CN101007046A - A plasma substitute and its application for treating hemorrhagic shock - Google Patents
A plasma substitute and its application for treating hemorrhagic shock Download PDFInfo
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- CN101007046A CN101007046A CN 200610001867 CN200610001867A CN101007046A CN 101007046 A CN101007046 A CN 101007046A CN 200610001867 CN200610001867 CN 200610001867 CN 200610001867 A CN200610001867 A CN 200610001867A CN 101007046 A CN101007046 A CN 101007046A
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Abstract
The invention disclosed a kind of medicine that can treat hemorrhagic shock, especially a kind of blood plasma substitute which contains one active ingredient. The ingredient can not only expand the blood volume, it can also improve the blood rheology and relieve inflamed damage. The blood plasma substitute which has the two functions is provided in the invention. There's also provided a active ingredient which is a physically acceptable polyose high molecular compound. The active ingredient is prepared by raw plant such as astragali radix. The blood plasma substitute in the invention can be used as medicine to treat hemorrhagic shock.
Description
Technical field
The present invention relates to a kind of medicine that in the treatment hemorrhagic shock, uses, particularly a kind of blood plasma substitute.
Background technology
Hemorrhagic shock (hemorrhagic shock, be called for short HS) be a kind of common shock, cause that because of losing blood circulation volume die-offs, often occur in hemorrhage after the wound, digestive tract hemorrhage, postoperative hemorrhage or dysfunction of blood coagulation, a kind of for hypovolemic shock (hypovolemic shock).Large quantity of moisture, salt, plasma protein and blood formed element are seriously lost in the hemorrhagic shock, replenish as untimely, and patient's life security will be subjected to serious threat.
Blood plasma substitute can make blood volume, and recovery is normal rapidly, is not subjected to the restriction of blood group, does not have the blood transfusion risk of disease transmission, is the important drugs of rescuing and treating hemorrhagic shock, extensive use in medical treatment and first aid in wartime at ordinary times.Except that replenishment of blood content, blood plasma substitute also can be used as the substitute of autotransfusion and hemodilution.
Broadly, blood plasma substitute comprises crystal saline solution and colloid solution, and in the practical application, blood plasma substitute often refers in particular to colloid solution.Use wider native plasma succedaneum to be albumin clinically, artificial blood plasma substitute has macrodex and 40, hetastarch and gelatin etc.Albumin is acknowledged as the blood plasma substitute of performance optimal, but it is limited to originate, and the blood borne disease transmission danger is arranged again, so use when hypovolemic shock companion hypoproteinemia.Gelatin class material was brought into use from 1915, its dilatation effect a little less than, and can cause anaphylactoid reaction etc.Dextran was brought into use from 1945, can the long period keep osmotic pressure during the macrodex dilatation, but influential to coagulation function, and can cause allergic reaction; Playing a role clearly of Dextran 40 microcirculation improvement, but can cause renal dysfunction.Hetastarch was brought into use from 1962, and the dilatation effect is obvious, but also had above-mentioned to the influence of coagulation function, renal function or the report that causes allergic reaction.
This shows that ideal artificial blood plasma substitute should be avoided the generation of above-mentioned untoward reaction as much as possible when guaranteeing the dilatation effect.The dilatation effect realizes by keeping of osmotic pressure, if blood plasma substitute possesses the hemorheological function of improvement in dilatation, then can increase the transportation of oxygen and nutritional labeling, microcirculation improvement, diuresis improves renal function, strengthens the rescued effect of hemorrhagic shock.From pathologic angle, the damage of endothelium and the seepage of blood capillary are key factor (see Roberts JS, Bratton SL, the Drugs.1998 May that causes above-mentioned untoward reaction; 55 (5): 621-30), in other words, hemorrhagic shock and the inflammatory damage that takes place in the perfusion again are the main causes that blood plasma substitute causes untoward reaction.
The blood plasma substitute of present technology, all can not provide the effect that improves hemorheology, alleviates inflammatory damage simultaneously, so can not be in hemorrhagic shock capacity recovery, by the flow regime that changes blood plasma and blood formed element strengthen recovery effect, alleviate untoward reaction.
The Radix Astragali is one of Chinese medicine that present clinical practice is comparatively extensive, research is more deep.Pharmacological research proves that polysaccharide is wherein main a kind of effective ingredient.Astragalus polysaccharides has following several respects function: (1) enhancing human body immunity function (2) blood sugar regulation; improve symptom, blood fat reducing, minimizing albuminuria (3) the protection cardiovascular system of diabetes and renal complication thereof; protection cardiac muscle, vascular endothelial cell (4) improve diabetic animal microcirculation and hemorheology, suppress microangiopathies etc.Chinese patent application 00112326.2 discloses astragalus polysaccharides treatment cardiovascular diseases's function; Can be used as immune drug 02104043.5 disclose astragalus polysaccharides; 200410062299.X disclose the application of astragalus polysaccharides in blood lipid-lowering medicine and health product.
Summary of the invention
The objective of the invention is deficiency, a kind of novel blood plasma substitute is provided at existing blood plasma substitute, not only can expanding blood volume, and can improve hemorheology and microcirculation, the effect of enhancing capacity recovery; Lower the untoward reaction that volume expansion therapy may cause by suppressing inflammatory damage simultaneously.
Blood plasma substitute provided by the invention, it is a kind of isotonic solution.These solution contain a kind of active component, and described active component also has the ability of improving hemorheology and alleviating inflammatory damage except that the effect with expanding blood volume.This type of component contains physiologically acceptable polysaccharide macromolecular compound, and polysaccharide macromolecular compound wherein prepares with material of vegetable origin.
In order to obtain maximum effect, blood plasma substitute of the present invention contains the polysaccharide macromolecular compound by Radix Astragali preparation.
In the above-mentioned blood plasma substitute, described polysaccharide macromolecular compound is that physiologically acceptable, mean molecule quantity is 1-400 * 10
3D.
In the above-mentioned blood plasma substitute, the content of described polysaccharide macromolecular compound is 0.0005-10%.According to the present invention, blood plasma substitute of the present invention is the isotonic solution that contains physiologically acceptable polysaccharide macromolecular compound in normal saline.
This purpose can realize by a kind of method for preparing blood plasma substitute is provided.This method is a kind of isotonic solution of preparation, to wherein adding active component, it is characterized in that in isotonic solution, further adding physiologically acceptable polysaccharide macromolecular compound with the material of vegetable origin preparation, its content and physicochemical property should be guaranteed the effect of solution, keep the grade of solution simultaneously and open characteristic.
Another object of the present invention provides the purposes of above-mentioned blood plasma substitute as the treating hemorrhagic shock medicine.
Experiment shows, the present invention adopts above-mentioned blood plasma substitute treatment hemorrhagic shock, not only can expanding blood volume, also can increase the volume expansion therapy effect by improving hemorheology; In addition, can also alleviate the inflammatory damage that shock causes.Blood plasma substitute of the present invention can be used as the medicine of treatment hemorrhagic shock.
Description of drawings
For mtt assay detects not the cartogram of cell viability on the same group; Vertical coordinate is the absorbance at 595nm place; In the bar diagram,
A: normal control group;
B: lipopolysaccharide damage group;
C: blood plasma substitute protection group of the present invention.
The specific embodiment
The present invention be directed to the deficiency of existing blood plasma substitute, a kind of novel blood plasma substitute is provided.Not only can expanding blood volume, and can improve hemorheology and microcirculation, the effect of enhancing capacity recovery; Lower the untoward reaction that volume expansion therapy may cause by suppressing inflammatory damage simultaneously.
Blood plasma substitute of the present invention can be used as the medicine of treatment hemorrhagic shock.Not only can expanding blood volume, also can increase the volume expansion therapy effect by improving hemorheology; In addition, can also alleviate the inflammatory damage that shock causes.
Blood plasma substitute of the present invention is to prepare with conventional volume-gravimetric method under the drug manufacture condition.
According to the present invention, be 1-400 * 10 with an amount of physiologically acceptable mean molecule quantity
3The Powdered polysaccharide macromolecular compound of D is dissolved in an amount of volumetrical solution, and its concentration is 0.0005-10%, and percent wherein is mass/volume percent.Wherein used solvent is distilled water or normal saline.Then resulting solution is filtered, sterilizes, and make it become isotonic solution.
Result of study shows, the effect of solution of the presently claimed invention depends on the content and the physicochemical property of the active component in the blood plasma substitute of the present invention, the for example amount of polysaccharide macromolecular compound and physicochemical property thereof (see Table 1 and table 2), adding mean molecule quantity in isotonic solution is 1-400 * 10
3When D, content were the polysaccharide macromolecular compound of 0.0005-10%, the effect of solution significantly increased.
Resulting solution is water white liquid, does not contain pollutant or impurity, stable in properties.Can long term store, be no less than 2 years storage period.In chemical examination and bacteriology checking, do not observe pollutant.
The relation of desired active component content in table 1 therapeutic effect and the blood plasma substitute
| The content of active component in the blood plasma substitute, % | Be lower than 0.0005% | 0.0005-10％ | Be higher than 10% |
| Effect | Therapeutic effect descends | Optimum therapeuticing effect has no adverse reaction | Has untoward reaction |
The relation of the physicochemical property of desired active component in table 2 therapeutic effect and the blood plasma substitute
| Mean molecule quantity, D | Be lower than 1 * 10 3 | 1-400×10 3 | Be higher than 400 * 10 3 |
| Effect | Curative effect reduces, and toxicity increases | Optimum therapeuticing effect has no adverse reaction | Has untoward reaction |
Experimentation has disclosed the blood volume expansion effect of blood plasma substitute in the treatment hemorrhagic shock of requirement of the present invention; Has the effect of improving hemorheology and alleviating inflammatory damage simultaneously.For example, the description of test that carries out on the Human umbilical vein endothelial cells model of the hemorrhagic shock model of Wistar male rat and inflammatory damage the above-mentioned functions of blood plasma substitute of the present invention.
(routine operation separates femoral artery, common carotid artery and femoral vein and intubate to rat, makes the whole blood heparinization with 1 KUkg-1 heparin sodium venoclysis for 35mgkg-1, ip) anesthesia with 1% pentobarbital sodium.Carotid artery intubate and pressure transducer are linked with recording blood pressure, electrocardioelectrode is connected in animal foot record electrocardio and heart rate by the standard limb lead, the about 5cm record of anus rectal temperature is inserted in temperature sensor, femoral arteriography is connected in constant flow pump in order to blood-letting, femoral vein is used for whole blood and feeds back and administration, is incubated to animal with operating lamp.At the uniform velocity blood-letting is about 15 minutes, makes mean arterial pressure (MAP) reduce to 4.67～5.33 kPa, by adjusting blood loss this blood pressure level is kept 45 minutes, makes the hemorrhagic shock model.
Give blood plasma substitute of the present invention hemorrhagic shock rats is given treatment to, can observe amplification of animal blood volume and hemorheological improvement.For example, some time after giving blood plasma substitute of the present invention, the packed cell volume matched group of suffering a shock obviously descends (seeing Table 3) in the animal blood, and plasma viscosity obviously descends (seeing Table 4) than the normal saline matched group, and red cell deformability is than normal saline matched group obviously raise (seeing Table 5).
Table 3 hemorrhagic shock rats gives different time behind the blood plasma substitute of the present invention
The variation of packed cell volume
| Group | The shock back time (minute) | ||
| 15 | 30 | 120 | |
| The shock matched group gives blood plasma substitute group of the present invention | 43.04±0.26 41.26±0.16 | 45.03±0.22 41.08±0.13 | 46.01±0.18 43.03±0.25 |
Table 4 hemorrhagic shock rats gives different time behind the blood plasma substitute of the present invention
The variation of plasma viscosity
| Group | The shock back time (minute) | ||
| 15 | 30 | 120 | |
| The matched group that gives normal saline gives blood plasma substitute group of the present invention | 1.57±0.21 0.51±0.03 | 1.73±0.16 1.53±0.71 | 1.87±0.21 1.75±0.26 |
Table 5 hemorrhagic shock rats gives behind the blood plasma substitute of the present invention 40 minutes
The variation of red cell deformability
| Group | Red cell deformability |
| The matched group that gives normal saline gives blood plasma substitute group of the present invention | 3.71±0.18 5.56±0.26 |
Human umbilical vein endothelial cells system is with 10-100 * 10
3The density inoculation of individual/milliliter is with the lipopolysaccharide stimulation damaging cells of 1-100 mcg/ml concentration.
Give blood plasma substitute of the present invention, can observe protective effect endotheliocyte.For example, detect cell viability with mtt assay, lipopolysaccharide stimulates the damage group obviously to descend than the cellular control unit vigor, gives blood plasma substitute group of the present invention, and cell viability obviously improves (seeing Figure of description).
Claims (10)
1, a kind of blood plasma substitute is characterized in that, comprises a kind of active component, and described active component also has the ability of improving hemorheology and alleviating inflammatory damage except that the effect with expanding blood volume.
2, blood plasma substitute according to claim 1 is characterized in that, described active component is physiologically acceptable polysaccharide macromolecular compound with the material of vegetable origin preparation.
According to any described blood plasma substitute in claim 1 or 2, it is characterized in that 3, described active component is physiologically acceptable polysaccharide macromolecular compound with Radix Astragali preparation.
4, according to any described blood plasma substitute in the claim 1,2 or 3, it is characterized in that it contains physiologically acceptable mean molecule quantity is 1-400 * 10
3The polysaccharide macromolecular compound of D.
5, according to any described blood plasma substitute in the claim 1,2 or 3, it is characterized in that it contains physiologically acceptable polysaccharide macromolecular compound, content is 0.0005-10%.
6, according to any described blood plasma substitute in the claim 1 to 5, it is characterized in that it contains physiologically acceptable polysaccharide macromolecular compound in isotonic solution.
7, a kind of preparation method of blood plasma substitute according to claim 1, it is characterized in that in isotonic solution, further adding physiologically acceptable polysaccharide macromolecular compound with the material of vegetable origin preparation, its content and physicochemical property should be guaranteed the effect of solution, keep the grade of solution simultaneously and open characteristic.
8, the preparation method of blood plasma substitute according to claim 7 is characterized in that with a kind of mean molecule quantity be 1-400 * 10
3The polysaccharide macromolecular compound of D adds in the isotonic solution.
9, the preparation method of blood plasma substitute according to claim 7 is characterized in that the content of the polysaccharide macromolecular compound that added is 0.0005-10%.
10, in the claim 1 to 9 any described blood plasma substitute as the purposes for the treatment of hemorrhagic shock medicine.
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| CN 200610001867 CN101007046A (en) | 2006-01-25 | 2006-01-25 | A plasma substitute and its application for treating hemorrhagic shock |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102147418A (en) * | 2011-01-11 | 2011-08-10 | 深圳西德赛科技有限公司 | Novel hemorheology quality control combination containing polyalcohol |
| CN102334020A (en) * | 2011-01-11 | 2012-01-25 | 深圳西德赛科技有限公司 | Novel blood rheology quality control composition comprising ester compound |
-
2006
- 2006-01-25 CN CN 200610001867 patent/CN101007046A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102147418A (en) * | 2011-01-11 | 2011-08-10 | 深圳西德赛科技有限公司 | Novel hemorheology quality control combination containing polyalcohol |
| CN102334020A (en) * | 2011-01-11 | 2012-01-25 | 深圳西德赛科技有限公司 | Novel blood rheology quality control composition comprising ester compound |
| WO2012094809A1 (en) * | 2011-01-11 | 2012-07-19 | 深圳西德赛科技有限公司 | Hemorheology quality control composition comprising ester compound |
| CN102334020B (en) * | 2011-01-11 | 2013-05-01 | 深圳西德赛科技有限公司 | Novel blood rheology quality control composition comprising ester compound |
| CN102147418B (en) * | 2011-01-11 | 2013-09-11 | 深圳西德赛科技有限公司 | Novel hemorheology quality control combination containing polyalcohol |
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