CN103372007B - Chukrasone B treats in preparation or prevents the application in the medicine of acute heart failure - Google Patents
Chukrasone B treats in preparation or prevents the application in the medicine of acute heart failure Download PDFInfo
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- CN103372007B CN103372007B CN201310280847.5A CN201310280847A CN103372007B CN 103372007 B CN103372007 B CN 103372007B CN 201310280847 A CN201310280847 A CN 201310280847A CN 103372007 B CN103372007 B CN 103372007B
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- heart failure
- acute heart
- medicine
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- chukrasone
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- 206010007556 Cardiac failure acute Diseases 0.000 title claims abstract description 18
- 239000003814 drug Substances 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 229930187319 chukrasone Natural products 0.000 title abstract description 4
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 abstract description 12
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- 230000000747 cardiac effect Effects 0.000 description 6
- 241000282465 Canis Species 0.000 description 3
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 3
- 229960002275 pentobarbital sodium Drugs 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- 208000006193 Pulmonary infarction Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000005622 photoelectricity Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000007575 pulmonary infarction Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
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- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Do you the invention provides Chukrasone? B treats in preparation or prevents the application in the medicine of heart failure.The Chukrasone that the present invention relates to? the purposes of B in preparation treatment acute heart failure medicine belongs to first public, because framework types belongs to brand-new framework types, and the activity of its treatment acute heart failure is unexpectedly strong, there is not the possibility being provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, be used for the treatment of acute heart failure simultaneously and obviously there is significant progress.
Description
Invention field
The present invention relates to ChukrasoneB treat in preparation or prevent the application in the medicine of acute heart failure.
Background technology
Heart failure (heartfailure, HF) refers to that cardiac function is abnormal and causes heart pump blood volume can not meet a kind of pathological and physiological condition of tissue metabolism's needs.Cause of disease inducement causes structure function low and Progressive symmetric erythrokeratodermia morbidity because cardiac overload, cardiac muscle itself, the limited any reason of diastole cause initial myocardial damage; And infect, anemia, gestation, childbirth, cardiac arrhythmia, pulmonary infarction, hyperthyroidism, diabetes, suppression heart medicine bring out and increase the weight of HF.Pathogeny thinks that the mechanism that HF occurs to develop is abnormal hemodynamics in the past; The later stage eighties 20th century recognizes that the activation of nerve-endocrine hormone plays an important role (sympathetic ↑ NE ↑ RAS ↑ wait activation); Specify that after the nineties that " Myocardial Remodeling " (remodelling) is the fundamental mechanism causing the generation of heart failure to develop gradually.
The Compound C hukrasoneB that the present invention relates to is one and delivers (Liu in 2012, H.B.etal., 2012.ChukrasonesAandB:PotentialKv1.2PotassiumChannelBloc kerswithNewSkeletonsfromChukrasiatabularis.OrganicLetter s14 (17), 4438 – 4441.) New skeleton compound, this compound has brand-new framework types, current purposes only relates to potassium-channel inhibit activities (Liu, H.B.etal., 2012.ChukrasonesAandB:PotentialKv1.2PotassiumChannelBloc kerswithNewSkeletonsfromChukrasiatabularis.OrganicLetter s14 (17), 4438 – 4441.), the purposes of the ChukrasoneB that the present invention relates in preparation treatment acute heart failure medicine is belonged to first public, because framework types belongs to brand-new framework types, and the activity of its treatment acute heart failure is unexpectedly strong, there is not the possibility being provided any enlightenment by other compounds, possesses outstanding substantive distinguishing features, be used for the treatment of acute heart failure simultaneously and obviously there is significant progress.
Summary of the invention
The invention provides ChukrasoneB treat in preparation or prevent the application in the medicine of acute heart failure.
Described Compound C hukrasoneB structure is as shown in formula I:
The purposes of the ChukrasoneB that the present invention relates in preparation treatment acute heart failure medicine belongs to first public, because framework types belongs to brand-new framework types, and the activity of its treatment acute heart failure is unexpectedly strong, there is not the possibility being provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, be used for the treatment of acute heart failure simultaneously and obviously there is significant progress.
Detailed description of the invention
The preparation method of Compound C hukrasoneB involved in the present invention is see document (Liu, H.B.etal., 2012.ChukrasonesAandB:PotentialKv1.2PotassiumChannelBloc kerswithNewSkeletonsfromChukrasiatabularis.OrganicLetter s14 (17), 4438 – 4441.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not by any restriction of specific embodiment, but be limited by claim.
Embodiment 1: the preparation of Compound C hukrasoneB tablet involved in the present invention:
Get 20 g of compound ChukrasoneB, add the customary adjuvant 180 grams preparing tablet, mixing, conventional tablet presses makes 1000.
Embodiment 2: the preparation of Compound C hukrasoneB capsule involved in the present invention:
Get 20 g of compound ChukrasoneB, add prepare capsule customary adjuvant as starch 180 grams, mixing, encapsulatedly makes 1000.
Its pharmaceutically active is further illustrated below by pharmacodynamic experiment.
Test example: ChukrasoneB is to the therapeutical effect of dog acute heart failure
1 material animal health adult dogs body weight 12.5 ~ 13.5kg.Pentobarbital sodium (Sigma, import subpackage, specification: 25g); Instrument U.S. BIC16 leads physiograph (production of BIC Corp. of the U.S.); Electromagnetic flowmeter (MFV-3200 type): Japanese photoelectricity company produces.
2 test methods and result
Dog is divided at random NS group (waiting capacity solvent), gastric infusion ChukrasoneB2.0mg/kg group, 1.0mg/kg group, 0.2mg/kg group, often organizes 6.Fasting is after 12 hours, and intravenous injection pentobarbital sodium 40mg/kg anaesthetizes, tracheal intubation, artificial respiration, monitoring aortic pressure (AP) and electrocardiogram.Breast is opened in left side, plugs in conduit to left room pressure and rate of pressure change (± dp/dt thereof from the apex of the heart
max).Waltan-Brodie strain bow is implanted left ventricle antetheca, measures myocardial contraction.With electromagnetic flowmeter determination ascending aorta blood flow.Using ascending aorta flow as cardiac output (CO), calculate cardiac index (CI), index (SI) of often fighting, work done (SW) of often fighting, left heart work done (LVW).Parameters record and BIC physiograph.Postoperative half an hour, parameters reaches stable.From femoral vein constant speed gasing injection pentobarbital sodium (0.5mL/kgmin), with ± dp/dt
maxdropping to about 1000mHg/s is that leading indicator forms acute heart failure.After acute heart failure model stability, each treated animal duodenum gives relative medicine.Between group, T inspection, carries out statistical procedures.
Table 1ChukrasoneB is on the impact (n=6, X ± s) of heart failure canine dp/dt
Compare with NS group,
p<0.05,
p<0.01
Table 2ChukrasoneB is on the impact (n=6, X ± s) of heart failure canine cardiac work
* p<0.05 is compared, * * p<0.01 with before administration; Compare with NS group
p<0.05,
p<0.01
Result is as shown in table 1,2, and instillation various dose ChukrasoneB can increase SW, the LVW ,+dp/dt (comparing with model group matched group, p<0.05orp<0.01) of Heart Failure Dogs.Gavage various dose ChukrasoneB can increase SW, the LVW ,+dp/dt (comparing with model group matched group, p<0.01orp<0.05) of Heart Failure Dogs.
Table 3ChukrasoneB is on the kinemic impact of heart failure canine (n=6, X ± s)
* p<0.05 is compared, * * p<0.01 with before administration; Compare with NS group
p<0.05,
p<0.01
Result is as shown in table 3, and instillation various dose ChukrasoneB can increase the cardiac output (comparing with model control group, p<0.01orp<0.05) of Heart Failure Dogs.Gavage various dose ChukrasoneB can increase the cardiac output (comparing with model control group, p<0.01orp<0.05) of Heart Failure Dogs.
Conclusion: ChukrasoneB significantly can improve acute heart failure, can be used for preparing the medicine for the treatment of or preventing heart failure.
Claims (1)
1.ChukrasoneB preparation treatment or prevention acute heart failure medicine in application, described Compound C hukrasoneB structure as
formula Ishown in:
formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310280847.5A CN103372007B (en) | 2013-07-04 | 2013-07-04 | Chukrasone B treats in preparation or prevents the application in the medicine of acute heart failure |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310280847.5A CN103372007B (en) | 2013-07-04 | 2013-07-04 | Chukrasone B treats in preparation or prevents the application in the medicine of acute heart failure |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103372007A CN103372007A (en) | 2013-10-30 |
| CN103372007B true CN103372007B (en) | 2015-11-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310280847.5A Expired - Fee Related CN103372007B (en) | 2013-07-04 | 2013-07-04 | Chukrasone B treats in preparation or prevents the application in the medicine of acute heart failure |
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| Country | Link |
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| CN (1) | CN103372007B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103751176B (en) * | 2013-11-22 | 2016-05-18 | 淄博齐鼎立专利信息咨询有限公司 | The application of Trigoxyphin K in treatment or prophylaxis of acute heart failure medicine |
-
2013
- 2013-07-04 CN CN201310280847.5A patent/CN103372007B/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| Chukrasones A and B: Potential Kv1.2 Potassium Channel Blockers with New Skeletons from Chukrasia tabularis;Liu, H. B. et al.;《Organic Letters 》;20121231;第14卷(第17期);第4438–4441页 * |
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| Publication number | Publication date |
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| CN103372007A (en) | 2013-10-30 |
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Inventor after: Ni Ruiqin Inventor after: Sun Fengyan Inventor before: Ding Shengyu |
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Effective date of registration: 20170113 Address after: Xiangyang Road 261021 in Shandong province Weifang city Weicheng District No. 34, building 4, unit 1, No. 401 Patentee after: Ni Ruiqin Address before: 266000 Licang, Qingdao, No. nine East water road, No. 320, No. Patentee before: Gu Xiangmao |
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