
- 238000011200 topical administration Methods 0.000 description 4
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 4
- 229960001600 xylazine Drugs 0.000 description 4
- UNPLRYRWJLTVAE-UHFFFAOYSA-N Cloperastine hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)OCCN1CCCCC1 UNPLRYRWJLTVAE-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229920004890 Triton X-100 Polymers 0.000 description 3
- 239000013504 Triton X-100 Substances 0.000 description 3
- 230000036982 action potential Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000003030 auditory receptor cell Anatomy 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 230000005779 cell damage Effects 0.000 description 3
- 208000037887 cell injury Diseases 0.000 description 3
- 210000000860 cochlear nerve Anatomy 0.000 description 3
- 210000000959 ear middle Anatomy 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 210000003990 interdental cell Anatomy 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000001936 parietal effect Effects 0.000 description 3
- 230000035479 physiological effects, processes and functions Effects 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 238000002203 pretreatment Methods 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 239000007845 reactive nitrogen species Substances 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000012764 semi-quantitative analysis Methods 0.000 description 3
- 210000000645 stria vascularis Anatomy 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000012385 systemic delivery Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000000451 tissue damage Effects 0.000 description 3
- 231100000827 tissue damage Toxicity 0.000 description 3
- 238000012384 transportation and delivery Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 229940127600 A2A receptor antagonist Drugs 0.000 description 2
- 241000197194 Bulla Species 0.000 description 2
- 230000005788 Cochlea function Effects 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- 206010029350 Neurotoxicity Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 206010044221 Toxic encephalopathy Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000002582 adenosine A1 receptor agonist Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 210000003984 auditory pathway Anatomy 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 208000002352 blister Diseases 0.000 description 2
- 230000001120 cytoprotective effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 230000002631 hypothermal effect Effects 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000007135 neurotoxicity Effects 0.000 description 2
- 231100000228 neurotoxicity Toxicity 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000010255 response to auditory stimulus Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- YFJCRJZTDYDCRZ-MCDZGGTQSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol;hydrochloride Chemical compound Cl.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YFJCRJZTDYDCRZ-MCDZGGTQSA-N 0.000 description 1
- KYOSRONGDTVPDJ-NVQRDWNXSA-N (2r,3r,4s,5r)-2-(6-anilinopurin-9-yl)-5-(hydroxymethyl)-2-propan-2-yloxolane-3,4-diol Chemical compound C1=NC2=C(NC=3C=CC=CC=3)N=CN=C2N1[C@]1(C(C)C)O[C@H](CO)[C@@H](O)[C@H]1O KYOSRONGDTVPDJ-NVQRDWNXSA-N 0.000 description 1
- AHAPTFOPJBIRLR-HZHPXBFKSA-N (2r,3r,4s,5r)-2-[2-chloro-6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(Cl)=NC(NC3CCCC3)=C2N=C1.O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(Cl)=NC(NC3CCCC3)=C2N=C1 AHAPTFOPJBIRLR-HZHPXBFKSA-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
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
- WBLZUCOIBUDNBV-UHFFFAOYSA-N 3-nitropropanoic acid Chemical compound OC(=O)CC[N+]([O-])=O WBLZUCOIBUDNBV-UHFFFAOYSA-N 0.000 description 1
- CCTQEHDMZKCPPK-UHFFFAOYSA-N 5-(2-phenylethylamino)-3h-1,3,4-thiadiazole-2-thione Chemical compound S1C(=S)NN=C1NCCC1=CC=CC=C1 CCTQEHDMZKCPPK-UHFFFAOYSA-N 0.000 description 1
- 229940077122 Adenosine A1 receptor agonist Drugs 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010011891 Deafness neurosensory Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 208000009966 Sensorineural Hearing Loss Diseases 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 230000003542 behavioural effect 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
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000002639 bone cement Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 231100000890 cochlea damage Toxicity 0.000 description 1
- 210000002777 columnar cell Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000004590 drinking behavior Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000020595 eating behavior Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 210000004209 hair Anatomy 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000005065 mining Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 231100000199 ototoxic Toxicity 0.000 description 1
- 230000002970 ototoxic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000011422 pharmacological therapy Methods 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 210000001191 round window ear Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 231100000879 sensorineural hearing loss Toxicity 0.000 description 1
- 208000023573 sensorineural hearing loss disease Diseases 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000003454 tympanic membrane Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Images
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
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Otolaryngology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NZ57046908 | 2008-08-11 | ||
| NZ570469 | 2008-08-11 | ||
| PCT/NZ2009/000164 WO2010019057A1 (en) | 2008-08-11 | 2009-08-11 | The treatment of hearing loss |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011530585A true JP2011530585A (ja) | 2011-12-22 |
| JP2011530585A5 JP2011530585A5 (enExample) | 2012-09-20 |
Family
ID=41669060
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011522927A Withdrawn JP2011530585A (ja) | 2008-08-11 | 2009-08-11 | 難聴の治療法 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20110207689A1 (enExample) |
| EP (1) | EP2328577A4 (enExample) |
| JP (1) | JP2011530585A (enExample) |
| CN (1) | CN102159209A (enExample) |
| AU (1) | AU2009280369A1 (enExample) |
| CA (1) | CA2733918A1 (enExample) |
| MX (1) | MX2011001551A (enExample) |
| WO (1) | WO2010019057A1 (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6279496B2 (ja) * | 2015-01-08 | 2018-02-14 | 積水化成品工業株式会社 | 発泡粒子及び発泡成形体 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5248770A (en) * | 1984-10-26 | 1993-09-28 | The United States Of America, As Represented By The Department Of Health And Human Services | Molecular probes for adenosine receptors |
| US4968672A (en) * | 1987-01-02 | 1990-11-06 | The United States Of America As Represented By The Department Of Health And Human Services | Adenosine receptor prodrugs |
| SE9401499D0 (sv) * | 1994-05-02 | 1994-05-02 | Item Dev Ab | New method of treatment |
| AU2603197A (en) * | 1996-04-10 | 1997-10-29 | United States Of America, Represented By The Secretary, Department Of Health And Human Services, The | Use of an a1 adenosine receptor agonist to treat cerebral ischaemia |
| US6649621B2 (en) * | 1997-12-16 | 2003-11-18 | The United States Of America As Represented By The Secretary Of The Navy | Prevention or reversal of sensorineural hearing loss (SNHL) through biologic mechanisms |
| US6177434B1 (en) * | 1997-12-16 | 2001-01-23 | The United States Of America As Represented By The Secretary Of The Navy | Prevention or reversal of sensorineural hearing loss (SNHL) through biologic mechanisms |
| WO2004096256A1 (en) * | 2001-01-23 | 2004-11-11 | The United States Of America, As Represented By The Secretary Of The Navy | Methods for preventing and treating loss of balance function due to oxidative stress |
| EP2278999B1 (en) * | 2008-04-21 | 2025-01-29 | Dompé farmaceutici S.p.A. | Auris formulations for treating otic diseases and conditions |
-
2009
- 2009-08-11 MX MX2011001551A patent/MX2011001551A/es not_active Application Discontinuation
- 2009-08-11 CA CA2733918A patent/CA2733918A1/en not_active Abandoned
- 2009-08-11 CN CN2009801365537A patent/CN102159209A/zh active Pending
- 2009-08-11 EP EP09806903A patent/EP2328577A4/en not_active Withdrawn
- 2009-08-11 JP JP2011522927A patent/JP2011530585A/ja not_active Withdrawn
- 2009-08-11 AU AU2009280369A patent/AU2009280369A1/en not_active Abandoned
- 2009-08-11 WO PCT/NZ2009/000164 patent/WO2010019057A1/en not_active Ceased
- 2009-08-11 US US13/058,437 patent/US20110207689A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2733918A1 (en) | 2010-02-18 |
| CN102159209A (zh) | 2011-08-17 |
| US20110207689A1 (en) | 2011-08-25 |
| EP2328577A4 (en) | 2011-10-19 |
| MX2011001551A (es) | 2011-03-29 |
| AU2009280369A1 (en) | 2010-02-18 |
| WO2010019057A1 (en) | 2010-02-18 |
| EP2328577A1 (en) | 2011-06-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Pourbakht et al. | Ebselen attenuates cochlear damage caused by acoustic trauma | |
| Yamashita et al. | Post-exposure treatment attenuates noise-induced hearing loss | |
| Sergi et al. | Cisplatin ototoxicity in the guinea pig: vestibular and cochlear damage | |
| Hu et al. | R-phenylisopropyladenosine attenuates noise-induced hearing loss in the chinchilla | |
| Shoji et al. | Differential protective effects of neurotrophins in the attenuation of noise-induced hair cell loss | |
| Himeno et al. | Intra-cochlear administration of dexamethasone attenuates aminoglycoside ototoxicity in the guinea pig | |
| Yamashita et al. | Delayed production of free radicals following noise exposure | |
| US9889107B2 (en) | Methods and compositions for preventing and treating auditory dysfunctions | |
| US6649621B2 (en) | Prevention or reversal of sensorineural hearing loss (SNHL) through biologic mechanisms | |
| Tsukasaki et al. | Acute changes in cochlear potentials due to cisplatin | |
| KR101429735B1 (ko) | 와우각 흥분독성에 의해 유발된 이명의 치료를 위한 nmda 수용체 길항제의 용도 | |
| EP3322412B1 (en) | Use of amitriptyline for blocking brain hemichannels and method for potentiating its effect in vivo | |
| US20100254907A1 (en) | Methods for the treatment of tinnitus induced by cochlear excitotoxicity | |
| Harris et al. | Prevention of noise-induced hearing loss with Src-PTK inhibitors | |
| Abaamrane et al. | Long-term administration of magnesium after acoustic trauma caused by gunshot noise in guinea pigs | |
| US10966940B2 (en) | Methods for the treatment of tinnitus induced by cochlear excitotoxicity | |
| Wong et al. | Post exposure administration of A1 adenosine receptor agonists attenuates noise-induced hearing loss | |
| Manalo et al. | Adenosine A2B receptor: A pathogenic factor and a therapeutic target for sensorineural hearing loss | |
| Mom et al. | Monitoring of functional changes after transient ischemia in gerbil cochlea | |
| Niu et al. | The signal transduction pathway for the dopamine D1 receptor in the guinea-pig cochlea | |
| Bielefeld | Protection from noise-induced hearing loss with Src inhibitors | |
| JP2011530585A (ja) | 難聴の治療法 | |
| Bielefeld et al. | Protection from impulse noise-induced hearing loss with novel Src-protein tyrosine kinase inhibitors | |
| TAŞ et al. | Effects of intratympanic steroid on cisplatin ototoxicity: An electrophysiological and ultrastructural study Cisplatin ototoksisitesinde intratimpanik steroid etkinligi: Elektrofizyolojik ve ultrastruktürel bir çalısma | |
| US20240294925A1 (en) | Method of Treatment for Auditory Dysfunction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120801 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120801 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20130816 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130816 |