CN1203860C - 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 - Google Patents
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 Download PDFInfo
- Publication number
- CN1203860C CN1203860C CNB011159901A CN01115990A CN1203860C CN 1203860 C CN1203860 C CN 1203860C CN B011159901 A CNB011159901 A CN B011159901A CN 01115990 A CN01115990 A CN 01115990A CN 1203860 C CN1203860 C CN 1203860C
- Authority
- CN
- China
- Prior art keywords
- ion channel
- sodium ion
- channel blocker
- formulation
- preparation
- 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
- 229960001138 acetylsalicylic acid Drugs 0.000 title claims abstract description 37
- 108010052164 Sodium Channels Proteins 0.000 title claims abstract description 22
- 102000018674 Sodium Channels Human genes 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 230000002195 synergetic effect Effects 0.000 title claims abstract description 11
- 230000036592 analgesia Effects 0.000 title claims abstract description 9
- 241000124008 Mammalia Species 0.000 title claims abstract description 6
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 title abstract description 41
- 239000003814 drug Substances 0.000 title abstract description 22
- 229940079593 drug Drugs 0.000 title abstract description 6
- 229940125794 sodium channel blocker Drugs 0.000 claims abstract 2
- 239000003195 sodium channel blocking agent Substances 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims description 12
- 239000003053 toxin Substances 0.000 claims description 11
- 231100000765 toxin Toxicity 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 8
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical group 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 7
- 229950010357 tetrodotoxin Drugs 0.000 claims description 7
- 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 7
- 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 6
- 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 6
- 229960001860 salicylate Drugs 0.000 claims description 5
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 230000037396 body weight Effects 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- -1 ethoxytetrodotoxin Chemical compound 0.000 claims description 3
- 238000010255 intramuscular injection Methods 0.000 claims description 3
- 239000007927 intramuscular injection Substances 0.000 claims description 3
- 229940035676 analgesics Drugs 0.000 claims description 2
- 239000000730 antalgic agent Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 10
- 229940122204 Cyclooxygenase inhibitor Drugs 0.000 claims 8
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 claims 8
- STNXQECXKDMLJK-UHFFFAOYSA-N (4betaO)-4,9-anhydro-tetrodotoxin Natural products C12C(C3(O)CO)OC4(O)C5OC2N=C(N)NC15C(O)C3O4 STNXQECXKDMLJK-UHFFFAOYSA-N 0.000 claims 2
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 claims 2
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical group CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 claims 2
- STNXQECXKDMLJK-NLWUVLGBSA-N anhydroepitetrodotoxin Chemical compound C12C([C@@]3(O)CO)O[C@@]4(O)[C@H]5OC2N=C(N)N[C@@]15[C@H](O)[C@@H]3O4 STNXQECXKDMLJK-NLWUVLGBSA-N 0.000 claims 2
- 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 2
- 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 2
- 239000007972 injectable composition Substances 0.000 claims 1
- 239000003650 oxygenase inhibitor Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 108700012359 toxins Proteins 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 15
- 230000000202 analgesic effect Effects 0.000 abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 206010067484 Adverse reaction Diseases 0.000 abstract 1
- 230000006838 adverse reaction Effects 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- 208000002193 Pain Diseases 0.000 description 15
- 230000036407 pain Effects 0.000 description 12
- 241000054452 Takifugu ocellatus Species 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 230000000146 antalgic effect Effects 0.000 description 8
- 150000003180 prostaglandins Chemical class 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 230000001629 suppression Effects 0.000 description 8
- 108091006146 Channels Proteins 0.000 description 7
- 229910001415 sodium ion Inorganic materials 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 6
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 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
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 101800004538 Bradykinin Proteins 0.000 description 4
- 102400000967 Bradykinin Human genes 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000003907 antipyretic analgesic agent Substances 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 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 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 208000005374 Poisoning Diseases 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- 231100000572 poisoning Toxicity 0.000 description 3
- 230000000607 poisoning effect Effects 0.000 description 3
- 229960004889 salicylic acid Drugs 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 208000000094 Chronic Pain 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
- 241001465754 Metazoa Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 208000007107 Stomach Ulcer Diseases 0.000 description 2
- 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 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 description 2
- 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 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 108010017796 epoxidase Proteins 0.000 description 2
- 201000005917 gastric ulcer Diseases 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000008058 pain sensation Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000003594 spinal ganglia Anatomy 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 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
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- IVHCXWQZKOPFIL-UHFFFAOYSA-N C(C=1C(O)=CC=CC1)(=O)O.FC1=CC=CC=C1 Chemical class C(C=1C(O)=CC=CC1)(=O)O.FC1=CC=CC=C1 IVHCXWQZKOPFIL-UHFFFAOYSA-N 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- 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 1
- 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 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 208000004454 Hyperalgesia Diseases 0.000 description 1
- 208000035154 Hyperesthesia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 101710138657 Neurotoxin Proteins 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 241000124033 Salix Species 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 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 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 208000025865 Ulcer 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
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000005298 acute pain Diseases 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
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 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
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000009535 clinical urine test Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 230000002079 cooperative effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 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
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 231100000857 poor renal function Toxicity 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 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 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 229940116269 uric acid Drugs 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003313 weakening effect Effects 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)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (9)
| 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 |
| JP2003506913A JP2004534821A (ja) | 2001-06-22 | 2002-06-18 | 哺乳動物に相乗的鎮痛効果をもたらすための薬剤製造におけるナトリウムチャンネル遮断化合物とアスピリンの使用 |
| US10/480,288 US20040192659A1 (en) | 2001-06-22 | 2002-06-18 | Use of na+ channel blockers and aspirin in manufacturing drugs for producing analgesia synergistically in mammals |
| 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 |
| EP02754135A EP1405639B1 (en) | 2001-06-22 | 2002-06-18 | Use of sodium channel blocking compounds and aspirin in manufacturing drugs for producing synergistic analgesic effect in mammals |
| CA002493885A CA2493885C (en) | 2001-06-22 | 2002-06-18 | Use of sodium channel blocking compounds and aspirin in manufacturing drugs for producing synergistically analgesic effect in mammals |
| ES02754135T ES2296975T3 (es) | 2001-06-22 | 2002-06-18 | Uso de compuestos bloqueantes de canales de sodio y aspirina en la produccion de farmacos para producir efectos analgesicos sinergisticos en mamiferos. |
| DE60223681T 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 |
| US12/249,802 US20090105197A1 (en) | 2001-06-22 | 2008-10-10 | Use of Sodium Channel Blocking Compounds and Aspirin in Manufacturing Drugs for Producing Analgesia Synergistically in Mammals |
Applications Claiming Priority (1)
| 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 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1393223A CN1393223A (zh) | 2003-01-29 |
| CN1203860C true CN1203860C (zh) | 2005-06-01 |
Family
ID=4662323
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB011159901A Expired - Fee Related 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 |
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 |
| KR20070092698A (ko) * | 2004-09-22 | 2007-09-13 | 라보라토리오스 델 드라. 에스테브.에스.에이. | 말초 신경적으로 유발된 신경병증성 통증을 치료하기 위한테트로도톡신 및 그것의 유도체 |
| US20100144767A1 (en) * | 2005-08-25 | 2010-06-10 | Wex Pharmaceuticals, Inc. | Use of sodium channel blockers for the treatment of visceral pain or pain caused by cancer treatment |
| CA2619668A1 (en) * | 2005-08-25 | 2007-03-01 | Edge Renfeng Wang | Use of sodium channel blockers for the management of musculoskeletal pain |
| GB0603008D0 (en) * | 2006-02-14 | 2006-03-29 | Portela & Ca Sa | Method |
| WO2007110221A1 (en) * | 2006-03-27 | 2007-10-04 | Wex Pharmaceuticals Inc. | Use of sodium channel blockers for the treatment of neuropathic pain developing as a consequence of chemotherapy |
| 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 |
| US4022899A (en) * | 1973-06-12 | 1977-05-10 | 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 |
| 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 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
- 2002-06-18 EP EP02754135A patent/EP1405639B1/en not_active Expired - Lifetime
- 2002-06-18 CA CA002493885A patent/CA2493885C/en not_active Expired - Fee Related
- 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
-
2008
- 2008-10-10 US US12/249,802 patent/US20090105197A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1405639A1 (en) | 2004-04-07 |
| US20090105197A1 (en) | 2009-04-23 |
| JP2004534821A (ja) | 2004-11-18 |
| DE60223681D1 (de) | 2008-01-03 |
| CA2493885C (en) | 2007-08-21 |
| EP1405639A4 (en) | 2004-08-04 |
| US20040192659A1 (en) | 2004-09-30 |
| CA2493885A1 (en) | 2003-01-03 |
| ES2296975T3 (es) | 2008-05-01 |
| CN1393223A (zh) | 2003-01-29 |
| WO2003000268A8 (en) | 2004-03-04 |
| EP1405639B1 (en) | 2007-11-21 |
| WO2003000268A1 (en) | 2003-01-03 |
| DE60223681T2 (de) | 2008-10-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Thomas | Opioid-induced bowel dysfunction | |
| Crystal et al. | Pharmacokinetic properties of an FDA‐approved intranasal nalmefene formulation for the treatment of opioid overdose | |
| US20160045449A1 (en) | Formulations and Methods for Attenuating Respiratory Depression Induced by Opioid Overdose | |
| Kusuda et al. | Choline attenuates inflammatory hyperalgesia activating nitric oxide/cGMP/ATP-sensitive potassium channels pathway | |
| US20090105197A1 (en) | Use of Sodium Channel Blocking Compounds and Aspirin in Manufacturing Drugs for Producing Analgesia Synergistically in Mammals | |
| CN1747725A (zh) | 用于治疗上呼吸道阻塞的组合物及方法 | |
| Scott et al. | Exploitation of the nicotinic anti-inflammatory pathway for the treatment of epithelial inflammatory diseases | |
| Chhabra et al. | Sugammadex versus neostigmine for reversal of neuromuscular blockade in adults and children: a systematic review and meta-analysis of randomized controlled trials | |
| Kraft | Methylnaltrexone, a new peripherally acting mu-opioid receptor antagonist being evaluated for the treatment of postoperative ileus | |
| US20030199496A1 (en) | Pharmaceutical compositions containing alpha3beta4 nicotinic receptor antagonists and methods of their use | |
| Gray | Systematic review of the safety of buprenorphine methadone and naltrexone | |
| Gutirrez | Clinical case of rapid opiate detoxification under anesthesia | |
| Ackermann | Peptidergic innervation of periarticular tissue: a study in the rat | |
| CA2613030C (en) | Agent for the treatment of herpes virus-derived pain | |
| Picker et al. | Effects of neuropeptide Y on the discriminative stimulus and antinociceptive properties of morphine | |
| Pleuvry | Anxiolytics and hypnotics | |
| Bilfinger et al. | The use of morphine in surgery: an overview | |
| Seow et al. | Failure of IV atropine to abolish nasal irritation caused by chlormethiazole infusion in elderly patients undergoing spinal anaesthesia | |
| Ramirez et al. | Pharmacology of Opioids | |
| MANJUSHA et al. | Comparison of Efficacy and Safety Between Sugammadex and Neostigmine in Reversal of Vecuronium Induced Neuromuscular Blockade in Adults | |
| Beaussier et al. | Duration of the pharmacodynamic interaction between pancuronium and mivacurium | |
| Silver et al. | Pharmacological agents and acupuncture in rehabilitation | |
| Spreng et al. | PREVENTION OF POSTOPERATIVE PAIN–A series of randomized clinical trials | |
| Currow | Pharmacological approaches to | |
| Mazy et al. | EFFECTS OF NALBUPHINE OR NALBUPHINE–NALOXONE ON RECOVERY AND POSTOPERATIVE ANALGESIA |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20050601 Termination date: 20120622 |