GB2450747A - Treatment of sensorineural hearing loss - Google Patents
Treatment of sensorineural hearing loss Download PDFInfo
- Publication number
- GB2450747A GB2450747A GB0713139A GB0713139A GB2450747A GB 2450747 A GB2450747 A GB 2450747A GB 0713139 A GB0713139 A GB 0713139A GB 0713139 A GB0713139 A GB 0713139A GB 2450747 A GB2450747 A GB 2450747A
- Authority
- GB
- United Kingdom
- Prior art keywords
- agent
- par
- auditory
- agent according
- cell
- 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- Withdrawn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
- 208000009966 Sensorineural Hearing Loss Diseases 0.000 title claims abstract description 36
- 206010011891 Deafness neurosensory Diseases 0.000 title claims description 32
- 208000023573 sensorineural hearing loss disease Diseases 0.000 title claims description 32
- 231100000879 sensorineural hearing loss Toxicity 0.000 title claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 243
- 210000002569 neuron Anatomy 0.000 claims abstract description 85
- 238000000034 method Methods 0.000 claims abstract description 57
- 102000002020 Protease-activated receptors Human genes 0.000 claims abstract description 35
- 108050009310 Protease-activated receptors Proteins 0.000 claims abstract description 35
- 210000000130 stem cell Anatomy 0.000 claims abstract description 32
- 229960004072 thrombin Drugs 0.000 claims abstract description 29
- 108090000190 Thrombin Proteins 0.000 claims abstract description 25
- 239000000556 agonist Substances 0.000 claims abstract description 24
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims abstract description 23
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims abstract description 23
- 229960000187 tissue plasminogen activator Drugs 0.000 claims abstract description 22
- 108010088842 Fibrinolysin Proteins 0.000 claims abstract description 16
- 229940012957 plasmin Drugs 0.000 claims abstract description 16
- 230000004069 differentiation Effects 0.000 claims abstract description 13
- 230000014511 neuron projection development Effects 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 108010001779 Ancrod Proteins 0.000 claims abstract description 8
- 229960004233 ancrod Drugs 0.000 claims abstract description 8
- 238000002513 implantation Methods 0.000 claims abstract description 5
- 210000004027 cell Anatomy 0.000 claims description 74
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 49
- 108090000623 proteins and genes Proteins 0.000 claims description 47
- 239000012634 fragment Substances 0.000 claims description 44
- 239000007943 implant Substances 0.000 claims description 40
- 108091005804 Peptidases Proteins 0.000 claims description 36
- 239000004365 Protease Substances 0.000 claims description 35
- 101001028689 Homo sapiens Protein JTB Proteins 0.000 claims description 34
- 102100037171 Protein JTB Human genes 0.000 claims description 34
- 102000004169 proteins and genes Human genes 0.000 claims description 33
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 26
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 102100037132 Proteinase-activated receptor 2 Human genes 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 20
- NTQVODZUQIATFS-WAUHAFJUSA-N (2s)-2-[[(2s)-6-amino-2-[[2-[[(2s,3s)-2-[[(2s)-2-[[(2s)-2-amino-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]hexanoyl]amino]-3-methylbutanoic acid Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O NTQVODZUQIATFS-WAUHAFJUSA-N 0.000 claims description 19
- 101710121435 Proteinase-activated receptor 2 Proteins 0.000 claims description 19
- 230000003213 activating effect Effects 0.000 claims description 19
- 108020001507 fusion proteins Proteins 0.000 claims description 16
- 102000037865 fusion proteins Human genes 0.000 claims description 16
- 210000002241 neurite Anatomy 0.000 claims description 16
- 102100037133 Proteinase-activated receptor 3 Human genes 0.000 claims description 12
- 101710121425 Proteinase-activated receptor 3 Proteins 0.000 claims description 12
- 229920001184 polypeptide Polymers 0.000 claims description 12
- 101710186509 Partitioning defective 3 homolog Proteins 0.000 claims description 10
- 102100023710 Proteinase-activated receptor 4 Human genes 0.000 claims description 10
- 101710121439 Proteinase-activated receptor 4 Proteins 0.000 claims description 10
- 210000002768 hair cell Anatomy 0.000 claims description 10
- 230000000638 stimulation Effects 0.000 claims description 10
- 230000024245 cell differentiation Effects 0.000 claims description 9
- 239000002243 precursor Substances 0.000 claims description 9
- 208000003098 Ganglion Cysts Diseases 0.000 claims description 8
- 208000005400 Synovial Cyst Diseases 0.000 claims description 8
- 230000004936 stimulating effect Effects 0.000 claims description 8
- 230000001976 improved effect Effects 0.000 claims description 7
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 150000003384 small molecules Chemical class 0.000 claims description 4
- SGPMJRPYYIJZPC-JYAZKYGWSA-N (2s,3s)-2-[[(2s)-2-[[(2s)-2-amino-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-n-[2-[[(2s)-1-[[(2s)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]-3-methylpentanamide Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(C)C)C(N)=O SGPMJRPYYIJZPC-JYAZKYGWSA-N 0.000 claims description 3
- 108010063157 2-furoyl-LIGRLO-amide Proteins 0.000 claims description 3
- HOWDUIVVWDUEED-WAUHAFJUSA-N Ser-Leu-Ile-Gly-Lys-Val-Amide Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(N)=O HOWDUIVVWDUEED-WAUHAFJUSA-N 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- 108010054243 seryl-leucyl-isoleucyl-glycyl-lysyl-valinamide Proteins 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 2
- 230000017363 positive regulation of growth Effects 0.000 claims description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 4
- PVPBBTJXIKFICP-UHFFFAOYSA-N (7-aminophenothiazin-3-ylidene)azanium;chloride Chemical compound [Cl-].C1=CC(=[NH2+])C=C2SC3=CC(N)=CC=C3N=C21 PVPBBTJXIKFICP-UHFFFAOYSA-N 0.000 claims 1
- 108010022999 Serine Proteases Proteins 0.000 abstract description 6
- 102000012479 Serine Proteases Human genes 0.000 abstract description 6
- 108010003179 seryl-leucyl-isoleucyl-glycyl-lysyl-valine Proteins 0.000 abstract 1
- 108010063955 thrombin receptor peptide (42-47) Proteins 0.000 abstract 1
- 150000007523 nucleic acids Chemical group 0.000 description 45
- 241000282414 Homo sapiens Species 0.000 description 40
- 102000035195 Peptidases Human genes 0.000 description 32
- 235000018102 proteins Nutrition 0.000 description 32
- 108020004707 nucleic acids Proteins 0.000 description 31
- 102000039446 nucleic acids Human genes 0.000 description 31
- 206010011878 Deafness Diseases 0.000 description 30
- 125000003275 alpha amino acid group Chemical group 0.000 description 30
- 108090000631 Trypsin Proteins 0.000 description 28
- 102000004142 Trypsin Human genes 0.000 description 28
- 239000012588 trypsin Substances 0.000 description 28
- 208000016354 hearing loss disease Diseases 0.000 description 26
- 235000019419 proteases Nutrition 0.000 description 24
- 235000001014 amino acid Nutrition 0.000 description 21
- 230000027455 binding Effects 0.000 description 20
- 238000009739 binding Methods 0.000 description 20
- 150000001413 amino acids Chemical class 0.000 description 18
- 108060003951 Immunoglobulin Proteins 0.000 description 17
- 231100000895 deafness Toxicity 0.000 description 17
- 102000018358 immunoglobulin Human genes 0.000 description 17
- 108091028043 Nucleic acid sequence Proteins 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 210000001323 spiral ganglion Anatomy 0.000 description 14
- 150000001875 compounds Chemical group 0.000 description 12
- 239000000427 antigen Substances 0.000 description 11
- 108091007433 antigens Proteins 0.000 description 11
- 102000036639 antigens Human genes 0.000 description 11
- 231100000888 hearing loss Toxicity 0.000 description 11
- 230000010370 hearing loss Effects 0.000 description 11
- 230000004031 neuronal differentiation Effects 0.000 description 11
- 108091023037 Aptamer Proteins 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 238000003776 cleavage reaction Methods 0.000 description 9
- 238000010494 dissociation reaction Methods 0.000 description 9
- 230000005593 dissociations Effects 0.000 description 9
- 238000009396 hybridization Methods 0.000 description 9
- 230000007017 scission Effects 0.000 description 9
- 239000003446 ligand Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 210000003477 cochlea Anatomy 0.000 description 7
- 210000000860 cochlear nerve Anatomy 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 208000016621 Hearing disease Diseases 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- -1 antibody Proteins 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000013598 vector Substances 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 244000068988 Glycine max Species 0.000 description 4
- 235000010469 Glycine max Nutrition 0.000 description 4
- 102000013566 Plasminogen Human genes 0.000 description 4
- 108010051456 Plasminogen Proteins 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 210000001052 bipolar neuron Anatomy 0.000 description 4
- 210000000133 brain stem Anatomy 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000004379 membrane Anatomy 0.000 description 4
- 230000003955 neuronal function Effects 0.000 description 4
- 230000001953 sensory effect Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- 101710089384 Extracellular protease Proteins 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 3
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 3
- 102000039536 PAR family Human genes 0.000 description 3
- 108091067368 PAR family Proteins 0.000 description 3
- 108010070503 PAR-2 Receptor Proteins 0.000 description 3
- 102000032628 PAR-2 Receptor Human genes 0.000 description 3
- 102000001938 Plasminogen Activators Human genes 0.000 description 3
- 108010001014 Plasminogen Activators Proteins 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 238000004422 calculation algorithm Methods 0.000 description 3
- 210000005056 cell body Anatomy 0.000 description 3
- 239000012707 chemical precursor Substances 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 3
- 210000000959 ear middle Anatomy 0.000 description 3
- 210000005069 ears Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000008447 perception Effects 0.000 description 3
- 238000002823 phage display Methods 0.000 description 3
- 229940127126 plasminogen activator Drugs 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 241001514645 Agonis Species 0.000 description 2
- 208000015068 Central auditory processing disease Diseases 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- 206010011903 Deafness traumatic Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 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
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 101000605403 Homo sapiens Plasminogen Proteins 0.000 description 2
- 101000651439 Homo sapiens Prothrombin Proteins 0.000 description 2
- 208000030979 Language Development disease Diseases 0.000 description 2
- 201000009906 Meningitis Diseases 0.000 description 2
- 208000002946 Noise-Induced Hearing Loss Diseases 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 108010094028 Prothrombin Proteins 0.000 description 2
- 102100027378 Prothrombin Human genes 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
- 241000270295 Serpentes Species 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 101710162629 Trypsin inhibitor Proteins 0.000 description 2
- 229940122618 Trypsin inhibitor Drugs 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- 201000002664 drug-induced hearing loss Diseases 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000012678 infectious agent Substances 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- HCZKYJDFEPMADG-TXEJJXNPSA-N masoprocol Chemical compound C([C@H](C)[C@H](C)CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-TXEJJXNPSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000007514 neuronal growth Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 229940039716 prothrombin Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000002753 trypsin inhibitor Substances 0.000 description 2
- 239000002435 venom Substances 0.000 description 2
- 210000001048 venom Anatomy 0.000 description 2
- 231100000611 venom Toxicity 0.000 description 2
- ANAMCEKSRDPIPX-GFGQVAFXSA-N (2s)-n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-2-[[(2s)-2-[[(2s,3r)-2-amino-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanamide Chemical compound NC(N)=NCCC[C@@H](C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)O)CC1=CC=CC=C1 ANAMCEKSRDPIPX-GFGQVAFXSA-N 0.000 description 1
- BBAOHIALRKLBRD-OZDPOCAXSA-N (2s)-n-[2-[[(2s)-6-amino-1-[[(2s)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]-1-[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carboxamide Chemical compound C([C@H](NC(=O)[C@@H](N)C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)C1=CC=C(O)C=C1 BBAOHIALRKLBRD-OZDPOCAXSA-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
- 102400000069 Activation peptide Human genes 0.000 description 1
- 101800001401 Activation peptide Proteins 0.000 description 1
- 206010002961 Aplasia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 101000772006 Bombus ignitus Venom serine protease Bi-VSP Proteins 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008164 Cerebrospinal fluid leakage Diseases 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 108020004394 Complementary RNA Proteins 0.000 description 1
- 208000000781 Conductive Hearing Loss Diseases 0.000 description 1
- 206010010280 Conductive deafness Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 241000271532 Crotalus Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 206010015108 Epstein-Barr virus infection Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 108091006020 Fc-tagged proteins Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000331546 Grubea cochlear Species 0.000 description 1
- 241001188564 Gymnosoma par Species 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000032041 Hearing impaired Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 101000603877 Homo sapiens Nuclear receptor subfamily 1 group I member 2 Proteins 0.000 description 1
- 101001098560 Homo sapiens Proteinase-activated receptor 2 Proteins 0.000 description 1
- 101000713170 Homo sapiens Solute carrier family 52, riboflavin transporter, member 1 Proteins 0.000 description 1
- 101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 description 1
- 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 1
- 206010048865 Hypoacusis Diseases 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- 206010056677 Nerve degeneration Diseases 0.000 description 1
- 102000008730 Nestin Human genes 0.000 description 1
- 108010088225 Nestin Proteins 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108010044027 PAR-1-activating peptide Proteins 0.000 description 1
- 102100032341 PCNA-interacting partner Human genes 0.000 description 1
- 101710196737 PCNA-interacting partner Proteins 0.000 description 1
- 102100040853 PRKC apoptosis WT1 regulator protein Human genes 0.000 description 1
- 101710162991 PRKC apoptosis WT1 regulator protein Proteins 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 206010036626 Presbyacusis Diseases 0.000 description 1
- 108091008103 RNA aptamers Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 101100221606 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS7 gene Proteins 0.000 description 1
- 108090000083 Serine Endopeptidases Proteins 0.000 description 1
- 102000003667 Serine Endopeptidases Human genes 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 108091027076 Spiegelmer Proteins 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 102100024270 Transcription factor SOX-2 Human genes 0.000 description 1
- 108060005989 Tryptase Proteins 0.000 description 1
- 102000001400 Tryptase Human genes 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 241000271897 Viperidae Species 0.000 description 1
- 229940045942 acetone sodium bisulfite Drugs 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- PYMYPHUHKUWMLA-MROZADKFSA-N aldehydo-L-ribose Chemical compound OC[C@H](O)[C@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-MROZADKFSA-N 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 210000003984 auditory pathway Anatomy 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 108010008663 cinnamoyl-LIGRLO-amide Proteins 0.000 description 1
- 210000000262 cochlear duct Anatomy 0.000 description 1
- 210000003952 cochlear nucleus Anatomy 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 208000023563 conductive hearing loss disease Diseases 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 239000003398 denaturant Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- VHJLVAABSRFDPM-ZXZARUISSA-N dithioerythritol Chemical compound SC[C@H](O)[C@H](O)CS VHJLVAABSRFDPM-ZXZARUISSA-N 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 210000003027 ear inner Anatomy 0.000 description 1
- 238000000635 electron micrograph Methods 0.000 description 1
- 210000003060 endolymph Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- HCZKYJDFEPMADG-UHFFFAOYSA-N erythro-nordihydroguaiaretic acid Natural products C=1C=C(O)C(O)=CC=1CC(C)C(C)CC1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-UHFFFAOYSA-N 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 102000047823 human PLAT Human genes 0.000 description 1
- 229940039715 human prothrombin Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000012804 iterative process Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229960003951 masoprocol Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000005055 nestin Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000004766 neurogenesis Effects 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 210000001517 olfactory receptor neuron Anatomy 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
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 210000004049 perilymph Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 208000009800 presbycusis Diseases 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000001079 scala tympani Anatomy 0.000 description 1
- 210000001605 scala vestibuli Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002265 sensory receptor cell Anatomy 0.000 description 1
- 102000027509 sensory receptors Human genes 0.000 description 1
- 108091008691 sensory receptors Proteins 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 108010004116 seryl-leucyl-isoleucyl-glycyl-arginyl-leucinamide Proteins 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- YNJORDSKPXMABC-UHFFFAOYSA-M sodium;2-hydroxypropane-2-sulfonate Chemical compound [Na+].CC(C)(O)S([O-])(=O)=O YNJORDSKPXMABC-UHFFFAOYSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 229940035024 thioglycerol Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 230000036964 tight binding Effects 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 125000002640 tocopherol group Chemical class 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 230000001810 trypsinlike Effects 0.000 description 1
- 210000003454 tympanic membrane Anatomy 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000001720 vestibular Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/18—Internal ear or nose parts, e.g. ear-drums
-
- 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
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4833—Thrombin (3.4.21.5)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/484—Plasmin (3.4.21.7)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/49—Urokinase; Tissue plasminogen activator
-
- 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)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- Transplantation (AREA)
- Otolaryngology (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0713139A GB2450747A (en) | 2007-07-06 | 2007-07-06 | Treatment of sensorineural hearing loss |
| PCT/GB2008/050542 WO2009007746A2 (fr) | 2007-07-06 | 2008-07-07 | Traitement d'une déficience auditive sensorineurale |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0713139A GB2450747A (en) | 2007-07-06 | 2007-07-06 | Treatment of sensorineural hearing loss |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB0713139D0 GB0713139D0 (en) | 2007-08-15 |
| GB2450747A true GB2450747A (en) | 2009-01-07 |
Family
ID=38440509
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0713139A Withdrawn GB2450747A (en) | 2007-07-06 | 2007-07-06 | Treatment of sensorineural hearing loss |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB2450747A (fr) |
| WO (1) | WO2009007746A2 (fr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102016110642A1 (de) | 2016-06-09 | 2017-12-14 | Nordmark Holding Gmbh | Verwendung von Ancrod zur Vorbeugung und/oder Behandlung von Ischämie |
| GB201615714D0 (en) | 2016-09-15 | 2016-11-02 | Univ Of Sheffield The | Otic progenitor identification and isolation |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999043809A2 (fr) * | 1998-02-27 | 1999-09-02 | The Regents Of The University Of California | Recepteur 4 active par la protease et ses utilisations |
| WO2000063371A1 (fr) * | 1999-04-15 | 2000-10-26 | University Of Southampton | Recepteurs par-2 actives par des proteases |
| WO2001094411A1 (fr) * | 2000-06-05 | 2001-12-13 | The Regents Of The University Of California | Peptides modulant des recepteurs actives par des recepteurs de protease et methodes d'utilisation |
| WO2004073504A2 (fr) * | 2003-02-20 | 2004-09-02 | Proteon Therapeutics, Llc | Techniques de traitement et de prevention de maladies de conduits biologiques |
| US20060104944A1 (en) * | 2004-11-18 | 2006-05-18 | Mousa Shaker A | Activators and inhibitors of protease activated receptor2 (PAR2) and methods of use |
| WO2007049096A1 (fr) * | 2005-10-25 | 2007-05-03 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Procede d’expansion de cellules endotheliales progenitrices |
| EP1845104A1 (fr) * | 2004-12-28 | 2007-10-17 | Kowa Company. Ltd. | Agoniste du récepteur par-2 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02292226A (ja) * | 1989-05-08 | 1990-12-03 | Shigemi Fujisaki | 障害された神経細胞賦活予防治療剤 |
| US5523292A (en) * | 1992-10-14 | 1996-06-04 | Schwartz; Robert | Method of preventing restenosis following coronary angioplasty |
| NZ510456A (en) * | 1998-09-15 | 2004-01-30 | Univ Melbourne | A method of treatment and agents useful for same |
| JP4065642B2 (ja) * | 2000-02-24 | 2008-03-26 | 扶桑薬品工業株式会社 | 消化器系疾患の予防、治療用組成物 |
| TWI257307B (en) * | 2000-07-12 | 2006-07-01 | Orthologic Corp | Pharmaceutical composition for cardiac tissue repair |
| US7067492B2 (en) * | 2001-09-06 | 2006-06-27 | Omnio Ab | Method of promoting healing of a tympanic membrane perforation |
| US6787135B2 (en) * | 2002-03-13 | 2004-09-07 | William Beaumont Hospital | Modification of vitreal matrix metalloproteinase activity |
| US20050232925A1 (en) * | 2002-03-18 | 2005-10-20 | Sukhatme Vikas P | Protease activity of thrombin inhibits angiogenesis |
-
2007
- 2007-07-06 GB GB0713139A patent/GB2450747A/en not_active Withdrawn
-
2008
- 2008-07-07 WO PCT/GB2008/050542 patent/WO2009007746A2/fr active Application Filing
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999043809A2 (fr) * | 1998-02-27 | 1999-09-02 | The Regents Of The University Of California | Recepteur 4 active par la protease et ses utilisations |
| WO2000063371A1 (fr) * | 1999-04-15 | 2000-10-26 | University Of Southampton | Recepteurs par-2 actives par des proteases |
| WO2001094411A1 (fr) * | 2000-06-05 | 2001-12-13 | The Regents Of The University Of California | Peptides modulant des recepteurs actives par des recepteurs de protease et methodes d'utilisation |
| WO2004073504A2 (fr) * | 2003-02-20 | 2004-09-02 | Proteon Therapeutics, Llc | Techniques de traitement et de prevention de maladies de conduits biologiques |
| US20060104944A1 (en) * | 2004-11-18 | 2006-05-18 | Mousa Shaker A | Activators and inhibitors of protease activated receptor2 (PAR2) and methods of use |
| EP1845104A1 (fr) * | 2004-12-28 | 2007-10-17 | Kowa Company. Ltd. | Agoniste du récepteur par-2 |
| WO2007049096A1 (fr) * | 2005-10-25 | 2007-05-03 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Procede d’expansion de cellules endotheliales progenitrices |
Non-Patent Citations (2)
| Title |
|---|
| Ann. Otol. Rhinol. Laryngol., Vol.112, 2003, Mora, R. et al., "Intravenous infusion of recombinant...", pp.665-670 * |
| Int. Tinnitus J., Vol.11, 2005, Mora, R. et al., "The use of recombinant tissue-type plasminogen activator...", pp.181-184 * |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0713139D0 (en) | 2007-08-15 |
| WO2009007746A2 (fr) | 2009-01-15 |
| WO2009007746A3 (fr) | 2009-03-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7091423B2 (ja) | 改変ｃｄ１６が関係するポリペプチド、細胞、及び方法 | |
| JP4456275B2 (ja) | 細胞表面分子誘導性マクロファージ活性化 | |
| JP4243355B2 (ja) | 細胞膜に固定された抗凝固性融合タンパク質 | |
| McLane et al. | Disintegrins in health and disease | |
| US7837993B2 (en) | Methods and compositions for regeneration of aged skeletal muscle tissues | |
| TWI486168B (zh) | 治療內皮功能不良之方法 | |
| BR112012002151A2 (pt) | Métodos para expressar uma desintegrina e metaloproteinase com proteína de motivo trombospondina, para produzir uma composição de desintegrina e metaloproteinase com proteína de motivo trombospondina, para produzir uma composição de desintegrina e metaloproteinase com proteína de motivo trombospondina,e, composição de proteína de desintegrina e metaloproteinase com proteína de motivo trombospondina. | |
| UA120596C2 (uk) | Моноклональне антитіло проти інгібітора шляху тканинного фактора (tfpi) | |
| JP3410103B2 (ja) | シュワン細胞の分離および培養 | |
| MXPA05006853A (es) | Usos de citocinas de mamifero; reactivos relacionados. | |
| CN107638565A (zh) | 用于治疗与masp‑2依赖性补体活化相关的状况的方法 | |
| US20210147798A1 (en) | Artificially Manipulated Immune Cell | |
| CN104177464B (zh) | Cd83在联合治疗中的用途 | |
| KR102456795B1 (ko) | 세타-디펜신들로 염증성 프로테아제들의 차단 | |
| Hall et al. | Gas6 binding to photoreceptor outer segments requires γ-carboxyglutamic acid (Gla) and Ca2+ and is required for OS phagocytosis by RPE cells in vitro | |
| CN101970472A (zh) | Rtef-1变体及其用于抑制血管发生的用途 | |
| US7935341B2 (en) | Antibodies to complementary peptides of thrombin or portions thereof | |
| AU2016257722A1 (en) | Methods for enhancing an immune response with a CTLA-4 antagonist | |
| US20140288010A1 (en) | Compositions and Methods for Increasing Stem Cell Survival | |
| US9475876B2 (en) | Anti oncostatin M receptor beta antibody used for treating atopic dermatitis | |
| GB2450747A (en) | Treatment of sensorineural hearing loss | |
| JPH08507754A (ja) | Ｍｈｃ−１拘束性抗原提示におけるａｔｐ−ユビキチン依存蛋白分解の役割およびそのインヒビター | |
| KR102211959B1 (ko) | Ｄｕｓｐ５를 유효성분으로 모두 포함하는 골대사성 질환의 예방 또는 치료용 약학적 조성물 | |
| US20030077757A1 (en) | Method of treating aging-related disorders | |
| TW200900077A (en) | Therapeutic agent for interstitial pulmonary disease comprising anti-HMGB-1 antibody |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |