CN111514156A - Application of ginsenoside Rg3 in treating acute myocardial infarction - Google Patents
Application of ginsenoside Rg3 in treating acute myocardial infarction Download PDFInfo
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- CN111514156A CN111514156A CN202010023010.2A CN202010023010A CN111514156A CN 111514156 A CN111514156 A CN 111514156A CN 202010023010 A CN202010023010 A CN 202010023010A CN 111514156 A CN111514156 A CN 111514156A
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Abstract
The invention relates to application of ginsenoside Rg3 in preventing and treating acute myocardial infarction.
Description
Technical Field
The invention relates to the field of medicines, in particular to an anti-myocardial infarction therapeutic application of ginsenoside Rg 3.
Background
Acute Myocardial Infarction (AMI) refers to acute necrosis of a portion of the myocardium resulting from persistent and severe myocardial ischemia. Acute myocardial infarction refers to ischemic necrosis of local myocardium caused by acute occlusion and blood flow interruption of coronary artery, and acute myocardial infarction is a serious type of coronary heart disease. The basic cause is atherosclerosis of the coronary arteries, resulting in severe stenosis of the lumen and insufficient blood supply to the myocardium, while collateral circulation is not fully established. On the basis, once the blood supply is further sharply reduced or interrupted, the myocardium is seriously and durably subjected to acute ischemia for more than 1 hour, and the myocardial infarction can occur. Clinically, chest pain, acute circulatory dysfunction and a series of characteristic electrocardiogram changes reflecting myocardial damage, ischemia, necrosis and the like are frequently shown. The clinical manifestations often show persistent severe poststernal pain, acute circulatory dysfunction, arrhythmia, heart failure, fever, elevated white blood cell count and serum markers of myocardial injury and progressive electrocardiographic evolution of acute myocardial injury and necrosis. China has a remarkable rising trend in recent years, newly issues at least 50 ten thousand every year, and finds out at least 200 ten thousand.
Ginsenoside Rg3(Ginsenoside Rg3) is a natural saponin compound, and is mainly present in Notoginseng radix. Although, 200510078482.3(CN1879640A) discloses: the application of the ginsenosides Rh2, Ck and Rg3 in increasing myocardial contractility, however, no document reports that the ginsenosides CK can be used for treating acute myocardial infarction, and the treatment of the acute myocardial infarction is irrelevant to the increase of the myocardial contractility, so that CN1879640A is irrelevant to the application, and the invention has innovation.
Disclosure of Invention
The invention aims to provide medical application of ginsenoside Rg3 in treating acute myocardial infarction.
The invention provides application of ginsenoside Rg3 in preparation of a pharmaceutical composition for treating acute myocardial infarction.
The invention provides application of ginsenoside Rg3 in preparation of a pharmaceutical composition for preventing acute myocardial infarction.
The invention provides application of ginsenoside Rg3 in preparation of a pharmaceutical composition for treating or preventing acute myocardial infarction
In a second aspect, the invention provides a pharmaceutical composition for treating or preventing myocardial infarction, which comprises a therapeutically effective amount of ginsenoside Rg3, wherein the concentration of ginsenoside Rg3 is 1-36mg/kg, preferably 5.2 mg/kg.
The invention arose in part from the unexpected discovery that: the ginsenoside Rg3 can obviously reduce the infarct size of ischemic myocardium of rats. Therefore, the ginsenoside Rg3 is expected to be developed into a medicine for treating acute myocardial infarction, and the medicine for treating acute myocardial infarction can be various forms of substances, including but not limited to: drugs, health products, foods, daily necessities, and the like. The therapeutic drugs prepared from the ginsenoside Rg3 can be used for preventing and treating acute myocardial infarction and the like.
The ginsenoside Rg3 of the present invention can be obtained commercially from Sigma chemical Co, Dowman Stokes Biotech, etc., or can be isolated from notoginsenoside by conventional methods in the art. The purity of the product meets the pharmaceutical standard.
The ginsenoside Rg3 of the invention is prepared into a medicament as an example. The ginsenoside Rg3 can be used independently or in the form of a pharmaceutical composition. The pharmaceutical composition comprises the ginsenoside Rg3 as an active ingredient and a pharmaceutically acceptable carrier. Preferably, the pharmaceutical composition of the present invention contains 0.1 to 99.9% by weight of the ginsenoside Rg3 of the present invention as an active ingredient. The pharmaceutical carrier does not damage the pharmaceutical activity of the ginsenoside Rg 3.
Such pharmaceutically acceptable carriers include, but are not limited to: lecithin, aluminum stearate, alumina, ion exchange materials, self-emulsifying drug delivery systems, tweens or other surfactants, serum proteins, buffer substances such as phosphates, glycine, sorbic acid, water, salts, electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, magnesium silicate, mixtures of saturated fatty acid partial glycerides, and the like.
Other conventional pharmaceutical adjuvants such as binder (e.g. microcrystalline cellulose), filler (e.g. starch, glucose, anhydrous lactose and lactose beads), disintegrant (e.g. crosslinked PVP, croscarmellose sodium, low-substituted hydroxypropylcellulose), lubricant (e.g. magnesium stearate), and absorption enhancer, adsorption carrier, flavoring agent, sweetening agent, excipient, diluent, wetting agent, etc.
The ginsenoside Rg3 and the pharmaceutical composition thereof can be prepared according to the conventional method in the field and can be administrated by intestinal or parenteral or local routes. The oral preparation comprises capsule, tablet, oral liquid, granule, pill, powder, pellet, and unguent; parenteral preparations include injections and the like; topical preparations include creams, patches, ointments, sprays, and the like. Oral formulations are preferred.
The administration route of the ginsenoside Rg3 and the pharmaceutical composition thereof can be oral, sublingual, transdermal, intramuscular or subcutaneous, skin mucosa, vein, urethra, vagina and the like.
Besides the preparation of medicines, various food additives such as antioxidants, pigments, enzyme preparations and the like can be added into the ginsenoside Rg3 to prepare health-care food according to the conventional method in the field.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers. All percentages, ratios, proportions, or parts are by weight unless otherwise specified.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.
The features mentioned above with reference to the invention, or the features mentioned with reference to the embodiments, can be combined arbitrarily. All the features disclosed in this specification may be combined in any combination and each feature disclosed in this specification may be replaced by alternative features serving the same, equivalent or similar purpose. Thus, unless expressly stated otherwise, the features disclosed are merely generic examples of equivalent or similar features.
The ginsenoside Rg3 has effect in reducing myocardial infarction area of operation rat, and resisting myocardial ischemia, and can reduce myocardial infarction area of AMI model rat by 12%. By comparison with the equimolar doses of Fc, the effects of Rg3 were slightly lower than Fc (22.5% and 13.5%, respectively) compared to the Fc (8mg/kg) and Rg3(5.2mg/kg) doses.
Drawings
FIG. 1 Effect of ginsenoside Rg3 on the percentage of acute myocardial infarction area of rat
FIG. 2 pathological pictures of rat myocardial infarction treatment groups
FIG. 3 Effect of notoginsenoside Fe on the percentage of acute myocardial infarction area of rat
FIG. 4 Effect of notoginsenoside R1 on the percentage of acute myocardial infarction area in rats
Example 1
First, experimental material
1.1 medicinal materials
Ginsenoside Rg3 (molecular weight 622.44, HPLC purity more than or equal to 99%, Chinese medicine research institute); salvia miltiorrhiza Bunge injecta (purchased from Shanghai green grain pharmaceutical industry, batch number: 1505031);
1.2 Experimental animals
SD rats weighing 220 ± 20g, provided by the experimental animals center of the university of medicine in shanghai, animal certification No.: SYXK (Shanghai) 2008-0016. Placing in conventional breeding environment, and freely taking food and drinking water.
Secondly, the method comprises the following steps:
the model making method comprises the following steps: SD rats 30 (provided by the animal experiment center of the university of medicine in shanghai), body weight: 220- & gt, 270 g. Rat pentobarbital (35mg/kg) was anesthetized and fixed supine; cutting the center of the neck, separating trachea, performing tracheotomy, inserting a respiratory tube, and adjusting the frequency and tidal volume of a respirator; the chest (3-4 intercostals) is opened through the median incision of the sternum, a thin operation needle and a six-gauge thread are inserted into the left auricle and then the pulmonary artery is ligated out of the cone. The standard for judging the success of the anterior descending branch of the suture is observed by naked eyes (the blood supply area of the anterior descending branch is dark or pale), so that the chest is closed quickly. The sham operation group only threaded around the anterior descending branch of the left coronary artery without ligation, the same as the operation group.
TTC dyeing: freezing and storing at the temperature of minus 20 ℃, taking out until the heart is frozen hard, and cutting the heart into 5-6 slices along the long axis of the left ventricle, wherein each slice is 3-4 mm thick. Then placing the mixture into 0.5% TTC solution, incubating the mixture for 15min at 37 ℃, taking out the myocardial slices and fixing the myocardial slices in 4% formaldehyde solution.
Index collection: the myocardial tablets are in two different colors, and the red is normal myocardial tissue; white or grayish black is necrotic myocardial tissue. The myocardium was cut in two different colors and then dried with filter paper, and the weight was weighed. Calculated according to the following formula: area of myocardial ischemia (%) — total heart weight ÷ weight of infarcted myocardium × 100%. Meanwhile, a part of the heart is collected for pathological section analysis.
Third, design of experiment
2.2.5 Experimental design for acute myocardial infarction of rat
Surgical blank group: 5 patients were given 0.9% Normal Saline (NS) post-operatively.
A positive drug group: 5 patients were administered with the injection of Salvia miltiorrhiza (23mg/kg) after surgery.
Fc group: 5, notoginsenoside Fc (8mg/kg) was administered after surgery.
Rg3 administration group: 5 patients were administered with ginsenoside Rg3(5.2mg/kg) after surgery.
Notoginsenoside Fe: 5, after operation, the notoginsenoside Fe (4.1mg/kg)
Notoginsenoside R1: 5, after operation, notoginsenoside R1(4.1mg/kg)
Fourthly, conclusion:
FIG. 1 shows that: the ginsenoside Rg3 has the function of obviously reducing the myocardial infarction area percentage of an operative rat. And the blank control group has obvious difference significance (P < 0.001) with the 5.2mg/kg administration group. Each administration group was significantly different from the control group.
FIG. 2 shows that: the percentage of infarct size of the group treated with ginsenoside Rg3 was significantly less than that of the control group (P < 0.001).
Comparison of effects of positive drug DS (Salvia miltiorrhiza Bunge injection) and Fe group
Comparison of effects of the positive drugs DS (Salvia miltiorrhiza Bunge injection) and R1 groups
Example 2
A medicinal preparation of ginsenoside Rg3 is prepared from the following raw materials in parts by weight:
dissolving ginsenoside Rg3 in small amount of water; respectively sieving microcrystalline cellulose, mannitol and sodium carboxymethyl starch with 100 mesh sieve, mixing, adding ginsenoside Rg3 solution, stirring, making soft material with 2% hydroxyethyl methylcellulose solution as binder, sieving with 80 mesh sieve, granulating, and drying wet granules in oven at 40 deg.C by blowing; sieving the dry granules with a 80-mesh sieve, grading, mixing with calcium stearate, and encapsulating.
Example 3
A medicinal preparation of ginsenoside Rg3 is prepared from the following raw materials in parts by weight:
dissolving ginsenoside Rg3 in small amount of water; respectively sieving microcrystalline cellulose, mannitol and sodium carboxymethyl starch with 100 mesh sieve, mixing, adding ginsenoside Rg3 solution, stirring, making soft material with 2% hydroxyethyl methylcellulose solution as binder, sieving with 80 mesh sieve, granulating, and drying wet granules in oven at 40 deg.C by blowing; sieving the dried granules with a 80-mesh sieve, granulating, and tabletting.
Example 4
A medicinal preparation of ginsenoside Rg3 is prepared from the following raw materials in parts by weight:
ginsenoside Rg 320 mg
Adding water for injection to 1000.0mL
Adding injectable water into ginsenoside Rg3, adjusting to total volume of 1000ml, filtering with 0.22um microporous filter membrane, and packaging.
Example 5
A medicinal preparation of ginsenoside Rg3 is prepared from the following raw materials in parts by weight:
ginsenoside Rg 350.0mg
Making into 500ml injection, packaging, and lyophilizing;
dissolving with 500ml water for injection to obtain solution I, and keeping the temperature at 80 deg.C; dissolving ginsenoside Rg 350 mg in water for injection, slowly adding into solution I, dissolving, keeping the temperature for 60 min, cooling to room temperature, filtering with microporous membrane, packaging into 1000 bottles, and lyophilizing.
The freeze-drying process comprises freezing at-15 deg.C for molding, cooling at-40 deg.C, vacuum drying under freezing, slowly heating after 36 hr, and sealing at 25 deg.C.
Example 6
The products of examples 2-5 are used in the preparation of pharmaceutical compositions for the treatment of acute myocardial infarction.
The products of examples 2-5 were significantly effective in the treatment of acute myocardial infarction.
Claims (3)
1. An application of ginsenoside Rg3 in preparing a pharmaceutical composition for treating or preventing acute myocardial infarction is characterized in that the pharmaceutical composition can be prepared according to a conventional method in the field and can be administrated through an intestinal tract, a parenteral tract or a local route.
2. The use of ginsenoside Rg3 in the preparation of pharmaceutical composition according to claim 1, wherein the oral preparation comprises capsule, tablet, oral liquid, granule, pill, powder, pellet, paste, etc.; parenteral preparations include injections and the like; topical preparations include creams, patches, ointments, sprays, and the like; the health food is prepared by adopting antioxidant, pigment and enzyme preparation according to the conventional method in the field.
3. The use of ginsenoside Rg3 in the preparation of pharmaceutical composition according to claims 1-2, wherein the administration route is oral, sublingual, transdermal, intramuscular or subcutaneous, mucocutaneous, intravenous, urethral, vaginal, etc.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202010023010.2A CN111514156A (en) | 2015-12-07 | 2015-12-07 | Application of ginsenoside Rg3 in treating acute myocardial infarction |
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| CN201510896908.XA CN106822162A (en) | 2015-12-07 | 2015-12-07 | The therapeutic action of ginseng sapoglycoside Rg 3 acute myocardial infarction |
| CN202010023010.2A CN111514156A (en) | 2015-12-07 | 2015-12-07 | Application of ginsenoside Rg3 in treating acute myocardial infarction |
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| CN201510896908.XA Division CN106822162A (en) | 2015-12-07 | 2015-12-07 | The therapeutic action of ginseng sapoglycoside Rg 3 acute myocardial infarction |
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| CN109620837A (en) * | 2019-02-18 | 2019-04-16 | 烟台汉麻生物技术有限公司 | Application of the ginseng sapoglycoside Rg 3 in preparation prevention and/or treatment Severe Acute Pancreatitis SAP drug |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1569011A (en) * | 2003-07-24 | 2005-01-26 | 山东绿叶天然药物研究开发有限公司 | Application of 20(R)-ginsenoside-Rg3 in the preparing process of medicine for treating or preventing cardiovascular and cerebrovascular disease |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1569011A (en) * | 2003-07-24 | 2005-01-26 | 山东绿叶天然药物研究开发有限公司 | Application of 20(R)-ginsenoside-Rg3 in the preparing process of medicine for treating or preventing cardiovascular and cerebrovascular disease |
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