Mitiglittol taurine oral liquid as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of medicines, and provides a miglittol taurine oral liquid and a preparation method and application thereof, carboxymethyl chitosan, xanthan gum and sodium alginate are sequentially added into a miglittol and taurine aqueous solution, dissolving and uniform mixing are carried out, and then sterilization, subpackaging and sealing are carried out. According to the technical scheme, the taurine and the miglittol are combined to prepare the oral liquid, and the two components are water-soluble components which are quickly dissolved out and can quickly reach the intestinal tract to take effect compared with other dosage forms, so that the adverse reaction on the gastrointestinal tract is reduced; xanthan gum and sodium alginate are used as stabilizers of the oral liquid, and the xanthan gum is used for forming an elastic grid structure, so that component separation and precipitation are effectively prevented; the sodium alginate can form irreversible gel, has the drug carrier capacity, enhances the drug solubility, and can cooperate with the xanthan gum to enhance the thickening property and the stability and improve the texture and the taste of the oral liquid. The traditional Chinese medicine composition has an obvious effect when being applied to medicines for treating type 2 diabetes, and can reduce body weight, maintain blood sugar level and reduce adverse reactions.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and specifically relates to a miglitol taurine oral liquid and a preparation method and application thereof. Background Art

[0002] According to the International Diabetes Federation (IDF) Global Diabetes Map, the number of adult diabetes patients in my country will reach 143 million in 2023, and the number of pre-diabetes patients in China will reach 148 million. Among them, type 2 diabetes patients account for more than 90% of diabetes patients.

[0003] Among adult diabetic patients in my country, only 16.5% of them have achieved blood sugar control. Diet therapy, exercise therapy, and drug therapy can only control the condition, but cannot cure diabetes. Even after treatment, the symptoms disappear, and blood sugar and urine sugar return to normal, but the glucose tolerance curve will still be abnormal. As the disease progresses, blood sugar exceeds the upper limit of the normal range for a long time, and various organs suffer from chronic progressive lesions, and even functional impairment and failure, which can lead to cardiovascular and cerebrovascular diseases, blindness, renal failure, amputation, etc. They are extremely dangerous and not only significantly weaken the quality of life of patients, but also directly endanger their lives and health. For patients with a history of diabetes for 3 years, 5 years, and more than 10 years, the probability of developing diabetic complications is approximately 46%, 61%, and 98%, respectively.

[0004] Most of the diabetes drugs currently on the market have adverse reactions such as hypoglycemia, weight gain, gastrointestinal reactions, and may also cause kidney and liver damage. In addition, as the duration of medication increases, drug resistance and secondary failure become a major obstacle to the long-term therapeutic effect of the drug.

[0005] Based on this, a miglitol taurine oral solution and a preparation method and application thereof are studied and involved. Summary of the invention

[0006] The present invention provides a method for preparing a miglitol taurine oral liquid, which comprises the steps of sequentially adding carboxymethyl chitosan, xanthan gum and sodium alginate to a miglitol and taurine aqueous solution, dissolving and mixing, sterilizing in a sterilizing tank, and then packaging into glass bottles and sealing. In the technical scheme, taurine and miglitol are used together to prepare an oral liquid, both of which are water-soluble components, and an oral liquid dosage form is adopted. Compared with other dosage forms, the two active ingredients dissolve faster and can reach the intestines to take effect faster, thereby solving the technical problems of hypoglycemia, weight gain, liver and kidney function damage, drug resistance, secondary failure and the like existing in the existing prepared diabetes drugs.

[0007] The present invention is achieved through the following technical solutions: A method for preparing a miglitol-taurine oral liquid comprises the following steps: sequentially adding carboxymethyl chitosan, xanthan gum and sodium alginate into a miglitol-taurine aqueous solution, dissolving and mixing, sterilizing, packaging and sealing.

[0008] In the technical scheme of the present application, taurine is 2-aminoethanesulfonic acid, which is one of the most abundant amino acids in various tissues and organs, and plays an important role in maintaining the normal physiological functions of humans and animals. Nutritional supplements containing taurine were approved by the FDA in 1984. Studies have shown that taurine has a wide range of health and pharmacological effects, including lowering blood pressure, lowering blood sugar, protecting the liver, enhancing immunity, anti-inflammatory, anti-oxidation, protecting the heart, and so on. Taurine also has the effect of reducing weight, and obesity is an important risk factor for type 2 diabetes. Taurine interacts with insulin receptor proteins without replacing the binding of insulin to the receptor, exerting insulin-like effects, coordinating insulin or superimposing insulin's regulatory effects on sugar metabolism, and participating in maintaining the body's glucose homeostasis. As an endogenous cell protector, taurine can effectively reduce diabetic hyperglycemia and protect the endocrine function of pancreatic β cells.

[0009] α-Glucosidase is an intestinal enzyme located in the brush border of the small intestine that hydrolyzes oligosaccharides and disaccharides into glucose and other monosaccharides. α-Glucosidase inhibitors prevent the breakdown of larger carbohydrates into glucose and reduce the increase in blood sugar levels after a meal. As an α-glucosidase inhibitor, miglitol binds to and inhibits α-glucosidase. Miglitol is not broken down in the body and is excreted from the body as a prototype by the kidneys. It does not damage the liver and kidneys, and only causes adverse reactions such as gastrointestinal bloating.

[0010] It can be seen that the technical solution uses miglitol and taurine in combination and is prepared into an oral solution for the treatment of type 2 diabetes. It can not only control the blood sugar stability of type 2 diabetes, but also control body weight, delay or even reverse the course of diabetes. Compared with the existing diabetes drugs that have problems such as unstable blood sugar, such as hypoglycemia, weight gain, etc., it has better effects in controlling blood sugar and reducing weight.

[0011] The technical solution of the present application sequentially adds carboxymethyl chitosan, xanthan gum, and sodium alginate to the aqueous solution of miglitol and taurine, and xanthan gum and sodium alginate are mainly used as stabilizers for the oral solution of miglitol and taurine. Xanthan gum can form an elastic grid structure in the process of preparing the solution, prevent the separation and precipitation of components, and has a good thickening effect. The added sodium alginate can form a thermally irreversible gel, has the ability of a drug carrier, enhances the solubility of the drug, can cooperate with xanthan gum to enhance the thickening and stability, and can also improve the texture and mouthfeel of the oral solution. Carboxymethyl chitosan is an important biopolymer with good solubility, can be used as a carrier of drugs to achieve controlled release of drugs, and has good anti-inflammatory and antibacterial effects.

[0012] Optionally, carboxymethyl chitosan, xanthan gum and sodium alginate are added to the aqueous solution of miglitol and taurine in sequence. The specific operation is: 50 parts of miglitol and 300-500 parts of taurine are dissolved in a little water, and then 200 parts of carboxymethyl chitosan, 5 parts of xanthan gum and 10 parts of sodium alginate are added, and then water is added to a specified volume.

[0013] Optionally, after dissolution and mixing, the concentration of miglitol is 5 mg / ml and the concentration of taurine is 30-50 mg / ml.

[0014] Optionally, carboxymethyl chitosan, xanthan gum and sodium alginate are sequentially added to the aqueous solution of miglitol and taurine to dissolve, and the specific operation of the dissolution is: swelling the added carboxymethyl chitosan, xanthan gum and sodium alginate by stirring or dissolving the carboxymethyl chitosan, xanthan gum and sodium alginate by heating, and then stirring evenly.

[0015] Optionally, the packaging is into glass bottles, and the glass bottles are 10ml glass bottles.

[0016] Optionally, the glass bottle is a 10 ml low-borosilicate glass bottle.

[0017] Optionally, the specific sterilization operation is to pass saturated circulating steam through the jacket and the tank of the sterilization tank for 30 minutes, and then take it out after cooling.

[0018] Optionally, the xanthan gum and sodium alginate are both stabilizers; and the carboxymethyl chitosan is an antibacterial agent.

[0019] Another object of the present application is to provide a miglitol taurine oral solution, which is prepared according to the miglitol taurine oral solution preparation method described in the above steps.

[0020] In addition to the main drugs Miglitol and taurine, carboxymethyl chitosan, xanthan gum, and sodium alginate are harmless to the human body, and the prepared oral liquid does not contain preservatives, solid pharmaceutical excipients, and other ingredients. The overall formula of Miglitol Taurine Oral Liquid is simple and safe. In addition to having a good effect on the treatment of type 2 diabetes, the choice of oral liquid dosage form can reduce the resistance of patients who need to take medication for a long time, and is more friendly to patients with poor medication compliance or inconvenient swallowing.

[0021] Another purpose of the present application is to use the obtained miglitol taurine oral solution in the preparation of drugs for treating type 2 diabetes.

[0022] Compared with the prior art, the present invention has the following beneficial effects: 1) This technical solution combines taurine and miglitol to make an oral solution. Both active ingredients are water-soluble and dissolve quickly. The oral solution dosage form can reach the intestines faster than other dosage forms and has a significant effect on the treatment of type 2 diabetes. It can also reduce body weight and maintain blood sugar levels, solving the technical problems of hypoglycemia, weight gain, liver and kidney damage, drug resistance, secondary failure, etc. in the existing prepared diabetes drugs.

[0023] 2) In the preparation method of miglitol taurine oral liquid in this technical scheme, xanthan gum and sodium alginate are used as stabilizers for the oral liquid, mainly because xanthan gum can form a good elastic grid structure, which can effectively prevent the separation and precipitation of components and has a good thickening effect; and sodium alginate can form a thermally irreversible gel, has drug carrier capacity, enhances drug solubility, and can cooperate with xanthan gum to enhance thickening and stability, thereby improving the texture and taste of the oral liquid.

[0024] 3) Carboxymethyl chitosan in this technical solution is a water-soluble derivative of chitosan, which has good biocompatibility and degradability, is non-toxic, and has many medical effects, among which the antibacterial effect has been confirmed by many studies, and the antibacterial effect of 2% concentration is significant. In the present invention, carboxymethyl chitosan with a substitution degree of ≥90% and a deacetylation degree of ≥90% is used to prepare a 2% substrate solution as the antibacterial agent in the present invention, and can also be used as a thickener and stabilizer.

[0025] 4) This technical solution uses saturated circulating steam for sterilization in a sterilization tank with stirring and jacket. Compared with sterilization in an autoclave after filling, this method does not have a sterilization cold spot, can better ensure the sterilization effect, occupies a smaller area of ​​equipment, and saves more energy.

[0026] 5) The components involved in the miglitol taurine oral solution of this technical solution, in addition to the main drugs miglitol and taurine, only add stabilizers and natural antibacterial agents that are harmless to the human body. The overall oral solution has a simple formula and safe ingredients, which can reduce the resistance of patients who need to take medication for a long time, and is also more friendly to patients with poor medication compliance or inconvenient swallowing. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 Figure 2 shows the weight changes of four groups of mice tested at fixed times each week. Figure 2 This is the fasting blood glucose change chart of four groups of mice fasting for 8 hours at a fixed time each week; Figure 3 At the end of the experiment, the subjects were fasted for 12 hours and fed with 2.5 g / kg glucose. Blood was collected from the tail vein at 0 hours, 0.5 hours, 1 hour, and 2 hours to test the changes in glucose tolerance. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with embodiments. The illustrative embodiments of the present invention and their description are only used to explain the present invention and are not intended to limit the present invention.

[0029] Embodiment 1: Add about 50L of purified water to the sterilization tank, add 0.5kg of miglitol and 3kg of taurine, and stir to dissolve. Then add 2kg of carboxymethyl chitosan, 0.05kg of xanthan gum, and 0.1kg of sodium alginate, and add water to make up to 100L. Stir to completely dissolve the excipients. Saturated circulating steam is introduced into the jacket of the sterilization tank. After the temperature in the tank rises to 100°C, saturated circulating steam is also introduced into the tank, the temperature rises to 115°C, and the pressure in the tank rises to 0.10MPa. Maintain for 30 minutes to complete sterilization. After the 10ml low-borosilicate glass bottle for oral liquid is cleaned and sterilized on the automatic cleaning and sterilization machine, it is filled and sealed with a cap in a Class A clean environment.

[0030] Test results: After being placed at 40±2℃ and 75±5% relative humidity for 3 months, the content and related substances detected were not significantly different from those in 0 month, and there was no adverse trend. At the same time, the microbial limit test still maintained sterility.

[0031] Embodiment 2: Add about 50L of purified water to the sterilization tank, add 0.5kg of miglitol and 5kg of taurine, and stir to dissolve. Then add 2kg of carboxymethyl chitosan, 0.05kg of xanthan gum, and 0.1kg of sodium alginate, and add water to make up to 100L. Stir to completely dissolve the excipients. Saturated circulating steam is introduced into the jacket of the sterilization tank. After the temperature in the tank rises to 100°C, saturated circulating steam is also introduced into the tank, the temperature rises to 115°C, and the pressure in the tank rises to 0.10MPa. Maintain for 30 minutes to complete sterilization. After the 10ml low-borosilicate glass bottle for oral liquid is cleaned and sterilized on the automatic cleaning and sterilization machine, it is filled and sealed with a cap in a Class A clean environment.

[0032] Test results: After being placed at 40±2℃ and 75±5% relative humidity for 3 months, the content and related substances detected were not significantly different from those in 0 month, and there was no adverse trend. At the same time, the microbial limit test still maintained sterility.

[0033] Embodiment 3: Add about 50L of purified water to the sterilization tank, add 0.5kg of miglitol and 4kg of taurine, and stir to dissolve. Then add 2kg of carboxymethyl chitosan, 0.05kg of xanthan gum, and 0.1kg of sodium alginate, and add water to make up to 100L. Stir to dissolve the excipients completely. Saturated circulating steam is introduced into the jacket of the sterilization tank. After the temperature in the tank rises to 100°C, saturated circulating steam is also introduced into the tank, the temperature rises to 115°C, and the pressure in the tank rises to 0.10MPa. Maintain for 30 minutes to complete sterilization. After the 10ml low-borosilicate glass bottle for oral liquid is cleaned and sterilized on the automatic cleaning and sterilization machine, it is filled and sealed with a cap in a Class A clean environment.

[0034] Test results: After being placed at 40±2℃ and 75±5% relative humidity for 3 months, the content and related substances detected were not significantly different from those in 0 month, and there was no adverse trend. At the same time, the microbial limit test still maintained sterility.

[0035] Experimental mice were used as experimental subjects to detect the body weight and glucose tolerance of the mice after taking the miglitol taurine oral solution prepared in Example 1, Example 2 or Example 3.

[0036] Experimental preparation: Five-week-old C57BLKS / J-db / db type Ⅱ diabetic male mice weighing 20-25 g were selected as experimental subjects and divided into groups A, B, C, and D, with 5 mice in each group.

[0037] Group A was the miglitol tablet group, which was fed orally with a tube of miglitol 2.5 mg / kg / d. The miglitol tablets were crushed and weighed, and then mixed with 0.5 ml of water before feeding; Group B was a miglitol 5 mg / ml, taurine 30 mg / ml concentration group, and was orally gavaged with 0.5 ml / kg / d of oral solution (i.e., the miglitol taurine oral solution prepared in Example 1); Group C consisted of a miglitol 5 mg / ml and taurine 50 mg / ml concentration group, and was orally gavaged with an oral solution of 0.5 ml / kg / d (i.e., the miglitol taurine oral solution prepared in Example 2).

[0038] Group D was the control group and was fed with 0.5 ml / kg / d of normal saline.

[0039] After 6 weeks of continuous administration, the drug feeding was stopped and normal feeding was continued for 2 weeks.

[0040] Detection method: 1. Test the weight of mice at a fixed time every week; 2. Fasting blood sugar was collected from the tail vein of mice at a fixed time every week after fasting for 8 hours, and tested with a blood glucose meter and blood glucose test strips; 3. At the end of the experiment, fast for 12 hours, feed 2.5g / kg glucose, and test glucose tolerance at 0h, 0.5h, 1h, and 2h. The specific results are shown in Table 1 (see Table 1). Figure 1 as shown).

[0041]

[0042] Table 1 Analysis shows that the weight of mice in each group before and after treatment is shown in Table 1: Compared with the untreated control group, Group D, it can be seen that the miglitol tablet group, Group A, the miglitol combined with taurine group, Group B and Group C can all slow down the weight gain of diabetic mice, and the high-dose taurine group, Group C, is more obvious. After 4 weeks of treatment, compared with the untreated control group, Group D, the miglitol combined with high-dose taurine group, Group C, slowed down the weight gain significantly. After stopping the medication, the miglitol tablet group, Group A, rebounded.

[0043] It can be seen that the miglitol taurine oral solution prepared in Example 1 (Group B) and Example 2 (Group C) has a significant effect on the treatment of type 2 diabetes and a more significant effect on slowing down the increase in weight compared to the use of miglitol tablets alone.

[0044] The fasting blood glucose results of each group of mice are shown in Table 2 ( Figure 2 shown):

[0045] Table 2 Analysis shows that: Compared with the untreated control group, group D, all three drug groups were able to lower blood sugar, and the miglitol combined with high-dose taurine group, i.e., group C (Example 2) was more obvious. After drug withdrawal, the blood sugar rebound of the miglitol tablet group, i.e., group A, exceeded that of the untreated group, and the effect of the high-dose taurine group, i.e., group C, was more lasting.

[0046] It can be seen that the miglitol taurine oral solution prepared in Example 1 and Example 2 has obvious advantages in reducing diabetic hyperglycemia and delaying the progression of diabetes in the treatment of type 2 diabetes, and can maintain blood sugar levels after drug withdrawal.

[0047] The glucose tolerance test data of each group of mice after 2 weeks of drug withdrawal are shown in Table 3 ( Figure 3 shown):

[0048] Table 3 Analysis shows that: After 2 weeks of drug withdrawal, mice in group A that used miglitol tablets alone had a greater rebound and higher glucose tolerance data than the untreated control group D. Miglitol combined with taurine, i.e., the miglitol taurine oral solution prepared in Example 1 and Example 2, had the effect of reducing glucose tolerance in mice, regardless of whether it was a low-dose group or a high-dose group, and the high-dose group had a more obvious protective effect on impaired glucose tolerance in mice.

[0049] Based on the above analysis, the miglitol taurine oral solution prepared in Example 1 and Example 2 has a significant effect on the treatment of diabetes, specifically in slowing down weight gain, maintaining blood sugar stability, and protecting kidney and liver functions, and has a good effect on drug resistance. Compared with the use of miglitol tablets alone, the advantages are more obvious.

[0050] However, the blood sugar lowering effect of taurine alone is not obvious in the short term, and the test data during the experimental period is worse than that of miglitol alone. However, the combination of taurine and miglitol, miglitol taurine oral solution, is more effective in treating type 2 diabetes.

[0051] The specific implementation methods described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific implementation method of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for preparing miglitol taurine oral solution, characterized in that: Carboxymethyl chitosan, xanthan gum and sodium alginate are added to the aqueous solution of miglitol and taurine in sequence, dissolved and mixed, sterilized, packaged and sealed.

2. The method for preparing a miglitol taurine oral solution according to claim 1, characterized in that: Carboxymethyl chitosan, xanthan gum and sodium alginate are added to the aqueous solution of miglitol and taurine in sequence. The specific operation is: 50 parts of miglitol and 300-500 parts of taurine are dissolved in a little water, and then 200 parts of carboxymethyl chitosan, 5 parts of xanthan gum and 10 parts of sodium alginate are added in sequence, and water is added to the specified volume.

3. A method for preparing a miglitol taurine oral solution according to claim 1 or 2, characterized in that: After dissolution and mixing, the concentration of miglitol is 5 mg / ml and the concentration of taurine is 30-50 mg / ml.

4. The method for preparing a miglitol taurine oral solution according to claim 3, characterized in that: Carboxymethyl chitosan, xanthan gum and sodium alginate are sequentially added to the aqueous solution of miglitol and taurine to dissolve. The specific operation of the dissolution is: swelling the added carboxymethyl chitosan, xanthan gum and sodium alginate by stirring or dissolving the carboxymethyl chitosan, xanthan gum and sodium alginate by heating, and then stirring evenly.

5. The method for preparing a miglitol taurine oral solution according to claim 1, characterized in that: The packaging is into glass bottles, and the glass bottles are 10ml glass bottles.

6. The method for preparing a miglitol taurine oral solution according to claim 5, characterized in that: The glass bottle is a 10 ml low borosilicate glass bottle.

7. The method for preparing a miglitol taurine oral solution according to claim 4, characterized in that: The specific operation of sterilization is to pass saturated circulating steam into the jacket and tank of the sterilization tank for 30 minutes.

8. The method for preparing a miglitol taurine oral solution according to claim 1, characterized in that: The xanthan gum and sodium alginate are both stabilizers, and the carboxymethyl chitosan is an antibacterial agent.

9. A miglitol taurine oral solution, characterized in that: Miglitol taurine oral solution obtained according to the preparation method of miglitol taurine oral solution according to any one of claims 1 to 8.

10. Use of the miglitol taurine oral solution obtained according to the preparation method according to any one of claims 1 to 8 in the preparation of a drug for treating type 2 diabetes.

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