Application of pharmaceutical composition containing hypoglycemic synergistic prescription in preparation of medicine for preventing and treating diabetes mellitus

Abstract

The invention belongs to the technical field of medicines, and provides a pharmaceutical composition containing a hypoglycemic synergistic prescription and application of the pharmaceutical composition in preparation of a medicine for preventing and treating diabetes mellitus, and the pharmaceutical composition for preventing and treating diabetes mellitus is composed of the hypoglycemic synergistic prescription and pioglitazone. The pharmaceutical composition for preventing and treating diabetes disclosed by the invention has a synergistic effect in a manner of combined application of Chinese and western medicines, improves the curative effect, reduces the drug dosage and reduces possible adverse reactions caused by single drug treatment.

Description

Technical Field

[0001] The invention belongs to the field of medical technology and relates to use of a pharmaceutical composition containing a blood sugar lowering and synergistic enhancing formula in preparing a drug for preventing and treating diabetes. Background Art

[0002] Diabetes refers to a metabolic disease characterized by long-term high blood sugar, which is caused by insufficient insulin secretion or / and its biological function disorder under the combined effects of genetic and environmental factors. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 2 diabetes is mainly caused by the defect of pancreatic β-cell function and insulin resistance in the patient's body, which reduces the metabolic function of insulin in assisting glucose into cells, and the relatively insufficient insulin secretion leads to high blood sugar in patients.

[0003] Diabetes belongs to the category of "Xiaoke disease" in traditional Chinese medicine, which is characterized by polydipsia, polyphagia, polyuria, weight loss or sweet urine. Ancient doctors divided this disease into three types: upper, middle and lower. This disease is mostly caused by exogenous damp-heat evil, congenital deficiency, overeating of fatty and sweet food, excessive labor and desire, emotional disorder, etc., which lead to lung dryness, stomach heat, kidney deficiency and triple burner disease, and finally form a disease with yin deficiency as the main symptom and excessive dryness and heat as the symptom. The two are mutually causal, and there are many variations. Doctors in successive dynasties advocated the treatment of "Xiaoke disease" based on the principles of clearing heat, promoting fluid and quenching thirst, nourishing the liver and kidneys, and replenishing qi and nourishing yin.

[0004] Clinically, there are many drugs that can effectively control patients' blood sugar, such as nateglinide, metformin, liraglutide, pioglitazone and dapagliflozin. Although Western medicines lower blood sugar quickly, they have a single target and need to be taken for a long time, so they can easily cause drug dependence and toxic side effects such as hypoglycemia, gastrointestinal reactions, liver and kidney damage, etc. In addition, Western medicines are expensive and can easily cause a financial burden on patients. Summary of the invention

[0005] In order to make up for the deficiencies of the prior art, the present invention provides a new drug composition for preventing and treating diabetes with a reasonable formula and definite efficacy. The drug composition of the present invention uses Chinese and Western medicines in combination to improve the efficacy, reduce the drug dosage, and reduce the adverse reactions that may occur in single drug treatment.

[0006] The present invention also provides medical use of the above-mentioned drug composition for preventing and treating diabetes.

[0007] Specifically, the technical problem to be solved by the present invention is achieved through the following technical solutions.

[0008] The invention provides a pharmaceutical composition containing a hypoglycemic and synergistic formula, wherein the pharmaceutical composition for preventing and treating diabetes is composed of the hypoglycemic and synergistic formula and pioglitazone, wherein the mass ratio of the hypoglycemic and synergistic formula to the pioglitazone is 15-18:1.

[0009] Preferably, the mass ratio of the glucose-lowering and synergistic-enhancing prescription to pioglitazone is 16:1.

[0010] The blood sugar lowering and synergistic effect prescription of the present invention is prepared from 30g of astragalus, 30g of bitter melon, 20g of mulberry leaf, 15g of polygonatum, 15g of dendrobium, 9g of Shenqu, 6g of Panax notoginseng and 9g of cinnamon bark.

[0011] Furthermore, the preparation method of the hypoglycemic and synergistic prescription of the present invention is: weigh each medicinal material according to the ratio, wash the medicinal materials, mix them, add 5-7 times the total weight of the medicinal materials, and boil them twice, each time for 0.5-1.5 hours, combine the two decoctions, filter, and concentrate to obtain a fluid extract with a specific gravity of 1.25-1.35 at 60°C, and concentrate and dry.

[0012] Preferably, the preparation method of the hypoglycemic and synergistic prescription of the present invention is: weigh each medicinal material according to the ratio, wash the medicinal materials, mix them, add 5.5 times the total weight of the medicinal materials, and boil them for 3 times, each time for 1 hour, combine the 3 decoctions, filter, and concentrate to obtain a fluid extract with a specific gravity of 1.3 at 60°C, and concentrate and dry.

[0013] The pharmaceutical composition of the present invention also includes pharmaceutically acceptable excipients; the pharmaceutically acceptable excipients are selected from one or more of diluents, excipients, fillers, binders, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, lubricants, surfactants, coating materials, colorants, pH regulators, antioxidants or antibacterial agents.

[0014] The pharmaceutical composition of the present invention is a single compound preparation or a combination of two separate single preparations.

[0015] Preferably, the dosage form of the single compound preparation or the combination of two separate single preparations includes solutions, drops, tablets, capsules, granules, films, gels, powders, emulsions, suspensions, pills, suppositories, aerosols, sprays, powder mists, patches, ointments or creams.

[0016] Preferably, the dosage form of the single compound preparation or the combination of two separate single preparations is a tablet.

[0017] The present invention also provides application of the pharmaceutical composition for preventing and treating diabetes in preparing drugs for treating diabetes.

[0018] The blood sugar lowering and efficacy enhancing formula is a traditional Chinese medicine blood sugar lowering compound formulated on the basis of clinical experience combined with modern pharmacological research. It is composed of astragalus, bitter melon, mulberry leaves, polygonatum, dendrobium, Panax notoginseng, Shenqu, and cinnamon.

[0019] Pioglitazone belongs to the thiazolidinedione drug class. It can enhance insulin sensitivity to a certain extent by activating peroxisome proliferator-activated receptor-γ and has been proven to effectively lower blood sugar.

[0020] The inventors found in the course of their research that the above two drugs, when used in combination, have a significant synergistic effect in the treatment of diabetes.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] Animal experiments show that the pharmaceutical composition of the present invention has a significant effect on the treatment of diabetes. The pharmaceutical composition of the present invention reduces blood sugar 2 hours after a meal, reduces glucose tolerance, reduces insulin tolerance, and has a significant effect on the treatment of diabetes in rats. The therapeutic effect of the combined group is significantly better than that of the Jiangtang Zengxiao prescription group and the pioglitazone group. The combination of Jiangtang Zengxiao prescription and pioglitazone achieves a synergistic effect in improving the blood sugar status of rats.

[0023] The invention uses Chinese and Western medicines in combination to improve the efficacy, reduce the drug dosage, and reduce the adverse reactions that may occur in single drug treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Comparison of 2-hour postprandial blood glucose levels of model rats on the 7th day after modeling. Different lowercase letters in the graph bars indicate significant differences (P<0.05).

[0025] Figure 2 Comparison of 2h postprandial blood glucose levels in rats after 4 weeks of administration. Different lowercase letters in the graph bars indicate significant differences (P<0.05).

[0026] Figure 3 Comparison of glucose tolerance in rats. Different lowercase letters in the graph bars indicate significant differences (P<0.05).

[0027] Figure 4 Comparison of insulin tolerance in rats. Different lowercase letters in the graph bars indicate significant differences (P<0.05). Specific embodiments

[0028] The content of the present invention is further described in detail below through specific implementation methods, but this should not be understood as the scope of the above subject matter of the present invention is limited to the following examples. The following examples are used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. If a person of ordinary skill in the art modifies or replaces the technical solution of the present invention with an equivalent without departing from the essence and scope of the technical solution of the present invention, it still belongs to the scope of protection of the present invention.

[0029] The preparation method of the hypoglycemic and synergistic prescription used in the following embodiments of the present invention is as follows: weigh each medicinal material according to the ratio, wash the medicinal materials, mix them, add 5.5 times the total weight of the medicinal materials, and boil them 3 times, each time for 1 hour, combine the 3 decoctions, filter, and concentrate to obtain a fluid extract with a specific gravity of 1.3 at 60°C, concentrate and dry.

[0030] Example 1 Study on the effect of the pharmaceutical composition of the present invention on treating diabetes

[0031] 1. Materials and Methods

[0032] After 5 days of adaptive feeding, 8 clean SD rats were randomly selected as the normal control group and fed with growth maintenance feed. The remaining rats were fed with high-fat feed for 3 weeks, fasted for 12 hours but not water, and injected intraperitoneally with 35 mg / kg streptozotocin. Before use, streptozotocin was dissolved in citric acid-sodium citrate buffer with a pH value of 4.5. On the 7th day after the injection of streptozotocin, after fasting for 12 hours but not water, the rats were gavaged with glucose solution at a dose of 2 g / kg, and the blood sugar of the rats was measured 2 hours after the meal. The blood sugar concentration ≥11.1 mmol / L represented a successful model.

[0033] The rats with successful modeling were randomly divided into 4 groups, with 8 rats in each group, namely the model control group, the combination group, the hypoglycemic and synergistic prescription group, and the pioglitazone group.

[0034] Blood sugar lowering and efficacy enhancing prescription group: 0.64g / kg of blood sugar lowering and efficacy enhancing prescription was administered intragastrically daily.

[0035] Pioglitazone group: 0.04 g / kg pioglitazone was administered intragastrically daily.

[0036] Combination group: daily gavage of 0.32g / kg hypoglycemic and enhancing formula + 0.02g / kg pioglitazone.

[0037] Rats in the normal control group and the model control group were intragastrically administered with an equal volume of normal saline daily for 4 weeks.

[0038] 2. Index detection

[0039] 2.1 After the experiment, the body weight and 2-hour postprandial blood glucose of rats in each group were measured.

[0040] The night before the blood glucose test, the rats were fasted but not watered for 12 hours. On the test day, the rats were weighed and gavaged with 2 g / kg glucose solution. Blood was collected from the tail vein 2 hours later, and the blood glucose concentration was measured with a blood glucose meter.

[0041] 2.2 Oral glucose tolerance test (OGTT) in rats

[0042] After the experiment, the rats were fasted but not watered for 12 h and then gavaged with 2 g / kg glucose solution. Blood was collected from the tail vein at 0, 30, 60, 90 and 120 min after gavage. Blood glucose concentration was measured with a blood glucose meter, and the area under the OGTT curve was calculated, which was glucose tolerance.

[0043] 2.3 Insulin tolerance test (ITT)

[0044] At the end of the OGTT test, the rats were fasted but not watered for 6 h, and 0.5 U / kg insulin aspart injection was injected intraperitoneally. Blood was collected from the tail vein at 0, 30, 60, 90, and 120 min to measure blood glucose concentration, and the area under the ITT curve was calculated, which was the insulin tolerance.

[0045] 3. Statistical Analysis

[0046] Graphpad Prism 9.0 software was used for data processing, and the measured data were expressed as mean ± standard deviation. One-way analysis of variance was used for comparison among multiple groups, and SNK-q was used for pairwise comparison among groups. The difference was considered statistically significant when P < 0.05.

[0047] 4. Experimental Results

[0048] 4.1 Effects on 2-hour postprandial blood glucose in rats

[0049] On the 7th day after rat modeling, compared with the normal control group, the blood sugar level of each group increased significantly 2 hours after meal, exceeding the diabetes identification standard of 11.1mmol / L, indicating that the modeling was successful. Figure 1 .

[0050] After 4 weeks of intragastric administration, compared with the model control group, the combination group significantly reduced blood sugar 2 hours after meal, and its effect of reducing blood sugar 2 hours after meal was significantly better than the group using only the hypoglycemic and synergistic prescription and the group using only pioglitazone.

[0051] The pharmaceutical composition of the present invention can significantly reduce blood sugar 2 hours after a meal. The two active ingredients of the hypoglycemic and synergistic formula and pioglitazone show significant synergistic effects in reducing blood sugar 2 hours after a meal. Figure 2 .

[0052] 4.2 Effects on glucose tolerance in rats

[0053] Compared with the model control group, the glucose tolerance of rats in the combination group was significantly reduced, and the combination group improved the glucose tolerance of the experimental rats and improved the blood sugar lowering ability of the rats. The effect of the combination group on reducing glucose tolerance was significantly better than that of the group using the Jiangtang Zhengying Recipe alone and the group using pioglitazone alone. The pharmaceutical composition of the present invention can significantly reduce glucose tolerance, and the two active ingredients of the Jiangtang Zhengying Recipe and pioglitazone show significant synergistic effects in reducing glucose tolerance. The results are shown in Figure 3 .

[0054] 4.3 Effects on insulin tolerance in rats

[0055] Compared with the model control group, the insulin tolerance of rats in the combination group was significantly reduced. The effect of the combination group on reducing insulin tolerance was significantly better than that of the single-use group of the Jiangtang Zhengxiao Recipe and the single-use group of pioglitazone. The pharmaceutical composition of the present invention can significantly reduce insulin tolerance, and the two active ingredients of the Jiangtang Zhengxiao Recipe and pioglitazone show significant synergistic effects in reducing insulin tolerance. The results are shown in Figure 4 .

[0056] The pharmaceutical composition of the present invention reduces blood sugar 2 hours after a meal, reduces glucose tolerance, reduces insulin tolerance, and has a significant therapeutic effect on diabetes in rats. The therapeutic effect of the combined group is significantly better than that of the Jiangtang Zengxiao prescription group and the pioglitazone group. The combined use of the Jiangtang Zengxiao prescription and pioglitazone achieves a synergistic effect in improving the blood sugar status of rats.

[0057] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A pharmaceutical composition containing a glucose-lowering and synergistic prescription, characterized in that: The medicine composition for preventing and treating diabetes is composed of a glucose-lowering and synergistic prescription and pioglitazone, wherein the mass ratio of the glucose-lowering and synergistic prescription to the pioglitazone is 15-18:

1.

2. The pharmaceutical composition containing the glucose-lowering and synergistic effect-enhancing prescription according to claim 1, characterized in that: The mass ratio of the glucose-lowering and synergistic-enhancing prescription to pioglitazone is 16:

1.

3. The pharmaceutical composition containing the hypoglycemic and synergistic prescription according to any one of claims 1 or 2, characterized in that: The blood sugar lowering and efficacy enhancing prescription is prepared from 30g of astragalus, 30g of bitter melon, 20g of mulberry leaf, 15g of polygonatum, 15g of dendrobium, 9g of Shenqu, 6g of Panax notoginseng and 9g of cinnamon bark.

4. The pharmaceutical composition containing the hypoglycemic and synergistic prescription according to claim 3, characterized in that: The preparation method of the hypoglycemic and synergistic prescription is as follows: weigh each medicinal material according to the ratio, wash the medicinal materials, mix them, add 5-7 times of the total weight of the medicinal materials, and boil them twice, each time for 0.5-1.5 hours, combine the two decoctions, filter, and concentrate to obtain a fluid extract with a specific gravity of 1.25-1.35 at 60° C., and concentrate and dry.

5. The pharmaceutical composition containing the glucose-lowering and synergistic effect-enhancing prescription according to claim 4, characterized in that: The preparation method of the hypoglycemic and synergistic prescription is as follows: weigh each medicinal material according to the ratio, wash the medicinal materials, mix them, add 5.5 times of the total weight of the medicinal materials, and boil them for 3 times, each time for 1 hour, combine the 3 decoctions, filter, and concentrate to obtain a fluid extract with a specific gravity of 1.3 at 60° C., and concentrate and dry.

6. The pharmaceutical composition containing the glucose-lowering and synergistic effect-enhancing prescription according to any one of claims 1 or 2, characterized in that: The pharmaceutical composition also includes pharmaceutically acceptable excipients; the pharmaceutically acceptable excipients are selected from one or more of diluents, excipients, fillers, binders, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, lubricants, surfactants, coating materials, colorants, pH regulators, antioxidants or antibacterial agents.

7. The pharmaceutical composition containing the glucose-lowering and synergistic effect-enhancing prescription according to claim 6, characterized in that: The pharmaceutical composition is a single compound preparation or a combination of two separate single preparations.

8. The pharmaceutical composition containing the glucose-lowering and synergistic effect-enhancing prescription according to claim 7, characterized in that: The dosage form of the single compound preparation or the combination of two separate single preparations includes solutions, drops, tablets, capsules, granules, films, gels, powders, emulsions, suspensions, pills, suppositories, aerosols, sprays, powder mists, patches, ointments or creams.

9. The pharmaceutical composition containing the glucose-lowering and synergistic effect-enhancing prescription according to claim 7, characterized in that: The dosage form of the single compound preparation or the combination of two separate single preparations is a tablet.

10. Use of the pharmaceutical composition containing the glucose-lowering and efficacy-enhancing formula according to any one of claims 1 or 2 in the preparation of drugs for treating diabetes.

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