Ginseng-aconitum carmichaeli heart-strengthening pill with reduced toxic and side effects and preparation method and application thereof

Abstract

The invention belongs to the technical field of Chinese patent medicine preparations, and particularly relates to a ginseng-radix aconiti lateralis praeparata heart-strengthening pill with reduced toxic and side effects and a preparation method and application thereof. The ginseng-radix aconiti lateralis preparata heart-strengthening pill is prepared from the following traditional Chinese medicine raw materials: ginseng, radix aconiti lateralis preparata, white mulberry root-bark, polyporus umbellatus, semen lepidii and rheum officinale. The ginseng-radix aconiti lateralis praeparata heart-strengthening pill has a good detoxification effect on radix aconiti lateralis praeparata, meanwhile, the effects of tonifying qi, supporting yang, strengthening the heart and inducing diuresis of the ginseng-radix aconiti lateralis praeparata heart-strengthening pill can be improved, and the problems that in clinical application, due to long-term taking of the ginseng-radix aconiti lateralis praeparata heart-strengthening pill by a patient, the medicine side effect is high, and the safety is low are effectively solved.

Description

Technical Field

[0001] The invention belongs to the technical field of Chinese patent medicine preparations, and particularly relates to a Shenfu Qiangxin pill with reduced toxic and side effects, and a preparation method and use thereof. Background Art

[0002] "Shenfu Qiangxin Pills" are derived from the Shenfu Decoction in "Furen Liangfang" and the Jijiaolihuang Pills in "Jinkui Yaolue". Shenfu Qiangxin Pills are made of ginseng, processed aconite, mulberry bark, umbellate, scutellaria baicalensis, and rhubarb, which are crushed into fine powder, sieved, and mixed. 130-150g of refined honey is added to every 100g of powder to make large honey pills. Shenfu Qiangxin Pills have the effects of invigorating qi and yang, strengthening the heart and promoting diuresis. They are suitable for the symptoms of palpitations, shortness of breath, chest tightness and shortness of breath, and facial and limb edema caused by chronic heart failure, which belongs to the patients with heart and kidney yang deficiency.

[0003] However, the processed aconite in Shenfu Qiangxin Pill contains a large amount of diterpenoid alkaloids, which can be divided into three types: diester type, monoester type or alcoholamine type alkaloids. Diester type alkaloids (e.g., aconitine) are the main toxic components, while the toxicity of monoester type alkaloids is only 1 / 200 of that of diester type alkaloids. Aconitine is a potent neurotoxin that can inhibit nerve conduction and respiratory centers, leading to respiratory failure and death. In view of the toxicity of diester type alkaloids, the content of aconitine is strictly limited in the current Shenfu Qiangxin Pill standard. However, since processed aconite is used as a raw material in Shenfu Qiangxin Pill and the dosage is large, although the detoxification effect of ginseng on diester type alkaloids is taken into account in the formulation, in clinical application, the diseases treated by Shenfu Qiangxin Pill require long-term medication, which often leads to side effects in patients during the medication process. Therefore, when taking Shenfu Qiangxin Pill, it is necessary to strictly follow the doctor's instructions and the usage and dosage in the instructions, and do not take it in excess or for a long time. If symptoms of poisoning such as nausea, vomiting, dizziness, palpitations, and difficulty breathing occur, the medication should be stopped immediately and medical attention should be sought.

[0004] In recent years, in order to improve the safety of Shenfu Qiangxin Pills, the inventors have conducted in-depth research on how to reduce the toxicity of processed aconite based on the detoxification mechanism of ginseng, and unexpectedly found that adding ginseng polypeptides to the Chinese patent medicine preparation can significantly inhibit the body's absorption of diester alkaloids and promote their metabolism, thereby significantly reducing the toxic and side effects of Shenfu Qiangxin Pills.

[0005] At present, there are no reports on its use. Summary of the invention

[0006] In order to further reduce the potential risks of the Shenfu Qiangxin Pill currently used in clinical practice and to further improve the safety of medication, the present invention conducts secondary development on this traditional Chinese patent medicine and provides a Shenfu Qiangxin Pill with reduced toxic and side effects, as well as a preparation method and use thereof.

[0007] Specifically, the present invention is realized through the following technical solutions:

[0008] In the first aspect, the present invention provides a Shenfu Qiangxin Pill with reduced toxic and side effects, which is made from the following Chinese medicinal raw materials: ginseng, processed aconite root, mulberry bark, Poria cocos, scutellaria baicalensis and rhubarb. In the preparation method of the Shenfu Qiangxin Pill, the processed aconite root is first made into enteric-coated microspheres, and then ginseng polypeptide enteric-coated microspheres are added, and then the Shenfu Qiangxin Pill is prepared together with other raw materials.

[0009] As an optional method, in the above-mentioned Shenfu Qiangxin Pill, the Shenfu Qiangxin Pill is made of the following Chinese medicinal raw materials in parts by weight: 150-250 parts of ginseng, 120-200 parts of processed aconite, 150-250 parts of mulberry bark, 225-375 parts of Poria, 180-300 parts of Lemongrass seeds and 90-150 parts of rhubarb.

[0010] As an optional method, in the above-mentioned Shenfu Qiangxin Pill, the Shenfu Qiangxin Pill is made of the following Chinese medicinal raw materials in parts by weight: 200 parts of ginseng, 160 parts of processed aconite, 200 parts of mulberry bark, 300 parts of Poria, 240 parts of Lemongrass seeds and 120 parts of rhubarb.

[0011] As an optional method, in the above-mentioned Shenfu Qiangxin Pill, the ginseng polypeptide is Glu-Gly-Ala-Val-Met-Leu-Phe-Arg, and the weight ratio of processed aconite to ginseng polypeptide is 16:1.

[0012] As an optional mode, in the above-mentioned Shenfu Qiangxin Pills, the ginseng polypeptide is extracted from ginseng or prepared by solid phase synthesis method.

[0013] In the second aspect, the present invention provides a preparation method of the Shenfu Qiangxin Pills described in the first aspect, the preparation method comprising the following steps: taking the above 6 medicinal materials, first making the processed aconite into enteric-coated microspheres, and then adding ginseng polypeptide enteric-coated microspheres for later use; crushing ginseng, mulberry bark, Poria, scutellaria baicalensis and rhubarb into fine powder, mixing with the above enteric-coated microspheres, sieving, mixing, adding refined honey, and making large honey pills.

[0014] As an optional manner, in the above-mentioned preparation method, the preparation method of enteric-coated microspheres containing processed aconite root is as follows: processed aconite root is crushed into 80 mesh fine powder, and then mixed with appropriate amounts of microcrystalline cellulose and magnesium lauryl sulfate, extruded and dried to obtain a sphere core, appropriate amounts of cross-linked polyvinylpyrrolidone and chitosan are mixed to prepare a coating liquid, the coating liquid is evenly sprayed on the sphere core in a coating pan, and granules are obtained after drying, acrylic resin is prepared into a coating liquid, the coating liquid is sprayed on the granules in a coating pan, and the enteric-coated microspheres are obtained after drying.

[0015] Preferably, the weight ratio of processed aconite root, microcrystalline cellulose and magnesium lauryl sulfate is 2:3:1. The weight ratio of cross-linked polyvinylpyrrolidone and chitosan is 1:8.

[0016] As an optional manner, in the above-mentioned preparation method, the preparation method of ginseng polypeptide enteric-coated microspheres is as follows: ginseng polypeptide is mixed with appropriate amounts of microcrystalline cellulose and mannitol to prepare an aqueous solution, which is then freeze-dried, the obtained powder is extruded to obtain a spherical core, appropriate amounts of cross-linked polyvinylpyrrolidone, chitosan and citric acid fatty acid glyceride are mixed to prepare a coating liquid, the coating liquid is evenly sprayed on the spherical core in a coating pan, and particles are obtained after drying, acrylic resin is prepared into a coating liquid, the coating liquid is sprayed on the particles in a coating pan, and the enteric-coated microspheres are obtained after drying.

[0017] Preferably, the weight ratio of ginseng polypeptide, microcrystalline cellulose and mannitol is 3:90:7. The weight ratio of cross-linked polyvinylpyrrolidone, chitosan and citric acid fatty acid glyceride is 2:5:1.

[0018] In the third aspect, the present invention provides use of the Shenfu Qiangxin Pills described in the first aspect or the Shenfu Qiangxin Pills prepared by the preparation method described in the second aspect in preparing medicines having the effects of invigorating qi and yang, strengthening the heart and promoting diuresis.

[0019] As an optional mode, in the above-mentioned use, the drug is used for the symptoms of palpitations, shortness of breath, chest tightness and shortness of breath, and facial and limb edema caused by chronic heart failure, which belongs to the patients with heart and kidney yang deficiency.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The Shenfu Qiangxin Pill of the present invention is an upgraded product prepared by improving the preparation method of Shenfu Qiangxin Pill. The Shenfu Qiangxin Pill of the present invention has a good detoxification effect on processed aconite, and can also increase the efficacy of Shenfu Qiangxin Pill in invigorating qi and yang, strengthening the heart and promoting diuresis, and effectively solves the problem of strong drug side effects and low safety caused by long-term use of Shenfu Qiangxin Pill by patients in clinical applications. DETAILED DESCRIPTION

[0022] The present invention will be further described with reference to specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the scope of the present invention.

[0023] If no specific techniques or conditions are specified in the examples, the techniques or conditions described in the literature in the field or the product instructions are used. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0024] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0025] Preparation Example:

[0026] Example:

[0027] The Shenfu Qiangxin Pill with reduced toxic side effects is made from the following Chinese medicinal ingredients: 20g of ginseng, 16g of processed aconite root, 20g of mulberry bark, 30g of Poria cocos, 24g of scutellaria baicalensis fruit and 12g of rhubarb.

[0028] First, the processed aconite root is made into enteric-coated microspheres, and then the ginseng polypeptide enteric-coated microspheres are added for later use; ginseng, mulberry bark, umbellate, scutellaria baicalensis and rhubarb are crushed into fine powder, mixed with the above enteric-coated microspheres, sieved, mixed, and refined honey is added, and 130-150g of refined honey is added to every 100g of powder to make large honey pills. In the above-mentioned ginseng-aconite heart-strengthening pills, the ginseng polypeptide is Glu-Gly-Ala-Val-Met-Leu-Phe-Arg, and the weight ratio of the processed aconite root to the ginseng polypeptide is 16:1.

[0029] The preparation method of enteric-coated microspheres containing processed aconite is as follows: processed aconite is crushed into 80 mesh fine powder, mixed with appropriate amount of microcrystalline cellulose and magnesium lauryl sulfate, extruded and dried to obtain a ball core, appropriate amount of cross-linked polyvinylpyrrolidone and chitosan are mixed to prepare a coating liquid, the coating liquid is evenly sprayed on the ball core in a coating pan, and granules are obtained after drying, acrylic resin is prepared into a coating liquid, the coating liquid is sprayed on the granules in a coating pan, and the enteric-coated microspheres are obtained after drying. Among them, the weight ratio of processed aconite, microcrystalline cellulose, and magnesium lauryl sulfate is 2:3:1. The weight ratio of cross-linked polyvinylpyrrolidone and chitosan is 1:8.

[0030] The preparation method of ginseng polypeptide enteric microspheres is as follows: ginseng polypeptide is mixed with appropriate amounts of microcrystalline cellulose and mannitol to prepare an aqueous solution, which is then freeze-dried, the obtained powder is extruded to obtain a spherical core, an appropriate amount of cross-linked polyvinylpyrrolidone, chitosan and citric acid fatty acid glyceride are mixed to prepare a coating liquid, the coating liquid is evenly sprayed on the spherical core in a coating pan, and the particles are obtained after drying, acrylic resin is prepared into a coating liquid, the coating liquid is sprayed on the particles in a coating pan, and the enteric microspheres are obtained after drying. Among them, the weight ratio of ginseng polypeptide, microcrystalline cellulose and mannitol is 3:90:7. The weight ratio of cross-linked polyvinylpyrrolidone, chitosan and citric acid fatty acid glyceride is 2:5:1.

[0031] Comparative Example (commercially available Shenfu Qiangxin Pill formula):

[0032] Shenfu Qiangxin Pill is made of the following Chinese medicinal ingredients: 20g of ginseng, 16g of processed aconite root, 20g of mulberry bark, 30g of Poria cocos, 24g of scutellaria baicalensis and 12g of rhubarb.

[0033] The Shenfu Qiangxin Pill is prepared by the following method: take the above 6 medicinal materials, crush ginseng, processed aconite root, mulberry bark, Poria cocos, scutellaria baicalensis seed, and rhubarb into fine powder, sieve, and mix well, add 130-150g of refined honey to every 100g of powder to make large honey pills.

[0034] Effect embodiment:

[0035] Effect Example 1: Effect of Ginseng Peptide on the Transport Behavior of Diester Aconitine in Caco-2 Cell Model

[0036] 1.1 Main reagents:

[0037] Aconitine and aconitine were purchased from the China Food and Drug Administration with a purity of 98%. Ginseng polypeptide (Glu-Gly-Ala-Val-Met-Leu-Phe-Arg) and licorice polypeptide (Glu-Gly-Asp-Ile-Val-Lys-Ala-Pro) were solid-phase synthesized by commercial companies. Caco-2 cells were purchased from the Peking Union Medical College Cell Resource Center, and the cell passage number used in the experiment was 25-35 generations.

[0038] 1.2 Main experimental methods:

[0039] 1.2.1 Cell culture:

[0040] Caco-2 cells were cultured in DMEM high-glucose complete medium at 37°C and 5% CO. 2 When the cells reached about 80% confluence, they were subcultured at a trypsin digestion ratio of 1:3, and then the cells in the logarithmic growth phase were used for the experiment. 5 Cells / mL were seeded in 24-well culture plates, and drugs were added when the experimental conditions were reached.

[0041] 1.2.2MTT experiment:

[0042] The cells in the logarithmic phase were digested with trypsin and collected by centrifugation after termination to prepare a cell suspension. The cell count was adjusted to a concentration of 1×10 5 cells / mL, after the cell suspension is prepared, gently mix and add 100μL to each well. Place the inoculated cell culture plate in the incubator and culture for 48h. After washing the cells once with HBSS, add different concentrations of drug solution and 200μL of 1% ethanol with a volume fraction of co-solvent, and add blank HBSS solution to the control group. After the drugs acted for 3h, perform the MTT experiment and use an enzyme reader to detect the absorbance at 490nm.

[0043] 1.2.3 Determination of Caco cell alkaline phosphatase:

[0044] On the 18th day of culture, the culture medium from the brush border (AP) side and the basement membrane (BL) side were collected and alkaline phosphatase assay was performed according to the requirements of the kit (purchased from Nanjing Jiancheng Biological Research Institute).

[0045] 1.2.4 Transport experiment:

[0046] Before the experiment, each well was washed twice with 37°C HBSS solution. When studying absorption, 100 μg / mL aconitine, 100 μg / mL aconitine, aconitine + ginseng polypeptide (100 μg / mL + 100 μg / mL), aconitine + licorice polypeptide (100 μg / mL + 100 μg / mL), aconitine + ginseng polypeptide (100 μg / mL + 100 μg / mL), aconitine + licorice polypeptide (100 μg / mL + 100 μg / mL) 0.4 mL was added to the AP side of each well, 0.6 mL of HBSS solution was added to the BL side, and the wells were placed in an incubator for culture. 0.3 mL of samples were taken from the BL side at 5, 10, 15, 30, 45, 60, 90, and 150 min, and 0.3 mL of HBSS solution at the same temperature was added. When studying the efflux, 100 μg / mL aconitine, 100 μg / mL aconitine, aconitine + ginseng polypeptide (100 μg / mL + 100 μg / mL), aconitine + licorice polypeptide (100 μg / mL + 100 μg / mL), aconitine + ginseng polypeptide (100 μg / mL + 100 μg / mL), and 0.6 mL of aconitine + licorice polypeptide (100 μg / mL + 100 μg / mL) were added to the BL side of each well, and 0.4 mL of HBSS solution was added to the AP side. 0.2 mL of samples were taken from the AP side at 15, 30, 45, 60, 90, and 150 min, respectively, and 0.2 mL of HBSS solution at the same temperature was added. Subsequent operations were the same as above.

[0047] 1.2.5 Determination of the content of aconitine and aconitine:

[0048] The contents of aconitine and aconitine were determined by HPLC-MS.

[0049] 1.2.6 Statistical analysis:

[0050] All data are expressed as mean ± standard deviation. SPSS 23.0 software was used for statistical analysis, and p < 0.05 indicated significant differences. 实验组 / A 对照组 ×100%; apparent permeability coefficient P app =(dQ / dt) / (A×ρ 0 ), dQ / dt is the drug transport amount per unit time (μg / s), A is the Transwell membrane area (0.33 cm 2 , ρ 0is the initial drug concentration (μg / mL); efflux ratio (PDR) = P app (BL→AP) / P app (AP→BL). Since rehydration is required after each sampling, the drug concentration is diluted, so the cumulative transport concentration TR of the drug is required. cum (μg / L) for calibration: Cumulative transfer volume = TR cum ×V R , where ρ n( μg / mL ) is the measured value of the nth sample concentration; V n (mL) is the sampling volume of the nth sample; V R (mL) is the volume on the receiving side.

[0051] 1.3 Experimental results:

[0052] 1.3.1 Toxicity of various experimental drugs to Caco-2 cells:

[0053] The MTT method was used to detect the inhibitory effect of the test drugs on cells. The experimental results showed that at a concentration of 200 μg / mL (higher than the concentration of the test drugs used in subsequent experiments), the cell survival rate of each test drug group (aconitine, aconitine, ginseng polypeptide, and licorice polypeptide) was above 95%. This shows that the drug has no effect on the survival of Caco-2 cells at this concentration, and the transport experiment can be carried out.

[0054] 1.3.2 Alkaline phosphatase assay results:

[0055] After 18 days of culture of Caco-2 cells, alkaline phosphatase was mostly confined to the AP side, and the enzyme activity on the AP side was much greater than that on the BL side, indicating that the cell growth had formed polarity and could be used for experiments.

[0056] 1.3.3 Absorption and transport of aconitine and aconitine:

[0057] The experimental results showed that the apparent permeability coefficient (P app ) about 1×10 - 5 cm / s, and the apparent permeability coefficient from BL to AP side is about 1.5×10 -5 cm / s. It increased with the extension of incubation time within 150 min; the efflux to absorption ratio was close to 1.5, so it was speculated that the transport of aconitine and aconitine in the Caco-2 cell model was mainly passive transport.

[0058] 1.3.4 Effect of polypeptides on the transport behavior of aconitine and aconitine:

[0059] The experimental results are shown in Table 1. The experimental results show that when ginseng polypeptide (Glu-Gly-Ala-Val-Met-Leu-Phe-Arg) is used in combination with aconitine at a weight ratio of 1:1, ginseng polypeptide significantly reduces the absorption of aconitine, that is, the cumulative transport amount and permeability coefficient from the AP to the BL side are significantly reduced (p<0.01). However, the combined use of ginseng polypeptide has no significant effect on the transport of aconitine from the BL to the AP side (data not shown). However, ginseng polypeptide has no effect on the transport of aconitine from the AP to the BL side. This shows that ginseng polypeptide only has an inhibitory effect on the transport of diester-type alkaloids (aconitine), but has no effect on the transport of monoester-type alkaloids (aconitine). The inhibitory effect of ginseng polypeptide on the transport of aconitine may be the reason why it has a detoxifying effect on aconitine.

[0060] In addition, the effect of licorice polypeptide (Glu-Gly-Asp-Ile-Val-Lys-Ala-Pro) on the transport of aconitine and aconitine was also investigated. The results showed that licorice polypeptide had no significant effect on the transport of aconitine and aconitine from the AP to the BL side. This suggests that the inhibitory effect of ginseng polypeptide on the transport of aconitine from the AP to the BL side is unique to ginseng polypeptide (Glu-Gly-Ala-Val-Met-Leu-Phe-Arg).

[0061] Table 1: Effects of peptides on the transport behavior of aconitine and aconitine (from AP to BL side)

[0062] Group Cumulative transport amount / ng <![CDATA[P app ×10 -6 cm / s]]> Aconitine 3125.36±82.19 11.29±1.03 Aconitine + Ginseng Peptide <![CDATA[2374.25±76.41 ** ]]> <![CDATA[7.63±0.65 ** ]]> Aconitine + Licorice Peptide 3078.97±84.65 10.87±0.97 Aconitine 3218.13±77.26 10.31±0.94 Aconitine + Ginseng polypeptide 3184.32±81.43 9.85±0.82 Aconitine + Licorice Peptide 3065.76±79.24 9.92±0.89

[0063] Note: Compared with the aconitine group, ** p<0.01.

[0064] Effect Example 2: Effect of Shenfu Qiangxin Pills (Example) and Shenfu Qiangxin Pills (Comparative Example) on Adriamycin-induced Comparison of therapeutic effects on chronic heart failure in rats

[0065] 2.1 Experimental drugs:

[0066] The examples (Shenfu Qiangxin Pills of the present invention) and comparative examples (Shenfu Qiangxin Pills) prepared in the above preparation examples section.

[0067] 2.2 Experimental Animals:

[0068] 50 SPF grade SD male rats, 180±220 g, were purchased from Liaoning Changsheng Biotechnology Co., Ltd. After the rats were adaptively raised for 7 days, 10 rats were randomly selected as the blank group.

[0069] The remaining rats were intraperitoneally injected with doxorubicin to induce a chronic heart failure model. Doxorubicin for injection (doxorubicin hydrochloride) was prepared into a 0.15 mg / mL solution with normal saline, and intraperitoneally injected at a dose of 1.5 mg / kg, i.e. 1 mL / 100 g, twice a week, on Mondays and Thursdays, with an interval of 3 days between each administration, for a total of 7 weeks, and then stopped for 2 weeks. The cumulative dosage of doxorubicin reached 21 mg / kg.

[0070] After the last injection, an echocardiogram was performed. The rats were anesthetized by intraperitoneal injection of 5% chloral hydrate 0.5mL / 100g and fixed in a supine position on a constant temperature experimental table for rats. The MyLabFive color echocardiogram diagnostic instrument was used, and the smallest probe was coated with coupling agent to detect the size and function of the rats' hearts. The detection indicators included: left ventricular end-systolic diameter (LVDs), left ventricular end-diastolic diameter (LVDd), ejection fraction (EF) and left ventricular shortening fraction (FS). Each rat was measured 3 times, and the average value was taken. The EF value was more than 10% lower than the EF value of the normal group. There was a significant difference between the groups, indicating that the model was successfully prepared. The rats with successful models were screened out and randomly divided into a model group, an embodiment group and a comparative group, with 10 mice in each group.

[0071] 2.3 Experimental methods:

[0072] After the rats with successful models were screened and grouped, the Example group and the Comparative Example group were gavaged with the corresponding pellets and the suspension obtained by adding purified water, the gavage volume was 1 mL / 100 g body weight, and the gavage amount was 3.0 g crude drug / Kg body weight, the Model group was gavaged with 1 mL / 100 g body weight of purified water, and the Blank group was raised normally. The gavage was continued for 2 weeks, once a day.

[0073] 24 hours after the last administration, rats were anesthetized by intraperitoneal injection of 5% chloral hydrate 0.5mL / 100g and fixed on the rat constant temperature laboratory table in supine position. After chest hair removal and skin preparation, MyLabFive color echocardiography diagnostic instrument was used to detect the cardiac function of rats with the smallest probe coated with coupling agent. The left ventricular end-systolic diameter (LVDs), left ventricular end-diastolic diameter (LVDd), ejection fraction (EF) and left ventricular shortening fraction (FS) were measured continuously for 3 cardiac cycles, and the average values ​​were taken.

[0074] After the cardiac color ultrasound imaging test, the abdominal skin and muscle tissue were cut in turn to expose the abdominal aorta, and blood was collected by needle puncture, kept at 4°C for 2 hours, centrifuged at 3000 rpm for 15 minutes, and serum was separated and packaged, and immediately stored at -20°C and -70°C the next day. ELISA method was used to detect brain natriuretic peptide (BNP) content and lactate dehydrogenase (LDH) activity.

[0075] 2.4 Statistical analysis methods:

[0076] GraphPad Prism 8.0 was used for statistical analysis. One-Way ANOVA was used to compare the means among multiple groups, and p < 0.05 indicated statistically significant differences.

[0077] 2.5 Experimental results:

[0078] 2.5.1 Cardiac function test results:

[0079] The results of cardiac function test are shown in Table 2. The experimental results showed that compared with the blank group, the LVDs and LVDd of the rats in the model group were significantly increased ( * p<0.05, ** p<0.01, EF and FS were significantly decreased ( ** p<0.01), which indicates that intraperitoneal injection of doxorubicin can lead to decreased cardiac function and reduced myocardial contractility in experimental animals.

[0080] Compared with the model group, the Shenfu Qiangxin Pills prepared by the method of the present invention and the commercial Shenfu Qiangxin Pills can improve the cardiac function of the model group animals to varying degrees, and the effect of the Shenfu Qiangxin Pills prepared by the method of the present invention is better than that of the commercial Shenfu Qiangxin Pills ( # p<0.05, ## p<0.01).

[0081] Table 2: Effects of the Example Group (Shenfu Qiangxin Pills of the present invention) and the Comparative Example Group (Shenfu Qiangxin Pills) on the Results of Cardiac Function Tests in Rats with Chronic Heart Failure Induced by Adriamycin

[0082] Group LVDs(mm) LVDd(mm) EF(%) FS(%) Blank group 1.78±0.25 4.58±0.53 94.13±3.12 61.17±2.17 Model Group <![CDATA[3.41±0.48 ** ]]> <![CDATA[5.78±0.42 * ]]> <![CDATA[78.74±2.51 ** ]]> <![CDATA[40.62±1.48 ** ]]> Example Group <![CDATA[2.05±0.37 ## ]]> <![CDATA[4.92±0.41 # ]]> <![CDATA[86.24±2.16 # ]]> <![CDATA[50.29±3.15 ## ]]> Comparative group <![CDATA[2.74±0.31 # ]]> 5.25±0.38 81.43±3.24 <![CDATA[46.57±2.31 # ]]>

[0083] Note: Comparison between model group and blank group: * p<0.05, ** p<0.01; compared with the two drug-treated groups and the model group: # p<0.05, ## p<0.01.

[0084] 2.5.2LDH and BNP test results:

[0085] LDH is a key enzyme that regulates the conversion of pyruvate into lactate in the anaerobic glycolysis of glucose. It is usually present in the mitochondria of tissue cells such as the heart, skeletal muscle, and liver. When myocardial damage occurs, the myocardial cell membrane ruptures, and the mitochondria and cytoplasmic substances leak into the intercellular fluid and peripheral blood. BNP is a natural hormone with biological activity synthesized by myocardial cells, which is mainly expressed in the ventricles. When the left ventricle is dysfunctional, BNP is rapidly synthesized and released into the blood due to myocardial dilation.

[0086] The results of LDH and BNP detection are shown in Table 3. The experimental results showed that compared with the blank group, the LDH and BNP levels of the rats in the model group were significantly increased ( ** p<0.01), which indicated that intraperitoneal injection of doxorubicin could induce myocardial damage in experimental animals.

[0087] Compared with the model group, the Shenfu Qiangxin Pills prepared by the method of the present invention and the commercially available Shenfu Qiangxin Pills can relieve the symptoms of chronic heart failure in experimental animals to varying degrees, and the effect of the Shenfu Qiangxin Pills prepared by the method of the present invention is better than that of the commercially available Shenfu Qiangxin Pills ( # p<0.05, ## p<0.01).

[0088] Table 3: Effects of the Example Group (Shenfu Qiangxin Pills of the present invention) and the Comparative Example Group (Shenfu Qiangxin Pills) on the LDH and BNP test results of rats with heart failure model

[0089] Group LDH activity (U / L) BNP concentration (pg / mL) Blank group 12475.32±3587.18 314.18±65.37 Model Group <![CDATA[21783.16±3485.29 ** ]]> <![CDATA[425.31±87.52 ** ]]> Example Group <![CDATA[13547.48±2835.46 ## ]]> <![CDATA[344.65±59.36 ## ]]> Comparative group <![CDATA[17492.75±2941.73 # ]]> <![CDATA[385.47±51.28 ## ]]>

[0090] Note: Comparison between model group and blank group: * p<0.05, ** p<0.01; compared with the two drug-treated groups and the model group: # p<0.05, ## p<0.01.

[0091] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A Shenfu Qiangxin Pill with reduced toxic and side effects, characterized in that: The Shenfu Qiangxin Pill is made of the following Chinese medicinal raw materials: ginseng, processed aconite root, mulberry bark, Poria cocos, scutellaria baicalensis and rhubarb. In the preparation method of the Shenfu Qiangxin Pill, the processed aconite root is first made into enteric-coated microspheres, and then ginseng polypeptide enteric-coated microspheres are added, and then the Shenfu Qiangxin Pill is prepared together with other raw materials.

2. The Shenfu Qiangxin Pill according to claim 1, characterized in that: The Shenfu Qiangxin Pill is prepared from the following Chinese medicinal raw materials in parts by weight: 150-250 parts of ginseng, 120-200 parts of processed aconite root, 150-250 parts of mulberry bark, 225-375 parts of umbellatus, 180-300 parts of scutellaria baicalensis seeds and 90-150 parts of rhubarb.

3. The Shenfu Qiangxin Pill according to claim 2, characterized in that: The Shenfu Qiangxin Pill is prepared from the following Chinese medicinal raw materials in parts by weight: 200 parts of ginseng, 160 parts of processed aconite root, 200 parts of white mulberry bark, 300 parts of umbellatus, 240 parts of scutellaria baicalensis seeds and 120 parts of rhubarb.

4. The Shenfu Qiangxin Pill according to claim 1, characterized in that: The ginseng polypeptide is Glu-Gly-Ala-Val-Met-Leu-Phe-Arg, and the weight ratio of the processed aconite root to the ginseng polypeptide is 16:

1.

5. The Shenfu Qiangxin Pill according to claim 1, characterized in that: The ginseng polypeptide is extracted from ginseng or prepared by a solid phase synthesis method.

6. The method for preparing the Shenfu Qiangxin Pill according to any one of claims 1 to 5, characterized in that: The preparation method comprises the following steps: taking the above 6 medicinal materials, first preparing the processed aconite into enteric-coated microspheres, then adding ginseng polypeptide enteric-coated microspheres for later use; grinding ginseng, mulberry bark, umbellate, scutellaria baicalensis and rhubarb into fine powder, mixing with the above enteric-coated microspheres, sieving, mixing, adding refined honey, and preparing large honey pills.

7. The preparation method according to claim 6, characterized in that: The preparation method of enteric-coated microspheres containing processed aconite root is as follows: processed aconite root is crushed into 80 mesh fine powder, mixed with appropriate amount of microcrystalline cellulose and magnesium lauryl sulfate, extruded and dried to obtain a sphere core, appropriate amount of cross-linked polyvinylpyrrolidone and chitosan are mixed to prepare a coating liquid, the coating liquid is evenly sprayed on the sphere core in a coating pan, and granules are obtained after drying, acrylic resin is prepared into a coating liquid, the coating liquid is sprayed on the granules in a coating pan, and the enteric-coated microspheres are obtained after drying.

8. The preparation method according to claim 6, characterized in that: The preparation method of ginseng polypeptide enteric-coated microspheres is as follows: ginseng polypeptide is mixed with appropriate amounts of microcrystalline cellulose and mannitol to prepare an aqueous solution, which is then freeze-dried, the obtained powder is extruded to obtain a spherical core, appropriate amounts of cross-linked polyvinylpyrrolidone, chitosan and citric acid fatty acid glyceride are mixed to prepare a coating liquid, the coating liquid is evenly sprayed on the spherical core in a coating pan, and particles are obtained after drying, acrylic resin is prepared into a coating liquid, the coating liquid is sprayed on the particles in a coating pan, and the enteric-coated microspheres are obtained after drying.

9. Use of the Shenfu Qiangxin Pills according to claims 1 to 5 or the Shenfu Qiangxin Pills prepared by the preparation method according to any one of claims 6 to 8 in preparing medicines with the effects of invigorating qi and promoting yang, strengthening the heart and promoting diuresis.

10. The use according to claim 9, characterized in that: The medicine is used for the symptoms of palpitations, shortness of breath, chest tightness and shortness of breath, and facial and limb edema caused by chronic heart failure, which belongs to the patients with heart and kidney yang deficiency.