WO2013189229A1

WO2013189229A1 - New use of 20(s)-protopanoxadiol

Info

Publication number: WO2013189229A1
Application number: PCT/CN2013/076347
Authority: WO
Inventors: 许长江; 张文静; 潘欣萍; 汪沁琳; 杨子荣
Original assignee: 上海中药创新研究中心
Priority date: 2012-06-19
Filing date: 2013-05-28
Publication date: 2013-12-27
Also published as: CN103505462A; CN103505462B

Abstract

The present invention relates to a new use of 20(S)-protopanoxadiol, and in particular, to an application of 20(S)-protopanoxadiol in preparing the medicines for preventing and treating ischemic heart diseases. Pharmacodynamics studies have found that 20(S)-protopanoxadiol can reduce myocardial histological damages caused by ischemia and ischemia reperfusion, reduce enzyme indicators related to infarct size and myocardial necrosis, and reduce the drift of J-spot on an electrocardiogram.

Description

20 (S) - New use of protopanaxadiol

The present invention relates to a novel use of 20(S)-protopanaxadiol, and more particularly to the use of 20(S)-protopanaxadiol for the preparation of a medicament for the prevention and treatment of ischemic heart disease. Background technique

In China, cardiovascular diseases (including hypertension and coronary heart disease) have become the main diseases that endanger human health and life. In 2002, the death rate of heart disease among residents of Dacheng, China was 75.68/100,000, second only to malignant tumors and cerebrovascular accidents, ranking third in death.

Myocardial ischemic heart disease, also known as coronary heart disease, refers to heart disease caused by myocardial ischemia or hypoxia due to stenosis or obstruction of coronary atherosclerosis, resulting in coronary atherosclerosis. The most common type of organ lesions. Clinical manifestations include stable angina, unstable angina, arrhythmia, and cardiogenic shock. Unstable angina can develop into acute myocardial infarction (AMI) or even sudden death.

Coronary heart disease is known as the "number one killer" in developed countries, and the incidence rate in developing countries is also increasing. The World Health Organization (WHO) predicts that cardiovascular disease will be the number one cause of death worldwide by 2020.

At present, the treatment of coronary heart disease mainly includes three methods: drug treatment, interventional therapy and bypass surgery. Among them, drug treatment is the most basic treatment, according to the WHO ATC code can be divided into calcium channel blockers, heart disease medications, peripheral vasodilators and other 9 categories.

Clinically used drugs for the treatment of myocardial ischemia are mostly Ginkgo biloba, alprostadil, amlodipine, ginseng, fructose diphosphate, nifedipine, puerarin, isosorbide mononitrate, breviscapine, notoginsenoside and other drugs. Among them, cardiovascular drugs mainly based on traditional Chinese medicine or traditional Chinese medicine are widely used, and the advantages are that the curative effect is exact, the side effects are small, and the recognition potential is increasing, so the market potential is huge.

During heart valve replacement surgery, it is necessary to give cardiac arrest to the patient, establish extracorporeal circulation, and cause myocardial ischemia after the aorta is blocked. After the aorta is opened, it causes myocardial ischemia-reperfusion injury.

Protopanaxadiol is an in vivo metabolite of diol group ginsenosides, which is divided into 20-(S) protopanaxadiol (20(s)-protopanaxadiol, 20(S)-dammarane-24. -ene-3β,12β,20-three Alcohol) and 20 (R)-protopanaxadiol (20(R)-protopanaxadiol, 20(R)-damran-24-ene-3β, 12β, 20-three

20-(S) Protopanaxadiol 20-() Protopanaxadiol Patent CN200910139993.X discloses the protopanaxadiol saponin in Panax notoginseng for use in atherosclerotic diseases.

Patent CN03132958.6 discloses the use of 20(R)-ginsenoside-RG3 in the preparation and prevention of cardiovascular and cerebrovascular diseases.

Up to now, there have been no patent reports on the treatment of myocardial ischemic heart disease by 20(S)-protopanaxadiol.

Literature: Guo Yucheng, Tang Xudong et al reported that Panax notoginseng saponins can inhibit the activation of NF-B in neutrophils, reduce the expression of ICAN-1 and neutrophil infiltration, thereby improving myocardial microcirculation and protecting the heart muscle. (Guo Yucheng, Tang Xudong, Gu Dayong, Jiang Dachun, Jiang Jianqing, Experimental study on the protective effect of Panax notoginseng saponins on myocardial ischemia-reperfusion injury, J.of Chinese Nierocireulation Oct, 2004, Vol.8.No.5); Jin Ming, Qu Shao Chun reported that ginseng diol saponin injection (IPQDS) has protective effects on myocardial ischemia-reperfusion injury in rats, possibly enhancing its antioxidant enzyme activity, reducing oxidative damage of free radicals to the myocardium, and reducing endogenous vasoactive activity. The release of substance ET and Ang ll, correcting the imbalance of PGI2 / TXA2 and other mechanisms (Jin Ming, Qu Shaochun, Yu Xiaofeng, Xu Huan, Pei Da, ginseng diol saponin injection on myocardial ischemia reperfusion injury in rats Impact, Tianjin Traditional Chinese Medicine, Apr.2006, Vol.23 No.2). Wu Shufang et al. reported the anti-experimental myocardial ischemia effect and mechanism of American ginseng leaf 20s-protopanaxadiol saponins (Wu Shufang et al. Anti-experimental myocardial ischemia effect and mechanism of American ginseng leaf 20s-protocormone saponins) , Chinese Journal of Pharmaceutical Sciences, 2002, 02)

The above studies suggest that saponins have potential protection against myocardial reperfusion injury. Function, but the above studies are all a mixture of various saponin compounds, failing to indicate which saponin compound plays a role. Secondly, the myocardial protection of these compounds can only be observed at larger doses, that is, the effective dose in the body is above 100 mg/kg. Since diol saponins can be rapidly converted into various metabolites in vivo after oral administration, including Rg3, Rh2, compound-K and PPD, these metabolites are significantly different from the original ginsengdiol saponins in their mechanisms. The role has not been reported. Summary of the invention

It is an object of the present invention to provide a new use of 20-(S)-protopanaxadiol.

The present invention provides the use of 20-(S)-protopanaxadiol for the preparation of a medicament for the prevention and treatment of ischemic heart disease.

The ischemic heart disease is selected from coronary heart disease or coronary atherosclerotic heart disease.

Preferably, the ischemic heart disease of the present invention is myocardial ischemia and myocardial ischemia-reperfusion injury. The myocardial ischemia and myocardial ischemia-reperfusion injury are asymptomatic myocardial ischemia, angina pectoris, myocardial infarction, ischemic cardiomyopathy and/or sudden death.

Preferably, myocardial ischemia and myocardial ischemia-reperfusion injury also include myocardial ischemia and myocardial ischemia-reperfusion injury caused by cardiac arrest and resuscitation due to treatment needs.

Further preferably, myocardial ischemia and myocardial ischemia-reperfusion injury also include myocardial ischemia and myocardial ischemia-reperfusion injury caused by cardiac valve replacement.

In the above application of the present invention, 20(S)-protopanaxadiol is a 20(S)-protopanaxadiol formulation consisting of 20(S)-protopanaxadiol and a pharmaceutically acceptable carrier or adjuvant.

The 20(S)-protopanaxadiol preparation is an injection, a tablet, a capsule, a solution (oral), a gas (powder) spray, a patch, a granule, a sublingual tablet or a pill.

The advantages of the invention are:

1. The prior art discloses that the 20(S)-proto-ginsengdiol group (PQDS) is isolated and purified from the total saponins of Panaxquinquefolium L. leaves of the genus Panaxacion quinquefolium L., mainly containing the ginsengdiol group saponin Rb. Rb ₂ , Rb ₃ , Rd monomer components, combined with other drugs for the treatment of myocardial ischemia. The structure of each monomer is as follows:

Ginsenoside Rd Ginsenoside Rbl

Ginsenoside Rb3 Ginsenoside Rb2

Compared with the prior art, the 20(S)-protopanaxadiol studied by the inventors is an in vivo metabolite of the diol group ginsenoside, which is derived from the source of the prior art material and differs in structure.

2. Through pharmacodynamic studies, it was found that 20(S)-protopanaxadiol can reduce myocardial damage caused by ischemia and ischemia-reperfusion, reduce the infarct area and myocardial necrosis related enzymes, and make the electrocardiogram J point displacement Decrease to provide a basis for the 20(S)-protopanaxadiol formulation or composition for ischemic heart disease.

3, cardiovascular disease treatment drugs are currently prone to rash, bleeding, arrhythmia, headache, vertigo, etc., prone to drug resistance and dependence. The 20(S)-protopanaxadiol is derived from plant raw materials, has a simple production process and low cost, and has the advantages of small side effects, safety and reliability compared with other drugs for treating cardiovascular diseases. Therefore, it can be used as one of the drugs for treating cardiovascular diseases.

4, through experiments we found that 20 (S) - protopanaxadiol derivatives for the pre

Bloody heart disease also shows good activity. DRAWINGS

Figure 1: 20(S)-proto-ginseng, treated in vitro cultured myocardium Comparison of the protective effects of cells. The results of this experiment indicate that PPD protects cardiomyocytes significantly better than ginsenoside Rbl. detailed description

The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.

Experimental Example 1: Effect of Hydrogen Peroxide Treatment on Cardiomyocytes Cultured in Vitro

In order to investigate the myocardial protective function of the metabolite 20 (S)-protopanaxadiol saponin (PPD) of the original ginsengdiol saponin, the main diol saponin Rbl in the original ginseng diol saponin group was used to compare PPD. And the protective effect of Rbl on hydrogen peroxide-treated in vitro cultured cardiomyocytes.

1. Test materials

1.1 Test sample: 20(S)-protopanaxadiol (PPD), Rbl is provided by Shanghai Traditional Chinese Medicine Innovation Research Center;

1.2 Experimental equipment:

Clean Workbench, Shanghai Dianshan Lake Purification Equipment Factory;

Constant temperature C0 ₂ incubator, Forma, USA;

Enzyme-linked immunosorbent assay, BioTek, USA;

Inverted biological microscope, Chongqing optical instrument;

Bench-top constant temperature shaker, Taicang 巿 science and education equipment factory.

1.3 Experimental reagents: DMEM medium (GIBCO), trypsin (GIBCO) fetal bovine serum (GIBCO), MTT (Sino-A-Biotel), DMSO (National Pharmaceutical Group Chemical Reagent Co., Ltd.), DMSO (Sigma); hydrogen peroxide (Zhongguo Group Chemical Reagent Co., Ltd.).

1.4 Cell line: The cell line was provided by the Chinese Academy of Sciences cells.

H9C2 cells, cultured in high glucose DMEM medium, containing 15% calf serum, 37 ° C, 5%

C0 ₂ .

2. Experimental method:

The protective effect of PPD and Rbl against hydrogen peroxide damage was studied in vitro cultured H9C2 cells, and IC ₅ was compared. value.

2.1 Take a bottle of cells in good condition in the exponential growth phase and make a cell suspension.

2.2 Cell count, and dilute the cell density to lxlO ⁵ / ml. 2.3 The cell suspension was inoculated on a 96-well plate, ΙΟΟμΙ/well, and cultured in a constant temperature C0 ₂ incubator.

2.4 Add the above test compounds separately, and set a blank control. The final concentration of the compound is 0.1, 0.5, 1 , 2, 5, ΙΟ μΜ, and culture at each concentration of 3 replicate wells. 2.5 Continue to add hydrogen peroxide, each well ΙΟμΙ, the final concentration is ΙΟΟ μΜ, culture in the incubator. 2.6 配 Use PBS to prepare 5mg/ml solution, add MTT to 96-well plate, ΙΟμΙ/well, react for 4 hours in the incubator, then aspirate the supernatant, add PBS 150μ1/well, continue incubation, and dissolve the precipitate.

2.7 The absorbance of each well was measured by an enzyme-linked immunosorbent assay at a wavelength of 570 nm, and the cell growth inhibition rate and protective effect (reversal rate) were calculated.

Cell growth inhibition rate % = (negative control group OD value - treatment group OD value) / (negative control group OD value - blank group OD value) xl 00%

2.8 Each compound was repeated three times.

3. The results are shown in Figure 1:

It can be seen from Figure 1 that 20 (S)-protopanaxadiol (PPD) protects the myocardium significantly stronger than the original ginseng diol saponin Rbl.

Experimental Example 2: Effects on myocardial ischemia and ischemia-reperfusion injury models

To further confirm the effect of 20(S)-protopanaxadiol on myocardial protection, the following example was the pharmacological efficacy of 20(S)-protopanaxadiol on animal models of myocardial ischemia and ischemia-reperfusion injury.

1. Test materials

1.1 Test sample

20(S)-proto-ginsengdiol (PPD), provided by Shanghai Research Institute of Traditional Chinese Medicine; 20(S)-protocanthodiol is formulated into a suspension according to the following method: Weigh 100mg sample, add 10ml 0.5% CMC -Na grinding, formulated into a 10mg/ml suspension

1.2 Positive control sample

Name: Nifedipine tablets, provided by Shanghai Pharmaceutical (Group) Co., Ltd. Xinyi Pharmaceutical General Factory, the specifications are: lOmg/tablet, batch number: Chinese medicine standard H31021222; traits: film-coated tablets; storage method: storage at room temperature;

Preparation: After milling, add 0.5% CMC-Na to prepare a suspension with a content of 2mg/ml.

1.3 Other drugs Ulatan, batch number HG 22-771-68, Caoyang No. 2 Middle School Chemical Plant, formulated with 25% solution of normal saline.

2. Test animals

SD rats, male and female, weight: 220-250 g, purchased from Shanghai Slack Laboratory Animal Responsibility Co., Ltd.; Certificate No.: SCXK (Shanghai) 2002-0010

Feeding conditions: SPF-level rat experimental breeding room, temperature: 23 ± 1 °C, humidity: 40 ~ 70%, light: 12 hours alternating light and dark.

Drinking water: filtered water, free to drink

Feed: Rat whole-nutrient pellet feed, Songjiang pier test animal breeding field

3, test equipment

MP 150 systems, ECG100C amplifiers, BIOPAC systems Inc., AcqKnowledge Ver 3.9.0 processing software;

722 grating spectrophotometer, Shanghai Third Analytical Instrument Factory;

ALC-V8B animal respirator, Shanghai Alcott Biotechnology Co., Ltd.

4, the kit

NBT stain, batch number: 20071101, produced by Shanghai Qianjin Chemical Reagent Factory;

Lactate dehydrogenase (LDH) test kit, dinitrophenyl phthalate coloration;

Creatine kinase (CK) test kit, phosphomolybdic acid method;

The above test boxes are all produced by Nanjing Jiancheng Technology Co., Ltd.

5, experimental grouping

5.1 Myocardial ischemia: (9 groups)

Sham operation group: intraperitoneal injection of NS 0.5ml/100g;

Model group: intraperitoneal injection of NS 0.5 ml/100g;

The experimental group: 20(S)-proto-ginsengdiol group and 20(S)-protopanaxadiol high-dose group (referred to as PPD group and PPD high-dose group), respectively, intraperitoneal injection of 25mg/kg/day and 50mg/kg/曰

Positive control group: Nifedipine was intragastrically administered at a dose of 10 mg/kg.

The above drugs were administered in addition to nifedipine in accordance with the administration volume of 0.5 ml/100 g. 5.2 ischemia reperfusion (five groups)

Sham operation group: intraperitoneal injection of NS 0.5ml/100g;

Model group: intraperitoneal injection of NS 0.5 ml/100g;

Positive control group: Nifedipine, administered by intragastric administration, at a dose of 10 mg/kg.

The above drugs were administered in addition to nifedipine in accordance with the administration volume of 0.5 ml/100 g.

5.3 administration time

The rats were administered continuously for 7 days before the test, once a day; the last dose of each group of myocardial ischemia was 30 minutes before anesthesia ligation; the groups of ischemia-reperfusion were administered once 30 minutes before anesthesia ligation, and once again during reperfusion.

6, experimental methods

6.1 Test procedure

Animals were started 7 days before the test, once daily, for 7 days. After 30 minutes of the last administration on the day of the test, anesthesia was given by intraperitoneal injection of urethane 1.2 g/kg, fixed in the supine position, inserted into the tracheal cannula, connected to the ventilator, and needled into the limbs with a needle electrode to measure the II lead electrocardiogram, left 3 - 4 open the chest between the intercostals, expose the heart, lift the pericardium with ophthalmology, carefully tear open, use (3*6, 3/8) round needle, 00000 silk thread under the left atrial appendage.

In the myocardial ischemia group (except the sham operation group), the left coronary artery was ligated in the arterial cone and the coronary sulcus, and then the thoracic cavity was closed by suturing. The sham operation group only threaded without ligation, immediately timed, closed the chest, and removed the ventilator to resume spontaneous breathing.

The ischemia-reperfusion group (except the sham operation group) was threaded under the left front technique with a non-invasive suture needle. The two ends of the line passed through a 1.5 cm long 1.5 mm polyethylene tube. After 3 minutes, the suture was tightened and pushed out. The polyethylene tube was used to block the left artery of the coronary artery, immediately timed, closed the chest, and the ventilator was removed to restore spontaneous breathing. After 1 hour of ischemia, the blood supply was restored for reperfusion and re-administered after reperfusion. The animals were sacrificed 3 hours after ligation, and the abdominal aorta was sputum blood. The LDH and CK indexes were measured by centrifugation, and the effects of the test samples on myocardial changes induced by myocardial ischemia were observed. Taking the heart for histology (change in infarct area) on the recorded electrocardiogram: 10, 20, 30, and 60 minutes after ligation, 15 after reperfusion, 30 45 60 and 120 min ECG ST or J height, and statistical analysis of the absolute value of the change. Changes in T-wave and J-point of electrocardiogram in rats; myocardial infarct size in rats; serum creatine kinase (CK) and lactate dehydrogenase (LDH).

7. Experimental results:

7.1 Effects on infarct size: Results are shown in Table 1

Table 1: Effect on myocardial infarct size in rats with permanent ischemia and ischemia-reperfusion ( ^x s)

Note: Compared with sham group, *** P <0.001; comparison with the control group ^# P ^{<0.05, ## P <0.01,} ### P <0.001 The results in Table 1 show that:

The infarct level of the negative control group was significantly increased compared with the sham operation group (PO.001);

Compared with the negative control group, the intraperitoneal administration of 20(S)-protopanaxadiol 50 mg/kg significantly reduced the area of myocardial infarction-induced myocardial infarction (p<0.05), and the positive control nifedipine 10 mg/kg. A significant decrease in infarction was also observed (p < 0.01).

Compared with the negative control group, intraperitoneal injection of 20(S)-protopanaxadiol at 25 mg/kg and 50 mg/kg reduced the area of myocardial infarction induced by myocardial ischemia-reperfusion (p<0.05 and p). <0.01), the infarct size of nifedipine was significantly different (p<0.01).

7.2 Effect on serum enzyme content: See Table 2 3

Table 2: Effect on serum LDH activity in rats with permanent ischemia and ischemia-reperfusion (s)

Note: Compared with sham group, *** P <0.001; compared with the negative control group, ^{^{# P <0.05, ## P <}} 0.01, ### P <0.001

Note: Compared with sham group, *** P <0.001; comparison with the control group ^# P ^{<0.05, ## P <0.01,} ### P <0.001 The results are shown in Table 23:

Consistent with the histological test results, the serum enzyme levels associated with myocardial necrosis were significantly increased in the negative control group, and the LDH and CK activities were significantly different from those in the sham-operated group (p<0.01). Myocardial ischemia and deficiency The activities of LDH and CK in the blood reperfusion group 20(S)-pro-ginsengdiol group were significantly lower than those in the negative control group (p<0.05). The positive drug nifedipine also significantly reduced the LDH and CK values in the serum of myocardial ischemia-reperfusion injury, which was not significantly different from the 20(S)-pro-ginsengdiol group.

7.3 Effect on ST segment or J point on ECG:

7.3.1 Effect of J-point displacement in myocardial ischemic rats: See Table 4-1

Table 4-1: Effect on J-point displacement in rats with myocardial ischemia (士s)

Note: Compared with the sham operation group, **P<0.01, *P<0.05

The results from Table 4-1 show:

Myocardial ischemia: The data of ST segment or J point change on the II lead electrocardiogram of the rats showed that the J point of the negative control group rapidly increased or decreased after myocardial ischemia, reached the highest at 20 minutes, and then gradually decreased, which was different from the sham operation group. Significantly; there was no significant difference between the drop of J point in each drug-administered group and the negative control group.

7.3.2 Effect on J-point displacement in rats with ischemia-reperfusion: See Table 4-2

Table 4-2: Effect on J-point displacement in rats with ischemia-reperfusion ( ^x ± s)

J point displacement (mV, ^±s)

Group ligation reperfusion

lOmin 20min 30min 60min 15 min 30min 60min 90min 120min

P month control group 0.19±0.24 OJSiO.lS** 0.19±0.13* 0.12±0.08 0.13±0.07 0.15±0.08 PPD group 0.13±0.12 0.17±0.17 0.26±0.14 0.27±0.21 0.14±0.15 0.11±0.09 0.07±0.05 0.09±0.05 0.08±0.05

PPD high dose group 0.16±0.13 0.19±0.09 ^# 0.19±0.07 ^{# #} 0.24±0.12 ^{# #} 0.14±0.08 0.10±0.05 0.11±0.07 0.10±0.05 0.07±0.05 Nifedipine group 0.09±0.08 0.11±0.07 ^{# #} 0.15± 0.08 ^{# #} 0.15±0.08 ^{# #} 0.07±0.05 ^# 0.09±0.09 0.08±0.08 0.07±0.04 0.06±0.05 Note: Compared with the sham operation group, **P<0.01, *P<0.05; compared with the negative control group ^# P < 0.05, ^{# #} P < 0.01. Table 4-2 shows: After ligation in the ischemia-reperfusion group, the ST segment or J point of the negative control group increased rapidly, and the difference was higher than that of the sham operation group at 20 to 60 minutes. The difference was very significant after reperfusion. 15 minutes and 120 minutes were higher than the sham operation group, there was a significant difference; the high dose of 20(S)-pro-ginsengdiol group was administered before ligation, and the displacement of point J at 20 minutes was significantly smaller than that of the negative control group. At 60 minutes, it was still smaller than the negative control group, and the difference was significant. At the time of reperfusion, the displacement of the J point of the 20(S)-pro-ginsengdiol group decreased rapidly, but there was no significant difference with the negative control group; the positive control group of nifedipine made The displacement of point J at 10-60 minutes after ischemia and 15 minutes after reperfusion decreased significantly compared with the negative control group.

There was no significant difference in the incidence of arrhythmias in each group of animals.

8. Conclusion

Intraperitoneal administration of 20(S)-protopanaxadiol can reduce myocardial damage caused by ischemia and ischemia-reperfusion, reduce infarct size, decrease enzymatic index related to myocardial necrosis, and decrease electrocardiogram J point displacement . Its effect is slightly weaker than that of 10 mg/kg of nifedipine.

The treatment of cardiovascular diseases is currently prone to rash, bleeding, arrhythmia, headache, dizziness, etc., which are prone to drug resistance and dependence. The 20(S)-protopanaxadiol is derived from plant raw materials, has a simple production process and low cost, and has the advantages of small side effects, safety and reliability compared with other drugs for treating cardiovascular diseases. Therefore, it can be used as one of the drugs for treating cardiovascular diseases.

Example 1: Preparation method of 20(S)-protopanaxadiol

1. 5.0 kg of notoginseng, add n-butanol and sodium ethoxide, put in the reaction kettle, stir, pass oxygen, keep bubbles in the bubbling continuously, heat up, react for 72 hours; add n-butanol after cooling The saturated water was washed twice, and the aqueous layer was separated. The n-butanol was concentrated to dryness under reduced pressure, and n-butanol was recovered. The residue was stirred with water, extracted three times with ethyl acetate, and the aqueous layer was discarded. Washed twice with saturated brine and separated into water;

2. Anhydrous sodium sulfate was added to the ethyl acetate layer, dried, and the ethyl acetate layer was concentrated to dryness under reduced pressure to yield ethyl acetate.

3. Add ethyl acetate to the crude product, mix it, place it on a silica gel column, perform column chromatography, and then use petroleum. Ether (60-90 ° C) - ethyl acetate (3: 1) 200 liters and petroleum ether (60-90 ° C) - ethyl acetate (1:1) 500 liters eluted, the eluent was collected to TLC The components of each eluate were monitored, and the one-component eluate was concentrated under reduced pressure and dried in vacuo to give 20 (S)-original ginseng diol.

Example 2: 20(S)-protopanaxadiol oral solution

Tween-80 20g, dissolved in water, add 20g (S)-protopanaxadiol 10g, grind to make colostrum, add water to 1000ml, that is, get oral liquid.

Example 3: 20(S)-protopanaxadiol capsule

20(S)-original ginseng diol 10g, add lactose 300g, mix well, use 70% ethanol as binder, granulate, and put into capsules, that is, capsules, each containing 20(S)-former ginseng II 50 mg of alcohol.

Example 4: 20(S)-protopanaxdiol tablets

20(S)-original ginseng diol 10g, add lactose 300g, mix, use 70% ethanol as binder, granulate, dry, add magnesium stearate, tablet, get tablets, each tablet contains 20 (S) - Protopanaxadiol 50 mg. Example 5: 20(S)-protopanaxadiol injection

20(S)-original ginseng diol 10g, sodium chloride 100g, 1000ml water for injection is dissolved in a rare tank, stirred, cooled, decolorized, filtered, sterilized, sealed, and the injection is obtained. Although the present invention has been described in detail above with the aid of the general description, the specific embodiments and the examples of the present invention, it will be obvious to those skilled in the art . Therefore, such modifications or improvements made without departing from the spirit of the invention are intended to be within the scope of the invention. Industrial applicability

The invention discloses a new use of 20(S)-protopanaxadiol, mainly for preventing and treating ischemic heart disease, in particular coronary heart disease, coronary atherosclerotic heart disease, myocardial ischemia And diseases such as myocardial ischemia-reperfusion injury, cardiovascular disease treatment drugs are currently prone to rash, bleeding, arrhythmia, headache, dizziness, etc., prone to drug resistance and dependence. The 20(S)-protopanaxadiol is derived from plant materials, has a simple production process and low cost, and has the advantages of small side effects, safety and reliability as compared with other drugs for treating cardiovascular diseases. Therefore, it can be used as a treatment for cardiovascular diseases

Claims

1. The use of 20(S)-protopanaxadiol in the preparation of a medicament for preventing and treating ischemic heart disease.

2. Use according to claim 1, characterized in that the ischemic heart disease is coronary heart disease or coronary atherosclerotic heart disease.

3. Use according to claim 1 or 2, characterized in that the ischemic heart disease is selected from the group consisting of myocardial ischemia and myocardial ischemia-reperfusion injury.

4. Use according to claim 3, characterized in that myocardial ischemia and myocardial ischemia reperfusion injury are asymptomatic myocardial ischemia, angina pectoris, myocardial infarction, ischemic cardiomyopathy and/or sudden death.

6. The use according to claim 3, wherein the myocardial ischemia and myocardial ischemia-reperfusion injury further comprises myocardial ischemia and myocardial ischemia caused by cardiac arrest and resuscitation due to treatment needs. Perfusion damage.

7. The use according to claim 3, wherein the myocardial ischemia and myocardial ischemia reperfusion injury further comprises myocardial ischemia and myocardial ischemia-reperfusion injury caused by cardiac valve replacement.

The use according to any one of claims 1 to 7, wherein the 20(S)-protopanaxadiol is composed of 20(S)-protopanaxadiol and a pharmaceutically acceptable carrier or adjuvant. 20(S)-protopanaxadiol formulation.

9. The use according to claim 8, wherein the 20(S)-protopanaxadiol preparation is selected from the group consisting of an injection, a tablet, a capsule, an oral solution, an aerosol, a patch, a granule, and a sublingual Tablet or drop pills