CA2657532C - Methods for treating pain and screening analgesic compounds - Google Patents
Methods for treating pain and screening analgesic compounds Download PDFInfo
- Publication number
- CA2657532C CA2657532C CA2657532A CA2657532A CA2657532C CA 2657532 C CA2657532 C CA 2657532C CA 2657532 A CA2657532 A CA 2657532A CA 2657532 A CA2657532 A CA 2657532A CA 2657532 C CA2657532 C CA 2657532C
- Authority
- CA
- Canada
- Prior art keywords
- rgia
- tyr
- iodo
- alpha
- terminus
- 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
- 208000002193 Pain Diseases 0.000 title claims abstract description 24
- 230000036407 pain Effects 0.000 title claims abstract description 23
- 238000012216 screening Methods 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims description 32
- 150000001875 compounds Chemical class 0.000 title abstract description 38
- 230000000202 analgesic effect Effects 0.000 title description 6
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims abstract description 100
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims abstract description 100
- 238000007792 addition Methods 0.000 claims description 45
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 claims description 40
- 229940043131 pyroglutamate Drugs 0.000 claims description 40
- 239000003814 drug Substances 0.000 claims description 31
- 239000013543 active substance Substances 0.000 claims description 28
- 230000000694 effects Effects 0.000 claims description 27
- 238000012986 modification Methods 0.000 claims description 27
- 230000004048 modification Effects 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 210000002865 immune cell Anatomy 0.000 claims description 26
- 208000035475 disorder Diseases 0.000 claims description 24
- 229940079593 drug Drugs 0.000 claims description 22
- 206010061218 Inflammation Diseases 0.000 claims description 20
- 230000004054 inflammatory process Effects 0.000 claims description 20
- 230000002401 inhibitory effect Effects 0.000 claims description 17
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- 229940000406 drug candidate Drugs 0.000 claims description 16
- 238000013508 migration Methods 0.000 claims description 16
- 230000005012 migration Effects 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 10
- 238000004166 bioassay Methods 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 208000025747 Rheumatic disease Diseases 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000006073 displacement reaction Methods 0.000 claims description 3
- 230000012292 cell migration Effects 0.000 claims description 2
- 101100109292 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) arg-13 gene Proteins 0.000 claims 12
- 102220501721 Ubiquitin-like modifier-activating enzyme 1_S4A_mutation Human genes 0.000 claims 9
- 102220495859 Putative protein ZBED10P_Y10F_mutation Human genes 0.000 claims 8
- 101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 claims 3
- 101100230376 Acetivibrio thermocellus (strain ATCC 27405 / DSM 1237 / JCM 9322 / NBRC 103400 / NCIMB 10682 / NRRL B-4536 / VPI 7372) celI gene Proteins 0.000 claims 1
- 241000352333 Amegilla alpha Species 0.000 claims 1
- 239000000730 antalgic agent Substances 0.000 abstract description 8
- 206010065390 Inflammatory pain Diseases 0.000 abstract description 7
- 208000004296 neuralgia Diseases 0.000 abstract description 7
- 208000021722 neuropathic pain Diseases 0.000 abstract description 7
- 208000027866 inflammatory disease Diseases 0.000 abstract description 5
- 206010003246 arthritis Diseases 0.000 abstract description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 28
- 241000700159 Rattus Species 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 18
- 102000004196 processed proteins & peptides Human genes 0.000 description 16
- 239000000203 mixture Substances 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 13
- 229960004373 acetylcholine Drugs 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 210000003497 sciatic nerve Anatomy 0.000 description 12
- 101000983962 Conus victoriae Alpha-conotoxin Vc1a Proteins 0.000 description 11
- 230000004044 response Effects 0.000 description 11
- 229920001184 polypeptide Polymers 0.000 description 9
- 108010058699 Choline O-acetyltransferase Proteins 0.000 description 8
- 102100023460 Choline O-acetyltransferase Human genes 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 230000003447 ipsilateral effect Effects 0.000 description 8
- 210000000287 oocyte Anatomy 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 239000003053 toxin Substances 0.000 description 8
- 231100000765 toxin Toxicity 0.000 description 8
- 108700012359 toxins Proteins 0.000 description 8
- 206010020751 Hypersensitivity Diseases 0.000 description 7
- 208000026935 allergic disease Diseases 0.000 description 7
- 230000009610 hypersensitivity Effects 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 241000237970 Conus <genus> Species 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- 108050003126 conotoxin Proteins 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000004968 inflammatory condition Effects 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000003556 assay Methods 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 102000009660 Cholinergic Receptors Human genes 0.000 description 4
- 108010009685 Cholinergic Receptors Proteins 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- -1 isothionates Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 102200063830 rs4880 Human genes 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 241000252212 Danio rerio Species 0.000 description 3
- 208000028389 Nerve injury Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000009510 drug design Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 230000008764 nerve damage Effects 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 102220243676 rs1555601019 Human genes 0.000 description 3
- 210000003594 spinal ganglia Anatomy 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229930003347 Atropine Natural products 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 208000001640 Fibromyalgia Diseases 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 2
- 102000004310 Ion Channels Human genes 0.000 description 2
- 108090000862 Ion Channels Proteins 0.000 description 2
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical group NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 101100328158 Mus musculus Clmp gene Proteins 0.000 description 2
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003502 anti-nociceptive effect Effects 0.000 description 2
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 2
- 229960000396 atropine Drugs 0.000 description 2
- 210000003030 auditory receptor cell Anatomy 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 208000001088 cerebrotendinous xanthomatosis Diseases 0.000 description 2
- 125000003636 chemical group Chemical group 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 229960002173 citrulline Drugs 0.000 description 2
- 235000013477 citrulline Nutrition 0.000 description 2
- 230000001427 coherent effect Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 2
- 229960003132 halothane Drugs 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000003040 nociceptive effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 239000002435 venom Substances 0.000 description 2
- 231100000611 venom Toxicity 0.000 description 2
- 210000001048 venom Anatomy 0.000 description 2
- 108091058551 α-conotoxin Proteins 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 229940121683 Acetylcholine receptor antagonist Drugs 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 101710103951 Alpha-conotoxin BuIA Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010006811 Bursitis Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 241000032223 Conus bullatus Species 0.000 description 1
- 241000307707 Conus pergrandis Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 241000237858 Gastropoda Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 1
- 101000679245 Homo sapiens Neuronal acetylcholine receptor subunit alpha-10 Proteins 0.000 description 1
- 101000822093 Homo sapiens Neuronal acetylcholine receptor subunit alpha-9 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical group OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
- 102100025136 Macrosialin Human genes 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 102100022598 Neuronal acetylcholine receptor subunit alpha-10 Human genes 0.000 description 1
- 102100021520 Neuronal acetylcholine receptor subunit alpha-9 Human genes 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 208000000491 Tendinopathy Diseases 0.000 description 1
- 206010043255 Tendonitis Diseases 0.000 description 1
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 241000269370 Xenopus <genus> Species 0.000 description 1
- HKLNEDCUFIFQMN-VAXZQHAWSA-N [Ni].NNC1=CC=C(C2=CC=C(NN)C=C2)C=C1.O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO Chemical compound [Ni].NNC1=CC=C(C2=CC=C(NN)C=C2)C=C1.O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO HKLNEDCUFIFQMN-VAXZQHAWSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000008043 acidic salts Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000010205 computational analysis Methods 0.000 description 1
- KJQOYUHYAZGPIZ-PIJHVLQJSA-N conotoxin vc1.1 Chemical compound C([C@H]1C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H]2NC(=O)[C@@H](NC(=O)CN)CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC2=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CC(O)=O)C(=O)N1)C(N)=O)=O)[C@@H](C)CC)C1=CN=CN1 KJQOYUHYAZGPIZ-PIJHVLQJSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 125000002228 disulfide group Chemical group 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 210000003027 ear inner Anatomy 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 231100000573 exposure to toxins Toxicity 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 210000002768 hair cell Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 239000003127 mollusc venom Substances 0.000 description 1
- 201000005518 mononeuropathy Diseases 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 239000003367 nicotinic antagonist Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000007414 peripheral immune response Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 238000013081 phylogenetic analysis Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229940001607 sodium bisulfite Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229940001482 sodium sulfite Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000004865 vascular response Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000001720 vestibular Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1767—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
- G01N33/9406—Neurotransmitters
- G01N33/944—Acetylcholine
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Transplantation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83146806P | 2006-07-18 | 2006-07-18 | |
| US60/831,468 | 2006-07-18 | ||
| PCT/US2007/016163 WO2008011006A2 (en) | 2006-07-18 | 2007-07-17 | Methods for treating pain and screening analgesic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2657532A1 CA2657532A1 (en) | 2008-01-24 |
| CA2657532C true CA2657532C (en) | 2019-06-18 |
Family
ID=38957314
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2657532A Expired - Fee Related CA2657532C (en) | 2006-07-18 | 2007-07-17 | Methods for treating pain and screening analgesic compounds |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9717775B2 (enExample) |
| EP (1) | EP2051726B1 (enExample) |
| JP (2) | JP5558817B2 (enExample) |
| AU (1) | AU2007275764B2 (enExample) |
| CA (1) | CA2657532C (enExample) |
| WO (1) | WO2008011006A2 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9284358B2 (en) | 2006-07-18 | 2016-03-15 | University Of Utah Research Foundation | Conotoxin peptides |
| JP5558817B2 (ja) * | 2006-07-18 | 2014-07-23 | ユニバーシティ・オブ・ユタ・リサーチ・ファウンデイション | 痛みの処置方法および鎮痛化合物のスクリーニング方法 |
| JP6681826B2 (ja) * | 2013-05-31 | 2020-04-15 | ザ ユニバーシティ オブ ユタ リサーチ ファウンデイション | コノトキシンペプチド、医薬組成物およびそれらの使用 |
| KR102170077B1 (ko) * | 2018-05-21 | 2020-10-27 | 인하대학교 산학협력단 | Prss14/st14의 자가분해 고리부분을 특이적으로 인식하는 단일클론항체 및 이의 용도 |
| EP4393502A2 (en) * | 2018-12-26 | 2024-07-03 | Skinmed Co., Ltd. | Acetylcholine receptor inhibitory peptides and uses thereof |
| US11612661B2 (en) | 2019-01-04 | 2023-03-28 | Kineta Chronic Pain, Llc | Conotoxin peptide analogs and uses for the treatment of pain and inflammatory conditions |
| SG11202106847SA (en) * | 2019-01-04 | 2021-07-29 | Kineta Chronic Pain Llc | Conotoxin peptide analogs and uses for the treatment of pain and inflammatory conditions |
| US12227771B2 (en) | 2019-05-17 | 2025-02-18 | Janssen Pharmaceutica Nv | Expression systems and methods of use thereof |
| CN113493502B (zh) * | 2020-04-01 | 2023-09-12 | 广西大学 | α-芋螺毒素肽TxIE、其药物组合物及用途 |
| EP4378950A4 (en) * | 2021-07-27 | 2025-10-15 | Skinmed Co Ltd | OPTIMIZED SHORTENED PEPTIDE THAT BINDS TO THE ACETYLCHOLINE RECEPTOR, AND ITS USE |
| CN117794942A (zh) * | 2021-07-27 | 2024-03-29 | 思亲美有限公司 | 乙酰胆碱受体结合优化短肽及其用途 |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4352883A (en) | 1979-03-28 | 1982-10-05 | Damon Corporation | Encapsulation of biological material |
| US4353888A (en) | 1980-12-23 | 1982-10-12 | Sefton Michael V | Encapsulation of live animal cells |
| US4883666A (en) | 1987-04-29 | 1989-11-28 | Massachusetts Institute Of Technology | Controlled drug delivery system for treatment of neural disorders |
| US5158881A (en) | 1987-11-17 | 1992-10-27 | Brown University Research Foundation | Method and system for encapsulating cells in a tubular extrudate in separate cell compartments |
| US5283187A (en) | 1987-11-17 | 1994-02-01 | Brown University Research Foundation | Cell culture-containing tubular capsule produced by co-extrusion |
| DE3829766A1 (de) | 1988-09-01 | 1990-03-22 | Akzo Gmbh | Verfahren zur herstellung von membranen |
| DE3829752A1 (de) | 1988-09-01 | 1990-03-22 | Akzo Gmbh | Integrale asymmetrische polyaethersulfonmembran, verfahren zur herstellung und verwendung zur ultrafiltration und mikrofiltration |
| US5082670A (en) | 1988-12-15 | 1992-01-21 | The Regents Of The University Of California | Method of grafting genetically modified cells to treat defects, disease or damage or the central nervous system |
| US5084350A (en) | 1990-02-16 | 1992-01-28 | The Royal Institution For The Advance Of Learning (Mcgill University) | Method for encapsulating biologically active material including cells |
| US5618531A (en) | 1990-10-19 | 1997-04-08 | New York University | Method for increasing the viability of cells which are administered to the brain or spinal cord |
| SG47470A1 (en) | 1991-04-25 | 1998-04-17 | Univ Brown Res Found | Implantable biocompatible immunoisolatory vehicle for delivery of a selected therapeutic products |
| US5854217A (en) | 1992-09-28 | 1998-12-29 | Bearsden Bio, Inc. | Allosteric modulators of the NMDA receptor and their use in the treatment of CNS disorders and enhancement of CNS function |
| WO1994025503A1 (en) | 1993-04-27 | 1994-11-10 | Cytotherapeutics, Inc. | Membrane formed by an acrylonitrile-based polymer |
| AU688776B2 (en) | 1993-06-23 | 1998-03-19 | Brown University Research Foundation | Method and apparatus for sealing implantable, membrane encapsulation devices |
| ES2178654T3 (es) | 1993-08-12 | 2003-01-01 | Neurotech Sa | Capsulas biocompatibles inmonoaisladoras que contienen celulas geneticamente alteradas para el suministro de moleculas biologicamente activas. |
| US5550050A (en) | 1994-04-15 | 1996-08-27 | Cytotherapeutics, Inc. | Method for implanting encapsulated cells in a host |
| US5840576A (en) | 1994-07-20 | 1998-11-24 | Cytotherapeutics, Inc. | Methods and compositions of growth control for cells encapsulated within bioartificial organs |
| US5834029A (en) | 1994-07-20 | 1998-11-10 | Cytotherapeutics, Inc. | Nerve guidance channel containing bioartificial three-dimensional hydrogel extracellular matrix derivatized with cell adhesive peptide fragment |
| US5837234A (en) | 1995-06-07 | 1998-11-17 | Cytotherapeutics, Inc. | Bioartificial organ containing cells encapsulated in a permselective polyether suflfone membrane |
| IN181898B (enExample) | 1995-06-07 | 1998-10-24 | Cytotherapeutics Inc | |
| WO1997012635A1 (en) | 1995-10-02 | 1997-04-10 | Cytotherapeutics, Inc. | Method for treating amyotrophic lateral sclerosis |
| WO1997035478A1 (en) * | 1996-03-26 | 1997-10-02 | The Regents Of The University Of California | Selective target cell activation by expression of a g protein-coupled receptor activated superiorly by synthetic ligand |
| US5844077A (en) | 1997-04-28 | 1998-12-01 | Cytotherapeutics, Inc. | Use of conantokins for producing analgesia or for neuroprotection |
| WO1999033482A1 (en) * | 1997-12-31 | 1999-07-08 | University Of Utah Research Foundation | Uses of alpha-conotoxin peptides |
| AU3473800A (en) * | 1999-01-29 | 2000-08-18 | University Of Utah Research Foundation | Conotoxin peptides |
| JP2002534996A (ja) * | 1999-01-29 | 2002-10-22 | ユニバーシティ・オブ・ユタ・リサーチ・ファウンデーション | アルファ−コノトキシン・ペプチド |
| AU780460B2 (en) * | 1999-09-15 | 2005-03-24 | Janssen Pharmaceutica N.V. | Nicotinic acetylcholine receptor alpha10 subunit |
| EP1090991A1 (en) * | 1999-09-29 | 2001-04-11 | Sanofi-Synthelabo | Novel nicotinic acetylcholine receptor subunit, its isolation and use |
| US20030109670A1 (en) * | 2001-02-09 | 2003-06-12 | University Of Utah Research Foundation | Cone snail peptides |
| AUPR409401A0 (en) * | 2001-03-29 | 2001-04-26 | University Of Melbourne, The | Analgesic compound |
| US20110092448A1 (en) * | 2005-08-02 | 2011-04-21 | Metabolic Pharmaceuticals Limited | Peptide Conjugate for Oral Delivery of Hydrophilic Peptide Analgesics |
| AU2006236006B2 (en) * | 2006-04-13 | 2012-09-06 | The University Of Queensland | Cyclised a-conotoxin peptides |
| JP5558817B2 (ja) * | 2006-07-18 | 2014-07-23 | ユニバーシティ・オブ・ユタ・リサーチ・ファウンデイション | 痛みの処置方法および鎮痛化合物のスクリーニング方法 |
| US9284358B2 (en) | 2006-07-18 | 2016-03-15 | University Of Utah Research Foundation | Conotoxin peptides |
-
2007
- 2007-07-17 JP JP2009520801A patent/JP5558817B2/ja not_active Expired - Fee Related
- 2007-07-17 CA CA2657532A patent/CA2657532C/en not_active Expired - Fee Related
- 2007-07-17 AU AU2007275764A patent/AU2007275764B2/en not_active Ceased
- 2007-07-17 US US12/307,953 patent/US9717775B2/en active Active - Reinstated
- 2007-07-17 WO PCT/US2007/016163 patent/WO2008011006A2/en not_active Ceased
- 2007-07-17 EP EP07796903.8A patent/EP2051726B1/en not_active Not-in-force
-
2014
- 2014-06-05 JP JP2014116680A patent/JP5953338B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP5953338B2 (ja) | 2016-07-20 |
| US9717775B2 (en) | 2017-08-01 |
| AU2007275764B2 (en) | 2013-11-14 |
| EP2051726B1 (en) | 2018-04-18 |
| JP2009545526A (ja) | 2009-12-24 |
| US20090203616A1 (en) | 2009-08-13 |
| EP2051726A2 (en) | 2009-04-29 |
| JP2014210784A (ja) | 2014-11-13 |
| JP5558817B2 (ja) | 2014-07-23 |
| CA2657532A1 (en) | 2008-01-24 |
| WO2008011006A3 (en) | 2008-06-19 |
| WO2008011006A2 (en) | 2008-01-24 |
| AU2007275764A1 (en) | 2008-01-24 |
| EP2051726A4 (en) | 2012-06-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9717775B2 (en) | Methods for treating pain and screening analgesic compounds | |
| US9284358B2 (en) | Conotoxin peptides | |
| ES2446292T3 (es) | Tratamiento del accidente cerebrovascular y otras enfermedades sin inhibir los canales de calcio de tipo N | |
| AU2015226911B2 (en) | Non-narcotic CRMP2 peptides targeting sodium channels for chronic pain | |
| US8716436B2 (en) | Mu opioid receptor agonist analogs of the endomorphins | |
| Ung et al. | Tripeptide motifs in biology: targets for peptidomimetic design | |
| Zhang et al. | Development of multifunctional and orally active cyclic peptide agonists of opioid/neuropeptide FF receptors that produce potent, long-lasting, and peripherally restricted antinociception with diminished side effects | |
| US10633417B2 (en) | Conotoxin peptides, pharmaceutical compositions and uses thereof | |
| US20170369531A1 (en) | Mu opioid receptor agonist analogs of the endomorphins | |
| US8101573B2 (en) | α-conotoxin MII analogs | |
| EP2580233B1 (en) | Materials and method for suppressing inflammatory and neuropathic pain | |
| WO1993010145A1 (en) | Compositions for delayed treatment of ischemia-related neuronal damage | |
| AU2022246283A1 (en) | Use of adnf polypeptides in therapy | |
| EP3220940B1 (en) | Compositions and methods for modulating at2r activity | |
| AU2014200739A1 (en) | Methods for treating pain and screening analgesic compounds | |
| Polt | Glycopeptides as Analgesics: Non-Toxic Alternatives to Morphine for Combat Casualty Care | |
| HK1246811B (en) | Mu opioid receptor agonist analogs of the endomorphins |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20220301 |
|
| MKLA | Lapsed |
Effective date: 20200831 |