DE60223681T2 - Verwendung von natriumkanalblockern und aspirin zur herstellung von medikamenten zum erzeugen eines synergistischen analgetischen effekts in säugetieren - Google Patents
Verwendung von natriumkanalblockern und aspirin zur herstellung von medikamenten zum erzeugen eines synergistischen analgetischen effekts in säugetieren Download PDFInfo
- Publication number
- DE60223681T2 DE60223681T2 DE60223681T DE60223681T DE60223681T2 DE 60223681 T2 DE60223681 T2 DE 60223681T2 DE 60223681 T DE60223681 T DE 60223681T DE 60223681 T DE60223681 T DE 60223681T DE 60223681 T2 DE60223681 T2 DE 60223681T2
- Authority
- DE
- Germany
- Prior art keywords
- aspirin
- sodium channel
- compound
- tetrodotoxin
- channel blocking
- 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 - Lifetime
Links
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 title claims description 39
- 229960001138 acetylsalicylic acid Drugs 0.000 title claims description 38
- 230000000202 analgesic effect Effects 0.000 title claims description 16
- 239000003814 drug Substances 0.000 title claims description 13
- 230000002195 synergetic effect Effects 0.000 title claims description 9
- 241000124008 Mammalia Species 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 239000003195 sodium channel blocking agent Substances 0.000 title claims 2
- 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 claims description 43
- 229950010357 tetrodotoxin Drugs 0.000 claims description 39
- 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 claims description 39
- 108010052164 Sodium Channels Proteins 0.000 claims description 26
- 102000018674 Sodium Channels Human genes 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 25
- 230000000903 blocking effect Effects 0.000 claims description 15
- 230000037396 body weight Effects 0.000 claims description 8
- RPQXVSUAYFXFJA-HGRQIUPRSA-N saxitoxin Chemical compound NC(=O)OC[C@@H]1N=C(N)N2CCC(O)(O)[C@@]22N=C(N)N[C@@H]12 RPQXVSUAYFXFJA-HGRQIUPRSA-N 0.000 claims description 7
- RPQXVSUAYFXFJA-UHFFFAOYSA-N saxitoxin hydrate Natural products NC(=O)OCC1N=C(N)N2CCC(O)(O)C22NC(N)=NC12 RPQXVSUAYFXFJA-UHFFFAOYSA-N 0.000 claims description 7
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 6
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 claims description 5
- 229960000616 diflunisal Drugs 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 4
- -1 ethoxytetrodotoxin Chemical compound 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- COVOMQKTVSVWBZ-CJCGOCGYSA-N deoxytetrodotoxin Chemical compound O1C(C2(O)CO)(O)OC3C(O)C1[C@@H]1CN=C(N)NC12C3O COVOMQKTVSVWBZ-CJCGOCGYSA-N 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- SVOKHTHBCRETOQ-CNKCMGRGSA-N methoxytetrodotoxin Chemical compound OC1C(C2O)OC3(O)OC2[C@@H]2[C@@H](OC)N=C(N)NC21C3(O)CO SVOKHTHBCRETOQ-CNKCMGRGSA-N 0.000 claims description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 229960001860 salicylate Drugs 0.000 claims description 3
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 3
- 229960004889 salicylic acid Drugs 0.000 claims description 3
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 9
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 claims 6
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 claims 2
- MWPMJZZQPDXVJT-UHFFFAOYSA-N Tetrodonic acid Natural products N1C(N)=NC2OC(C(O)=O)C31C2C(O)C(O)(CO)C(O)C3O MWPMJZZQPDXVJT-UHFFFAOYSA-N 0.000 claims 2
- MWPMJZZQPDXVJT-JTUKEBEQSA-N tetrodonicacid Chemical compound [C@]12([C@H](C(O)=O)O[C@@H]3N=C(N1)N)[C@@H]3[C@@H](O)[C@@](O)(CO)[C@H](O)[C@@H]2O MWPMJZZQPDXVJT-JTUKEBEQSA-N 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 229960004025 sodium salicylate Drugs 0.000 claims 1
- 208000002193 Pain Diseases 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 11
- 230000036407 pain Effects 0.000 description 10
- 229940079593 drug Drugs 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000011734 sodium Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 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 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 230000036592 analgesia Effects 0.000 description 5
- 230000001754 anti-pyretic effect Effects 0.000 description 5
- 150000003180 prostaglandins Chemical class 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 229940035676 analgesics Drugs 0.000 description 4
- 239000000730 antalgic agent Substances 0.000 description 4
- 239000002221 antipyretic Substances 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 101800004538 Bradykinin Proteins 0.000 description 3
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 3
- 102100035792 Kininogen-1 Human genes 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 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
- 230000004941 influx Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 125000005273 2-acetoxybenzoic acid group Chemical class 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000004547 Hallucinations Diseases 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 208000004454 Hyperalgesia Diseases 0.000 description 2
- 208000035154 Hyperesthesia Diseases 0.000 description 2
- 206010065390 Inflammatory pain Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 102000003929 Transaminases Human genes 0.000 description 2
- 108090000340 Transaminases Proteins 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 238000005452 bending Methods 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 210000003594 spinal ganglia Anatomy 0.000 description 2
- 238000010972 statistical evaluation Methods 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UHFFFAOYSA-N 2-{[3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 description 1
- HVYWMOMLDIMFJA-UHFFFAOYSA-N 3-cholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 HVYWMOMLDIMFJA-UHFFFAOYSA-N 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 208000001762 Gastric Dilatation Diseases 0.000 description 1
- 206010017788 Gastric haemorrhage Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000019025 Hypokalemia Diseases 0.000 description 1
- 208000004404 Intractable Pain Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101710138657 Neurotoxin Proteins 0.000 description 1
- 101100264172 Oryza sativa subsp. japonica XIAO gene Proteins 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010046274 Upper gastrointestinal haemorrhage Diseases 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 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
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000003179 convulsant agent Substances 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 230000000917 hyperalgesic effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 210000000929 nociceptor Anatomy 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 230000008052 pain pathway Effects 0.000 description 1
- 208000005877 painful neuropathy Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 208000024896 potassium deficiency disease Diseases 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009044 synergistic interaction Effects 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 208000004371 toothache Diseases 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
- 230000018405 transmission of nerve impulse Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011159901A CN1203860C (zh) | 2001-06-22 | 2001-06-22 | 钠离子通道阻断剂和阿司匹林在制备用于对哺乳动物进行协同镇痛的药物中的应用 |
| CN01115990 | 2001-06-22 | ||
| PCT/CN2002/000428 WO2003000268A1 (en) | 2001-06-22 | 2002-06-18 | Use of na+ channel blockers and aspirin in manufacturing drugs for producing analgesia synergistically in mammals |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60223681D1 DE60223681D1 (de) | 2008-01-03 |
| DE60223681T2 true DE60223681T2 (de) | 2008-10-30 |
Family
ID=4662323
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60223681T Expired - Lifetime DE60223681T2 (de) | 2001-06-22 | 2002-06-18 | Verwendung von natriumkanalblockern und aspirin zur herstellung von medikamenten zum erzeugen eines synergistischen analgetischen effekts in säugetieren |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US20040192659A1 (enExample) |
| EP (1) | EP1405639B1 (enExample) |
| JP (1) | JP2004534821A (enExample) |
| CN (1) | CN1203860C (enExample) |
| CA (1) | CA2493885C (enExample) |
| DE (1) | DE60223681T2 (enExample) |
| ES (1) | ES2296975T3 (enExample) |
| WO (1) | WO2003000268A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1568999A (zh) | 2003-07-14 | 2005-01-26 | 南宁枫叶药业有限公司 | 稳定的医药用河豚毒素冷冻干燥制剂 |
| CA2581083A1 (en) * | 2004-09-22 | 2006-03-30 | Helmut Henrich Buschmann | Tetrodotoxin and its derivatives for the treatment of peripheral-nervously derived neuropathic pain |
| CA2619668A1 (en) * | 2005-08-25 | 2007-03-01 | Edge Renfeng Wang | Use of sodium channel blockers for the management of musculoskeletal pain |
| WO2007025212A2 (en) * | 2005-08-25 | 2007-03-01 | Wex Pharmaceuticals, Inc. | Use of sodium channel blockers for the treatment of visceral pain or pain caused by cancer treatment |
| GB0603008D0 (en) * | 2006-02-14 | 2006-03-29 | Portela & Ca Sa | Method |
| CN101563079B (zh) * | 2006-03-27 | 2012-12-05 | 威克斯药业有限公司 | 钠通道阻滞剂在制备治疗由于化疗而产生的神经病理性疼痛的药物中的用途 |
| CN100438873C (zh) * | 2006-06-26 | 2008-12-03 | 黄致强 | 将河鲀毒素作为镇痛药的耐受抑制剂在制备复方镇痛制剂中的应用 |
| CN104118237A (zh) * | 2013-04-27 | 2014-10-29 | 王静娴 | 编号文件夹 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3966934A (en) * | 1971-12-08 | 1976-06-29 | Astra Pharmaceutical Products, Inc. | Synergistic local anesthetic compositions |
| US3892847A (en) * | 1973-08-14 | 1975-07-01 | Astra Pharma Prod | Spinal anesthesia using small amount of saxitoxin |
| US4022899A (en) * | 1973-06-12 | 1977-05-10 | Astra Pharmaceutical Products, Inc. | Synergistic local anesthetic compositions |
| JPS5594319A (en) * | 1979-01-09 | 1980-07-17 | Yoshio Otaka | Drug for external use consisting of liver oil of swellfish |
| US6759057B1 (en) * | 1986-06-12 | 2004-07-06 | The Liposome Company, Inc. | Methods and compositions using liposome-encapsulated non-steroidal anti-inflammatory drugs |
| US5814655A (en) * | 1996-11-14 | 1998-09-29 | Insite Vision Incorporated | Non-steroidal ophthalmic mixtures |
| US6030974A (en) * | 1997-04-02 | 2000-02-29 | The Regents Of The University Of California | Method of anesthesia |
| GB2339534A (en) * | 1998-07-16 | 2000-02-02 | Edko Trading Representation | Epidural or intrathecal administration of NSAID's |
| CN1284536C (zh) * | 2000-09-18 | 2006-11-15 | 威克斯医药有限公司 | 河豚毒素或蛤蚌毒素及其类似物在制备用于全身镇痛的镇痛药中的应用 |
-
2001
- 2001-06-22 CN CNB011159901A patent/CN1203860C/zh not_active Expired - Fee Related
-
2002
- 2002-06-18 CA CA002493885A patent/CA2493885C/en not_active Expired - Fee Related
- 2002-06-18 EP EP02754135A patent/EP1405639B1/en not_active Expired - Lifetime
- 2002-06-18 WO PCT/CN2002/000428 patent/WO2003000268A1/zh not_active Ceased
- 2002-06-18 US US10/480,288 patent/US20040192659A1/en not_active Abandoned
- 2002-06-18 ES ES02754135T patent/ES2296975T3/es not_active Expired - Lifetime
- 2002-06-18 JP JP2003506913A patent/JP2004534821A/ja active Pending
- 2002-06-18 DE DE60223681T patent/DE60223681T2/de not_active Expired - Lifetime
-
2008
- 2008-10-10 US US12/249,802 patent/US20090105197A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN1393223A (zh) | 2003-01-29 |
| EP1405639B1 (en) | 2007-11-21 |
| JP2004534821A (ja) | 2004-11-18 |
| WO2003000268A8 (en) | 2004-03-04 |
| CA2493885C (en) | 2007-08-21 |
| EP1405639A1 (en) | 2004-04-07 |
| CN1203860C (zh) | 2005-06-01 |
| ES2296975T3 (es) | 2008-05-01 |
| CA2493885A1 (en) | 2003-01-03 |
| WO2003000268A1 (en) | 2003-01-03 |
| US20040192659A1 (en) | 2004-09-30 |
| DE60223681D1 (de) | 2008-01-03 |
| US20090105197A1 (en) | 2009-04-23 |
| EP1405639A4 (en) | 2004-08-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AT389997B (de) | Verfahren zur herstellung analgetischer und anti-inflammatorischer mittel | |
| DE2920739C2 (enExample) | ||
| DE69737592T2 (de) | Mittel gegen juckreiz | |
| DE69635959T2 (de) | Behandlung negativer und kognitiver symptome der schizophrenie mit antagonisten der glycinaufnahme | |
| DE60218193T2 (de) | Verwendung von 2-oxo-1-pyrrolidin-derivaten zur herstellung eines arzneimittels zur behandlung von dyskinesia | |
| DE10197266T5 (de) | Verfahren zur örtlichen Betäubung und Schmerzstillung | |
| DE3390116C2 (de) | Verbesserte, Koffein enthaltende, analgetische und antiinflammatorische Mittel | |
| EP2323645A1 (de) | Verwendung niedrig-dosierter lokalanästhetika oder derivate davon zur therapie chronischer schmerzen, insbesondere migräne | |
| DE60223681T2 (de) | Verwendung von natriumkanalblockern und aspirin zur herstellung von medikamenten zum erzeugen eines synergistischen analgetischen effekts in säugetieren | |
| DE60111025T2 (de) | Verwendung von Topiramat zur Behandlung und Diagnostizierung von Atemstörungen während des Schlafens und Mittel zur Durchführung der Behandlung und Diagnose | |
| EP2001456B1 (de) | Verwendung von zusammensetzungen enthaltend kappa-opioidrezeptor-antagonisten zur behandlung von dissoziativen störungen | |
| CH659946A5 (de) | Analgetische und antiinflammatorische, ibuprofen enthaltende pharmazeutische zubereitung. | |
| WO2004108062A2 (de) | Prophylaxe und/oder therapie bei der portalen hypertonie | |
| EP2050435B1 (de) | Hustenpräparat | |
| WO2003099265A2 (de) | Pharmazeutische wirkstoffkombination sowie deren verwendung | |
| DE60206169T2 (de) | Kombination enthaltend einen p-gp hemmer und einen antiepileptischen wirkstoff | |
| EP1605976B1 (de) | Kombination von phenylcarbonsäureamiden mit blockern des ikr-kanals und deren verwendung zur behandlung von vorhofarrhythmien | |
| DE3545201A1 (de) | Synergistische kombination von flupirtin und 4-acetamido-phenol | |
| WO1998058639A1 (de) | Synergistisch wirkende zusammensetzungen zur selektiven bekämpfung von tumorgewebe | |
| DE10318714B4 (de) | Wirkstoff-Kombinationen und Therapien zur Bekämpfung des Alkoholmissbrauches | |
| DE1667925A1 (de) | Arzneimittel | |
| DE3348444C2 (de) | Analgetische und antiinflammatorische Mittel | |
| DE69009538T2 (de) | In der Therapeutik anwendbare Zusammensetzung mit aggregationshemmender Wirkung auf Blutplättchen. | |
| AT389999B (de) | Verfahren zur herstellung analgetischer und antiinflammatorischer mittel | |
| DE102011108116A1 (de) | Reserpin zur Behandlung von kognitiven Störungen des zentralen Nervensystems |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |