CN103316004B - Pharmaceutical composition used for preventing and controlling metabolic syndrome and application thereof - Google Patents
Pharmaceutical composition used for preventing and controlling metabolic syndrome and application thereof Download PDFInfo
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- CN103316004B CN103316004B CN201310295127.6A CN201310295127A CN103316004B CN 103316004 B CN103316004 B CN 103316004B CN 201310295127 A CN201310295127 A CN 201310295127A CN 103316004 B CN103316004 B CN 103316004B
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- aliskiren
- pharmaceutical composition
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- ligustrazine phosphate
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 25
- 208000001145 Metabolic Syndrome Diseases 0.000 title abstract description 9
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 title abstract description 9
- UXOWGYHJODZGMF-QORCZRPOSA-N Aliskiren Chemical compound COCCCOC1=CC(C[C@@H](C[C@H](N)[C@@H](O)C[C@@H](C(C)C)C(=O)NCC(C)(C)C(N)=O)C(C)C)=CC=C1OC UXOWGYHJODZGMF-QORCZRPOSA-N 0.000 claims abstract description 37
- KWWLGXNRLABSMP-UHFFFAOYSA-N phosphoric acid;2,3,5,6-tetramethylpyrazine Chemical compound OP(O)(O)=O.CC1=NC(C)=C(C)N=C1C KWWLGXNRLABSMP-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229960004601 aliskiren Drugs 0.000 claims abstract description 29
- 230000004060 metabolic process Effects 0.000 claims description 26
- 208000011580 syndromic disease Diseases 0.000 claims description 26
- 239000007787 solid Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 4
- 239000008280 blood Substances 0.000 abstract description 12
- 230000037396 body weight Effects 0.000 abstract description 12
- 210000004369 blood Anatomy 0.000 abstract description 10
- 239000000203 mixture Substances 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 7
- 230000036772 blood pressure Effects 0.000 abstract description 5
- 150000003839 salts Chemical class 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 3
- 206010067484 Adverse reaction Diseases 0.000 abstract 1
- 230000006838 adverse reaction Effects 0.000 abstract 1
- 241000700159 Rattus Species 0.000 description 14
- 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 11
- 239000008103 glucose Substances 0.000 description 11
- 239000000890 drug combination Substances 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 7
- 108010023302 HDL Cholesterol Proteins 0.000 description 6
- FINHMKGKINIASC-UHFFFAOYSA-N Tetramethylpyrazine Chemical compound CC1=NC(C)=C(C)N=C1C FINHMKGKINIASC-UHFFFAOYSA-N 0.000 description 6
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 6
- 150000001720 carbohydrates Chemical class 0.000 description 5
- 235000014633 carbohydrates Nutrition 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000000291 postprandial effect Effects 0.000 description 5
- 230000001603 reducing effect Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 230000035488 systolic blood pressure Effects 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102000019197 Superoxide Dismutase Human genes 0.000 description 2
- 108010012715 Superoxide dismutase Proteins 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 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
- 230000035485 pulse pressure Effects 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 108090001067 Angiotensinogen Proteins 0.000 description 1
- 102000004881 Angiotensinogen Human genes 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical group OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 241000244365 Ligusticum sinense Species 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 208000007683 Pediatric Obesity Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 229940044478 aliskiren 150 mg Drugs 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 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 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000001399 anti-metabolic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 1
- 201000008980 hyperinsulinism Diseases 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000007410 oral glucose tolerance test Methods 0.000 description 1
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000003234 polygenic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 108700022737 rat Fat1 Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000002461 renin inhibitor Substances 0.000 description 1
- 229940086526 renin-inhibitors Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Grouping | Sample size (only) | Dosage |
Model group | 12 | The purified water of same volume |
Aliskiren group | 12 | 15mg·kg -1·d -1Aliskiren |
Ligustrazine phosphate group | 12 | 2.5 mg·kg -1·d -1Ligustrazine phosphate |
Drug combination group | 12 | 15mg·kg -1·d -1Aliskiren+2.5mgkg -1·d -1Ligustrazine phosphate |
Group | Body weight (g) | SBP(mmHg) | DBP(mmHg) |
Model group | 439±42 | 171.5±18.2 | 93.2±11.9 |
Aliskiren group | 426±35 | 137.6±14.3 | 97.2±13.2 |
Ligustrazine phosphate group | 442±39 | 168.9±16.7 | 98.3±13.5 |
Drug combination group | 363±36 ★★●▼▼ | 133.6±15.0 ★★▼▼ | 92.9±12.4 |
Group | Fasting glucose | Post-prandial glycemia | Difference |
Model group | 6.10±0.52 | 8.59±0.41 | 2.49±0.34 |
Aliskiren group | 5.74±0.32 ★ | 8.16±0.38 | 2.42±0.39 |
Ligustrazine phosphate group | 6.12±0.39 | 8.68±0.46 | 2.56±0.51 |
Drug combination group | 5.27±0.32 ★★●▼▼ | 7.10±0.40 ★★●●▼▼ | 1.83±0.32 ★★●▼▼ |
Group | TC | TG | HDL-C |
Model group | 3.50±0.48 | 1.35±0.20 | 0.79±0.29 |
Aliskiren group | 3.19±0.46 | 1.16±0.18 | 0.85±0.33 |
Ligustrazine phosphate group | 3.08±0.51 | 1.04±0.23 ★ | 0.82±0.30 |
Drug combination group | 2.93±0.40 ★ | 1.10±0.14 ★ | 0.93±0.27 |
Claims (3)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN201310295127.6A CN103316004B (en) | 2013-07-15 | 2013-07-15 | Pharmaceutical composition used for preventing and controlling metabolic syndrome and application thereof |
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Application Number | Priority Date | Filing Date | Title |
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CN201310295127.6A CN103316004B (en) | 2013-07-15 | 2013-07-15 | Pharmaceutical composition used for preventing and controlling metabolic syndrome and application thereof |
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Publication Number | Publication Date |
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CN103316004A CN103316004A (en) | 2013-09-25 |
CN103316004B true CN103316004B (en) | 2014-06-25 |
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CN201310295127.6A Active CN103316004B (en) | 2013-07-15 | 2013-07-15 | Pharmaceutical composition used for preventing and controlling metabolic syndrome and application thereof |
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CN (1) | CN103316004B (en) |
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2013
- 2013-07-15 CN CN201310295127.6A patent/CN103316004B/en active Active
Non-Patent Citations (6)
Title |
---|
刘会田等.川芎嗪对42例代谢综合征患者血栓前状态的影响.《临床内科杂志》.2005,第22卷(第7期),489-490. |
天然生物碱川芎嗪通过阻断PDGF-β受体介导的ERK和/或p38信号通路抑制高糖高胰岛素和过氧化氢诱导的肝星状细胞的活化;张峰等;《中华中医药杂志》;20130531;第28卷(第5期);1174-1182 * |
川芎嗪对42例代谢综合征患者血栓前状态的影响;刘会田等;《临床内科杂志》;20050731;第22卷(第7期);489-490 * |
张峰等.天然生物碱川芎嗪通过阻断PDGF-β受体介导的ERK和/或p38信号通路抑制高糖高胰岛素和过氧化氢诱导的肝星状细胞的活化.《中华中医药杂志》.2013,第28卷(第5期),1174-1182. |
张雅娉等.肾素抑制剂阿利吉仑.《中国临床药理学杂志》.2012,第28卷(第3期),221-224. |
肾素抑制剂阿利吉仑;张雅娉等;《中国临床药理学杂志》;20120331;第28卷(第3期);221-224 * |
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CN103316004A (en) | 2013-09-25 |
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