A traditional Chinese medicine composition for reducing lipid, a preparation method and application thereof

Abstract

The application belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for reducing lipid, a preparation method and application. The traditional Chinese medicine composition for reducing lipid provided by the application comprises a lipid-reducing core component and an auxiliary component. The lipid-reducing core component is composed of Camellia pitardii and Dalbergia odorifera. The auxiliary component comprises hawthorn and Salvia miltiorrhiza. The traditional Chinese medicine composition for reducing lipid provided by the application has a simple composition, can significantly improve the blood lipid indexes of a hyperlipidemia model animal, can reduce the body weight of the model animal, and can reduce the expression amount of the inflammatory factor TNF-alpha of the hyperlipidemia model animal.

Description

[0001] Priority Application

[0002] This application claims priority to Chinese Invention Patent Application No. 2024119186453, “A Traditional Chinese Medicine Composition for Reducing Lipids and Preparation Method and Application,” filed on December 24, 2024, which is incorporated by reference in its entirety. TECHNICAL FIELD

[0003] The present application belongs to the technical field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine composition for reducing lipids and a preparation method and application thereof. BACKGROUND

[0004] Hyperlipidemia has become a common clinical disease and is one of the “three big killers” that threaten human life and health. It is closely related to the occurrence of various cardiovascular diseases. Therefore, studying effective lipid-lowering programs is of great significance for the prevention and treatment of cardiovascular diseases. According to statistics, the market size of blood lipid-lowering drugs in China has been increasing continuously. The market size increased from 27.44 billion yuan in 2017 to 40.23 billion yuan in 2021. In 2022, the market size of lipid-lowering drugs in China was about 47 billion yuan, with a compound annual growth rate of 10.0%. In the sales share of lipid-lowering drugs in public hospitals, statins dominated the market. Other traditional Chinese medicine lipid-lowering drugs such as Xuezhikang and probucol also occupy a place in the market.

[0005] Chemical drugs have obvious clinical treatment effects, but have problems such as single action target and easy to cause adverse reactions (such as blood sugar disorder, rhabdomyolysis, abnormal liver function, etc.). Compared with chemical drugs, traditional Chinese medicine has the advantages of high safety, multiple pathways, and low price in the treatment of reducing blood lipids. In addition, traditional Chinese medicine not only can reduce blood lipids, but also has multiple effects such as antioxidant, blood glucose lowering, and immune enhancement, and can achieve the treatment of both symptoms and root causes. Therefore, traditional Chinese medicine lipid-lowering drugs can provide patients with safer and more effective treatment options. However, traditional Chinese medicine faces problems such as unclear treatment mechanism and not obvious treatment effect. Therefore, improving the efficacy and safety of traditional Chinese medicine treatment is the key to developing new traditional Chinese medicine.

[0006] The patent with the publication number CN110742990A and the invention name "A traditional Chinese medicine composition for treating non-alcoholic simple fatty liver, preparation and application" discloses an active composition, which comprises 24-36 parts of fructus randiae, 8-12 parts of radix alismatis, 8-12 parts of curcuma, 8-12 parts of radix astragali, 8-12 parts of hawthorn, 8-12 parts of lotus leaf, 8-12 parts of radix salviae miltiorrhizae and 2-4 parts of radix notoginseng powder. The active composition has the effects of removing dampness and promoting bile secretion, removing oiliness and reducing blood lipids, and the like. It is verified by experiments that the active composition has a curative effect on non-alcoholic simple fatty liver and can eliminate multiple liver function abnormality indexes of patients with non-alcoholic simple fatty liver. However, the active composition adds multiple heat-clearing and purgative ingredients (such as radix alismatis and lotus leaf), but these ingredients have a relatively large stimulation on the gastrointestinal tract. In addition, the radix notoginseng powder is not suitable for all people.

[0007] In summary, it is necessary to propose new methods and strategies to improve the prior art. SUMMARY

[0008] The purpose of the present application is to provide a traditional Chinese medicine composition for reducing lipid, a preparation method and application, which partially solve or alleviate the above-mentioned deficiencies in the prior art. The present application specifically adopts the following technical solutions.

[0009] In one aspect, the present application provides a traditional Chinese medicine composition for reducing lipid, which comprises a lipid-reducing core component and an auxiliary component. The lipid-reducing core component is composed of fructus randiae and lignum aloes. The auxiliary component comprises hawthorn and radix salviae miltiorrhizae. The weight ratio of fructus randiae to lignum aloes in the lipid-reducing core component is 6-10:1. The weight ratio of hawthorn to radix salviae miltiorrhizae in the auxiliary component is 1:5-1. The total weight of the lipid-reducing core component is less than the total weight of the auxiliary component.

[0010] Further, the weight ratio of fructus randiae to lignum aloes in the lipid-reducing core component comprises 6:1, 7:1, 8:1, 9:1 or 10:1.

[0011] Further, the weight ratio of hawthorn to radix salviae miltiorrhizae in the auxiliary component comprises 1:1, 2:1, 3:1, 4:1 or 5:1.

[0012] In some preferred embodiments, the weight ratio of hawthorn to radix salviae miltiorrhizae in the auxiliary component is 1:1.

[0013] Further, the weight ratio of the lipid-reducing core component to the auxiliary component is 13:40-35:40.

[0014] Further, the traditional Chinese medicine composition specifically comprises the following materials in the weight parts: 10-40 parts of fructus randiae, 3-10 parts of lignum aloes, 20-40 parts of hawthorn and 20-40 parts of radix salviae miltiorrhizae.

[0015] Further, the traditional Chinese medicine composition specifically comprises the following materials in weight parts: Loropetalum chinense 10-30 parts, Oudou 3-7 parts, Crataegus pinnatifida 20-30 parts, and Salvia miltiorrhiza 20-30 parts.

[0016] In some preferred embodiments, the traditional Chinese medicine composition for reducing lipid comprises Crataegus pinnatifida 20 parts, Salvia miltiorrhiza 20 parts, Loropetalum chinense 30 parts, and Oudou 5 parts.

[0017] In some preferred embodiments, the traditional Chinese medicine composition for reducing lipid comprises Crataegus pinnatifida 20 parts, Salvia miltiorrhiza 20 parts, Loropetalum chinense 30 parts, and Oudou 5 parts.

[0018] More preferably, the traditional Chinese medicine composition comprises Loropetalum chinense 10 g, Oudou 3 g, Crataegus pinnatifida 20 g, and Salvia miltiorrhiza 20 g.

[0019] Further, the Oudou comprises Oudou medicinal materials and Oudou oil prepared by extraction of the Oudou medicinal materials.

[0020] Further, the Oudou medicinal materials comprise Oudou powder and / or Oudou sheet materials.

[0021] Further, the traditional Chinese medicine composition is extracted by water extraction and / or alcohol extraction.

[0022] The present application also provides a preparation method.

[0023] The preparation method of the traditional Chinese medicine composition comprises the following steps:

[0024] S01: prepare the first material comprising the following materials in weight parts: Loropetalum chinense 10-40 parts, Crataegus pinnatifida 20-40 parts, and Salvia miltiorrhiza 20-40 parts; and prepare Oudou in weight parts 3-10 parts as the second material;

[0025] S02: add 10-20 times the volume of pure water to the first material, soak thoroughly, and then extract at 90-100°C for 60-100 min to obtain the first extract; add 5-10 times the volume of pure water to the first material again, continue to extract at 90-100°C for 60-100 min; then add the second material, and extract for 10-30 min to obtain the second extract; combine the two extracts, concentrate, and dry to obtain the dry extract.

[0026] In some preferred embodiments, the extraction temperature is 95-100°C; and the extraction time after adding the second material is 10-20 min.

[0027] Further, the preparation method further comprises the following steps:

[0028] S02: After the first material and the second material are mixed evenly, 6-10 times the volume of high-concentration ethanol based on the weight of the material is added, and the mixture is soaked by ultrasonic treatment, and then extracted at 60-75℃ by reflux for 60-100 minutes, and the first extract is obtained by filtration; 6-10 times the volume of high-concentration ethanol is added again, and the mixture is extracted at 60-75℃ by reflux for 60-100 minutes, and the second extract is obtained by filtration; the two extracts are combined, concentrated, and dried to obtain a dry extract.

[0029] In some preferred embodiments, the ultrasonic treatment time is 30-60 minutes; the reflux extraction temperature is 65-75℃; the ethanol used is high-concentration ethanol, for example 75% ethanol; and the volume of high-concentration ethanol added for the first time is 8-10 times the weight of the material.

[0030] A traditional Chinese medicine preparation comprising the traditional Chinese medicine composition of any one of the preceding embodiments and / or other pharmaceutically acceptable excipients and / or adjuvants.

[0031] As used herein, "pharmaceutically acceptable" means that the compound, material, composition, and / or dosage form is suitable for use with patients without undue toxicity, irritation, allergic response, other complication, commensurate with a reasonable benefit / risk ratio, within the scope of sound medical judgment. "Pharmaceutically acceptable excipients and / or adjuvants" means a pharmaceutically acceptable carrier, diluent, or excipient that is suitable for use in the manufacturing process of a drug at an appropriate step.

[0032] Further, the dosage form of the traditional Chinese medicine preparation includes granules, powders, tablets, capsules, and / or pills.

[0033] For example, for oral administration in the form of tablets, the active traditional Chinese medicine composition can be mixed with a pharmaceutically acceptable orally non-toxic inert carrier (such as glycerol, mannitol, sorbitol, etc.), and can also be mixed with a lubricant (such as talc, colloidal silicon dioxide, magnesium stearate, etc.), a preservative, a dispersant, or a disintegrant to prepare a predetermined dosage form.

[0034] In the traditional Chinese medicine composition for lowering lipid provided by the present application, the Camellia pitardii has the effects of lowering lipid and promoting digestion; the Olibanum is warm in nature, pungent and diffusive in property, and has the effects of activating blood and resolving stasis, and stopping bleeding and relieving pain; and the Olibanum is combined with the Camellia pitardii to form the lipid-lowering core component of the present application. In addition, the Fructus Crataegi and the Salvia miltiorrhiza are also used. The Fructus Crataegi is sour and sweet in taste, and is flat in property, and enters the spleen meridian of foot-taiyin and the liver meridian of foot-jueyin, and has the effects of removing stagnation, breaking knot, promoting blood flow, and resolving stasis. It can remove all stagnation and stasis, and the blood stasis and qi mass are all removed. The Salvia miltiorrhiza is bitter in taste and cold in nature, and enters the heart meridian of hand-shaoyin and the liver meridian of jueyin, and is a ministerial drug in the blood aspect. The Bencao (Materia Medica) states that it can remove stasis, break blood stasis, produce new blood, dredge blood vessels, and promote blood flow.

[0035] Beneficial technical effects:

[0036] (1) This invention provides a novel lipid-lowering traditional Chinese medicine composition. This composition has a simplified structure containing only four components, yet it demonstrates significant lipid-lowering effects in both cell experiments and animal studies. Verification shows that the lipid-lowering traditional Chinese medicine composition provided by this invention can significantly improve various lipid indicators in hyperlipidemic animal models, reduce the body weight of these models, and decrease the expression of the inflammatory factor TNF-α in hyperlipidemic animal models. Furthermore, its efficacy is superior to that of the chemical drug rosuvastatin. These results demonstrate that the lipid-lowering traditional Chinese medicine composition provided by this invention has excellent lipid-lowering effects (including reducing blood lipids and body weight). In addition, due to the simplified composition provided by this invention, the overall drug safety is high, and standardized quality control monitoring is easier to achieve in industrial production.

[0037] (2) Specifically, the lipid-lowering traditional Chinese medicine composition provided by the present invention uses partridge tea and sandalwood as the core lipid-lowering components, combined with hawthorn and salvia miltiorrhiza. Through rigorous exploration of the material ratio, the present invention has obtained a final compound that can simultaneously achieve good efficacy and high safety.

[0038] (3) This invention establishes a lipid accumulation model using HepG2 cells to screen the optimal ratio and extraction method of lipid-lowering compositions. The optimally matched lipid-lowering traditional Chinese medicine composition can reduce lipid accumulation in HepG2 cells and reduce intracellular triglyceride (TG) content.

[0039] (4) This invention established an acute hyperlipidemia animal model by intraperitoneal injection of 75% egg yolk milk into mice. The levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) in mouse serum were measured. In the high-dose group of the lipid-lowering traditional Chinese medicine composition, the levels of TC, TG, and LDL-C in the serum of mice were significantly reduced, while the level of HDL-C was significantly increased. In terms of reducing TC and TG, the lipid-lowering traditional Chinese medicine composition experimental group was superior to the rosuvastatin group (positive control group). The experimental results show that the lipid-lowering traditional Chinese medicine composition of this invention can significantly reduce the levels of TC, TG, and LDL-C in the serum of hyperlipidemic mice and increase the level of HDL-C, demonstrating good in vivo lipid-lowering activity.

[0040] (5) This invention establishes a high-fat diet-induced hyperlipidemia rat model to investigate the effect of the lipid-lowering traditional Chinese medicine composition on the body weight of hyperlipidemic rats. The lipid-lowering traditional Chinese medicine composition of this invention can significantly reduce the levels of TC, TG, and LDL-C in the serum of hyperlipidemic rats and increase the level of HDL-C, demonstrating good in vivo lipid-lowering activity. In addition, the weight gain rate of rats given the lipid-lowering traditional Chinese medicine composition decreased, and the effect was better than that of the positive control group, further proving that the lipid-lowering traditional Chinese medicine composition of this invention has the effect of reducing body weight. Attached Figure Description

[0041] In order to more clearly illustrate the technical solutions of the embodiments of the present application or the prior art, the following will briefly introduce the drawings needed to be used in the embodiments or prior art description. In all the drawings, similar elements or parts are generally identified by similar reference signs. In the drawings, each element or part is not necessarily drawn according to the actual proportion. Obviously, the drawings described below are some embodiments of the present application, and for those skilled in the art, other drawings can also be obtained from these drawings without creative labor.

[0042] Figure 1 For the weight gain rate of the chronic hyperlipidemia model rats in one of the embodiments of the present application;

[0043] Figure 2 For the liver condition of the chronic hyperlipidemia model rats in one of the embodiments of the present application;

[0044] Figure 3 For the determination of the content of inflammatory factors in the serum of the chronic hyperlipidemia model rats in one of the embodiments of the present application. DETAILED DESCRIPTION

[0045] In order to make the purpose, technical solutions and advantages of the embodiments of the present application more clear, the following will combine the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are some of the embodiments of the present application, not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0046] In this paper, "and / or" includes any and all combinations of one or more listed related items.

[0047] In this paper, "multiple" means two or more, that is, it includes two, three, four, five, etc.

[0048] In this specification, the term "about" typically means + / - 5% of the stated value, more typically + / - 4% of the stated value, more typically + / - 3% of the stated value, more typically + / - 2% of the stated value, even more typically + / - 1% of the stated value, even more typically + / - 0.5% of the stated value.

[0049] In this specification, certain embodiments can be disclosed in a format indicating that the embodiment does not include, or excludes, certain other embodiments. It is understood that the word "comprising" is not used in a limiting sense and is intended to mean the listed steps or options as well as any other steps or options not recited. It is further understood that embodiments, which do not include, or exclude a "specific feature / s", are intended to be encompassed by the verb "comprising" and its conjugates.

[0050] Example 1

[0051] The present example provides a Chinese medicine composition for reducing blood lipid, comprising the following raw materials in parts by weight: hawthorn 20 parts, salvia miltiorrhiza 20 parts, partridge tea 30 parts, and agarwood powder 5 parts; wherein the partridge tea and the agarwood form a blood lipid-reducing core component; the hawthorn and the salvia miltiorrhiza serve as auxiliary components. The preparation method comprises pretreatment, extraction, and post-treatment, and the details are as follows.

[0052] A. Pretreatment: The raw materials of hawthorn, salvia miltiorrhiza, and partridge tea in the formula are crushed to pass through a 40-60 mesh sieve to obtain material a for standby; the raw material of agarwood powder in the formula is crushed to pass through a 40-60 mesh sieve to obtain material b for standby.

[0053] B. Extraction: 10 times the volume of pure water based on the weight of the material a is added, soaked for 30 min, and then extracted at 95-100°C for 60 min. The first extract is obtained by filtration. 8 times the volume of pure water based on the weight of the material is added again, and the extraction is continued at 95-100°C for 80 min. The material b is added and boiled for 10 min. The second extract is obtained by filtration. The two extracts are combined, concentrated, and dried to obtain a dry extract.

[0054] C. Post-treatment: The dry extract is crushed to obtain a fine powder, and an appropriate amount of excipient is added to obtain a Chinese medicine preparation that helps reduce blood lipid.

[0055] The present example provides a Chinese medicine composition for reducing blood lipid (referred to as composition 1). The effect of composition 1 on the oil red O staining of HepG2 cells and the determination of the TG content in the cells are detected by cell experiments. The damage degree of composition 1 to HepG2 cells is detected by MTT experiments to evaluate the in-vitro blood lipid-reducing activity of composition 1.

[0056] The results show that compared with the blank group, a large number of red lipid droplets appear in the model group (without any drug treatment), and the TG content of the model group is significantly increased (P<0.001). Compared with the model group, the number and size of red lipid droplets in the experimental group are significantly reduced (P<0.001) with good dose dependence. Further, the higher the concentration of composition 1, the fewer the number of red lipid droplets. The above results show that the composition 1 prepared in this embodiment can effectively reduce the TG content in the oleic acid-induced HepG2 cells, reduce the lipid accumulation of HepG2 cells, and has good in vitro lipid-lowering activity.

[0057] Table 1 CCK8 toxicity detection of lipid-lowering composition of Example 1

[0058]

[0059] Table 2 Pharmacodynamics of Example 1 lipid-lowering composition of cell experiment

[0060]

[0061] Further verification is carried out by establishing an animal hyperlipidemia model, including establishing a mouse acute hyperlipidemia model and a rat chronic hyperlipidemia model.

[0062] Mouse acute hyperlipidemia model:

[0063] An acute hyperlipidemia animal model is constructed by intraperitoneal injection of 75% egg yolk emulsion in mice, and the total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), and high density lipoprotein (HDL-C) in the serum of the mouse model are detected to further verify that the lipid-lowering composition of Example 1 has a significant lipid-lowering effect.

[0064] Experimental method:

[0065] Take several fresh eggs, make a small hole at the bottom to empty the egg white, and gently place the egg yolk in the empty beaker. Insert the needle tube into the egg yolk membrane to suck the egg yolk liquid into a 100 mL volumetric flask, dilute 75 mL of egg yolk liquid with physiological saline to 100 mL. Stir the egg yolk emulsion solution with a magnetic stirrer for 10 min to make the egg yolk emulsion solution uniform to reduce errors. Prepare it temporarily when used.

[0066] Precisely weigh 5.00 g of CMC-Na into a beaker, add 800 mL of purified water, stir uniformly, and place in a 1000 mL volumetric flask. Add purified water to the mark. Prepare a 0.5% CMC-Na solution.

[0067] Precisely weigh 6.5 mg of rosuvastatin (1.30 mg / kg) into a 100 mL volumetric flask, suspend with 0.5% CMC-Na solution, and make up to 100 mL. Prepare a 0.065 mg / mL drug solution sample.

[0068] Respectively, 1.23 g of compound (2.47 g / kg) was precisely weighed and placed in a 10 mL volumetric flask, and 0.5% CMC-Na solution was used for suspension and constant volume to 10 mL. The compound solution sample of 123 mg / mL was prepared.

[0069] The mice were randomly divided into 6 groups, 6 in each group, and set as blank control group, 75% egg yolk milk high-fat model group, composition 1 administration group (low dose 1.24 g / kg, medium dose 2.47 g / kg, high dose 4.94 g / kg), and rosuvastatin as a positive drug control group. The blank control group and the 75% egg yolk milk high-fat model group were given 0.5% CMC-Na by gavage at 0.2 ml / 10g per day, and the rest of the drug groups were given the corresponding drugs by gavage at 0.2 ml / 10g per day. Continuous administration for 5 days, 2h after the last administration, 75% egg yolk milk physiological saline solution 0.5 ml / one was injected intraperitoneally to each group to cause experimental hyperlipidemia. After 8h, fasting, 12h after gavage, blood was taken after 1h. The serum was separated by enucleation blood collection method, and the contents of TC, TG, LDL-C and HDL-C were determined. The experiment proved that the high dose group of composition 1 had a significant effect of reducing TC, TG and LDL-C.

[0070] Table 3 Evaluation of the pharmacodynamic effect of the lipid-lowering composition of Example 1 based on the mouse experiment

[0071]

[0072] Note: compared with the blank group a p<0.05, b p<0.01; compared with the model group c p<0.05, d p<0.01.

[0073] Compared with the blank group, the contents of TC, TG and LDL-C in the serum of the model group mice were significantly increased, and the content of HDL-C was significantly decreased. Compared with the model group, the contents of TC, TG and LDL-C in the serum of the positive group mice were significantly reduced, and the content of HDL-C was significantly increased. The contents of TC, TG and LDL-C in the serum of the high dose group of composition 1 were significantly reduced, and the content of HDL-C was significantly increased.

[0074] The above results show that the experimental group is better than the positive control group in reducing TC and TG. Specifically, composition 1 can significantly reduce the contents of TC, TG and LDL-C in the serum of hyperlipidemic mice, increase the content of HDL-C, and has good in vivo lipid-lowering activity.

[0075] Chronic hyperlipidemia model of rats:

[0076] The high-fat diet is used to induce a hyperlipidemia model of rats, and the total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) in the serum of the rats are detected, and the composition 1 provided by the application has an improving effect on the blood lipid indexes of the hyperlipidemia rats.

[0077] Table 4: Evaluation table of the lipid-lowering effect of the composition of Example 1 based on the rat experiment

[0078]

[0079] Note: The high / medium / low doses of the composition 1 in Table 4 are 3.9 g / kg, 1.95 g / kg, and 0.975 g / kg, respectively.

[0080] Compared with the blank group, the contents of TC, TG, and LDL-C in the serum of the model group rats are significantly increased, and the content of HDL-C is significantly decreased. Compared with the model group, the contents of TC, TG, and LDL-C in the serum of the positive group mice are significantly decreased, and the content of HDL-C is significantly increased. The contents of TC, TG, and LDL-C in the serum of the high-dose group of the composition 1 are significantly decreased, and the content of HDL-C is significantly increased. And it is better than the positive control group in reducing TC and TG and LDL-C. Specifically, the composition 1 can significantly reduce the contents of TC, TG, and LDL-C in the serum of the hyperlipidemia rats, and increase the content of HDL-C, and has good in vivo lipid-lowering activity.

[0081] Further, 60 SPF SD rats that pass the quarantine are randomly divided into a high-dose group, a medium-dose group, a low-dose group, a positive control group (given rosuvastatin), a model group, and a normal control group according to the weight sequence, 10 rats per group. The model group and the normal control group are given the same volume of solvent (0.5% carboxymethyl cellulose solution). The hyperlipidemia model animals are fed with high-fat feed, and the normal control group animals are fed with breeding feed, and the animals are fed for 4 weeks before administration. During the administration period, the normal control group animals are fed with breeding feed, and the animals in the other groups are fed with high-fat feed. The rats are weighed before the experiment, after modeling, and after administration, and the results are as follows Figure 1 , wherein the administration group represents the high dose of the composition 1, 3.9 g / kg. Figure 1 It can be seen that under the condition of continuous feeding of high-fat feed, the weight gain rate of the rats in the administration group decreases, and the effect is better than that of the positive control group, which proves that the traditional Chinese medicine composition for lipid-lowering of Example 1 also has the effect of reducing weight.

[0082] Further, the next day after the last administration, the rats are anesthetized with chloral hydrate, the abdominal aorta is bled, the weight is weighed, and the liver tissue is taken, as shown in Figure 2 .

[0083] Figure 2It can be seen that the color and appearance of the liver of the high (MLGmH), medium (MLGmM) and low dose (MLGmL) groups of composition 1 and the model control group rats are obviously different from those of the normal control group. The model group is a fatty liver caused by high fat, and the color of the normal liver section is uniform without obvious fat particles. However, obvious yellow fat particles can be seen on the section of the fatty liver.

[0084] Therefore, composition 1 can improve the histopathological changes of the liver of hyperlipidemic rats, effectively reduce the vacuolation of liver cells, reduce the accumulation of fat in the liver, and effectively restore the normal morphology of liver cells.

[0085] Further, the content of the inflammatory factor TNF-α in the serum of the rats was determined, and the experimental results are shown in Table 4. Figure 3 The results show that, compared with the control group, the content of TNF-α in the serum of the model group rats is obviously increased, the content of the inflammatory factor TNF-α in the positive control group and the medium and high dose groups of composition 1 is obviously reduced after administration, and the efficacy of composition 1 is obviously better than that of the positive control group, and the effect of the high dose group of composition 1 is the best.

[0086] Example 2

[0087] Another example of a traditional Chinese medicine composition for reducing blood lipids is provided in this example, which comprises the following raw materials in parts by weight: hawthorn 20 parts, salvia miltiorrhiza 20 parts, partridge tea 30 parts, and jatamansi oil (jatamansi volatile oil extracted from 5 parts of jatamansi medicinal materials); wherein the partridge tea and the jatamansi oil constitute a blood lipid-lowering core component; and the hawthorn and the salvia miltiorrhiza serve as auxiliary components. The preparation method comprises pretreatment, extraction, and post-treatment, and the details are as follows.

[0088] A. Pretreatment: The raw materials of hawthorn, salvia miltiorrhiza, and partridge tea in the formula are crushed to pass through a 40-60 mesh sieve to obtain material a for standby, and the jatamansi oil in the formula is used as material b for standby.

[0089] B. Extraction: 10 times the volume of pure water based on the weight of the material is added to material a, soaked for 30 min, and then extracted by decoction at 95-100℃ for 60 min to obtain the first extract. 8 times the volume of pure water based on the weight of the material is added again, and the extraction by decoction is continued at 95-100℃ for 80 min. Then, material b is added and decocted for 10 min. The filtrate is obtained as the second extract. The two extracts are combined, concentrated, and dried to obtain a dry extract.

[0090] C. Post-treatment: The dry extract is crushed to obtain a fine powder, and an appropriate amount of excipient is added to obtain the target traditional Chinese medicine composition which helps to reduce blood lipids.

[0091] The present embodiment provides a traditional Chinese medicine composition for reducing lipid (referred to as composition 2), cell experiment detects the influence of composition 2 on HepG2 cell oil red O staining and intracellular TG content determination, the damage degree of HepG2 cell of composition 2 is detected by MTT experiment, and the in vitro lipid-lowering activity of composition 2 is evaluated.

[0092] Compared with the blank group, a large number of red lipid droplets appeared in the model group, and the TG content of the model group was significantly increased (P<0.001). Compared with the model group, the number and size of red lipid droplets in composition 2 were significantly reduced (P<0.001), with good dose dependence. The higher the concentration of composition 2, the fewer the number of red lipid droplets. The above results show that composition 2 can reduce the TG content in oleic acid-induced HepG2 cells and reduce the lipid accumulation of HepG2 cells, and has good in vitro lipid-lowering activity.

[0093] Table 5 CCK8 toxicity detection of lipid-lowering composition of example 2

[0094]

[0095] Table 6 Pharmacodynamics of lipid-lowering composition of example 2

[0096]

[0097] The same measurement method as in example 1 was used to further confirm that composition 2 has a significant lipid-lowering effect in animal experiments.

[0098] Experimental method:

[0099] Take several fresh eggs, open a small hole at the bottom to empty the egg white, and gently place the yolk in the empty beaker. Insert the needle tube into the yolk membrane and suck the yolk liquid. Place 75mL of yolk liquid in a 100mL volumetric flask and dilute to 100mL with physiological saline. Stir the yolk emulsion solution with a magnetic stirrer for 10min to make the yolk emulsion solution uniform to reduce errors. Prepare it immediately before use.

[0100] Precisely weigh 5.00g of CMC-Na and place it in a beaker. Add 800mL of purified water and stir until uniform. Place it in a 1000mL volumetric flask and add purified water to the mark. Prepare a 0.5% CMC-Na solution.

[0101] Precisely weigh 6.5mg of rosuvastatin (1.30mg / kg) and place it in a 100mL volumetric flask. Mix with 0.5% CMC-Na solution to make up to 100mL, and prepare a 0.065mg / mL drug solution sample.

[0102] Accurately weigh 1.17 g of the compound (2.34 g / kg) into separate 10 mL volumetric flasks, suspend in 0.5% CMC-Na solution, and dilute to 10 mL. Prepare a 117 mg / mL compound drug solution sample.

[0103] Mice were randomly divided into 6 groups (n=6 per group): a blank control group, a 75% egg yolk milk high-fat model group, and drug treatment groups (low dose 1.17 g / kg, medium dose 2.34 g / kg, high dose 4.68 g / kg). Rosuvastatin served as a positive control group. Administered via gavage, the blank control group and the 75% egg yolk milk high-fat model group received 0.2 ml / 10 g of 0.5% CMC-Na daily, while the other drug groups received 0.2 ml / 10 g of the corresponding drug daily via gavage. Drug administration continued for 5 days. Two hours after the last administration, each group received an intraperitoneal injection of 0.5 ml / mouse of 75% egg yolk milk saline solution to induce experimental hyperlipidemia. After 8 hours of fasting, the mice were administered the drug via gavage 12 hours later, and blood was collected 1 hour later. Serum was separated by centrifugation using the enucleation method to determine the levels of TC, TG, LDL-C, and HDL-C.

[0104] Table 7. Evaluation of the efficacy of the lipid-lowering composition in Example 2 based on animal experiments.

[0105]

[0106] Note: Compared with the blank group a p<0.05, b p<0.01; compared with the model group c p<0.05, d p<0.01.

[0107] Example 3

[0108] This embodiment provides another example of a traditional Chinese medicine composition for lowering lipids, comprising the following parts by weight of medicinal herbs: 20 parts hawthorn, 20 parts salvia miltiorrhiza, 30 parts partridge tea, and 5 parts sandalwood. Partridge tea and sandalwood constitute the core lipid-lowering components; hawthorn and salvia miltiorrhiza serve as auxiliary components. The preparation method includes pretreatment, extraction, and post-treatment.

[0109] Mix all materials thoroughly, add 8 times the weight of the materials by volume of 75% ethanol, sonicate for 30 min, reflux extract at 65-75℃ for 60 min, filter to obtain the first filtrate, add 6 times the weight of the materials by volume of 75% ethanol again, reflux extract at 65-75℃ for 60 min, filter to obtain the second filtrate. Combine the two extracts, concentrate, and dry to obtain the dry extract.

[0110] The present embodiment provides a traditional Chinese medicine composition for reducing lipid (referred to as composition 3), cell experiment detects the influence of composition 3 on HepG2 cell oil red O staining and intracellular TG content determination, MTT experiment is used to detect the damage degree of composition 3 to HepG2 cell, and the in vitro lipid-lowering activity of composition 3 is evaluated. Compared with the blank group, a large number of red lipid droplets appear in the model group, and the TG content of the model group is significantly increased (P<0.001). Compared with the model group, the number and size of red lipid droplets in composition 3 are significantly reduced (P<0.001), which has good dose dependence. The higher the concentration of composition 3, the fewer the number of red lipid droplets. The above results show that composition 3 can reduce the TG content in HepG2 cells induced by oleic acid, reduce the lipid accumulation of HepG2 cells, and has good in vitro lipid-lowering activity.

[0111] Table 8 CCK8 toxicity detection of lipid-lowering composition of example 3

[0112]

[0113] Table 9 pharmacodynamics of lipid-lowering composition of example 3 of cell experiment

[0114]

[0115] Example 4

[0116] The present embodiment provides another traditional Chinese medicine composition for reducing lipid, which comprises the following raw materials by weight: 20 parts of hawthorn, 20 parts of salvia miltiorrhiza, 30 parts of partridge tea and 5 parts of olibanum volatile oil extracted from olibanum medicinal materials. The preparation method comprises pretreatment, extraction and post-treatment.

[0117] All materials are mixed uniformly, 8 times the volume of 75% ethanol is added, ultrasonic treatment is carried out for 30 min, reflux extraction is carried out at 65-75℃ for 60 min, filtration is carried out, the first filtrate is obtained, 6 times the volume of 75% ethanol is added again, reflux extraction is carried out at 65-75℃ for 60 min, filtration is carried out, the second filtrate is obtained; the two extraction liquids are combined, concentrated, dried to obtain dry paste.

[0118] The present embodiment provides a traditional Chinese medicine composition for reducing lipid (referred to as composition 4). The influence of composition 4 on oil red O staining of HepG2 cells and intracellular TG content determination were detected by cell experiment, the damage degree of composition 4 on HepG2 cells was detected by MTT experiment, and the in vitro lipid-lowering activity of composition 4 was evaluated. Compared with the blank group, a large number of red lipid droplets appeared in the model group, and the TG content of the model group was significantly increased (P<0.001). Compared with the model group, the number and size of red lipid droplets in composition 4 were significantly reduced (P<0.001), which had good dose dependence. The higher the concentration of composition 4, the fewer the number of red lipid droplets. The above results show that composition 4 can reduce the TG content in oleic acid-induced HepG2 cells and reduce the lipid accumulation in HepG2 cells, and has good in vitro lipid-lowering activity.

[0119] Table 10 CCK8 toxicity detection of lipid-lowering composition of example 4

[0120]

[0121] Table 11 Pharmacodynamics of lipid-lowering composition of example 4 in cell experiment

[0122]

[0123] Example 5

[0124] The present embodiment further provides component screening verification of the above-mentioned traditional Chinese medicine composition for reducing lipid.

[0125] Firstly, the present embodiment provides a composition without jianghong as a comparison.

[0126] Comparative composition 1: Zhujiaocha 30 parts, Zexie 10 parts, Jianghuang 10 parts, Huangqi 10 parts, Shanzha 10 parts, Holley 10 parts, Danshen 10 parts, Sanqi powder 3 parts.

[0127] Table 12 Comparison of cell survival rate in CCK-8 toxicity detection

[0128]

[0129] Note: Generally, cell survival rate less than 50% indicates high toxicity. Generally, the drug concentration with cell survival rate greater than 70% is selected as the effective drug concentration.

[0130] Table 13 Pharmacodynamic detection based on triglyceride reduction rate

[0131]

[0132] Note: The higher the triglyceride reduction rate (TG), the better the efficacy.

[0133] The above experimental results show that the lipid-lowering composition shown in composition 1 has more obvious efficiency in reducing triglycerides than the comparative composition at the same drug dose; in addition, the lipid-lowering composition shown in composition 1 has higher cell survival rate than the comparative composition at the same drug dose, proving that the toxicity of composition 1 is smaller and the drug is safer.

[0134] In addition, the present embodiment also provides effect verification of other composition ratios.

[0135]

[0136] Table 14 Comparison of cell survival rate in CCK-8 toxicity detection

[0137]

[0138] Table 15 Drug efficacy detection based on triglyceride reduction rate

[0139]

[0140] The above experimental results show that when the total amount of the lipid-lowering core component is greater than the total amount of the auxiliary component (comparative composition 3), the toxicity of the composition is the lowest but the drug efficacy is the weakest; when the total amount of the auxiliary component is increased and the total amount of the lipid-lowering core component is further reduced (comparative composition 4), the toxicity of the composition is increased, but the highest dose of 1200 µg / mL can still make the cell survival rate higher than 50%, so the weight ratio of the lipid-lowering core component to the auxiliary component in the composition should not be less than 13:40.

[0141] Further, the drug efficacy of composition 1 and comparative composition 2 is verified in a mouse acute hyperlipidemia model. The mouse acute hyperlipidemia model is established in the same manner as in Example 1.

[0142] By injecting 75% egg yolk emulsion into the abdominal cavity of mice, an acute hyperlipidemia animal model is constructed, and by detecting the total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) in the serum of mice, it is found that the composition 1 provided by the present application has an improving effect on the blood lipid indicators of hyperlipidemic mice, can reduce the contents of TC, TG, and LDL-C in the serum of mice, and increase the content of HDL-C. The drug efficacy is obviously improved after adding jiangxiang.

[0143] Table 16 Comparison of blood lipid detection of mice

[0144]

[0145] Note: The high / medium / low doses of composition 1 are 4.94 g / kg, 2.47 g / kg, and 1.24 g / kg, respectively. The dose of comparative composition 2 is 4.94 g / kg.

[0146] The embodiments of the present application are described above with reference to the accompanying drawings, but the present application is not limited to the above-described specific embodiments, and the above-described specific embodiments are merely illustrative, but not restrictive, and a person of ordinary skill in the art can make many forms under the inspiration of the present application without departing from the purpose of the present application and the scope protected by the claims, and these all belong to the protection of the present application.

Claims

1. A traditional Chinese medicine composition for reducing lipid, characterized in that, The composition comprises a lipid-lowering core component and an auxiliary component, wherein the lipid-lowering core component comprises Fructus Loropetali and Olibanum; the auxiliary component comprises Fructus Crataegi and Radix Salviae Miltiorrhizae; the weight ratio of Fructus Loropetali to Olibanum in the lipid-lowering core component is 6:1; the weight ratio of Fructus Crataegi to Radix Salviae Miltiorrhizae in the auxiliary component is 1:1; the total weight of the lipid-lowering core component is less than the total weight of the auxiliary component; and the weight ratio of the lipid-lowering core component to the auxiliary component is 35:

40.

2. The traditional Chinese medicine composition of claim 1, wherein, The traditional Chinese medicine composition comprises the following components in parts by weight: Fructus Loropetali 30 parts, Olibanum 5 parts, Fructus Crataegi 20 parts, and Radix Salviae Miltiorrhizae 20 parts.

3. The traditional Chinese medicine composition of claim 2, wherein, The Olibanum is Olibanum medicinal material or Olibanum oil prepared by extraction of the Olibanum medicinal material.

4. The traditional Chinese medicine composition of claim 1, wherein, The traditional Chinese medicine composition is obtained by water extraction or alcohol extraction.

5. The preparation method of the traditional Chinese medicine composition according to claim 1, characterized in that, The method comprises the following steps: S01: preparing a first material comprising the following components in parts by weight: Fructus Loropetali 30 parts, Fructus Crataegi 20 parts, and Radix Salviae Miltiorrhizae 20 parts; Olibanum 5 parts by weight is prepared as a second material; S02: adding 10-20 times the volume of pure water to the first material, and then sufficiently soaking and extracting at 90-100℃ for 60-100 minutes to obtain a first extract; adding 5-10 times the volume of pure water to the first material again, and then continuing to extract at 90-100℃ for 60-100 minutes; then adding the second material, and extracting for 10-30 minutes to obtain a second extract; combining the two extracts, and then concentrating and drying to obtain a dry extract.

6. The preparation method of the traditional Chinese medicine composition according to claim 1, characterized in that, The method comprises the following steps: S01: preparing a first material comprising the following components in parts by weight: Fructus Loropetali 30 parts, Fructus Crataegi 20 parts, and Radix Salviae Miltiorrhizae 20 parts; Olibanum 5 parts by weight is prepared as a second material; S02: mixing the first material and the second material uniformly, and then adding 6-10 times the volume of high-concentration ethanol, and then ultrasonically treating to obtain a first extract; adding 6-10 times the volume of high-concentration ethanol again, and then refluxing at 60-75℃ for 60-100 minutes to obtain a second extract; combining the two extracts, and then concentrating and drying to obtain a dry extract.

7. A traditional Chinese medicine preparation, characterized in that, The traditional Chinese medicine composition of any one of claims 1-4.

8. The traditional Chinese medicine preparation of claim 7, characterized in that, The dosage form of the traditional Chinese medicine preparation comprises granules, powder, tablets, capsules, and / or pills.

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