CN1781554A - 一种预测acei类降压药药效的复方药 - Google Patents
一种预测acei类降压药药效的复方药 Download PDFInfo
- Publication number
- CN1781554A CN1781554A CNA2005101155528A CN200510115552A CN1781554A CN 1781554 A CN1781554 A CN 1781554A CN A2005101155528 A CNA2005101155528 A CN A2005101155528A CN 200510115552 A CN200510115552 A CN 200510115552A CN 1781554 A CN1781554 A CN 1781554A
- Authority
- CN
- China
- Prior art keywords
- acei
- adrb2
- effect
- drug effect
- hypotensor
- 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.)
- Granted
Links
- 239000003814 drug Substances 0.000 title claims abstract description 45
- 150000001875 compounds Chemical class 0.000 title claims abstract description 28
- 230000000694 effects Effects 0.000 title claims abstract description 27
- 101150033809 ADRB2 gene Proteins 0.000 claims abstract description 20
- 239000005557 antagonist Substances 0.000 claims abstract description 4
- 229940123415 Beta 2 adrenoreceptor antagonist Drugs 0.000 claims abstract description 3
- 230000000857 drug effect Effects 0.000 claims description 56
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 claims description 24
- 229960004530 benazepril Drugs 0.000 claims description 24
- 229940079593 drug Drugs 0.000 claims description 24
- 229960000830 captopril Drugs 0.000 claims description 8
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 claims description 8
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 claims description 8
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 claims description 7
- 229960002490 fosinopril Drugs 0.000 claims description 7
- 102100039705 Beta-2 adrenergic receptor Human genes 0.000 claims description 6
- 229960003401 ramipril Drugs 0.000 claims description 6
- 101710152983 Beta-2 adrenergic receptor Proteins 0.000 claims description 5
- 229960001632 labetalol Drugs 0.000 claims description 5
- 229960002052 salbutamol Drugs 0.000 claims description 5
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 claims description 4
- 108010061435 Enalapril Proteins 0.000 claims description 4
- 239000000556 agonist Substances 0.000 claims description 4
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 4
- 229960005025 cilazapril Drugs 0.000 claims description 4
- HHHKFGXWKKUNCY-FHWLQOOXSA-N cilazapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 HHHKFGXWKKUNCY-FHWLQOOXSA-N 0.000 claims description 4
- 229960000873 enalapril Drugs 0.000 claims description 4
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 claims description 4
- 229960002582 perindopril Drugs 0.000 claims description 4
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 claims description 4
- 229940077927 altace Drugs 0.000 claims description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 claims 4
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims 2
- SSMSBSWKLKKXGG-UHFFFAOYSA-N 1-(2-chlorophenyl)-2-isopropylaminoethanol Chemical compound CC(C)NCC(O)C1=CC=CC=C1Cl SSMSBSWKLKKXGG-UHFFFAOYSA-N 0.000 claims 2
- 239000002083 C09CA01 - Losartan Substances 0.000 claims 2
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims 2
- JOATXPAWOHTVSZ-UHFFFAOYSA-N Celiprolol Chemical compound CCN(CC)C(=O)NC1=CC=C(OCC(O)CNC(C)(C)C)C(C(C)=O)=C1 JOATXPAWOHTVSZ-UHFFFAOYSA-N 0.000 claims 2
- 108010007859 Lisinopril Proteins 0.000 claims 2
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 claims 2
- 229960002320 celiprolol Drugs 0.000 claims 2
- 229950011462 clorprenaline Drugs 0.000 claims 2
- 229960002848 formoterol Drugs 0.000 claims 2
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 claims 2
- 229960002394 lisinopril Drugs 0.000 claims 2
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 claims 2
- 229960004773 losartan Drugs 0.000 claims 2
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 claims 2
- VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 claims 2
- 229960004255 nadolol Drugs 0.000 claims 2
- 229960002288 procaterol Drugs 0.000 claims 2
- FKNXQNWAXFXVNW-BLLLJJGKSA-N procaterol Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)[C@@H](NC(C)C)CC FKNXQNWAXFXVNW-BLLLJJGKSA-N 0.000 claims 2
- 229960003712 propranolol Drugs 0.000 claims 2
- 229960000195 terbutaline Drugs 0.000 claims 2
- 229960004699 valsartan Drugs 0.000 claims 2
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 claims 2
- 229960004017 salmeterol Drugs 0.000 claims 1
- 231100000331 toxic Toxicity 0.000 abstract description 4
- 230000002588 toxic effect Effects 0.000 abstract description 4
- 229940121786 Beta 2 adrenoreceptor agonist Drugs 0.000 abstract 1
- 101000959437 Homo sapiens Beta-2 adrenergic receptor Proteins 0.000 description 33
- 102000017919 ADRB2 Human genes 0.000 description 32
- 108090000623 proteins and genes Proteins 0.000 description 29
- 230000036772 blood pressure Effects 0.000 description 26
- 238000000034 method Methods 0.000 description 18
- 230000035772 mutation Effects 0.000 description 18
- 239000007788 liquid Substances 0.000 description 15
- 230000037396 body weight Effects 0.000 description 14
- 206010020772 Hypertension Diseases 0.000 description 12
- 238000003752 polymerase chain reaction Methods 0.000 description 12
- 230000000391 smoking effect Effects 0.000 description 12
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 10
- 229910052753 mercury Inorganic materials 0.000 description 10
- 239000002220 antihypertensive agent Substances 0.000 description 9
- 229940127088 antihypertensive drug Drugs 0.000 description 9
- 230000035487 diastolic blood pressure Effects 0.000 description 9
- 238000001962 electrophoresis Methods 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 230000003276 anti-hypertensive effect Effects 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 102000005862 Angiotensin II Human genes 0.000 description 6
- 101800000733 Angiotensin-2 Proteins 0.000 description 6
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 6
- 229950006323 angiotensin ii Drugs 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 230000035488 systolic blood pressure Effects 0.000 description 6
- 102220624485 Beta-2 adrenergic receptor_G16R_mutation Human genes 0.000 description 5
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000012937 correction Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000002547 new drug Substances 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 238000012827 research and development Methods 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- 102220006123 rs1042713 Human genes 0.000 description 4
- 101800000734 Angiotensin-1 Proteins 0.000 description 3
- 102400000344 Angiotensin-1 Human genes 0.000 description 3
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 3
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000001631 hypertensive effect Effects 0.000 description 3
- 230000001077 hypotensive effect Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 229940126649 ADRB2 agonist Drugs 0.000 description 2
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 2
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- 108050000824 Angiotensin II receptor Proteins 0.000 description 2
- 102000008873 Angiotensin II receptor Human genes 0.000 description 2
- 108090001067 Angiotensinogen Proteins 0.000 description 2
- 102000004881 Angiotensinogen Human genes 0.000 description 2
- 102000015427 Angiotensins Human genes 0.000 description 2
- 108010064733 Angiotensins Proteins 0.000 description 2
- 208000007530 Essential hypertension Diseases 0.000 description 2
- 101100378542 Homo sapiens ADRB2 gene Proteins 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- -1 albuterol compound Chemical class 0.000 description 2
- 229960002478 aldosterone Drugs 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000035622 drinking Effects 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 239000002532 enzyme inhibitor Substances 0.000 description 2
- 229940125532 enzyme inhibitor Drugs 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000036454 renin-angiotensin system Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 2
- 229940048102 triphosphoric acid Drugs 0.000 description 2
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 108090000227 Chymases Proteins 0.000 description 1
- 102000003858 Chymases Human genes 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 206010041277 Sodium retention Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 description 1
- 102000000072 beta-Arrestins Human genes 0.000 description 1
- 108010080367 beta-Arrestins Proteins 0.000 description 1
- 108010051210 beta-Fructofuranosidase Proteins 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000001573 invertase Substances 0.000 description 1
- 235000011073 invertase Nutrition 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- 239000011654 magnesium acetate Substances 0.000 description 1
- 229940069446 magnesium acetate Drugs 0.000 description 1
- 235000011285 magnesium acetate Nutrition 0.000 description 1
- 210000004914 menses Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 108010021724 tonin Proteins 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124629 β-receptor antagonist Drugs 0.000 description 1
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Description
基因型 | 观察数 | 收缩压下降(mmHg) | 舒张压下降(mmHg) | ||||||||
均数 | 标准差 | 关联系数 | 标准误 | P值 | 均数 | 标准差 | 关联系数 | 标准误 | P值 | ||
A组RR§GRGG | 10618191 | 12.716.617.4 | 17.719.416.7 | -3.4-3.8 | 2.02.3 | 0.0990.092 | 8.812.112.0 | 11.513.413.1 | 2.71.9 | 1.41.6 | 0.0540.245 |
B组RR§GRGG | 219323103 | 8.610.311.0 | 15.114.715.3 | 1.82.9 | 1.21.7 | 0.1290.088 | 4.94.76.2 | 10.110.210.5 | -0.41.2 | 0.81.1 | 0.6290.310 |
合并组RR§GRGG | 325504194 | 9.912.514.0 | 16.116.816.2 | 2.43.2 | 1.11.4 | 0.0200.024 | 6.27.38.9 | 10.711.912.1 | 0.71.4 | 0.70.9 | 0.3470.150 |
基因型 | SBP有效 | DBP有效 | ||||||||||
基础SBP≥140 | 用药后SBP<140 | % | 优势比 | 95%可信区间 | P值 | 基础DBP≥90 | 用药后DBP<90 | % | 优势比 | 95%可信区间 | P值 | |
A组RR§GRGG | 19428991 | 7211143 | 37.138.447.3 | 1.000.991.56 | -0.6-1.50.9-2.8 | -0.9660.141 | 17825384 | 7811345 | 43.844.753.6 | 1.001.071.47 | -0.7-1.60.8-2.6 | -0.7370.178 |
B组RR§GRGG | 9916983 | 317034 | 31.341.441.0 | 1.001.881.61 | -1.0-3.40.8-3.2 | -0.0380.174 | 7615079 | 369051 | 47.460.064.6 | 1.001.932.06 | -1.1-3.51.0-4.1 | -0.0330.040 |
合并组RR§GRGG | 293458174 | 10318177 | 34.839.544.3 | 1.001.261.52 | -0.9-1.81.0-2.4 | -0.1890.065 | 254403163 | 11420396 | 44.950.458.9 | 1.001.291.63 | -0.9-1.81.1-2.5 | -0.1410.027 |
Claims (4)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNA021238758A CN1465712A (zh) | 2002-07-05 | 2002-07-05 | 一种预测acei类降压药药效的试剂盒、方法、软件和复方药 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA021238758A Division CN1465712A (zh) | 2002-07-05 | 2002-07-05 | 一种预测acei类降压药药效的试剂盒、方法、软件和复方药 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1781554A true CN1781554A (zh) | 2006-06-07 |
CN100377744C CN100377744C (zh) | 2008-04-02 |
Family
ID=34142537
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA021238758A Pending CN1465712A (zh) | 2002-07-05 | 2002-07-05 | 一种预测acei类降压药药效的试剂盒、方法、软件和复方药 |
CNB2005101155528A Expired - Lifetime CN100377744C (zh) | 2002-07-05 | 2002-07-05 | 一种预测acei类降压药药效的复方药 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA021238758A Pending CN1465712A (zh) | 2002-07-05 | 2002-07-05 | 一种预测acei类降压药药效的试剂盒、方法、软件和复方药 |
Country Status (1)
Country | Link |
---|---|
CN (2) | CN1465712A (zh) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101029336B (zh) * | 2006-03-01 | 2010-11-03 | 北京华安佛医药研究中心有限公司 | 预测5-羟色胺再摄取抑制剂类药物作用效果的试剂盒 |
CN101063166B (zh) * | 2006-04-30 | 2012-07-25 | 安徽省生物医学研究所 | 预测血管紧张素转换酶抑制剂类药物作用效果的试剂盒 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2214143A1 (en) * | 1995-04-07 | 1996-10-10 | Marc De Gasparo | Combination compositions containing benazepril or benazeprilat and valsartan |
US20010044584A1 (en) * | 1997-08-28 | 2001-11-22 | Kensey Kenneth R. | In vivo delivery methods and compositions |
JP2003518493A (ja) * | 1999-12-24 | 2003-06-10 | スミスクライン ビーチャム パブリック リミテッド カンパニー | 新規治療方法 |
CN1144582C (zh) * | 2000-11-28 | 2004-04-07 | 中国药科大学 | 治疗呼吸系统疾病的无氟里昂药用气雾剂 |
-
2002
- 2002-07-05 CN CNA021238758A patent/CN1465712A/zh active Pending
- 2002-07-05 CN CNB2005101155528A patent/CN100377744C/zh not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
CN100377744C (zh) | 2008-04-02 |
CN1465712A (zh) | 2004-01-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2007038670A2 (en) | Methods and compositions for screening and treatment of disorders of blood glucose regulation | |
CN109082464B (zh) | 一种检测高血压药物代谢相关基因的引物组和试剂盒 | |
Pan et al. | Linkage analysis with candidate genes: the Taiwan young-onset hypertension genetic study | |
Kui et al. | The relationship between polymorphisms at 17 gene sites and hypertension among the Aboriginal Tibetan people | |
CN101008032A (zh) | 多态性位点基因型预测磺脲类药物作用效果的用途和方法 | |
CN1781554A (zh) | 一种预测acei类降压药药效的复方药 | |
CN1858240A (zh) | 预测血管紧张素ii受体拮抗剂类降压药作用的方法及应用 | |
Park et al. | Identification of novel variants in transforming growth factor‐beta 1 (TGFB1) gene and association analysis with bone mineral density | |
Basak et al. | Association of angiotensinogen T174M and M235T gene variants with development of hypertension in Turkish subjects of Trakya region | |
CN1217008C (zh) | 一种预测acei类降压药药效的方法 | |
CN1679943A (zh) | 一种改善acei类降压药药效的复方药 | |
Chern et al. | Molecular genetic study of hypertension | |
CN1858241A (zh) | 预测血管紧张素ii受体拮抗剂类降压药作用的方法及应用 | |
CN100338228C (zh) | 一种预测2型糖尿病易感性的试剂 | |
CN1858242A (zh) | 一种预测血管紧张素ii受体拮抗剂类降压药药物作用的方法及其应用 | |
CN101063166A (zh) | 预测血管紧张素转换酶抑制剂类药物作用效果的试剂盒 | |
CN1279183C (zh) | 检测儿童失神癫痫主效基因cacna1h突变基因的方法及cacna1h突变基因 | |
CN1766127A (zh) | 一种鉴定pgc-1基因启动子-1998位snp分子标记的引物、方法及试剂盒 | |
Giordano et al. | Linkage disequilibrium between intra‐locus variants in the aminopeptidase n gene and test of their association with coeliac disease | |
CN101063165A (zh) | 预测血管紧张素转换酶抑制剂类药物作用效果的方法 | |
Cagnard et al. | Systematic Candidate Gene Investigations in the SPA2 Locus (9q32) Show an Association Between TNFSF8 and... | |
KR101208188B1 (ko) | 천식과 관련된 slc6a7 유전자 다형성 | |
US20040072230A1 (en) | Human SORBS1 genetic variations contribute to insulin resistance, obesity, type 2 diabetes, and hypertension | |
US20070243528A1 (en) | Methods for detecting polymorphisms using arms or rflp | |
WO2002029097A2 (en) | Methods relating to polymorphisms in the human gpr10 gene |
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 | ||
ASS | Succession or assignment of patent right |
Owner name: SHENZHEN OSA MEDICINE CO., LTD. Free format text: FORMER OWNER: ANHUI BIOLOGICAL MEDICAL INST. Effective date: 20080822 |
|
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20080822 Address after: Shenzhen Nanshan District hi tech Zone, a high-tech incubator in Central District 1-301 Patentee after: SHENZHEN AUSA PHARMED Co.,Ltd. Address before: Building 5, Hefei biological medicine garden, Tianda Road, hi tech Development Zone, West Changjiang Road, Hefei, Anhui Patentee before: Anhui Biological Medical Institute |
|
ASS | Succession or assignment of patent right |
Owner name: SHENZHEN AUSA PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: SHENZHEN AOSA MEDICINE CO., LTD.;ANHUI BIOLOGICAL MEDICAL INSTITUTE Effective date: 20110330 |
|
C41 | Transfer of patent application or patent right or utility model | ||
COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 518000 1-301, BIOLOGICAL INCUBATOR, GAOXIN MIDDLE ROAD 1, MIDDLE AREA OF HIGH-TECH. ZONE, NANSHAN DISTRICT, SHENZHEN CITY TO: 518057 1/F (EAST SIDE) AND 2-3/F OF BUILDING 3, 1-2/F OF BUILDING 2, 3RD PHASE OF BIOLOGICAL INCUBATOR, NO. 16, GAOXIN MIDDLE ROAD 1, NANSHAN HIGH-TECH. ZONE, SHENZHEN CITY, GUANGDONG PROVINCE |
|
TR01 | Transfer of patent right |
Effective date of registration: 20110330 Address after: 518057, Shenzhen Nanshan hi tech Zone, Guangdong hi tech incubator, No. 16, No. three, No. 2, building first, second, building 3, 1, East and 2, 3 Patentee after: SHENZHEN AUSA PHARMACEUTICAL Co.,Ltd. Address before: 518000 a biological incubator in central high tech Zone, Shenzhen, Nanshan District 1-301 Patentee before: SHENZHEN AUSA PHARMED Co.,Ltd. |
|
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Compound medicine for predicting ACEI pressure reducing medicine effect Effective date of registration: 20120628 Granted publication date: 20080402 Pledgee: Shenzhen tekall Zhitong financing Limited by Share Ltd. Pledgor: SHENZHEN AUSA PHARMACEUTICAL Co.,Ltd. Registration number: 2012990000333 |
|
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20130318 Granted publication date: 20080402 Pledgee: Shenzhen tekall Zhitong financing Limited by Share Ltd. Pledgor: SHENZHEN AUSA PHARMACEUTICAL Co.,Ltd. Registration number: 2012990000333 |
|
PLDC | Enforcement, change and cancellation of contracts on pledge of patent right or utility model | ||
PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Compound medicine for predicting ACEI pressure reducing medicine effect Effective date of registration: 20130523 Granted publication date: 20080402 Pledgee: China Everbright Bank Shenzhen Bagualing branch Pledgor: SHENZHEN AUSA PHARMACEUTICAL Co.,Ltd. Registration number: 2013990000312 |
|
PLDC | Enforcement, change and cancellation of contracts on pledge of patent right or utility model | ||
PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20160705 Granted publication date: 20080402 Pledgee: China Everbright Bank, Limited by Share Ltd, Shenzhen, Bagualing branch Pledgor: SHENZHEN AUSA PHARMACEUTICAL Co.,Ltd. Registration number: 2013990000312 |
|
PLDC | Enforcement, change and cancellation of contracts on pledge of patent right or utility model | ||
PM01 | Change of the registration of the contract for pledge of patent right |
Change date: 20160705 Registration number: 2013990000312 Pledgee after: China Everbright Bank, Limited by Share Ltd, Shenzhen, Bagualing branch Pledgee before: China Everbright Bank Shenzhen Bagualing branch |
|
CX01 | Expiry of patent term |
Granted publication date: 20080402 |
|
CX01 | Expiry of patent term | ||
DD01 | Delivery of document by public notice |
Addressee: Yu Hongyu Document name: Notice of Patent Expiration and Termination |
|
DD01 | Delivery of document by public notice |