CN109091478A - Application of the allantoin in preparation inhibiting hyperuricemia and anti-gout drugs - Google Patents
Application of the allantoin in preparation inhibiting hyperuricemia and anti-gout drugs Download PDFInfo
- Publication number
- CN109091478A CN109091478A CN201710467560.1A CN201710467560A CN109091478A CN 109091478 A CN109091478 A CN 109091478A CN 201710467560 A CN201710467560 A CN 201710467560A CN 109091478 A CN109091478 A CN 109091478A
- Authority
- CN
- China
- Prior art keywords
- hyperuricemia
- gout
- allantoin
- uric acid
- 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.)
- Pending
Links
- 201000001431 Hyperuricemia Diseases 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 229960002708 antigout preparations Drugs 0.000 title claims abstract description 17
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 13
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 title abstract description 78
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 title abstract description 39
- 229960000458 allantoin Drugs 0.000 title abstract description 39
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims abstract description 33
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims abstract description 33
- 229940116269 uric acid Drugs 0.000 claims abstract description 33
- 201000005569 Gout Diseases 0.000 claims abstract description 18
- 230000036541 health Effects 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 12
- 230000009467 reduction Effects 0.000 claims abstract description 7
- 210000004369 blood Anatomy 0.000 claims abstract description 6
- 239000008280 blood Substances 0.000 claims abstract description 6
- 238000005259 measurement Methods 0.000 claims abstract description 5
- IYDGMDWEHDFVQI-UHFFFAOYSA-N phosphoric acid;trioxotungsten Chemical compound O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.OP(O)(O)=O IYDGMDWEHDFVQI-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 17
- 229940079593 drug Drugs 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 4
- 239000004202 carbamide Substances 0.000 claims description 3
- 238000010255 intramuscular injection Methods 0.000 claims description 3
- 239000007927 intramuscular injection Substances 0.000 claims description 3
- 238000010253 intravenous injection Methods 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 238000013459 approach Methods 0.000 claims description 2
- 238000013270 controlled release Methods 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 210000004877 mucosa Anatomy 0.000 claims description 2
- 238000013268 sustained release Methods 0.000 claims description 2
- 239000012730 sustained-release form Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 210000002966 serum Anatomy 0.000 abstract description 13
- 108020004999 messenger RNA Proteins 0.000 abstract description 11
- 102100036930 Solute carrier family 22 member 6 Human genes 0.000 abstract description 7
- 206010067484 Adverse reaction Diseases 0.000 abstract description 4
- 230000006838 adverse reaction Effects 0.000 abstract description 4
- 241000699670 Mus sp. Species 0.000 abstract description 3
- 101000713272 Homo sapiens Solute carrier family 22 member 4 Proteins 0.000 abstract 1
- 108091006739 SLC22A6 Proteins 0.000 abstract 1
- 102100036928 Solute carrier family 22 member 4 Human genes 0.000 abstract 1
- 230000006806 disease prevention Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 19
- 239000000243 solution Substances 0.000 description 14
- 239000003826 tablet Substances 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- -1 imidazoles heterocyclic compounds Chemical class 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 210000002700 urine Anatomy 0.000 description 7
- 101710102683 Solute carrier family 22 member 6 Proteins 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 210000001643 allantois Anatomy 0.000 description 5
- WHQCHUCQKNIQEC-UHFFFAOYSA-N benzbromarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(Br)=C(O)C(Br)=C1 WHQCHUCQKNIQEC-UHFFFAOYSA-N 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000029142 excretion Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000010172 mouse model Methods 0.000 description 5
- 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 4
- 102100034343 Integrase Human genes 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 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 4
- 239000000975 dye Substances 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 235000001727 glucose Nutrition 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- DIBAKBGYJUCGDL-UHFFFAOYSA-N 2,6-diamino-n-[1-[(2-amino-2-oxoethyl)amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]hexanamide Chemical compound NCCCCC(N)C(=O)NC(C(=O)NCC(N)=O)CC1=CN=CN1 DIBAKBGYJUCGDL-UHFFFAOYSA-N 0.000 description 3
- 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 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 3
- 229960003459 allopurinol Drugs 0.000 description 3
- 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 3
- 108010026970 bursopoietin Proteins 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 230000008859 change Effects 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
- 239000007902 hard capsule Substances 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 229950000193 oteracil Drugs 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 239000007901 soft capsule Substances 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 208000010444 Acidosis Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 101000713281 Mus musculus Solute carrier family 22 member 6 Proteins 0.000 description 2
- 108091006764 Organic cation transporters Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- IAPCTXZQXAVYNG-UHFFFAOYSA-M Potassium 2,6-dihydroxytriazinecarboxylate Chemical compound [K+].[O-]C(=O)C1=NC(=O)NC(=O)N1 IAPCTXZQXAVYNG-UHFFFAOYSA-M 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000012445 acidic reagent Substances 0.000 description 2
- 230000002961 anti-hyperuricemic effect Effects 0.000 description 2
- 229960002529 benzbromarone Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 210000001508 eye Anatomy 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000037427 ion transport Effects 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 239000008299 semisolid dosage form Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 2
- 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
- RYYCJUAHISIHTL-UHFFFAOYSA-N 5-azaorotic acid Chemical compound OC(=O)C1=NC(=O)NC(=O)N1 RYYCJUAHISIHTL-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 208000036487 Arthropathies Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 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
- 239000001828 Gelatine Substances 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 101100094850 Mus musculus Slc22a4 gene Proteins 0.000 description 1
- 101100094860 Mus musculus Slc22a6 gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 240000005373 Panax quinquefolius Species 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 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
- 208000025865 Ulcer Diseases 0.000 description 1
- 108010092464 Urate Oxidase Proteins 0.000 description 1
- 206010046337 Urate nephropathy Diseases 0.000 description 1
- 108010093894 Xanthine oxidase Proteins 0.000 description 1
- 102100033220 Xanthine oxidase Human genes 0.000 description 1
- 229940123769 Xanthine oxidase inhibitor Drugs 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033558 biomineral tissue development Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229940095672 calcium sulfate Drugs 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 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
- 229940040145 liniment Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- JKQOBWVOAYFWKG-UHFFFAOYSA-N molybdenum trioxide Chemical compound O=[Mo](=O)=O JKQOBWVOAYFWKG-UHFFFAOYSA-N 0.000 description 1
- NAFSTSRULRIERK-UHFFFAOYSA-M monosodium urate Chemical compound [Na+].N1C([O-])=NC(=O)C2=C1NC(=O)N2 NAFSTSRULRIERK-UHFFFAOYSA-M 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 238000013546 non-drug therapy Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000001751 uricolytic effect Effects 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000003064 xanthine oxidase inhibitor Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4166—1,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Mycology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses application of the allantoin in inhibiting hyperuricemia and/or the preparation of anti-gout drugs and/or health care product, hyperuricemia includes that uric acid in blood concentration caused by primary and secondary hyperuricemia and various factors is higher than (male) 420 μm of ol/L, (female) 357 μm of ol/L (measurement of phosphotungstic acid reduction method), or uricase-peroxidase conjugate method measurement is higher than the adult of 420 μm of ol/L, gout includes primary gout and secondary gout.It is a discovery of the invention that allantoin can significantly reduce mice serum uric acid level, the mRNA expression of OAT1, OCTN1 are dramatically increased.Allantoin can be used for preparing treatment inhibiting hyperuricemia and/or anti-gout drugs and/or health care product, reduce adverse reaction, provide a kind of solution safely, effectively, economic for the treatment and prevention of disease.
Description
Technical field
The present invention relates to the new opplication of allantoin in medicine preparation, relate generally to allantoin in preparing anti-gout drugs
Application, in particular to allantoin preparation inhibiting hyperuricemia drug and/or health care product in application, belong to medical science neck
Domain.
Background technique
Gout be monosodium urate mineralization formed crystal caused by arthropathy, with purine metabolic disturbance and (or) uric acid arrange
It is directly related to let out the caused hyperuricemia of reduction.
Newest viewpoint thinks that the clinical disease course of gout includes: (1) hyperuricemia, no uric acid crystal, no gout symptom；
(2) observe that uric acid crystal or calculus exist, no gout symptom；(3) internal deposition uric acid crystal, gout acute attack or has hair
Make history；(4) severe gout has tophus to be formed, and causes gouty arthritis,chronic and gouty nephropathy.
Hyperuricemia refers to the state of adult blood plasma uric acid concentration >=7mg/dL (male) or 5.6mg/dL (women), is
Caused by uric acid generates increase and (or) excretion reduction in human body.
The treatment of hyperuricemia can be divided into drug therapy and non-drug therapy.Clinical Report shows that non-drug is controlled
Treatment is only capable of reducing about 10~18% plasma uric acid levels, therefore is necessary to the drug therapy of hyperuricemia.
The therapeutic agent of hyperuricemia can be divided into anti-trioxypurine drug and control the anti-inflammatory drug of acute inflammation breaking-out.Drop urine
The uricosureic agent that sour medicine can be divided the xanthine oxidase inhibitor for reducing uric acid and generating by mechanism of action, increase uric acid excretion
With uricolytic uricase three classes.But existing each drug has different degrees of adverse reaction, super quick anti-such as allopurinol
Syndrome is answered, so not ideal enough.
Allantoin (Allantoin) belongs to imidazoles heterocyclic compounds.Chemical name: N- (2,5- dioxo alkyl imidazole -4- base)
Urea, molecular formula C4H6O3N4.Water can be dissolved in.Sterling be it is non-toxic and tasteless, it is nonirritant, without hypersensitive white crystal, non-aqueous
Solution, dry air, pH are in both sexes in strong base solution to be able to maintain stabilization in 4~9 solution.Allantoin is widely present
In in the urine of mammal and the embryo of animal and plant, it is found in earliest because of it in allantois juice of ox, therefore named allantoin.Urine
Bursin, which has, promotes cell to increase, the physiological function of cutin-softening layer albumen；It is mixed with Aluminium Hydroxide, for digesting
The treatment of road ulcer；It can also be used to treatment xerodermia and scaling dermatopathy；Furthermore it is hard to can also be used in diabetes, liver
The treatment of change, cancer, osteomyelitis etc..Its chemical structure is as follows:
In recent years, the pharmacological actions such as the decompression of allantoin are reported, but to its preparation inhibiting hyperuricemia and/or
There is not been reported for effect in anti-gout drugs and/or health care product.
Summary of the invention
Present invention solves the technical problem that being to provide allantoin in preparation inhibiting hyperuricemia and/or anti-gout drugs
And/or the application in health care product, to provide a kind of solution that adverse reaction is slight for anti-trioxypurine treatment.
For this purpose, the present invention provides the following technical scheme that
Invention provides application of the allantoin in preparation inhibiting hyperuricemia and/or anti-gout drugs or/and health care product.
Further, the hyperuricemia includes but is not limited to blood caused by primary and secondary and various factors
Uric acid concentration is higher than (male) 420 μm of ol/L, (female) 357 μm of ol/L (measurement of phosphotungstic acid reduction method) or uricase-peroxidating in liquid
The measurement of object enzyme coupling method is higher than the adult of 420 μm of ol/L.
Further, the gout includes but is not limited to primary gout and secondary gout.
Further, the allantoin can routinely the anti-of various dosage forms be made in formulation method with pharmaceutically acceptable auxiliary material
Hyperuricemia and/or anti-gout drugs.
Further, the allantoin can include that health food and the acceptable auxiliary material of functional food are routinely made with health care product
The health care product of various inhibiting hyperuricemias and/or antigout is made in agent method.
Therefore the present invention further relates to the pharmaceutical composition using the compounds of this invention as active constituent.The pharmaceutical composition can
It is prepared according to method well known in the art.Can by invent the allantoin and one or more pharmaceutically acceptable solids or
Any dosage form used with human or animal is made in liquid excipient and/or auxiliary material combination.The compounds of this invention is in its pharmaceutical composition
Content in object is usually 0.1-99%.
Further, the invention further relates to the Halth-care compositions using the compounds of this invention as active constituent.The composition
It can be prepared according to method well known in the art.It can be connect on the allantoin and one or more health care products and food by inventing
Any dosage form used with human or animal is made in the solid or liquid excipient and/or auxiliary material combination received.The compounds of this invention exists
Content in its pharmaceutical composition is usually 0.1-99%.
The compounds of this invention can be administered in a unit containing its pharmaceutical composition, and administration route can be stomach
Enteron aisle or non-bowel, such as oral, intravenous injection, intramuscular injection, subcutaneous injection, nasal cavity, oral mucosa, eye, lung and respiratory tract, skin
Skin, vagina, rectum etc..
The drug combination dosage form includes oral preparation, injecting medicine-feeding form, skin and mucosa approach form of administration.
Application according to claim 7, it is characterised in that: affiliated oral preparation include tablet, sustained release agent, capsule,
Controlled release agent, pill, liquid preparation, the injecting medicine-feeding form include intramuscular injection, intravenous injection, intravenous drip.
Form of administration can be liquid dosage form, solid dosage forms or semisolid dosage form.Liquid dosage form can be solution (including
True solution and colloidal solution), emulsion (including o/w type, w/o type and emulsion), suspension, injection (including liquid drugs injection, powder-injection
And infusion), eye drops, nasal drop, lotion and liniment etc.；Solid dosage forms can be tablet (including ordinary tablet, enteric coatel tablets, lozenge,
Dispersible tablet, chewable tablets, effervescent tablet, oral disnitegration tablet), capsule (including hard capsule, soft capsule, capsulae enterosolubilis), granule, dissipate
Agent, pellet, dripping pill, suppository, film, patch, the agent of gas (powder) mist, spray etc.；Semisolid dosage form can be ointment, gel
Agent, paste etc..
It is sustained release preparation, controlled release preparation, targeting preparation and various that the compounds of this invention, which can be made ordinary preparation, also be made,
Particulate delivery system.
In order to which tablet is made in the compounds of this invention, various excipient well known in the art can be widely used, including dilute
Release agent, binder, wetting agent, disintegrating agent, lubricant, glidant.Diluent can be starch, dextrin, sucrose, glucose, cream
Sugar, mannitol, sorbierite, xylitol, microcrystalline cellulose, calcium sulfate, calcium monohydrogen phosphate, calcium carbonate etc.；Wetting agent can be water, second
Alcohol, isopropanol etc.；Adhesive can be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, Arabic gum
Slurry, gelatine size, sodium carboxymethylcellulose, methylcellulose, carboxylic propyl methocel, ethyl cellulose, acrylic resin, card
Wave nurse, polyvinylpyrrolidone, polyethylene glycol etc.；Disintegrating agent can be dried starch, microcrystalline cellulose, low substituted hydroxy-propyl fiber
Element, crosslinked polyvinylpyrrolidone, croscarmellose sodium, sodium carboxymethyl starch, sodium bicarbonate and citric acid, polyoxy second
Alkene sorbitan fatty acid ester, dodecyl sodium sulfate etc.；Lubricant and glidant can be talcum powder, silica, tristearin
Hydrochlorate, tartaric acid, atoleine, polyethylene glycol etc..
Tablet can also be further made to coating tablet, such as sugar coated tablet, thin membrane coated tablet, enteric coated tablets or double
Synusia and multilayer tablet.
In order to which capsule is made in administration unit, effective component the compounds of this invention and diluent, glidant can be mixed
It closes, mixture is placed directly in hard capsule or soft capsule.It can also effective component the compounds of this invention is first and diluent, bonding
Particle or pellet is made in agent, disintegrating agent, then is placed in hard capsule or soft capsule.It is used to prepare each dilute of the compounds of this invention tablet
Release agent, binder, wetting agent, disintegrating agent, glidant kind can also be used for preparing the capsule of the compounds of this invention.
For injection is made in the compounds of this invention, water, ethyl alcohol, isopropanol, propylene glycol or their mixture can be used
Make solvent and appropriate solubilizer commonly used in the art, cosolvent, pH adjustment agent, osmotic pressure regulator is added.Solubilizer or hydrotropy
Agent can be poloxamer, lecithin, hydroxypropyl-β-cyclodextrin etc.；PH adjustment agent can be phosphate, cruel hydrochlorate, hydrochloric acid, hydrogen
Sodium oxide molybdena etc.；Osmotic pressure regulator can be sodium chloride, mannitol, glucose, phosphate, acetate etc..Such as prepare freeze-dried powder
Mannitol, glucose etc. can be also added as proppant in injection.
In addition, if desired, colorant, preservative, fragrance, corrigent or other additions can also be added into pharmaceutical preparation
Agent.To reach medication purpose, enhance therapeutic effect, drug of the invention or pharmaceutical composition can use any well known medication
Administration.The dosage of the compounds of this invention pharmaceutical composition according to the property and severity to be prevented or be treated disease,
The individual instances of patient or animal, administration route and dosage form etc. can have large-scale variation.In general, the compounds of this invention
Daily Suitable dosage ranges be 0.001-400mg/kg weight.Above-mentioned dosage with a dosage unit or can be divided into several doses
Unit administration is measured, this depends on the clinical experience of doctor and includes the dosage regimen with other treatment means.
The compound of the present invention or composition can individually be taken, or merge use with other treatment drug or symptomatic drugs.
When the compound of the present invention and other therapeutic agents, which exist, to act synergistically, its dosage should be adjusted according to the actual situation.
The beneficial effects of the present invention are: the present invention uses antihyperuricemic disease mouse model, to the anti-antihyperuricemic of allantoin
Disease and/or anti-gout drugs, the especially effect of reduction serum uric acid level are investigated, the results show that being administered orally urine
Bursin can significantly reduce mice serum uric acid level, can dramatically increase the mRNA expression of OAT1, OCTN1, so for high urine
The Prevention of acidaemia and/or gout and treatment provide a kind of solution safely, effectively, economic.
Detailed description of the invention
Fig. 1 allantoin is horizontal on hyperuricemia model mice serum uric acid (UA) to be influenced.N=10.
MRNA expression shadow of Fig. 2 allantoin to hyperuricemia model mouse organic anion transporter 1 (OAT1)
It rings.N=3.
MRNA expression of Fig. 3 allantoin to hyperuricemia model mouse Organic Cation Transporter Gene 1 (OCTN1)
It influences.N=3.
Specific embodiment
To keep the purpose of the present invention, technical solution, advantage clearer, the present invention is made below in conjunction with attached drawing further
Detailed description.
It is horizontal that 1. allantoin of experimental example reduces hyperuricemia model mice serum uric acid (UA).
Experimental material: kunming mice is purchased from Fukang biotech inc of China of Beijing.Oteracil Potassium, allantois
Element, allopurinol, Benzbromarone are purchased from Sigma-Aldrich (Sigma-Aldrich, Germany).Sodium carboxymethylcellulose
Purchased from Sinopharm Chemical Reagent Co., Ltd..Uric acid reagent box is purchased from Zhongsheng Beikong Biological Science & Technology Co., Ltd..
Solution is prepared: 1% sodium carboxymethylcellulose being dissolved, is boiled, solvent is used as after cooling, by allantoin, Oxonic Acid
Potassium, allopurinol, Benzbromarone dissolve respectively is configured to suspension.
Experimental group: 18-20g mouse is randomly divided into Normal group, model group, Benzbromarone group (25mgkg-1, sun
Property control), allantoin is low, high dose group (100,400mgkg-1), every group 10.
Intraperitoneal injection Oteracil Potassium 300mgkg-1, Normal group inject 1% carboxylic of equivalent daily daily in addition to control group
Methylcellulose sodium solution, continuous modeling 8 days, then by grouping administration, administration put to death mouse after 14 days, and eye rear vein beard takes
Blood, stands 2h, 5000rpm, 4 DEG C of centrifugation 10min and takes serum, measures serum uric acid level with uric acid reagent box.
As a result: after animal pattern takes orally allantoin (100,400mg/kg), serum uric acid level can a degree of drop
It is low, prompt oral allantoin that can play inhibiting hyperuricemia and/or antigout effect.
1. allantoin of table on hyperuricemia model mice serum uric acid level influence (N=10).
Compared with the control group, a:P < 0.01, compared with model group, b:P < 0.05, c:P < 0.01.
2. allantoin of experimental example expresses water to the mRNA of hyperuricemia model mouse organic anion transporter 1 (OAT1)
It is flat to influence.N=3.
Experimental group: 18-20g mouse is randomly divided into Normal group, model group, Benzbromarone group (25mgkg-1, sun
Property control), allantoin is low, high dose group (100,400mgkg-1), every group 10.Related solution prepares with experimental program with real
Apply example 1.Reverse Transcriptase kit, SYBR green dyestuff are purchased from Bao Yi Bioisystech Co., Ltd (TAKARA, Japan).Draw
Object is purchased from Sheng Gong bioengineering limited liability company, way of purification HAP.
Table 2.OAT1 primer and internal control primer sequence.
Mouse put to death after, take mouse kidney, using Trizol method extract kidney in total serum IgE, with ultraviolet specrophotometer into
Row RNA is quantitative, then carries out reverse transcription with Reverse Transcriptase kit and obtain corresponding cDNA, is carried out using SYBRGreen dyestuff glimmering in real time
Fluorescent Quantitative PCR, observation mRNA express situation of change.
As a result: animal pattern, which takes orally allantoin (400mg/kg), can dramatically increase the expression of OAT1, as shown in table 3, urine
Bursin may play the effect for increasing uric acid transporter excretion and reducing Plasma Uric Acid concentration by the expression of increase ion transport body
Fruit.
3. allantoin of table influences the mRNA expression of hyperuricemia model mouse OAT1.N=3.
Compared with the control group, a:P < 0.05, compared with model group, b:P < 0.05, c:P < 0.01.
3. allantoin of experimental example expresses the mRNA of hyperuricemia model mouse Organic Cation Transporter Gene 1 (OCTN1)
Level influences.(N=3).
Experimental group: 18-20g mouse is randomly divided into Normal group, model group, Benzbromarone group (25mgkg-1, sun
Property control), allantoin is low, high dose group (100,400mgkg-1), every group 10.Related solution is prepared with experimental program with real
Apply example 2.Reverse Transcriptase kit, SYBR green dyestuff are purchased from Bao Yi Bioisystech Co., Ltd (TAKARA, Japan).Draw
Object is purchased from Sheng Gong bioengineering limited liability company, way of purification HAP.
Table 4.OCTN1 primer and internal control primer sequence.
Mouse put to death after, take mouse kidney, using Trizol method extract kidney in total serum IgE, with ultraviolet specrophotometer into
Row RNA is quantitative, then carries out reverse transcription with Reverse Transcriptase kit and obtain corresponding cDNA, is carried out using SYBRGreen dyestuff glimmering in real time
Fluorescent Quantitative PCR, observation mRNA express situation of change.
As a result: animal pattern, which takes orally allantoin (100mg/kg), can dramatically increase the expression of OCTN1, as shown in table 5, allantois
Element may play the effect for increasing uric acid transporter body excretion and reducing Plasma Uric Acid concentration by the expression of increase ion transport body
Fruit.
5. allantoin of table influences the mRNA expression of hyperuricemia model mouse OCTN1.(N=3).
Compared with the control group, a:P < 0.05, compared with model group, b:P < 0.05, c:P < 0.01.
In conclusion the present invention is using antihyperuricemic disease mouse model to allantoin inhibiting hyperuricemia and/or antigout
Drug and/or health care product, especially the effect of reduction serum uric acid level is investigated, the results show that passing through gastric infusion allantois
Element can significantly reduce mice serum uric acid level, can dramatically increase the mRNA expression of OAT1, OCTN1.Therefore, allantois is known as
Inhibiting hyperuricemia and/or antigout effect.Using allantoin as active material, it is used alone or/and other is living with pharmacology
Property compound and/or extract composition compound use, the anti-of various dosage forms is made according to the conventional preparation method of pharmaceutical field
Hyperuricemia and/or anti-gout drugs and/or health care product, or with other medicine for improving uric acid excretion and/or xanthine oxidase
Compound preparation is made in inhibitor etc., can be high urine for reducing the adverse reaction in drug effect in the case where keeping curative effect
The Prevention of acidaemia and/or gout and treatment provide a kind of solution safely, effectively, economic.
Finally, it is stated that the above examples are only used to illustrate the technical scheme of the present invention rather than limits, although passing through ginseng
According to the preferred embodiment of this non-invention, invention has been described, but it should be understood by one skilled in the art that can be with
Various changes are made to it on carrying out upper and details, without departing from this hair defined by appended claims specification
Bright spirit and scope.
Claims (7)
1. (2,5- dioxo -4- imidazoline piperidinyl) urea of the N- as shown in formula I and its pharmaceutically acceptable salt are anti-in preparation
Application in hyperuricemia and/or antigout product
2. application according to claim 1, the hyperuricemia is to lead to caused by primary and secondary and various factors
It crosses phosphotungstic acid reduction method measurement male's uric acid in blood concentration and is higher than 420 μm of ol/L, women uric acid in blood concentration is higher than 357 μ
Mol/L, or uric acid concentration in adult blood is measured by uricase-peroxidase conjugate method and is higher than 420 μm of ol/L.
3. application according to claim 1, the gout is primary gout and secondary gout.
4. a kind of application of pharmaceutical composition in preparation inhibiting hyperuricemia and/or antigout product, which is characterized in that contain
N- (2,5- dioxo -4- imidazoline piperidinyl) urea and its pharmaceutically acceptable salt of claim 1 and pharmaceutically acceptable
Carrier.
5. application according to claim 1, which is characterized in that the product is selected from drug or health care product.
6. application according to claim 4, which is characterized in that the pharmaceutical composition is selected from oral preparation, is administered to medicament
Type, skin and mucosa approach form of administration.
7. application according to claim 6, feature is selected from tablet, sustained release agent, capsule, controlled release agent, dripping pill in oral preparation
Agent, liquid preparation, the injecting medicine-feeding form are selected from intramuscular injection, intravenous injection, intravenous drip.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710467560.1A CN109091478A (en) | 2017-06-20 | 2017-06-20 | Application of the allantoin in preparation inhibiting hyperuricemia and anti-gout drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710467560.1A CN109091478A (en) | 2017-06-20 | 2017-06-20 | Application of the allantoin in preparation inhibiting hyperuricemia and anti-gout drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109091478A true CN109091478A (en) | 2018-12-28 |
Family
ID=64795658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710467560.1A Pending CN109091478A (en) | 2017-06-20 | 2017-06-20 | Application of the allantoin in preparation inhibiting hyperuricemia and anti-gout drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109091478A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113509464A (en) * | 2021-07-16 | 2021-10-19 | 华侨大学 | Intestinal luminal uric acid adsorbent and application and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015102642A1 (en) * | 2014-01-03 | 2015-07-09 | Scioderm, Inc. | Allantoin compositions for treating inflammatory skin conditions |
| WO2016105448A1 (en) * | 2014-12-22 | 2016-06-30 | Darryl Rideout | Imidazoline receptor type 1 ligands for use as therapeutics |
-
2017
- 2017-06-20 CN CN201710467560.1A patent/CN109091478A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015102642A1 (en) * | 2014-01-03 | 2015-07-09 | Scioderm, Inc. | Allantoin compositions for treating inflammatory skin conditions |
| WO2016105448A1 (en) * | 2014-12-22 | 2016-06-30 | Darryl Rideout | Imidazoline receptor type 1 ligands for use as therapeutics |
Non-Patent Citations (1)
| Title |
|---|
| D. MASSEOUD 等: "Overview of Hyperuricaemia and Gout", 《CURRENT PHARMACEUTICAL DESIGN》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113509464A (en) * | 2021-07-16 | 2021-10-19 | 华侨大学 | Intestinal luminal uric acid adsorbent and application and preparation method thereof |
| CN113509464B (en) * | 2021-07-16 | 2023-10-20 | 华侨大学 | Uric acid adsorbent in intestinal cavity and application and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1930002B1 (en) | Use of hydroxybenzoic acid ester compounds for the manufacture of a medicament for the prevention and treatment of hpv infection | |
| CN105878322B (en) | It is a kind of to crystallize sunflower disk extract prepared by enzymatic isolation method and preparation method thereof | |
| CN103833713B (en) | Nicousamide brilliant type III, its method for making and its pharmaceutical composition and purposes | |
| CN107530304A (en) | The suppression of OLIG2 activity | |
| CN105434417A (en) | Application of salvianolic acid A in preparation of medicine for resisting tunica intima thickening, post-angioplasty restenosis and/or in-stent restenosis | |
| CN109223707A (en) | A kind of uricase external-use gel preparation, preparation method and the usage | |
| CN109985033A (en) | Salvianolic acid C is preparing the application in anti-cerebral apoplexy drug | |
| CN105902506A (en) | Sacubitril/valsartan preparation and application thereof | |
| CN109091478A (en) | Application of the allantoin in preparation inhibiting hyperuricemia and anti-gout drugs | |
| CN109718230A (en) | Application of the salviandic acid A in preparation inhibiting hyperuricemia and anti-gout drugs | |
| CN103054932B (en) | Principal columns of a hall tree extract is preparing the application in treating Gastric Ulcer Treatment | |
| CN115531393A (en) | Application of ergosterol in preparation of medicine for preventing and treating gastric ulcer | |
| CN113181167B (en) | Application of curatin in preparation of medicine for treating myocardial hypertrophy | |
| WO2013111729A1 (en) | Pharmaceutical composition and quasi-drug cosmetic using same | |
| CN112999213A (en) | Application of Bexarotene in preparation of anti-pituitary adrenocorticotropic hormone adenoma medicine | |
| CN115920059B (en) | FXR receptor inhibition composition, preparation method and application thereof in prevention and treatment of coronavirus | |
| CN102716128A (en) | Pharmaceutical composition for treating asthma | |
| CN102342949A (en) | Application of phlorhizin in preparation of drug for treating hyperuricemia | |
| KR20200026156A (en) | Pharmatheutical composition comprising Tenofovir disoproxil fumarate for preventing or treating of hepatic fibrosis | |
| CN106456576A (en) | Method of treating advanced non-alcoholic steatohepatitis | |
| CN105748427B (en) | A kind of Topiroxostat enteric coatel tablets and preparation method thereof | |
| CN105934245B (en) | The therapeutic agent or prophylactic of multiple sclerosis | |
| WO2021110064A1 (en) | New multi-functional oligopeptides | |
| CN100998587A (en) | Application of 5-hydroxy furfurol for preparing medicine | |
| CN113398114B (en) | Application of 3,7,8,4' -tetrahydroxyflavone in preparing anti-cardiovascular disease medicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20181228 |