CN101601678A - The application of icariine in the preparation medicament for expanding vascellum - Google Patents
The application of icariine in the preparation medicament for expanding vascellum Download PDFInfo
- Publication number
- CN101601678A CN101601678A CNA2008101115878A CN200810111587A CN101601678A CN 101601678 A CN101601678 A CN 101601678A CN A2008101115878 A CNA2008101115878 A CN A2008101115878A CN 200810111587 A CN200810111587 A CN 200810111587A CN 101601678 A CN101601678 A CN 101601678A
- Authority
- CN
- China
- Prior art keywords
- icariine
- endothelium
- preparation
- application
- effect
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention adopts blood vessel isolated perfusion technology by improved vascular resistance and antiotasis test determination method, has studied the influence of icariine to the blood vessel dilating effect.Found that icariine has concentration dependent diastole effect to the arterial ring that exsomatizes, this effect produces by the mode of endothelium-dependent relaxation and the non-dependence of endothelium, and has the pharmacological action characteristics of part calcium antagonist.Therefore, find that icariine has the new pharmacological action of direct expansion artery blood vessel, can be used for the preparation of cardiovascular and cerebrovascular diseases medicine.
Description
Technical field
The present invention relates to the application of icariine, more specifically relate to application and the application in preparation treatment cardiovascular and cerebrovascular diseases medicament thereof of icariine in the preparation medicament for expanding vascellum.
Background technology
Herba Epimedii is the Chinese medicine of using always, is Berberridaceae section Epimedium (Epimedium genus) plant.Pharmacopoeia of People's Republic of China (version in 2000) has recorded following five kinds of epimedium herbs, and medical material is exsiccant aerial parts.Be Herba Epimedii, arrow leaf Herba Epimedii, pubescence Herba Epimedii, Epimedium wushanense, Herba Epimedii etc.Herba Epimedii mainly contains the flavonoid glycoside (icariine) that isopentene group replaces.Its main pharmacodynamics is invigorating the kidney and strengthening the bones, strengthens endocrine, has hormonal action, can promote medullary cell DNA to contain to become, and promotes the growth of osteocyte.
In the Herba Epimedii application facet, be according to it basically: kidney invigorating and YANG supporting, functions such as timid wind dehumidifying cure mainly effect.As (function with cure mainly) in the Pharmacopoeia of the People's Republic of China (version in 2005, an one) the Herba Epimedii bar be: kidney-replenishing, bone and muscle strengthening, timid rheumatism.Be used for impotence and seminal emission, the muscles and bones flaccidity is soft, rheumatic arthralgia, numbness contracture; Climacteric hypertension.
Retrieval icariine Chinese patent, 19 of total publications, wherein relate to 3 of preparation method patents extracting the purification aspect, relate to and be used for 2 of slimming preparation patents, relate to and be used for 4 of sexual function adjusting preparation patents, relate to immunologic rejection, rheumatism, each 1 of resisting hyperosteogeny preparation patent, 7 of other patents.Do not find that icariine is used to prepare the patent of treatment cardiovascular and cerebrovascular diseases medicament aspect.
In recent years existing indivedual researcheres are noticed the effect of icariine to blood vessel, but are to be confined to icariine to suppressing the PDE5 enzyme mostly, promote NO to discharge and reach the vascular smooth muscle relaxation effect; Also have a small amount of research think icariine be by to the influence of vascular smooth muscle cell apoptosis to blood vessel generation effect; Do not see of the effect of direct research icariine, thereby limited the application of Herba Epimedii blood vessel.
Summary of the invention
The purpose of this invention is to provide the application of icariine in the preparation medicament for expanding vascellum, the application in the medicine of preparation treatment cardiovascular and cerebrovascular disease.
For observing icariine directly to the regulating action of tremulous pulse, improved vascular resistance and antiotasis test determination method that the present invention is reported with reference to Chinese patent 200510061549.2, adopt blood vessel isolated perfusion technology, to get rid of the influence of various nerves in the experiment made on the living, humoral factor to the effect of icariine expansion artery.
Found that, icariine has concentration dependent diastole effect to the arterial ring that exsomatizes, this effect produces by the mode of endothelium-dependent relaxation and the non-dependence of endothelium, the former may be by activating vascular endothelial cell nitric oxide-guanylate cyclase approach, antagonism alpha-2-adrenoceptor agonist, and the calcium channel of the InsP3 sensitivity on the blocking-up vascular smooth muscle cell endoplasmic reticulum is relevant, and have the pharmacological action characteristics of part calcium antagonist.Therefore, find that icariine has the new pharmacological action of direct expansion artery, can be used for the treatment of cardiovascular and cerebrovascular disease.
Icariine of the present invention can become preparation with the pharmaceutical excipient combined preparation that pharmacodynamics allows.
The dosage form of icariine of the present invention and pharmaceutical excipient preparation is mainly ejection preparation, comprises liquid drugs injection, transfusion and lyophilized injectable powder.
The form of medication of described preparation mainly selects intravenously administrable.
Discover that according to us icariine can be applied to prepare the medicine for the treatment of cardiovascular and cerebrovascular disease, its mechanism of action is that it is directly to the regulating action of blood vessel.
The present invention is further illustrated below in conjunction with embodiment.
The specific embodiment
The preparation of isolated rat aortic annulus
1. experiment medicine
The icariine of the purity that icariine is buied by market＞98%.Molecular formula: C
33H
40O
15, molecular weight 676.65, mp:231 ℃-232 ℃, faint yellow needle.Recrystallizing methanol, measuring purity through HPLC is that 99.1%. dissolves (comprising 5 μ l/ml acetic acid) with Krebs-Henseleit (K-H) liquid, is mixed with 10
-2Mol/L solution faces with before being made into 250mmol/L solution.
2. experimental procedure:
Cleaning level male Sprague-Dawley (SD) rat, body weight 240-260g.
Rapidly free SD rat chest aorta places 4 ℃ to contain 95%O
2And 5%CO
2In the pre-saturated K-H liquid of mist, connective tissue around rejecting is cut into the vascular ring of 3-4mm, during notice that protection vascular ring inner membrance is not damaged.Test needs factually, adopt the method for cotton swab friction vascular ring inner surface, the part vascular ring is prepared into the model of removing endothelium.Then vascular ring is hung in the bath that presets 10mL K-H liquid, an end is fixed, and an end connects Medlab bio signal acquisition system by tonotransducer.Continuing logical 95%O
2And 5%CO
2The state of mist under, regulate its basic tension force to 2.0g, and stablize 60min down at 37 ℃, during every 15min change liquid 1 time.With KCl (60mmolL
-1) repetitive stimulation 3 times, to bring out the maximum shrinkage amplitude of blood vessel.After treating that vascular ring is stable again, with benzene oxygen epinephrine (phenylephrine, PE) (1 μ molL
-1) vasoconstrictive ring peaking, add acetylcholine (acetylcholine, Ach) (10 μ molL
-1) check blood vessel endothelium integrity.If make the pre-shrunk vascular ring diastole of PE more than 80% after adding Ach, can think that endothelium is complete; Otherwise, think that then endothelium removes.With PE (1 μ molL
-1) or KCI (60mmolL
-1) to bring out maximum shrinkage amplitude be 100%, brings out the variation that ratio between the maximum shrinkage amplitude reflects antiotasis to add antiotasis amplitude and PE or KCI behind the medicine.
Embodiment 1 icariine is to the effect of isolated aortic ring systolic and diastolic function
(1) observes icariine to the tensile influence of base state vascular ring
Test method is identical with above-mentioned experimental procedure
The icariine source is the same.Adopt accumulation dosing method, every 10min adds icariine 1 time, observes accumulation and gives icariine 2 * 10
-5-6.4 * 10
-4Mol/L, the effect of endothelium complete sum endothelium being removed vascular ring; Matched group replaces appearance addings such as icariine with K-H liquid.The result shows: accumulation gives icariine 2 * 10
-5-6.4 * 10
-4Mol/L, basic tension force complete to endothelium or the vascular ring removed does not all make significant difference, and sees Table 1, table 2.
Table 1 icariine is to the complete tensile influence of the base state aortic annulus (unit: g) of endothelium
The tensile influence of the base state aortic annulus (unit: g) that table 1 icariine is removed endothelium
(2) icariine is to PE or the tensile influence of KCI preshrinking vascular ring
With 60mmolL
-1KCl or 0.3 μ molL
-1The vascular ring that PE preshrinking endothelium is complete, every 10min1 accumulation adds icariine 2 * 10
-5-6.4 * 10
-4Mol/L observes it preshrinking endothelium complete sum endothelium is removed the tensile effect of vascular ring; Matched group replaces appearance addings such as icariine with K-H liquid.The result shows: the vascular ring that Herba Epimedii is removed the pre-shrunk endothelium complete sum of PE shows as concentration dependent diastole effect, and the effect when complete than endothelium is more weak to the diastole effect of the vascular ring of removing endothelium, referring to table 3, table 4; Each concentration icariine all can not make KCl induce the remarkable diastole of vascular ring that the endothelium of contraction is complete or remove, and the effect when complete than endothelium is more weak to the diastole effect of the vascular ring of removing endothelium, sees Table 5, table 6.
Table 3 icariine is to the complete tensile influence of the base state aortic annulus (unit: %) of the pre-shrunk endothelium of benzene oxygen epinephrine
Annotate:
+P＜0.05,
++P＜0.01.
The tensile influence of the base state aortic annulus (unit: %) that table 4 icariine is removed the pre-shrunk endothelium of benzene oxygen epinephrine
Annotate:
+P＜0.05,
++P＜0.01.
Table 5 icariine is to the complete tensile influence of the base state aortic annulus (unit: %) of the pre-shrunk endothelium of KCl
Annotate:
+P＜0.05,
++P＜0.01.
The tensile influence of the base state aortic annulus (unit: %) that table 6 icariine is removed the pre-shrunk endothelium of KCl
Annotate:
+P＜0.05,
++P＜0.01.
Embodiment 2 icariines are to the effect of different pretreatment aortic annulus systolic and diastolic functions
(1) icariine is to the effect of the complete vascular ring of endothelium
With nitricoxide synthase (NOS) the left-handed nitro arginine methyl esters of inhibitor (L-NAME) (0.1mmolL
-1) or PGSI indometacin (10 μ molL
-1) vascular ring 15min that the pretreatment endothelium is complete, then use 80mmolL
-1KCI preshrinking blood vessel, method of cumulative scale adds icariine 2 * 10
-5-6.4 * 10
-4Mol/L observes the effect of vasoconstrictive ring strain; Matched group replaces appearance addings such as icariine with K-H liquid.
The vascular ring L-NAME 100 μ molL that endothelium is complete
-1Or indometacin 10 μ molL
-1After incubating in advance, can significantly suppress the vasorelaxation action of icariine 40-640 μ mol/L, the results are shown in Table 7.
Table 7 icariine is to the complete tensile influence of the base state aortic annulus (unit: %) of the pre-shrunk endothelium of KCl
Annotate:
+P＜0.05,
++P＜0.01.
Embodiment 3 icariines to endothelium remove the effect tremulous pulse of two kinds of contractile responses due to the vascular ring PE stable after, change no calcium K-H liquid flushing 4 times, immersion balance 20min in no calcium K-H liquid again, adding PE1.0 μ molL
-1Vasoconstrictive shrinks back 5min and adds CaCl
21.25mmolL
-1To recover the normal Ca of K-H liquid
2+Shrinking promptly appears in concentration, vascular ring once more; Wait to shrink stable back earlier with K-H liquid flushing 4 times, change no calcium K-H liquid flushing after the balance again, soak balance, question response is got back to baseline and is added icariine 4.0 * 10
-4Mol/L is hatched 20min, repeats above step.Relatively muscular tension changes before and after the administration.Icariine 4.0 * 10
-4Mol/L makes PE 1.0 μ molL
-1The contraction that calcium release causes in the inducing cell significantly descends; The contraction that icariine makes PE cause that miscarriage is given birth in the extracellular Ca2 also significantly descends, and the results are shown in Table 8.
Table 7 icariine is to the influence (unit: g) of the two kinds of contractile responses of rat chest aorta due to the PE
| Group | ??n | Interior calcium discharges | Stream in the outer calcium |
| Matched group | ??10 | ??0.3±0.1 | ??1.7±0.2 |
| Icariine | ??10 | ??0.1±0.1 ++ | ??1.2±0.2 + |
Annotate:
+P＜0.05,
++P＜0.01.
From above-mentioned test as can be seen, icariine has vasorelaxation action, different according to the vascular ring performance that icariine in the experiment is removed the pre-shrunk endothelium complete sum of PE, the prompting icariine is main to be that mode by blood vessel endothelium dependency and the non-dependence of endothelium produces effect; Simultaneously experimental result show also that icariine discharges the interior calcium of blood vessel endothelium smooth muscle cell and outer calcium in stream certain resistance inhibitor action is arranged.These results of study can enlarge the new application of Herba Epimedii, also further point out icariine can be applied to the cardiovascular and cerebrovascular diseases medicine.
Claims (5)
1. the application of icariine in the preparation medicament for expanding vascellum.
2. the application of icariine according to claim 1 in the preparation medicament for expanding vascellum is characterized in that: the application in preparation treatment cardiovascular and cerebrovascular diseases medicament.
3. the application of icariine according to claim 1 in the preparation medicament for expanding vascellum is characterized in that: described icariine can become preparation with the pharmaceutical excipient combined preparation that pharmacodynamics allows.
4. the application of icariine according to claim 3 in the preparation medicament for expanding vascellum, it is characterized in that: described dosage form is an injection.
5. the application of icariine according to claim 3 in the preparation medicament for expanding vascellum, it is characterized in that: the form of medication of described preparation is an intravenously administrable.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008101115878A CN101601678A (en) | 2008-06-10 | 2008-06-10 | The application of icariine in the preparation medicament for expanding vascellum |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008101115878A CN101601678A (en) | 2008-06-10 | 2008-06-10 | The application of icariine in the preparation medicament for expanding vascellum |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101601678A true CN101601678A (en) | 2009-12-16 |
Family
ID=41467671
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008101115878A Pending CN101601678A (en) | 2008-06-10 | 2008-06-10 | The application of icariine in the preparation medicament for expanding vascellum |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101601678A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102247398A (en) * | 2011-08-05 | 2011-11-23 | 遵义医学院 | Application of icariin to preparation of medicaments for preventing and treating pulmonary artery hypertension and complications thereof |
| CN110840906A (en) * | 2019-12-02 | 2020-02-28 | 遵义医科大学 | Application of icariin in preparation of medicine for treating hypoxic pulmonary hypertension |
-
2008
- 2008-06-10 CN CNA2008101115878A patent/CN101601678A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102247398A (en) * | 2011-08-05 | 2011-11-23 | 遵义医学院 | Application of icariin to preparation of medicaments for preventing and treating pulmonary artery hypertension and complications thereof |
| CN110840906A (en) * | 2019-12-02 | 2020-02-28 | 遵义医科大学 | Application of icariin in preparation of medicine for treating hypoxic pulmonary hypertension |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ang et al. | Sexual arousal in sexually sluggish old male rats after oral administration of Eurycoma longifolia Jack | |
| Campos et al. | Pro-erectile effects of an alkaloidal rich fraction from Aspidosperma ulei root bark in mice | |
| CN101601678A (en) | The application of icariine in the preparation medicament for expanding vascellum | |
| CN104490868A (en) | Application of atractylenolide-II derivative in preparation of platelet aggregation resisting drug and platelet aggregation resisting drug | |
| CN1813711B (en) | Use of isoflavone compound | |
| CN100356932C (en) | Use of astragalus root in preparing medicine for dilating blood vessel | |
| CN107744571B (en) | Pharmaceutical composition for improving vascular endothelial dysfunction and preparation method and application thereof | |
| CN101172124B (en) | Novel uses of pennycress, pharmaceutical composition containing the pennycress and preparation method thereof | |
| CN1846734A (en) | Prince's-feather prepn and its prepn process and application | |
| Verma et al. | Resurgence of herbal antihypertensives in management of hypertension | |
| CN101606944A (en) | The application of vitexin rhamnoside in the preparation medicament for expanding vascellum | |
| CN104490869A (en) | Application of atractylenolide-III derivative in preparation of platelet aggregation resisting drug and platelet aggregation resisting drug | |
| CN1785195A (en) | Application of buxenine for preparing medicine for dilation of blood-vessel | |
| CN101219129A (en) | Application of sodium ferulic acid in preparing medicament for expanding vascellum | |
| CN1778324A (en) | Effective part of nightshadeleaf ironweed for antiscolic medicines and its preparation and use | |
| CN101112417B (en) | Rheum defervescence liniment and method for preparing the same | |
| CN102429952A (en) | Application of humifuse euphorbia herb ethanol extract to preparation of vascular dilation medicament | |
| CN104042621A (en) | Use of andrographolide and its derivatives in preparation of drugs for preventing and treating hand-foot-and-mouth disease | |
| CN100525803C (en) | Medical use of iris | |
| CN105168201B (en) | Application of the Vitexin in pain medication after preparing iatrotechnics | |
| CN102119933A (en) | Application of taurochenodeoxycholic acid in prevention and treatment of liver injury | |
| CN113967220B (en) | Pharmaceutically active composition with acute myocardial infarction curative effect | |
| CN102872044B (en) | Application of Gypensapogenin A in medicaments for vasodilator | |
| CN106474171A (en) | Manyprickle acanthopanax general flavone composition and preparation method thereof | |
| CN103211864B (en) | Melastoma dodecandrum Lour extract product and application of Melastoma dodecandrum Lour in preparation of medicines for treating AIDS |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Zhang Zhengsheng Document name: Notification of Publication of the Application for Invention |
|
| DD01 | Delivery of document by public notice |
Addressee: Zhang Xiaofang Document name: Notification of before Expiration of Request of Examination as to Substance |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20091216 |