AU2009280369A1 - The treatment of hearing loss - Google Patents
The treatment of hearing loss Download PDFInfo
- Publication number
- AU2009280369A1 AU2009280369A1 AU2009280369A AU2009280369A AU2009280369A1 AU 2009280369 A1 AU2009280369 A1 AU 2009280369A1 AU 2009280369 A AU2009280369 A AU 2009280369A AU 2009280369 A AU2009280369 A AU 2009280369A AU 2009280369 A1 AU2009280369 A1 AU 2009280369A1
- Authority
- AU
- Australia
- Prior art keywords
- noise
- adenosine receptor
- receptor agonist
- adenosine
- exposure
- 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.)
- Abandoned
Links
- 238000011282 treatment Methods 0.000 title claims description 52
- 208000016354 hearing loss disease Diseases 0.000 title description 22
- 206010011878 Deafness Diseases 0.000 title description 21
- 230000010370 hearing loss Effects 0.000 title description 20
- 231100000888 hearing loss Toxicity 0.000 title description 20
- 239000003379 purinergic P1 receptor agonist Substances 0.000 claims description 153
- 101150007969 ADORA1 gene Proteins 0.000 claims description 134
- 229940122614 Adenosine receptor agonist Drugs 0.000 claims description 116
- 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 claims description 94
- 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 89
- 210000003477 cochlea Anatomy 0.000 claims description 52
- 239000003814 drug Substances 0.000 claims description 52
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 44
- 229960005305 adenosine Drugs 0.000 claims description 44
- 238000000034 method Methods 0.000 claims description 44
- 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 35
- 206010011903 Deafness traumatic Diseases 0.000 claims description 22
- 208000002946 Noise-Induced Hearing Loss Diseases 0.000 claims description 22
- 230000006378 damage Effects 0.000 claims description 22
- -1 ([1 S-[1 a Chemical compound 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 239000012528 membrane Substances 0.000 claims description 13
- 230000001154 acute effect Effects 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 12
- 150000003254 radicals Chemical class 0.000 claims description 11
- 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 10
- 230000002035 prolonged effect Effects 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- GWVQGVCXFNYGFP-PFHKOEEOSA-N (2s,3s,4r,5r)-5-[6-(cyclopentylamino)purin-9-yl]-n-ethyl-3,4-dihydroxyoxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC=NC(NC3CCCC3)=C2N=C1 GWVQGVCXFNYGFP-PFHKOEEOSA-N 0.000 claims description 7
- 239000000556 agonist Substances 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
- 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 6
- 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 claims description 6
- 229950000347 selodenoson Drugs 0.000 claims description 6
- 208000037816 tissue injury Diseases 0.000 claims description 6
- 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 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 5
- XRLDSWLMHUQECH-UHFFFAOYSA-N cyclopentanecarboxamide Chemical compound NC(=O)C1CCCC1 XRLDSWLMHUQECH-UHFFFAOYSA-N 0.000 claims description 5
- 229930195712 glutamate Natural products 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 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 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 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
- 238000002347 injection Methods 0.000 description 42
- 239000007924 injection Substances 0.000 description 42
- 241001465754 Metazoa Species 0.000 description 40
- 238000011084 recovery Methods 0.000 description 33
- 241000700159 Rattus Species 0.000 description 31
- 230000004044 response Effects 0.000 description 29
- 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 28
- 230000000694 effects Effects 0.000 description 26
- 239000000243 solution Substances 0.000 description 26
- 210000002768 hair cell Anatomy 0.000 description 25
- 230000013707 sensory perception of sound Effects 0.000 description 25
- 239000003981 vehicle Substances 0.000 description 23
- 238000002474 experimental method Methods 0.000 description 15
- 210000000133 brain stem Anatomy 0.000 description 14
- 210000002985 organ of corti Anatomy 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 238000012744 immunostaining Methods 0.000 description 12
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 230000006727 cell loss Effects 0.000 description 10
- 210000000067 inner hair cell Anatomy 0.000 description 10
- 108050000203 Adenosine receptors Proteins 0.000 description 9
- 102000009346 Adenosine receptors Human genes 0.000 description 9
- 208000014674 injury Diseases 0.000 description 9
- 230000010412 perfusion Effects 0.000 description 9
- 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 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 208000027418 Wounds and injury Diseases 0.000 description 8
- 210000003027 ear inner Anatomy 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 238000001543 one-way ANOVA Methods 0.000 description 8
- 230000036542 oxidative stress Effects 0.000 description 8
- 230000036760 body temperature Effects 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 241000283707 Capra Species 0.000 description 6
- 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 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000007912 intraperitoneal administration Methods 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
- 229940044601 receptor agonist Drugs 0.000 description 6
- 239000000018 receptor agonist Substances 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 6
- 241000197194 Bulla Species 0.000 description 5
- 206010063602 Exposure to noise Diseases 0.000 description 5
- 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 5
- 241000700157 Rattus norvegicus Species 0.000 description 5
- 238000010162 Tukey test Methods 0.000 description 5
- 208000002352 blister Diseases 0.000 description 5
- 230000000763 evoking effect Effects 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 210000004049 perilymph Anatomy 0.000 description 5
- 238000002203 pretreatment Methods 0.000 description 5
- 238000007619 statistical method Methods 0.000 description 5
- 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
- 230000008901 benefit Effects 0.000 description 4
- 210000000238 cell of claudius Anatomy 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229960003299 ketamine Drugs 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000011200 topical administration Methods 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 238000011870 unpaired t-test 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
- 230000005788 Cochlea function Effects 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
- 108010009711 Phalloidine Proteins 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
- 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000000354 cell of hensen Anatomy 0.000 description 3
- 230000001684 chronic effect Effects 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
- 230000036541 health Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 230000035479 physiological effects, processes and functions Effects 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 3
- 210000001191 round window ear Anatomy 0.000 description 3
- 210000004761 scalp Anatomy 0.000 description 3
- 230000001953 sensory effect Effects 0.000 description 3
- 210000001323 spiral ganglion Anatomy 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 238000012385 systemic delivery Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 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
- 108010060263 Adenosine A1 Receptor Proteins 0.000 description 2
- 102000030814 Adenosine A1 receptor Human genes 0.000 description 2
- 241000700112 Chinchilla Species 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
- 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
- 230000004913 activation Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 210000003984 auditory pathway Anatomy 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000005779 cell damage Effects 0.000 description 2
- 239000000039 congener Substances 0.000 description 2
- 230000001120 cytoprotective effect Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 238000009826 distribution Methods 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
- 230000002631 hypothermal effect Effects 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 210000003990 interdental cell Anatomy 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
- 230000007246 mechanism Effects 0.000 description 2
- 210000001259 mesencephalon Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 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
- 238000002360 preparation method Methods 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 210000000645 stria vascularis Anatomy 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 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
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- RIRGCFBBHQEQQH-SSFGXONLSA-N (-)-n6-(2-phenylisopropyl)adenosine Chemical compound C([C@@H](C)NC=1C=2N=CN(C=2N=CN=1)[C@H]1[C@@H]([C@H](O)[C@@H](CO)O1)O)C1=CC=CC=C1 RIRGCFBBHQEQQH-SSFGXONLSA-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
- 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 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
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 101100298998 Caenorhabditis elegans pbs-3 gene Proteins 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 241000833010 Claudius Species 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
- 208000016952 Ear injury Diseases 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000013875 Heart injury Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010021113 Hypothermia Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 229930040373 Paraformaldehyde 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
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 208000020339 Spinal injury Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- OBAAIGREYDUOHX-ZGOQAQPGSA-N [(2r,3s,4r,5r)-3,4-dihydroxy-5-[6-[[(3r)-oxolan-3-yl]amino]purin-9-yl]oxolan-2-yl]methyl n-ethylcarbamate Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(=O)NCC)O[C@H]1N1C2=NC=NC(N[C@H]3COCC3)=C2N=C1 OBAAIGREYDUOHX-ZGOQAQPGSA-N 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
- 229940099424 adenocard Drugs 0.000 description 1
- 229940121359 adenosine receptor antagonist Drugs 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 230000004888 barrier function 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
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 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
- 208000029028 brain injury Diseases 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 231100000890 cochlea damage Toxicity 0.000 description 1
- 210000000262 cochlear duct Anatomy 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000895 deafness Toxicity 0.000 description 1
- 230000006735 deficit 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
- 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 1
- 230000004590 drinking behavior Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004634 feeding behavior Effects 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
- 235000019322 gelatine Nutrition 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 210000003128 head Anatomy 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 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
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 229940110728 nitrogen / oxygen Drugs 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 231100000199 ototoxic Toxicity 0.000 description 1
- 230000002970 ototoxic effect Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002093 peripheral effect 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
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000012764 semi-quantitative analysis Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 210000002205 spiral ligament of cochlea Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- 229950011435 tecadenoson Drugs 0.000 description 1
- 239000012085 test solution Substances 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
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 238000012800 visualization Methods 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
-
- 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 (1)
| Publication Number | Publication Date |
|---|---|
| AU2009280369A1 true AU2009280369A1 (en) | 2010-02-18 |
Family
ID=41669060
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2009280369A Abandoned AU2009280369A1 (en) | 2008-08-11 | 2009-08-11 | The treatment of hearing loss |
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 |
| JP2011530585A (ja) | 2011-12-22 |
| CN102159209A (zh) | 2011-08-17 |
| US20110207689A1 (en) | 2011-08-25 |
| EP2328577A4 (en) | 2011-10-19 |
| MX2011001551A (es) | 2011-03-29 |
| WO2010019057A1 (en) | 2010-02-18 |
| EP2328577A1 (en) | 2011-06-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Shoji et al. | Differential protective effects of neurotrophins in the attenuation of noise-induced hair cell loss | |
| Pourbakht et al. | Ebselen attenuates cochlear damage caused by acoustic trauma | |
| Sergi et al. | Cisplatin ototoxicity in the guinea pig: vestibular and cochlear damage | |
| KR101429735B1 (ko) | 와우각 흥분독성에 의해 유발된 이명의 치료를 위한 ｎｍｄａ 수용체 길항제의 용도 | |
| US8507525B2 (en) | Methods for the treatment of tinnitus induced by cochlear excitotoxicity | |
| US9889107B2 (en) | Methods and compositions for preventing and treating auditory dysfunctions | |
| US10966940B2 (en) | Methods for the treatment of tinnitus induced by cochlear excitotoxicity | |
| Abaamrane et al. | Long-term administration of magnesium after acoustic trauma caused by gunshot noise in guinea pigs | |
| Manalo et al. | Adenosine A2B receptor: A pathogenic factor and a therapeutic target for sensorineural hearing loss | |
| Wong et al. | Post exposure administration of A1 adenosine receptor agonists attenuates noise-induced hearing loss | |
| Kempfle et al. | Experimental drugs for the prevention or treatment of sensorineural hearing loss | |
| Bako et al. | The ototoxic effect of locally applied kanamycin and furosemide in guinea pigs | |
| Bielefeld | Protection from noise-induced hearing loss with Src inhibitors | |
| JP2008513407A (ja) | 中枢神経由来の神経障害性疼痛の治療用テトロドトキシンおよびその誘導体 | |
| AU2009280369A1 (en) | The treatment of hearing loss | |
| JP2015511242A (ja) | 病変性前庭障害の治療に使用するカルシニューリン阻害剤 | |
| CN113855803B (zh) | Prmt5抑制剂在用于制备听力保护药物中的用途 | |
| US12162935B2 (en) | Regimens, compositions and methods with capsaicin and TNF-alpha inhibitor | |
| US20240294925A1 (en) | Method of Treatment for Auditory Dysfunction | |
| Öntepeli et al. | Audiometry results and TEOAE and DPOAE amplitudes in men taking a phosphodiesterase type 5 inhibitor for erectile dysfunction | |
| Bremer et al. | Ototoxic study-‐I | |
| Perez et al. | Local drug delivery for inner ear therapy | |
| Abernathy | Aminoglycoside-Induced Otoneurotoxicity: Analysis of Inner Hair Cell Synaptic Plasticity Following Drug Exposure | |
| Magarinos et al. | frontiers REVIEW in Aging Neuroscience published: 21 April 2015 doi: 10.3389/fnagi. 2015.00058 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |