A traditional Chinese medicine composition for treating arrhythmia and a preparation method thereof

Abstract

The present application relates to a kind of traditional Chinese medicine composition for treating arrhythmia disease and its preparation method, the traditional Chinese medicine composition is by the following weight ratio of active ingredient composition: radix codonopsis extract 28~32 parts, radix ophiopogonis extract 37~43 parts, radix notoginseng extract 4~8 parts, amber 3~5 parts, extract of gancao 18~22 parts.The effective material component content of traditional Chinese medicine composition in the present application has the advantage of stable quality.The preparation method process has scientific feasibility, high extraction efficiency, and good market application prospect.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine composition for treating arrhythmia and its preparation method, belonging to the field of traditional Chinese medicine technology. Background Technology

[0002] In recent years, with the increasing aging of Chinese society, the incidence of senile arrhythmias has been rising year by year. Arrhythmias are caused by impaired cardiac conduction, and their clinical manifestations include chest tightness, shortness of breath, palpitations, and abnormal heart rhythm. Arrhythmias are considered critical illnesses, and antiarrhythmic drugs are commonly used. While these drugs can improve clinical symptoms, they also have high levels of side effects. Traditional Chinese medicine (TCM) has significant advantages in treating these diseases. The TCM composition for treating arrhythmias described in this invention is Wenxin Granules, prepared from herbs such as Codonopsis pilosula, Polygonatum sibiricum, Panax notoginseng, amber, and Nardostachys jatamansi. It has the effects of invigorating qi and nourishing yin, promoting blood circulation and removing blood stasis. It can be used for palpitations, shortness of breath, and fatigue caused by qi and yin deficiency and blood stasis in the heart vessels, as well as symptoms such as chest tightness, chest pain, and premature ventricular contractions.

[0003] The applicant of this invention has filed multiple prior patent applications for this product, with application numbers as follows: 01131734.5 (A traditional Chinese medicine for treating arrhythmia and its preparation method), 200410081398.2 (A traditional Chinese medicine preparation for treating arrhythmia and its preparation method), 200530090041.6 (Drug packaging box), 200610042976.0 (Preparation method and quality control method), 200610042974.1 (Quality testing standard method), 200810232536.0 (Application in the prevention and treatment of allergic diseases), and 200810183930. .X (Application in fracture medicines), 201510145198.7 (Detection method of volatile components in Wenxin granules), 201610013406.2 (High performance liquid chromatography detection method), 201811308826.9 (Application of Codonopsis pilosula glycoside analogs in the preparation of drugs for treating arrhythmia), 201910483321.4 (Iso-piperane type diterpenoids and their preparation methods), 202210084515.9 (Detection method of Wenxin traditional Chinese medicine composition), 202210355751.X (Detection of volatile components of Nardostachys jatamansi and construction of fingerprint spectrum method).

[0004] A systematic review of existing technical literature on this product by the applicant of this invention reveals that the quality standard for Wenxin Granules, as recorded in the 2020 edition of the Chinese Pharmacopoeia, is: each bag contains not less than 17.0 mg of Panax notoginseng saponin R1 (C47H80O18), ginsenoside Rg1, and ginsenoside Rb1. Dosage and administration: Dissolve in boiling water. One bag (9g / bag) at a time, three times a day. The preparation process of this product is as follows: Amber is crushed into fine powder, volatile oil is extracted from Nardostachys jatamansi, and the aqueous solution after extraction is collected; Panax notoginseng is crushed into coarse powder and extracted twice with 80% ethanol under reflux for 2 hours each time, filtered, the filtrates are combined, and concentrated under reduced pressure to a clear extract; the residue is decocted twice with water, the first time for 2 hours and the second time for 1.5 hours, and the decoctions are combined; Codonopsis pilosula and Polygonatum sibiricum are decocted twice with water, and the decoctions are combined with the above decoctions and filtered; the filtrate is concentrated to a clear extract with a relative density, ethanol is added to make the alcohol content reach 65%, stirred, and allowed to stand for 24 hours, filtered, and the filtrate is concentrated under reduced pressure to a thick extract, which is then combined with the Panax notoginseng extract and mixed evenly. Add the above-mentioned amber powder, sucrose, betacyclodextrin, aspartame, and dextrin, mix well, granulate, dry, spray in spikenard volatile oil, mix well, and make granules; or add the above-mentioned amber powder, aspartame, dextrin, and an appropriate amount of soluble starch, mix well, granulate, dry, spray in spikenard volatile oil, mix well, and make granules without sucrose, thus obtaining the final product.

[0005] Wenxin Granules enjoy a good reputation in the market for traditional Chinese medicine treatment of arrhythmia, and its sales volume has been increasing year by year. However, the product contains Nardostachys jatamansi, amber, Polygonatum sibiricum, Panax notoginseng, and Codonopsis pilosula, all of which are precious medicinal materials. Nardostachys jatamansi and amber are rare varieties of traditional Chinese medicine, and the resources of these medicinal materials are very scarce.

[0006] Improving the enrichment and utilization rate of the effective components of the aforementioned medicinal materials to address the increasingly strained resources of traditional Chinese medicine is an urgent task. However, in actual clinical application, the large dosage of this herbal composition causes inconvenience for some elderly patients and also results in significant resource waste. Therefore, we have found that the clinical efficacy of the herbal preparation made using the above method needs further optimization and improvement. Researching and developing a stable herbal preparation with better efficacy and a higher degree of enrichment of active ingredients is particularly pressing. Summary of the Invention

[0007] The purpose of this invention is to provide a traditional Chinese medicine composition for treating arrhythmia and its preparation method. This traditional Chinese medicine composition has reliable clinical efficacy, high concentration of effective ingredients, can greatly reduce the dosage for patients, save raw material costs, and improve the utilization rate of medicinal resources.

[0008] The traditional Chinese medicine composition of this invention includes: Codonopsis pilosula extract, Polygonatum sibiricum extract, Panax notoginseng extract, and Nardostachys chinensis extract. These active ingredients have the advantages of high content and stable quality. The preparation method is scientifically feasible, has high extraction efficiency, and shows good market application prospects.

[0009] The technical solution of this invention is as follows:

[0010] A traditional Chinese medicine composition for treating arrhythmia, the composition comprising the following active ingredients in the indicated weight ratios: 28-32 parts of Codonopsis pilosula extract, 37-43 parts of Polygonatum sibiricum extract, 4-8 parts of Panax notoginseng extract, 3-5 parts of amber, and 18-22 parts of Nardostachys jatamansi extract.

[0011] A preferred embodiment of the traditional Chinese medicine composition of the present invention is composed of the following active ingredients in the indicated weight ratios: 30 parts Codonopsis pilosula extract, 30 parts Polygonatum sibiricum extract, 60 parts Panax notoginseng extract, 4 parts amber, and 20 parts Nardostachys jatamansi extract.

[0012] As a preferred embodiment of the present invention, the content of the Codonopsis pilosula extract is ≥50%, and the active ingredients of the Codonopsis pilosula extract include a mixture of one or more of the following: Codonopsis pilosula polysaccharides, Codonopsis pilosula saponins, and Codonopsis pilosula glycosides.

[0013] As a preferred embodiment of the present invention, the content of the Polygonatum extract is ≥50%, and the active ingredients of the Polygonatum extract include a mixture of one or more of Polygonatum polysaccharides, Polygonatum saponins, and Polygonatum polyphenols.

[0014] As a preferred embodiment of the present invention, the content of the Panax notoginseng extract is ≥60%, and the active ingredients of the Panax notoginseng extract include one or more of the following: Panax notoginseng saponins, ginsenoside Rg1, ginsenoside Rb1, ginsenoside Rd, Panax notoginseng polysaccharides, volatile oil, amino acids, and total polysaccharides.

[0015] As a preferred embodiment of the present invention, the content of the spikenard extract is ≥40%, and the active ingredients of the spikenard extract include one or more of the following: flavonoids, polysaccharides, volatile oils, triterpenoids, phenols, coumarins, and spikenardone.

[0016] As a preferred embodiment of the present invention, the preparation method of the Codonopsis pilosula extract is as follows: take Codonopsis pilosula medicinal material, add water at a weight ratio of 7 to 11 times that of the medicinal material, add cellulase at a dosage of 0.05 to 1.5%, heat at a temperature of 40 to 55°C, extract 1 to 2 times, each enzymatic hydrolysis time is 0.5 to 1.5 hours, filter, combine the filtrates, concentrate the filtrate to obtain a clear extract, add ethanol to make the alcohol content reach 60 to 75%, stir, let stand for 8 to 24 hours, filter, concentrate the filtrate under reduced pressure to a dry extract powder, and obtain the Codonopsis pilosula extract.

[0017] As a further preferred embodiment of the present invention, the preparation method of the Polygonatum extract is as follows: take Polygonatum medicinal material, add water at a weight ratio of 8 to 12 times that of the medicinal material, heat and decoct twice, with a 1-hour interval between each decoction, filter, combine the filtrates, concentrate the filtrate to a clear extract of Polygonatum extract with a relative density of 1.10 to 1.30 (60°C), select AB-8 macroporous resin, the ratio of the amount of Polygonatum extract to the amount of AB-8 resin is 0.3 to 0.5, the mass concentration of the sample Polygonatum extract is 0.7 to 1.2 mg / ml, the equilibration adsorption time is 8 to 12 hours, elute with pure water for 3 to 5 column volumes, collect the eluent of different concentrations of 40% to 60% ethanol-water, elute for 3 to 6 column volumes, collect the eluent, and concentrate to obtain Polygonatum extract.

[0018] Preferably, the preparation method of the Panax notoginseng extract is as follows: Panax notoginseng is pulverized into particles passing through a 20-mesh sieve, refluxed with 75-90% ethanol, and ethanol is added at a weight ratio of 8-11 times that of the medicinal material. The extraction is performed 1-3 times, with each decoction lasting 0.5-1.5 hours. The extract is filtered, the filtrates are combined, and concentrated under reduced pressure to obtain a Panax notoginseng concentrate. The concentrate is loaded onto a D101 macroporous resin, washed with water for 3-5 column volumes, then washed with 20-40% ethanol for 4-6 column volumes, and eluted with 60-80% ethanol for 3-6 column volumes. The Panax notoginseng eluent is collected, concentrated, and dried to obtain the Panax notoginseng extract.

[0019] Preferably, the preparation method of the spikenard extract is as follows: take spikenard medicinal material, add water at a weight ratio of 8 to 12 times, extract 1 to 3 times, each time decoction time is 1 to 1.5 hours, steam distill for 1 to 2 hours, collect spikenard volatile oil, combine the above spikenard extract filtrate, concentrate under reduced pressure to a clear paste, add chitosan at a mass fraction of 1.5 to 2.5%, heat and stir evenly at 55°C, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain spikenard extract.

[0020] The preparation method of the traditional Chinese medicine composition of the present invention includes the following steps:

[0021] (1) Take Codonopsis pilosula medicinal material, add water at a weight ratio of 7 to 11 times that of the medicinal material, add 0.05 to 1.5% of cellulase, heat at 40 to 55℃, extract 1 to 2 times, each enzymatic hydrolysis time is 0.5 to 1.5 hours, filter, combine the filtrates, concentrate the filtrate to obtain a clear extract, add ethanol to make the alcohol content reach 60 to 75%, stir, let stand for 8 to 24 hours, filter, concentrate the filtrate under reduced pressure to a dry extract powder, and obtain Codonopsis pilosula extract;

[0022] (2) Take Polygonatum sibiricum, add water at a weight ratio of 8 to 12 times, heat and decoct 1 to 2 times, each decoction time is 0.5 to 1.5 hours, filter, combine the filtrates, concentrate the filtrate to a clear extract of Polygonatum sibiricum with a relative density of 1.10 to 1.30 (60℃), select AB-8 macroporous resin, the ratio of the amount of Polygonatum sibiricum extract to the amount of AB-8 resin is 0.3 to 0.5, the mass concentration of the sample Polygonatum sibiricum extract is 0.7 to 1.2 mg / ml, the equilibration adsorption time is 8 to 12 hours, elute with pure water for 3 to 5 column volumes, collect the eluent of different concentrations of 40% to 60% ethanol-water, elute for 3 to 6 column volumes, collect the eluent, concentrate to obtain Polygonatum sibiricum extract;

[0023] (3) Take Panax notoginseng and crush it into particles passing through 20 mesh. Reflux with 75-90% ethanol, add 8-11 times the amount of ethanol by weight of the medicinal material, and extract 1-3 times. Each decoction time is 0.5-1.5 hours. Filter, combine the filtrates, concentrate under reduced pressure to obtain Panax notoginseng concentrate. Load the concentrate onto D101 macroporous resin, wash with water for 3-5 column volumes, then wash with 20-40% ethanol for 4-6 column volumes, elute with 60-80% ethanol for 3-6 column volumes, collect the Panax notoginseng eluent, concentrate and dry it to obtain Panax notoginseng extract.

[0024] (4) The amber is pulverized into fine powder of 100-200 nm using ultra-micro pulverization.

[0025] (5) Take Nardostachys jatamansi medicinal material, add water at a weight ratio of 8 to 12 times, extract 1 to 3 times, each time decoction time is 1 to 1.5 hours, steam distill for 1 to 2 hours, collect Nardostachys jatamansi volatile oil, combine the above Nardostachys jatamansi extract filtrate, concentrate under reduced pressure to a clear paste, add chitosan at a mass fraction of 1.5 to 2.5%, heat and stir evenly at 55℃, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys jatamansi extract;

[0026] ⑹ Take the Codonopsis pilosula extract from step (1), Polygonatum sibiricum extract from step (2), Panax notoginseng extract from step (3), amber ultrafine powder from step (4), Nardostachys jatamansi extract and volatile oil from step (5), mix them well, and add pharmaceutical excipients to make various oral preparations.

[0027] A further preferred embodiment of the present invention is the method for preparing the traditional Chinese medicine composition, which includes the following steps:

[0028] (1) Take Codonopsis pilosula, add water at a weight ratio of 10 times that of the medicinal material, add 1% cellulase, heat to 50℃, extract twice, each time for 1 hour, filter, combine the filtrates, concentrate the filtrate to obtain a clear extract, add ethanol to make the alcohol content reach 70%, stir, let stand for 12 hours, filter, concentrate the filtrate under reduced pressure to a dry extract powder, and obtain Codonopsis pilosula extract.

[0029] (2) Take Polygonatum sibiricum, add water at a weight ratio of 10 times that of the medicinal material, heat and decoct twice, with a 1-hour interval between each decoction, filter, combine the filtrates, and concentrate the filtrate to a clear extract of Polygonatum sibiricum with a relative density of 1.10-1.30 (60℃). Select AB-8 macroporous resin, with the ratio of the amount of Polygonatum sibiricum extract to the amount of AB-8 resin being 0.3-0.5, and the mass concentration of the sample Polygonatum sibiricum extract being 0.7-1.2 mg / ml. Equilibrate the adsorption time for 8-12 hours, elute with pure water for 3-5 column volumes, collect the eluents of different concentrations in 40%-60% ethanol-water, elute for 3-6 column volumes, collect the eluents, and concentrate them to obtain the Polygonatum sibiricum extract.

[0030] (3) Take Panax notoginseng and crush it into particles passing through 20 mesh. Reflux with 80% ethanol, add ethanol at a weight ratio of 10 times that of the medicinal material, extract twice, and decoct for 1 hour each time. Filter, combine the filtrates, concentrate under reduced pressure to obtain Panax notoginseng concentrate; load the concentrate onto D101 macroporous resin, wash with water for 4 column volumes, then wash with 30% ethanol for 6 column volumes, elute with 60-80% ethanol for 6 column volumes, collect the Panax notoginseng eluent, concentrate and dry to obtain Panax notoginseng extract;

[0031] (4) The amber is pulverized into fine powder of 100-200 nm using ultra-micro pulverization.

[0032] (5) Take Nardostachys jatamansi, add water at a ratio of 9 times the weight of the herb, extract twice, each time for 1 hour, steam distill for 1.5 hours, collect the volatile oil of Nardostachys jatamansi, combine the above Nardostachys jatamansi extract filtrate, concentrate under reduced pressure to a clear paste, add 2% chitosan by mass, heat and stir evenly at 55℃, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys jatamansi extract.

[0033] ⑹ Take the Codonopsis pilosula extract from step (1), Polygonatum sibiricum extract from step (2), Panax notoginseng extract from step (3), amber ultrafine powder from step (4), Nardostachys jatamansi extract and volatile oil from step (5), mix them well, and add pharmaceutical excipients to make various oral preparations.

[0034] The novel preparation process of this invention can also be used to prepare different oral Chinese medicine preparations such as granules, capsules, tablets or pills to meet the medication needs of different types of patients.

[0035] Granules: The traditional Chinese medicine mixture prepared in this invention is mixed with appropriate amounts of betacyclodextrin, aspartame, dextrin, starch, lactose, mannitol, sodium carboxymethyl starch, and microcrystalline cellulose, granulated, dried, and mixed again to form granules.

[0036] Capsules: The traditional Chinese medicine mixture prepared according to this invention is granulated by adding appropriate excipients such as calcium dihydrogen phosphate, sodium carboxymethyl starch, pregelatinized starch, magnesium stearate, talc, and micronized silica gel, and then filled into capsules to make capsules.

[0037] Droplets: The traditional Chinese medicine mixture prepared according to the present invention is mixed with a suitable matrix, stearic acid, PEG4000, PEG6000, poloxamer, glyceryl monostearate, polyoxyethylene pyrrolidone insect wax, beeswax, and hot melt, and the above matrix excipients are stirred evenly and dripped to make droplets.

[0038] Tablets: The traditional Chinese medicine mixture prepared according to the present invention is mixed evenly with appropriate amounts of starch, lactose, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, magnesium stearate, talc, starch paste and other excipients, granulated and compressed into tablets.

[0039] To further demonstrate the innovativeness of the preparation process technology of this invention, the following is a summary of the numerous process research and screening schemes from the previous stage:

[0040] 1. Process optimization of Polygonatum extract

[0041] 1.1 Orthogonal Experimental Design

[0042] The Polygonatum sibiricum herb was weighed and extracted using a water decoction method. The extract (%) and total polysaccharide content were used as evaluation indicators, and the amount of water added, extraction time, and number of extractions were investigated as factors. An L9 (3 factors, 3 levels) orthogonal experiment was conducted to optimize the extraction process conditions. The content determination method used in this invention was based on the determination method in the 2020 edition of the Chinese Pharmacopoeia. The polysaccharide content of Polygonatum sibiricum was determined using ultraviolet-visible spectrophotometry.

[0043] Table 1. Factor Levels of Orthogonal Experiment

[0044]

[0045] Table 2 Results of the orthogonal experiment

[0046]

[0047] According to the experimental results in Table 2, the optimal preparation and extraction process is: 10 times the amount of water, decocted twice, and each decoction lasts for 60 minutes.

[0048] 1.2 Optimal purification process of Polygonatum sibiricum

[0049] Take Polygonatum sibiricum medicinal material, add water at a weight ratio of 10 times that of the medicinal material, heat and decoct twice, with a 1-hour interval between each decoction, filter, combine the filtrates, and concentrate the filtrate to a clear extract of Polygonatum sibiricum extract with a relative density of 1.15 (60℃). Use AB-8 macroporous resin, with a loading ratio of Polygonatum sibiricum extract to AB-8 resin of 0.36, and a loading concentration of 0.9 mg / ml. Equilibrate for 10 hours, elute with pure water for 4 column volumes, collect the eluents of different concentrations in 50% ethanol-water, elute for 5 column volumes, collect the eluents, and concentrate to obtain Polygonatum sibiricum extract. The purification of Polygonatum sibiricum extract according to the above optimized enrichment process is shown in Table 3.

[0050] Table 3 Validation Experiment of Polygonatum Extraction and Purification Process

[0051]

[0052]

[0053] As can be seen from the results in Table 3 above, the preferred purification process of Polygonatum sibiricum of the present invention has a feasible enrichment effect. The total polysaccharide content of Polygonatum sibiricum extract is 49.67% to 51.04%, and the total saponin content of Polygonatum sibiricum is 2.87% to 3.45%. Therefore, the extraction and purification process of Polygonatum sibiricum polysaccharide components of the present invention is stable and feasible.

[0054] 2. Process optimization of Codonopsis pilosula extract

[0055] 2.1 Optimization of Codonopsis pilosula extraction process

[0056] This invention investigates the effects of water volume, number of decoctions, and extraction time on the extraction rate of Codonopsis pilosula extract, and optimizes the optimal extraction process parameters. The invention uses HPLC and the sulfuric acid-phenol method to determine the content of Codonopsis pilosula polysaccharides. Extract yield (%) = Codonopsis pilosula extract powder / Codonopsis pilosula × 100%.

[0057] Table 4 Comparison of Codonopsis pilosula enzymatic hydrolysis method and traditional extraction process

[0058]

[0059]

[0060] As shown in Table 4, the enzymatic hydrolysis technology used in experiments 4, 5, and 6 of this invention can reduce the resistance of the mass transfer barrier of the cell wall of Codonopsis pilosula, allowing the effective components in Codonopsis pilosula to dissolve from the cell membrane, thereby increasing the extraction rate of Codonopsis pilosula polysaccharides (35.14%–38.57%) and the content of Codonopsis pilosula polysaccharides in the extract (7.69–8.38 mg / g).

[0061] 2.2 Extraction and purification process of Codonopsis pilosula

[0062] Take Codonopsis pilosula medicinal material, add water at a ratio of 10 times the weight of the medicinal material, add 1% cellulase, heat to 50℃, extract twice, each time for 1 hour, filter, combine the filtrates, concentrate the filtrate to obtain a clear extract, add ethanol to make the alcohol content reach 70%, stir, let stand for 12 hours, filter, concentrate the filtrate under reduced pressure to a dry extract powder, and obtain Codonopsis pilosula extract; the content test shows that the total polysaccharide content of the Codonopsis pilosula extract of this invention is 45.35%, the total saponin content is 6.29%, and the content of codonopsis pilosula glycoside is 1.98%.

[0063] 3. Process optimization of Panax notoginseng extract

[0064] The Panax notoginseng herb was pulverized into particles passing through a 20-mesh sieve, extracted twice by refluxing with 80% ethanol, each extraction lasting 1 hour. The filtrates were combined and concentrated under reduced pressure to obtain a concentrated Panax notoginseng extract. The extract was loaded onto a D101 macroporous resin, washed with water for 4 column volumes, then washed with 30% ethanol for 6 column volumes, and eluted with 60-80% ethanol for 6 column volumes. The eluent was collected, concentrated, and dried to obtain the purified Panax notoginseng product. The content determination in this invention uses high-performance liquid chromatography (HPLC), with acetonitrile-water as the mobile phase, gradient elution, a detection wavelength of 203 nm, an injection volume of 10 μL, and a flow rate of 1.0 mL / min. -1 The total content of notoginsenoside R1, ginsenoside Rg1, Rb1 and ginsenoside Re in Panax notoginseng extract was determined to be over 83.16%.

[0065] 4. Processing technology of Nardostachys jatamansi extract

[0066] Take *Nardostachys chinensis* (Gynostemma pentaphyllum) and add water in a ratio of 9 times its weight. Decoction is performed twice, each time for 1 hour. Steam distillation is then carried out for 1.5 hours. The volatile oil of *Nardostachys chinensis* is collected. The filtrates from the above *Nardostachys chinensis* extract are combined and concentrated under reduced pressure to obtain a clear extract. Chitosan (1.5–2.5% by mass) is added, and the mixture is heated and stirred evenly at 50–60°C. After refrigeration and standing for 8–16 hours, the mixture is filtered. The filtrate is spray-dried into a dry powder, sieved, and the *Nardostachys chinensis* extract is obtained. Content analysis shows that the *Nardostachys chinensis* extract contains 23.3% *Nardostachys chinensis* flavonoids, 12.1% *Nardostachys chinensis* polysaccharides, 3.8% *Nardostachys chinensis* triterpenoids, and 2.6% *Nardostachys chinensis* phenols.

[0067] Beneficial effects of the traditional Chinese medicine composition of the present invention

[0068] (1) The innovation of this invention lies in providing a stable traditional Chinese medicine composition with a high content of active ingredients, specifically including the following: ① Optimization of the extraction and purification process of Polygonatum sibiricum, ultimately obtaining a total polysaccharide content of 49.67%–51.04% and a total saponin content of 2.87%–3.45% in the Polygonatum sibiricum extract. ② Optimization of the extraction process of Codonopsis pilosula. This invention adopts the enzymatic hydrolysis method of Codonopsis pilosula, which can reduce the mass transfer barrier resistance of the cell wall of Codonopsis pilosula, allowing the effective components in Codonopsis pilosula to be completely dissolved from the cell membrane, thereby increasing the polysaccharide extraction rate (22.14%–23.57%) and the polysaccharide content in the extract (7.69–8.38 mg / g). ③ Process optimization of Panax notoginseng extract: This invention employs macroporous resin elution purification technology to increase the content of effective components in Panax notoginseng extract. The optimal process yields Panax notoginseng extract with a total content of over 83.16% for notoginsenoside R1, ginsenoside Rg1, Rb1, and ginsenoside Re. ④ Process optimization of Nardostachys jatamansi extract: This invention also employs chitosan purification technology to enrich the effective components in Nardostachys jatamansi extract, ultimately obtaining Nardostachys jatamansi extract containing 23.3% Nardostachys jatamansi flavonoids, 12.1% Nardostachys jatamansi polysaccharides, 3.8% Nardostachys jatamansi triterpenoids, and 2.6% Nardostachys jatamansi phenols.

[0069] (2) Pharmacological experiments show that the herbal composition of this invention can significantly delay the onset of arrhythmia induced by barium chloride solution in rats and shorten its duration. This further confirms that the herbal composition of this invention has a strong protective effect against arrhythmia. Detailed Implementation

[0070] The following are specific embodiments of the present invention, used to illustrate the technical solutions to the technical problems to be solved in this application, and to help those skilled in the art to understand the present invention. However, the implementation of the technical solutions of the present invention is not limited to these embodiments.

[0071] Example 1: Preparation of the traditional Chinese medicine composition granules of the present invention

[0072] (1) Take 300g of Codonopsis pilosula, add water in a ratio of 10 times the weight of the medicinal material, add 1% cellulase, heat to 50℃, extract twice, each time for 1 hour, filter, combine the filtrates, concentrate the filtrate to obtain a clear extract, add ethanol to make the alcohol content reach 70%, stir, let stand for 12 hours, filter, concentrate the filtrate under reduced pressure to a dry extract powder, and obtain Codonopsis pilosula extract;

[0073] (2) Take 400g of Polygonatum sibiricum, add water at a ratio of 10 times the weight of the medicinal material, heat and decoct twice, with a 1-hour interval between each decoction, filter, combine the filtrates, and concentrate the filtrate to a clear extract of Polygonatum sibiricum with a relative density of 1.10-1.30 (60℃). Use AB-8 macroporous resin, with a loading ratio of 0.4 between the amount of Polygonatum sibiricum extract and the amount of AB-8 resin, and a loading concentration of 1mg / ml. Equilibrate for 10 hours, elute with pure water for 3-5 column volumes, collect the eluents of different concentrations in 60% ethanol-water, elute for 5 column volumes, collect the eluents, and concentrate to obtain the Polygonatum sibiricum extract.

[0074] (3) Take 60g of Panax notoginseng, crush it into particles passing through 20 mesh, reflux with 80% ethanol, add ethanol at a weight ratio of 10 times that of the medicinal material, extract twice, each time decoction time is 1 hour, filter, combine the filtrates, concentrate under reduced pressure to obtain Panax notoginseng concentrate; load the concentrate onto D101 macroporous resin, wash with water for 4 column volumes, then wash with 30% ethanol for 6 column volumes, elute with 60% ethanol for 6 column volumes, collect the Panax notoginseng eluent, concentrate and dry to obtain Panax notoginseng extract;

[0075] (4) Grind 40g of amber into fine powder of 100-200nm using ultra-micro pulverization;

[0076] (5) Take 200g of Nardostachys jatamansi, add water at a ratio of 9 times the weight of the herb, extract twice, each time for 1 hour, steam distill for 1.5 hours, collect the volatile oil of Nardostachys jatamansi, combine the above Nardostachys jatamansi extract filtrate, concentrate under reduced pressure to a clear paste, add 2% chitosan by mass, heat and stir evenly at 55℃, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys jatamansi extract;

[0077] ⑹ Take the Codonopsis pilosula extract from step (1), Polygonatum sibiricum extract from step (2), Panax notoginseng extract from step (3), amber ultrafine powder from step (4), and Nardostachys jatamansi extract from step (5). Mix them well, spray in Nardostachys jatamansi volatile oil, add appropriate amounts of betacyclodextrin, aspartame, and dextrin. The ratio of the above mixture to the pharmaceutical excipients is 1:dosage. Granulate and dry to make 1000g granules.

[0078] Example 2: Preparation of capsules containing the traditional Chinese medicine composition of the present invention

[0079] (1) Take 280g of Codonopsis pilosula, add water at a ratio of 11 times the weight of the medicinal material, add 0.8% cellulase, heat to 40℃, extract once, each time for 1.5h, filter, combine the filtrates, concentrate the filtrate to obtain a clear extract, add ethanol to make the alcohol content reach 60%, stir, let stand for 8 hours, filter, concentrate the filtrate under reduced pressure to a dry extract powder, and obtain Codonopsis pilosula extract;

[0080] (2) Take 430g of Polygonatum sibiricum, add water at a ratio of 12 times the weight of the medicinal material, heat and decoct once, each decoction time is 1.5h, filter, combine the filtrates, concentrate the filtrate to a clear extract of Polygonatum sibiricum with a relative density of 1.15 (60℃), select AB-8 macroporous resin, the ratio of the amount of Polygonatum sibiricum extract to the amount of AB-8 resin is 0.5, the mass concentration of the sample Polygonatum sibiricum extract is 0.7mg / ml, the equilibration adsorption time is 12 hours, elute with pure water for 3 to 5 column volumes, collect the eluent of different concentrations in 60% ethanol-water, elute for 3 to 6 column volumes, collect the eluent, concentrate to obtain Polygonatum sibiricum extract;

[0081] (3) Take 40g of Panax notoginseng, crush it into particles passing through 20 mesh, reflux with 90% ethanol, add ethanol at a weight ratio of 11 times that of the medicinal material, extract once, each time decoction time is 1.5 hours, filter, combine the filtrates, concentrate under reduced pressure to obtain Panax notoginseng concentrate; load the concentrate onto D101 macroporous resin, wash with water for 3-5 column volumes, then wash with 20% ethanol for 4-6 column volumes, elute with 60% ethanol for 3-6 column volumes, collect the Panax notoginseng eluent, concentrate and dry to obtain Panax notoginseng extract;

[0082] (4) Grind 30g of amber into fine powder of 100-200nm using ultra-micro pulverization;

[0083] (5) Take 220g of Nardostachys jatamansi, add water at a ratio of 12 times the weight of the herb, extract once, each time for 1.5 hours, steam distill for 2 hours, collect the volatile oil of Nardostachys jatamansi, combine the above Nardostachys jatamansi extract filtrate, concentrate under reduced pressure to a clear paste, add 2.5% chitosan by mass, heat and stir evenly at 55℃, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys jatamansi extract;

[0084] ⑹ Take the Codonopsis pilosula extract from step (1), Polygonatum sibiricum extract from step (2), Panax notoginseng extract from step (3), amber ultrafine powder from step (4), and Nardostachys jatamansi extract from step (5), mix them well, spray in Nardostachys jatamansi volatile oil, add calcium dihydrogen phosphate, sodium carboxymethyl starch, magnesium stearate, granulate, dry, fill into capsules, and make capsules.

[0085] Example 3: Preparation of the herbal medicine composition drop pills of the present invention

[0086] (1) Take 320g of Codonopsis pilosula, add water at a ratio of 7 times the weight of the medicinal material, add 1.1% cellulase, heat to 55℃, extract twice, each time for 0.5h, filter, combine the filtrates, concentrate the filtrate to obtain a clear extract, add ethanol to make the alcohol content reach 75%, stir, let stand for 24 hours, filter, concentrate the filtrate under reduced pressure to a dry extract powder, and obtain Codonopsis pilosula extract;

[0087] (2) Take 370g of Polygonatum sibiricum, add water at a ratio of 8 times the weight of the medicinal material, heat and decoct twice, each time for 0.5h, filter, combine the filtrates, concentrate the filtrate to a clear extract of Polygonatum sibiricum with a relative density of 1.10-1.30 (60℃), select AB-8 macroporous resin, the ratio of the amount of Polygonatum sibiricum extract to the amount of AB-8 resin is 0.3-0.5, the mass concentration of the Polygonatum sibiricum extract is 0.7-1.2mg / ml, the equilibration adsorption time is 8-12 hours, elute with pure water for 3-5 column volumes, collect the eluent of different concentrations of 40%-60% ethanol-water, elute for 3-6 column volumes, collect the eluent, concentrate to obtain Polygonatum sibiricum extract;

[0088] (3) Take 80g of Panax notoginseng, crush it into particles passing through 20 mesh, reflux with 75% ethanol, add ethanol at a weight ratio of 8 times that of the medicinal material, extract 3 times, each time decoction time is 0.5 hours, filter, combine the filtrates, concentrate under reduced pressure to obtain Panax notoginseng concentrate; load the concentrate onto D101 macroporous resin, wash with water for 3-5 column volumes, then wash with 20% ethanol for 4-6 column volumes, elute with 80% ethanol for 3-6 column volumes, collect the Panax notoginseng eluent, concentrate and dry to obtain Panax notoginseng extract;

[0089] (4) Grind 50g of amber into fine powder of 100-200nm using ultra-micro pulverization;

[0090] (5) Take 180g of Nardostachys jatamansi, add water at a ratio of 8 times the weight of the herb, extract 3 times, each time decoct for 1 hour, steam distill for 1 hour, collect the volatile oil of Nardostachys jatamansi, combine the above Nardostachys jatamansi extract filtrate, concentrate under reduced pressure to a clear paste, add chitosan with a mass fraction of 1.5%, heat and stir evenly at 55℃, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys jatamansi extract;

[0091] ⑹ Take the Codonopsis pilosula extract from step (1), Polygonatum sibiricum extract from step (2), Panax notoginseng extract from step (3), amber ultrafine powder from step (4), and Nardostachys jatamansi extract from step (5), mix them evenly, spray in Nardostachys jatamansi volatile oil, add PEG4000, PEG6000, heat melt, and the above matrix excipients, stir evenly, and drip to make drop pills.

[0092] Example 4: Preparation of tablets based on the traditional Chinese medicine composition of the present invention

[0093] (1) Take 320g of Codonopsis pilosula, add water in a ratio of 9 times the weight of the medicinal material, add 1% cellulase, heat to 50℃, extract twice, each time for 1 hour, filter, combine the filtrates, concentrate the filtrate to obtain a clear extract, add ethanol to make the alcohol content reach 70%, stir, let stand for 12 hours, filter, concentrate the filtrate under reduced pressure to a dry extract powder, and obtain Codonopsis pilosula extract;

[0094] (2) Take 370g of Polygonatum sibiricum, add water at a ratio of 10 times the weight of the medicinal material, heat and decoct twice, each time for 1 hour, filter, combine the filtrates, concentrate the filtrate to a clear extract of Polygonatum sibiricum with a relative density of 1.15 (60℃), select AB-8 macroporous resin, the ratio of the amount of Polygonatum sibiricum extract to the amount of AB-8 resin is 0.3, the mass concentration of the Polygonatum sibiricum extract is 1.1mg / ml, the equilibration adsorption time is 10 hours, elute with pure water for 3 to 5 column volumes, collect the eluent of different concentrations in 50% ethanol-water, elute for 3 to 6 column volumes, collect the eluent, concentrate to obtain Polygonatum sibiricum extract;

[0095] (3) Take 80g of Panax notoginseng, crush it into particles passing through 20 mesh, reflux with 80% ethanol, add ethanol at a weight ratio of 10 times that of the medicinal material, extract twice, each time decoction time is 0.5 hours, filter, combine the filtrates, concentrate under reduced pressure to obtain Panax notoginseng concentrate; load the concentrate onto D101 macroporous resin, wash with water for 3-5 column volumes, then wash with 40% ethanol for 4-6 column volumes, elute with 70% ethanol for 3-6 column volumes, collect the Panax notoginseng eluent, concentrate and dry to obtain Panax notoginseng extract;

[0096] (4) Grind 50g of amber into fine powder of 100-200nm using ultra-micro pulverization;

[0097] (5) Take 180g of Nardostachys jatamansi, add water in a ratio of 10 times the weight of the herb, extract twice, each time for 1.5 hours, steam distill for 1.5 hours, collect the volatile oil of Nardostachys jatamansi, combine the above Nardostachys jatamansi extract filtrate, concentrate under reduced pressure to a clear paste, add 2% chitosan by mass, heat and stir evenly at 55℃, refrigerate and stand for 12 hours, filter, spray dry the filtrate into a dry paste powder, sieve to obtain Nardostachys jatamansi extract;

[0098] ⑹ Take the Codonopsis pilosula extract from step (1), Polygonatum sibiricum extract from step (2), Panax notoginseng extract from step (3), amber ultrafine powder from step (4), and Nardostachys jatamansi extract from step (5), mix them evenly, spray in Nardostachys jatamansi volatile oil, add starch, substituted hydroxypropyl cellulose, magnesium stearate, and starch paste, mix evenly, granulate, and compress into tablets.

[0099] Example 5: Preparation of the herbal composition granules of the present invention

[0100] (1) Take 320g of Codonopsis pilosula, add water in a ratio of 10 times the weight of the medicinal material, add 1.2% cellulase, heat to 45℃, extract twice, each time for 0.5h, filter, combine the filtrates, concentrate the filtrate to obtain a clear extract, add ethanol to make the alcohol content reach 65%, stir, let stand for 12 hours, filter, concentrate the filtrate under reduced pressure to a dry extract powder, and obtain Codonopsis pilosula extract;

[0101] (2) Take 370g of Polygonatum sibiricum, add water at a ratio of 9 times the weight of the medicinal material, heat and decoct twice, with a 1-hour interval between each decoction, filter, combine the filtrates, and concentrate the filtrate to a clear extract of Polygonatum sibiricum with a relative density of 1.20 (60℃). Use AB-8 macroporous resin, with the ratio of the amount of Polygonatum sibiricum extract to the amount of AB-8 resin being 0.3 to 0.5, and the mass concentration of the Polygonatum sibiricum extract being 0.9 mg / ml. Equilibrate the adsorption time for 10 hours, elute with pure water for 3 to 5 column volumes, collect the eluents of different concentrations in 60% ethanol-water, elute for 3 to 6 column volumes, collect the eluents, and concentrate them to obtain the Polygonatum sibiricum extract.

[0102] (3) Take 80g of Panax notoginseng, crush it into particles passing through 20 mesh, reflux with 80% ethanol, add ethanol at a weight ratio of 10 times that of the medicinal material, extract twice, each time decoction time is 1 hour, filter, combine the filtrates, concentrate under reduced pressure to obtain Panax notoginseng concentrate; load the concentrate onto D101 macroporous resin, wash with water for 3-5 column volumes, then wash with 30% ethanol for 4-6 column volumes, elute with 70% ethanol for 3-6 column volumes, collect the Panax notoginseng eluent, concentrate and dry to obtain Panax notoginseng extract;

[0103] (4) Grind 50g of amber into fine powder of 100-200nm using ultra-micro pulverization;

[0104] (5) Take 180g of Nardostachys jatamansi, add water in a ratio of 10 times the weight of the herb, extract twice, each time for 1.5 hours, steam distill for 1 hour, collect the volatile oil of Nardostachys jatamansi, combine the above Nardostachys jatamansi extract filtrate, concentrate under reduced pressure to a clear paste, add 2% chitosan by mass, heat and stir evenly at 55℃, refrigerate and stand for 12 hours, filter, spray dry the filtrate into a dry paste powder, sieve to obtain Nardostachys jatamansi extract;

[0105] ⑹ Take the Codonopsis pilosula extract from step (1), Polygonatum sibiricum extract from step (2), Panax notoginseng extract from step (3), amber ultrafine powder from step (4), and Nardostachys jatamansi extract from step (5), mix them, spray in Nardostachys jatamansi volatile oil, add dextrin, starch, lactose, sodium carboxymethyl starch, mix well, granulate, dry, mix well, and make granules.

[0106] Comparative Example 1: Preparation of the stabilized particles of the present invention (closest to prior art CN01131734.5)

[0107] The present invention is prepared according to the prior art CN01131734.5, which is closest to the prior art. The specific scheme is as follows:

[0108] Take 300g of Codonopsis pilosula, 400g of Polygonatum sibiricum, 60g of Panax notoginseng, 40g of amber, and 200g of Nardostachys jatamansi.

[0109] Preparation method: The above five ingredients are prepared by grinding amber into fine powder, extracting volatile oil from nardostachys jatamansi, and collecting the aqueous solution after extraction separately; grinding Panax notoginseng into coarse powder, and extracting twice with 80% ethanol under reflux for 2 hours each time, filtering, combining the filtrates, and concentrating under reduced pressure to a suitable clear extract, adding water to the residue and decocting twice, the first time for 2 hours and the second time for 1.5 hours, and combining the decoctions; adding water to Codonopsis pilosula and Polygonatum sibiricum and decocting twice, the first time for 2 hours and the second time for 1.5 hours, combining the decoctions with the above decoctions, filtering; concentrating the filtrate to a clear extract with a relative density of 1.20-1.30 (60℃), adding ethanol to make the alcohol content reach 65%, stirring, standing for 24 hours, filtering, concentrating the filtrate under reduced pressure to a suitable thick extract, combining it with the Panax notoginseng extract, and mixing well. Add the above-mentioned amber powder, 518g of sucrose, 100g of betacyclodextrin, 2.47g of aspartame, and an appropriate amount of dextrin. Mix well, granulate, dry, spray in spikenard volatile oil, mix well, and make 1000g of granules.

[0110] The contents of the granules prepared by the method of the preferred embodiment of the present invention and the granules prepared according to the method of comparative example 1 of the present invention (closest to the prior art CN01131734.5) were compared. The content determination can be performed according to the detection method in the relevant patent application 202210084515.9, and is calculated as the total amount of Panax notoginseng saponin R1 (C47H80O18), ginsenoside Rg1 (C42H72O14), and ginsenoside Rb1 (C54H92O23). The chromatographic conditions used acetonitrile as mobile phase A and water as mobile phase B, with the following gradient elution program: From 0 to 12 min, the volume ratio of mobile phase A was 16–19%, and the volume ratio of mobile phase B was 84–81%; from 12 to 35 min, the volume ratio of mobile phase A was 19–24%, and the volume ratio of mobile phase B was 81–76%; from 35 to 38 min, the volume ratio of mobile phase A was 24–28%, and the volume ratio of mobile phase B was 76–72%; from 38 to 60 min, the volume ratio of mobile phase A was 28–31%, and the volume ratio of mobile phase B was 72–69%; from 60 to 70 min, the volume ratio of mobile phase A was 31–43%, and the volume ratio of mobile phase B was 69–57%. The detection column temperature was 20–30 °C, and the detection wavelength was 203 nm. The theoretical plate number, calculated based on the ginsenoside Rg1 peak, should not be less than 2000. Specific content indicators are as follows.

[0111] Table 5 Comparison of the content of the granules of this invention with the drug closest to the prior art.

[0112]

[0113] As shown in Table 5, the traditional Chinese medicine composition prepared by this invention has a further enrichment and improvement in the content of effective ingredients compared with the drug in Comparative Example 1, especially in the content of total saponins, total polysaccharides of Polygonatum sibiricum, total polysaccharides of Codonopsis pilosula, and total flavonoids of Nardostachys jatamansi, which are significantly improved.

[0114] Experimental Example 1: Pharmacological Experiment of the Traditional Chinese Medicine Composition of the Present Invention on Antiarrhythmia

[0115] 1. Experimental Materials

[0116] 1.1 Medicines and Reagents

[0117] The traditional Chinese medicine composition of this invention is a drug prepared according to the method of Example 1 of this invention.

[0118] (1) Take 300g of Codonopsis pilosula, add water in a ratio of 10 times the weight of the medicinal material, add 1% cellulase, heat to 50℃, extract twice, each time for 1 hour, filter, combine the filtrates, concentrate the filtrate to obtain a clear extract, add ethanol to make the alcohol content reach 70%, stir, let stand for 12 hours, filter, concentrate the filtrate under reduced pressure to a dry extract powder, and obtain Codonopsis pilosula extract;

[0119] (2) Take 400g of Polygonatum sibiricum, add water at a ratio of 10 times the weight of the medicinal material, heat and decoct twice, with a 1-hour interval between each decoction. Filter, combine the filtrates, and concentrate the filtrate to a clear extract of Polygonatum sibiricum with a relative density of 1.10–1.30 (60℃). Use AB-8 macroporous resin, with a loading ratio of 0.4 between the amount of Polygonatum sibiricum extract and the amount of AB-8 resin. The mass concentration of the loaded Polygonatum sibiricum extract is 1 mg / ml. Allow the adsorption to equilibrate for 10 hours, then elute with pure water for 3–5 column volumes, and collect 60% of the extract. ethanol-water The above-mentioned eluents of different concentrations were used to elute for 5 column volumes. The eluents were collected and concentrated to obtain the Polygonatum extract.

[0120] (3) Take 60g of Panax notoginseng, crush it into particles passing through 20 mesh, reflux with 80% ethanol, add ethanol at a weight ratio of 10 times that of the medicinal material, extract twice, each time decoction time is 1 hour, filter, combine the filtrates, concentrate under reduced pressure to obtain Panax notoginseng concentrate; load the concentrate onto D101 macroporous resin, wash with water for 4 column volumes, then wash with 30% ethanol for 6 column volumes, elute with 60% ethanol for 6 column volumes, collect the Panax notoginseng eluent, concentrate and dry to obtain Panax notoginseng extract;

[0121] (4) Grind 40g of amber into fine powder of 100-200nm using ultra-micro pulverization;

[0122] (5) Take 200g of Nardostachys jatamansi, add water at a ratio of 9 times the weight of the herb, extract twice, each time for 1 hour, steam distill for 1.5 hours, collect the volatile oil of Nardostachys jatamansi, combine the above Nardostachys jatamansi extract filtrate, concentrate under reduced pressure to a clear paste, add 2% chitosan by mass, heat and stir evenly at 55℃, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys jatamansi extract;

[0123] ⑹ Take the Codonopsis pilosula extract from step (1), Polygonatum sibiricum extract from step (2), Panax notoginseng extract from step (3), amber ultrafine powder from step (4), and Nardostachys jatamansi extract from step (5). Mix them well, spray in Nardostachys jatamansi volatile oil, add appropriate amounts of betacyclodextrin, aspartame, and dextrin, granulate, and dry to make granules.

[0124] Positive control group drug: propafenone, 50 mg / tablet. The control group drug was prepared by the method in Example 1 of patent 01131734.5 and is called group 01131734.5. Saline group: 0.9% physiological saline, barium chloride (prepared to a concentration of 5%), chloral hydrate (prepared to a concentration of 10%).

[0125] 1.2 Experimental Apparatus

[0126] Electronic balance: provided by Shanghai Balance Instrument Factory and Science and Technology Experiment Center; Powerlab multi-channel physiological recorder.

[0127] 1.3 Experimental Animals and Grouping

[0128] Forty healthy adult Wistar rats, regardless of sex, weighing (200±20) g, were purchased from the Experimental Animal Center of Shaanxi University of Traditional Chinese Medicine (renamed: commercially available). The 40 rats were randomly divided into 4 groups of 10 rats each: normal control group (physiological saline), positive control group (propafenone), 01131734.5 group, and the herbal composition group of this invention.

[0129] 1.4 Experimental Methods

[0130] After acclimatizing the rats in the experimental group for 2-3 days, the dosage for each group was the same, with a dose of 110 mg / kg administered by gavage with physiological saline. －1 Positive control group (dose 50 mg / kg) －1 Group 01131734.5 (dose 426 mg / kg) －1 The oral dose of the herbal composition of this invention is 213 mg / kg. －1Rats in each experimental group were administered the drug via gavage once daily for 7 consecutive days. Thirty minutes after the last dose, rats were anesthetized via intraperitoneal injection of 10% chloral hydrate at a dose of 250 mg / kg. The rats were then fixed supine on a board and connected to a multi-lead electrophysiological analyzer to record the electrocardiogram (ECG) in lead II. Thirty minutes after anesthesia, a 0.5% barium chloride solution was rapidly injected via the sublingual vein at a dose of 4 mg / kg, ideally within 5 seconds. ECG recordings in lead II were started immediately, and the onset and duration of arrhythmias in each group were observed.

[0131] 2. Experimental Detection Results

[0132] 2.1 Effects on barium chloride-induced ventricular fibrillation in rats

[0133] Table 6. Effects of each drug group on barium chloride-induced ventricular fibrillation in rats.

[0134]

[0135] Note: Compared with the normal group, *P<0.01.

[0136] As shown in Table 6, after one week of treatment, compared with the normal control group, the herbal composition group, the 01131734.5 group, and the positive control group all effectively reduced the incidence of ventricular fibrillation induced by barium chloride solution in rats, with significant differences (P<0.01). The above demonstrates that the herbal composition group of this invention has significant therapeutic and protective effects against ventricular fibrillation in barium chloride rats and can reduce the incidence of ventricular fibrillation in experimental rats.

[0137] 2.2 Effects on barium chloride-induced arrhythmias in rats

[0138] Table 7. Effects of each drug group on barium chloride-induced arrhythmia in rats.

[0139]

[0140] Note: Compared with the normal group, *P<0.01; compared with the positive control drug, ■ P<0.01.

[0141] As shown in Table 7, the positive control group (propafenone), the 01131734.5 group, and the herbal composition group of this invention all significantly delayed the onset of barium chloride-induced arrhythmias in rats and shortened their duration, showing a significant difference compared to the normal control group (P < 0.01). Therefore, compared to the 01131734.5 group, the herbal composition group of this invention, with a 50% dosage, has a significant advantage in delaying the onset of barium chloride-induced arrhythmias in rats and shortening their duration, which is statistically significant (P < 0.01).

[0142] In summary, the herbal composition of this invention can significantly delay the onset of barium chloride-induced arrhythmia in rats and shorten its duration. This further confirms that the animal experimental results of this invention show that, compared with group 01131734.5, the herbal composition of this invention achieves an effect comparable to that of group 01131734.5 with a dosage reduced by half. The herbal composition of this invention has a strong protective effect against arrhythmia. These pharmacological effects form the pharmacological basis for treating arrhythmia, thus demonstrating the outstanding beneficial effects of the herbal composition of this invention.

Claims

1. A traditional Chinese medicine composition for treating arrhythmia, characterized in that, The traditional Chinese medicine composition consists of the following active ingredients in the indicated weight ratios: 28-32 parts Codonopsis pilosula extract, 37-43 parts Polygonatum sibiricum extract, 4-8 parts Panax notoginseng extract, 3-5 parts amber, and 18-22 parts Nardostachys jatamansi extract. The preparation method includes the following steps: (1) Take Codonopsis pilosula medicinal material, add water at a weight ratio of 7 to 11 times that of the medicinal material, add 0.05 to 1.5% cellulase, heat at 40 to 55℃, extract 1 to 2 times, each enzymatic hydrolysis time is 0.5 to 1.5 hours, filter, combine the filtrates, concentrate the filtrate to obtain a clear extract, add ethanol to make the alcohol content reach 60 to 75%, stir, let stand for 8 to 24 hours, filter, concentrate the filtrate under reduced pressure to a dry extract powder, and obtain Codonopsis pilosula extract; (2) Take Polygonatum sibiricum, add water at a weight ratio of 8 to 12 times, heat and decoct 1 to 2 times, with each decoction lasting 0.5 to 1.5 hours. Filter, combine the filtrates, and concentrate the filtrate to a clear extract of Polygonatum sibiricum with a relative density of 1.10 to 1.30 (60℃). Use AB-8 macroporous resin, with the ratio of the amount of Polygonatum sibiricum extract to the amount of AB-8 resin being 0.3 to 0.

5. The mass concentration of the Polygonatum sibiricum extract is 0.7 to 1.2 mg / ml. Equilibrate the adsorption time to 8 to 12 hours. Elute with pure water for 3 to 5 column volumes, collect the eluent of different concentrations of 40% to 60% ethanol-water, elute for 3 to 6 column volumes, collect the eluent, and concentrate it to obtain the Polygonatum sibiricum extract. (3) Take Panax notoginseng and crush it into particles passing through 20 mesh. Reflux with 75-90% ethanol, add 8-11 times the weight of the medicinal material in ethanol, and extract 1-3 times. Each decoction time is 0.5-1.5 hours. Filter, combine the filtrates, concentrate under reduced pressure to obtain Panax notoginseng concentrate. Load the concentrate onto D101 macroporous resin, wash with water for 3-5 column volumes, then wash with 20-40% ethanol for 4-6 column volumes, elute with 60-80% ethanol for 3-6 column volumes, collect the Panax notoginseng eluent, concentrate and dry it to obtain Panax notoginseng extract. (4) The amber is pulverized into fine powder of 100-200 nm using ultra-micro pulverization. (5) Take Nardostachys jatamansi medicinal material, add water at a weight ratio of 8 to 12 times, extract 1 to 3 times, each time decoction time is 1 to 1.5 hours, steam distill for 1 to 2 hours, collect Nardostachys jatamansi volatile oil, combine the above Nardostachys jatamansi extract filtrate, concentrate under reduced pressure to a clear paste, add chitosan at a mass fraction of 1.5 to 2.5%, heat and stir evenly at 55℃, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys jatamansi extract; ⑹ Take the Codonopsis pilosula extract from step (1), Polygonatum sibiricum extract from step (2), Panax notoginseng extract from step (3), amber ultrafine powder from step (4), Nardostachys jatamansi extract and volatile oil from step (5), mix them well, and add pharmaceutical excipients to make various oral preparations.

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