CN102429952A - Application of humifuse euphorbia herb ethanol extract to preparation of vascular dilation medicament - Google Patents
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Abstract
The invention discloses application of a Chinese medicinal humifuse euphorbia herb ethanol extract to the preparation of a vascular dilation medicament. Chinese medicinal humifuse euphorbia herb can be combined with a pharmacodynamically-allowed medicinal excipient to be prepared into preparations, mainly being solid preparations, mainly including tablets, capsules (including soft capsules) and dripping pills. As proved by researches, the humifuse euphorbia herb ethanol extract has a novel concentration-dependent artery dilation pharmacological action which is generated in an endodermis-dependent way, and the mechanism is relevant to Akt- and SOCE-eNOS-cGMP signaling pathways and is partially relevant to the opening of high-conductance calcium-activated potassium channels on the vascular smooth muscle. In the invention, humifuse euphorbia herb is applied to treatment of different vascular diseases under the vascular dilation action of the humifuse euphorbia herb ethanol extract, so that the medicinal range of the conventional Chinese medicinal humifuse euphorbia herb is expanded, and the Chinese medicinal humifuse euphorbia herb ethanol extract can be used for preparing a medicament for treating heart cerebrovascular diseases.
Description
Technical field
The present invention relates to a kind of application of Herba Euphorbiae Humifusae ethanol extraction, relate in particular to the application of Herba Euphorbiae Humifusae extract in the preparation medicament for expanding vascellum.
Background technology
Hypertension is global common cardiovascular disease, and prevalence is high, and mortality rate that related complication causes and disability rate are positioned at the prostatitis of human diseases again, and be very big to human health risk, brings great burden for society and family
[1]Show that according to national findings of the survey and China cardiovascular diseases investigation report the hypertensive sickness rate of China was 11.9% in 1991, then rose to 18.8% to 2004 annual morbidities; China hyperpietic surpasses 1.6 hundred million at present, but also in quick growth trend, has caused great burden to society.Hypertension, is developed as one pleases like unreasonable efficacious therapy as the important risk factor of cardiovascular and cerebrovascular vessel incident, will cause target organ damages such as the heart, brain, kidney, blood vessel, causes the cardiovascular and cerebrovascular vessel incident.The purpose of hypertension therapeutic is not only to bring high blood pressure down, and the more important thing is the protection target organ, reduces cardiovascular diseases's incidence rate, case fatality rate and disability rate, improves patient's quality of life, prolongs patient's life-span.Existing Altace Ramipril can only relief of symptoms, and drug dependence is stronger, and side effect is big.And herbal toxic effect is less, and aboundresources, and development prospect is wide.Over past ten years, from natural product, seek new composition that physiologically active is arranged or lead compound have become global concern and research with developing new drug or health food focus; Seek low toxicity of new generation, the natural Altace Ramipril resource of many target spots and its functional factor is analyzed, and then the Development and Production new drug that goes out to expand blood vessel is expected to become the new way of vascular conditions such as treatment hypertension, coronary heart disease.
Herba Euphorbiae Humifusae be Euphorbiaceae Euphorbia Radix seu Caulis Parthenocissi tricuspidatae (
Euporbia humifusaWilld) or Herba Euphorbiae supinae (
E. maculataL.) dry herb." Chinese pharmacopoeia and Compendium of Material Medica are all recorded Herba Euphorbiae Humifusae to go through version.Main chemical compositions is a flavonoid, like Quercetin and monoglycosides thereof, isoquercitrin, astragaloside etc.; Coumarins has scopoletin, umbelliferone, eupatolide; Organic acid has gallic acid and Palmic acid etc.Studied confirmation, that Herba Euphorbiae Humifusae has is antibiotic, hemostasis, antioxidation, protect the liver, suppress effects such as renal dysfunction, antitumor, blood pressure lowering
[1,2]Clinical practice and experimentation confirm that Herba Euphorbiae Humifusae has good curative effect to bacillary dysentery, chronic colitis, diarrhoea, metrorrhagia, bronchorrhagia, gastrorrhagia etc.But Herba Euphorbiae Humifusae it be unclear that as the treatment whether heat and toxic materials clearing away medicine can be used for vascular complications such as heart and brain kidney separately up to now.The preparation of Herba Euphorbiae Humifusae medicament for expanding vascellum and exploitation, the people's healthy living level is improved in the new drug market that can enrich China, also will produce good economic benefit.
Summary of the invention
For realizing above-mentioned purpose, the invention provides the application of Chinese medicine Herba Euphorbiae Humifusae ethanol extraction in the preparation medicament for expanding vascellum.
The application of said Herba Euphorbiae Humifusae ethanol extraction in preparation brings high blood pressure down medicine.
Said Herba Euphorbiae Humifusae ethanol extraction becomes preparation with the pharmaceutical excipient combined preparation.
The dosage form of said preparation is a solid preparation.
Said solid preparation is any in tablet, capsule, the drop pill.
Said capsule is a soft capsule.
The form of medication of said preparation is an oral administration.
Be to observe the direct regulating action of Herba Euphorbiae Humifusae ethanol extraction to tremulous pulse, the present invention adopts the myocardium vessel tension determining method, to get rid of the influence to the Herba Euphorbiae Humifusae vasodilative effect of various nerves in the experiment made on the living, humoral factor.The result finds; The Herba Euphorbiae Humifusae ethanol extraction has concentration dependent diastole effect to isolated aortic ring; This effect is by the mediation of endothelium-dependent relaxation NO-cGMP approach, and its mechanism possibly play a role through following 3 kinds of mechanism: (1) is activated the Akt-eNOS signal path and is promoted endotheliocyte to discharge the mechanism of nitric oxide (NO); (2) Ca that handles through the calcium pond
2+Interior stream (store-operated Ca
2+Entry SOCE) activates eNOS and promotes endotheliocyte to discharge the mechanism of NO; (3) large conductance calcium activated potassium channel is open relevant on part and the vascular smooth muscle.
Discover that according to above the Herba Euphorbiae Humifusae ethanol extraction has the new pharmacological action of endothelium-dependent relaxation expansion artery, but the vasodilator smooth muscle is applicable to vascular conditions such as treatment hypertension and coronary heart disease.
Potential effect of the present invention is: secondary development is carried out to the new pharmacological action of Chinese medicine Herba Euphorbiae Humifusae in (1), expands the medicinal scope of Herba Euphorbiae Humifusae; (2) utilize the vasodilative effect of Herba Euphorbiae Humifusae, the Herba Euphorbiae Humifusae ethanol extraction is applied to prepare the medicine of vascular conditions such as treatment hypertension.
Figure of description
Fig. 1 for illustrate Herba Euphorbiae Humifusae ethanol extraction (EEH) to the pre-shrunk endothelium of phyenlephrinium (PE) complete (+Endo) remove and (Endo) after influence of aortic annulus stretching reaction (A) and nitric oxide synthase inhibitor activity L-NAME and the guanylate cyclase inhibitor ODQ pretreatment EEH made the chart of influence (B) of the stretching reaction of the complete aortic annulus generation of PE preshrinking endothelium with endothelium;
Fig. 2 is for illustrating in the no calcium liquid chart that (B) EEH behind (A) and L type calcium channel blocker diltiazem pretreatment makes the influence of the complete aortic annulus generation of PE preshrinking endothelium diastole effect;
Fig. 3 illustrates the Ca that the calcium pond is handled
2+Interior stream (strore-operated Ca
2+Entry, SOCE) after the regulator pretreatment EEH to the chart of the complete aortic annulus effects on diastolic function of PE preshrinking endothelium;
Fig. 4 illustrates after the Akt signal blocker agent wortmannin pretreatment EEH to the chart of the complete aortic annulus effects on diastolic function of PE preshrinking endothelium;
Fig. 5 illustrates after the different potassium channel blocker pretreatment EEH to the chart of the complete aortic annulus effects on diastolic function of PE preshrinking endothelium;
Fig. 6 illustrates after the pretreatment of cyclooxygenase-2 inhibitors indomethacin EEH to the chart of the complete aortic annulus effects on diastolic function of PE preshrinking endothelium.
The specific embodiment
Below in conjunction with embodiment and accompanying drawing to the detailed description of the invention.
The preparation of embodiment 1 isolated rat aortic annulus
1. experiment medicine
Herba Euphorbiae Humifusae is purchased the Chinese crude drug company limited in Tai'an, Shandong, identifies through Chinese medicine teaching and research room of Taishan Hospital; Herba Euphorbiae Humifusae ethanol extraction (EEH) is prepared by Taishan Hospital's drug research.Medical material adds 8 times of amount ethanol, reflux, extract, 2 times, and each 50 min, merging filtrate filters, and concentrates, and lyophilization is to doing.
2. experimental procedure
Cleaning level male Sprague-Dawley (SD) rat, body weight 250 ~ 300 g, anti-company provides by Shandong, Jining, Shandong, animal quality certification SCXK Shandong 20080002.
Rapidly free SD rat chest aorta places 4 ℃ to contain 95%O
2And 5%CO
2, in the pre-saturated K-H liquid of mist, connective tissue around rejecting is cut into the long vascular ring of 2-3 mm.According to the experiment needs, adopt cotton swab friction vascular ring inner surface to remove endotheliocyte, the part vascular ring is prepared into the model of endothelium-denuded.Vascular ring is hung in 37 ℃ of preheating capacity are the bath of 5 mL K-H liquid, and an end is fixed, and an end connects Medlab bio signal acquisition system through tonotransducer.Continuing logical 95%O
2And 5%CO
2Under the state of mist, regulate its basic tension force to 1.0 g, and under 37 ℃, stablize 60 min, during per 15 min change liquid 1 time.Use 60 mmolL
-1KC1 stimulates peaking, with the flushing of K-H liquid, repeats 3 times, to bring out the maximum shrinkage amplitude of vascular ring then.After treating that vascular ring is stable again, with 1 μ molL
-1(phenylephrine, PE) vasoconstrictive ring peaking add 1 μ molL to phyenlephrinium
-1Acetylcholine (acetylcholine, ACh) check blood vessel endothelium integrity.Make the pre-shrunk vascular ring diastole of PE more than 80% after adding ACh, can think that endothelium is complete; If make PE not diastole of pre-shrunk vascular ring or diastole below 10% after adding ACh, think that then endothelium removes.With 1 μ molL
-1It is 100% that PE brings out maximum shrinkage amplitude, brings out the variation of the ratio reflection antiotasis between the maximum shrinkage amplitude with antiotasis amplitude behind the adding medicine and PE.
According to the method for instance 1, the stable back of vascular ring is observed:
(1) EEH to the tensile influence of PE preshrinking arterial ring (
n=6)
With PE (1 μ molL
-1) after the preshrinking blood vessel reaches stable state, adopting accumulation dosing method, per 3 min add the Herba Euphorbiae Humifusae ethanol extraction 1 time, observe accumulation and add EEH (0.1 ~ 100 μ gmL
-1) effect of endothelium complete sum endothelium being removed vascular ring.
(2) L-NAME to the influence of the inductive stretching reaction of EEH (
n=6)
The complete aortic annulus of endothelium is with nitric oxide synthase inhibitors L-NAME (10 μ molL
-1) behind pretreatment 20 min, reuse PE (1 μ molL
-1) after the preshrinking blood vessel reached stable state, accumulative total added EEH (0.1 ~ 100 μ gmL
-1) observe the variation of antiotasis.
(3) ODQ to the influence of the inductive stretching reaction of EEH (
n=6)
The complete aortic annulus of endothelium is with guanylate cyclase inhibitor ODQ (10 μ molL
-1) behind pretreatment 20 min, reuse PE (1 μ molL
-1) after the preshrinking blood vessel reached stable state, accumulative total added the variation that EEH observes antiotasis.
(4) result
The Herba Euphorbiae Humifusae ethanol extraction demonstrates endothelium-dependent relaxation vasorelaxation action (seeing Figure 1A), and this effect can be by 10 μ molL
-1L-NAME and 10 μ molL
-1ODQ blocks (*
P<0.01), explain that its endothelium-dependent relaxation vasodilator effect is by NO-cGMP approach mediation (seeing Figure 1B).
According to the method for instance 1, the stable back of vascular ring is observed:
(1) EEH to the tensile influence of PE preshrinking arterial ring in the no calcium liquid (
n=6)
In no calcium liquid, with 1 μ molL
-1PE preshrinking rat aorta ring adopts accumulation dosing method, and per 3 min add the Herba Euphorbiae Humifusae ethanol extraction 1 time, observe variable concentrations EEH (0.1 ~ 100 μ gmL
-1) to the influence of the complete vascular ring diastole of endothelium effect.
(2) L-type calcium channel blocker diltiazem to the influence of the inductive vasorelaxation action of EEH (
n=6)
The complete aortic annulus of endothelium is with L-type calcium channel blocker diltiazem (10 μ molL
-1) behind pretreatment 20 min, reuse PE (1 μ molL
-1) after the preshrinking blood vessel reached stable state, accumulative total added EEH (0.1 ~ 100 μ gmL
-1) observe the variation of antiotasis.
(3) Ca of cellular calcium pond manipulation
2+In stream (SOCE) regulator to the influence of the inductive vasorelaxation action of EEH (
n=6)
The aortic annulus that endothelium is complete is used SOCE activator thapsigargin (1 μ molL respectively
-1) and SOCE inhibitor Gd
3+(10 μ molL
-1) and 2-APB (75 μ molL
-1) behind pretreatment 20 min, reuse PE (1 μ molL
-1) after the preshrinking blood vessel reached stable state, accumulative total added EEH (0.1 ~ 100 μ gmL
-1) observe the variation of antiotasis.
(4) result
In no calcium liquid, the inductive concentration dependent vascular ring of EEH diastole effect is obviously weakened (*
P<0.01) (seeing Fig. 2 A).Yet, L-type calcium channel blocker diltiazem (10 μ molL
-1) pretreatment to EEH inductive vascular ring diastole do not have obvious influence (seeing Fig. 2 B).Explanation is Ca in the inductive vasodilation of EEH
2+Interior stream is not through L-type calcium channel but realizes through other approach.Recent research shows
[3], SOCE is playing a significant role aspect vasodilation and the activation eNOS.Yet, reports such as Dimmeler
[4], non-Ca-dependent Akt-eNOS signal can activate eNOS.For the vasorelaxation action of confirmation EEH and the relation between the Ca-dependent, observed its influence to vasorelaxation action with the SOCE regulator.Use SOCE activator thapsigargin (through suppressing sarcoplasmic reticulum/endoplasmic reticulum Ca
2+ATPase activates SOCE, an activator of SOCE via inhibition of sarcoplasmic/endoplasmic reticulum Ca
2+ATPase) behind complete vascular ring 20 min of pretreatment endothelium, find that the vasodilator effect of EEH is obviously blocked (*
P<0.01) (see figure 3).Equally, SOCE inhibitor Gd
3+Also obviously block the inductive vasorelaxation action (* of EEH with 2-APB
P<0.01) (see figure 3).Above result shows that the vasodilator effect of Herba Euphorbiae Humifusae ethanol extraction is realized through activating the SOCE-eNOS-cGMP signal pathway.
Embodiment 4 Akt/eNOS signal paths are to the inductive aortic annulus effects on diastolic function of EEH
According to above-mentioned experimental result, discovery Herba Euphorbiae Humifusae ethanol extraction is brought into play vasorelaxation action through mediation SOCE-eNOS-cGMP signal path.Yet whether non-Ca-dependent Akt/eNOS signal path is participated and it be not immediately clear.Therefore, we investigate the relation of inductive vasorelaxation action of Herba Euphorbiae Humifusae ethanol extraction and Akt signaling molecule.And according to the method for instance 1, the stable back of vascular ring is observed:
(1) wortmannin (wortmannin) to the influence of the inductive vasorelaxation action of EEH (
n=6)
The complete aortic annulus of endothelium is with Akt signal blocker agent wortmannin (100 nmolL
-1) behind pretreatment 20 min, reuse PE (1 μ molL
-1) after the preshrinking blood vessel reached stable state, accumulative total added EEH (0.1 ~ 100 μ gmL
-1) observe the variation of antiotasis.
(2) result
Research shows that the phosphorylation of Akt phosphorylation and downstream eNOS thereof is the important channel of the synthetic NO of endotheliocyte under the physiological status
[3]Reports such as Dimmeler
[4], non-Ca-dependent Akt-eNOS signal can activate eNOS.From protein level, eNOS has the general features of Akt effect substrate, and receives the regulation and control of Akt.Whether relevant for the vasorelaxation action of verifying the Herba Euphorbiae Humifusae ethanol extraction with non-Ca-dependent Akt signal pathway, observed its influence with the Akt inhibitor to vasorelaxation action.With the complete vascular ring of Akt inhibitor wortmannin pretreatment endothelium, find that wortmannin obviously blocks the inductive vasorelaxation action (* of EEH
P<0.01) (see figure 4).Above result shows that the inductive vasorelaxation action of Herba Euphorbiae Humifusae ethanol extraction is realized through mediation Akt-eNOS-cGMP signal pathway.
According to the method for instance 1, the stable back of vascular ring is observed:
(1) EEH is to the influence of potassium-channel
The complete vascular ring of endothelium is through potassium channel blocker TEA 100 μ molL
-1, glibenclamide (glibenclamide) 10 μ molL
-1Behind pretreatment 20 min, reuse PE (1 μ molL
-1) after the preshrinking blood vessel reached stable state, accumulative total added EEH (0.1 ~ 100 μ gmL
-1) observe the variation of antiotasis.
(2) result
Mainly contain 4 kinds of potassium channels on the vascular smooth muscle: large conductance calcium activated potassium channel (BK
Ca); Voltage-dependent potassium channel (Kv); Inward rectifyimg potassium channel (Kir); ATP sensitive potassium channel (K
ATP).BK
CaBe the advantage passage of delivery outward current on the vascular smooth muscle, regulate vascular smooth muscle relax contract with small artery muscle-derived anxiety aspect important function is arranged, the BK of vascular smooth muscle during hypertension
CaSensitivity increases, but does not cause stretching reaction, but weakens the contraction enhancing trend of resistance vessel; K
ATPExtremely important in the formation of basic potassium ion electric current under some VSMC physiological statuss, possibly relate to the adjusting of antiotasis, K when cardiovascular disease
ATPExpression can change
[6-8], research in recent years shows that potassium channel has been the novel targets of essential hypertension gene therapy.This experimental result finds that TEA and glibenclamide handle the vasodilator effect of back EEH all by part blocking-up (*
P<0.01) (see figure 5).Explain that large conductance calcium activated potassium channel is relevant on Herba Euphorbiae Humifusae ethanol extraction vasodilator mechanism part and the vascular smooth muscle, and irrelevant with the ATP sensitive potassium channel.
According to the method for instance 1, the stable back of vascular ring is observed:
(1) indomethacin (indomethacin) to the influence of the inductive vasorelaxation action of Herba Euphorbiae Humifusae ethanol extraction (
n=6)
The complete vascular ring of endothelium is through cyclooxygenase-2 inhibitors indomethacin 10 μ molL
-1Behind pretreatment 20 min, reuse PE (1 μ molL
-1) after the preshrinking blood vessel reached stable state, accumulative total added EEH (0.1 ~ 100 μ gmL
-1) observe the variation of antiotasis.
(2) result
Inquire into cyclooxygenase and whether participate in the vasorelaxation action of Herba Euphorbiae Humifusae ethanol extraction; The complete vascular ring of endothelium with the indomethacin pretreatment after, find that the effect that the Herba Euphorbiae Humifusae ethanol extraction makes the pre-shrunk blood vessel of PE produce diastole do not have the obvious variation (see figure 6).Vasodilator effect and cyclooxygenase approach that the Herba Euphorbiae Humifusae ethanol extraction is described are irrelevant.
The partial reference document that the present invention relates to:
[1] Chu Xiaolan, model Cui Sheng. the chemical constituent of Radix seu Caulis Parthenocissi tricuspidatae class Chinese herbal medicine and pharmacological research overview [J]. Chinese wild plant resource, 1998,17 (2): 18;
[2] Zhang Renxia, Zhang Ping Sheng, Sun Yongqing, etc. the preliminary study of Herba Euphorbiae supinae hypotensive effect [J]. Chinese Medicine Leader, 2009,6 (34): 114-115;
[3]?Parekh?AB,?Putney?JW,?Jr.?Store-operated?calcium?channels.?Physiological?Reviews，2005,?85,?757-810；
[4]?Dimmeler?S,?Fleming?I,?Fisslthaler?B,?et?al.?Activation?of?nitric?oxide?synthase?in?endothelial?cells?by?Akt-dependent?phosphorylation.?Nature,?1999,?399,?601-605.
[5]?Fulton?D,?Gratton?JP,?McCabe?TJ,?et?al.?Regulation?of?endothelium-derived?nitric?oxide?production?by?the?protein?kinase?Akt.?Nature,?1999,?399(?10)?:?597-?601.
[6]?RenY,?Xu?X,?Wang?X.?Altered?mRNA?expression?of?ATP-sensitive?and?inward?rectifier?potassium?channel?subunits?in?streptozotocin-induced?diabetic?rat?heart?and?aorta.?J?Pharmacol?Sci,?2003,?93?(4)?:?4782483；
[7]?Chatterjee?S,?Al-Mehdi?AB,?Levitan?I,?et?al.?Shear?stress?increases?expression?of?a?K
ATP?channel?in?rat?and?bovine?puirnonary?vascular?endothelial?cells.?Am?J?Physiol?Cell?Physiol,?2003,?285?(4):?C959-C967；
[8]?RenYJ,?Xu?XH,?Zhong?CB,?et?al.?Hypercholesterolemia?alters?vascular?functions?and?gene?expression?of?potassium?channels?in?rat?aortic?smooth?muscle?cells.?Acta?Pharmacol?Sin,?2001,?22?(3):?274-278。
Claims (7)
1. the application of Herba Euphorbiae Humifusae ethanol extraction in the preparation medicament for expanding vascellum.
2. the application of Herba Euphorbiae Humifusae ethanol extraction according to claim 1 in the preparation medicament for expanding vascellum is characterized in that: the application of Herba Euphorbiae Humifusae ethanol extraction in preparation brings high blood pressure down medicine.
3. the application of Herba Euphorbiae Humifusae ethanol extraction according to claim 1 and 2 in the preparation medicament for expanding vascellum, it is characterized in that: the Herba Euphorbiae Humifusae ethanol extraction becomes preparation with the pharmaceutical excipient combined preparation.
4. the application of Herba Euphorbiae Humifusae ethanol extraction according to claim 3 in the preparation medicament for expanding vascellum, it is characterized in that: the dosage form of said preparation is a solid preparation.
5. the application of Herba Euphorbiae Humifusae ethanol extraction according to claim 4 in the preparation medicament for expanding vascellum, it is characterized in that: said solid preparation is any in tablet, capsule, the drop pill.
6. the application of Herba Euphorbiae Humifusae ethanol extraction according to claim 5 in the preparation medicament for expanding vascellum, it is characterized in that: said capsule is a soft capsule.
7. the application of Herba Euphorbiae Humifusae ethanol extraction according to claim 3 in the preparation medicament for expanding vascellum, it is characterized in that: the form of medication of said preparation is an oral administration.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103830448A (en) * | 2014-02-28 | 2014-06-04 | 重庆希尔安药业有限公司 | Medicament composition for treating coronary heart disease stenocardia and preparation method thereof |
| CN104825683A (en) * | 2015-04-28 | 2015-08-12 | 淄博齐鼎立专利信息咨询有限公司 | Application method of traditional Chinese medicine composition in preparation of drugs for vascular dilation |
| CN115778930A (en) * | 2022-12-08 | 2023-03-14 | 陕西中医药大学 | Application of dithioacetal compound with vasodilation activity in preparing medicine with vasodilation activity |
-
2011
- 2011-12-08 CN CN201110403743XA patent/CN102429952A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 唐万菊: "《用乙醇泡地锦草治疗输液渗漏致硬结的临床观察》", 《中国实用医药》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103830448A (en) * | 2014-02-28 | 2014-06-04 | 重庆希尔安药业有限公司 | Medicament composition for treating coronary heart disease stenocardia and preparation method thereof |
| CN104825683A (en) * | 2015-04-28 | 2015-08-12 | 淄博齐鼎立专利信息咨询有限公司 | Application method of traditional Chinese medicine composition in preparation of drugs for vascular dilation |
| CN115778930A (en) * | 2022-12-08 | 2023-03-14 | 陕西中医药大学 | Application of dithioacetal compound with vasodilation activity in preparing medicine with vasodilation activity |
| CN115778930B (en) * | 2022-12-08 | 2024-02-27 | 陕西中医药大学 | Application of dithioacetal compound with vasodilation activity in preparation of medicament with vasodilation activity |
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Application publication date: 20120502 |