Preparation method of magnesium acetyltaurate and application of magnesium acetyltaurate in preparation of hypoglycemic drugs or health care products

Abstract

The invention discloses a preparation method of magnesium acetyltaurate and application of the magnesium acetyltaurate in preparation of hypoglycemic drugs or health care products, research finds that magnesium acetyltaurate has an obvious hypoglycemic effect, and results of repeated verification of mouse sugar tolerance animal experiments of single-time administration and multiple-time administration of magnesium acetyltaurate prove that the magnesium acetyltaurate has the obvious hypoglycemic effect. The magnesium acetyltaurate can reduce the blood sugar level of the mouse, basically has no influence on the weight of the mouse, can be used as a medicine for reducing the blood sugar, and has good development and application prospects. The preparation method disclosed by the invention is simple to operate and low in cost, and large-scale preparation of magnesium acetyltaurate can be realized.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a preparation method of magnesium acetyl taurate and application of the magnesium acetyl taurate in the preparation of blood sugar lowering drugs or health products. Background Art

[0002] With the rapid development of domestic society and the substantial improvement of people's living standards, the incidence of type II diabetes in my country has increased significantly year by year, and type II diabetes has become one of the common chronic diseases among Chinese residents. Currently available hypoglycemic drugs include insulin, metformin, α-glucosidase inhibitors, polysaccharide competitive inhibitors, etc.

[0003] Taurine is widely present in mammalian tissues and many foods, and its content is particularly high in excitable tissues such as the heart, eyes, brain, and muscles. Taurine has been described as having pleiotropic cellular and physiological functions, especially in the context of metabolic homeostasis. Genetic reduction of taurine levels leads to muscle atrophy, decreased exercise capacity, and mitochondrial dysfunction in multiple tissues, while taurine supplementation reduces mitochondrial redox stress, improves exercise capacity, and inhibits body weight. N-acetyltaurine is a particularly interesting but less studied secondary metabolite of taurine. A research paper published by Jonathan Z. Long's team at Stanford University in the top academic journal Nature (Wei, W., Lyu, X., Markhard, A L et al. PTER is a N-acetyltaurine hydrolase that regulates feeding and obesity. Nature (2024)) shows the important role of acetyltaurine in reducing food intake and anti-obesity in mammals.

[0004] Magnesium is one of the essential elements for the human body. Magnesium ions can activate a variety of enzymes in the human body. Magnesium deficiency in the human body may lead to the loss of a variety of cell functions. At present, many studies have shown that the level of magnesium in the human body is related to diabetes. Magnesium acetyltaurate is a stable magnesium salt of acetyltaurine, which has the characteristics of being easily absorbed and penetrating the blood-brain barrier. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide a method for preparing magnesium acetyl taurate and its application in preparing hypoglycemic drugs or health products in view of the deficiencies in the above-mentioned prior art.

[0006] In order to solve the above technical problems, the technical solution adopted by the present invention is: in the first aspect of the present invention, the use of magnesium acetyl taurate in the preparation of hypoglycemic drugs or health products is provided.

[0007] Preferably, magnesium acetyltaurate is used as the sole active ingredient, or is used together with other hypoglycemic drugs as active ingredients.

[0008] Preferably, the other hypoglycemic drugs include at least one of metformin, insulin, α-glucosidase inhibitors, and polysaccharide competitive inhibitors.

[0009] The second aspect of the present invention provides a hypoglycemic drug or health product, which uses magnesium acetyltaurate as the only active ingredient, or uses magnesium acetyltaurate and other hypoglycemic drugs as active ingredients.

[0010] Preferably, the other hypoglycemic drugs include at least one of metformin, insulin, α-glucosidase inhibitors, and polysaccharide competitive inhibitors.

[0011] Preferably, the medicine or health product further comprises at least one of a pharmaceutically acceptable salt, a co-crystal, a prodrug, a solvate, and a metabolite.

[0012] Preferably, the drug is prepared into a clinically acceptable drug preparation according to conventional drug preparation methods.

[0013] Preferably, the drug is in the form of tablets, capsules, injections, granules or other clinically acceptable dosage forms.

[0014] In the above-mentioned hypoglycemic drugs or health products, the structural formula of magnesium acetyl taurate is as follows:

[0015]

[0016] In a third aspect, the present invention provides a method for preparing magnesium acetyl taurate in the application as described above or in the hypoglycemic drug or health product, comprising the following steps:

[0017] S1. Mix magnesium taurine and glacial acetic acid evenly, and heat to reflux for 0.5 to 1 h;

[0018] S2, adding sulfuric acid to the product obtained in step S1, adding for 5 to 15 minutes, and then continuing to stir at reflux temperature for 8 to 16 hours;

[0019] S3, concentrating and evaporating the product obtained in S2 under reduced pressure;

[0020] S4. Add water to completely dissolve the product obtained in S3, raise the temperature to 50-60° C., add ethanol dropwise to precipitate white powder, and then filter and dry to obtain magnesium acetyl taurate.

[0021] Preferably, the preparation method of magnesium acetyl taurate comprises the following steps:

[0022] S1. Mix 2.5-10 g of magnesium taurine and 12.5-50 mL of glacial acetic acid in a reaction vessel, and heat under reflux for 0.5-1 h;

[0023] S2, adding 0.5-2 g of 98 wt% sulfuric acid to the product obtained in step S1, adding for 5-15 min, and then continuing to stir at reflux temperature for 8-16 h;

[0024] S3, transfer the product obtained in S2 to a concentration bottle, concentrate under reduced pressure and evaporate to dryness to obtain a white block solid;

[0025] S4. Add deionized water to completely dissolve the white block solid obtained in S3, raise the temperature to 50-60° C., add 45-60 mL of ethanol dropwise to precipitate a white powder, and then filter the solid product, rinse with ethanol, and dry to obtain magnesium acetyl taurate.

[0026] The beneficial effects of the present invention are:

[0027] The present invention provides a preparation method of magnesium acetyltaurine and its application in the preparation of hypoglycemic drugs or health products. The present invention finds through research that magnesium acetyltaurine has an obvious hypoglycemic effect. The present invention is confirmed by repeated verification results of single administration and multiple administration of magnesium acetyltaurine in mice glucose tolerance animal experiments. Magnesium acetyltaurine can reduce the blood sugar level of mice and has basically no effect on the weight of mice. It can be used as a hypoglycemic drug and has good development and application prospects. The preparation method of the present invention is simple to operate, low in cost, and can achieve large-scale preparation of magnesium acetyltaurine. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is the change curve of blood glucose in mice after a single administration in Example 3;

[0029] Figure 2 This is the curve of changes in mouse body weight after multiple administrations in Example 4. DETAILED DESCRIPTION

[0030] The present invention is further described in detail below in conjunction with embodiments so that those skilled in the art can implement the invention with reference to the description.

[0031] It should be understood that the terms such as “having”, “including” and “comprising” used herein do not exclude the existence or addition of one or more other elements or combinations thereof.

[0032] The test methods used in the following examples are conventional methods unless otherwise specified. The materials and reagents used in the following examples are all commercially available unless otherwise specified. In the following examples, if no specific conditions are specified, the experiments were carried out under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used, if the manufacturer is not specified, are all conventional products that can be purchased commercially.

[0033] Example 1 Preparation method of magnesium acetyl taurate

[0034] Weigh 5g of magnesium taurine, mix it with 25mL of glacial acetic acid in a reaction container, heat it to reflux temperature 125℃ and react for 1h; add 1g of 98% concentrated sulfuric acid dropwise for 10min, and then continue to stir and react at reflux temperature for 12h. After the reaction is completed, transfer the reaction solution to a concentration bottle, concentrate and evaporate to dryness under reduced pressure to obtain 7.4g of white block solid; add 15mL of water to dissolve, heat it to 55℃, add 50mL of ethanol dropwise, the system becomes turbid and white powder precipitates; filter, rinse the wet product with 20mL of ethanol, and dry it with air at 90℃ to obtain 5.4g of white powder of magnesium acetyl taurate.

[0035] Example 2 Diabetic mouse modeling method

[0036] The experimental animals used were healthy female C57 mice, weighing 18-22 g.

[0037] 40 mice weighing (20±2)g were taken, of which 8 were blank control group, and the rest were divided into groups, marked and weighed. The normal group mice were fed with ordinary maintenance feed, and the other 4 groups were fed with high-fat feed. After feeding for 4 weeks, the other 4 groups were fasted but not watered for 8 hours, and streptozotocin (STZ) 100mg / kg body weight was injected intraperitoneally, with an injection volume of 0.2ml / 20g body weight. The blank control group was given the same dose of 0.9% saline intraperitoneally. After continuing to feed the corresponding feed for 7 days, fast for 4 hours, and test the fasting blood glucose of each group of mice. The blood glucose value ≥11.1mmol / L was considered a successful model.

[0038] Example 3 Effect of a single dose of magnesium acetyl taurate on blood glucose in mice

[0039] 1. Experimental Grouping

[0040] There were 8 normal mice and 32 diabetic model mice. The diabetic mice were randomly divided into 4 groups, with 8 mice in each group. The diabetic mouse modeling method was referred to Example 2.

[0041] The groups are shown in Table 1.

[0042] Table 1. Mice dosing groups

[0043]

[0044]

[0045] 2. Experimental steps

[0046] The test mice were weighed and recorded before administration. The human insulin positive control group was administered by tail vein injection, and the low-dose and high-dose groups of magnesium acetyl taurate were administered by gavage. The mice were fasted for 8 hours before administration, and the blood glucose levels of the mice were tested at 0, 0.5, 1, and 2 hours after administration. Blood was collected from the tail vein and the blood glucose level of the mice was tested using a Roche blood glucose meter.

[0047] 3. Experimental results

[0048] The experimental results are shown in Table 2 and Figure 1 .

[0049] Table 2. Effect of single administration on blood glucose in mice

[0050]

[0051] From the experimental results in Table 2, we can see that:

[0052] (1) The blood glucose levels of mice in the model control group before administration were significantly higher than those in the blank group, indicating that the model was successfully established;

[0053] (2) The blood glucose levels of the blank control group and the model control group did not fluctuate significantly within 0.5 to 2 hours after administration of 0.9% saline; the blood glucose levels of the human insulin positive control group decreased significantly within 0.5 to 2 hours after administration, indicating that the experimental method is reliable.

[0054] (3) Within 0.5 to 2 hours after administration, the human insulin positive control group, the low-dose group and the high-dose group all showed a clear trend of lowering blood glucose levels, and the difference was statistically significant compared with the model control group.

[0055] (4) Within 0.5 to 2 hours after administration, there was a significant difference in the rate of decrease in blood glucose levels between the low-dose and high-dose groups of magnesium acetyl taurate, showing a dose-dependent and positive correlation. The higher the dose of magnesium acetyl taurate, the greater the decrease in blood glucose levels in mice.

[0056] The above experimental results show that magnesium acetyltaurate has a lowering effect on the blood sugar of diabetic mice and can be developed into a blood sugar-lowering drug or health product; it can also be used in the preparation of auxiliary treatment drugs or health products for diabetes.

[0057] Example 4 Effects of repeated administration of magnesium acetyl taurate on body weight of mice

[0058] 1. Experimental Grouping

[0059] The experimental animals used were healthy female C57 mice, weighing 18-22 g, 5 mice in each group, randomly divided into 3 groups.

[0060] The groups are shown in Table 3.

[0061] Table 3. Mice dosing groups

[0062] Group dose Blank control group 0.9% saline Magnesium acetyl taurate low dose group 100mg / kg Magnesium acetyltaurate high dose group 500mg / kg

[0063] 2. Experimental steps

[0064] The test mice were weighed and recorded before administration, maintained on normal feed, and weighed once a week for 4 weeks. After weighing, the mice were gavage-administered.

[0065] 3. Experimental results

[0066] The experimental results are shown in Table 4 and Figure 2 .

[0067] Table 4. Effects of multiple administrations on the body weight of mice

[0068]

[0069] From the experimental results in Table 4, it can be seen that when low-dose and high-dose magnesium acetyltaurate were administered for 4 weeks, compared with the blank control group, there was no significant difference in the initial body weight of normal mice before administration or during administration.

[0070] The above experimental results show that magnesium acetyltaurate has little effect on the body weight of normal mice, has good safety, and can be developed into a hypoglycemic drug or health product; it can also be used in the preparation of auxiliary treatment drugs or health products for diabetes.

[0071] Although the embodiments of the present invention have been disclosed as above, they are not limited to the applications listed in the specification and the implementation modes. They can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to specific details.

Claims

1. Application of magnesium acetyl taurate in the preparation of hypoglycemic drugs or health products.

2. The use according to claim 1, characterized in that: Magnesium acetyltaurate as the sole active ingredient or as a co-active ingredient with other hypoglycemic agents.

3. The use according to claim 2, characterized in that: Other hypoglycemic drugs include at least one of metformin, insulin, α-glucosidase inhibitors, and polysaccharide competitive inhibitors.

4. A hypoglycemic drug or health product, which contains magnesium acetyltaurate as the only active ingredient, or contains magnesium acetyltaurate and other hypoglycemic drugs as active ingredients.

5. The hypoglycemic drug or health product according to claim 4, characterized in that: Other hypoglycemic drugs include at least one of metformin, insulin, α-glucosidase inhibitors, and polysaccharide competitive inhibitors.

6. The hypoglycemic drug or health product according to claim 4, characterized in that: The medicine or health product also includes at least one of a pharmaceutically acceptable salt, a co-crystal, a prodrug, a solvate, and a metabolite.

7. The hypoglycemic drug or health product according to claim 4, characterized in that: The drug is prepared into a clinically acceptable drug preparation according to a conventional drug preparation method.

8. The hypoglycemic drug or health product according to claim 4, characterized in that: The dosage form of the drug is tablets, capsules, injections, granules or other clinically acceptable dosage forms.

9. A method for preparing magnesium acetyl taurate in the use as claimed in any one of claims 1 to 3 or in the hypoglycemic drug or health product as claimed in any one of claims 4 to 8, characterized in that: The following steps are involved: S1. Mix magnesium taurine and glacial acetic acid evenly, and heat to reflux for 0.5 to 1 h; S2, adding sulfuric acid to the product obtained in step S1, adding for 5 to 15 minutes, and then continuing to stir at reflux temperature for 8 to 16 hours; S3, concentrating and evaporating the product obtained in S2 under reduced pressure; S4. Add water to completely dissolve the product obtained in S3, raise the temperature to 50-60° C., add ethanol dropwise to precipitate white powder, and then filter and dry to obtain magnesium acetyl taurate.

10. The method for preparing magnesium acetyl taurate according to claim 9, characterized in that: The following steps are involved: S1. Mix 2.5-10 g of magnesium taurine and 12.5-50 mL of glacial acetic acid in a reaction vessel, and heat under reflux for 0.5-1 h; S2, adding 0.5-2 g of 98 wt% sulfuric acid to the product obtained in step S1, adding for 5-15 min, and then continuing to stir at reflux temperature for 8-16 h; S3, transfer the product obtained in S2 to a concentration bottle, concentrate under reduced pressure and evaporate to dryness to obtain a white block solid; S4. Add deionized water to completely dissolve the white block solid obtained in S3, raise the temperature to 50-60° C., add 45-60 mL of ethanol dropwise to precipitate a white powder, and then filter the solid product, rinse with ethanol, and dry to obtain magnesium acetyl taurate.

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