Pharmaceutical composition for preventing and treating type 2 diabetes mellitus and application thereof

Abstract

The invention relates to the technical field of diabetes treatment, in particular to a pharmaceutical composition for preventing and treating type 2 diabetes and application of the pharmaceutical composition. The medicine composition comprises a traditional Chinese medicine composition, bifidobacterium triple viable bacteria and chromium, the traditional Chinese medicine composition is prepared from rhizoma dioscoreae, radix puerariae, endothelium corneum gigeriae galli, prepared rhizoma polygonati, fructus lycii and fructus phyllanthi. The pharmaceutical composition provided by the invention improves blood lipid metabolism of patients with type 2 diabetes mellitus, relieves insulin resistance, and also has a certain protection effect on pancreatic beta cells.

Description

Technical Field

[0001] The present invention relates to the technical field of diabetes treatment, and in particular to a drug combination for preventing and treating type 2 diabetes and application thereof. Background Art

[0002] Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease caused by absolute or relative insufficiency of insulin secretion and decreased insulin sensitivity of target tissues or organs in the body. It is characterized by hyperglycemia and glucose metabolism disorders. The main clinical symptoms are "three mores and one less" (more drinking, more eating, more urination, and weight loss).

[0003] Many unhealthy lifestyles of modern people, such as long-term sitting, high-calorie / high-sugar and high-fat diet, mental stress, circadian rhythm disorders, etc., can cause pancreatic beta cell damage and dysfunction (beta cell dysfunction), impaired insulin secretion or tissue insulin resistance (insulin resistance, IR), which can be manifested in the early stage as impaired fasting glucose (IFG: i.e., fasting venous plasma glucose ≥6.1mmol / L, <7.0mmol / L, 2 hours after glucose load venous plasma glucose <7.8mmol / L) or impaired glucose tolerance (IGT: i.e., fasting venous plasma glucose <6.1mmol / L, 2 hours after glucose load venous plasma glucose ≥7.8mmol / L, <11.1mmol / L). Abnormal IFG and IGT are collectively referred to as impaired glucose regulation (IGR), also known as prediabetes.

[0004] The prevalence, disability, mortality and overall health hazards of diabetes have ranked third among non-communicable diseases. It is the main cause of premature illness and death in humans, especially early-onset cardiovascular and cerebrovascular diseases, amputation and renal failure. It seriously affects the quality of life of patients and shortens life expectancy, which brings huge medical and financial burdens to countries and regions.

[0005] At present, the clinical treatment of T2DM mainly adopts comprehensive treatment measures such as lifestyle intervention (diet control, moderate exercise, etc.), drugs such as sulfonylureas, biguanides and other oral hypoglycemic drugs, insulin, blood pressure and blood lipid management to meet the standards and pay attention to the prevention of complications. However, most Western medicines have a single pathway of action and many adverse reactions. Long-term and high-dose use of hypoglycemic drugs in a considerable number of patients can cause gastrointestinal reactions, hypoglycemia, liver and kidney damage, and lactic acidosis. In addition, some patients have poor compliance with frequent insulin injections, resulting in a considerable number of T2DM patients The treatment compliance rate is still not optimistic. Therefore, it is crucial to find practical and feasible early intervention measures to block or delay the progression of T2DM lesions. Summary of the invention

[0006] In order to solve the above problems, the present invention provides a drug combination for preventing and treating type 2 diabetes and application thereof. The drug combination provided by the present invention can prevent and treat type 2 diabetes.

[0007] In order to achieve the above object, the present invention provides the following technical solutions:

[0008] The present invention provides a drug combination for preventing and treating type 2 diabetes, comprising a Chinese medicine composition, a triple viable bifidobacterium and chromium;

[0009] The mass ratio of the Chinese medicine composition to the triple viable bifidobacterium and chromium is 0.09:3.64:0.0455;

[0010] The Chinese medicine composition is prepared from Chinese yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry and emblica;

[0011] The bifidobacterium triple live bacteria includes Bifidobacterium longum, Lactobacillus acidophilus and Enterococcus faecalis.

[0012] Preferably, the mass ratio of the yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry and emblica is 3:3:1.5:1.5:1.5:1.1.

[0013] Preferably, the preparation method of the Chinese medicine composition comprises the following steps:

[0014] 1) mixing the Chinese yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry fruit, and emblica fruit with water and soaking them to obtain a soaking material;

[0015] 2) decocting the soaking material obtained in step 1) to obtain a decoction, and drying the decoction to obtain a traditional Chinese medicine composition.

[0016] Preferably, in step 1), the mass ratio of the total mass of yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry and emblica to water is 1:8;

[0017] The soaking time is 2h.

[0018] Preferably, the decoction is performed twice in step 2), each time for 30 minutes.

[0019] The present invention also provides the use of the drug combination described in the above technical solution in the preparation of drugs for preventing and treating type 2 diabetes.

[0020] The present invention also provides the use of the drug combination described in the above technical solution in the preparation of a drug for improving glucose tolerance in patients with type 2 diabetes.

[0021] The present invention also provides the use of the drug combination described in the above technical solution in the preparation of a drug for improving abnormal blood lipid metabolism in patients with type 2 diabetes.

[0022] Preferably, dyslipidemia is improved by lowering the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol.

[0023] The present invention also provides the use of the drug combination described in the above technical solution in the preparation of a drug for protecting pancreatic β cells.

[0024] The mechanism of the drug combination provided by the present invention for preventing and treating type 2 diabetes is: improving blood lipid metabolism, alleviating insulin resistance, and protecting pancreatic β cells.

[0025] The drug combination provided by the present invention can be used as both medicine and food, retains the three medicinal and edible products of yam, kudzu root and chicken's gizzard lining, empirically combines the three medicinal and edible medicinal materials of polygonatum, wolfberry and emblica, innovatively adds triple live bifidobacterium and chromium to treat type 2 diabetes, and creates a unique drug combination product of jingqi shan kudzu for preventing and treating type 2 diabetes.

[0026] Beneficial effects of the present invention:

[0027] The drug combination provided by the present invention improves the blood lipid metabolism of patients with type 2 diabetes, reduces insulin resistance, and also has a certain protective effect on pancreatic β cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required to be used in the embodiments are briefly introduced below.

[0029] Figure 1 The results of body weight, FBG, IPGTT, and HOMA-IR of mice in each group. The comparison between blank group and Model group *P<0.05, **P<0.01; the comparison between Model group and JQSG group #P<0.05, ##P<0.01

[0030] Figure 2The blood lipid levels of mice in each group, the comparison between blank group and Model group *P<0.05, **P<0.01; the comparison between Model group and JQSG group ##P<0.01;

[0031] Figure 3 The results of HE staining of pancreatic islets of mice in each group;

[0032] Figure 4 The figures are the results of insulin immunofluorescence staining of mice in each group. DETAILED DESCRIPTION

[0033] The present invention provides a drug combination for preventing and treating type 2 diabetes, comprising a Chinese medicine composition, a triple viable bifidobacterium and chromium; the mass ratio of the Chinese medicine composition to the triple viable bifidobacterium and chromium is 0.09:3.64:0.0455; the Chinese medicine composition is prepared from Chinese yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry fruit and emblica fruit; the triple viable bifidobacterium comprises long bifidobacterium, lactobacillus acidophilus and enterococcus faecalis. The present invention does not specifically limit the source of the above-mentioned Chinese medicine, and conventional commercially available ones can be used.

[0034] In the present invention, the mass ratio of yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry and emblica is preferably 3:3:1.5:1.5:1.5:1.1.

[0035] In the present invention, the preparation method of the Chinese medicine composition preferably comprises the following steps:

[0036] 1) mixing the Chinese yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry fruit, and emblica fruit with water and soaking them to obtain a soaking material;

[0037] 2) decocting the soaking material obtained in step 1) to obtain a decoction, and drying the decoction to obtain a traditional Chinese medicine composition.

[0038] In the present invention, the mass ratio of the total mass of the Chinese yam, kudzu root, chicken gizzard lining, processed polygonatum, wolfberry fruit and emblica fruit to water is preferably 1:8. In the present invention, the soaking time is preferably 2 hours. In the present invention, the number of decoctions is preferably 2 times, and each time is preferably 30 minutes.

[0039] In the present invention, the Chinese medicine composition, the triple viable bifidobacterium and the chromium in the drug combination are packaged separately. In the present invention, the triple viable bifidobacterium is a commercially available triple viable bifidobacterium capsule, with batch number 22120240982 and approval number S10950032, purchased from Shanghai Xinyi Pharmaceutical Co., Ltd. The present invention has no special limitation on the source of chromium, and commercially available chromium capsules can be used, such as those purchased from SOLGAR Company in the United States.

[0040] The present invention also provides the use of the drug combination described in the above technical solution in the preparation of drugs for preventing and treating type 2 diabetes. The present invention has no special limitation on the dosage form and preparation method of the drug, and those skilled in the art can follow the routine method.

[0041] The present invention also provides the use of the drug combination described in the above technical solution in the preparation of a drug for improving glucose tolerance in patients with type 2 diabetes. The present invention has no special limitation on the dosage form and preparation method of the drug, and those skilled in the art can follow the routine method.

[0042] The present invention also provides the use of the drug combination described in the above technical solution in the preparation of a drug for improving dyslipidemia in patients with type 2 diabetes. The present invention preferably improves dyslipidemia by reducing the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol. The present invention does not specifically limit the dosage form and preparation method of the drug, and those skilled in the art can follow the routine.

[0043] The present invention also provides the use of the drug combination described in the above technical solution in the preparation of a drug for protecting pancreatic β cells. The present invention has no special limitation on the dosage form and preparation method of the drug, and those skilled in the art can follow the routine method.

[0044] In order to further illustrate the present invention, the present invention is described in detail below in conjunction with embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0045] Example 1

[0046] 1 Materials and Operation

[0047] 1.1 Experimental Materials

[0048] 1.1.1 Test materials

[0049] The experiment requires 20 C57BL / 6J mice, SPF grade, 6-week-old males. The initial weight range of each experimental group was 15-18g, purchased from Beijing Huafukang Biotechnology Co., Ltd., with an experimental animal production license of SCXK (Beijing) 2019-0008. The mice were raised in an SPF-grade animal breeding room in accordance with relevant domestic and foreign animal standards, moved freely, and drank urban drinking water sterilized at 121°C for 20 minutes. The feed was customized, and the research team added it according to the experimental needs. The experimental period was 16 weeks in total. From the first week of the experiment, high-fat feeding and gavage of Jingqi Shange (i.e., a traditional Chinese medicine composition, hereinafter referred to as JQSG) were started until the end of the experiment. In the 8th week, the mice were intraperitoneally injected with STZ to create a model, and the general status of the mice, such as weight and spirit, was observed and recorded during the period.

[0050] Other materials required for the experiment: Jingqi Shankudzu product, the drug combination of the present invention is added to pure water to dissolve it. Mouse shavings bedding, mouse basic feed and T2DM modeling special high-fat feed (20% protein + 20% carbohydrates + 60% fat) are stored. The high-fat feed needs to be refrigerated at 4°C when used, and frozen at -20°C when not in use. The palatability of high-fat feed is slightly lower than that of ordinary feed. Animals are prone to anorexia and low feed intake, and the odor is not good when left at room temperature. Gradual food replacement and fasting methods can be used, and feed can be added in small amounts and multiple times.

[0051] 1.2 Experimental procedures

[0052] 1.2.1 Preparation of intragastric gavage reagent

[0053] The preparation of the drug combination intragastric gavage reagent of the present invention: the drug combination is composed of yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry, emblica, triple live bifidobacterium and chromium;

[0054] Weigh 30g of Chinese yam, 30g of kudzu root, 15g of chicken's gizzard lining, 15g of polygonatum processed, 15g of wolfberry fruit, and 10g of emblica fruit, add 8 times the amount of water to the above-mentioned medicinal pieces and soak them for 2h, decoct them twice, decoct them for 30min each time, filter the medicinal residues, mix the decoctions obtained by the two decoctions and remove the moisture with a rotary evaporator to obtain 23g of dry Chinese medicine powder, calculate the mouse dosage according to the equivalent dose ratio converted by body surface area between humans and animals to be 2.99g / Kg, add 2.99g of Chinese medicine powder to 10ml of distilled water to obtain a Chinese medicine solution with a concentration of 0.299g / ml, extract the configured Chinese medicine solution according to the intragastric administration amount of 0.1ml / 10g for mice, and administer it intragastricly, once / day, about 0.09g;

[0055] Similarly, the dosage of the three live bifidobacteria is calculated to be 3.64 g / time, once / day (3.64×10 7 CFU), dissolved in 0.2 ml distilled water and administered intragastrically;

[0056] Similarly, the chromium content was calculated to be 45.5 μg / time / day. Based on 6 mice per cage and 4-7 ml of water per day per mouse, a total of 273 ug of chromium for 6 mice was dissolved in 24-42 ml of distilled water for the mice to drink.

[0057] Bifidobacterium triple live bacteria capsules were purchased from Shanghai Xinyi Pharmaceutical Co., Ltd., and chromium capsules were purchased from SOLGAR Company in the United States.

[0058] 1.2.2 T2DM mouse modeling and grouping and drug administration

[0059] Twenty male C57 mice were divided into three groups using the average weight method, with 6 mice in each group. They were blank control group, model group, and JQSG treatment group, and two more mice were used to prevent death. There was no statistical difference in weight between the mouse groups. During the experiment, the blank group was fed with ordinary feed throughout the whole process, the model group was fed with high-fat feed, and the JQSG treatment group was fed with high-fat feed and continued to be treated by gavage for 16 weeks. The blank group and the model group were gavaged with the same dose of distilled water at the same time as the JQSG treatment group every day. Observe the weight, mental state, behavioral performance, and death of the mice, and keep good experimental records.

[0060] 1.2.3 Index determination

[0061] After the last oral gavage treatment at week 16, the mice were fasted overnight. The next day, all mice were subjected to an intraperitoneal glucose tolerance test (IPGTT). After the experiment, the mice were anesthetized with 10% chloral hydrate and the eyeballs were removed for blood collection. The blood was allowed to stand for 2 hours and then centrifuged at 3000r / min at 4°C for 10 minutes to collect the supernatant. The levels of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), and insulin were tested strictly according to the instructions of the reagents. The mice were dissected and the pancreas was dissected for fixation, dehydration, embedding, sectioning, HE, and insulin immunofluorescence staining.

[0062] 1.3 Data processing

[0063] After the experimental data were entered into the Excel table and confirmed to be correct, the data obtained from the application study were analyzed using SPSS21.0 software, and the independent sample t test was used between the groups. P<0.05 was statistically significant, and P<0.01 was extremely significant. GraphPadprism 9.0 software was used for graphical data analysis.

[0064] 2 Experimental results

[0065] 2.1 Body weight, FBG, IPGTT, and HOMA-IR of mice in each group

[0066] Figure 1 In Figure A, we can see that JQSG delayed the weight gain caused by high-fat diet in the experiment. Figure 1In B, the fasting blood glucose of the Model group mice was significantly higher than that of the control group after treatment (P<0.01), while JQSG significantly improved this phenomenon (P<0.05); in C, compared with the Model group, JQSG significantly reduced the fasting insulin level (P<0.01); in D, HOMA-IR was calculated according to the formula, and JQSG significantly improved HOMA-IR (P<0.05). Figure 1 Figures E and F show the performance of each group of mice in the IPGTT. The results showed that compared with the blank group, the blood glucose level of the mice in the model group increased significantly after glucose loading, indicating that their glucose tolerance was impaired. However, the mice treated with JQSG showed better blood glucose control under the same conditions, and their blood glucose curve was significantly lower than that of the Model group, and the area under the curve was also significantly lower than that of the Model group (P<0.01), indicating that JQSG can effectively improve the glucose tolerance of mice.

[0067] 2.2 Effect of JQSG on blood lipids in T2DM mice

[0068] In this example, the effect of JQSG on blood lipid levels in T2DM mice was further analyzed. The results showed that compared with the Model group, the serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels of the JQSG-treated mice were significantly reduced, and compared with the control group, the high-density lipoprotein cholesterol (HDL-C) level in the Model group was significantly reduced (P<0.01), and there was no significant difference between JQSG and the Model group (P>0.05). In general, JQSG has an improving effect on abnormal lipid metabolism in T2DM mice.

[0069] 2.3 Effect of JQSG on pancreatic islet histopathology in T2DM mice

[0070] Figure 3 The results of HE staining of pancreatic islets of mice in each group are shown. It can be observed from the figure that the pancreatic islet structure of the blank group mice is intact, the cells are neatly arranged, and the cell nuclei are clearly visible. In contrast, the pancreatic islet structure of the Model group mice was significantly damaged, the cells were disordered, the cell nuclei were condensed, and the number of pancreatic islet cells decreased, which indicates that the high-fat diet combined with STZ modeling successfully induced damage to pancreatic β cells. The pancreatic islet structure of the JQSG-treated group mice was relatively intact, the cells were arranged more orderly, the cell nuclei were normal in morphology, and the number of pancreatic islet cells increased compared with the model group, indicating that JQSG has a certain protective effect on pancreatic β cells.

[0071] 2.4 Effects of JQSG on pancreatic β cells in T2DM mice

[0072] Figure 4The results of insulin immunofluorescence staining of mice in each group are shown. It can be observed from the figure that the number of pancreatic β cells in the blank group mice is large, insulin expression is strong, and the cell morphology is normal. In contrast, the number of pancreatic β cells in the Model group mice is significantly reduced, insulin expression is weak, and the cell morphology is irregular, while the number of pancreatic β cells in the JQSG treatment group mice is increased compared with the model group, insulin expression is relatively strong, and the cell morphology is relatively normal, indicating that JQSG has a protective effect on pancreatic β cells and can improve the secretion of insulin in β cells.

[0073] It can be concluded from the above embodiments that after JQSG was gavaged to treat T2DM mice in the present invention, it was observed that the coat color, spirit, and activity of the mice were well improved. Model had a significant effect on the increase of body weight after modeling, and the weight gain of the mice in the JQSG treatment group was significantly slower than that in the model group, indicating that JQSG may have a certain positive effect on the weight control of T2DM mice. In addition, the fasting blood glucose FBG and the area under the glucose tolerance curve of the mice in the JQSG treatment group were significantly lower than those in the model group, indicating that JQSG can effectively improve the blood sugar control of T2DM mice. In terms of insulin resistance index (HOMA-IR), the HOMA-IR value of the mice in the JQSG treatment group was significantly lower than that in the model group. In terms of blood lipids, the levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) in the JQSG treatment group mice were all reduced, indicating that JQSG has a positive regulatory effect on the blood lipid metabolism of T2DM mice. HE and insulin immunofluorescence staining results showed that the pathological changes of pancreatic islet tissues in the JQSG-treated mice were significantly improved compared with those in the model group, the number of pancreatic β cells increased, the cell morphology tended to be normal, and the insulin secretion function was restored. These results indicate that JQSG can not only improve the blood glucose and lipid metabolism of T2DM mice, but also protect pancreatic β cells and promote their functional recovery. In summary, JQSG shows good application prospects in the prevention and treatment of T2DM.

[0074] Although the above embodiment describes the present invention in detail, it is only a part of the embodiments of the present invention, not all of the embodiments. People can also obtain other embodiments based on this embodiment without creativity, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A drug combination for preventing and treating type 2 diabetes, characterized in that: It includes a Chinese medicine composition, a triple live bifidobacterium and chromium; The mass ratio of the Chinese medicine composition to the triple viable bifidobacterium and chromium is 0.09:3.64:0.0455; The Chinese medicine composition is prepared from Chinese yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry and emblica; The bifidobacterium triple live bacteria includes Bifidobacterium longum, Lactobacillus acidophilus and Enterococcus faecalis.

2. The drug combination according to claim 1, characterized in that The mass ratio of the Chinese yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry fruit and emblica fruit is 3:3:1.5:1.5:1.5:

1.

3. The drug combination according to claim 1, characterized in that The preparation method of the Chinese medicine composition comprises the following steps: 1) mixing the Chinese yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry fruit, and emblica fruit with water and soaking them to obtain a soaking material; 2) decocting the soaking material obtained in step 1) to obtain a decoction, and drying the decoction to obtain a traditional Chinese medicine composition.

4. The drug combination according to claim 2, characterized in that The mass ratio of the total mass of yam, kudzu root, chicken's gizzard lining, processed polygonatum, wolfberry and emblica to water in step 1) is 1:8; The soaking time is 2h.

5. The pharmaceutical combination according to claim 2, characterized in that: The decoction in step 2) is performed twice, each time for 30 minutes.

6. Use of the drug combination according to any one of claims 1 to 5 in the preparation of drugs for preventing and treating type 2 diabetes.

7. Use of the drug combination according to any one of claims 1 to 5 in the preparation of a drug for improving glucose tolerance in patients with type 2 diabetes.

8. Use of the drug combination according to any one of claims 1 to 5 in the preparation of a drug for improving abnormal blood lipid metabolism in patients with type 2 diabetes.

9. The use according to claim 8, characterized in that: Improves dyslipidemia by lowering total cholesterol, triglycerides and low-density lipoprotein cholesterol levels.

10. Use of the drug combination according to any one of claims 1 to 5 in the preparation of a drug for protecting pancreatic β cells.

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