A traditional Chinese medicine formula with lipid-lowering efficacy, Qulinghuazhuo granules and a preparation method thereof

Abstract

The application discloses a traditional Chinese medicine composition with lipid-lowering efficacy, Quling Huatu granules and a preparation method thereof, and belongs to the technical field of Chinese patent medicines. The traditional Chinese medicine composition comprises the following components in parts by weight: 5-10 parts of red yeast rice, 10-30 parts of poria cocos, 5-15 parts of atractylodes, 5-15 parts of dried ginger and 5-15 parts of costus. The atractylodes, the poria cocos and the costus in the application can dispel cold, invigorate the spleen, warm the middle and harmonize the stomach, so that the qi of the spleen and stomach runs smoothly. Meanwhile, the Quling Huatu granules contain statin components, can inhibit the synthesis of excessive cholesterol in the body, increase the synthesis of low-density protein receptors, reduce the blood cholesterol and low-density protein cholesterol levels, prevent the further development of cardiovascular diseases, and also do not cause problems such as liver and kidney function damage and gastrointestinal discomfort.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine formula with lipid-lowering effects, Quling Huazhuo granules and their preparation method. Background Technology

[0002] With the improvement of people's living standards, changes in dietary structure, faster pace of life, and increased stress, the "three highs" (high blood pressure, high blood sugar, and high cholesterol) have gradually become more serious. Hyperlipidemia is not only an independent disease, but also a contributing factor to many other diseases such as hypertension, coronary heart disease, diabetes, and stroke.

[0003] Hyperlipidemia is a metabolic disease caused by abnormal lipid metabolism, resulting in elevated levels of one or more lipids in the blood plasma. It manifests as hypercholesterolemia, triglycerides, or a mixed type of hyperlipidemia, and is a major cause of atherosclerosis, cardiovascular and cerebrovascular diseases, and fatty liver. Currently, the main treatment drugs are phenoxyaromatic acids, statins, and polyunsaturated fatty acids. While these drugs have definite lipid-lowering effects clinically, their applicability is limited, and long-term use may lead to adverse reactions such as liver and kidney damage, gastrointestinal reactions, and myopathy. In addition, traditional Chinese medicine is also used clinically to treat hyperlipidemia, such as Jiangzhi Tongluo capsules, Jiangzhi Ning granules, and Xuezhikang capsules. However, compared with Western medicine, their pharmacological research is not clear enough, their onset of action is slower, and they are also accompanied by certain gastrointestinal discomfort and liver and kidney damage, and may even occasionally cause reversible increases in serum aminotransferase and creatine phosphokinase. Therefore, finding lipid-lowering drugs with significant efficacy, clear pharmacological mechanisms, and gastrointestinal protective effects remains a hot topic in new drug development. Summary of the Invention

[0004] In view of the above-mentioned shortcomings in the prior art, the present invention provides a traditional Chinese medicine formula with lipid-lowering effect, Quling Huazhuo granules and its preparation method, which can effectively reduce blood lipids, and while treating hyperlipidemia, it will not damage liver and kidney function or cause gastrointestinal discomfort.

[0005] To achieve the above objectives, the technical solution adopted by the present invention to solve its technical problem is as follows:

[0006] A traditional Chinese medicine formula with lipid-lowering effects includes the following components in parts by weight:

[0007] 5-10 parts red yeast rice, 10-30 parts poria cocos, 5-15 parts atractylodes lancea, 5-15 parts dried ginger, and 5-15 parts costus root.

[0008] Furthermore, it includes the following components in parts by weight:

[0009] 5-10 parts red yeast rice, 10-20 parts poria cocos, 10-15 parts atractylodes lancea, 10-15 parts dried ginger, and 8-15 parts costus root.

[0010] Furthermore, it includes the following components in parts by weight:

[0011] 6 parts red yeast rice, 20 parts poria cocos, 12 parts atractylodes lancea, 10 parts dried ginger, and 12 parts costus root.

[0012] A traditional Chinese medicine preparation with lipid-lowering effects, wherein the preparation is made into granules, tablets, capsules or powders using the above-mentioned traditional Chinese medicine formula.

[0013] A method for preparing Quling Huazhuo granules using the above-mentioned traditional Chinese medicine formula, characterized by comprising the following steps:

[0014] (1) Wash each component and then pulverize it into powder with a particle size of 100-200 mesh. Then mix the powders of each component evenly.

[0015] (2) At 45-60℃, the powder obtained in step (1) is subjected to ultrasonic extraction with a solvent of 6-10 times its weight. After extraction for 45-90 min, the extract is collected and concentrated to obtain an extract.

[0016] (3) Mix the extract with the excipients and stir until homogeneous. Adjust the humidity with ethanol to obtain the soft material.

[0017] (4) The soft material is made into wet granules and then dried at 60-80°C.

[0018] Furthermore, the extraction solvent is methanol, 75-95% ethanol, or anhydrous ethanol.

[0019] Furthermore, the excipients include dextrin and powdered sugar, in a weight ratio of 1:3:1 to the extract.

[0020] Furthermore, the sugar powder is sucrose powder, and the dextrin is soluble dextrin.

[0021] The above-mentioned traditional Chinese medicine formulas or preparations are used in the preparation of drugs for diseases caused by hyperlipidemia.

[0022] The beneficial effects of this invention are:

[0023] The Quling Huazhuo granules in this invention contain statins, which can inhibit excessive cholesterol synthesis in the body, increase the synthesis of low-density lipoprotein receptors, lower blood cholesterol and low-density lipoprotein cholesterol levels, prevent the further development of cardiovascular disease, and at the same time, do not damage liver and kidney function. Atractylodes lancea, Poria cocos, and Aucklandia lappa can dispel cold, strengthen the spleen, warm the middle jiao and harmonize the stomach, ensuring smooth flow of qi in the spleen and stomach. With the overall synergistic effect, this formula has a clear efficacy in preventing and treating hyperlipidemia. Attached Figure Description

[0024] Figure 1 This is a graph showing the effect of drugs on the body weight of hyperlipidemic mice.

[0025] Figure 2 Liver index of mice in each group (* indicates significant difference);

[0026] Figure 3 The graph shows the serum levels of various markers in mice from each group (* indicates significant differences).

[0027] Figure 4 The images show the histopathological results of different groups of hyperlipidemic mice. In the images, A shows H&E staining of mouse liver; and B shows Oil Red O staining of mouse liver.

[0028] Figure 5 H&E staining images of major organs in mice from different groups. Detailed Implementation

[0029] The specific embodiments of the present invention are described below to enable those skilled in the art to understand the present invention. However, it should be understood that the present invention is not limited to the scope of the specific embodiments. For those skilled in the art, various changes are obvious as long as they are within the spirit and scope of the present invention as defined and determined by the appended claims. All inventions utilizing the concept of the present invention are protected.

[0030] Example 1

[0031] A novel lipid-lowering drug, Quling Huazhuo Granules, comprises 6g of red yeast rice, 20g of Poria cocos, 12g of Atractylodes lancea, 10g of dried ginger, and 12g of Aucklandia lappa. The preparation method is as follows:

[0032] (1) Wash all Chinese medicinal herbs and set aside;

[0033] (2) Take the prescribed amounts of red yeast rice, poria cocos, atractylodes lancea, dried ginger, and costus root, grind them into powder using a Chinese herbal medicine grinder with a particle size of 100 mesh, and mix thoroughly.

[0034] (3) Add 6 times the amount of methanol to the powder obtained in step (2), and extract the effective components by ultrasonic extraction in a 50°C water bath for 45 minutes;

[0035] (4) The methanol extract in step (3) is concentrated by rotary evaporation in a water bath at 60°C to obtain a thick extract.

[0036] (5) Mix the thick paste obtained in step (4) with soluble dextrin and sugar powder in a ratio of 1:1:3. During the process, add an appropriate amount of 80% ethanol in small amounts to adjust the humidity to obtain a soft material.

[0037] (6) Place the soft material obtained in step (5) into a gyratory pellet mill and pass it through a 12-mesh sieve to make wet pellets;

[0038] (7) Place the granules obtained in step (6) into a 60°C oven to dry, remove large granules and fine powder with a 14-mesh sieve and a 60-mesh sieve respectively, and after granulation, dry granules are obtained.

[0039] (8) Seal and package the dry granules obtained in (7) into 60g mixed Chinese medicine granules in each package and store them in a dry place.

[0040] Example 2

[0041] A new lipid-lowering drug, Quling Huazhuo Granules, comprises 5g of red yeast rice, 12g of Poria cocos, 8g of Atractylodes lancea, 6g of dried ginger, and 10g of Aucklandia lappa. The preparation method is the same as in Example 1.

[0042] Example 3

[0043] A new lipid-lowering drug, Quling Huazhuo Granules, comprises 10g of red yeast rice, 30g of Poria cocos, 15g of Atractylodes lancea, 12g of dried ginger, and 15g of Aucklandia lappa. The preparation method is the same as in Example 1.

[0044] Experimental Example 1:

[0045] The difference between this experiment and Example 1 is that the extract was anhydrous ethanol and the extraction time was 60 minutes. Everything else was the same as in Example 1.

[0046] Experimental Example 2:

[0047] The difference between this experiment and Example 1 is that the extract was 75% ethanol and the extraction time was 90 minutes; all other aspects were the same as in Example 1.

[0048] Experimental Example 3:

[0049] The difference between this experiment and Example 1 is that the extract was anhydrous ethanol, the extraction ratio was 8 times, and the extraction time was 45 minutes. Everything else was the same as in Example 1.

[0050] Experiment Example 4:

[0051] The difference between this experiment and Example 1 is that the extract was 75% ethanol, the extraction ratio was 8 times, and the extraction time was 60 minutes. Everything else was the same as in Example 1.

[0052] Experimental Example 5:

[0053] The difference between this experiment and Example 1 is that the extraction factor was 8 times and the extraction time was 90 minutes, while everything else was the same as in Example 1.

[0054] Experimental Example 6:

[0055] The difference between this experiment and Example 1 is that the extract was 75% ethanol and the extraction ratio was 10 times. Everything else was the same as in Example 1.

[0056] Experiment Example 7:

[0057] The difference between this experiment and Example 1 is that the extraction factor was 10 times and the extraction time was 60 minutes, while everything else was the same as in Example 1.

[0058] Experimental Example 8:

[0059] The difference between this experiment and Example 1 is that the extractant was anhydrous ethanol, the extraction ratio was 10 times, and the extraction time was 90 minutes. Everything else was the same as in Example 1.

[0060] Test case

[0061] 1. Detection of effective ingredient content

[0062] The content of the active ingredients obtained in Example 1 and Experiments 1 to 8 was detected by high performance liquid chromatography, and the results are shown in Table 1.

[0063] Table 1 Content of effective ingredients

[0064]

[0065] Analysis of variance of the results in the table above shows that the extraction solution and the material-to-liquid ratio have the greatest impact on the content of lovastatin and the yield of the extract. Taking into account energy saving and actual production conditions, the best results were obtained by using 75% ethanol as the extraction solvent and ultrasonic extraction for 90 minutes at a material-to-liquid ratio of 1:6 (Experimental Example 2).

[0066] 2. Pharmacodynamic studies were conducted on the Quling Huazhuo granules prepared using the method described in Experimental Example 2.

[0067] This invention utilizes animal experiments to investigate the lipid-lowering effect and biosafety of Quling Huazhuo Granules. The specific implementation methods and results are as follows:

[0068] (1) Animals: Forty male C57BL / 6 mice, aged 7-8 weeks, were randomly divided into four groups: a blank control group (n=10), a high-fat model group (n=10), a compound preparation group (n=10), and a single red yeast rice group (n=10).

[0069] (2) Modeling: The blank control group was given a basal diet, while the other groups were given a Western diet (21% fat, 0.15% cholesterol, and 34% sucrose) to establish a hyperlipidemia model. During the experiment, the hyperlipidemia model group and the drug group were fed a high-fat diet throughout the entire period. On day 70 of modeling, three mice from each of the blank control group and the hyperlipidemia model group were randomly selected, and blood was collected from the orbital sinus to measure the levels of TC, TG, HDL-C, and LDL-C. When there was a significant difference between the two groups, the hyperlipidemia model was successfully established.

[0070] (3) Administration: Single red yeast rice and compound preparations were prepared with lovastatin at a mass concentration of 5 mg / Kg as the standard. They were administered by gavage once a day at a volume of 0.01 ml / g for 8 to 10 weeks. The high-fat model group was administered an equal volume of physiological saline by gavage.

[0071] (5) Detection indicators: The weight of mice was measured and recorded every two weeks; after the treatment cycle, blood was collected from the eyeballs. The levels of TG, TC, HDL-C and LDL-C in the serum were measured, and the liver and major organs were dissected for H&E and Oil Red O staining, and the average liver index of each group was calculated.

[0072] (5) Results

[0073] 1) Quling Huazhuo Granules improve symptoms of hyperlipidemia in mice

[0074] like Figure 1 , 2 As shown in the figure, during the first 63 days of the experiment, the body weight of mice in each group showed a uniform increasing trend. On day 70 of the modeling process, the average body weight of mice in the high-fat model group reached 32.72 g, which was 23.3% higher than that of the blank control group. After drug administration, the average body weight of mice in the high-fat model group continued to increase during the administration period, while the body weight of mice in the single red yeast rice group and the compound preparation group tended to plateau. After the administration, the body weight of mice in the single red yeast rice group and the compound preparation group decreased by 15.9% and 12.7% respectively compared with the high-fat model group, indicating that both single red yeast rice and the compound preparation could significantly control the body weight of mice with hyperlipidemia. After the administration, the average liver index of mice in each group was measured. The liver index of mice in the high-fat model group and the single red yeast rice group was significantly different from that of the blank control group (P<0.05), while the liver index of mice in the compound preparation group was not significantly different from that of mice in the blank control group (P>0.05). This indicates that the compound preparation can effectively inhibit liver hypertrophy caused by hyperlipidemia and maintain stable liver function.

[0075] After treatment, the average levels of triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in the serum of mice in each group were measured. The results are shown in Table 2. Figure 3 As shown.

[0076] In the control group, all four indicators were within the normal range. The high-fat model group showed significantly higher levels of TC, HDL-C, and LDL-C compared to the control group (P<0.01), indicating that a high-fat, high-sugar diet does indeed induce hyperlipidemia in mice. Compared to the high-fat model group, the compound preparation group showed significantly lower levels of TG, TC, HDL-C, and LDL-C (P<0.05), indicating that Quling Huazhuo granules can effectively reduce triglyceride, total cholesterol, high-density lipoprotein, and low-density lipoprotein levels in hyperlipidemic mice. For mice treated with red yeast rice alone, there were no significant differences in TC, HDL-C, and LDL-C compared to the high-fat model group (P>0.05), only a significant decrease in TG levels, indicating that red yeast rice alone cannot effectively control the various indicators in mice. Overall, Quling Huazhuo granules can significantly improve blood lipid levels and liver indicators in hyperlipidemic mice.

[0077] Table 2. Blood lipid levels in mice from different experimental groups

[0078]

[0079] 2) Effects of Quling Huazhuo Granules on the Histopathology of Hyperlipidemic Mice

[0080] HE staining results of mouse livers showed that the liver cells in the blank control group were neatly arranged, clearly defined, and had centrally located, plump, and round nuclei. In the high-fat model group, the livers of mice showed significant fat deposition, with densely and disorderedly arranged, unclear cell structure, and nuclei pushed to one side. Compared to the high-fat model group, the liver cells in the single red yeast rice group showed relative improvement, but a small number of fat vacuoles remained. The livers of mice in the compound preparation group showed no significant difference from the blank control group; the liver cells were normal in morphology and neatly arranged, indicating that Quling Huazhuo granules can reduce or inhibit fat accumulation in the liver and maintain stable liver function. Oil Red O staining results showed that the high-fat model group was bright red with significant fat deposition; the blank control group showed normal morphology. Compared to the high-fat model group, the single red yeast rice group and the compound preparation group showed significant improvement. The single red yeast rice group still had some fat deposition in its liver, while the Oil Red O staining results of the compound preparation group were closest to the blank group, with almost no fat deposition. These results indicate that Quling Huazhuo granules can effectively reduce the abnormal deposition of fat and lipids in the liver. Figure 4 As shown.

[0081] 3) Biosafety assessment of Quling Huazhuo Granules

[0082] No sudden death occurred in mice during treatment with single-origin red yeast rice and compound preparations. After treatment, mice were euthanized and their hearts, livers, spleens, lungs, and kidneys were isolated and stained with H&E. The results confirmed (e.g.) Figure 5Compared with the control group, after treatment with the compound preparation, no obvious morphological changes or pathological damage were observed in the major tissues and organs of the mice, which preliminarily proves that Quling Huazhuo Granules have good biocompatibility and low toxicity in treatment.

[0083] The above results indicate that the Quling Huazhuo Granules prepared in this application not only have excellent lipid-lowering effects, but also do not cause pathological damage to organs such as the heart, liver, spleen, lungs, and kidneys, and have excellent clinical application prospects.

[0084] Finally, it should be noted that the above specific embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to examples, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications and substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A traditional Chinese medicine with lipid-lowering effects, characterized in that, Made from the following parts by weight of active pharmaceutical ingredient: 5-10 parts red yeast rice, 10-30 parts poria cocos, 5-15 parts atractylodes lancea, 5-15 parts dried ginger, and 5-15 parts costus root.

2. The traditional Chinese medicine according to claim 1, characterized in that, Made from the following parts by weight of active pharmaceutical ingredient: 5-10 parts red yeast rice, 10-20 parts poria cocos, 10-15 parts atractylodes lancea, 10-15 parts dried ginger, and 8-15 parts costus root.

3. The traditional Chinese medicine according to claim 2, characterized in that, Made from the following parts by weight of active pharmaceutical ingredient: 6 parts red yeast rice, 20 parts poria cocos, 12 parts atractylodes lancea, 10 parts dried ginger, and 12 parts costus root.

4. A traditional Chinese medicine preparation with lipid-lowering effects, characterized in that, The traditional Chinese medicine preparation is a granule, tablet, capsule or powder made from the traditional Chinese medicine as described in any one of claims 1 to 3.

5. A method for preparing Quling Huazhuo granules using the traditional Chinese medicine according to any one of claims 1 to 3, characterized in that, Includes the following steps: (1) Wash each raw material and then pulverize it into powder with a particle size of 100-200 mesh. Then mix the powders of each raw material evenly. (2) At 45~60℃, add 6~10 times the weight of solvent to the powder obtained in step (1), and perform ultrasonic extraction at 150W power and 40KHz frequency. After extraction for 45~90min, collect and concentrate the extract to obtain the extract. (3) Mix the extract with the excipients and stir evenly, and adjust the humidity with ethanol to obtain the soft material; (4) The soft material is made into wet granules and then dried at 60~80℃.

6. The method according to claim 5, characterized in that, The extraction solvent is methanol, 75-95% ethanol, or anhydrous ethanol.

7. The method according to claim 5, characterized in that, The excipients are dextrin and powdered sugar, in a weight ratio of 1:3:1 to the extract.

8. The method according to claim 7, characterized in that, The sugar powder is sucrose powder, and the dextrin is soluble dextrin.

9. The use of the traditional Chinese medicine as described in any one of claims 1 to 3 or the traditional Chinese medicine preparation as described in claim 4 in the preparation of a medicine for the condition caused by hyperlipidemia.

Images