CN103356673B - The application of Houttuynoid A in the medicine preparing treatment or preventing chronic heart failure - Google Patents
The application of Houttuynoid A in the medicine preparing treatment or preventing chronic heart failure Download PDFInfo
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- CN103356673B CN103356673B CN201310255827.2A CN201310255827A CN103356673B CN 103356673 B CN103356673 B CN 103356673B CN 201310255827 A CN201310255827 A CN 201310255827A CN 103356673 B CN103356673 B CN 103356673B
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- heart failure
- chronic heart
- houttuynoid
- treatment
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- 206010007558 Cardiac failure chronic Diseases 0.000 title claims abstract description 20
- 239000003814 drug Substances 0.000 title claims abstract description 8
- FHNVKCJCSKWUFS-YLUJEXTNSA-N 4-[5,7-dihydroxy-4-oxo-3-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-2-yl]-7-hydroxy-2-nonyl-1-benzofuran-3-carbaldehyde Chemical compound C=12C(C=O)=C(CCCCCCCCC)OC2=C(O)C=CC=1C=1OC2=CC(O)=CC(O)=C2C(=O)C=1O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O FHNVKCJCSKWUFS-YLUJEXTNSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 230000000694 effects Effects 0.000 abstract description 5
- 229930190556 houttuynoid Natural products 0.000 abstract 3
- 206010007556 Cardiac failure acute Diseases 0.000 abstract 1
- 230000001154 acute effect Effects 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 206010019280 Heart failures Diseases 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 4
- 238000007914 intraventricular administration Methods 0.000 description 3
- 241000700157 Rattus norvegicus 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
- 239000002775 capsule Substances 0.000 description 2
- 230000004217 heart function Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- 208000006193 Pulmonary infarction Diseases 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000003602 anti-herpes 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
- 230000036772 blood pressure Effects 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 230000009194 climbing 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
- 238000005516 engineering process Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- 230000002107 myocardial effect Effects 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
- 230000035935 pregnancy Effects 0.000 description 1
- 230000007575 pulmonary infarction Effects 0.000 description 1
- 238000007634 remodeling Methods 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
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Do you the invention provides Houttuynoid? does the application of A in the medicine preparing treatment or preventing chronic heart failure, propose Houttuynoid particularly? A is to the therapeutical effect of acute and chronic heart failure.The Houttuynoid that the present invention relates to? the purposes of A in preparation treatment chronic heart failure belongs to first public, because framework types belongs to brand-new framework types, and the activity of its treatment chronic 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 chronic heart failure simultaneously and obviously there is significant progress.
Description
Invention field
The present invention relates to the application of HouttuynoidA in the medicine preparing treatment or preventing chronic 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 H outtuynoidA that the present invention relates to is one and delivers (Chen in 2012, S.D.etal., 2012.HouttuynoidA-E, Anti-HerpesSimplexVirusActiveFlavonoidswithNovelSkeleton sfromHouttuyniacordata.OrganicLetters14 (7), 17724 – 1775.) New skeleton compound, this compound has brand-new framework types, current purposes only relates to anti-herpes simplex virus activity (Chen, S.D.etal., 2012.HouttuynoidA-E, Anti-HerpesSimplexVirusActiveFlavonoidswithNovelSkeleton sfromHouttuyniacordata.OrganicLetters14 (7), 17724 – 1775.), the purposes of the HouttuynoidA that the present invention relates in preparation treatment chronic heart failure is belonged to first public, because framework types belongs to brand-new framework types, and the activity of its treatment chronic 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 chronic heart failure simultaneously and obviously there is significant progress.
Summary of the invention
The invention provides the application of HouttuynoidA in the medicine preparing treatment or preventing chronic heart failure.
Described compound H outtuynoidA structure is as shown in formula I:
The purposes of the HouttuynoidA that the present invention relates in preparation treatment chronic heart failure belongs to first public, because framework types belongs to brand-new framework types, and the activity of its treatment chronic 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 chronic heart failure simultaneously and obviously there is significant progress.
Detailed description of the invention
The preparation method of compound H outtuynoidA involved in the present invention is see document (Chen, S.D.etal., 2012.HouttuynoidA-E, Anti-HerpesSimplexVirusActiveFlavonoidswithNovelSkeleton sfromHouttuyniacordata.OrganicLetters14 (7), 17724 – 1775.).
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 H outtuynoidA tablet involved in the present invention:
Get 20 g of compound HouttuynoidA, add the customary adjuvant 180 grams preparing tablet, mixing, conventional tablet presses makes 1000.
Embodiment 2: the preparation of compound H outtuynoidA capsule involved in the present invention:
Get 20 g of compound HouttuynoidA, add prepare capsule customary adjuvant as starch 180 grams, mixing, encapsulatedly makes 1000.
Its pharmaceutically active is further illustrated below by pharmacodynamic experiment.
Experimental example HouttuynoidA is on the impact of chronic heart failure rat
Test method and result
Rat 100, male and female half and half, get 100 lumbar injection doxorubicin hydrochloride 2mg/kg, 1 time weekly, totally 6 weeks.Be divided into 10 groups at random, i.e. NS group, Captopril tablets 12.5mg/kg group, gastric infusion HouttuynoidA0.2mg/kg group, gastric infusion HouttuynoidA2.5mg/kg group, gastric infusion HouttuynoidA5.0mg/kg group.Within 5th week, rise and give each group of HouttuynoidA gavage, administration 21 days every day.20% urethane 1.1g/kg intraperitoneal injection of anesthesia, peeling operation trachea intubate, the total tremulous pulse in right side of simultaneously dissociating, inserts homemade heart catherization (diameter 1mm is full of 1% heparin) through it, traces blood pressure curve; Continue again to insert, make it enter left ventricle by left arterial lobe, trace intraventricular pressure curve, Automatic analysis left ventricular systolic pressure (LVSP), maximum the climbing speed (+dp/dt of intraventricular pressure
max), intraventricular pressure maximum falling speed (-dp/dt
max) and survey the data such as myocardium maximal velocity of contraction (Vpm).Separately get 10 rats as Normal group, do not give doxorubicin hydrochloride, all the other operations are with above-mentioned, and between group, T inspection, carries out statistical procedures.
Table 1HouttuynoidA is on the impact (n=10) of chronic heart failure Cardiac Function in Rat
Compare with NS group,
△: p<0.05,
△ △: p<0.01
Table 1 result of the test shows that HouttuynoidA gastric infusion 0.2mg/kg group can raise the LVSP of the Heart Failure Wistar Rats caused by doxorubicin hydrochloride ,+dp/dt
max,-dp/dt
maxwith the reduction (comparing with NS group, P<0.05) of Vpm; HouttuynoidA gastric infusion 2.5mg/kg, 5.0mg/kg significantly can raise the LVSP of the Heart Failure Wistar Rats caused by doxorubicin hydrochloride ,+dp/dt
max,-dp/dt
maxwith the reduction (comparing with NS group, P<0.01) of Vpm.
Conclusion: HouttuynoidA has the effect of significant treatment or preventing chronic heart failure, can be used for preparing the medicine for the treatment of or preventing chronic heart failure.
Claims (1)
1.HouttuynoidA preparation treatment or preventing chronic heart failure medicine in application, described compound H outtuynoidA structure as
formula Ishown in:
formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310255827.2A CN103356673B (en) | 2013-06-24 | 2013-06-24 | The application of Houttuynoid A in the medicine preparing treatment or preventing chronic heart failure |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310255827.2A CN103356673B (en) | 2013-06-24 | 2013-06-24 | The application of Houttuynoid A in the medicine preparing treatment or preventing chronic heart failure |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103356673A CN103356673A (en) | 2013-10-23 |
| CN103356673B true CN103356673B (en) | 2015-11-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310255827.2A Expired - Fee Related CN103356673B (en) | 2013-06-24 | 2013-06-24 | The application of Houttuynoid A in the medicine preparing treatment or preventing chronic heart failure |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103356673B (en) |
-
2013
- 2013-06-24 CN CN201310255827.2A patent/CN103356673B/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| Houttuynoid A-E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata;Chen, S. D. et al.;《Organic Letters 》;20121231;第14卷(第7期);第1772-1775页 * |
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| Publication number | Publication date |
|---|---|
| CN103356673A (en) | 2013-10-23 |
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Effective date of registration: 20151028 Address after: 266000 Licang, Qingdao, No. nine East water road, No. 320, No. Applicant after: Gu Xiangmao Address before: 210009 Gulou District, Jiangsu, Nanjing Gu Ping Kong, No. 4 Applicant before: Ding Shengyu |
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| C41 | Transfer of patent application or patent right or utility model | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhang Yanxia Inventor after: Zhang Zizhi Inventor before: Ding Shengyu |
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| TR01 | Transfer of patent right |
Effective date of registration: 20170125 Address after: 262700 Shandong city in Weifang Province, Shouguang City, Yinhai Road No. 18, building 19, unit 4, No. 301 Patentee after: Zhang Yanxia Patentee after: Lin Lina Address before: 266000 Licang, Qingdao, No. nine East water road, No. 320, No. Patentee before: Gu Xiangmao |
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Granted publication date: 20151125 Termination date: 20180624 |
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| CF01 | Termination of patent right due to non-payment of annual fee |