A traditional Chinese medicine composition, a pharmaceutical preparation, and their preparation methods and uses

Abstract

The present invention relates to the field of traditional Chinese medicine, and specifically provides a traditional Chinese medicine composition, a pharmaceutical preparation, and their preparation methods and uses. It is obtained by repeatedly optimizing the composition and content of the traditional Chinese medicine compound through clinical research and basic research. In the formula, Coptis chinensis is used as the monarch drug; Rheum palmatum, Anemarrhena asphodeloides, and Paeonia lactiflora are used as the ministerial drugs; Aurantium reticulatum and Monascus purpureus are used as adjuvant drugs; and Zingiber officinale is used as the guiding drug to reduce the cold nature of various drugs. When all the drugs are combined, none can be missing, and they work together to clear heat and lower turbidity, and reduce blood sugar and weight, having an obvious therapeutic effect on obesity, the inducement of diabetes, and diabetic patients (especially early-stage "hot-state" patients), and significantly improving the therapeutic effect on diabetes.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and particularly to a traditional Chinese medicine composition, a pharmaceutical preparation, and their preparation methods and uses. Background Art

[0002] In the past 30-odd years, the prevalence of diabetes in China has increased significantly. Among the diabetic population, type 2 diabetes (T2DM) accounts for more than 90%. The course of such patients lasts for decades, and with the prolongation of the disease duration, various complications such as blood vessels, nerves, kidneys, and gastrointestinal tract occur, seriously affecting the quality of life of patients. Despite lifestyle changes and various drug options, achieving stable and lasting blood glucose control and effectively preventing T2DM-related cardiovascular complications remains a challenging task in clinical management.

[0003] Traditional Chinese medicine has a long history in the treatment of diabetes. A large amount of evidence-based medicine has confirmed that traditional Chinese medicine has preventive or therapeutic effects in the prevention and treatment of diabetes. This prescription is based on the Dahuang Huanglian Xiexin Decoction, which is one of the classic ancient prescriptions in traditional Chinese medicine. It originated from "Treatise on Febrile Diseases - Differentiation and Treatment of Taiyang Disease, Lower Part, Article 7". For the syndrome of stuffiness and fullness in the epigastrium, with a soft feeling on pressing and a floating pulse at the Guan position, the Dahuang Huanglian Xiexin Decoction is the main treatment. This prescription is extremely simple, consisting of two liang of rhubarb and one liang of coptis, and is a clearing agent for purging fire and reducing heat, suitable for the syndrome of pathogenic heat congesting and accumulating in the middle jiao.

[0004] Chinese patent document CN112741872A discloses a traditional Chinese medicine composition for blood glucose control in diabetic patients, which is composed of kudzu root, scutellaria baicalensis, coptis chinensis, red peony root, anemarrhena asphodeloides, and american ginseng. While clearing heat and reducing blood sugar, it also has the effect of supplementing qi and nourishing yin. Although it can be widely applied to the diabetic population, it is not effective enough for the inducements of diabetes such as obesity, non-alcoholic fatty liver, and the early stage of diabetes. Summary of the Invention

[0005] Therefore, the technical problem to be solved by the present invention is to overcome the defects of insufficient effects on obesity, non-alcoholic fatty liver, and the early stage of diabetes in the traditional Chinese medicine composition for treating diabetes in the prior art, and to provide a traditional Chinese medicine composition, a pharmaceutical preparation, and their preparation methods and uses. The traditional Chinese medicine composition and the pharmaceutical preparation can significantly reduce weight and lipid levels, improve liver function, and increase insulin sensitivity while reducing blood sugar.

[0006] The present invention provides a traditional Chinese medicine composition. Calculated by weight parts, the raw materials of the traditional Chinese medicine composition include 2-10 parts of raw rhubarb, 6-35 parts of coptis, 10-65 parts of anemarrhena asphodeloides, 10-65 parts of red peony root, 1.5-9 parts of red yeast rice, 3-20 parts of dried tangerine peel, and 3-15 parts of dried ginger.

[0007] Further, by weight parts, the raw materials of the traditional Chinese medicine composition include 4.5 parts of Rheum officinale, 15 parts of Coptis chinensis, 30 parts of Anemarrhena asphodeloides, 30 parts of Paeonia lactiflora, 3 parts of Monascus purpureus, 9 parts of Citrus reticulata Blanco, and 6 parts of Zingiber officinale; or, 2 parts of Rheum officinale, 6 parts of Coptis chinensis, 10 parts of Anemarrhena asphodeloides, 10 parts of Paeonia lactiflora, 1.5 parts of Monascus purpureus, 3 parts of Citrus reticulata Blanco, and 3 parts of Zingiber officinale; or, 10 parts of Rheum officinale, 35 parts of Coptis chinensis, 65 parts of Anemarrhena asphodeloides, 65 parts of Paeonia lactiflora, 9 parts of Monascus purpureus, 20 parts of Citrus reticulata Blanco, and 15 parts of Zingiber officinale.

[0008] Among them, Rheum officinale is also known as Shengjun, and it is the rhizome of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. of the Polygonaceae family. The raw medicine is sorted to remove impurities, moistened until the internal and external humidity is uniform, sliced or cut into small pieces, and then dried in the sun.

[0009] Coptis chinensis is also called Huanglian, and it is the dried rhizome of Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao or Coptis teeta Wall. of the Ranunculaceae family. The raw materials are sorted to remove impurities, washed with mud and sand, moistened thoroughly, sliced, and dried in the shade.

[0010] Monascus purpureus is the red yeast rice formed by the mycelium of Monascus purpureus Went parasitizing on polished round-grained rice. The raw materials are screened to remove ash and sorted to remove impurities.

[0011] The present invention also provides a preparation method of the above-mentioned traditional Chinese medicine composition. Weigh Rheum officinale, Coptis chinensis, Anemarrhena asphodeloides, Paeonia lactiflora, Monascus purpureus, Citrus reticulata Blanco, and Zingiber officinale according to the selected weight parts, mix them and extract by a conventional extraction method or extract them separately by a conventional extraction method and then mix them to obtain the product.

[0012] In the present invention, the conventional extraction method includes one or several of decoction extraction, maceration extraction, percolation extraction, reflux extraction, ultrasonic extraction, and steam distillation extraction; the extraction solvent is selected from water or an alcohol solution with a volume percentage of 5-98%; the extraction times are at least 1 time; the extraction time is at least 10 min.

[0013] Further, the ratio of the volume of the extraction solvent to the weight of the raw materials of the medicine ≥ 2 L / kg. Or the amount of the extraction solvent is preferably 2-5 cm higher than the drug surface.

[0014] Further, the alcohol solution is an aqueous solution containing alcohol, and the alcohol can be ethanol or methanol, etc. The extraction times can be 1-5 times or 1-3 times. The extraction time can be 20-240 min or 30-120 min. The ratio of the volume of the extraction solvent to the weight of the raw materials of the medicine can be 3-20 L / kg or 5-10 L / kg. It can also be refined by a conventional refining method, such as but not limited to column chromatography, membrane filtration and other methods.

[0015] The present invention also provides a pharmaceutical preparation, which comprises the Chinese medicine composition described above or the Chinese medicine composition prepared by the preparation method described above.

[0016] Further, the pharmaceutical preparation is a clinically acceptable dosage form prepared by adding or not adding conventional excipients to the Chinese medicine composition described above or the Chinese medicine composition prepared by the preparation method described above according to a conventional process.

[0017] Further, the pharmaceutical preparation is a liquid preparation, granule, capsule or tablet; and / or,

[0018] The conventional excipients are selected from at least one of pharmaceutically acceptable solvents, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, glidants, flavoring agents, preservatives, suspending agents, pH regulators.

[0019] Among them, the liquid preparation can be a solution, decoction, suspension or emulsion, etc.

[0020] The present invention also provides a preparation method of the pharmaceutical preparation described in any one of the above, which comprises the following steps:

[0021] Take raw rhubarb, coptis, anemarrhena, red peony root, dried tangerine peel and dried ginger, respectively prepare them into granules according to a conventional process and then mix them to obtain mixed granules; take red yeast rice, decoct it with water, filter it, and mix the filtrate with the mixed granules to obtain the product; or,

[0022] Mix raw rhubarb, coptis, anemarrhena, red peony root, dried tangerine peel and dried ginger, and then prepare them into granules according to a conventional process; take red yeast rice, decoct it with water, filter it, and mix the filtrate with the granules to obtain the product; or,

[0023] Mix raw rhubarb, coptis, anemarrhena, red peony root, dried tangerine peel, dried ginger and red yeast rice, and then extract them by a conventional extraction method or extract them separately by a conventional extraction method and then mix them, filter, take the filtrate, concentrate, dry and granulate to obtain the product.

[0024] Further, the conventional process for preparing the granules according to the conventional process includes extraction, filtration, concentration, drying and granulation.

[0025] In the present invention, the conventional extraction method includes one or more of decoction extraction, maceration extraction, percolation extraction, reflux extraction, ultrasonic extraction and steam distillation extraction; the extraction solvent is selected from water or an alcohol solution with a volume percentage of 5-98%; the extraction times are at least 1 time; the extraction time is at least 10 min.

[0026] Further, the ratio of the volume of the extraction solvent to the weight of the raw drug ≥ 2 L / kg. Or the amount of the extraction solvent is preferably 2-5 cm higher than the drug surface.

[0027] Filtration can be but is not limited to filtration using gauze or filter membranes, etc. Concentration can be carried out by low-temperature concentration at 40-60°C. The drying can be but is not limited to drying methods such as spray drying or microwave drying. The granulation can be carried out by dry granulation or wet granulation.

[0028] During the process of preparing into granules according to the conventional process, conventional excipients can be added or not added.

[0029] The time for decocting red yeast rice with water is at least 10 min, for example, it can be 10-30 min.

[0030] The present invention also provides that the above-mentioned traditional Chinese medicine composition, or the above-mentioned preparation method, or any one of the above-mentioned pharmaceutical preparations, or the pharmaceutical preparation prepared by the above-mentioned preparation method has at least one of the following uses (1)-(6):

[0031] (1) Use in the preparation of a drug for inhibiting body weight gain and / or reducing lipid and / or reducing blood sugar;

[0032] (2) Use in the preparation of a drug for preventing or treating diabetes and / or hyperlipidemia;

[0033] (3) Use in the preparation of a drug for preventing or treating non-alcoholic fatty liver and / or abnormal liver function;

[0034] (4) Use in the preparation of a drug for reducing the level of serum ALT or AST, reducing liver weight or reducing liver organ coefficient;

[0035] (5) Use in the preparation of a drug for preventing or treating or alleviating impaired glucose tolerance;

[0036] (6) Use in the preparation of a drug for preventing or treating or alleviating insulin resistance or hyperinsulinemia or increasing insulin sensitivity.

[0037] Furthermore, the impaired glucose tolerance refers to impaired glucose tolerance or impairment; preventing or treating or alleviating impaired glucose tolerance means inhibiting the increase in blood sugar caused by oral glucose or increasing the tolerance to glucose; reducing lipid means reducing the level of at least one of GLU, TC, and LDL-C in the serum.

[0038] The technical solution of the present invention has the following advantages:

[0039] 1. The traditional Chinese medicine composition provided by the present invention is obtained through repeated optimization of the composition and content of the traditional Chinese medicine compound in clinical research and basic research. In the formula, Coptis chinensis is used as the monarch drug. Coptis chinensis is bitter and cold, purging fire and strengthening yin, purging the fire in the middle jiao; Rhubarb, Anemarrhena asphodeloides, and Paeonia lactiflora are used as ministerial drugs. Rhubarb is bitter and cold, purging heat and promoting defecation, purging the fire in the lower jiao. Anemarrhena asphodeloides is bitter and cold, purging fire and nourishing yin to moisten the lungs. Paeonia lactiflora is slightly bitter and cold, and is good at moving in the blood aspect. It can not only cool the heat in the blood, but also promote the qi stagnation in the blood. Aurantii Fructus Immaturus and Monascus purpureus are used as adjuvant drugs. Aurantii Fructus Immaturus invigorates the spleen and regulates qi, and Monascus purpureus reduces lipid and turbidity; Ginger is used as the guiding drug, which can reduce the cold nature of various drugs; All the drugs are used together, and none of them can be missing, jointly exerting the effects of clearing heat and reducing turbidity, reducing blood sugar and weight. It has obvious therapeutic effects on obesity, non-alcoholic fatty liver, which are the inducements of diabetes, and early diabetes, significantly improving the therapeutic effect on diabetes.

[0040] 2. The traditional Chinese medicine composition of the present invention not only has an obvious inhibitory effect on weight gain caused by high-fat diet, inhibits the blood sugar increase caused by oral glucose, significantly reduces the blood sugar value after injecting insulin, but also can reduce the levels of GLU, TC, and LDL-C in the serum, indicating that the traditional Chinese medicine composition of the present invention has obvious effects of inhibiting weight gain, reducing lipid, and reducing blood sugar, and can be used for preventing or treating diabetes, hyperlipidemia, preventing or treating or alleviating impaired glucose tolerance, insulin resistance, and hyperinsulinemia, and improving insulin sensitivity, etc.

[0041] The traditional Chinese medicine composition of the present invention can also reduce the levels of ALT and AST, reduce the liver weight and liver organ coefficient, indicating that it can prevent or treat non-alcoholic fatty liver and liver function abnormalities.

[0042] The traditional Chinese medicine composition or pharmaceutical preparation of the present invention is a target formula created for the "heat" state of type 2 diabetes (T2DM). It can play the role of multiple targets and multiple effect mechanisms of traditional Chinese medicine. It can not only target and reduce blood sugar and reduce weight, but also comprehensively adjust the "heat" state of T2DM as a whole. At the same time, it has no obvious side effects and adverse reactions. With the advantage of simultaneous regulation of state and target, it is of great benefit to achieving stable and lasting blood sugar control and effectively preventing T2DM-related complications.

[0043] 3. The pharmaceutical preparation provided by the present invention can be prepared into various dosage forms according to actual applications in the future. For example, it can be, but is not limited to, liquid preparations, granules, capsules, or tablets. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for the description of the specific embodiments or the prior art. Obviously, the following drawings are some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0045] Figure 1 They are the body weight and fasting blood glucose of mice in each group at 12 weeks of high-fat diet in Experimental Example 1 of the present invention.

[0046] Figure 2 They are the body weights of mice in each group during the drug administration period in Experimental Example 1 of the present invention.

[0047] Figure 3 They are the levels of GLU, TC, and LDL-C in the sera of mice in each group in Experimental Example 1 of the present invention.

[0048] Figure 4 They are the levels of ALT and AST in the sera of mice in each group, the liver weight, and the liver organ coefficient (Liver weight / body weight) in Experimental Example 1 of the present invention.

[0049] Figure 5 They are the blood glucose levels and the AUC of the oral glucose tolerance test (AUC of OGTT) of mice in each group during the oral glucose tolerance test (OGTT) in Experimental Example 1 of the present invention.

[0050] Figure 6 They are the blood glucose levels and the AUC of the insulin tolerance test (AUC of ITT) of mice in each group in the insulin tolerance test (ITT) in Experimental Example 1 of the present invention.

[0051] Figure 7 They are the detection results of FINS and HOMA-IR in the sera of mice in each group in Experimental Example 1 of the present invention.

[0052] Figure 8 They are the gross pictures of mice in each group after continuous gavage for 14 weeks in Experimental Example 1 of the present invention.

[0053] Figure 9 They are the gross pictures of the livers of mice in each group after continuous gavage for 14 weeks in Experimental Example 1 of the present invention.

[0054] Figure 10 They are the pathological HE staining pictures of the livers of mice in each group after continuous gavage for 14 weeks in Experimental Example 1 of the present invention. Detailed implementation manners

[0055] The following embodiments are provided to better further understand the present invention. They are not limited to the described optimal implementation manner, and do not constitute a limitation to the content and protection scope of the present invention. Any product that is the same as or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with those of other prior arts falls within the protection scope of the present invention.

[0056] For those without specific experimental procedures or conditions indicated in the examples, the operations or conditions of the conventional experimental procedures described in the literature in this field can be followed. For reagents or instruments without the manufacturer indicated, they are all conventional reagent products that can be obtained through commercial purchase. All medicinal materials passed the quality inspection.

[0057] Example 1

[0058] This example provides a traditional Chinese medicine composition, including 4.5 g of Rheum officinale, 15 g of Coptis chinensis, 30 g of Anemarrhena asphodeloides, 30 g of Paeonia lactiflora, 3 g of Monascus purpureus, 9 g of Citrus reticulata and 6 g of Zingiber officinale.

[0059] This example provides a pharmaceutical preparation containing the above traditional Chinese medicine composition, and its preparation method is as follows:

[0060] Weigh Rheum officinale, Coptis chinensis, Anemarrhena asphodeloides, Paeonia lactiflora, Citrus reticulata and Zingiber officinale according to the above weights, and extract them by boiling with water twice. The first time is for 2 hours, and the second time is for 1 hour. The amount of added water should be appropriate to submerge the drug surface by 3 cm. Combine the decoction solutions. After filtration, concentrate at a low temperature of 65 °C, spray dry, and granulate by dry granulation to obtain granules of Rheum officinale, granules of Coptis chinensis, granules of Anemarrhena asphodeloides, granules of Paeonia lactiflora, granules of Citrus reticulata and granules of Zingiber officinale, and then mix them to obtain mixed granules.

[0061] Weigh Monascus purpureus according to the above weight, boil it with water for 15 min, and the amount of added water should be appropriate to submerge the drug surface by 3 cm. After filtering with gauze, take the filtrate. Dissolve the above mixed granules with the filtrate to obtain a solution.

[0062] Example 2

[0063] This example provides a traditional Chinese medicine composition, including 2 g of Rheum officinale, 6 g of Coptis chinensis, 10 g of Anemarrhena asphodeloides, 10 g of Paeonia lactiflora, 1.5 g of Monascus purpureus, 3 g of Citrus reticulata and 3 g of Zingiber officinale.

[0064] This example provides a pharmaceutical preparation containing the above traditional Chinese medicine composition, and its preparation method is as follows: Weigh Rheum officinale, Coptis chinensis, Anemarrhena asphodeloides, Paeonia lactiflora, Citrus reticulata and Zingiber officinale according to the above weights and mix them, then extract by boiling with water twice. The first time is for 2 hours, and the second time is for 1 hour. The amount of added water should be appropriate to submerge the drug surface by 2 cm. Combine the decoction solutions. After filtration, concentrate at a low temperature of 65 °C, spray dry, and granulate by dry granulation to obtain mixed granules.

[0065] Weigh Monascus purpureus according to the above weight, boil it with water for 15 min, and the amount of added water should be appropriate to submerge the drug surface by 2 cm. After filtering with gauze, take the filtrate. Dissolve the above mixed granules with the filtrate to obtain a solution.

[0066] Example 3

[0067] This embodiment provides a traditional Chinese medicine composition, including 10 g of Rheum officinale, 35 g of Coptis chinensis, 65 g of Anemarrhena asphodeloides, 65 g of Paeonia lactiflora, 9 g of Monascus purpureus, 20 g of Citrus reticulata and 15 g of Zingiber officinale.

[0068] This embodiment provides a pharmaceutical preparation containing the above traditional Chinese medicine composition, and its preparation method is as follows: Weigh Rheum officinale, Coptis chinensis, Anemarrhena asphodeloides, Paeonia lactiflora, Citrus reticulata, Zingiber officinale and Monascus purpureus according to the above weights and mix them. Add water and decoct for the first time for 2 hours and the second time for 1 hour. The amount of added water should be appropriate to submerge the drug surface by 5 cm, and combine the decoction liquid. After filtration, concentrate at a low temperature of 65 °C, spray dry, and granulate by dry granulation to obtain the granule.

[0069] Experimental Example 1 Effects of Jiangtang Qingre Prescription on Diabetic Model Mice

[0070] 1. Experimental Method

[0071] (1) Animal Grouping and Administration

[0072] 120 healthy male C57BL / 6J mice, SPF grade, 5 weeks old, provided by Jiangsu Jicui Yakang Biotechnology Co., Ltd. and raised in the Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences. The breeding environment is a clean animal room, the indoor temperature is controlled at 22 - 25 °C, the humidity is 55 ± 5%, and there is a 12 / 12 hour light-dark cycle (light time 7:00 - 19:00), and food and water are freely available. Feed adaptively for one week.

[0073] Model establishment: Randomly select 30 mice as the blank control group, and the remaining mice are the model group. The blank control group is fed with standard feed, and the model group is fed with 60% high-fat feed (D12492, Open Source Diet). The model group is fed a high-fat diet for 12 weeks. When the average fasting blood glucose of the mice's body weight and daytime fasting for 6 hours is higher than 10.5 mmol / L and there is a significant difference compared with the blank control group, the diabetic model is successfully established.

[0074] Grouping and administration: After the successful establishment of the model, according to the random number table method, the model group is randomly divided into the model group (HFD), the western medicine group (HFD + MET), the low-dose traditional Chinese medicine group (HFD + JQFL), the medium-dose traditional Chinese medicine group (HFD + JQFM), and the high-dose traditional Chinese medicine group (HFD + JQFH), with 16 mice in each group. The blank control group is randomly divided into the blank group (NCD) and the blank + medium-dose traditional Chinese medicine group (NCD + JQFM), with 15 mice in each group (see Table 1, Figure 1)。The medium-dose traditional Chinese medicine group was calculated according to the equivalent dose conversion between animals and humans (9.1:1). Calculated based on the crude drug amount, the dose of Jiangtang Qingre Prescription for humans was 1.625 g / kg / d, and for mice it was 14.7875 g / kg / d. The low-dose and high-dose traditional Chinese medicine groups were respectively 1 / 2 times (7.394 g / kg / d) and 2 times (29.575 g / kg / d) of the medium-dose traditional Chinese medicine group. Among them, Jiangtang Qingre Prescription was the pharmaceutical preparation prepared according to Example 1 above. Before use, it was diluted with distilled water and administered by gavage. The western medicine group was administered metformin hydrochloride tablets at a dose of 300 mg / kg / d. Before use, it was diluted with distilled water and administered by gavage. The blank group and the model group were gavaged with distilled water. Gavage was performed continuously for 14 weeks. Animal experiments strictly followed the ethical requirements of the "Experimental Animal Management Regulations of the Institute of Basic Theory of Chinese Academy of Chinese Medical Sciences" and the "Experimental Animal Management Regulations" of the National Science and Technology Commission, and were approved by the Animal Protection and Use Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences (Ethical batch number: IACUC-GAMH-2022-004).

[0075] Table 1 Body weights and fasting blood glucose levels of mice in each group at 12 weeks of high-fat diet

[0076]

[0077] Note: Compared with NCD, P < 0.001.

[0078] (2) Weighing and detection

[0079] The body weights of the mice were weighed with an electronic weighing scale and recorded once a week at a fixed weighing time.

[0080] (3) Blood biochemical detection

[0081] After blood was taken from the eyeballs of the mice and allowed to stand for 2 hours at 4°C, it was centrifuged at 3000 revolutions for 15 minutes to separate the serum. The contents of glucose (GLU), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the serum were detected on an automatic biochemical analyzer. The liver was weighed during sampling.

[0082] (4) Detection of glucose metabolism indicators

[0083] Oral glucose tolerance test (OGTT) was performed after continuous administration for 12 weeks. The mice were fasted overnight for 14 h, and then administrated with 20% glucose by gavage at a dose of 2 g / kg. Blood samples were collected from the tip of the tail at 0 min, 15 min, 30 min, 60 min, 90 min, and 120 min, and blood glucose was measured with a handheld blood glucose meter. The area under the curve (AUC) of the blood glucose-time curve was calculated.

[0084] Insulin tolerance test (ITT) was performed after continuous administration for 13 weeks. The mice were fasted during the day for 4 h, and then administrated with insulin by intraperitoneal injection at a dose of 0.75 U / Kg. Blood samples were collected from the tip of the tail at 0 min, 15 min, 30 min, 60 min, 90 min, and 120 min, and blood glucose was measured with a handheld blood glucose meter. The area under the curve (AUC) of the blood glucose-time curve was calculated.

[0085] (5) Detection of insulin resistance

[0086] Blood was collected from the eyeballs and the serum was reserved. The fasting insulin level (FINS) of each group of mice was detected with an insulin ELISA kit (CCM-90080, Crystal Chem). The insulin resistance index (HOMA-IR) of the steady-state model was calculated, and HOMA-IR = (FBG × FINS) / 22.5.

[0087] 2. Data processing

[0088] SPSS 26.0 software was used for data processing and statistical analysis. The data were expressed as mean ± standard deviation. If the data met the normal distribution and homogeneity of variance, one-way ANOVA (ANOVA test) was used. If the data did not meet the normal distribution or homogeneity of variance, non-parametric tests were used. A P value < 0.05 was considered statistically significant.

[0089] 3. Experimental results

[0090] (1) Results of body weight detection

[0091] Table 2 Effects of the traditional Chinese medicine composition of the present invention on the body weight of diabetic mice (n = 12 - 16, )(Unit: g)

[0092]

[0093] Note: Compared with NCD, P < 0.001; compared with HFD, *P < 0.05, **P < 0.01, ***P < 0.001.

[0094] Table 3 Effects of the traditional Chinese medicine composition of the present invention on the body weight of diabetic mice (n = 12 - 16, )(Unit: g)

[0095]

[0096] Note: Compared with NCD, P < 0.001; compared with HFD, *P < 0.05, **P < 0.01, ***P < 0.001.

[0097] As shown in Tables 2 - 3 and Figure 2 , where NCD + JQFM represents the blank + medium-dose traditional Chinese medicine group, NCD represents the blank group, HFD represents the model group, HFD + MET represents the western medicine group, HFD + JQFL represents the low-dose traditional Chinese medicine group, HFD + JQFM represents the medium-dose traditional Chinese medicine group, and HFD + JQFH represents the high-dose traditional Chinese medicine group. At 12 weeks of high-fat diet (i.e., 0 weeks of drug administration), compared with the blank group, there was a significant difference in body weight in the model group, indicating that the model was successfully established. At the same time, there was no significant difference in body weight between the model group and each drug administration group, indicating that the baselines of each high-fat group were consistent. As time increased, the body weight of the mice in the model group continued to increase, while the body weight of the drug administration groups increased slowly, showing a significant inhibitory effect on the body weight increase induced by high-fat diet. At the same time, there was an obvious dose-dependent relationship among the low, medium, and high doses of traditional Chinese medicine. The control effect of the traditional Chinese medicine composition of the present invention on body weight increase was basically the same as that of the positive control drug metformin.

[0098] (2) Results of blood biochemical tests

[0099] Table 4 Effects of the traditional Chinese medicine composition of the present invention on serum GLU, TC, and LDL-C in diabetic mice

[0100]

[0101]

[0102] Note: Compared with NCD, P < 0.001; compared with HFD, *P < 0.05, **P < 0.01, ***P < 0.001.

[0103] The results are shown in Tables 4 and 5, Figure 3 、 Figure 4, where NCD+JQFM represents the blank + medium-dose traditional Chinese medicine group, NCD represents the blank group, HFD represents the model group, HFD+MET represents the western medicine group, HFD+JQFL represents the low-dose traditional Chinese medicine group, HFD+JQFM represents the medium-dose traditional Chinese medicine group, and HFD+JQFH represents the high-dose traditional Chinese medicine group. Compared with the blank group, the serum GLU of the mice in the model group was significantly increased (P<0.001), indicating that the diabetic mouse model was successfully established. At the same time, the serum blood lipids TC and LDL-C of the mice in the model group were both significantly increased (P<0.001), suggesting that a high-fat diet may cause hyperlipidemia in the mice in the model group. After treatment with the traditional Chinese medicine composition and the positive control drug metformin, the levels of serum GLU, TC, and LDL-C in the mice were all significantly decreased (P<0.05, P<0.001).

[0104] Table 5 Effects of the traditional Chinese medicine composition of the present invention on serum ALT, AST, and liver weight of diabetic mice

[0105]

[0106]

[0107] Note: Compared with NCD, P<0.001; compared with HFD, ***P<0.001.

[0108] Compared with the blank group, the levels of serum ALT and AST, as well as the liver weight and liver organ coefficient of the mice in the model group were significantly increased (P<0.001), suggesting that the high-fat-induced mice may have non-alcoholic fatty liver and accompanied by abnormal liver function. After treatment with the traditional Chinese medicine composition and the positive control drug metformin, the levels of serum liver function ALT and AST, as well as the liver weight and liver organ coefficient of the mice were all significantly decreased (P<0.001).

[0109] (3) Detection results of glucose metabolism indexes

[0110] Table 6 Effects of the traditional Chinese medicine composition of the present invention on glucose tolerance of diabetic mice

[0111]

[0112] Note: Compared with NCD, ##P<0.01, P<0.001; compared with HFD, *P<0.05, **P<0.01, ***P<0.001.

[0113] It can be seen from the results of the OGTT experiment that compared with the blank group, the blood glucose value of the mice in the model group was significantly increased (P < 0.001), indicating that the glucose tolerance of the mice in the model group was decreased. When the ability of the body to consume glucose decreased, after exogenous glucose was administered, the blood glucose increased relatively rapidly and decreased slowly. Compared with the model group, the traditional Chinese medicine composition of the present invention significantly decreased the blood glucose values of the mice at 0, 90, and 120 min after glucose administration (P < 0.05, P < 0.01, P < 0.001). Although there was no significant difference in the area under the curve between each administration group and the model group, there was a downward trend, and the decrease was the most in the high-dose traditional Chinese medicine group. It shows that the traditional Chinese medicine composition of the present invention can inhibit the increase in blood glucose caused by oral glucose and enhance the ability of the mouse body to tolerate sugar. The above results suggest that the traditional Chinese medicine composition of the present invention has a good regulatory effect on glucose tolerance abnormality induced by high fat in mice.

[0114] Table 7 Effects of the traditional Chinese medicine composition of the present invention on insulin tolerance in diabetic mice

[0115]

[0116] Note: Compared with NCD, P < 0.001; compared with HFD, *P < 0.05, **P < 0.01, ***P < 0.001.

[0117] It can be seen from the results of the ITT experiment that compared with the blank group, the blood glucose value of the mice in the model group decreased slowly and increased rapidly (P < 0.001), indicating that the sensitivity of the mice in the model group to insulin decreased. Compared with the model group, the traditional Chinese medicine composition of the present invention significantly decreased the blood glucose values of the mice at 15, 30, 60, 90, and 120 min after insulin injection (P < 0.05, P < 0.01, P < 0.001). The area under the curve of each administration group was significantly lower than that of the model group (P < 0.01, P < 0.001), indicating that the traditional Chinese medicine composition of the present invention can significantly enhance the ability of the mouse body to tolerate insulin. The above results suggest that the traditional Chinese medicine composition of the present invention can significantly improve the efficiency of the mouse body to uptake and utilize glucose induced by high fat and enhance insulin sensitivity.

[0118] (4) Results of insulin resistance detection

[0119] The detection results are shown in Table 8 and Figure 7 , where NCD + JQFM represents the blank + medium-dose traditional Chinese medicine group, NCD represents the blank group, HFD represents the model group, HFD + MET represents the western medicine group, HFD + JQFL represents the low-dose traditional Chinese medicine group, HFD + JQFM represents the medium-dose traditional Chinese medicine group, and HFD + JQFH represents the high-dose traditional Chinese medicine group.

[0120] Table 8 Effects of the traditional Chinese medicine composition of the present invention on FINS and HOMA-IR in diabetic mice

[0121]

[0122] Note: Compared with NCD, P < 0.001; compared with HFD, ***P < 0.001.

[0123] Compared with the blank group, the levels of FINS and HOMA-IR in the model group mice were significantly increased (P < 0.001), indicating the presence of hyperinsulinemia and insulin resistance in this model. Compared with the model group, the FINS levels in the mice of each group of the traditional Chinese medicine composition of the present invention decreased to a certain extent. Although there was no statistical difference, the insulin resistance index HOMA-IR was significantly decreased, especially in the high-dose traditional Chinese medicine group (P < 0.001), which was equivalent to the efficacy of the positive control drug metformin. The results suggest that the traditional Chinese medicine composition of the present invention can reduce the FINS level in high-fat-induced mice and effectively improve insulin resistance.

[0124] In summary, the traditional Chinese medicine composition or pharmaceutical preparation of the present invention not only has a significant inhibitory effect on the weight gain caused by high-fat diet, inhibits the blood glucose increase caused by oral glucose, and significantly reduces the blood glucose value after insulin injection, but also can reduce the levels of GLU, TC and LDL-C in the serum, indicating that the traditional Chinese medicine composition of the present invention has obvious effects of inhibiting weight gain, reducing lipid and lowering blood glucose, and can be used for preventing or treating diabetes, hyperlipidemia, non-alcoholic fatty liver, preventing or treating or alleviating impaired glucose tolerance, insulin resistance and hyperinsulinemia, and improving insulin sensitivity, etc.

[0125] Obviously, the above embodiments are only examples given for clear illustration and are not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or alterations can be made based on the above description. It is not necessary and impossible to enumerate all the implementation manners here. And the obvious changes or alterations derived therefrom still fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition, characterized in that, Calculated by weight parts, the raw materials of the traditional Chinese medicine composition are composed of the following: 2-10 parts of Rheum officinale, 6-35 parts of Coptis chinensis, 10-65 parts of Anemarrhena asphodeloides, 10-65 parts of Paeonia lactiflora, 1.5-9 parts of Monascus purpureus, 3-20 parts of Citrus reticulata Blanco, and 3-15 parts of Zingiber officinale Rosc.

2. The traditional Chinese medicine composition according to claim 1, wherein Calculated by weight parts, the raw materials of the traditional Chinese medicine composition are composed of the following: 4.5 parts of Rheum officinale, 15 parts of Coptis chinensis, 30 parts of Anemarrhena asphodeloides, 30 parts of Paeonia lactiflora, 3 parts of Monascus purpureus, 9 parts of Citrus reticulata Blanco, and 6 parts of Zingiber officinale Rosc.; or, 2 parts of Rheum officinale, 6 parts of Coptis chinensis, 10 parts of Anemarrhena asphodeloides, 10 parts of Paeonia lactiflora, 1.5 parts of Monascus purpureus, 3 parts of Citrus reticulata Blanco, and 3 parts of Zingiber officinale Rosc.; or, 10 parts of Rheum officinale, 35 parts of Coptis chinensis, 65 parts of Anemarrhena asphodeloides, 65 parts of Paeonia lactiflora, 9 parts of Monascus purpureus, 20 parts of Citrus reticulata Blanco, and 15 parts of Zingiber officinale Rosc.

3. A method for preparing the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, Weigh Rheum officinale, Coptis chinensis, Anemarrhena asphodeloides, Paeonia lactiflora, Monascus purpureus, Citrus reticulata Blanco, and Zingiber officinale Rosc. according to the selected weight parts, mix them and extract by conventional extraction methods or extract them separately by conventional extraction methods and then mix them to obtain the product.

4. The preparation method of the traditional Chinese medicine composition according to claim 3, characterized in that, The conventional extraction methods are selected from one or more of decoction extraction, maceration extraction, percolation extraction, reflux extraction, ultrasonic extraction, and steam distillation extraction; the extraction solvent is selected from water or an alcohol solution with a volume percentage of 5-98%; the extraction times are at least 1 time; the extraction time is at least 10 min.

5. A pharmaceutical preparation, characterized in that, It is made from the traditional Chinese medicine composition described in claim 1 or 2 or the traditional Chinese medicine composition prepared by the preparation method described in claim 3 or 4.

6. The pharmaceutical preparation according to claim 5, characterized in that, The pharmaceutical preparation is made by adding or not adding conventional excipients to the traditional Chinese medicine composition described in claim 1 or 2 or the traditional Chinese medicine composition prepared by the preparation method described in claim 3 or 4, and making it into a clinically acceptable dosage form according to conventional processes.

7. The pharmaceutical preparation according to claim 6, characterized in that, The pharmaceutical preparation is a liquid preparation, granule, capsule, or tablet; and / or, the conventional excipients are selected from at least one of pharmaceutically acceptable solvents, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, glidants, flavoring agents, preservatives, suspending agents, and pH regulators.

8. A method for preparing a pharmaceutical preparation according to any one of claims 5-7, characterized in that, It includes the following steps: Take Rheum officinale, Coptis chinensis, Anemarrhena asphodeloides, Paeonia lactiflora, Citrus reticulata Blanco, and Zingiber officinale Rosc., prepare them into granules by conventional processes respectively and then mix them to obtain mixed granules; take Monascus purpureus, decoct it with water, filter it, and mix the filtrate with the mixed granules to obtain the product; or, Take Rheum officinale, Coptis chinensis, Anemarrhena asphodeloides, Paeonia lactiflora, Citrus reticulata Blanco, and Zingiber officinale Rosc., mix them and prepare them into granules by conventional processes; take Monascus purpureus, decoct it with water, filter it, and mix the filtrate with the granules to obtain the product; or, Take Rheum officinale, Coptis chinensis, Anemarrhena asphodeloides, Paeonia lactiflora, Citrus reticulata Blanco, Zingiber officinale Rosc., and Monascus purpureus, mix them and extract by conventional extraction methods or extract them separately by conventional extraction methods and then mix them, filter, take the filtrate, concentrate, dry, and granulate it to obtain the product.

9. The traditional Chinese medicine composition described in claim 1 or 2 or the traditional Chinese medicine composition prepared by the preparation method described in claim 3 or 4 or the pharmaceutical preparation described in any one of claims 5-7 or the pharmaceutical preparation prepared by the preparation method described in claim 8 has at least one of the following uses (1)-(4): (1) Use in the preparation of a drug for inhibiting body weight gain; (2) Use in the preparation of a drug for preventing or treating diabetes and / or hyperlipidemia; (3) Use in the preparation of a medicament for preventing or treating non-alcoholic fatty liver; (4) Use in the preparation of a medicament for preventing, treating or alleviating insulin resistance or enhancing insulin sensitivity.

10. The traditional Chinese medicine composition described in claim 1 or 2, or the traditional Chinese medicine composition prepared by the preparation method described in claim 3 or 4, or the pharmaceutical preparation described in any one of claims 5-7, or the pharmaceutical preparation prepared by the preparation method described in claim 8 has at least one of the following uses (1)-(3): (1) Use in the preparation of a medicament for inhibiting lipid-lowering and / or blood sugar-lowering; (2) Use in the preparation of a medicament for reducing the levels of serum ALT or AST, reducing liver weight or reducing liver organ coefficient; (3) Use in the preparation of a medicament for preventing, treating or alleviating impaired glucose tolerance.

11. The use according to claim 10, characterized in that, The impaired glucose tolerance refers to impaired glucose tolerance or glucose intolerance; preventing, treating or alleviating impaired glucose tolerance means inhibiting the increase in blood sugar caused by oral glucose or enhancing the tolerance to glucose; lipid-lowering means reducing the level of at least one of TC and LDL-C in serum.

12. Use of the traditional Chinese medicine composition described in claim 1 or 2, or the traditional Chinese medicine composition prepared by the preparation method described in claim 3 or 4, or the pharmaceutical preparation described in any one of claims 5-7, or the pharmaceutical preparation prepared by the preparation method described in claim 8 in the preparation of a medicament for preventing or treating hyperinsulinemia.

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