Traditional Chinese medicine composition for treating acute heart failure and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating acute heart failure and a preparation method thereof. A compound formed by combining propylene glycol monooleate and cathepsin K covers the surface of a mesoporous carbon sphere with a high specific surface area, freezing nano spray drying is performed, the obtained nano particles adsorb a repair promoting solution, and the prepared load reducing particles can target myocardial cells for treatment; after aesculus chinensis, affine cudweed and witch hazel are crushed and extracted, the obtained blood vessel expanding extract is mixed with a blood circulation promoting solution, blood vessels are effectively expanded, the blood flow volume is increased, sodium carboxymethyl cellulose is modified by hydrochloric acid and then reacts with calcium carbonate, and formed modified calcium carboxymethyl cellulose is high in disintegration performance; the anti-infection and side effect reducing agent is sprayed on the surface of the tablet for treating acute heart failure, and the prepared traditional Chinese medicine composition for treating acute heart failure has the advantages of high disintegration speed, comprehensive and efficient treatment effect, long-acting effect, strong drug stability and high bioavailability.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine composition for treating acute heart failure and a preparation method thereof. Background Art

[0002] Acute heart failure refers to a syndrome in which the heart is unable to effectively pump blood to meet the metabolic needs of tissues throughout the body due to a sudden and sharp decline in heart function, accompanied by pulmonary and systemic venous congestion. It can occur in patients who do not have heart disease, or it may be an acute exacerbation of chronic heart failure.

[0003] When patients are emotionally excited or exposed to external stimuli, their blood pressure suddenly soars. The heart cannot adapt to this drastic change in pressure, which can easily induce acute heart failure. When the amount of fluid in the body increases significantly in a short period of time, the heart needs to pump more blood, and the heart's preload rises sharply. The heart cannot effectively cope with it, which can also lead to heart failure. The treatment of acute heart failure not only focuses on emergency treatment in the acute phase, but also includes subsequent rehabilitation management. By correcting water and electrolyte disorders and acid-base imbalances, preventing thrombosis and other measures, the occurrence of complications can be reduced and the patient's recovery can be promoted. Currently, existing drug preparation technologies for the treatment of acute heart failure have the following problems: First, drug stability is insufficient, and some drugs are easily degraded during storage and transportation, affecting efficacy and safety; second, existing drugs for the treatment of acute heart failure have poor oral absorption and low bioavailability, and require frequent administration or high doses, increasing the risk of side effects; third, existing dosage forms are difficult to meet the requirements of rapid onset of effect and continuous release of effective components. Summary of the Invention

[0004] In view of the above situation, in order to overcome the defects of the prior art, the present invention provides a traditional Chinese medicine composition for treating acute heart failure and a preparation method thereof. In order to solve the problems of insufficient stability, low bioavailability, inability to quickly take effect, and inability to release long-term drugs for the existing treatment of acute heart failure, the present invention uses a mixture of load-reducing particles, vasodilator preparations, and anti-infection and side effect-reducing agents. The prepared traditional Chinese medicine composition for treating acute heart failure has high therapeutic effect, long-term effect, strong drug stability, and high bioavailability.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is as follows: the present invention provides a traditional Chinese medicine composition for treating acute heart failure, and the raw materials for preparing the traditional Chinese medicine composition for treating acute heart failure specifically include the following components in parts by weight: 23-26 parts of load-reducing particles, 12-14 parts of vasodilator preparations, 2-5 parts of Andrographis paniculata, 3.2-4.7 parts of wild chrysanthemum, 1.8-2.2 parts of neem, 1.4-1.7 parts of ophiopogon polysaccharide, 0.8-1.2 parts of sesamin, and 0.6-1.1 parts of cornus officinalis extract.

[0006] Preferably, the raw materials for preparing the load-reducing particles include the following components in parts by weight: 5-8 parts of propylene glycol monooleate, 6-11 parts of cathepsin K, 15-19 parts of mesoporous carbon spheres, 1.4-1.8 parts of astragaloside IV, 2.6-3.9 parts of Prussian blue nanozyme, 1.3-1.6 parts of hydrochlorothiazide, and 2.2-2.4 parts of fucosylated chondroitin sulfate.

[0007] Preferably, the raw materials for preparing the vasodilator preparation include the following components in parts by weight: 3-3.5 parts of nitroglycerin, 2.8-3.2 parts of isosorbide mononitrate, 2.8-3.6 parts of horse chestnut, 1.9-2.3 parts of Artemisia selengensis, 2.4-2.8 parts of witch hazel, 5-7 parts of sodium carboxymethyl cellulose, 0.4-0.7 parts of hydrochloric acid, and 4.8-5.6 parts of calcium carbonate.

[0008] Preferably, the method for preparing the load-reducing particles comprises the following steps: S1. Place propylene glycol monooleate, cathepsin K, and 70% ethanol solution in a thermostatic stirrer with a power of 2.2-2.6 kW, maintain constant stirring at 40-45°C for 1.2-1.4 h, and at a constant stirring speed of 300 r / min, and stir to react to obtain a complex solution; S2, placing the mesoporous carbon spheres, anhydrous ethanol, and the complex solution prepared in S1 into a stirring tank with a power of 1.5-1.8 kW, a stirring temperature of 25-30°C, a stirring time of 18-23 min, and a stirring speed of 200-300 r / min, and after mixing, placing the mixture into a vacuum freeze-nano spray dryer with a power of 2.3-2.8 kW, a vacuum degree of -0.05 MPa, a freeze-nano spray drying temperature of -40°C, a freeze-nano spray drying particle size of 100 nm, and a freeze-nano spray drying time of 2.5-3 h to obtain nanoparticles; S3. Place astragaloside IV, Prussian blue nanozyme, hydrochlorothiazide, acetone, acetonitrile, and anhydrous ethanol into a stirring tank with a power of 1.5-1.8 kW, stir at a temperature of 28-33°C, a stirring time of 20-30 min, and a stirring speed of 400 r / min, and mix and dissolve to obtain a repair-promoting solution; S4, placing the nanoparticles prepared in S2 into the repair-promoting solution prepared in S3, stirring at a temperature of 28-33°C, a stirring time of 23-35 min, and a stirring speed of 300-500 r / min for sufficient adsorption to obtain a load-reducing composition; S5. Mix the fucosylated chondroitin sulfate with ultrapure water, place the mixture in a stirring tank with a power of 1.5-1.8 kW, stir at a temperature of 33-40° C., stir for 13-18 minutes, and stir at a speed of 200-300 r / min to dissolve the mixture to obtain a polysaccharide solution; S6. Add the load-reducing composition prepared in S4 to the polysaccharide solution prepared in S5, stir at a temperature of 28-35°C, a stirring time of 20-25 min, and a stirring speed of 200-300 r / min, mix, place at a temperature of 30-35°C for 2-3 hours, and air-dry to obtain load-reducing particles.

[0009] Furthermore, in S1, the mass fraction of the propylene glycol monooleate in the 70% ethanol solution is 15-22%, and in S2, the material-liquid ratio of the mesoporous carbon spheres to anhydrous ethanol is 1:500 g / mL.

[0010] Furthermore, in S3, the mass fraction of astragaloside IV in anhydrous ethanol is 1.5-2.2%, the mass fraction of Prussian blue nanozyme in acetonitrile is 1.8-2.4%, and the mass fraction of hydrochlorothiazide in acetone is 3%.

[0011] Preferably, the method for preparing the vasodilator preparation comprises the following steps: L1. Place nitroglycerin, isosorbide mononitrate, and ultrapure water in a 1.8 kW ultrasonic stirrer at an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 25°C, and a stirring time of 10 min, and mix to obtain a blood circulation promoting solution; L2. Place horse chestnut, wormwood, and witch hazel in a grinder with a power of 1.7-2.2 kW, grind at a temperature of 25-30°C, grind for 12-18 min, and grind at a speed of 1000-1400 r / min. After grinding, place the grinded materials with ultrapure water in an ultrasonic extractor with a power of 1.3-1.6 kW, extract at an extraction pressure of 1.5 MPa, an extraction frequency of 25 kHz, an extraction temperature of 40-45°C, and an extraction time of 8-13 min to obtain a vasodilator extract; L3, placing the vasodilator extract prepared in L2 and the blood circulation promoting solution prepared in L1 into a stirring tank with a power of 1.5-1.8 kW, stirring at a temperature of 23-28°C, a stirring time of 15-20 minutes, and a stirring speed of 200-300 r / min, and mixing to obtain a viscous mixture; L4. Place sodium carboxymethyl cellulose, ultrapure water, hydrochloric acid, and calcium carbonate into a reactor with a power of 2.2-2.6 kW, the reaction temperature is 40° C., the reaction time is 1.2-2.4 h, and the reaction speed is 300-500 r / min to obtain modified carboxymethyl cellulose calcium; L5. Add the modified carboxymethyl cellulose calcium prepared in L4 into the viscous mixture prepared in L3, stir at a temperature of 23-28°C, for 15-20 min, at a speed of 300-500 r / min, and mix thoroughly to obtain a vasodilator preparation.

[0012] Furthermore, in L1, the mass fraction of the isosorbide mononitrate in ultrapure water is 1.3-1.7%, and in L2, the solid-liquid ratio of the horse chestnut to ultrapure water is 1:3.5 g / mL.

[0013] Furthermore, in L4, the mass fraction of the sodium carboxymethyl cellulose in ultrapure water is 1%.

[0014] The present invention also provides a method for preparing a Chinese medicine composition for treating acute heart failure, which specifically comprises the following steps: Step 1: Put Andrographis paniculata, Chrysanthemum indica, and Azadirachta indica into a grinder with a power of 1.5-1.8 kW, the grinding temperature is 23-28 ° C, the grinding time is 15-20 min, the grinding speed is 3500-4500 r / min, and after grinding, filter with sterile gauze, put them into a stirring tank with a power of 1.5-1.8 kW, stir at a temperature of 23-28 ° C, stir for 15-20 min, stir at a speed of 200-300 r / min, mix and dissolve to obtain an anti-infection and side effect reducing agent; Step 2: Place the load-reducing particles and the vasodilator into a stirring tank with a power of 1.5-1.8 kW, the stirring temperature is 23-28° C., the stirring time is 10-15 minutes, the stirring speed is 300 r / min, and after mixing evenly, place them into a pharmaceutical tablet press with a power of 1.8-2.2 kW, the tableting temperature is 20-25° C., the tableting time is 18-22 minutes, and the tableting diameter is 8-12 mm. After tableting, tablets for treating acute heart failure are obtained; Step 3: The anti-infection and side effect reducing agent prepared in step 1 is evenly sprayed on the surface of the sheet for treating acute heart failure prepared in step 2 using a sprayer with a power of 1.6-2.3 kW, a spraying time of 13-18 min, and a spraying temperature of 25-30°C. The sheet is placed at a temperature of 25-28°C for 2-2.5 hours and air-dried to obtain a traditional Chinese medicine composition for treating acute heart failure.

[0015] Preferably, in step 1, the mass fraction of the Ophiopogon japonicus polysaccharide in the 70% ethanol solution is 5-8%. The beneficial effects achieved by the present invention are as follows: The present invention uses propylene glycol monooleate and cathepsin K for constant temperature stirring. Cathepsin K can recognize and act on the extracellular matrix of myocardial cells. Propylene glycol monooleate has high lipophilicity and can interact with the lipid bilayer of the cell membrane, making it easier to penetrate the cell membrane, thereby promoting drug absorption. When propylene glycol monooleate comes into contact with cathepsin K, its hydrophobic part interacts with the hydrophobic region of cathepsin K, causing water molecules to be squeezed out. The two combine to form a stable complex. The complex solution is covered on the surface of mesoporous carbon spheres with a high specific surface area. After freeze-nano spray drying, the obtained nanoparticles can be targeted Myocardial cells are treated. Astragaloside IV has antioxidant, anti-inflammatory and angiogenic effects. It regulates the expression of calcium-sensitive receptors and promotes calcium influx, thereby enhancing myocardial contractility. Prussian blue nanozymes have superoxide dismutase-like activity, which can significantly reduce ROS levels in cells, reduce the damage of oxidative stress to myocardial cells, and improve lung ventilation and gas exchange function. Hydrochlorothiazide inhibits sodium and chloride ion transporters in renal tubular epithelial cells, reduces the reabsorption of sodium and chloride, and increases the excretion of sodium and water in urine. Nanoparticles fully adsorb the repair solution, and the mixture has good biocompatibility and can promote cell adhesion and growth. The polysaccharide solution obtained by the cloning of the heart muscle can repair damaged myocardial cells, repair heart valves, and improve the heart's pumping and contraction functions; nitroglycerin activates guanylate cyclase by releasing nitric oxide, increases the synthesis of cyclic guanosine monophosphate, and relaxes vascular smooth muscle; isosorbide mononitrate can improve blood circulation; the vasodilator extract obtained by crushing and extracting horse chestnut, wormwood, and witch hazel is mixed with a blood circulation-promoting solution to obtain a viscous mixture that dilates blood vessels, lowers blood pressure, and slows heart rate; sodium carboxymethyl cellulose is modified with hydrochloric acid and reacts with calcium carbonate to form a modified carboxymethyl cellulose calcium with a higher cross-linking density and a more stable structure, thereby enhancing The invention discloses a vasodilator preparation for treating acute heart failure by mixing modified carboxymethyl cellulose calcium with a viscous mixture to obtain a vasodilator preparation, which reduces the preload and postload of the heart, reduces myocardial oxygen consumption, relaxes blood vessels, and improves coronary blood flow; andrographis paniculata, wild chrysanthemum, and neem are crushed, the juice is filtered out, and the mixture is mixed with ophiopogon polysaccharide, sesamin, and cornus officinalis extract to obtain an anti-infection and side effect reducing agent, which can reduce the occurrence of side effects, has antibacterial and anti-infection effects, and maintains the stability of effective components. The anti-infection and side effect reducing agent is sprayed on the surface of a tablet for treating acute heart failure. The prepared traditional Chinese medicine composition for treating acute heart failure has a fast disintegration speed, comprehensive and efficient therapeutic effects, long-lasting effects, strong drug stability, and high bioavailability. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the present invention or the technical solutions in the prior art, the following will be described in a clear and easy-to-understand manner with reference to the accompanying drawings. Obviously, the drawings described below are only for the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0017] Figure 1 This is a scanning electron microscope image of the internal structure of the nanoparticles of the present invention; Figure 2 This is a graph showing the cure rate of acute heart failure in mice described in Experimental Example 1 of the present invention; Figure 3 This is a graph showing the cure rate of acute heart failure in mice after storage as described in Experimental Example 3 of the present invention; Figure 4 This is a graph showing the results of the mouse kidney organ index described in Experimental Example 3 of the present invention. DETAILED DESCRIPTION

[0018] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments; based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those familiar to those skilled in the art. Furthermore, any methods and materials similar or equivalent to those described herein can be applied to the present invention. The preferred embodiments and materials described herein are for illustrative purposes only and are not intended to limit the scope of this application.

[0020] The experimental methods in the following examples, unless otherwise specified, are conventional methods; the test materials and test strains used in the following examples, unless otherwise specified, are purchased from commercial channels.

[0021] Example 1: This example provides a Chinese medicine composition for treating acute heart failure and a preparation method thereof. The Chinese medicine composition for treating acute heart failure comprises the following components in parts by weight: 23 parts of load-reducing particles, 12 parts of vasodilator preparations, 2 parts of Andrographis paniculata, 3.2 parts of Chrysanthemum indica, 1.8 parts of Azadirachta indica, 1.4 parts of Ophiopogon japonicus polysaccharides, 0.8 parts of Sesamin, and 0.6 parts of Cornus officinalis extract.

[0022] The raw materials for preparing the load-reducing particles include the following components in parts by weight: 5 parts of propylene glycol monooleate, 6 parts of cathepsin K, 15 parts of mesoporous carbon spheres, 1.4 parts of astragaloside IV, 2.6 parts of Prussian blue nanozyme, 1.3 parts of hydrochlorothiazide, and 2.2 parts of fucosylated chondroitin sulfate.

[0023] The raw materials for preparing the vasodilator preparation include the following components in parts by weight: 3 parts of nitroglycerin, 2.8 parts of isosorbide mononitrate, 2.8 parts of horse chestnut, 1.9 parts of artemisia selengensis, 2.4 parts of witch hazel, 5 parts of sodium carboxymethyl cellulose, 0.4 parts of hydrochloric acid, and 4.8 parts of calcium carbonate.

[0024] The method for preparing the load-reducing particles specifically comprises the following steps: S1. Place propylene glycol monooleate, cathepsin K, and 70% ethanol solution in a 2.2 kW thermostatic stirrer at 40°C for 1.2 h at a speed of 300 r / min, and stir to obtain a complex solution. S2, placing the mesoporous carbon spheres, anhydrous ethanol, and the complex solution prepared in S1 into a stirring tank with a power of 1.5 kW, a stirring temperature of 25°C, a stirring time of 18 min, and a stirring speed of 200 r / min. After mixing, placing the mixture into a vacuum freeze-nano spray dryer with a power of 2.3 kW, a vacuum degree of -0.05 MPa, a freeze-nano spray drying temperature of -40°C, a freeze-nano spray drying particle size of 100 nm, and a freeze-nano spray drying time of 2.5 h to obtain nanoparticles; S3. Astragaloside IV, Prussian blue nanozyme, hydrochlorothiazide, acetone, acetonitrile, and anhydrous ethanol were placed in a 1.5 kW stirring tank at 28°C for 20 min at a stirring speed of 400 r / min to mix and dissolve to obtain a repair-promoting solution. S4, placing the nanoparticles prepared in S2 into the repair-promoting solution prepared in S3, stirring at a temperature of 28° C., a stirring time of 23 min, and a stirring speed of 300 r / min for sufficient adsorption to obtain a load-reducing composition; S5. Mix the fucosylated chondroitin sulfate with ultrapure water, place the mixture in a stirring tank with a power of 1.5 kW, stir at a temperature of 33°C, for 13 minutes, and at a stirring speed of 200 r / min to dissolve the mixture to obtain a polysaccharide solution; S6. Add the load-reducing composition prepared in S4 into the polysaccharide solution prepared in S5, stir at 28°C for 20 min, and stir at 200 r / min to mix. Place at 30°C for 2 h and air-dry to obtain load-reducing particles.

[0025] In S1, the mass fraction of the propylene glycol monooleate in the 70% ethanol solution is 15%. In S2, the material-liquid ratio of the mesoporous carbon spheres to anhydrous ethanol is 1:500 g / mL.

[0026] In S3, the mass fraction of astragaloside IV in anhydrous ethanol is 1.5%, the mass fraction of Prussian blue nanozyme in acetonitrile is 1.8%, and the mass fraction of hydrochlorothiazide in acetone is 3%.

[0027] The preparation method of the vasodilator preparation specifically comprises the following steps: L1. Place nitroglycerin, isosorbide mononitrate, and ultrapure water in a 1.8 kW ultrasonic stirrer at an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 25°C, and a stirring time of 10 min, and mix to obtain a blood circulation promoting solution; L2. Place horse chestnut, wormwood, and witch hazel in a 1.7 kW grinder at a grinding temperature of 25°C, a grinding time of 12 min, and a grinding speed of 1000 r / min. After grinding, place the mixture with ultrapure water in a 1.3 kW ultrasonic extractor at an extraction pressure of 1.5 MPa, an extraction frequency of 25 kHz, an extraction temperature of 40°C, and an extraction time of 8 min to obtain a vasodilator extract. L3, placing the vasodilator extract prepared in L2 and the blood circulation promoting solution prepared in L1 into a stirring tank with a power of 1.5 kW, stirring at a temperature of 23°C, a stirring time of 15 minutes, and a stirring speed of 200 r / min, and mixing to obtain a viscous mixture; L4. Sodium carboxymethyl cellulose, ultrapure water, hydrochloric acid, and calcium carbonate are placed in a 2.2 kW reactor. The reaction temperature is 40°C, the reaction time is 1.2 h, and the reaction speed is 300 r / min. After the reaction, modified carboxymethyl cellulose calcium is obtained. L5. Add the modified carboxymethyl cellulose calcium prepared in L4 into the viscous mixture prepared in L3. Stir at 23°C for 15 min at a speed of 300 r / min. Mix thoroughly to obtain a vasodilator preparation.

[0028] In L1, the mass fraction of the isosorbide mononitrate in ultrapure water is 1.3%, and in L2, the solid-liquid ratio of the horse chestnut to ultrapure water is 1:3.5 g / mL.

[0029] In L4, the mass fraction of the sodium carboxymethyl cellulose in ultrapure water is 1%.

[0030] This embodiment also provides a method for preparing a Chinese medicine composition for treating acute heart failure, which specifically comprises the following steps: Step 1: Put Andrographis paniculata, Chrysanthemum indica, and Azadirachta indica into a 1.5 kW grinder at a grinding temperature of 23° C., a grinding time of 15 min, and a grinding speed of 3500 r / min. After grinding, filter with sterile gauze, put them into a stirring tank with a power of 1.5 kW, stir at a temperature of 23° C., a stirring time of 15 min, and a stirring speed of 200 r / min, and mix and dissolve to obtain an anti-infection and side effect reducing agent; Step 2: Place the load-reducing particles and the vasodilator agent into a stirring tank with a power of 1.5 kW, at a stirring temperature of 23° C., a stirring time of 10 minutes, and a stirring speed of 300 r / min. After mixing evenly, place the mixture into a pharmaceutical tablet press with a power of 1.8 kW, at a tableting temperature of 20° C., a tableting time of 18 minutes, and a tablet diameter of 8 mm to obtain tablets for treating acute heart failure; Step 3: Use a 1.6 kW sprayer to spray the anti-infection and side effect-reducing agent prepared in step 1 evenly on the surface of the sheet for treating acute heart failure prepared in step 2 at a temperature of 25°C for 13 min. Place it at 25°C for 2 h and air-dry to obtain a traditional Chinese medicine composition for treating acute heart failure.

[0031] In step 1, the mass fraction of the Ophiopogon japonicus polysaccharide in the 70% ethanol solution is 5%.

[0032] Example 2: This example provides a Chinese medicine composition for treating acute heart failure and a preparation method thereof. The Chinese medicine composition for treating acute heart failure comprises the following components in parts by weight: 24 parts of load-reducing particles, 13 parts of vasodilator preparations, 3 parts of Andrographis paniculata, 4.2 parts of Chrysanthemum indica, 1.9 parts of Azadirachta indica, 1.6 parts of Ophiopogon japonicus polysaccharides, 0.9 parts of Sesamin, and 0.8 parts of Cornus officinalis extract.

[0033] The raw materials for preparing the load-reducing particles include the following components in parts by weight: 6 parts of propylene glycol monooleate, 9 parts of cathepsin K, 17 parts of mesoporous carbon spheres, 1.6 parts of astragaloside IV, 3.3 parts of Prussian blue nanozyme, 1.5 parts of hydrochlorothiazide, and 2.3 parts of fucosylated chondroitin sulfate.

[0034] The raw materials for preparing the vasodilator preparation include the following components in parts by weight: 3.2 parts of nitroglycerin, 2.9 parts of isosorbide mononitrate, 3.4 parts of horse chestnut, 2.1 parts of artemisia selengensis, 2.5 parts of witch hazel, 6 parts of sodium carboxymethyl cellulose, 0.5 parts of hydrochloric acid, and 5.2 parts of calcium carbonate.

[0035] The method for preparing the load-reducing particles specifically comprises the following steps: S1. Place propylene glycol monooleate, cathepsin K, and 70% ethanol solution in a 2.4 kW thermostatic stirrer at 43°C for 1.3 h at a speed of 300 r / min, and stir to obtain a complex solution. S2, placing the mesoporous carbon spheres, anhydrous ethanol, and the complex solution prepared in S1 into a stirring tank with a power of 1.7 kW, a stirring temperature of 26°C, a stirring time of 21 min, and a stirring speed of 200 r / min. After mixing, placing the mixture into a vacuum freeze-nano spray dryer with a power of 2.5 kW, a vacuum degree of -0.05 MPa, a freeze-nano spray drying temperature of -40°C, a freeze-nano spray drying particle size of 100 nm, and a freeze-nano spray drying time of 2.8 h to obtain nanoparticles; S3. Astragaloside IV, Prussian blue nanozyme, hydrochlorothiazide, acetone, acetonitrile, and anhydrous ethanol were placed in a 1.6 kW stirring tank at 30°C for 25 min at a stirring speed of 400 r / min to mix and dissolve to obtain a repair-promoting solution. S4, placing the nanoparticles prepared in S2 into the repair-promoting solution prepared in S3, stirring at a temperature of 31°C, a stirring time of 28 minutes, and a stirring speed of 400 r / min for sufficient adsorption to obtain a load-reducing composition; S5. Mix the fucosylated chondroitin sulfate with ultrapure water, place the mixture in a stirring tank with a power of 1.7 kW, stir at a temperature of 38°C, for 16 minutes, and at a stirring speed of 300 r / min to dissolve the mixture to obtain a polysaccharide solution; S6. Add the load-reducing composition prepared in S4 into the polysaccharide solution prepared in S5, stir at a temperature of 32°C, a stirring time of 23 min, and a stirring speed of 200 r / min, mix, place at a temperature of 32°C for 2.5 h, and air-dry to obtain load-reducing particles.

[0036] In S1, the mass fraction of the propylene glycol monooleate in the 70% ethanol solution is 18%. In S2, the material-liquid ratio of the mesoporous carbon spheres to anhydrous ethanol is 1:500 g / mL.

[0037] In S3, the mass fraction of astragaloside IV in anhydrous ethanol is 1.9%, the mass fraction of Prussian blue nanozyme in acetonitrile is 2.1%, and the mass fraction of hydrochlorothiazide in acetone is 3%.

[0038] The preparation method of the vasodilator preparation specifically comprises the following steps: L1. Place nitroglycerin, isosorbide mononitrate, and ultrapure water in a 1.8 kW ultrasonic stirrer at an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 25°C, and a stirring time of 10 min, and mix to obtain a blood circulation promoting solution; L2. Place horse chestnut, wormwood, and witch hazel in a 1.9 kW grinder at a grinding temperature of 27°C, a grinding time of 15 min, and a grinding speed of 1200 r / min. After grinding, place the grinded materials with ultrapure water in a 1.5 kW ultrasonic extractor at an extraction pressure of 1.5 MPa, an extraction frequency of 25 kHz, an extraction temperature of 43°C, and an extraction time of 11 min to obtain a vasodilator extract. L3, placing the vasodilator extract prepared in L2 and the blood circulation promoting solution prepared in L1 into a stirring tank with a power of 1.6 kW, stirring at a temperature of 26°C, a stirring time of 17 minutes, and a stirring speed of 300 r / min, and mixing to obtain a viscous mixture; L4. Sodium carboxymethyl cellulose, ultrapure water, hydrochloric acid, and calcium carbonate are placed in a 2.4 kW reactor. The reaction temperature is 40° C., the reaction time is 1.6 h, and the reaction speed is 400 r / min. After the reaction, modified carboxymethyl cellulose calcium is obtained. L5. Add the modified carboxymethyl cellulose calcium prepared in L4 into the viscous mixture prepared in L3, stir at 25°C for 18 min, and stir at 400 r / min to obtain a vasodilator preparation after mixing.

[0039] In L1, the mass fraction of the isosorbide mononitrate in ultrapure water is 1.5%, and in L2, the solid-liquid ratio of the horse chestnut to ultrapure water is 1:3.5 g / mL.

[0040] In L4, the mass fraction of the sodium carboxymethyl cellulose in ultrapure water is 1%.

[0041] This embodiment also provides a method for preparing a Chinese medicine composition for treating acute heart failure, which specifically comprises the following steps: Step 1: Put Andrographis paniculata, Chrysanthemum indica, and Azadirachta indica into a 1.6 kW grinder at a grinding temperature of 25°C, a grinding time of 18 minutes, and a grinding speed of 4000 r / min. After grinding, filter with sterile gauze, put them into a stirring tank with a power of 1.7 kW with Ophiopogon japonicus polysaccharide, sesamin, Cornus officinalis extract, and 70% ethanol solution, stir at a temperature of 25°C, a stirring time of 16 minutes, and a stirring speed of 300 r / min, mix and dissolve to obtain an anti-infection and side effect reducing agent; Step 2: Place the load-reducing particles and the vasodilator agent into a stirring tank with a power of 1.7 kW, the stirring temperature is 25° C., the stirring time is 12 minutes, the stirring speed is 300 r / min, and after mixing evenly, place them into a pharmaceutical tablet press with a power of 2.1 kW, the tableting temperature is 22° C., the tableting time is 20 minutes, and the tableting diameter is 11 mm. After tableting, tablets for treating acute heart failure are obtained; Step 3: The anti-infection and side effect reducing agent prepared in step 1 is evenly sprayed on the surface of the sheet for treating acute heart failure prepared in step 2 using a sprayer with a power of 1.9 kW, a spraying time of 16 min, and a spraying temperature of 28°C. The sheet is placed at a temperature of 26°C for 2.3 h and air-dried to obtain a traditional Chinese medicine composition for treating acute heart failure.

[0042] In step 1, the mass fraction of the Ophiopogon japonicus polysaccharide in the 70% ethanol solution is 6%.

[0043] Example 3: This example provides a Chinese medicine composition for treating acute heart failure and a preparation method thereof. The Chinese medicine composition for treating acute heart failure comprises the following components in parts by weight: 26 parts of load-reducing particles, 14 parts of vasodilator preparations, 5 parts of Andrographis paniculata, 4.7 parts of Chrysanthemum indica, 2.2 parts of Azadirachta indica, 1.7 parts of Ophiopogon japonicus polysaccharide, 1.2 parts of Sesamin, and 1.1 parts of Cornus officinalis extract.

[0044] The raw materials for preparing the load-reducing particles include the following components in parts by weight: 8 parts of propylene glycol monooleate, 11 parts of cathepsin K, 19 parts of mesoporous carbon spheres, 1.8 parts of astragaloside IV, 3.9 parts of Prussian blue nanozyme, 1.6 parts of hydrochlorothiazide, and 2.4 parts of fucosylated chondroitin sulfate.

[0045] The raw materials for preparing the vasodilator preparation include the following components in parts by weight: 3.5 parts of nitroglycerin, 3.2 parts of isosorbide mononitrate, 3.6 parts of horse chestnut, 2.3 parts of artemisia selengensis, 2.8 parts of witch hazel, 7 parts of sodium carboxymethyl cellulose, 0.7 parts of hydrochloric acid, and 5.6 parts of calcium carbonate.

[0046] The method for preparing the load-reducing particles specifically comprises the following steps: S1. Place propylene glycol monooleate, cathepsin K, and 70% ethanol solution in a 2.6 kW thermostatic stirrer at 45°C for 1.4 h at a speed of 300 r / min, and stir to obtain a complex solution. S2, placing the mesoporous carbon spheres, anhydrous ethanol, and the complex solution prepared in S1 into a stirring tank with a power of 1.8 kW, a stirring temperature of 30°C, a stirring time of 23 min, and a stirring speed of 300 r / min. After mixing, placing the mixture into a vacuum freeze-nano spray dryer with a power of 2.8 kW, a vacuum degree of -0.05 MPa, a freeze-nano spray drying temperature of -40°C, a freeze-nano spray drying particle size of 100 nm, and a freeze-nano spray drying time of 3 h to obtain nanoparticles; S3. Astragaloside IV, Prussian blue nanozyme, hydrochlorothiazide, acetone, acetonitrile, and anhydrous ethanol were placed in a 1.8 kW stirring tank at 33°C for 30 min at a stirring speed of 400 r / min to mix and dissolve to obtain a repair-promoting solution. S4, placing the nanoparticles prepared in S2 into the repair-promoting solution prepared in S3, stirring at a temperature of 33°C, a stirring time of 35 minutes, and a stirring speed of 500 r / min for sufficient adsorption to obtain a load-reducing composition; S5. Mix the fucosylated chondroitin sulfate with ultrapure water, place the mixture in a stirring tank with a power of 1.8 kW, stir at a temperature of 40°C, for 18 minutes, and at a stirring speed of 300 r / min to dissolve the mixture to obtain a polysaccharide solution; S6. Add the load-reducing composition prepared in S4 into the polysaccharide solution prepared in S5, stir at a temperature of 35°C, a stirring time of 25 min, and a stirring speed of 300 r / min, mix, place at a temperature of 35°C for 3 h, and air-dry to obtain load-reducing particles.

[0047] In S1, the mass fraction of the propylene glycol monooleate in the 70% ethanol solution is 22%. In S2, the material-liquid ratio of the mesoporous carbon spheres to anhydrous ethanol is 1:500 g / mL.

[0048] In S3, the mass fraction of astragaloside IV in anhydrous ethanol is 2.2%, the mass fraction of Prussian blue nanozyme in acetonitrile is 2.4%, and the mass fraction of hydrochlorothiazide in acetone is 3%.

[0049] The preparation method of the vasodilator preparation specifically comprises the following steps: L1. Place nitroglycerin, isosorbide mononitrate, and ultrapure water in a 1.8 kW ultrasonic stirrer at an ultrasonic frequency of 15 kHz, a stirring speed of 20,000 r / min, a stirring temperature of 25°C, and a stirring time of 10 min, and mix to obtain a blood circulation promoting solution; L2. Place horse chestnut, wormwood, and witch hazel in a 2.2 kW grinder at a grinding temperature of 30°C, a grinding time of 18 min, and a grinding speed of 1400 r / min. After grinding, place the mixture with ultrapure water in a 1.6 kW ultrasonic extractor at an extraction pressure of 1.5 MPa, an extraction frequency of 25 kHz, an extraction temperature of 45°C, and an extraction time of 13 min to obtain a vasodilator extract. L3, placing the vasodilator extract prepared in L2 and the blood circulation promoting solution prepared in L1 into a stirring tank with a power of 1.8 kW, stirring at a temperature of 28°C, a stirring time of 20 min, and a stirring speed of 300 r / min, and mixing to obtain a viscous mixture; L4. Sodium carboxymethyl cellulose, ultrapure water, hydrochloric acid, and calcium carbonate are placed in a 2.6 kW reactor. The reaction temperature is 40° C., the reaction time is 2.4 h, and the reaction speed is 500 r / min. After the reaction, modified carboxymethyl cellulose calcium is obtained. L5. Add the modified carboxymethyl cellulose calcium prepared in L4 into the viscous mixture prepared in L3. Stir at a temperature of 28°C for 20 min at a speed of 500 r / min. Mix thoroughly to obtain a vasodilator preparation.

[0050] In L1, the mass fraction of the isosorbide mononitrate in ultrapure water is 1.7%, and in L2, the solid-liquid ratio of the horse chestnut to ultrapure water is 1:3.5 g / mL.

[0051] In L4, the mass fraction of the sodium carboxymethyl cellulose in ultrapure water is 1%.

[0052] This embodiment also provides a method for preparing a Chinese medicine composition for treating acute heart failure, which specifically comprises the following steps: Step 1: Put Andrographis paniculata, Chrysanthemum indica, and Azadirachta indica into a 1.8 kW grinder at a grinding temperature of 28° C., a grinding time of 20 min, and a grinding speed of 4500 r / min. After grinding, filter with sterile gauze, put them into a stirring tank with a power of 1.8 kW with Ophiopogon japonicus polysaccharide, sesamin, Cornus officinalis extract, and 70% ethanol solution, stir at a temperature of 28° C., a stirring time of 20 min, and a stirring speed of 300 r / min, mix and dissolve to obtain an anti-infection and side effect reducing agent; Step 2: Place the load-reducing particles and the vasodilator agent into a stirring tank with a power of 1.8 kW, the stirring temperature is 28° C., the stirring time is 15 minutes, the stirring speed is 300 r / min, and after mixing evenly, place them into a pharmaceutical tablet press with a power of 2.2 kW, the tableting temperature is 25° C., the tableting time is 22 minutes, and the tableting diameter is 12 mm. After tableting, tablets for treating acute heart failure are obtained; Step 3: The anti-infection and side effect reducing agent prepared in step 1 is evenly sprayed on the surface of the sheet for treating acute heart failure prepared in step 2 using a sprayer with a power of 2.3 kW, a spraying time of 18 min, and a spraying temperature of 30°C. The sheet is placed at a temperature of 28°C for 2.5 hours and air-dried to obtain a traditional Chinese medicine composition for treating acute heart failure.

[0053] In step 1, the mass fraction of the Ophiopogon japonicus polysaccharide in the 70% ethanol solution is 8%.

[0054] Comparative Example 1: This comparative example provides a drug for treating acute heart failure and a preparation method thereof. The only difference from Example 1 is that the added load-reducing particles do not contain nanoparticles, and the remaining components, component contents, and method steps are the same as those in Example 1.

[0055] Comparative Example 2: This comparative example provides a drug for treating acute heart failure and a preparation method thereof. The only difference from Example 1 is that the added vasodilator preparation does not contain modified carboxymethylcellulose calcium, and the remaining components, component contents, and method steps are the same as those in Example 1.

[0056] Experimental Example 1: Test for determining efficacy in treating acute heart failure.

[0057] The experimental steps for determining the therapeutic efficacy of the Chinese medicinal composition for treating acute heart failure prepared in Examples 1-3 of the present invention on mice for acute heart failure are as follows: (1) Sixty 8-week-old SPF mice weighing 22 g were selected (purchased from Chengdu Dashuo Animal Co., Ltd.) and randomly divided into 6 groups of 10 mice each. The mice were housed in separate cages, kept clean and dry, at a temperature of 24°C and a humidity of 50%, with free access to food and water. (2) After 10 days of feeding, the mice were fasted for 12 hours and placed in an anesthesia induction box. The oxygen was turned on and the isoflurane concentration was adjusted to 5%. Anesthesia was induced for about 1 minute and then adjusted to 2% to maintain anesthesia. The mice were fixed in a supine position. The mouse hair in the surgical area on the left chest was removed and disinfected with iodine and 75% ethanol. A longitudinal incision about 1.5 cm long was made 2 mm away from the left edge of the sternum. A vertical mattress suture was performed at the incision to reserve sutures. The chest wall muscles were bluntly separated layer by layer. The chest cavity was quickly entered from the 3rd or 4th intercostal space. The intercostal space was opened with hemostatic forceps. The heart was gently squeezed in conjunction with the heartbeat to make it pop out of the hole. The heart was inserted 2 mm below the lower edge of the left atrial appendage. A 7-0 suture needle with thread was used to penetrate the left anterior descending coronary artery at a position 0.5 mm from the pulmonary artery cone. The needle was inserted with appropriate tightness to control the depth and width of the needle. After ligation, the outer surface of the left ventricular anterior wall was observed to see if it turned pale, confirming successful ischemia. After ligation, the heart was gently returned to the chest cavity, the chest cavity was squeezed to expel the air, and the sutures reserved at the incision were tightened to complete the operation. During the operation, the anesthetic concentration was gradually adjusted to zero. After removing the mask, the mouse was placed on a constant temperature pad for 5 minutes and allowed to wake up naturally to obtain an acute heart failure model mouse. (3) The Chinese medicine composition for treating acute heart failure prepared in Example 1-3 was applied to the inner wall of the mouse oral cavity using a sterile cotton swab, and was applied once a day, 0.8 g each time, for 7 consecutive days. As the Example 1-3 group, the medicine for treating acute heart failure prepared in Comparative Example 1-2 was applied to the inner wall of the mouse oral cavity using a sterile cotton swab, and was applied once a day, 0.8 g each time, for 7 consecutive days. As the Comparative Example 1-2 group, commercially available furosemide (purchased from Sigma-Aldrich Trading Co., Ltd.) was applied to the inner wall of the mouse oral cavity using a sterile cotton swab, and was applied once a day, 0.8 g each time, for 7 consecutive days. As the control group, 7 After 1 day, the left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension were evaluated by cardiac ultrasound. If the left ventricular ejection fraction and left ventricular fractional shortening returned to normal or near normal levels, and the left ventricular end-diastolic dimension and left ventricular end-systolic dimension improved significantly, it indicated that the cardiac systolic function had recovered. (4) Observe and record the recovery of cardiac contractile function of mice after 7 days, and calculate the cure rate of mice according to the formula: Cure rate of mice (%) = number of mice in each group with recovered cardiac contractile function / total number of mice in each group × 100%.

[0058] Result analysis: Figure 1 This is a scanning electron microscope image of the internal structure of the nanoparticles of the present invention. Figure 2This is a graph showing the cure rate of acute heart failure in mice described in Experimental Example 1 of the present invention. As shown in the figure, the Chinese medicine composition for treating acute heart failure prepared in Examples 1-3 was applied to the inner wall of the mouse oral cavity using a sterile cotton swab, applied once a day, 0.8 g each time, and applied continuously for 7 days. The cure rates of acute heart failure in the mice in the Example 1-3 groups were 93.3%, 96.7%, and 100%, respectively. The drug for treating acute heart failure prepared in Comparative Example 1-2 was applied to the inner wall of the mouse oral cavity using a sterile cotton swab, applied once a day, 0.8 g each time, and applied continuously for 7 days. The cure rates of acute heart failure in the mice in the Comparative Example 1-2 groups were 80% and 83.3%, respectively. Commercially available furosemide was applied to the inner wall of the mouse oral cavity using a sterile cotton swab, applied once a day, 0.8 g each time, and applied continuously for 7 days. The cure rate of acute heart failure in the mice in the control group was 50%, indicating that the Chinese medicine composition for treating acute heart failure prepared by the present invention has comprehensive and efficient therapeutic effects and high bioavailability.

[0059] Experimental Example 2: Disintegration rate measurement test.

[0060] The disintegration rate test steps for the Chinese medicine composition for treating acute heart failure prepared in Examples 1-3 of the present invention are as follows: (1) Take 6 tablets of the Chinese herbal composition for treating acute heart failure prepared in Examples 1-3 as tablet samples of Groups 1-3 of Examples, take 6 tablets of the drug for treating acute heart failure prepared in Groups 1-2 of Comparative Examples as tablet samples of Groups 1-2 of Comparative Examples, and take 6 tablets of commercially available furosemide (purchased from Sigma-Aldrich Trading Co., Ltd.) as tablet samples of the control group. Take 3 parallels for each group; (2) Place each group of tablet samples in step (1) into a beaker filled with ultrapure water at a temperature of 37°C, and use a stirring rod to evenly disperse each group of tablet samples in the beaker. Start a timer when stirring begins. When the tablet samples in the beaker are completely disintegrated, stop the timer and record the time required for disintegration; (3) Take 6 tablets of the Chinese herbal composition for treating acute heart failure prepared in Examples 1-3 as tablet samples of Groups 1-3 of Examples, take 6 tablets of the drug for treating acute heart failure prepared in Groups 1-2 of Comparative Examples as tablet samples of Groups 1-2 of Comparative Examples, and take 6 tablets of commercially available furosemide (purchased from Sigma-Aldrich Trading Co., Ltd.) as tablet samples of the control group. Take 3 parallels for each group; (4) Store each group of tablet samples at 20°C in the dark. On the 160th day of storage, perform the test according to step (2) and record the disintegration time of each group of tablet samples after 160 days of storage.

[0061] Table 1. Tablet sample disintegration time determination table

[0062] Result analysis: As shown in Table 1, the average disintegration time of the traditional Chinese medicine compositions for treating acute heart failure prepared in Examples 1-3 was significantly faster than that of the medicine for treating acute heart failure prepared in Comparative Example 2 and the commercially available furosemide in the control group. In addition, the average disintegration time of the traditional Chinese medicine compositions for treating acute heart failure prepared in Examples 1-3 did not change significantly after storage for 160 days, while the average disintegration time of the commercially available furosemide in the control group was significantly prolonged on the 160th day of storage. This indicates that the traditional Chinese medicine compositions for treating acute heart failure prepared by the present invention have a fast disintegration rate and can quickly exert a therapeutic effect.

[0063] Experimental Example 3: Stability and side effect determination test.

[0064] The steps for determining the stability and side effect-free nature of the Chinese medicinal compositions for treating acute heart failure prepared in Examples 1-3 of the present invention are as follows: (1) Sixty 8-week-old SPF mice weighing 22 g were selected (purchased from Chengdu Dashuo Animal Co., Ltd.) and randomly divided into 6 groups of 10 mice each. The mice were housed in separate cages, kept clean and dry, at a temperature of 24°C and a humidity of 50%, with free access to food and water. (2) After 10 days of feeding, the mice were fasted for 12 hours and placed in an anesthesia induction box. The oxygen was turned on and the isoflurane concentration was adjusted to 5%. Anesthesia was induced for about 1 minute and then adjusted to 2% to maintain anesthesia. The mice were fixed in a supine position. The mouse hair in the surgical area on the left chest was removed and disinfected with iodine and 75% ethanol. A longitudinal incision about 1.5 cm long was made 2 mm away from the left edge of the sternum. A vertical mattress suture was performed at the incision to reserve sutures. The chest wall muscles were bluntly separated layer by layer. The chest cavity was quickly entered from the 3rd or 4th intercostal space. The intercostal space was opened with hemostatic forceps. The heart was gently squeezed in conjunction with the heartbeat to make it pop out of the hole. The heart was inserted 2 mm below the lower edge of the left atrial appendage. A 7-0 suture needle with thread was used to penetrate the left anterior descending coronary artery at a position 0.5 mm from the pulmonary artery cone. The needle was inserted with appropriate tightness to control the depth and width of the needle. After ligation, the outer surface of the left ventricular anterior wall was observed to see if it turned pale, confirming successful ischemia. After ligation, the heart was gently returned to the chest cavity, the chest cavity was squeezed to expel the air, and the sutures reserved at the incision were tightened to complete the operation. During the operation, the anesthetic concentration was gradually adjusted to zero. After removing the mask, the mouse was placed on a constant temperature pad for 5 minutes and allowed to wake up naturally to obtain an acute heart failure model mouse. (3) The Chinese medicine composition for treating acute heart failure prepared in Example 1-3 and stored at 30°C for 120 days was applied to the inner wall of the mouse oral cavity using a sterile cotton swab, and the application was once a day, 0.8 g each time, for 7 consecutive days. As the Example 1-3 group, the medicine for treating acute heart failure prepared in Comparative Example 1-2 and stored at 30°C for 120 days was applied to the inner wall of the mouse oral cavity using a sterile cotton swab, and the application was once a day, 0.8 g each time, for 7 consecutive days. As the Comparative Example 1-2 group, the commercially available furosemide (purchased from Sigma-Aldrich Trading Co., Ltd.) that was stored at 30°C for 120 days was applied to the inner wall of the mouse oral cavity using a sterile cotton swab, and the application was once a day, 0.8 g each time, for 7 consecutive days. As the control group, 7 After 1 day, the left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic dimension, and left ventricular end-systolic dimension were evaluated by cardiac ultrasound. If the left ventricular ejection fraction and left ventricular fractional shortening returned to normal or near normal levels, and the left ventricular end-diastolic dimension and left ventricular end-systolic dimension improved significantly, it indicated that the cardiac systolic function had recovered. (4) Observe and record the recovery of cardiac contractile function of mice after 7 days, and calculate the cure rate of mice according to the formula: Cure rate of mice (%) = number of mice in each group with recovered cardiac contractile function / total number of mice in each group × 100%; (5) Kill the mice in each group by cervical dislocation. Isolate the kidneys of the mice in each group in step (4), rinse with 0.9% saline, dry the surface moisture with filter paper, and weigh them quickly. The kidney organ index (%) = kidney organ weight / mouse body weight × 100%. An increase in the kidney organ index indicates organ congestion, edema, or hyperplasia, while a decrease in the kidney organ index indicates organ atrophy or other degenerative changes. Record the results.

[0065] Result analysis: Figure 3This is a graph showing the cure rate of acute heart failure in mice after storage as described in Experimental Example 3 of the present invention. As shown in the figure, the Chinese medicine composition for treating acute heart failure prepared in Example 1-3, which was stored at 30°C for 120 days, was applied to the inner wall of the mouse oral cavity using a sterile cotton swab. The composition was applied once a day, 0.8 g each time, for 7 consecutive days. The cure rates of acute heart failure in the mice in the Example 1-3 groups were 93%, 93.3%, and 96.7%, respectively. The medicine for treating acute heart failure prepared in Comparative Example 1-2, which was stored at 30°C for 120 days, was applied to the inner wall of the mouse oral cavity using a sterile cotton swab. The composition was applied once a day, 0.8 g each time, for 7 consecutive days. The cure rates of acute heart failure in the mice in the Comparative Example 1-2 groups were 70% and 75.6%, respectively. The commercially available furosemide, which was stored at 30°C for 120 days, was applied to the inner wall of the mouse oral cavity using a sterile cotton swab. The composition was applied once a day, 0.8 g each time, for 7 consecutive days. The cure rate of acute heart failure in the mice in the control group was 30%. Figure 4 This is a graph showing the kidney organ index of mice described in Experimental Example 3 of the present invention. As shown in the figure, the kidney organ index of the mice in the control group is significantly higher than the kidney organ index of the mice in Examples 1-3 and Comparative Examples 1-2. This indicates that the Chinese medicine composition for treating acute heart failure prepared by the present invention has strong drug stability, can exert long-term effects, is easy to transport and store, and has no side effects on the kidneys after administration.

[0066] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

[0067] The present invention and its embodiments are described above. Such description is not restrictive. The drawings show only one embodiment of the present invention, and actual applications are not limited thereto. In short, if a person skilled in the art is inspired by the above, and does not deviate from the purpose of the present invention, any method and embodiment similar to the technical solution without creative design shall fall within the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating acute heart failure, characterized in that: The raw materials for preparing the Chinese medicine composition for treating acute heart failure specifically include the following components in parts by weight: 23-26 parts of load-reducing particles, 12-14 parts of vasodilator, 2-5 parts of Andrographis paniculata, 3.2-4.7 parts of Chrysanthemum indica, 1.8-2.2 parts of Azadirachta indica, 1.4-1.7 parts of Ophiopogon japonicus polysaccharide, 0.8-1.2 parts of Sesamin, and 0.6-1.1 parts of Cornus officinalis extract; The raw materials for preparing the load-reducing particles include the following components in parts by weight: 5-8 parts of propylene glycol monooleate, 6-11 parts of cathepsin K, 15-19 parts of mesoporous carbon spheres, 1.4-1.8 parts of astragaloside IV, 2.6-3.9 parts of Prussian blue nanozyme, 1.3-1.6 parts of hydrochlorothiazide, and 2.2-2.4 parts of fucosylated chondroitin sulfate; The raw materials for preparing the vasodilator preparation include the following components in parts by weight: 3-3.5 parts of nitroglycerin, 2.8-3.2 parts of isosorbide mononitrate, 2.8-3.6 parts of horse chestnut, 1.9-2.3 parts of artemisia selengensis, 2.4-2.8 parts of witch hazel, 5-7 parts of sodium carboxymethyl cellulose, 0.4-0.7 parts of hydrochloric acid, and 4.8-5.6 parts of calcium carbonate.

2. The Chinese medicine composition for treating acute heart failure according to claim 1, characterized in that The method for preparing the load-reducing particles specifically comprises the following steps: S1. Stirring propylene glycol monooleate, cathepsin K, and 70% ethanol solution to obtain a complex solution. S2, mixing the mesoporous carbon spheres with anhydrous ethanol and the complex solution prepared in S1, and then performing freeze nano spray drying to obtain nanoparticles; S3, stirring and dissolving astragaloside IV, Prussian blue nanozyme, hydrochlorothiazide, acetone, acetonitrile, and anhydrous ethanol to obtain a repair-promoting solution; S4, placing the nanoparticles prepared in S2 into the repair-promoting solution prepared in S3 for sufficient adsorption to obtain a load-reducing composition; S5. Dissolve the fucosylated chondroitin sulfate in ultrapure water, add the mixture to the load-reducing composition prepared in S4, mix the mixture, place the mixture at a temperature of 30-35° C. for 2-3 hours, and air-dry to obtain load-reducing particles.

3. The Chinese medicine composition for treating acute heart failure according to claim 2, characterized in that In S1, the mass fraction of the propylene glycol monooleate in the 70% ethanol solution is 15-22%. In S2, the material-liquid ratio of the mesoporous carbon spheres to anhydrous ethanol is 1:500 g / mL.

4. The Chinese medicine composition for treating acute heart failure according to claim 3, characterized in that In S3, the mass fraction of astragaloside IV in anhydrous ethanol is 1.5-2.2%, the mass fraction of Prussian blue nanozyme in acetonitrile is 1.8-2.4%, and the mass fraction of hydrochlorothiazide in acetone is 3%.

5. The Chinese medicine composition for treating acute heart failure according to claim 4, characterized in that In S5, the mass fraction of the fucosylated chondroitin sulfate in ultrapure water is 10%.

6. The Chinese medicine composition for treating acute heart failure according to claim 5, characterized in that The preparation method of the vasodilator preparation specifically comprises the following steps: L1. Mix nitroglycerin, isosorbide mononitrate, and ultrapure water to obtain a blood circulation promoting solution; L2, crushing horse chestnut, wormwood, and witch hazel, and extracting them with ultrapure water to obtain a vasodilator extract; L3, mixing the vasodilator extract prepared in L2 with the blood circulation promoting solution prepared in L1 to obtain a viscous mixture; L4, mixing sodium carboxymethyl cellulose, ultrapure water, hydrochloric acid, and calcium carbonate to obtain modified carboxymethyl cellulose calcium; L5. Add the modified carboxymethyl cellulose calcium prepared in L4 into the viscous mixture prepared in L3, and mix them to obtain a vasodilator preparation.

7. The Chinese medicine composition for treating acute heart failure according to claim 6, characterized in that In L1, the mass fraction of the isosorbide mononitrate in ultrapure water is 1.3-1.7%, and in L2, the solid-liquid ratio of the horse chestnut to ultrapure water is 1:3.5 g / mL.

8. The Chinese medicine composition for treating acute heart failure according to claim 7, characterized in that In L4, the mass fraction of the sodium carboxymethyl cellulose in ultrapure water is 1%.

9. A method for preparing a Chinese medicine composition for treating acute heart failure according to any one of claims 1 to 8, characterized in that: The specific steps include: Step 1: Grind andrographis paniculata, wild chrysanthemum, and neem, filter them with sterile gauze, mix and dissolve them with ophiopogon polysaccharide, sesamin, cornus officinalis extract, and 70% ethanol solution to obtain an anti-infection and side effect reducing agent; Step 2: uniformly mixing the load-reducing particles and the vasodilator, and tableting to obtain a tablet for treating acute heart failure; Step 3: spray the anti-infection and side effect reducing agent prepared in step 1 evenly on the surface of the sheet for treating acute heart failure prepared in step 2, place it at a temperature of 25-28°C for 2-2.5 hours, and air-dry it to obtain a Chinese medicine composition for treating acute heart failure.

10. The method for preparing the Chinese medicine composition for treating acute heart failure according to claim 9, wherein: In step 1, the mass fraction of the Ophiopogon japonicus polysaccharide in the 70% ethanol solution is 5-8%.

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