CN115998803B - Pharmaceutical composition for improving myocardial ischemia reperfusion injury and preparation method and application thereof - Google Patents
Pharmaceutical composition for improving myocardial ischemia reperfusion injury and preparation method and application thereof Download PDFInfo
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Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a pharmaceutical composition for improving myocardial ischemia reperfusion injury, a preparation method and application thereof, wherein the pharmaceutical composition comprises the following raw materials in parts by weight: 10-30 parts of semen euryales, 10-15 parts of radix puerariae, 8-15 parts of radix astragali, 6-10 parts of poria cocos and 5-8 parts of hawthorn. Animal experiments prove that the pharmaceutical composition can obviously reduce Fe in heart tissues 2+ The content of MDA obviously improves SOD activity, effectively reduces the myocardial infarction area of acute MIRI rats, relieves pathological changes, inhibits the increase of ST-segment displacement value, can better prevent and treat myocardial ischemia reperfusion injury and coronary heart disease, and has wide clinical application prospect.
Description
Technical Field
The invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a pharmaceutical composition prepared from traditional Chinese medicinal materials as raw materials, and a preparation method and application thereof.
Background
Myocardial ischemia is a major factor causing heart tissue damage and myocardial cell necrosis, and is a major cause of heart failure. Coronary Heart Disease (CHD), also known as ischemic heart disease, is the most common CVD, a cardiomyopathy that causes coronary artery occlusion due to interruption of myocardial blood supply, and is clinically manifested as Acute Myocardial Infarction (AMI). The most effective treatment for AMI is reperfusion in time, however, after the blood flow perfusion is restored, tissues and organs of many patients are damaged to different degrees, the tissue and organs are clinically called Myocardial Ischemia Reperfusion Injury (MIRI), the induction reason is complex, and the method mainly relates to oxidative stress, calcium overload, autophagy, inflammation, endoplasmic reticulum stress, mitochondrial dysfunction and the like, and no safe and effective treatment method is found at present.
At present, western medicines for treating myocardial ischemia clinically mainly comprise: statin drugs, beta-receptor blockers, calcium antagonists, nitrate drugs, etc., are expensive and have adverse reactions reported in clinical applications. The traditional Chinese medicine can obviously improve the MIRI degree, has the characteristics of multiple targets, multiple channels, less toxic and side effects and the like, and is widely focused by a plurality of researchers at home and abroad. Common traditional Chinese medicine compounds are as follows: the invention provides a pharmaceutical composition capable of effectively improving myocardial ischemia reperfusion injury, a preparation method and application thereof. At present, no relevant report on the aspect of improving or treating myocardial ischemia, coronary heart disease and the like by using the combination is seen.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition with obvious curative effect and controllable quality for improving myocardial ischemia reperfusion injury, and a preparation method and application thereof.
In order to achieve the above purpose, the invention is realized by adopting the following technical scheme:
a pharmaceutical composition for ameliorating myocardial ischemia reperfusion injury, comprising the following raw materials by weight: 10-30 parts of semen euryales, 10-15 parts of radix puerariae, 8-15 parts of radix astragali, 6-10 parts of poria cocos and 5-8 parts of hawthorn.
Preferably, the weight ratio of the semen euryales to the radix puerariae is 1:1, and the medicine in the mixed state has the best use effect.
Preferably, the raw materials comprise the following components in parts by weight: 10 parts of semen euryales, 10 parts of radix puerariae, 8 parts of radix astragali, 6 parts of poria cocos, and 5 parts of hawthorn.
The second object of the present invention is to provide a preparation method of the above pharmaceutical composition, comprising the steps of:
(1) Reflux extracting radix Puerariae, radix astragali, and fructus crataegi with ethanol, vacuum recovering ethanol extract, concentrating to obtain ethanol extract concentrate and residue;
(2) Decocting the above residues, semen euryales and Poria with water, filtering the decoction, concentrating the filtrate, centrifuging, collecting supernatant, concentrating, mixing with the ethanol extract concentrate of step (1), concentrating, and drying to obtain extract powder.
Preferably, the weight of the ethanol added in the step (1) is 8-12 times of the weight of the medicinal materials, namely, the weight of the ethanol added is 8-12 times of the weight of the kudzuvine root, the astragalus root and the hawthorn fruit, the concentration of the ethanol is 50-70 percent, and the reflux extraction is carried out for 1-2 times, and each time of the extraction lasts for 0.5-1.0 hour.
Preferably, the water adding amount in the step (2) is 10-16 times of the weight of the medicinal materials, namely, the weight of the added ethanol is 10-16 times of the weight of the gorgon euryale seed and the poria cocos, 2 times of decoction are carried out, each time is 0.5-1.0 hour, the decoction is combined, the decoction is concentrated to be equivalent to the crude drug amount of 0.6g/ml-1.0g/ml, the mixture is centrifuged, the supernatant is combined with the ethanol extract concentrate, the mixture is concentrated to have the relative density of 1.05-1.20 at the temperature of 40-60 ℃ and the mixture is dried at the temperature of 55-70 ℃ under vacuum and reduced pressure.
The third object of the present invention is to provide the application of the pharmaceutical composition in preparing medicines for treating myocardial ischemia reperfusion injury and coronary heart disease.
Preferably, the medicament is in the form of oral liquid, tablets, capsules or granules.
The beneficial effects of the invention are as follows:
(1) The preparation method comprises the steps of combining the root of kudzu vine, the semen euryales, the astragalus membranaceus and the like for the first time, applying modern extraction, refining and preparation technologies, preserving the active ingredients of the pharmaceutical composition to the greatest extent, and preparing a traditional Chinese medicine preparation for treating myocardial ischemia reperfusion injury and coronary heart disease;
(2) According to the compatibility principle of traditional Chinese medicine, the medicines are combined and mutually synergistic. In the recipe, pueraria lobata has the effects of relieving muscle and allaying fever, promoting the production of body fluid to quench thirst, promoting eruption, raising yang and relieving diarrhea, and activating meridians and collaterals. The main active ingredient of the medicine is puerarin, and pharmacological researches show that the medicine can effectively reduce blood fat and relieve coronary atherosclerosis and is used as a monarch drug; semen euryales with effects of tonifying kidney, securing essence, invigorating spleen, relieving diarrhea, removing dampness, and stopping leukorrhagia is prepared from starch and microelements; poria cocos has the effects of promoting diuresis, removing dampness, invigorating spleen and calming heart, and the poria cocos are ministerial medicines and play roles of tonifying kidney and strengthening spleen; the astragalus and the hawthorn are matched for assisting, the astragalus has the effects of promoting the production of body fluid and nourishing blood, and promoting the circulation of qi and relieving arthralgia; the hawthorn can promote qi circulation, remove blood stasis, remove turbidity and reduce lipid; the astragaloside IV and fructus crataegi total flavone can be used for preventing and treating cardiovascular diseases such as coronary heart disease and myocardial infarction by improving myocardial ischemia;
(3) Animal experiments prove that the pharmaceutical composition can obviously reduce Fe in heart tissues 2+ The content of MDA obviously improves SOD activity, effectively reduces the myocardial infarction area of acute MIRI rats, relieves pathological changes and inhibits the increase of ST-segment displacement values. According to the traditional Chinese medicine theory and scientific formula, the selected medicines are all medicine-food homologous traditional Chinese medicines, so that the medicine is safe and effective, has no toxic or side effect, and is simple, convenient and economic in raw materials.
Drawings
FIG. 1 is the effect on Myocardial Ischemia Reperfusion Injury (MIRI);
FIG. 2 is the effect on IR-induced oxidative stress and ferritin dependence in rats;
wherein FIG. 1-A is TTC staining; FIG. 1-B is infarct size/relative risk area; FIG. 1-C shows HE staining on the left and electrocardiogram on the right; FIG. 2-A is an immunofluorescence assay for detecting ROS expression; 2-B is ROS positive cell number/total cell number; 2-C is MDA and Fe in heart tissue 2+ Concentration, SOD activity.
Detailed Description
Example 1
200g of semen euryales, 200g of radix puerariae, 160g of radix astragali, 120g of poria cocos and 100g of hawthorn, wherein the radix puerariae, the radix astragali and the hawthorn are added with 60% ethanol which is 12 times of the weight of the medicinal materials, and are subjected to reflux extraction twice, each time for 1 hour, filtering, merging ethanol extracts, concentrating the ethanol under reduced pressure until no ethanol smell exists, merging the residues, the semen euryales and the poria cocos, adding 15 times of water into the medicinal materials, decocting twice, each time for 1 hour, merging decoction, filtering, concentrating the filtrate under reduced pressure until the amount of water is equal to 0.8g/ml of the crude drug, centrifuging, merging supernatant with the ethanol extract concentrate, concentrating the supernatant at 50 ℃ until the relative density is 1.10 (50 ℃), carrying out vacuum drying under reduced pressure to obtain 235.5g of dry extract powder, taking proper amount of dry extract powder, preparing soft capsule contents, and preparing gel capsules.
Example two
Extracting semen euryales 300g, radix Puerariae 200g, radix astragali 160g, poria 120g, and fructus crataegi 100g with ethanol of 60% weight ratio of radix Puerariae, radix astragali, and fructus crataegi twice under reflux for 1 hr each time, filtering, mixing the ethanol extracts, recovering ethanol under reduced pressure, concentrating until no ethanol smell, mixing the above residues with semen euryales and Poria, decocting with water of 15 times weight ratio of the medicinal materials twice each time for 1 hr, mixing decoctions, filtering, concentrating the filtrate under reduced pressure to 0.8g/ml, centrifuging, mixing the supernatant with the ethanol extract concentrate, concentrating at 50deg.C to relative density of 1.10 (50deg.C), vacuum drying under reduced pressure to obtain 235.5g dry extract powder, collecting dry extract powder, soybean oil, cera flava, and soybean phospholipid, and making into soft capsule, and making into capsule.
Example III
Extracting semen euryales 150g, radix Puerariae 200g, radix astragali 160g, poria 120g, and fructus crataegi 100g with ethanol of 60% weight ratio of 12 times of materials twice under reflux for 1 hr each time, filtering, mixing the ethanol extracts, recovering ethanol under reduced pressure, concentrating until no ethanol smell, mixing the above residues with semen euryales and Poria, decocting with water of 15 times of materials weight twice each time for 1 hr, mixing decoctions, filtering, concentrating the filtrate under reduced pressure to 0.8g/ml of crude drug weight, centrifuging, mixing the supernatant with the ethanol extract concentrate, concentrating at 50deg.C to relative density of 1.10 (50deg.C), vacuum drying under reduced pressure to obtain 235.5g dry extract powder, collecting dry extract powder, soybean oil, cera flava, and soybean phospholipid, making into soft capsule content, and making into capsule.
Example IV
Extracting radix Puerariae, radix astragali, and fructus crataegi with 70% ethanol 10 times of total weight of the materials twice under reflux for 50 min, filtering, mixing the ethanol extracts, recovering ethanol under reduced pressure, concentrating, mixing the above residues with semen euryales and Poria, decocting with 12 times of water for 1 hr, mixing decoctions, filtering, concentrating the filtrate under reduced pressure to 1g/ml, centrifuging, mixing the supernatant with the ethanol extract concentrate, concentrating at 60deg.C to relative density of 1.20 (50deg.C), vacuum drying to obtain 475.5g dry extract powder, mixing the dry extract powder with dextrin, granulating, drying at 60deg.C, and encapsulating to obtain hard capsule 1000 granule.
Example five
400g of semen euryales, 200g of radix puerariae, 200g of radix astragali, 100g of poria cocos and 100g of hawthorn, wherein the radix puerariae, the radix astragali and the hawthorn are added with 50% ethanol which is 8 times of the weight of the medicinal materials, the reflux extraction is carried out twice, each time for 1 hour, the filtering is carried out, the ethanol extract is combined, the ethanol is recovered under reduced pressure and concentrated until no alcohol smell exists, the above medicinal residues are combined with the semen euryales and the poria cocos, 10 times of water is added into the medicinal materials, the decoction is decocted for two times, each time for 40 minutes, the decoction is combined, the filtering is carried out, the filtrate is concentrated under reduced pressure until the amount of water is equivalent to 0.85g/ml of the crude drug, the supernatant is combined with the ethanol extract concentrate, the concentration is carried out at 60 ℃ until the relative density is 1.05 (50 ℃), the dry extract powder is obtained through vacuum drying under reduced pressure, the dry extract powder is taken, the dry extract powder is added with sugar powder and dextrin which are evenly mixed for wet granulation, the drying is carried out at 50 ℃, and 500g of particles are obtained, and split charging.
Example six
260g of semen euryales, 180g of radix puerariae, 120g of radix astragali, 80g of poria cocos and 60g of hawthorn, wherein the radix puerariae, the radix astragali and the hawthorn are added with 70% ethanol which is 12 times of the weight of the medicinal materials, and are subjected to reflux extraction twice, each time for 1 hour, filtering, merging ethanol extract liquid, recovering ethanol under reduced pressure, concentrating until no ethanol smell exists, merging the residues, the semen euryales and the poria cocos, adding 16 times of water into the medicinal materials, decocting twice, each time for 50 minutes, merging decoction liquid, filtering, concentrating the filtrate under reduced pressure until the concentration is equal to the crude drug weight of 0.9g/ml, centrifuging, merging supernatant and the ethanol extract concentrate, concentrating at 60 ℃ until the relative density is 1.15 (50 ℃), carrying out vacuum drying under reduced pressure to obtain 218.55g of dry extract powder, taking dry extract powder, adding dry starch (1:0.1), mixing uniformly, carrying out wet granulation, drying at 55 ℃, adding a proper amount of dry starch into dry particles, mixing uniformly, and tabletting.
In order to verify the influence of the medicine of the invention on myocardial ischemia reperfusion injury of rats, the following experiments are specially carried out:
1. materials and methods
1.1 sample: the medicament of the invention prepared according to the above example 1 gives dry extract powder;
1.2 experimental animals: 50 adult male SD rats, body weight (260-280 g), provided by Nanjing Qing Longshan animal breeding center, all animal experiments were completed at Nanjing university of traditional Chinese medicine laboratory animal center, laboratory ethical number: no.201910A046.
1.3 experimental method: SD rats were adaptively fed for 1 week, randomly divided into 5 groups a-E, respectively: sham surgery group, I/R group, I/R+QGD (0.1 g/kg), I/R+QGG (0.2 g/kg), I/R+DIL group (20 mg/kg); wherein, the I/R group is ischemia control group, the QGD is low dose group of dry extract powder prepared by the formula and the method of the first embodiment, the QGG is high dose group of dry extract powder prepared by the formula and the method of the first embodiment, and the DIL is positive drug diltiazem. Is prepared just before the stomach irrigation by using normal saline. The gavage administration was continued for 7 days, and the sham operation group and the I/R group were administered with an equal amount of physiological saline. On day 8, rats were anesthetized with 50mg/kg sodium pentobarbital, tracheal cannulated, midline thoracotomy, left Anterior Descending (LAD) vessel ligated with 5-0 gauge sterile suture needle for 40min of coronary occlusion, venous cannulated carefully pulled out, and ischemic myocardium reperfusion induced, with the same surgical protocol used in the sham-operated group. During the operation, the electrocardiogram is continuously monitored.
Immediately taking out the heart tissue after the rat is killed, performing TTC staining, immersing part of the heart tissue in 4% paraformaldehyde for HE staining, observing the heart tissue of the rat by adopting an immunofluorescence method, and detecting MDA and Fe in the heart tissue according to the specification of a detection kit 2+ Content and SOD activity, heart tissue was frozen and sectioned, and the number of ROS positive cells was counted under a fluorescence microscope.
2. Experimental results
2.1 Effect of the medicament of the invention on I/R-induced myocardial injury
The I/R-induced myocardial infarction area was measured using TTC staining. As shown in FIG. 1-A (TTC staining), and FIG. 1-B (infarct area/relative dangerous area) and Table 1, the I/R group significantly increased myocardial damage infarct area, and the I/R+QGD group, I/R+QGG group, and I/R+DIL group significantly decreased myocardial infarction area, as compared to the sham-operated group. The results show that the medicine provided by the invention can effectively improve the heart tissue injury induced by I/R (p <0.01, table 1).
TABLE 1 percentage of myocardial infarction area (x.+ -. S,%)
| Group of | Number of animals | Percentage of myocardial infarction area |
| Group A (Artificial operation group) | 10 | / |
| Group B (I/R) | 10 | 42.26±3.25 |
| Group C (I/R+QGD group) | 10 | 32.69±2.58* |
| Group D (I/R+QGG group) | 10 | 29.22±3.83* |
| Group E (I/R+DIL group) | 10 | 26.13±1.65 |
2.2 effects of the inventive medicament on cardiac tissue and electrocardiogram
Heart histopathological changes were observed using HE staining. As shown in FIG. 1-C (left HE staining), the sham myocardium has clear structure, aligned fibrous tissue, less edema, and less inflammatory cell infiltration. The myocardial structures of the I/R group are obviously damaged, fiber disorder, myocardial cytopenia, cell nucleus contraction and inflammatory cell infiltration. Compared with the I/R group, the QGG and DIL obviously lighten the histopathological changes, and the effect is slightly better than that of the QGD group.
And (3) observing an electrocardiogram II lead, wherein the electrocardiogram II lead is used for judging the occurrence of myocardial infarction of the front lower wall of the heart, and the observation area is the same as the myocardial infarction area of the left anterior descending branch of the coronary artery. As shown in fig. 1-C (right electrocardiogram), the sham-operated group electrocardiogram does not see significant ST elevation; compared with the false operation group, the I/R group electrocardiogram presents obvious T wave for obviously raising and mutating ST segment; the I/R+QGD group had significant ST elevation, but showed a downward trend compared to the I/R group. The I/R+QGG group and the I/R+DIL group have no obvious ST elevation, and the ST is obviously reduced compared with the I/R group.
The result shows that the medicine can effectively improve myocardial tissue injury caused by I/R and reduce obvious elevation of the ST segment of an electrocardiogram.
2.3 effects of the inventive drugs on IR-induced oxidative stress and ferritin dependency in rats
Immunofluorescence staining results showed that QGD, QGG and DIL all reduced I/R-induced elevated ROS levels as shown in FIG. 2-A (immunofluorescence assay for ROS expression), 2-B (ROS positive cell number/total cell number). QGG and DIL can obviously reduce Fe in heart tissue 2+ MDA content; QGD also reduces Fe in heart tissue 2+ The MDA content, however, was not significantly different from QGG and DIL. FIG. 2-C (MDA, fe in cardiac tissue) 2+ Concentration, SOD activity), I/R resulted in reduced SOD activity, and QGD, QGG, and DIL all increased SOD activity compared to I/R group.
The result shows that the medicine of the invention can effectively reduce the increase of ROS level caused by I/R, reduce Fe in heart tissue 2+ MDA content, has better iron death inhibiting ability (Table 2, p<0.01)。
Table 2 effect on MDA and SOD content in rat serum (x±s, n=10)
| Group of | MDA(μmol/g) | SOD/(10 3 U/g) |
| Group A (Artificial operation group) | 2.14±1.09 | 70.14±3.68 |
| Group B (I/R) | 4.38±2.16 | 36.23±2.17 |
| Group C (I/R+QGD group) | 3.25±1.27* | 53.52±1.58* |
| Group D (I/R+QGG group) | 2.84±0.95* | 60.75±1.12* |
| Group E (I/R+DIL group) | 2.57±1.12* | 63.38±0.88* |
The present invention has been completed and has been achieved with the above embodiments. It will be appreciated by persons skilled in the art that the present invention includes, but is not limited to, the drawings, the accompanying tables and what has been described in the foregoing embodiments. Any modifications which do not depart from the functionalities and principles of the present invention are intended to be included within the scope of the appended claims.
Claims (8)
1. A pharmaceutical composition for improving myocardial ischemia reperfusion injury, which is characterized by being prepared from the following raw materials in parts by weight: 10-30 parts of semen euryales, 10-15 parts of radix puerariae, 8-15 parts of radix astragali, 6-10 parts of poria cocos and 5-8 parts of hawthorn.
2. The pharmaceutical composition for improving myocardial ischemia reperfusion injury according to claim 1, wherein the weight ratio of gorgon fruit to kudzuvine root is 1:1.
3. The pharmaceutical composition for improving myocardial ischemia reperfusion injury according to claim 1, which is prepared from the following raw materials in parts by weight: 10 parts of semen euryales, 10 parts of radix puerariae, 8 parts of radix astragali, 6 parts of poria cocos, and 5 parts of hawthorn.
4. A method of preparing a pharmaceutical composition according to any one of claims 1-3, comprising the steps of:
(1) Reflux extracting radix Puerariae, radix astragali, and fructus crataegi with ethanol, vacuum recovering ethanol extract, concentrating to obtain ethanol extract concentrate and residue;
(2) Decocting the above residues, semen euryales and Poria with water, filtering the decoction, concentrating the filtrate, centrifuging, collecting supernatant, concentrating, mixing with the ethanol extract concentrate of step (1), concentrating, and drying to obtain extract powder.
5. The method of claim 4, wherein the ethanol added in step (1) is 8-12 times the weight of the medicinal material, and the concentration is 50-70%, and the extraction is performed by reflux-extracting for 1-2 times for 0.5-1.0 hr each time.
6. The method for preparing a pharmaceutical composition according to claim 4, wherein the water amount added in the step (2) is 10-16 times of the weight of the medicinal materials, the decoction is divided into 2 times of decoction, each time is 0.5-1.0 hour, the decoction is combined, the decoction is concentrated to the amount equivalent to 0.6g/ml-1.0g/ml of the crude drug, the mixture is centrifuged, the supernatant is combined with the alcohol extract concentrate, and the mixture is concentrated to the relative density of 1.05-1.20 at 40-60 ℃ and dried at 55-70 ℃ under vacuum and reduced pressure.
7. Use of a pharmaceutical composition according to any one of claims 1-3 for the preparation of a medicament for the treatment of coronary heart disease.
8. The use of a pharmaceutical composition according to claim 7 in the manufacture of a medicament for the treatment of coronary heart disease in the form of an oral liquid, a tablet, a capsule or a granule.
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| CN102150779A (en) * | 2011-03-24 | 2011-08-17 | 岑卫华 | Health food for regulating and stabilizing blood sugar and preparation method thereof |
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| CN102150779A (en) * | 2011-03-24 | 2011-08-17 | 岑卫华 | Health food for regulating and stabilizing blood sugar and preparation method thereof |
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| Title |
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| 保心汤对气虚血瘀型冠心病心绞痛患者生活质量的影响;邢之华, 林展增;安徽中医学院学报;-;第22卷(第03期);第19-21页 * |
| 葛根汤的临床运用;史定文, 李俊杰, 张玺英;中华中医药杂志;-;第6卷(第01期);第59-60页 * |
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