CN113440536B

CN113440536B - Medicine for preventing and treating diabetes and application thereof

Info

Publication number: CN113440536B
Application number: CN202110948395.8A
Authority: CN
Inventors: 刘春红; 姜北; 胡妮娜; 陈斌
Original assignee: Heilongjiang University of Chinese Medicine
Current assignee: Heilongjiang University of Chinese Medicine
Priority date: 2021-08-18
Filing date: 2021-08-18
Publication date: 2022-02-01
Anticipated expiration: 2041-08-18
Also published as: CN113440536A

Abstract

The invention relates to a medicament for preventing and treating diabetes and application thereof, wherein the medicament takes a combination of 2, 5-dimethyl pyrazine and isoengeletin as an active ingredient and also contains pharmaceutically acceptable auxiliary materials. The invention discovers that the combination of 2, 5-dimethyl pyrazine and isoengeletin as active ingredients can obviously and synergistically reduce the level of fasting blood glucose and fasting insulin of a model rat, and the invention proves that the combination of 2, 5-dimethyl pyrazine and isoengeletin has a synergistic effect of improving the insulin resistance of the rat, and the synergistic effect is unexpected by a person skilled in the art.

Description

Medicine for preventing and treating diabetes and application thereof

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to a medicine for preventing and treating diabetes and application thereof.

Background

Obesity and diabetes have become one of the biggest public health problems of the twenty-first century as a global epidemic, and more than 19 billion adults are overweight and more than 6 billion people are obese as reported by the world health organization in 2014. Obesity is a risk factor that causes a sharp increase in non-alcoholic fatty liver disease, type 2 diabetes, cardiovascular disease and cancer, all of which not only seriously affect the quality of life of humans, but also shorten the life span of humans. Especially type 2 diabetes, if not timely and effective treatment, complications such as coronary heart disease, cerebrovascular disease, nephropathy, retinopathy and the like are very easy to occur, and the complications become main reasons threatening the lives of patients with diabetes. Therefore, maintaining blood glucose levels close to the normal range is important for preventing diabetic complications.

Obesity and diabetes mellitus are endocrine-metabolic diseases with very complex etiology, and are endocrine-metabolic diseases caused by absolute or relative insufficiency of insulin in the body, and are marked by weight gain and chronically elevated blood glucose levels. At present, most of oral hypoglycemic drugs for treating obesity and diabetes have certain effects, but have the defects of easy rebound, multiple side effects and the like after drug withdrawal.

Currently, there are two main ways to treat diabetes:

1. oral hypoglycemic agent

(1) Biguanides (e.g., metformin) are drugs that have the ability to reduce glucose output by the liver and help muscle cells, fat cells and the liver to absorb more glucose from the blood, thereby lowering blood glucose levels.

(2) The main effect of oral hypoglycemic agents such as sulfonylureas (e.g., glimepiride, glyburide, gliclazide, and gliquidone) is to stimulate more insulin release from the islets.

(3) Thiazolidinediones (such as rosiglitazone and pioglitazone) can enhance insulin sensitivity and help muscle cells, fat cells and liver to absorb more glucose in the blood. However, rosiglitazone may increase the risk of heart disease.

(4) The action mechanism of the drugs of benzoic acid derivatives (such as repaglinide and nateglinide) is similar to that of sulfonylurea drugs, and mainly stimulates pancreas to produce more insulin to reduce blood sugar.

(5) The hypoglycemic agents such as alpha-glucosidase inhibitors (such as acarbose and voglibose) can inhibit the absorption of saccharides by the digestive tract of a human body, and mainly have the effect of reducing postprandial blood sugar.

2. Insulin-like drugs

If blood sugar is still not well controlled by changing lifestyle and using oral hypoglycemic drugs, or if you are adversely affected by taking other drugs, the doctor may advise you to use insulin. Currently, insulin cannot be taken orally, but only by subcutaneous injection using a syringe or insulin pen or the like.

The onset and duration of action of different insulin formulations also vary. The patient needs to select the insulin type suitable for the current disease condition of the patient and set the appropriate insulin injection time under the guidance of the doctor.

For best glycemic control, it is sometimes possible to premix multiple insulins and inject them. Generally, the frequency of insulin injections is 1-4 times per day.

In recent years, the discovery of active substances for the treatment of diabetes from traditional Chinese medicines has become a new direction of development. For example, granted chinese patent CN109620857B discloses an active component of peanut coat, which is obtained by leaching peanut coat with ethanol, filtering, concentrating, separating with macroporous adsorbent resin, and collecting the fraction. In anti-obesity and diabetes in vivo experiments, the diabetes animal model proves that the peanut coat active components can regulate adiponectin and leptin signal pathways to generate the effect of reducing weight and blood sugar, can obviously reduce the food intake, weight and blood sugar of experimental obesity mice and type 2 diabetes model mice, and has obvious improvement effect on the clinical symptoms of obesity and diabetes. Can be used in preparing food, health food and medicine for preventing and treating obesity and diabetes. For another example, chinese granted patent CN110384692B discloses the use of carnosic acid and rosmarinic acid in combination for the preparation of a medicament for the prevention and treatment of type ii diabetic nephropathy. The granted patent finds that carnosic acid and rosmarinic acid in a mass ratio of 6:1 can obviously and synergistically reduce fasting blood glucose of mice with type II diabetic nephropathy, can obviously and synergistically reduce urinary protein excretion rate and increase urinary creatinine content, and has an obvious synergistic improvement effect on renal functions of the mice with the diabetic nephropathy, which is unexpected by a person skilled in the art.

In the previous research work of the inventor of the application, the quality action and mechanism of the traditional Chinese medicine compound Tangxinkang on diabetes are intensively researched, for example, the influence of the Tangxinkang on the expression of the gene Scn4bmRNA of the myocardial tissue of a diabetic rat is also researched. The Chinese medicine compound Tangxinkang is prepared with pseudostellaria root, astragalus root, ophiopogon root, fragrant solomonseal rhizome, wolfberry fruit, red sage, ground beetle and other Chinese medicinal materials. However, since the traditional Chinese medicine preparation has the defects of complex active ingredients, low patient acceptance and the like, how to find the active ingredients from the traditional Chinese medicine compound Tangxinkang to find the active ingredients for treating diabetes is a technical problem to be solved urgently by the technical staff in the field, and the application is realized based on the research and the further research success.

Since the 80 th century of the 20 th century, researchers have made some studies and reports on the chemical components and pharmacological actions of Eupolyphaga Seu Steleophaga. For example, when identifying the volatile oil components of ground beetles, the Friedel-crafts incense and the like detects 2 pyrazine alkaloid components: 2, 5-dimethylpyrazine and 2, 3, 5, 6-tetramethylpyrazine. Similarly, the research on the chemical components and pharmacological action in astragalus is also more sufficient.

Disclosure of Invention

Based on the background technology, the technical problem to be solved by the invention is to provide a medicament for preventing and treating diabetes and application thereof. In order to realize the purpose of the invention, the following technical scheme is adopted:

the invention relates to a medicament for preventing and treating diabetes, which takes the combination of 2, 5-dimethyl pyrazine and isoengeletin as an active ingredient and also contains pharmaceutically acceptable auxiliary materials. The combination of the invention can synergistically reduce fasting insulin and fasting insulin, and has better effect on preventing and treating diabetes.

In a preferred embodiment of the present invention, the weight ratio of the 2, 5-dimethylpyrazine to the isoengeletin is 1-8: 1; preferably 4 to 6: 1; particularly preferably 5: 1.

in a preferred embodiment of the present invention, the drug is an injectable formulation or an oral formulation.

The invention also relates to the application of the medicine in preparing medicines for preventing and treating diabetes.

In a preferred embodiment of the invention, said use comprises lowering fasting plasma glucose and/or lowering fasting insulin.

Advantageous effects

The invention discovers that the combination of 2, 5-dimethyl pyrazine and isoengeletin with a specific mass ratio as an active ingredient can obviously and synergistically reduce the level of fasting blood glucose and fasting insulin of a model rat, and shows that the combination of 2, 5-dimethyl pyrazine and isoengeletin has a synergistic effect of improving the insulin resistance of the rat, and the synergistic effect is unexpected by a person skilled in the art.

Detailed Description

In order to further understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Unless otherwise specified, the reagents involved in the examples of the present invention are all commercially available products, and all of them are commercially available.

Example 1:

1.1 animals

70 Wistar rats, half of male and female, body mass (180 +/-20 g), provided by animal experiment center of Heilongjiang Chinese medicine university.

1.2 methods of administration

Randomly dividing 50 rats into a blank group, a model group, a rosiglitazone group, a 2, 5-dimethylpyrazine group, an isoengeletin group, a 2, 5-dimethylpyrazine group and an isoengeletin weight ratio of 1: the weight ratio of the group 1, the 2, 5-dimethyl pyrazine and the isoengeletin is 5: groups 1, 10 per group, induced the rat insulin resistance model with high-calorie feed plus low-dose injection of streptozotocin. The administration dosage of the rosiglitazone group is 0.2g/kg, the weight ratio of the 2, 5-dimethylpyrazine group to the isoengeletin group to the 2, 5-dimethylpyrazine to the isoengeletin group is 1: the weight ratio of the group 1, the 2, 5-dimethyl pyrazine and the isoengeletin is 5: the dosage of the rats in the group 1 is 1g/kg, the rats are continuously administrated by gastric gavage for 4 weeks, and the rats in the blank group and the model group are administrated with the same volume of physiological saline.

1.3 index detection

Fasting Blood Glucose (FBG) was measured with a glucometer; fasting Insulin (FINS) was measured by radioimmunoassay.

1.4 results of the experiment

The effect of the active ingredient on rat FBG is shown in table 1.

Table 1: effect of active ingredients on rat FBG

As shown in table 1, FBG levels were significantly increased and differences were very significant (P <0.01) when compared to the blank group. The weight ratio of the 2, 5-dimethyl pyrazine group, the isoengeletin group, the 2, 5-dimethyl pyrazine and the isoengeletin is 1: compared with the model group, the level of FBG of the rat is slightly reduced, and the weight ratio of the 2, 5-dimethyl pyrazine to the isoengeletin is 5: the level of FBG was significantly reduced in rats in group 1 and rosiglitazone, thus indicating that the weight ratio of 2, 5-dimethylpyrazine to isoengeletin was 5: the combination of 1 has a synergistic effect on reducing FBG.

The effect of the active ingredient on rat FINS is shown in table 2.

Table 2: effect of active ingredients on rat FINS

As shown in table 2, the levels of FINS were significantly increased and the difference was very significant (P <0.01) in the model group compared to the blank group. The weight ratio of the 2, 5-dimethyl pyrazine group, the isoengeletin group, the 2, 5-dimethyl pyrazine and the isoengeletin is 1: compared with the model group, the level of the rat FINS is slightly reduced, and the weight ratio of the 2, 5-dimethyl pyrazine to the isoengeletin is 5: the FINS levels in rats in group 1 and rosiglitazone groups were significantly reduced, thus indicating that the weight ratio of 2, 5-dimethylpyrazine to isoengeletin was 5: 1 has a synergistic effect on the reduction of FINS.

The foregoing describes preferred embodiments of the present invention, but is not intended to limit the invention thereto. Modifications and variations of the embodiments disclosed herein may be made by those skilled in the art without departing from the scope and spirit of the invention.

Claims

1. A medicine for preventing and treating diabetes, which takes a combination of 2, 5-dimethyl pyrazine and isoengeletin as an active ingredient and also contains pharmaceutically acceptable auxiliary materials, wherein the weight ratio of the 2, 5-dimethyl pyrazine to the isoengeletin is 4-6: 1.

2. the medicament of claim 1, wherein the weight ratio of the 2, 5-dimethylpyrazine to the isoengeletin is 5: 1.

3. the medicament of claim 1, which is an injectable formulation or an oral formulation.

4. The use of a medicament according to any one of claims 1 to 3 for the manufacture of a medicament for the prophylaxis or treatment of diabetes.

5. The use according to claim 4, comprising lowering fasting glucose and/or lowering fasting insulin.