Application of uremia clearing composition in preparation of medicine for treating metabolic diseases

Abstract

The invention belongs to the field of treatment of metabolic diseases by traditional Chinese medicines, and particularly relates to application of a uremia clearing composition in preparation of medicines for treating metabolic diseases. The uremia clearing composition comprises the following raw materials: rheum officinale, astragalus membranaceus, white mulberry root-bark, radix sophorae flavescentis, codonopsis pilosula, bighead atractylodes rhizome, poria cocos, radix polygoni multiflori preparata, radix paeoniae alba, salvia miltiorrhiza, ligusticum wallichii, chrysanthemum, ginger processed pinellia, plantain herb, radix bupleuri and liquorice in a mass ratio of 1: (3-5): (2-4): (1-3): (2-4): (4-6): (4-6): (4-6): (2-4): (4-6): (2-4): (2-3): (1-3): (4-6): (1-2): (0.5-2). The uremia clearing composition can remarkably regulate the blood sugar and blood fat metabolism level, pharmacological experiment research shows that compared with a model group, a low-dose group, a medium-dose group and a high-dose group of uremia clearing in the embodiment 1 have the advantages that the blood sugar is obviously reduced, the medium-dose group of uremia clearing in the embodiment 1 can remarkably reduce the level of triglyceride and total cholesterol, and the content of total cholesterol in uremia clearing in the embodiment 1 is reduced. The high-dose group can significantly reduce the levels of triglyceride, total cholesterol and low-density lipoprotein, and has a good application prospect.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine for treating metabolic diseases, and particularly relates to the application of a Niandutang composition in the preparation of a drug for treating metabolic diseases. Background Art

[0002] Metabolic diseases (such as diabetes, hyperlipidemia, etc.) have a pathogenesis involving multiple factors such as insulin resistance and disorders of glucose and lipid metabolism. They are caused by relative or absolute deficiency of insulin or defects in its utilization, manifested as hyperglycemia and glycosuria, often accompanied by dyslipidemia, and chronic complications of tissues and organs such as eyes, kidneys, nerves, skin, blood vessels, and heart diseases.

[0003] Western medicine for treating diabetes has the characteristics of strong blood glucose lowering effect and rapid onset. For example, metformin and insulin sensitizers can relieve symptoms, but there are problems such as gastrointestinal reactions, hypoglycemia risk, and drug resistance after long-term use. They often lack overall coordination and have obvious side effects, which are not conducive to long-term use by patients.

[0004] Diabetes belongs to the categories of "consumptive thirst", "consumptive itching" in traditional Chinese medicine. It was recognized in ancient China and was generally called consumptive thirst disease, and was retained in ancient literature under different names such as consumptive thirst, consumptive itching, and consumptive middle.

[0005] Traditional Chinese medicine can reduce blood glucose through multiple pathways and multiple targets, reduce the damage of diabetes to the body, and control and delay diabetic complications. Moreover, the active ingredients of traditional Chinese medicine have the advantages of stable curative effect, low toxicity, few adverse reactions, and convenient administration, and are especially suitable for preventing and treating diabetic complications. Therefore, traditional Chinese medicine has an irreplaceable advantage in the prevention and treatment of diabetes and its complications.

[0006] However, some studies focus on single active ingredients, while metabolic diseases require multi-target regulation, and single ingredients are difficult to comprehensively improve glucose and lipid metabolism. Complex traditional Chinese medicine prescriptions have problems such as complex ingredients, drug interactions, and difficult prediction of side effects. Therefore, using old drugs for new uses and studying the extraction methods of traditional prescriptions in an attempt to find better therapeutic effects and develop new indications is an important topic in this field currently. Summary of the Invention

[0007] Aiming at the deficiencies of the existing technology, the present invention provides the application of a Niandutang composition in the preparation of a drug for treating metabolic diseases.

[0008] In order to achieve the object of the present invention, the technical scheme adopted is as follows: The application of a Niandutang composition in the preparation of a drug for treating metabolic diseases.

[0009] Preferably, the metabolic disease is abnormal blood glucose and / or blood lipid metabolism.

[0010] Preferably, the Niandutang composition can reduce the blood sugar of the body.

[0011] Preferably, the Niandutang composition can reduce one or more of triglyceride, total cholesterol and low-density lipoprotein in the body.

[0012] Preferably, the Niandutang composition comprises the following raw materials: rhubarb, astragalus root, mulberry bark, lightyellow sophora root, pilose asiabell root, largehead atractylodes rhizome, poria, prepared fleece-flower root, white peony root, salvia miltiorrhiza, chuanxiong rhizome, chrysanthemum, pinellia ternata, plantain herb, bupleurum root and liquorice root.

[0013] Preferably, the mass ratio of rhubarb, astragalus root, mulberry bark, lightyellow sophora root, pilose asiabell root, largehead atractylodes rhizome, poria, prepared fleece-flower root, white peony root, salvia miltiorrhiza, chuanxiong rhizome, chrysanthemum, pinellia ternata, plantain herb, bupleurum root and liquorice root is: 3-30: 9-30: 6-12: 4.5-9: 9-30: 6-12: 9-15: 6-12: 6-15: 9-15: 3-9: 5-9: 3-9: 9-30: 3-9: 1.5-9.

[0014] Preferably, the mass ratio of rhubarb, astragalus root, mulberry bark, lightyellow sophora root, pilose asiabell root, largehead atractylodes rhizome, poria, prepared fleece-flower root, white peony root, salvia miltiorrhiza, chuanxiong rhizome, chrysanthemum, pinellia ternata, plantain herb, bupleurum root and liquorice root is: 1: 3-5: 2-4: 1-3: 2-4: 4-6: 4-6: 4-6: 2-4: 4-6: 2-4: 2-3: 1-3: 4-6: 1-2: 0.5-2.

[0015] Preferably, the preparation method of the Niandutang composition comprises mixing all the raw materials, decocting with water for 1-3 times, filtering, concentrating the filtrate into clear paste, drying, and pulverizing into fine powder to obtain the composition, or adding dextrin to the fine powder to make granules to obtain the composition.

[0016] Preferably, the filtrate is concentrated to a relative density of 1.1-1.25 at 80 °C, and the drying temperature is 50-70 °C.

[0017] Preferably, lecithin and polyglyceryl oleate are added to the water before decocting. The polyglyceryl oleate is diglycerol monooleate.

[0018] Preferably, based on the mass of water, 0.01-0.05% lecithin and 0.005-0.01% polyglyceryl oleate are added to the water before decocting.

[0019] Another object of the present invention is to provide a Niandutang composition, the raw materials of the composition comprising the following raw materials: rhubarb, astragalus root, mulberry bark, lightyellow sophora root, pilose asiabell root, largehead atractylodes rhizome, poria, prepared fleece-flower root, white peony root, salvia miltiorrhiza, chuanxiong rhizome, chrysanthemum, pinellia ternata, plantain herb, bupleurum root and liquorice root; the preparation method of the Niandutang composition comprises the following steps: Mix all the raw materials, decoct them with water 1 - 3 times, filter, concentrate the filtrate into a clear paste, dry it, and pulverize it into fine powder to obtain the product, or make fine powder into granules by adding dextrin. Lecithin and polyglyceryl oleate are also added to the water before decocting.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) It is found in the research of the present invention that the Uremia - Qing composition can significantly reduce the blood glucose of the body and regulate the blood glucose metabolism level. There is no statistical difference in blood glucose between the mice in each example group and the model group before administration. After 2 weeks of administration, compared with the model group, the blood glucose in the positive group, the low, medium, and high - dose groups of Example 1 decreased significantly, and the high - dose group of Example 1 was the most prominent, with extremely significant statistical differences (##p < 0.01). At the same dose, the hypoglycemic effect of Example 1 is significantly better than the compositions obtained by other preparation methods.

[0021] (2) The present invention also studied the blood lipid metabolism level of the model mice and found that on the basis of improving the specific blood glucose level, its blood lipid level was further improved, especially the triglyceride level. Specific Embodiments

[0022] The present invention will be further described below in conjunction with specific embodiments.

[0023] Application of Uremia - Qing Composition in Improving Blood Glucose and Blood Lipid Metabolism Diseases Example 1: Uremia - Qing Composition Raw materials: The mass ratio of rhubarb, astragalus, mulberry bark, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, poria cocos, polygonum multiflorum preparata, white peony root, salvia miltiorrhiza, ligusticum wallichii, chrysanthemum, pinellia ternata, plantain herb, bupleurum chinense, and licorice is 1:4:3:2:3:5:5:5:3:5:3:2.5:2:5:1.5:0.9; The preparation method is as follows: Weigh 40 g of rhubarb, 36 g of licorice, 160 g of astragalus, 120 g of mulberry bark, 80 g of sophora flavescens, 120 g of codonopsis pilosula, 200 g of atractylodes macrocephala, 200 g of poria cocos, 120 g of white peony root, 1000 g of chrysanthemum, 200 g of polygonum multiflorum preparata, 120 g of ligusticum wallichii, 200 g of salvia miltiorrhiza, 80 g of pinellia ternata, 200 g of plantain herb, and 60 g of bupleurum chinense, decoct them three times with 8 times the amount of water containing 0.01% lecithin and 0.01% diglycerol monooleate by mass concentration, each of the first and second times for 2 hours, and the third time for 1 hour. Combine the decoction liquid, filter, concentrate the filtrate to a clear paste with a relative density of 1.25 (80 °C), place it in an oven and dry it into a dry paste at 75 °C, and pulverize it into fine powder.

[0024] Example 2 The difference between this example and Example 1 lies in the different preparation methods. The specific preparation is as follows: Weigh 40 g of Rheum palmatum, 36 g of Glycyrrhiza uralensis, 160 g of Astragalus membranaceus, 120 g of Mori Cortex, 80 g of Sophora flavescens, 120 g of Codonopsis pilosula, 200 g of Atractylodes macrocephala, 200 g of Poria cocos, 120 g of Paeonia lactiflora, 1000 g of Chrysanthemi Flos, 200 g of Polygonum multiflorum preparatum, 120 g of Ligusticum wallichii, 200 g of Salvia miltiorrhiza, 80 g of Pinelliae Rhizoma preparatum, 200 g of Plantaginis Herba, and 60 g of Bupleuri Radix. Add 8 times the amount of water containing 0.02% (mass concentration) of diglycerol monooleate and decoct for three times, 2 hours for the first and second times, and 1 hour for the third time. Combine the decoctions, filter, concentrate the filtrate to a clear paste with a relative density of 1.25 (80 °C), place it in an oven and dry it into a dry paste at 75 °C, and then pulverize it into fine powder.

[0025] Example 3 The difference between this example and Example 1 lies in the different preparation methods, and the specific preparation is as follows: Weigh 40 g of Rheum palmatum, 36 g of Glycyrrhiza uralensis, 160 g of Astragalus membranaceus, 120 g of Mori Cortex, 80 g of Sophora flavescens, 120 g of Codonopsis pilosula, 200 g of Atractylodes macrocephala, 200 g of Poria cocos, 120 g of Paeonia lactiflora, 1000 g of Chrysanthemi Flos, 200 g of Polygonum multiflorum preparatum, 120 g of Ligusticum wallichii, 200 g of Salvia miltiorrhiza, 80 g of Pinelliae Rhizoma preparatum, 200 g of Plantaginis Herba, and 60 g of Bupleuri Radix. Add 8 times the amount of water containing 0.02% (mass concentration) of lecithin and decoct for three times, 2 hours for the first and second times, and 1 hour for the third time. Combine the decoctions, filter, concentrate the filtrate to a clear paste with a relative density of 1.25 (80 °C), place it in an oven and dry it into a dry paste at 75 °C, and then pulverize it into fine powder.

[0026] Example 4 The difference between this example and Example 1 lies in the different preparation methods, and the specific preparation is as follows: Weigh 40 g of Rheum palmatum, 36 g of Glycyrrhiza uralensis, 160 g of Astragalus membranaceus, 120 g of Mori Cortex, 80 g of Sophora flavescens, 120 g of Codonopsis pilosula, 200 g of Atractylodes macrocephala, 200 g of Poria cocos, 120 g of Paeonia lactiflora, 1000 g of Chrysanthemi Flos, 200 g of Polygonum multiflorum preparatum, 120 g of Ligusticum wallichii, 200 g of Salvia miltiorrhiza, 80 g of Pinelliae Rhizoma preparatum, 200 g of Plantaginis Herba, and 60 g of Bupleuri Radix. Add 8 times the amount of water and decoct for three times, 2 hours for the first and second times, and 1 hour for the third time. Combine the decoctions, filter, concentrate the filtrate to a clear paste with a relative density of 1.25 (80 °C), place it in an oven and dry it into a dry paste at 75 °C, and then pulverize it into fine powder.

[0027] Pharmacodynamic experiment: Therapeutic effect of the uremic-clearing composition of the present invention on hyperglycemic and hyperlipidemic mice 1 Experimental purpose This study aimed to systematically evaluate the blood glucose regulation effect and lipid metabolism improvement effect of tea pigment capsules prepared by different formulation processes on hyperglycemic model mice. Comprehensively analyze the blood glucose regulation efficacy and lipid metabolism improvement effect of the Uremiaqing composition of the present invention (Example 1) and its different process control products (Examples 2-4) on alloxan-induced hyperglycemic model mice, and focus on investigating the influence of preparation process optimization on drug efficacy, so as to provide a scientific basis for the secondary development of hypoglycemic preparations.

[0028] 2 Experimental materials 2.1 Test drugs Experimental group: Examples 1-4 were adopted; Positive control: Metformin hydrochloride enteric-coated suspension.

[0029] 2.2 Experimental animals SPF-grade male Kunming mice, with an initial body weight of 20±5 g, were provided by Beijing Vital River Laboratory Animal Technology Co., Ltd. They were raised in a barrier environment (temperature 25±1°C, humidity 55±5%, 12h light-dark cycle), and freely fed AIN-93M standard feed and sterilized pure water, and adaptively raised for 7 days.

[0030] 3 Experimental methods 3.1 A nine-group experimental system was established by using the stratified randomization grouping method: Blank control group (n = 10): Not modeled + gavaged with distilled water; Model control group (n = 10): Diabetic model + gavaged with distilled water; Positive control group (n = 10): Diabetic model + metformin 130 mg / kg / d; Low, medium, and high dose groups of Example 1 (n = 10): Diabetic model + composition of Example 1; Groups of Examples 2-4 (n = 10): Diabetic model + compositions of Examples 2-4; 3.2 Construction of diabetic model After fasting all mice for 12 h, they were intraperitoneally injected with 2% alloxan (200 mg / kg, prepared with pH 4.5 citric acid buffer solution). After 72 h, fasting blood glucose was measured (Roche Accu-Chek blood glucose meter), and then those with a blood glucose value > 16.0 mmol / L were screened and included in the hyperglycemic model animals (the modeling success rate was 85%).

[0031] 4 Administration method Except for the blank group and the model group, the mice in the other groups were given intragastric administration: the low-dose group of Example 1 was given an equivalent amount of 2 g crude drug / kg, the medium-dose group of Example 1, the groups of Examples 2-4 were given an equivalent amount of 4 g crude drug / kg, and the high-dose group of Example 1 was given an equivalent amount of 8 g crude drug / kg. The blank group and the model group were given an equal amount of distilled water respectively; the positive control group was given metformin hydrochloride suspension 130 mg / kg, once a day for 14 consecutive days.

[0032] 5 Detection of metabolic indexes After the last administration, the mice were fasted for 12 h, and the immediate blood glucose was detected by tail vein blood sampling. Then, blood was collected from the orbital venous plexus, and the serum was separated by centrifugation at 3000 rpm for 15 min. The contents of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL-C) were detected by an automatic biochemical analyzer. All data were expressed as Mean±SD, and analyzed by SPSS 13.0. For comparison between groups: for those meeting the conditions of parametric test, the one-way ANOVA+LSD method was used, and for non-parametric data, the Kruskal-Wallis H test was used. The significance level was set at α=0.05 (two-tailed).

[0033] The results of the hypoglycemic effect of the uremic clear composition prepared by the present invention are shown in Table 1.

[0034] Table 1

[0035] Note: Compared with the blank group, *P<0.05, **P<0.01; compared with the model group, #P<0.05, ##P<0.01; compared with the medium-dose group of Example 1, &P<0.05, &&P<0.01.

[0036] As can be seen from the model group in Table 1, the blood glucose value of the model mice before administration was 20.35±0.72 mmol / L. Compared with the blank group, the blood glucose in the model group increased extremely significantly (**P<0.01), indicating that the model was successfully established. There was no statistical difference in the blood glucose content between the mice in each example group and the model group before administration. After 2 weeks of administration, compared with the model group, the blood glucose in the positive group, the low-, medium- and high-dose groups of Example 1 decreased significantly, and the high-dose group of Example 1 was the most prominent, with extremely significant statistical difference (##p<0.01). The preparation methods of Examples 1-4 were different. From the results, it can be obtained that at the same dose, the hypoglycemic effect of Example 1 was significantly better.

[0037] The experimental results of the uremic clear composition of the present invention in improving blood lipid metabolism are shown in Table 2.

[0038] Table 2

[0039] Note: Compared with the blank group, *P < 0.05, **P < 0.01; compared with the model group, #P < 0.05, ##P < 0.01; compared with the dosage group in Example 1, &P < 0.05, &&P < 0.01.

[0040] As can be seen from the model group in Table 2, before administration, the triglyceride level of the model mice was 0.52 ± 0.04 mmol / L, the total cholesterol was 2.55 ± 0.07 mmol / L, and the low-density lipoprotein was 0.49 ± 0.02 mmol / L. Compared with the blank group, the contents of triglyceride, total cholesterol and low-density lipoprotein increased significantly, and there was a significant statistical difference between the two. After 2 weeks of administration, compared with the model group, the triglyceride and low-density lipoprotein in the positive group decreased, and the total cholesterol decreased insignificantly. The medium dosage group in Example 1 could significantly reduce the levels of triglyceride and total cholesterol, and the high dosage group could significantly reduce the levels of triglyceride, total cholesterol and low-density lipoprotein. Examples 2-4 had no obvious regulatory effect on blood lipid levels.

[0041] The above detailed description is a specific description of one of the feasible embodiments of the present invention, and this embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or change without departing from the present invention shall be included within the scope of the technical solution of the present invention.

Claims

1. Use of a urea-clearing composition in the preparation of drugs for treating metabolic diseases.

2. The use according to claim 1, characterized in that: The metabolic disease is abnormal blood sugar and blood lipid metabolism.

3. The use according to claim 1, characterized in that: The urea-clearing composition can lower the blood sugar of the body.

4. The use according to claim 1, characterized in that: The urine-clearing composition can improve the body's blood lipid metabolism level.

5. The use according to claim 1, characterized in that: The urine-clearing composition can reduce the levels of triglycerides, total cholesterol and low-density lipoprotein in the body.

6. The use according to any one of claims 1 to 5, characterized in that: The urea-clearing composition includes the following raw materials: rhubarb, astragalus, mulberry bark, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, poria, prepared polygonum multiflorum, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and licorice, with a mass ratio of 1:3-5:2-4:1-3:2-4:4-6:4-6:4-6:2-4:4-6:2-4:2-3:1-3:4-6:1-2:0.5-2.

7. The use according to claim 6, characterized in that: The preparation method of the urea-clearing composition comprises the following steps: Mix all the raw materials, add water to boil, filter, concentrate the filtrate to a clear paste with a relative density of 1.1-1.25 at 80°C, dry, concentrate the filtrate to a clear paste, dry, and grind it into fine powder or add dextrin to the fine powder to make granules.

8. The use according to claim 7, characterized in that: Before the decoction, lecithin and polyglycerol oleate are added into the water.

9. The use according to claim 8, characterized in that: Based on the mass of water, 0.01-0.05wt% of lecithin and 0.005-0.01wt% of polyglycerol oleate are added to the water before decocting.

10. A urea-clearing composition, characterized in that: The raw materials of the composition include the following raw materials: rhubarb, astragalus, mulberry bark, sophora flavescens, codonopsis pilosula, atractylodes macrocephala, tuckahoe, prepared shouwu, white peony root, salvia miltiorrhiza, chuanxiong, chrysanthemum, pinellia tuber, plantain, bupleurum and liquorice; the preparation method of the urine and poison clearing composition includes mixing all the raw materials, decocting with water for 1-3 times, filtering, concentrating the filtrate into a clear paste, drying, and adding dextrin to form granules; lecithin and polyglycerol oleate are also added to the water before decocting.

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