CN1861112B - Application of Qishen Yiqi dripping pills for preparing medicine to inhibit leakage of albumin - Google Patents
Application of Qishen Yiqi dripping pills for preparing medicine to inhibit leakage of albumin Download PDFInfo
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- CN1861112B CN1861112B CN2005100135048A CN200510013504A CN1861112B CN 1861112 B CN1861112 B CN 1861112B CN 2005100135048 A CN2005100135048 A CN 2005100135048A CN 200510013504 A CN200510013504 A CN 200510013504A CN 1861112 B CN1861112 B CN 1861112B
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Abstract
An application of the 'Qi-replenishing' Qishen dripping pill in preparing the medicines for preventing and treating the microcirculatory disturbance diseases caused by albumin leakage is disclosed.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to QISHEN YIQI DIWAN application in the albumin outside leakage medicine in preparation suppresses thin vein.
Background technology
The microcirculation disturbance that Radix Salviae Miltiorrhizae causes ischemia-reperfusion has prevention and therapeutical effect.Its mechanism of action comprises the protection vascular endothelial cell, remove peroxide, suppress leukocyte adheres to, suppresses mast cell degranulation, suppresses that the interior albumin of thin vein spills etc. with blood vessel endothelium.Radix Salviae Miltiorrhizae has been brought into play the microcirculation disturbance effect that its prevention and treatment ischemia-reperfusion cause by to microcirculatory too many levels, the comprehensive function of many target spots.Yet in the prevention of cardiovascular and cerebrovascular disease with when needing long-term treatment, Radix Salviae Miltiorrhizae needs intravenously administrable to be subjected to the restriction of each side factor.If oral red sage formulation also can be obtained and the intravenously administrable propinquity effect, will be very significant for prevention and treatment cardiovascular and cerebrovascular disease or other diseases with microcirculatory disturbances.
QISHEN YIQI DIWAN is made up of the Radix Astragali, Radix Salviae Miltiorrhizae, Radix Notoginseng and Lignum Dalbergiae Odoriferae, in order to the angina pectoris of treatment coronary heart disease with qi deficiency and blood stasis.Chinese patent CN1375316A discloses composition, method for making and the purposes aspect angina pectoris of said preparation, but this medicine albumin outside leakage and effect aspect the microcirculation improvement in anti-thin vein do not appear in the newspapers as yet.
Summary of the invention
The purpose of this invention is to provide QISHEN YIQI DIWAN application in the albumin outside leakage medicine in preparation suppresses thin vein.
The present invention by FITC (fluorescein) sign albumin outside leakage in the rat mesentery thin vein that ischemia-reperfusion is caused dynamically, seriality, visual observation, albuminous leaking outside all has inhibitory action significantly to visible QISHEN YIQI DIWAN oral administration early stage and late period to rat mesentery thin vein ischemia-reperfusion.
QISHEN YIQI DIWAN is to be prepared from by following component by weight percentage: the Radix Astragali 22.2%～66.8%, Radix Salviae Miltiorrhizae 11.6%～33.4%, Radix Notoginseng 2.5%～13.5%, Lignum Dalbergiae Odoriferae 14.5%～44.3%.Its best proportioning is the Radix Astragali 44.7%, Radix Salviae Miltiorrhizae 26.7%, Radix Notoginseng 6.3%, Lignum Dalbergiae Odoriferae 22.3%; Perhaps with the Radix Astragali 41.2%, Radix Salviae Miltiorrhizae 23.8%, Radix Notoginseng 4.5%, Lignum Dalbergiae Odoriferae 30.5%.
For a better understanding of the present invention, below by experiment its new purposes in pharmaceutical field is described.
One, QISHEN YIQI DIWAN before ischemia-reperfusion administration to the inhibitory action of albumin outside leakage in the rat mesentery thin vein
(1) experimental technique
1. test group and matched group
(1) normal control group: do not carry out ischemia-reperfusion and handle.
(2) ischemia-reperfusion group: after 10 minutes bases are observed, will also flow mesentery artery and vein vascular ligation 10 minutes (ischemia) simultaneously, and remove ligation (pouring into again) in observation portion with 4G polyethylene pipe.Time recorder is transferred to 0 place.Observed 30 minutes continuously at the same visual field.
(3) QISHEN YIQI DIWAN administration group: before 60 minutes, press the dosage of 0.4g/kg at ischemia-reperfusion, with the QISHEN YIQI DIWAN physiological saline solution, disposable filling stomach.
(4) Radix Salviae Miltiorrhizae intravenously administrable group: at ischemia-reperfusion before 10 minutes, slowly inject Radix Salviae Miltiorrhizae Injection 1ml (1g Radix Salviae Miltiorrhizae extract/ml) through jugular vein, the continuous injector of reuse is pressed the per hour dosage of 1.2g/kg, injects Danshen root injection continuously through jugular vein and finishes to observing.
2. experimental technique
Get the Wistar male rat (body weight 200～250g, Charles River laboratory animal, Tokyo) that Japan's celebrating answers university of private school charging no tuition medical board Experimental Animal Center to raise, anaesthetize by the dosage lumbar injection pentobarbital sodium of 30mg/kg.Insert and put the 3G polyethylene tube from right external jugular vein.Make 2～3cm otch along the abdomen median line, gently the ileum of nearly ileocecus is moved to outside the abdominal cavity, mesentery is launched on the platen with thin slide.Be holding temperature and humidity, continue the Krebs-Ringer buffer of 37 ℃ of droppings on unfolded mesenteric mesaraic surface.Mesentery is microcirculatory dynamically, with inverted biological microscope (Diaphot TMD-2S, Nikon, the Tokyo) observation that places in 37 ℃ of temperature chambers, and uses the high sensitivity camera photography, the S-VHS video-recorder recording.
Select diameter to be look-out station at the non-branching portion of thin vein between 25～40 μ m (more than the long 200 μ m).After 10 minutes bases are observed, with of the mesentery artery and vein vascular simultaneously ligation 10 minute (ischemia) of 4G polyethylene tube, remove ligation (perfusion again) with observation portion, time recorder is transferred to 0 place.Observed 30 minutes continuously at the same visual field.
3. assay method
Thin vein vascular permeability assay: the fluorescein-labeled albumin of FITC is pressed the dosage of 50mg, slowly inject through jugular vein.With fluorescence microscopy camera chain (C-2400-08, creek pine), be 420～490nm at wavelength, emission wavelength is that the fluorescence excitation element is luminous under the condition of 520nm, observes and write down the variation of the inside and outside FITC fluorescein of same thin vein.Change according to the FITC fluorescein that in the thin vein pipe, outside the thin vein pipe, spills, through the time calculate the albuminous situation that spills, with the variation of expression thin vein vascular permeability.
Each measured value of every group of 6 rats is handled with one-way analysis of variance (ANOVA), Fisher ' s posthoc test check.Each is organized numerical value and represents that with average ± standard error establishing P＜0.05 is significance.
(2) result
Fig. 1 shows the influence that rat mesentery thin vein FITC tagged albumin leaks outside after QISHEN YIQI DIWAN and Radix Salviae Miltiorrhizae intravenously administrable are to ischemia-reperfusion.When perfusion began again, leaking outside of the thin vein FITC tagged albumin of ischemia-reperfusion group compared remarkable increase with the normal control group.Along with dabbling carrying out again, the leaking outside of FITC tagged albumin of ischemia-reperfusion group continues to increase.The albumin outside leakage of perfusion early stage (pouring into again within 10 minutes) when the Radix Salviae Miltiorrhizae intravenously administrable fails to suppress perfusion beginning again and again, but compare significantly with ischemia-reperfusion group and to reduce pouring into late period leaking outside of (pouring into again 20 minutes and 30 minutes) Radix Salviae Miltiorrhizae intravenously administrable group FITC tagged albumin again.The QISHEN YIQI DIWAN group early stage just suppressed the FITC tagged albumin significantly and has leaked outside dabbling again, and in dabbling late period again, its effect that suppresses albumin outside leakage is identical with the Radix Salviae Miltiorrhizae intravenously administrable.
Two, QISHEN YIQI DIWAN behind ischemia-reperfusion administration to the inhibitory action of albumin outside leakage in the rat mesentery thin vein
(1) experimental technique
1. test group and matched group
(1) normal control group: do not carry out ischemia-reperfusion and handle.
(2) QISHEN YIQI DIWAN administration group: behind ischemia-reperfusion, QISHEN YIQI DIWAN is made into the solution of 50mg/ml with normal saline, drips (2.6ml/min) continuously on the mesentery surface of observing.
(3) SOD (superoxide dismutase) administration group: in the time of 10 minutes,, inject SOD continuously through jugular vein and finish to observing with the dosage that continuous injector is pressed 12000u/kg/hr at ischemia-reperfusion.
2. experimental technique: with embodiment one.
3. assay method: with embodiment one.
(2) result
Fig. 2 shows that ischemia-reperfusion adds the influence that QISHEN YIQI DIWAN and SOD leak outside to rat mesentery thin vein FITC tagged albumin after 10 minutes.When pouring into 10 minutes again (QISHEN YIQI DIWAN drop into SOD before), the spilling of the FITC tagged albumin of administration group behind administration group, the SOD after ischemia-reperfusion group, the QISHEN YIQI DIWAN all significantly more than the normal control group.The medicine group is when dropping into continuously SOD 20 minutes (pouring into again 30 minutes) behind the SOD, and leaking outside of FITC tagged albumin do not improved in the thin vein.Administration group after the QISHEN YIQI DIWAN when dropping into 20 minutes (pouring into 30 minutes) continuously, has been improved leaking outside of thin vein FITC tagged albumin significantly again.The outer leak rate of the FITC tagged albumin of administration group not only is markedly inferior to ischemia-reperfusion group after the QISHEN YIQI DIWAN, also is markedly inferior to administration group behind the SOD.Leaking outside of the rat mesentery thin vein FITC tagged albumin that administration causes ischemia-reperfusion behind the SOD do not have therapeutical effect in during this observation, and administration has therapeutical effect after the QISHEN YIQI DIWAN.
Peroxide injured blood vessel endothelium and blood vessel basement membrane that ischemia-reperfusion produces impel albumin outside leakage.The vaso-active substance that mast cell degranulation discharges has more aggravated albumin outside leakage.Albumin outside leakage and mast cell degranulation are one of important symbols of microcirculation disturbance.The present invention proves that QISHEN YIQI DIWAN not only has the effect that suppresses albumin outside leakage, and its inhibition albumin outside leakage acts on again, and perfusion is better than the Radix Salviae Miltiorrhizae intravenously administrable in early days.QISHEN YIQI DIWAN is with Radix Salviae Miltiorrhizae and Radix Notoginseng and the Radix Astragali, Lignum Dalbergiae Odoriferae compatibility, and its effect of safeguarding vascular permeability has obtained reinforcement, and the early stage albumin outside leakage of ischemia that independent use can not play a role to Radix Salviae Miltiorrhizae also has inhibitory action.
Description of drawings
Fig. 1: the pre-administration of QISHEN YIQI DIWAN to ischemia-reperfusion after the influence that leaks outside of rat mesentery thin vein FITC tagged albumin.
Fig. 2: after the QISHEN YIQI DIWAN administration to ischemia-reperfusion after the influence that leaks outside of rat mesentery thin vein FITC tagged albumin.
The specific embodiment
Below in conjunction with embodiment medicine of the present invention is described further, following each embodiment only is used to the present invention is described and is not limitation of the present invention.
Embodiment one
Get Radix Astragali 86.5g, Radix Salviae Miltiorrhizae 21.3g, Radix Notoginseng 3.5g, Lignum Dalbergiae Odoriferae 20.6g, adjuvant Polyethylene Glycol-6000 30g.Will be through Radix Salviae Miltiorrhizae, the Radix Notoginseng of pulverizing, decocting boils 2 times, adds 7 times of water gagings at every turn, each 2 hours, merge decoction liquor, filter, filtrate is concentrated into 900ml, add 95% ethanol, make determining alcohol reach 70%, left standstill 12～24 hours, filter, reclaim ethanol, being condensed into relative density is the extractum of 1.32～1.38 (50～60 ℃); To decoct with water 2 times through the Radix Astragali of pulverizing, add 6 times of water gagings at every turn, extracted successively 2 hours, 1 hour, merging filtrate is when being concentrated into the 1500ml left and right sides, adding 95% ethanol, to make determining alcohol be 60%, left standstill 12～24 hours, filters, filtrate recycling ethanol, when being concentrated into the 400ml left and right sides, adding 95% ethanol, to make determining alcohol be 80%, left standstill 12～24 hours, filter, filtrate recycling ethanol, being condensed into relative density is the extractum of 1.32～1.38 (50～60 ℃); Get Lignum Dalbergiae Odoriferae, add 5 times of water gagings, reflux, extract, 5 hours is collected volatile oil; Get above-mentioned Salvia miltiorrhiza and Panax notoginseng extractum, Radix Astragali extractum and Polyethylene Glycol-6000, water-bath is dissolved, and after change is even, adds volatile oil of Lignum Dalbergiae Odoriferae, and mixing moves in the drop pill machine, makes 1000 drop pill.
Embodiment two
Get Radix Astragali 40.6g, Radix Salviae Miltiorrhizae 44.8g, Radix Notoginseng 11.2g, Lignum Dalbergiae Odoriferae 38.6g, adjuvant Polyethylene Glycol-6000 30g makes Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
Embodiment three
Get Radix Astragali 77.3g, Radix Salviae Miltiorrhizae 22.8g, Radix Notoginseng 4.8g, Lignum Dalbergiae Odoriferae 30.5g, adjuvant Polyethylene Glycol-6000 28g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
Embodiment four
Get Radix Astragali 42.3g, Radix Salviae Miltiorrhizae 39.2g, Radix Notoginseng 8.2g, Lignum Dalbergiae Odoriferae 46.8g, adjuvant Polyethylene Glycol-6000 25g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
Embodiment five
Get Radix Astragali 65.2g, Radix Salviae Miltiorrhizae 38.9g, Radix Notoginseng 9.3g, Lignum Dalbergiae Odoriferae 32.5g, adjuvant Polyethylene Glycol-6000 40g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
Embodiment six
Get Radix Astragali 56.2g, Radix Salviae Miltiorrhizae 32.5g, Radix Notoginseng 6.2g, Lignum Dalbergiae Odoriferae 41.6g, adjuvant Polyethylene Glycol-6000 22g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
Embodiment seven
Get Radix Astragali 36.5g, Radix Salviae Miltiorrhizae 32.4g, Radix Notoginseng 6.2g, Lignum Dalbergiae Odoriferae 41.7g, adjuvant Polyethylene Glycol-6000 22g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
Embodiment eight
Get Radix Astragali 65.6g, Radix Salviae Miltiorrhizae 25.8g, Radix Notoginseng 9.5g, Lignum Dalbergiae Odoriferae 46.4g, adjuvant Polyethylene Glycol-6000 35g makes Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
Embodiment nine
Get Radix Astragali 35.5g, Radix Salviae Miltiorrhizae 50.8g, Radix Notoginseng 16.3g, Lignum Dalbergiae Odoriferae 52.3g, adjuvant Polyethylene Glycol-6000 35g, make Chinese medicine preparation of the present invention by the preparation technology of embodiment 1.
Claims (3)
1. QISHEN YIQI DIWAN application in the albumin outside leakage medicine in preparation suppresses thin vein, described QISHEN YIQI DIWAN is to be prepared from by following component by weight percentage: the Radix Astragali 22.2%～66.8%, Radix Salviae Miltiorrhizae 11.6%～33.4%, Radix Notoginseng 2.5%～13.5%, Lignum Dalbergiae Odoriferae 14.5%～44.3%.
2. QISHEN YIQI DIWAN according to claim 1 is the application in the albumin outside leakage medicine in preparation suppresses thin vein, described QISHEN YIQI DIWAN is to be prepared from by following component by weight percentage: the Radix Astragali 44.7%, Radix Salviae Miltiorrhizae 26.7%, Radix Notoginseng 6.3%, Lignum Dalbergiae Odoriferae 22.3%.
3. QISHEN YIQI DIWAN according to claim 1 is the application in the albumin outside leakage medicine in preparation suppresses thin vein, described QISHEN YIQI DIWAN is to be prepared from by following component by weight percentage: the Radix Astragali 41.2%, Radix Salviae Miltiorrhizae 23.8%, Radix Notoginseng 4.5%, Lignum Dalbergiae Odoriferae 30.5%.
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| CN2005100135048A CN1861112B (en) | 2005-05-13 | 2005-05-13 | Application of Qishen Yiqi dripping pills for preparing medicine to inhibit leakage of albumin |
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| CN2005100135048A CN1861112B (en) | 2005-05-13 | 2005-05-13 | Application of Qishen Yiqi dripping pills for preparing medicine to inhibit leakage of albumin |
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| CN1861112B true CN1861112B (en) | 2011-11-30 |
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| CN103385920A (en) * | 2012-05-07 | 2013-11-13 | 天士力制药集团股份有限公司 | Novel application of qi-tonifying dropping pill containing Radix astragali and root of red-rooted salvia |
| CN103520270A (en) * | 2012-07-02 | 2014-01-22 | 天士力制药集团股份有限公司 | Application of astragalus-salviae miltiorrhizae qi-benefiting dropping pills in resistance to anti-cancer medicine cardiotoxicity |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1375316A (en) * | 2002-02-07 | 2002-10-23 | 天津天士力制药股份有限公司 | Chinese medicine prepn. for treating coronary heart disease and angina pactoris and its prepn. process |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1375316A (en) * | 2002-02-07 | 2002-10-23 | 天津天士力制药股份有限公司 | Chinese medicine prepn. for treating coronary heart disease and angina pactoris and its prepn. process |
Non-Patent Citations (2)
| Title |
|---|
| 刘亚东等.自拟扩冠养心II、II号治疗冠心病的体会.内蒙古中医药 6.2004,(6),9，10. |
| 刘亚东等.自拟扩冠养心II、II号治疗冠心病的体会.内蒙古中医药 6.2004,(6),9,10. * |
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