AU695166B2 - Compositions and formulations for producing analgesia and for inhibiting progression of neuropathic pain disorders - Google Patents
Compositions and formulations for producing analgesia and for inhibiting progression of neuropathic pain disorders Download PDFInfo
- Publication number
- AU695166B2 AU695166B2 AU64002/96A AU6400296A AU695166B2 AU 695166 B2 AU695166 B2 AU 695166B2 AU 64002/96 A AU64002/96 A AU 64002/96A AU 6400296 A AU6400296 A AU 6400296A AU 695166 B2 AU695166 B2 AU 695166B2
- Authority
- AU
- Australia
- Prior art keywords
- snx
- omega
- conopeptide
- mviia
- binding
- 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.)
- Ceased
Links
- 208000004296 neuralgia Diseases 0.000 title claims abstract description 55
- 208000021722 neuropathic pain Diseases 0.000 title claims abstract description 54
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 24
- 208000035475 disorder Diseases 0.000 title claims abstract description 24
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 17
- 239000000203 mixture Substances 0.000 title claims description 46
- 238000009472 formulation Methods 0.000 title claims description 30
- 230000036592 analgesia Effects 0.000 title claims description 15
- 239000003814 drug Substances 0.000 claims abstract description 45
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 230000027455 binding Effects 0.000 claims description 106
- 230000000694 effects Effects 0.000 claims description 37
- 210000005036 nerve Anatomy 0.000 claims description 23
- 238000007913 intrathecal administration Methods 0.000 claims description 22
- 239000000872 buffer Substances 0.000 claims description 17
- 238000001802 infusion Methods 0.000 claims description 17
- 210000003405 ileum Anatomy 0.000 claims description 16
- 102000038650 voltage-gated calcium channel activity Human genes 0.000 claims description 15
- 108091023044 voltage-gated calcium channel activity Proteins 0.000 claims description 15
- 230000008602 contraction Effects 0.000 claims description 14
- 241000700199 Cavia porcellus Species 0.000 claims description 13
- 230000005764 inhibitory process Effects 0.000 claims description 12
- 229930182817 methionine Natural products 0.000 claims description 12
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 11
- -1 SNX-236 Proteins 0.000 claims description 10
- 230000000202 analgesic effect Effects 0.000 claims description 10
- BPKIMPVREBSLAJ-QTBYCLKRSA-N ziconotide Chemical compound C([C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]2C(=O)N[C@@H]3C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CSSC2)C(N)=O)=O)CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CSSC3)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(N1)=O)CCSC)[C@@H](C)O)C1=CC=C(O)C=C1 BPKIMPVREBSLAJ-QTBYCLKRSA-N 0.000 claims description 10
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 9
- 230000001537 neural effect Effects 0.000 claims description 9
- 208000028389 Nerve injury Diseases 0.000 claims description 8
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 8
- 230000008764 nerve damage Effects 0.000 claims description 8
- 230000002035 prolonged effect Effects 0.000 claims description 8
- 239000003963 antioxidant agent Substances 0.000 claims description 7
- 230000003078 antioxidant effect Effects 0.000 claims description 7
- 235000006708 antioxidants Nutrition 0.000 claims description 7
- 230000003647 oxidation Effects 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- 230000008061 calcium-channel-blocking effect Effects 0.000 claims description 6
- 239000007853 buffer solution Substances 0.000 claims description 4
- 108091058550 ω-conotoxin Proteins 0.000 claims description 4
- 238000013268 sustained release Methods 0.000 claims description 3
- 239000012730 sustained-release form Substances 0.000 claims description 3
- 150000003893 lactate salts Chemical group 0.000 claims description 2
- 101000594607 Conus magus Omega-conotoxin MVIIA Proteins 0.000 claims 5
- 101001122068 Conus tulipa Omega-conotoxin TVIA Proteins 0.000 claims 4
- 101000594611 Conus magus Omega-conotoxin MVIIB Proteins 0.000 claims 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 2
- 240000007594 Oryza sativa Species 0.000 claims 1
- 235000007164 Oryza sativa Nutrition 0.000 claims 1
- 235000009566 rice Nutrition 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 73
- 239000012528 membrane Substances 0.000 description 38
- 208000004454 Hyperalgesia Diseases 0.000 description 32
- 241000700159 Rattus Species 0.000 description 31
- 108090000765 processed proteins & peptides Proteins 0.000 description 28
- 208000002193 Pain Diseases 0.000 description 24
- 238000012360 testing method Methods 0.000 description 23
- 241001465754 Metazoa Species 0.000 description 21
- 230000036407 pain Effects 0.000 description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- 239000011780 sodium chloride Substances 0.000 description 20
- 235000001014 amino acid Nutrition 0.000 description 19
- 238000000034 method Methods 0.000 description 19
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 18
- 206010053552 allodynia Diseases 0.000 description 18
- 150000001413 amino acids Chemical class 0.000 description 18
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 210000004556 brain Anatomy 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 17
- 229960002591 hydroxyproline Drugs 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 15
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 230000004044 response Effects 0.000 description 14
- 210000000278 spinal cord Anatomy 0.000 description 14
- 229930006000 Sucrose Natural products 0.000 description 12
- 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 12
- 238000003556 assay Methods 0.000 description 12
- 238000006073 displacement reaction Methods 0.000 description 12
- 229940001447 lactate Drugs 0.000 description 12
- 230000036515 potency Effects 0.000 description 12
- 239000005720 sucrose Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 10
- 208000014674 injury Diseases 0.000 description 10
- 229960004452 methionine Drugs 0.000 description 10
- 208000033808 peripheral neuropathy Diseases 0.000 description 10
- 208000001294 Nociceptive Pain Diseases 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 210000003568 synaptosome Anatomy 0.000 description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- 229940098773 bovine serum albumin Drugs 0.000 description 8
- 239000011575 calcium Substances 0.000 description 8
- 210000000578 peripheral nerve Anatomy 0.000 description 8
- 206010029260 Neuroblastoma Diseases 0.000 description 7
- 230000002860 competitive effect Effects 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 201000001119 neuropathy Diseases 0.000 description 7
- 230000007823 neuropathy Effects 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- 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 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- 208000035154 Hyperesthesia Diseases 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 210000000576 arachnoid Anatomy 0.000 description 6
- 230000000903 blocking effect Effects 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 210000004209 hair Anatomy 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 230000037317 transdermal delivery Effects 0.000 description 6
- 229940127291 Calcium channel antagonist Drugs 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 239000000480 calcium channel blocker Substances 0.000 description 5
- 230000009137 competitive binding Effects 0.000 description 5
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 5
- 230000001473 noxious effect Effects 0.000 description 5
- 230000035945 sensitivity Effects 0.000 description 5
- 230000009870 specific binding Effects 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 239000011534 wash buffer Substances 0.000 description 5
- 229960002811 ziconotide Drugs 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108090000312 Calcium Channels Proteins 0.000 description 4
- 102000003922 Calcium Channels Human genes 0.000 description 4
- 108091006146 Channels Proteins 0.000 description 4
- 208000013586 Complex regional pain syndrome type 1 Diseases 0.000 description 4
- 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 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 4
- 201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 230000002708 enhancing effect Effects 0.000 description 4
- 210000002683 foot Anatomy 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 4
- 108010052968 leupeptin Proteins 0.000 description 4
- 230000003957 neurotransmitter release Effects 0.000 description 4
- 230000003040 nociceptive effect Effects 0.000 description 4
- 230000009871 nonspecific binding Effects 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 230000002269 spontaneous effect Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 210000000225 synapse Anatomy 0.000 description 4
- 230000008733 trauma Effects 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 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 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 102000004129 N-Type Calcium Channels Human genes 0.000 description 3
- 108090000699 N-Type Calcium Channels Proteins 0.000 description 3
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 239000012148 binding buffer Substances 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000009610 hypersensitivity Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 230000002981 neuropathic effect Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 230000009159 somatosensory pathway Effects 0.000 description 3
- 210000002330 subarachnoid space Anatomy 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 208000001387 Causalgia Diseases 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 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
- 239000004471 Glycine Substances 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 108010041640 SNX 202 Proteins 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 230000003502 anti-nociceptive effect Effects 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 239000012152 bradford reagent Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000002800 charge carrier Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 238000003350 crude synaptosomal preparation Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 2
- 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 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 230000006870 function Effects 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
- 229920000578 graft copolymer Polymers 0.000 description 2
- 210000000548 hind-foot Anatomy 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 229960005015 local anesthetics Drugs 0.000 description 2
- 210000005171 mammalian brain Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 210000002418 meninge Anatomy 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- 229940005483 opioid analgesics Drugs 0.000 description 2
- 230000008058 pain sensation Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000003961 penetration enhancing agent Substances 0.000 description 2
- 229950000964 pepstatin Drugs 0.000 description 2
- 108010091212 pepstatin Proteins 0.000 description 2
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 239000008191 permeabilizing agent Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 210000003446 pia mater Anatomy 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 210000004872 soft tissue Anatomy 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000003356 suture material Substances 0.000 description 2
- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
- KMPMSMYHNJUNSV-BYPYZUCNSA-N (2s)-4-methylsulfanyl-2-(sulfooxyamino)butanoic acid Chemical group CSCC[C@@H](C(O)=O)NOS(O)(=O)=O KMPMSMYHNJUNSV-BYPYZUCNSA-N 0.000 description 1
- FJQZXCPWAGYPSD-UHFFFAOYSA-N 1,3,4,6-tetrachloro-3a,6a-diphenylimidazo[4,5-d]imidazole-2,5-dione Chemical compound ClN1C(=O)N(Cl)C2(C=3C=CC=CC=3)N(Cl)C(=O)N(Cl)C12C1=CC=CC=C1 FJQZXCPWAGYPSD-UHFFFAOYSA-N 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- RWNNRGBCWXOVAC-UHFFFAOYSA-N 1,4-bis[bis(aziridin-1-yl)phosphoryl]piperazine Chemical compound C1CN1P(N1CCN(CC1)P(=O)(N1CC1)N1CC1)(=O)N1CC1 RWNNRGBCWXOVAC-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 229910001369 Brass Inorganic materials 0.000 description 1
- 241000252983 Caecum Species 0.000 description 1
- 102000004414 Calcitonin Gene-Related Peptide Human genes 0.000 description 1
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 241000237970 Conus <genus> Species 0.000 description 1
- 101000953562 Dendroaspis angusticeps Kunitz-type serine protease inhibitor homolog calcicludine Proteins 0.000 description 1
- 101000723297 Dendroaspis polylepis polylepis Calciseptin Proteins 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 241001269524 Dura Species 0.000 description 1
- 241000237858 Gastropoda Species 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 1
- FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
- 229930195722 L-methionine Natural products 0.000 description 1
- 208000034693 Laceration Diseases 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241000282553 Macaca Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010061296 Motor dysfunction Diseases 0.000 description 1
- MXNRLFUSFKVQSK-QMMMGPOBSA-O N(6),N(6),N(6)-trimethyl-L-lysine Chemical compound C[N+](C)(C)CCCC[C@H]([NH3+])C([O-])=O MXNRLFUSFKVQSK-QMMMGPOBSA-O 0.000 description 1
- PQNASZJZHFPQLE-UHFFFAOYSA-N N(6)-methyllysine Chemical compound CNCCCCC(N)C(O)=O PQNASZJZHFPQLE-UHFFFAOYSA-N 0.000 description 1
- RYFOQDQDVYIEHN-ZETCQYMHSA-N N,N-Dimethyllysine Chemical compound CN(C)[C@H](C(O)=O)CCCCN RYFOQDQDVYIEHN-ZETCQYMHSA-N 0.000 description 1
- 229940123579 N-type calcium channel antagonist Drugs 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 208000010886 Peripheral nerve injury Diseases 0.000 description 1
- 206010034620 Peripheral sensory neuropathy Diseases 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000002181 anti-sympathetic effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 239000010951 brass Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 238000004422 calculation algorithm Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 210000003703 cisterna magna Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000006334 disulfide bridging Effects 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 210000001951 dura mater Anatomy 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 239000005351 kimble Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 230000007383 nerve stimulation Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229940124583 pain medication Drugs 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002239 polyacrylonitrile Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- 201000005572 sensory peripheral neuropathy Diseases 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 210000001032 spinal nerve Anatomy 0.000 description 1
- 210000000273 spinal nerve root Anatomy 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 1
- 229950010357 tetrodotoxin Drugs 0.000 description 1
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 150000003668 tyrosines Chemical class 0.000 description 1
- 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- KNJNGVKTAFTUFL-OCMUWRIYSA-N ω-conotoxin Chemical compound N([C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]1C(N[C@@H](CSSC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H]1C(N[C@@H](CCCN=C(N)N)C(=O)N[C@H](CO)C(=O)NCC(=O)N[C@H](CCCCN)C(=O)N[C@H](CSSC1)C(N)=O)=O)=O)C(=O)[C@@H]1CSSC[C@@H](N)C(=O)N[C@H](CCCCN)C(=O)NCC(=O)N[C@H](CCCCN)C(=O)NCC(=O)N[C@H](C)C(=O)N[C@@H](CCCCN)C(=O)N1 KNJNGVKTAFTUFL-OCMUWRIYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A61P23/02—Local anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Anesthesiology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Control Of El Displays (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/496,847 US5795864A (en) | 1995-06-27 | 1995-06-27 | Stable omega conopetide formulations |
| US496847 | 1995-06-27 | ||
| US08/613,400 US6054429A (en) | 1996-03-08 | 1996-03-08 | Epidural method of producing analgesia |
| US613400 | 1996-03-08 | ||
| PCT/US1996/011041 WO1997001351A1 (en) | 1995-06-27 | 1996-06-26 | Compositions and formulations for producing analgesia and for inhibiting progression of neuropathic pain disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU6400296A AU6400296A (en) | 1997-01-30 |
| AU695166B2 true AU695166B2 (en) | 1998-08-06 |
Family
ID=27052304
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU64002/96A Ceased AU695166B2 (en) | 1995-06-27 | 1996-06-26 | Compositions and formulations for producing analgesia and for inhibiting progression of neuropathic pain disorders |
Country Status (13)
| Country | Link |
|---|---|
| EP (2) | EP1336409B1 (enExample) |
| JP (1) | JP2838073B2 (enExample) |
| AT (2) | ATE359086T1 (enExample) |
| AU (1) | AU695166B2 (enExample) |
| CA (1) | CA2224795C (enExample) |
| DE (3) | DE69637021T2 (enExample) |
| DK (2) | DK0835126T3 (enExample) |
| ES (2) | ES2194998T3 (enExample) |
| FR (1) | FR05C0027I2 (enExample) |
| LU (1) | LU91181I2 (enExample) |
| NL (1) | NL300201I2 (enExample) |
| PT (2) | PT1336409E (enExample) |
| WO (1) | WO1997001351A1 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5931809A (en) * | 1995-07-14 | 1999-08-03 | Depotech Corporation | Epidural administration of therapeutic compounds with sustained rate of release |
| CA2319038A1 (en) * | 1998-02-20 | 1999-08-26 | Zeneca Limited | Analgesic peptides from venom of grammostola spatulata and use thereof |
| AUPP627498A0 (en) | 1998-10-02 | 1998-10-22 | University Of Queensland, The | Novel peptides - i |
| EP2412719A1 (en) | 2002-12-02 | 2012-02-01 | Xenome Ltd | Chi-conotoxin peptides |
| WO2004050690A1 (en) | 2002-12-02 | 2004-06-17 | Xenome Ltd | NOVEL χ-CONOTOXIN PEPTIDES (-I) |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| EP1911763B1 (en) | 2003-01-28 | 2010-08-11 | Ironwood Pharmaceuticals, Inc. | Compositions for the treatment of gastrointestinal disorders |
| CA2540895C (en) | 2003-10-02 | 2016-08-02 | Elan Pharmaceuticals, Inc. | Combinations of ziconotide and opioids for reducing pain |
| GB0410215D0 (en) * | 2004-05-07 | 2004-06-09 | Lescroart Pol | Nerve damage |
| US8188048B2 (en) | 2006-06-23 | 2012-05-29 | Xenome Limited | Combination therapy |
| JP2010509209A (ja) * | 2006-11-04 | 2010-03-25 | エニジェン カンパニー リミテッド | 新規なω−コノトキシン |
| MX354786B (es) | 2007-06-04 | 2018-03-21 | Synergy Pharmaceuticals Inc | Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos. |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| EP2300044A4 (en) * | 2008-05-06 | 2012-04-18 | Relevare Aust Pty Ltd | METHOD AND COMPOSITIONS FOR TREATING PAIN WITH OMEGA CONOTOXINES |
| ES2522968T3 (es) | 2008-06-04 | 2014-11-19 | Synergy Pharmaceuticals Inc. | Agonistas de guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
| AU2009270833B2 (en) | 2008-07-16 | 2015-02-19 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| US20100221329A1 (en) | 2008-12-03 | 2010-09-02 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase c agonists and methods of use |
| MX381407B (es) | 2008-12-31 | 2025-03-12 | Ardelyx Inc | Compuestos y métodos para inhibir el antiporte mediado por intercambiador de iones de sodio/iones de hidrógeno (nhe) en el tratamiento de trastornos asociados con retención de fluido o sobrecarga de sal y trastornos del tracto gastrointestinal. |
| WO2018129556A1 (en) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| MX366293B (es) | 2012-08-21 | 2019-07-04 | Ardelyx Inc | Compuestos y metodos para inhibir al antipuerto mediado por nhe en el tratamiento de trastornos asociados con la retencion de fluidos o la sobrecarga de sal y trastornos del tracto gastrointestinal. |
| US10376481B2 (en) | 2012-08-21 | 2019-08-13 | Ardelyx, Inc. | Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| AU2014235215A1 (en) | 2013-03-15 | 2015-10-01 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| AU2014235209B2 (en) | 2013-03-15 | 2018-06-14 | Bausch Health Ireland Limited | Guanylate cyclase receptor agonists combined with other drugs |
| HRP20191000T1 (hr) | 2013-04-12 | 2019-09-20 | Ardelyx, Inc. | Spojevi za vezanje nhe3 i metode inhibiranja transporta fosfata |
| BR112015030326A2 (pt) | 2013-06-05 | 2017-08-29 | Synergy Pharmaceuticals Inc | Agonistas ultrapuros de guanilato ciclase c, método de fabricar e usar os mesmos |
| MX2019008171A (es) | 2017-01-09 | 2020-02-05 | Ardelyx Inc | Inhibidores del antiporte mediado por nhe. |
| MX395405B (es) | 2017-01-09 | 2025-03-25 | Ardelyx Inc | Compuestos útiles para tratar trastornos del tracto gastrointestinal. |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3926287A1 (de) * | 1989-08-09 | 1991-02-21 | Bernhard Clasbrummel | Medizinische anwendung von omega-conotoxin gvia oder omega-conotoxin gvia-analoga zur sympathikolyse |
| US5051403A (en) * | 1989-11-22 | 1991-09-24 | Neurex Corporation | Method of treating ischemia-related neuronal damage |
| AU3074592A (en) * | 1991-11-12 | 1993-06-15 | Neurex Corporation | Compositions for delayed treatment of ischemia-related neuronal damage |
| WO1993013128A1 (en) * | 1991-12-30 | 1993-07-08 | Neurex Corporation | Methods of producing analgesia and enhancing opiate analgesia |
| JPH06247879A (ja) * | 1993-02-17 | 1994-09-06 | Bristol Myers Squibb Co | デオキシチミジンヌクレオシドを含有する注射用製剤の安定化方法およびその方法によって得られる安定化注射用製剤 |
-
1996
- 1996-06-26 EP EP03007342A patent/EP1336409B1/en not_active Expired - Lifetime
- 1996-06-26 PT PT03007342T patent/PT1336409E/pt unknown
- 1996-06-26 DK DK96923511T patent/DK0835126T3/da active
- 1996-06-26 PT PT96923511T patent/PT835126E/pt unknown
- 1996-06-26 DE DE69637021T patent/DE69637021T2/de not_active Expired - Lifetime
- 1996-06-26 ES ES96923511T patent/ES2194998T3/es not_active Expired - Lifetime
- 1996-06-26 DK DK03007342T patent/DK1336409T3/da active
- 1996-06-26 AT AT03007342T patent/ATE359086T1/de active
- 1996-06-26 DE DE1996627153 patent/DE122005000043I2/de active Active
- 1996-06-26 DE DE69627153T patent/DE69627153T2/de not_active Expired - Lifetime
- 1996-06-26 AU AU64002/96A patent/AU695166B2/en not_active Ceased
- 1996-06-26 WO PCT/US1996/011041 patent/WO1997001351A1/en not_active Ceased
- 1996-06-26 AT AT96923511T patent/ATE235914T1/de active
- 1996-06-26 CA CA002224795A patent/CA2224795C/en not_active Expired - Fee Related
- 1996-06-26 ES ES03007342T patent/ES2283671T3/es not_active Expired - Lifetime
- 1996-06-26 EP EP96923511A patent/EP0835126B1/en not_active Expired - Lifetime
- 1996-06-27 JP JP8188120A patent/JP2838073B2/ja not_active Expired - Fee Related
-
2005
- 2005-06-23 FR FR05C0027C patent/FR05C0027I2/fr active Active
- 2005-07-06 LU LU91181C patent/LU91181I2/fr unknown
- 2005-07-13 NL NL300201C patent/NL300201I2/nl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2224795A1 (en) | 1997-01-16 |
| WO1997001351A1 (en) | 1997-01-16 |
| FR05C0027I2 (enExample) | 2006-12-29 |
| PT835126E (pt) | 2003-07-31 |
| DK0835126T3 (da) | 2003-07-14 |
| EP0835126B1 (en) | 2003-04-02 |
| FR05C0027I1 (enExample) | 2005-08-12 |
| JP2838073B2 (ja) | 1998-12-16 |
| AU6400296A (en) | 1997-01-30 |
| NL300201I1 (nl) | 2005-09-01 |
| EP0835126A1 (en) | 1998-04-15 |
| HK1058146A1 (en) | 2004-05-07 |
| DE69637021D1 (de) | 2007-05-24 |
| NL300201I2 (nl) | 2006-02-01 |
| ATE235914T1 (de) | 2003-04-15 |
| LU91181I2 (fr) | 2005-09-06 |
| DE122005000043I2 (de) | 2006-08-03 |
| EP1336409B1 (en) | 2007-04-11 |
| CA2224795C (en) | 2001-04-03 |
| DE69627153T2 (de) | 2003-12-04 |
| ES2194998T3 (es) | 2003-12-01 |
| DE69627153D1 (de) | 2003-05-08 |
| JPH09104634A (ja) | 1997-04-22 |
| ES2283671T3 (es) | 2007-11-01 |
| DK1336409T3 (da) | 2007-08-13 |
| EP1336409A1 (en) | 2003-08-20 |
| DE69637021T2 (de) | 2008-01-10 |
| ATE359086T1 (de) | 2007-05-15 |
| DE122005000043I1 (de) | 2006-06-29 |
| PT1336409E (pt) | 2007-06-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU695166B2 (en) | Compositions and formulations for producing analgesia and for inhibiting progression of neuropathic pain disorders | |
| US5891849A (en) | Methods and formulations for preventing progression of neuropathic pain | |
| US6054429A (en) | Epidural method of producing analgesia | |
| EP0625162B1 (en) | Methods of producing analgesia and enhancing opiate analgesia | |
| AU648052B2 (en) | Compositions for treating ischemia-related neuronal damage | |
| US5189020A (en) | Method of reducing neuronal damage using omega conotoxin peptides | |
| US6136786A (en) | Method for enhancing analgesia | |
| CN102202677A (zh) | 治疗疼痛的活性剂和方法 | |
| US20040138204A1 (en) | Compositions and methods for pain reduction | |
| JPH10511077A (ja) | Ｎ末端基で切断されたダイノルフィン類似体を用いた鎮痛方法 | |
| US5559095A (en) | Delayed treatment method of reducing ischemia-related neuronal damage | |
| WO1993010145A1 (en) | Compositions for delayed treatment of ischemia-related neuronal damage | |
| ES2524564T3 (es) | Identificación de nuevas toxinas antagonistas de canales de calcio de tipo T de aplicación analgésica | |
| HK1058146B (en) | Compositions and formulations for producing analgesia and for inhibiting progression of neuropathic pain disorders | |
| CN121471320A (zh) | 一种靶向trpv1的多肽及其应用 | |
| WO2023068949A1 (en) | Peptide and its uses | |
| Perry | Kinins as neuropeptides | |
| HK1013832B (en) | Methods of producing analgesia and enhancing opiate analgesia | |
| HK1006810B (en) | Compositions comprising omega conotoxin peptide derivatives and their use for treating ischemia-related neuronal damage |