JP5538359B2 - リポソームボツリヌス毒素を使用する膀胱機能障害の治療 - Google Patents
リポソームボツリヌス毒素を使用する膀胱機能障害の治療 Download PDFInfo
- Publication number
- JP5538359B2 JP5538359B2 JP2011503214A JP2011503214A JP5538359B2 JP 5538359 B2 JP5538359 B2 JP 5538359B2 JP 2011503214 A JP2011503214 A JP 2011503214A JP 2011503214 A JP2011503214 A JP 2011503214A JP 5538359 B2 JP5538359 B2 JP 5538359B2
- Authority
- JP
- Japan
- Prior art keywords
- bont
- bladder
- botulinum toxin
- formulation
- lipid
- 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.)
- Expired - Fee Related
Links
- 108030001720 Bontoxilysin Proteins 0.000 title claims description 101
- 229940053031 botulinum toxin Drugs 0.000 title claims description 100
- 238000011282 treatment Methods 0.000 title description 19
- 206010069632 Bladder dysfunction Diseases 0.000 title description 4
- 239000002502 liposome Substances 0.000 claims description 84
- 150000002632 lipids Chemical class 0.000 claims description 35
- 239000000203 mixture Substances 0.000 claims description 35
- 238000009472 formulation Methods 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 21
- 206010020853 Hypertonic bladder Diseases 0.000 claims description 20
- 208000009722 Overactive Urinary Bladder Diseases 0.000 claims description 18
- 208000020629 overactive bladder Diseases 0.000 claims description 18
- 210000003741 urothelium Anatomy 0.000 claims description 9
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 239000002577 cryoprotective agent Substances 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 claims 2
- 239000007864 aqueous solution Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000007710 freezing Methods 0.000 claims 1
- 210000003932 urinary bladder Anatomy 0.000 description 60
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 51
- 108010057266 Type A Botulinum Toxins Proteins 0.000 description 32
- 230000000694 effects Effects 0.000 description 23
- 239000003814 drug Substances 0.000 description 21
- 229940079593 drug Drugs 0.000 description 19
- 241000700159 Rattus Species 0.000 description 16
- 239000007924 injection Substances 0.000 description 15
- 238000002347 injection Methods 0.000 description 15
- 102000004183 Synaptosomal-Associated Protein 25 Human genes 0.000 description 12
- 108010057722 Synaptosomal-Associated Protein 25 Proteins 0.000 description 12
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- 238000010790 dilution Methods 0.000 description 10
- 239000012895 dilution Substances 0.000 description 10
- 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 10
- 239000002953 phosphate buffered saline Substances 0.000 description 10
- 210000002700 urine Anatomy 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 206010002091 Anaesthesia Diseases 0.000 description 8
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 8
- 102100025588 Calcitonin gene-related peptide 1 Human genes 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 230000037005 anaesthesia Effects 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 150000003904 phospholipids Chemical class 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 206010046555 Urinary retention Diseases 0.000 description 6
- 230000008602 contraction Effects 0.000 description 6
- 238000012377 drug delivery Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 231100000765 toxin Toxicity 0.000 description 6
- 230000002485 urinary effect Effects 0.000 description 6
- 208000005615 Interstitial Cystitis Diseases 0.000 description 5
- 230000004888 barrier function Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 210000004969 inflammatory cell Anatomy 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000003053 toxin Substances 0.000 description 5
- 108700012359 toxins Proteins 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 101000879393 Aplysia californica Synaptobrevin Proteins 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 206010071289 Lower urinary tract symptoms Diseases 0.000 description 4
- 206010046543 Urinary incontinence Diseases 0.000 description 4
- 230000001022 anti-muscarinic effect Effects 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 4
- 230000012202 endocytosis Effects 0.000 description 4
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 4
- 229960003132 halothane Drugs 0.000 description 4
- 238000012744 immunostaining Methods 0.000 description 4
- 230000008595 infiltration Effects 0.000 description 4
- 238000001764 infiltration Methods 0.000 description 4
- 230000028709 inflammatory response Effects 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 230000036724 intravesical pressure Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000003068 molecular probe Substances 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010005033 Bladder dilatation Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 3
- 229920002683 Glycosaminoglycan Polymers 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 238000009530 blood pressure measurement Methods 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000005538 encapsulation Methods 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000027939 micturition Effects 0.000 description 3
- 229960002748 norepinephrine Drugs 0.000 description 3
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
- OBYNJKLOYWCXEP-UHFFFAOYSA-N 2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]-4-isothiocyanatobenzoate Chemical compound C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C1=CC(N=C=S)=CC=C1C([O-])=O OBYNJKLOYWCXEP-UHFFFAOYSA-N 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010005052 Bladder irritation Diseases 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
- 206010021639 Incontinence Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 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 2
- 102000007327 Protamines Human genes 0.000 description 2
- 108010007568 Protamines Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 229920002385 Sodium hyaluronate Polymers 0.000 description 2
- 102000003566 TRPV1 Human genes 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- 210000000436 anus Anatomy 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 239000012830 cancer therapeutic Substances 0.000 description 2
- 229960002504 capsaicin Drugs 0.000 description 2
- 235000017663 capsaicin Nutrition 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- 238000001378 electrochemiluminescence detection Methods 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 229920002674 hyaluronan Polymers 0.000 description 2
- 229960003160 hyaluronic acid Drugs 0.000 description 2
- 229960004716 idoxuridine Drugs 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000012792 lyophilization process Methods 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 230000036453 micturition reflex Effects 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 210000001640 nerve ending Anatomy 0.000 description 2
- 210000004126 nerve fiber Anatomy 0.000 description 2
- 230000007383 nerve stimulation Effects 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 239000002581 neurotoxin Substances 0.000 description 2
- 231100000618 neurotoxin Toxicity 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000018 receptor agonist Substances 0.000 description 2
- 229940044601 receptor agonist Drugs 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 229940010747 sodium hyaluronate Drugs 0.000 description 2
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000005062 synaptic transmission Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 210000003708 urethra Anatomy 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 208000019206 urinary tract infection Diseases 0.000 description 2
- 210000001215 vagina Anatomy 0.000 description 2
- ATCJTYORYKLVIA-SRXJVYAUSA-N vamp regimen Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1.C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1.C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C(C45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 ATCJTYORYKLVIA-SRXJVYAUSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- YJGVMLPVUAXIQN-LGWHJFRWSA-N (5s,5ar,8ar,9r)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-LGWHJFRWSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- OIRDTQYFTABQOQ-KQYNXXCUSA-N Adenosine Natural products C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 229930183010 Amphotericin Natural products 0.000 description 1
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 1
- 206010056948 Automatic bladder Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 231100000699 Bacterial toxin Toxicity 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010005063 Bladder pain Diseases 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 241000193155 Clostridium botulinum Species 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010011017 Corneal graft rejection Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 206010063057 Cystitis noninfective Diseases 0.000 description 1
- 108010049140 Endorphins Proteins 0.000 description 1
- 102000009025 Endorphins Human genes 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 102000000393 Ghrelin Receptors Human genes 0.000 description 1
- 108010016122 Ghrelin Receptors Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 description 1
- 206010029279 Neurogenic bladder Diseases 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 102100040460 P2X purinoceptor 3 Human genes 0.000 description 1
- 101710189970 P2X purinoceptor 3 Proteins 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 108010009711 Phalloidine Proteins 0.000 description 1
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 208000000921 Urge Urinary Incontinence Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- -1 adenosine triphosphates Chemical class 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940009444 amphotericin Drugs 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 210000000467 autonomic pathway Anatomy 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 239000000688 bacterial toxin Substances 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 208000029162 bladder disease Diseases 0.000 description 1
- 210000005068 bladder tissue Anatomy 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940089093 botox Drugs 0.000 description 1
- 231100001103 botulinum neurotoxin Toxicity 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- 230000007665 chronic toxicity Effects 0.000 description 1
- 231100000160 chronic toxicity Toxicity 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 231100001010 corrosive Toxicity 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 230000002638 denervation Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000000883 ear external Anatomy 0.000 description 1
- 210000003027 ear inner Anatomy 0.000 description 1
- 206010014801 endophthalmitis Diseases 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960000752 etoposide phosphate Drugs 0.000 description 1
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000010820 immunofluorescence microscopy Methods 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- 239000002120 nanofilm Substances 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 102000045222 parkin Human genes 0.000 description 1
- 229940043138 pentosan polysulfate Drugs 0.000 description 1
- 102000014187 peptide receptors Human genes 0.000 description 1
- 108010011903 peptide receptors Proteins 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000012910 preclinical development Methods 0.000 description 1
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 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
- DSDNAKHZNJAGHN-MXTYGGKSSA-N resiniferatoxin Chemical compound C1=C(O)C(OC)=CC(CC(=O)OCC=2C[C@]3(O)C(=O)C(C)=C[C@H]3[C@@]34[C@H](C)C[C@@]5(O[C@@](O4)(CC=4C=CC=CC=4)O[C@@H]5[C@@H]3C=2)C(C)=C)=C1 DSDNAKHZNJAGHN-MXTYGGKSSA-N 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229940099989 rimso-50 Drugs 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- 238000009094 second-line therapy Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 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
- 239000002356 single layer Substances 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 206010041232 sneezing Diseases 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000007666 subchronic toxicity Effects 0.000 description 1
- 231100000195 subchronic toxicity Toxicity 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 206010046494 urge incontinence Diseases 0.000 description 1
- 230000036325 urinary excretion Effects 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 230000036318 urination frequency Effects 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- 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)
- A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
- A61K38/4893—Botulinum neurotoxin (3.4.24.69)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dispersion Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4253608P | 2008-04-04 | 2008-04-04 | |
| US61/042,536 | 2008-04-04 | ||
| US11026608P | 2008-10-31 | 2008-10-31 | |
| US61/110,266 | 2008-10-31 | ||
| PCT/US2009/039489 WO2009139984A2 (en) | 2008-04-04 | 2009-04-03 | Method of treatment for bladder dysfunction |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014000235A Division JP2014062125A (ja) | 2008-04-04 | 2014-01-06 | リポソームボツリヌス毒素を使用する膀胱機能障害の治療 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011516497A JP2011516497A (ja) | 2011-05-26 |
| JP2011516497A5 JP2011516497A5 (https=) | 2011-12-08 |
| JP5538359B2 true JP5538359B2 (ja) | 2014-07-02 |
Family
ID=41319235
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011503214A Expired - Fee Related JP5538359B2 (ja) | 2008-04-04 | 2009-04-03 | リポソームボツリヌス毒素を使用する膀胱機能障害の治療 |
| JP2014000235A Withdrawn JP2014062125A (ja) | 2008-04-04 | 2014-01-06 | リポソームボツリヌス毒素を使用する膀胱機能障害の治療 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014000235A Withdrawn JP2014062125A (ja) | 2008-04-04 | 2014-01-06 | リポソームボツリヌス毒素を使用する膀胱機能障害の治療 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20120093920A1 (https=) |
| EP (2) | EP2273976A2 (https=) |
| JP (2) | JP5538359B2 (https=) |
| KR (1) | KR20100131471A (https=) |
| CN (1) | CN102065841A (https=) |
| AU (1) | AU2009246834B2 (https=) |
| BR (1) | BRPI0911098A2 (https=) |
| CA (1) | CA2720523C (https=) |
| MX (1) | MX2010010635A (https=) |
| WO (1) | WO2009139984A2 (https=) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2649984A1 (en) | 2012-04-13 | 2013-10-16 | Lipotec, S.A. | Compounds which inhibit neuronal exocytosis |
| EP2649983A1 (en) | 2012-04-13 | 2013-10-16 | Lipotec, S.A. | Compounds which inhibit neuronal exocytosis (II) |
| CA2869599C (en) | 2012-04-13 | 2021-07-27 | Lubrizol Advanced Materials, Inc. | Compounds which inhibit neuronal exocytosis (ii) |
| EP2649985A1 (en) | 2012-04-13 | 2013-10-16 | Lipotec, S.A. | Compounds which inhibit neuronal exocytosis (III) |
| JP6463266B2 (ja) | 2012-08-31 | 2019-01-30 | タリス バイオメディカル エルエルシー | 膀胱癌の治療のためのオキサリプラチンを含む薬物送達システム及び方法 |
| AU2013308465B2 (en) | 2012-08-31 | 2018-05-17 | Taris Biomedical Llc | Drug delivery systems and methods for treatment of prostate disease comprising gemicitabine |
| ES2952675T3 (es) | 2013-10-22 | 2023-11-03 | Lipella Pharmaceuticals Inc | Administración de agentes mediante el uso de liposomas metaestables |
| US20150250717A1 (en) | 2014-03-06 | 2015-09-10 | Taris Biomedical Llc | Drug delivery systems and methods for treatment of bladder cancer with gemcitabine |
| US20160045623A1 (en) | 2015-04-03 | 2016-02-18 | Lipella Pharmaceuticals, Inc. | Systems and Methods to Image Intercellular and Intercompartmental Defects with Magnetic Resonance Imaging (MRI) |
| SG10201913998YA (en) | 2017-07-25 | 2020-03-30 | Taris Biomedical Llc | Methods of treating tumor metastasis |
| WO2019046311A1 (en) | 2017-08-28 | 2019-03-07 | Revance Therapeutics, Inc. | TRANSMUCOSAL COMPOSITIONS OF BOTULINUM TOXIN, KITS AND METHODS FOR TREATING BLADDER DISORDERS |
| IL302714B1 (en) | 2017-11-08 | 2026-01-01 | Taris Biomedical Llc | Methods for treating and maintaining bladder cancer using gemcitabine |
| KR102398743B1 (ko) * | 2020-09-03 | 2022-05-16 | 충남대학교병원 | 초음파유도 마이크로버블을 포함하는 배뇨장애 치료제 조성물 |
| TWI760996B (zh) * | 2020-12-25 | 2022-04-11 | 姜秉均 | 含有疏水性物質的奈米組成物及其製備方法與用途 |
| CN117883383A (zh) * | 2023-12-26 | 2024-04-16 | 中国康复研究中心 | 一种作为A型肉毒素载体的TiO2纳米粒子及制备方法 |
| US12272439B1 (en) | 2024-05-06 | 2025-04-08 | Immunitybio, Inc. | Distributed ledger for medicament administration tracking |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3693209B2 (ja) * | 1996-04-11 | 2005-09-07 | 三菱化学株式会社 | 閉鎖小胞の製造方法 |
| AU2002323151A1 (en) | 2001-08-13 | 2003-03-03 | University Of Pittsburgh | Application of lipid vehicles and use for drug delivery |
| US20030224020A1 (en) * | 2002-05-31 | 2003-12-04 | Zabudkin Alexander F. | Pharmaceutical preparation of botulinum neurotoxin, methods of synthesis and methods of clinical use |
| US20040067235A1 (en) * | 2002-07-29 | 2004-04-08 | Rajiv Doshi | Methods for the use of neurotoxin in the treatment of urologic disorders |
| EP1585504A4 (en) * | 2002-11-06 | 2009-07-15 | Azaya Therapeutics Inc | Protein stabilized liposomal formulations of pharmaceutical active ingredients |
| JP5815915B2 (ja) * | 2005-10-11 | 2015-11-17 | ユニバーシティー オブ ピッツバーグ − オブ ザ コモンウェルス システム オブ ハイヤー エデュケーション | 過活動膀胱障害の治療のためのスフィンゴミエリンリポソーム |
-
2009
- 2009-04-03 WO PCT/US2009/039489 patent/WO2009139984A2/en not_active Ceased
- 2009-04-03 CN CN2009801204554A patent/CN102065841A/zh active Pending
- 2009-04-03 MX MX2010010635A patent/MX2010010635A/es not_active Application Discontinuation
- 2009-04-03 KR KR1020107022175A patent/KR20100131471A/ko not_active Ceased
- 2009-04-03 AU AU2009246834A patent/AU2009246834B2/en not_active Ceased
- 2009-04-03 CA CA2720523A patent/CA2720523C/en not_active Expired - Fee Related
- 2009-04-03 BR BRPI0911098A patent/BRPI0911098A2/pt not_active IP Right Cessation
- 2009-04-03 JP JP2011503214A patent/JP5538359B2/ja not_active Expired - Fee Related
- 2009-04-03 EP EP09747070A patent/EP2273976A2/en not_active Withdrawn
- 2009-04-03 EP EP13156622.6A patent/EP2599476A1/en not_active Withdrawn
-
2011
- 2011-12-09 US US13/315,861 patent/US20120093920A1/en not_active Abandoned
-
2014
- 2014-01-06 JP JP2014000235A patent/JP2014062125A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| KR20100131471A (ko) | 2010-12-15 |
| CA2720523A1 (en) | 2009-11-19 |
| CA2720523C (en) | 2013-12-17 |
| JP2011516497A (ja) | 2011-05-26 |
| US20120093920A1 (en) | 2012-04-19 |
| EP2599476A1 (en) | 2013-06-05 |
| AU2009246834B2 (en) | 2012-12-06 |
| AU2009246834A1 (en) | 2009-11-19 |
| CN102065841A (zh) | 2011-05-18 |
| WO2009139984A2 (en) | 2009-11-19 |
| JP2014062125A (ja) | 2014-04-10 |
| WO2009139984A3 (en) | 2010-03-04 |
| EP2273976A2 (en) | 2011-01-19 |
| MX2010010635A (es) | 2010-12-17 |
| BRPI0911098A2 (pt) | 2015-10-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5538359B2 (ja) | リポソームボツリヌス毒素を使用する膀胱機能障害の治療 | |
| Liu et al. | Multifunctional hydrogel eye drops for synergistic treatment of ocular inflammatory disease | |
| Fraser et al. | Intravesical liposome administration—a novel treatment for hyperactive bladder in the rat | |
| JP6440691B2 (ja) | ボツリヌス神経毒を含む医薬組成物およびその使用 | |
| Li et al. | Targeting delivery of simvastatin using ICAM-1 antibody-conjugated nanostructured lipid carriers for acute lung injury therapy | |
| US10413517B2 (en) | Composition and method for the treatment of neurological diseases and cerebral injury | |
| Li et al. | Alleviating experimental pulmonary hypertension via co-delivering FoxO1 stimulus and apoptosis activator to hyperproliferating pulmonary arteries | |
| Tyagi et al. | Advances in intravesical therapy for urinary tract disorders | |
| Lv et al. | Chitosan as a promising materials for the construction of nanocarriers for diabetic retinopathy: an updated review | |
| US20120301540A1 (en) | Method of treatment for bladder dysfunction | |
| Zhang et al. | An injectable thermosensitive hyaluronic acid/pluronic F-127 hydrogel for deep penetration and combination therapy of frozen shoulder | |
| Zhang et al. | Inhalation of taraxasterol loaded mixed micelles for the treatment of idiopathic pulmonary fibrosis | |
| Fraser et al. | The future of bladder control—intravesical drug delivery, a pinch of pepper, and gene therapy | |
| Hussain et al. | Recent advances in pharmacotherapeutic paradigm of mild to recalcitrant atopic dermatitis | |
| He et al. | Targeted-lung delivery of bardoxolone methyl using PECAM-1 antibody-conjugated nanostructure lipid carriers for the treatment of lung inflammation | |
| Al Zamil | Short-term safety and efficacy of intravitreal 0.7-mg dexamethasone implants for pseudophakic cystoid macular edema | |
| Kaufman et al. | State of the art in intravesical therapy for lower urinary tract symptoms | |
| Crane et al. | Current therapeutic strategies in clinical urology | |
| Khan et al. | Ocular drug delivery: introduction and fundamental concept | |
| Hung et al. | Role of liposome in treatment of overactive bladder and interstitial cystitis | |
| Titiyal et al. | Comparative evaluation of once-daily and twice-daily dosing of topical bromfenac 0.09%: aqueous pharmacokinetics and clinical efficacy study | |
| Patel et al. | Microbubbles-based drug delivery for antiAlzheimer's drugs | |
| US9636299B2 (en) | Method for treating diabetic retinopathy | |
| US20240115503A1 (en) | Intravesical delivery of hydrophilic therapeutic agents using liposomes | |
| WO2026032238A1 (en) | Compositions and methods for treating tendon and ligament injuries utilizing biomaterials and adiponectin or its mimics |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111017 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20111017 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121005 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130419 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130719 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130905 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140106 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140120 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20140218 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140407 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5538359 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140428 |
|
| LAPS | Cancellation because of no payment of annual fees |