CN103751179B - The application of a kind of compound in treatment or prevention acute heart failure medicine - Google Patents
The application of a kind of compound in treatment or prevention acute heart failure medicine Download PDFInfo
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- CN103751179B CN103751179B CN201310629460.6A CN201310629460A CN103751179B CN 103751179 B CN103751179 B CN 103751179B CN 201310629460 A CN201310629460 A CN 201310629460A CN 103751179 B CN103751179 B CN 103751179B
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- heart failure
- mollolide
- compound
- treatment
- acute heart
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- 206010007556 Cardiac failure acute Diseases 0.000 title claims abstract description 18
- 150000001875 compounds Chemical class 0.000 title claims abstract description 17
- 239000003814 drug Substances 0.000 title claims abstract description 13
- 230000002265 prevention Effects 0.000 title claims description 12
- LDBZVNJHWKNRTA-GYLJPACSSA-N mollolide A Natural products C([C@@]12[C@H](O)[C@H]([C@](C2)(C)O)[C@H](O)C[C@H]1C(=O)C)[C@H]1OC(=O)C(C)(C)[C@]1(O)CCO LDBZVNJHWKNRTA-GYLJPACSSA-N 0.000 claims abstract description 29
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 206010019280 Heart failures Diseases 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 3
- 230000000747 cardiac effect Effects 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 5
- 241000282465 Canis Species 0.000 description 3
- 238000000034 method Methods 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 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- 150000004141 diterpene derivatives Chemical class 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
- 229960002275 pentobarbital sodium Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 241001290352 Caulerpa racemosa Species 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 241001465754 Metazoa Species 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
- 230000009471 action Effects 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 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
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- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 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
- 238000011156 evaluation 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
- 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
- 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
- 230000004060 metabolic process Effects 0.000 description 1
- 229930185342 mollolide Natural products 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
- 230000004962 physiological condition Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
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- 238000002627 tracheal intubation Methods 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a kind of compound Mollolide A treat in preparation or prevent the application in the medicine of heart failure, belong to first public, because framework types belongs to brand-new framework types, and the activity of its treatment acute heart failure is strong, possess outstanding substantive distinguishing features, be used for the treatment of acute heart failure simultaneously and obviously there is significant progress.
Description
Technical field
The present invention relates to the novelty teabag of a kind of compound Mollolide A, particularly relate to the application of Mollolide A in preparation treatment or prevention acute heart failure medicine.
Background technology
Heart failure (hear failure, 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 Mollolide A that the present invention relates to is one and delivers (Yong Li in 2013, et al., MollolideA, a Diterpenoid with a New1, 10:2, 3-Disecograyanane Skeleton from the Roots ofRhododendron molle Organic Letters, 2013, 15 (12): 3074 – 3077.) noval chemical compound, this compound has brand-new framework types, current purposes finds antibacterial (the Yong Li of its energy, et al., Mollolide A, a Diterpenoid with a New1, 10:2, 3-Disecograyanane Skeleton from the Roots ofRhododendron molle Organic Letters, 2013, 15 (12): 3074 – 3077.), the purposes of the Mollolide A that the present invention relates in preparation treatment or prevention acute heart failure medicine belongs to first public.
Summary of the invention
The present invention proposes the application of Mollolide A in preparation treatment or prevention acute heart failure medicine.Find out from pharmacological evaluation, Mollolide A has the effect for the treatment of preferably or prevention acute heart failure.Due to the pharmacological action of the first public Mollolide A of the present invention in treatment or prevention acute heart failure.
Described compound Mollolide A structure is as shown in formula I:
Formula I
Technical scheme of the present invention is: the application of Mollolide A, is specifically applied to preparation treatment or prevention acute heart failure medicine.The present invention finds by carrying out NS group contrast test to dog, and Mollolide A can increase the SW of Heart Failure Dogs, LVW ,+dp/dt, cardiac output.Therefore, Mollolide A for the preparation of the medicine of prevention heart failure, can have good development prospect.
The purposes of the Mollolide A that the present invention relates in preparation treatment or prevention acute heart failure medicine belongs to first public, because framework types belongs to brand-new framework types, and the activity of its treatment or prevention acute heart failure is strong, possess outstanding substantive distinguishing features, be used for the treatment of simultaneously or prevent acute heart failure obviously to have significant progress.
Detailed description of the invention
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.
The preparation method of compound Mollolide A involved in the present invention is see document (Ding-Quan Liu, et al., Mollolide A and B, two novel bisindole alkaloids from the green alga Caulerparacemosa.Fitoterapia, 91 (2013): 15 – 20.), prepare compound Mollolide A according to the method described above.
Embodiment 1: the preparation of compound Mollolide A tablet involved in the present invention:
Get 5 g of compound Mollolide A, add 195 grams, dextrin, mixing, Conventional compression makes 1000.
Embodiment 2: the preparation of compound Mollolide A capsule involved in the present invention:
Get 5 g of compound Mollolide A, add starch 195 grams, mixing, encapsulatedly makes 1000.
Its pharmaceutically active is further illustrated below by pharmacodynamic experiment.
Experimental example 1: adopt NS method assessing compound Mollolide A to the therapeutical effect of dog acute heart failure
1, method: dog is divided at random NS group (waiting capacity solvent), gastric infusion Mollolide A2.0mg/kg group, 1.0mg/kg group, 0.2mg/kg group, often organize 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.
2, result:
Table 1Mollolide A is on the impact (n=6, X ± s) of heart failure canine dp/dt
Compare with NS group, * * P<0.01*P<0.05
Table 2Mollolide A is on the impact (n=6, X ± s) of heart failure canine cardiac work
Compare with NS group, * * P<0.01*P<0.05; Compare with before administration,
##p<0.01
#p<0.05
Result is as shown in table 1,2, and instillation various dose Mollolide A can increase the SW of Heart Failure Dogs, LVW ,+dp/dt(compare with model group matched group, p<0.05or p<0.01).Gavage various dose Mollolide A can increase the SW of Heart Failure Dogs, LVW ,+dp/dt(compare with model group matched group, p<0.01or p<0.05).
Table 3Mollolide A is on the kinemic impact of heart failure canine (n=6, X ± s)
Compare with NS group, * * P<0.01*P<0.05; Compare with before administration,
##p<0.01
#p<0.05
Result is as shown in table 3, and instillation various dose Mollolide A can increase the cardiac output (comparing with model control group, p<0.01or p<0.05) of Heart Failure Dogs.Gavage various dose Mollolide A can increase the cardiac output (comparing with model control group, p<0.01or p<0.05) of Heart Failure Dogs.
Shown by above-described embodiment, Mollolide A of the present invention can increase the SW of Heart Failure Dogs, LVW ,+dp/dt, cardiac output.Prove thus, Mollolide A of the present invention significantly can improve acute heart failure, can be used for preparing the medicine for the treatment of or preventing heart failure.
Claims (1)
1. the application of compound in preparation treatment or prevention acute heart failure medicine, described compound Mollolide A structure is as shown in formula I:
Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310629460.6A CN103751179B (en) | 2013-11-29 | 2013-11-29 | The application of a kind of compound in treatment or prevention acute heart failure medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310629460.6A CN103751179B (en) | 2013-11-29 | 2013-11-29 | The application of a kind of compound in treatment or prevention acute heart failure medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103751179A CN103751179A (en) | 2014-04-30 |
| CN103751179B true CN103751179B (en) | 2015-10-07 |
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|---|---|---|---|
| CN201310629460.6A Expired - Fee Related CN103751179B (en) | 2013-11-29 | 2013-11-29 | The application of a kind of compound in treatment or prevention acute heart failure medicine |
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Inventor after: Yu Cuifeng Inventor after: Zhang Hu Inventor before: Wu Wenyuan |
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Effective date of registration: 20170227 Address after: 075721 Cypress Village, cypress Township, Weixian County, Hebei, China, No. 21, No. Patentee after: Yu Cuifeng Patentee after: Zhang Hu Address before: 325055 Zhejiang, Wenzhou, Longwan District, Haicheng street, Central South Road, No. 81 Patentee before: Tu Ruiqiang |
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Granted publication date: 20151007 Termination date: 20171129 |