CN103356671A - Application of Houttuynoid C in treating or preventing chronic heart failure - Google Patents
Application of Houttuynoid C in treating or preventing chronic heart failure Download PDFInfo
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- CN103356671A CN103356671A CN2013102551748A CN201310255174A CN103356671A CN 103356671 A CN103356671 A CN 103356671A CN 2013102551748 A CN2013102551748 A CN 2013102551748A CN 201310255174 A CN201310255174 A CN 201310255174A CN 103356671 A CN103356671 A CN 103356671A
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- Prior art keywords
- houttuynoid
- heart failure
- chronic heart
- treating
- application
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- 206010007558 Cardiac failure chronic Diseases 0.000 title claims abstract description 20
- FCUIRBQXJWMGLZ-YLUJEXTNSA-N 2-(3-decanoyl-7-hydroxy-1-benzofuran-4-yl)-5,7-dihydroxy-3-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one Chemical compound C=12C(C(=O)CCCCCCCCC)=COC2=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 FCUIRBQXJWMGLZ-YLUJEXTNSA-N 0.000 title abstract description 44
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 8
- 229930190556 houttuynoid Natural products 0.000 claims description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 206010007556 Cardiac failure acute Diseases 0.000 abstract 1
- 230000001154 acute effect Effects 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 9
- 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
- 206010019280 Heart failures Diseases 0.000 description 4
- 208000009889 Herpes Simplex Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 241000700584 Simplexvirus Species 0.000 description 4
- 230000003602 anti-herpes Effects 0.000 description 4
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 4
- 240000000691 Houttuynia cordata Species 0.000 description 3
- 235000013719 Houttuynia cordata Nutrition 0.000 description 3
- 229930003935 flavonoid Natural products 0.000 description 3
- 150000002215 flavonoids Chemical class 0.000 description 3
- 235000017173 flavonoids Nutrition 0.000 description 3
- 238000007914 intraventricular administration Methods 0.000 description 3
- 241000700157 Rattus norvegicus Species 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
- 210000004165 myocardium Anatomy 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
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 208000006193 Pulmonary infarction Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000037005 anaesthesia Effects 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
- 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
- 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
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 238000005259 measurement Methods 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
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides an application of Houttuynoid C in preparing a medicine for treating or preventing chronic heart failure, and specifically provides an effect of the Houttuynoid C in treating acute and chronic heart failure. The application of the Houttuynoid C in preparing a medicine for treating chronic heart failure is revealed for the first time; since a brand new skeleton type is adopted and the activity thereof in treating chronic heart failure is unexpectedly strong, the possibility of other compounds giving any prompt is avoided, and the Houttuynoid C has outstanding substantive features; and a remarkable progress is made in applying the Houttuynoid C to the treatment on chronic heart failure.
Description
Invention field
The present invention relates to the application of Houttuynoid C in the medicine of preparation treatment or preventing chronic heart failure.
Background technology
Heart failure (hear failure, HF) refers to that cardiac function causes the heart pump blood volume can not satisfy a kind of pathological and physiological condition of tissue metabolism's needs unusually.Cause of disease inducement causes initial myocardial damage because of cardiac overload, cardiac muscle itself, the limited any reason of diastole and causes structure function lowly and the morbidity of carrying out property; And infect, anemia, gestation, childbirth, cardiac arrhythmia, pulmonary infarction, hyperthyroidism, diabetes, inhibition heart medicine bring out and increase the weight of HF.Pathogeny thinks that in the past the mechanism of HF genesis is abnormal hemodynamics; The later stage eighties 20th century is recognized the activation of nerve-endocrine hormone play an important role (sympathetic ↑ NE ↑ RAS ↑ wait activation); Clear and definite gradually " Myocardial Remodeling " is the fundamental mechanism that causes the genesis of heart failure (remodelling) after the nineties.
The compound H outtuynoid C that the present invention relates to is one and delivered (Chen in 2012, S. D. et al., 2012. Houttuynoid A-E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.) New skeleton compound, this chemical compound has brand-new framework types, present purposes only relates to anti-herpes simplex virus activity (Chen, S. D. et al., 2012. Houttuynoid A-E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.), belong to open first for the purposes of the Houttuynoid C that the present invention relates in preparation treatment chronic heart failure, because framework types belongs to brand-new framework types, and its treatment chronic heart failure is unexpectedly active strong, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, be used for the treatment of simultaneously chronic heart failure and obviously have significant progress.
Summary of the invention
The invention provides the application of Houttuynoid C in the medicine of preparation treatment or preventing chronic heart failure.
Described compound H outtuynoid C-structure is shown in formula I:
Formula I
The purposes of the Houttuynoid C that the present invention relates in preparation treatment chronic heart failure belongs to open first, because framework types belongs to brand-new framework types, and its treatment chronic heart failure is unexpectedly active strong, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, be used for the treatment of simultaneously chronic heart failure and obviously have significant progress.
The specific embodiment
The preparation method of compound H outtuynoid C involved in the present invention is referring to document (Chen, S. D. et al., 2012. Houttuynoid A-E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subjected to any restriction of specific embodiment, but limited by claim.
Embodiment 1: the preparation of compound H outtuynoid C tablet involved in the present invention:
Get 20 and digest compound Houttuynoid C, add conventional adjuvant 180 grams of preparation tablet, mixing, conventional tablet machine are made 1000.
Embodiment 2: the preparation of compound H outtuynoid C capsule involved in the present invention:
Get 20 and digest compound Houttuynoid C, add conventional adjuvant such as starch 180 grams of preparation capsule, mixing is encapsulatedly made 1000.
Further specify its pharmaceutically active below by pharmacodynamic experiment.
Experimental example Houttuynoid C is on the impact of chronic heart failure rat
Test method and result
100 of rats, male and female half and half are got 100 lumbar injection doxorubicin hydrochloride 2mg/kg, and 1 time weekly, totally 6 weeks.Be divided at random 10 groups, namely NS organizes, Captopril tablets 12.5mg/kg group, gastric infusion Houttuynoid C 0.2mg/kg group, gastric infusion Houttuynoid C 2.5mg/kg group, gastric infusion Houttuynoid C 5.0mg/kg group.Play giving every day Houttuynoid C gavage each group the 5th week, administration 21 days.20% urethane 1.1g/kg intraperitoneal injection of anesthesia, peeling operation trachea and intubate, the total tremulous pulse in right side that dissociates simultaneously inserts homemade ventricle intubate (diameter 1mm is full of 1% heparin) through it, traces blood pressure curve; Continue again to insert, make it enter left ventricle by the left side arterial valve, trace the 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 data such as the myocardium maximal velocity of contraction of actual measurement (Vpm) etc.Other gets 10 rats as Normal group, does not give doxorubicin hydrochloride, and all the other operate with above-mentioned, and statistical procedures is carried out in the T check between group.
Table 1 Houttuynoid C is on the impact (n=10) of chronic heart failure Cardiac Function in Rat
Compare with the NS group,
△: p＜0.05,
△ △: p＜0.01
Table 1 result of the test shows can the raise LVSP of the Heart Failure Wistar Rats that caused by doxorubicin hydrochloride of Houttuynoid C gastric infusion 0.2mg/kg group ,+dp/dt
Max,-dp/dt
MaxReduction (comparing P＜0.05 with the NS group) with Vpm; Can significantly the raise LVSP of the Heart Failure Wistar Rats that caused by doxorubicin hydrochloride of Houttuynoid C gastric infusion 2.5mg/kg, 5.0mg/kg ,+dp/dt
Max,-dp/dt
MaxReduction (comparing P＜0.01 with the NS group) with Vpm.
Conclusion: Houttuynoid C 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.Houttuynoid the application of C in treatment or the medicine of preventing chronic heart failure, described compound H outtuynoid C-structure as
Formula IShown in:
Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310255174.8A CN103356671B (en) | 2013-06-24 | 2013-06-24 | The application of Houttuynoid C in the medicine preparing treatment or preventing chronic heart failure |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310255174.8A CN103356671B (en) | 2013-06-24 | 2013-06-24 | The application of Houttuynoid C in the medicine preparing treatment or preventing chronic heart failure |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103356671A true CN103356671A (en) | 2013-10-23 |
| CN103356671B CN103356671B (en) | 2015-11-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310255174.8A Expired - Fee Related CN103356671B (en) | 2013-06-24 | 2013-06-24 | The application of Houttuynoid C in the medicine preparing treatment or preventing chronic heart failure |
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| Country | Link |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101678027A (en) * | 2007-06-09 | 2010-03-24 | 东亚制药株式会社 | Pharmaceutical compositions for the treatment of chronic heart failure comprising pyrazolopyrimidinone derivative compound |
| CN101687858A (en) * | 2007-05-08 | 2010-03-31 | 比亚尔-珀特拉和Ca股份公司 | As 1 of dopamine-inhibitor, 3-glyoxalidine-2-40 thione derivatives |
-
2013
- 2013-06-24 CN CN201310255174.8A patent/CN103356671B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101687858A (en) * | 2007-05-08 | 2010-03-31 | 比亚尔-珀特拉和Ca股份公司 | As 1 of dopamine-inhibitor, 3-glyoxalidine-2-40 thione derivatives |
| CN101678027A (en) * | 2007-06-09 | 2010-03-24 | 东亚制药株式会社 | Pharmaceutical compositions for the treatment of chronic heart failure comprising pyrazolopyrimidinone derivative compound |
Non-Patent Citations (1)
| Title |
|---|
| CHEN, S. D. ET AL: "Houttuynoid A-E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata", 《ORGANIC LETTERS》 * |
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| Publication number | Publication date |
|---|---|
| CN103356671B (en) | 2015-11-25 |
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| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20151027 Address after: No. nine East water road, Licang District, Shandong, Qingdao Applicant after: Gu Xiangmao Address before: 210009 Gulou District, Jiangsu, Nanjing Gu Ping Kong, No. 4 Applicant before: Ding Shengyu |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Wan Bingjian Inventor before: Ding Shengyu |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170322 Address after: 238300 Wuwei County City, Wuhu Province, the town of well-being of the opening of the village of Wang Gao Village, Wang Village, No. 21 Patentee after: Wan Bingjian Address before: No. nine East water road, Licang District, Shandong, Qingdao Patentee before: Gu Xiangmao |
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| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20151125 Termination date: 20180624 |