CN103393703A - Application of Houttuynoid B in drugs treating myocardial ischemia - Google Patents
Application of Houttuynoid B in drugs treating myocardial ischemia Download PDFInfo
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- CN103393703A CN103393703A CN2013102558836A CN201310255883A CN103393703A CN 103393703 A CN103393703 A CN 103393703A CN 2013102558836 A CN2013102558836 A CN 2013102558836A CN 201310255883 A CN201310255883 A CN 201310255883A CN 103393703 A CN103393703 A CN 103393703A
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- houttuynoid
- myocardial ischemia
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- drugs
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- OXBQNNYXKZSXES-RDHYKQKTSA-N 5,7-dihydroxy-2-(7-hydroxy-2-nonyl-1-benzofuran-4-yl)-3-[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one Chemical compound C1=CC(O)=C2OC(CCCCCCCCC)=CC2=C1C=1OC2=CC(O)=CC(O)=C2C(=O)C=1O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O OXBQNNYXKZSXES-RDHYKQKTSA-N 0.000 title claims abstract description 44
- 208000031225 myocardial ischemia Diseases 0.000 title claims abstract description 23
- 239000003814 drug Substances 0.000 title claims abstract description 22
- 229940079593 drug Drugs 0.000 title claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 230000002265 prevention Effects 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 238000003304 gavage Methods 0.000 description 7
- 210000004165 myocardium Anatomy 0.000 description 7
- JLTCWSBVQSZVLT-CDIPANDDSA-N (2s)-n-[(2s)-6-amino-1-[(2-amino-2-oxoethyl)amino]-1-oxohexan-2-yl]-1-[(4r,7s,10s,13s,16s,19r)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-benzyl-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosan Chemical compound NCCCC[C@@H](C(=O)NCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](N)CSSC1.C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 JLTCWSBVQSZVLT-CDIPANDDSA-N 0.000 description 6
- 102000005320 Posterior Pituitary Hormones Human genes 0.000 description 6
- 108010070873 Posterior Pituitary Hormones Proteins 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 208000009889 Herpes Simplex Diseases 0.000 description 4
- 241000700584 Simplexvirus Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000003602 anti-herpes Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 240000000691 Houttuynia cordata Species 0.000 description 3
- 235000013719 Houttuynia cordata Nutrition 0.000 description 3
- 206010063837 Reperfusion injury Diseases 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 230000003203 everyday effect Effects 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
- 230000002496 gastric effect Effects 0.000 description 3
- 229930190556 houttuynoid Natural products 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 208000010125 myocardial infarction Diseases 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
- 239000002671 adjuvant Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000004 hemodynamic effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229960002275 pentobarbital sodium Drugs 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 230000002861 ventricular Effects 0.000 description 2
- 241000237970 Conus <genus> Species 0.000 description 1
- 206010011086 Coronary artery occlusion 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
- 208000007201 Myocardial reperfusion injury Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000003601 intercostal effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 229940079448 nitroglycerin 5 mg Drugs 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention provides application of Houttuynoid B in drugs treating or preventing myocardial ischemia. The application of the Houttuynoid B in preparation of anti-myocardial ischemia drugs involved in the invention is make known to the public for the first time. As the skeleton type belongs to a brand new skeleton type, and Houttuynoid B has unexpected strong inhibitory activity on myocardial ischemia, there exits no possibility that other compounds can give any enlightenment. The Houttuynoid B has prominent substantive features, and at the same time, application of it in resisting anti myocardial ischemia obviously has significant progress.
Description
Technical field
The present invention relates to the application of Houttuynoid B in preparation treatment or prevention myocardial ischemia drug.
Background technology
The inventor finds by a large amount of experiment, and Houttuynoid B has and resists myocardial ischemia/pharmacological action of reperfusion injury, the medical usage with prevention or treatment myocardial ischemia disease.
the compound H outtuynoid B 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 compound has brand-new framework types, present purposes only relates to the active Chen of anti-herpes simplex virus, 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.), for the purposes of Houttuynoid B in preparing medicaments for resisting myocardial ischemia that the present invention relates to, belong to open first, because framework types belongs to brand-new framework types, and its inhibition for myocardial ischemia is active unexpectedly strong, there do not is the possibility that is provided any enlightenment by other compounds, possesses outstanding substantive distinguishing features, be used to resisting myocardial ischemia, obviously has simultaneously significant progress.
Summary of the invention
The invention provides the application in the medicine of Houttuynoid B preparation treatment or prevention Ischemic/reperfusion.
The inventor has the effect for the treatment of or prevention myocardial ischemia drug disease by the Houttuynoid B that experimental results show that in the specific embodiment.
Described compound H outtuynoid B structure is as shown in formula I:
Formula I
It is open first that the purposes of Houttuynoid B in preparing medicaments for resisting myocardial ischemia that the present invention relates to belongs to, because framework types belongs to brand-new framework types, and its inhibition for myocardial ischemia is active unexpectedly strong, there do not is the possibility that is provided any enlightenment by other compounds, possess outstanding substantive distinguishing features, be used to resisting myocardial ischemia, obviously have simultaneously significant progress.
The specific embodiment
The preparation method of compound H outtuynoid B 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 be limited by claim.
Embodiment 1: the preparation of compound H outtuynoid B tablet involved in the present invention:
Get 20 and digest compound Houttuynoid B, add conventional adjuvant 180 grams that prepare tablet, mix, conventional tablet machine is made 1000.
Embodiment 2: the preparation of compound H outtuynoid B capsule involved in the present invention:
Get 20 and digest compound Houttuynoid B, add the conventional adjuvant such as starch 180 grams that prepare capsule, mix, encapsulatedly make 1000.
Below by pharmacodynamic experiment, further illustrate its pharmaceutically active.
Experimental example: the impact of Houttuynoid B on myocardial ischemia/reperfusion injury in rats
(1) experiment material: SD rat, male and female dual-purpose, body weight 190 ~ 210g.
(2) method and result
1) experimental technique
The acute myocardial ischemia experiment that pituitrin is induced: rat is divided into to 5 groups at random: positive drug matched group, model control group, 3 groups of administration groups, 8 every group.Administration group gastric infusion, positive drug matched group and model control group give the distilled water gavage of same volume every day, and each organizes continuous gavage 7d.All 1.5 ~ 2.0h lumbar injection pentobarbital sodium, 30 mg/kg anesthesia after the 7th day gavage, adopt MS2302 multimedia biological signal collecting analytical system to continue record standard II lead electrocardiogram.In positive drug matched group, model control group and administration group sublingual vein injection of pituitrin 5 IU/kg(5s, complete, the positive drug matched group is 10 min lumbar injection nitroglycerin 5 mg/kg before injection of pituitrin) the Electrocardiographic variation of continuous record 15 min after 10 min.If one of following variation in electrocardiogram, occurs: the T ripple is low flat, two-way, is inverted, and ST section level moves down >=0.05 mV, remembers 1 minute.Finally the total points of every rat is analyzed, as after the medication score, reduced, the prompting myocardial ischemia is improved.With changes in heart rate percentage rate before and after injection of pituitrin, represent the impact of medicine on heart rate.
Cardiac muscle ischemia resisting reperfusion injury experiment: rat is divided into to 5 groups at random: positive drug matched group, model control group, 3 groups of administration groups, 8 every group.Administration group gastric infusion, positive drug matched group and model control group give the distilled water gavage of same volume every day, and each organizes continuous gavage 7d.Record standard II lead electrocardiogram after the 30 mg/kg anesthesia of rats by intraperitoneal injection pentobarbital sodium.Tracheal intubation, meet artificial respirator (1.0 mlg
-1Min
-1), at 4th ~ 5 intercostals, open thoracic cavity, expose heart, at the pulmonary conus left border, left auricle lower edge 1mm place is with 320 silk thread ligation ramus descendens anterior arteriae coronariae sinistraes (positive drug matched group 3 min sublingual veines before following coronary artery occlusion are injected Propranolol 1.0 mg/kg).After ligation 30 min, cut off ligature, fill with again 30 min.Take out fast heart, with 0.9% sodium chloride, rinse well.Myocardium sheet is placed in 1% TTC solution, in 37 ℃ of hatching 5 min.After dyeing, dyestuff unnecessary on myocardium sheet is removed in water flushing immediately.Cut off the non-infarcted region cardiac muscle that each myocardium sheet is colored, undyed infarcted myocardium and ischemic myocardium are weighed.
Hemodynamics experiment: rat is divided into to 5 groups at random: positive drug matched group, model control group, 3 groups of administration groups, 8 every group.Administration group gastric infusion, positive drug matched group and model control group give the distilled water gavage of same volume every day, and each organizes continuous gavage 5d.Lumbar injection urethane 10 mg/kg anesthesia in the 6th day.Record standard II lead electrocardiogram.Vertically cut right skin of neck, separate right common carotid artery, insert the left ventricular catheter that has been full of heparin 0.9% sodium chloride, conduit is slowly inserted to left ventricular cavity.Cut the left lower extremity inside skin, separate femoral artery, insert ductus arteriosus.The cut-in pressure transducer, transport to multimedia bio signal monitor to signal and observe.After balance 30 min, record front each hemodynamic index of administration.
So data all represent with x ± s, experimental group and matched group data analysis are with the sided t check of two sample means.
2) result
The ischemia/reperfusion injury experimental result shows, under administration group, positive drug matched group, model control group myocardial infarction and ligature, myocardial Mass Measured percentage ratio is respectively in Table 1.
The impact of table 1 Houttuynoid B on scheming weight ratio under myocardial infarction and ligature
With model, compare * * p<0.01, * p<0.05
The impact of the acute myocardial ischemia that Houttuynoid B causes pituitrin is in Table 2.
The impact of the acute myocardial ischemia that table 2 Houttuynoid B causes pituitrin
With model, compare * * p<0.01, * p<0.05
Conclusion: Houttuynoid B can reduce the generation of myocardial infarction, and Houttuynoid B can obviously change the variation of electrocardio degree, does not change heart rate.Above experiment can illustrate, Houttuynoid B can prevent and treat myocardial ischemia.
Claims (1)
1.Houttuynoid B application in myocardial ischemia drug in treatment or prevention, described compound H outtuynoid B structure as
Formula IShown in:
Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310255883.6A CN103393703B (en) | 2013-06-24 | 2013-06-24 | The application of Houttuynoid B in preparation treatment myocardial ischemia drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310255883.6A CN103393703B (en) | 2013-06-24 | 2013-06-24 | The application of Houttuynoid B in preparation treatment myocardial ischemia drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103393703A true CN103393703A (en) | 2013-11-20 |
| CN103393703B CN103393703B (en) | 2016-02-24 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310255883.6A Active CN103393703B (en) | 2013-06-24 | 2013-06-24 | The application of Houttuynoid B in preparation treatment myocardial ischemia drug |
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| Country | Link |
|---|---|
| CN (1) | CN103393703B (en) |
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2013
- 2013-06-24 CN CN201310255883.6A patent/CN103393703B/en active Active
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 |
|---|---|
| CN103393703B (en) | 2016-02-24 |
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| Date | Code | Title | Description |
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| C41 | Transfer of patent application or patent right or utility model | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhu Ping Inventor after: Li Xue Inventor after: Ding Hao Inventor after: Tian Weimao Inventor after: Shu Gang Inventor after: Zhao Mingyi Inventor after: Li Jiaxin Inventor after: Zhu Shuoji Inventor after: Huang Chengfeng Inventor after: Li Jiani Inventor after: Zhu Xiaolan Inventor after: Mohammed Aszyford Inventor after: Li Xiaokang Inventor before: Ding Shengyu |
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| COR | Change of bibliographic data | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20151125 Address after: 510080, room 27, No. 103, compound 91, Dongchuan Road, Yuexiu District, Guangdong, Guangzhou Applicant after: Zhu Ping 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 | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20151201 Address after: 510080 No. 96, Dongchuan Road, Guangzhou, Guangdong, Yuexiu District Applicant after: Guangdong Prov. Cardiovascular disease Inst. Applicant after: Guangdong General Hospital Address before: 510080, room 27, No. 103, compound 91, Dongchuan Road, Yuexiu District, Guangdong, Guangzhou Applicant before: Zhu Ping |
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| C14 | Grant of patent or utility model | ||
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