CN1330298C - Oral liquid of metformin hydrochloride and preparation method - Google Patents

Abstract

The present invention discloses metformin hydrochloride oral liquid and a preparation method thereof. 25 to 100g/1000 ml of metformin hydrochloride as effective components is added, water is added, and the metformin hydrochloride and the water are heated for dissolving the metformin hydrochloride; steviosin is added, and the metformin hydrochloride, the water and the steviosin are stirred for 10 to 20 minutes for dissolving; orange essence and coconut essence are added, and the metformin hydrochloride, the water, the steviosin, the orange essence and the coconut essence are stirred for 10 to 20 minutes; finally, sodium benzoate is added, the metformin hydrochloride, the water, the steviosin, the orange essence, the coconut essence and the sodium benzoate are stirred for 10 to 20 minutes for dissolving, water is added to 1000 to 3000 ml, and then, the metformin hydrochloride, the water, the steviosin, the orange essence, the coconut essence and the sodium benzoate are stirred for 30 minutes, and the metformin hydrochloride oral liquid product is obtained by filtering, filling, moistly and heatedly sterilizing for 0.5 hour, sterilizing at 100(+/-)2 DEG C. and adding outer packing. The obtained medicament has stable properties, and the medicinal effect of the medicament is ensured. The preparation method has the advantages of simple and stable preparation process, easy control, simple equipment, low investment, simple operation, short production periodicity, etc. After the preparation is changed, patients are convenient to take, and the metformin hydrochloride oral liquid has the advantages of good mouth feel, rapid absorption and obvious curative effect.

Description

Metformin hydrochloride oral solution and preparation method thereof

technical field

The invention relates to a pharmaceutical preparation and a preparation method thereof, in particular to a metformin hydrochloride oral solution used in treating diabetes and a preparation method thereof.

Background technique

Diabetes is a common multiple disease. It is usually a chronic systemic disease caused by the absolute or relative insufficiency of insulin in the body and the decrease in insulin sensitivity in the body. The typical symptoms are polyuria, polydipsia, polyphagia, and Weight loss, often accompanied by fatigue, pale complexion. Itchy skin. Growth retardation. Severely ill patients sometimes cause complications, which bring great pain and inconvenience to patients. Both Chinese and Western medicine have some treatment methods for diabetes, and Chinese medicine also has treatment prescriptions. Among them, insulin-dependent (type I) mainly relies on insulin treatment, and non-insulin-dependent (type II) except diet therapy. ", "Jiangtangshu" and other Chinese medicine varieties, Western medicine varieties include "sulfonylureas", "biguanides", etc. Among them, biguanide hypoglycemic tablets (metformin tablets) are commonly used hypoglycemic drugs. The hypoglycemic tablet contains metformin hydrochloride (C ₄ H ₁₁ N ₅ ·HCl) which is more than 95% of the marked amount.

In recent years, metformin hydrochloride tablets are widely used as commonly used hypoglycemic drugs, and new dosage forms have also appeared. For example, the patent application "oral metformin hydrochloride sustained-release preparation and its preparation method" (02133574.5) relates to a drug that can be slowly released in the body and maintain blood sugar levels. The drug concentration is stable and the half-life is prolonged. It is used as a hypoglycemic drug for the treatment of type II diabetes. The sustained-release agent uses high-viscosity polymer materials to absorb water and swell to form a gel. It is made into a sustained-release tablet that is only taken once a day. The sustained-release agent is a polymer material and an auxiliary agent added to form a gel, and the process is long and the production cost is high.

The purpose of the present invention is exactly that the existing metformin hydrochloride common tablet can not play hypoglycemic effect very well, and take inconvenience characteristic, simultaneously, in order to increase the medicament variety for treating diabetes, to adapt to the needs of different diabetic patients, the inventor of this patent has studied The invention provides an oral solution of metformin hydrochloride, which is convenient for patients to take after the dosage form is changed, absorbs quickly and has remarkable curative effect.

Another object of the present invention is to provide a preparation method of metformin hydrochloride oral solution.

Contents of the invention

The metformin hydrochloride oral solution preparation scheme developed by the inventors is as follows: Metformin hydrochloride 25.0∽100g, stevia 0.4∽1.6g, orange essence 1.25∽5.00ml, coconut essence 1.25∽5.00ml, sodium benzoate 2.0∽8.0g Add appropriate amount of purified water to prepare 1000∽3000ml oral solution, the unit is determined according to the preparation amount in production, the weight unit can be g, kg, and the volume unit can be ml, L;

Its preparation method is to weigh the formula amount of metformin hydrochloride and add it to an appropriate amount of water, stir for 10 minutes to dissolve, then add stevia and stir for 10 to 20 minutes to dissolve, add orange essence and coconut essence and stir for 10 to 20 minutes, and finally add sodium benzoate and stir for 10 to 20 minutes. After dissolving in 20 minutes, add water to make up 1000∽3000ml, stir for 30 minutes, filter, fill, and sterilize with damp heat for 0.5 hours at a sterilization temperature of 100±2°C, and pack it to obtain metformin hydrochloride oral solution product.

According to the above-mentioned metformin hydrochloride oral solution, its preferred formula is: according to the compounding ratio of metformin hydrochloride 25.0g, stevioside 0.4g, orange essence 1.25ml, coconut essence 1.25ml, sodium benzoate 2.0g, add appropriate amount of purified water and mix to 1000ml oral solution.

According to the above-mentioned preparation method of metformin hydrochloride (C ₄ H ₁₁ N ₅ ·HCl) oral solution, it is best to take 25.0 g of metformin hydrochloride, add 100 ml of water, heat to 50 ° C to completely dissolve metformin hydrochloride, and then add 0.4 g of stevia , stir for 10 minutes to dissolve, add orange essence 1.25ml, coconut essence 1.25, stir for 10 minutes, finally add 2.0g of sodium benzoate and stir for 10 minutes to dissolve, add water to make up 1000ml, stir for 30 minutes, filter, fill, moist heat sterilization 0.5 Hours, sterilization temperature 100 ± 2 ℃, outer packaging, you can get metformin hydrochloride oral solution product.

Metformin hydrochloride (C ₄ H ₁₁ N ₅ ·HCl), is 1,1·dimethylbiguanide hydrochloride. Its (C ₄ H ₁₁ N ₅ ·HCl) content should not be less than 98.5% based on dry product calculation. Metformin hydrochloride is white crystal or crystalline powder, non-toxic and odorless. Metformin hydrochloride is easily soluble in water, slightly soluble in ethanol, and insoluble in chloroform or ether. It is currently mainly used as a hypoglycemic agent in the treatment of diabetes.

The content of metformin hydrochloride (C ₄ H ₁₁ N ₅ ·HCl) in 1000ml of metformin hydrochloride oral solution is 25∽50g.

Metformin hydrochloride oral solution of the present invention is obtained from the modified dosage form of the existing national standard chemical drug preparation "Metformin hydrochloride tablet". Because the tablet needs to add some excipients, and through compression molding, the dissolution rate is relatively slow, and the oral solution is added There are few excipients, the dispersion of the drug is large, the absorption is fast and the effect is quick, and the dispersion of the active ingredients is relatively uniform, which improves the compliance of patients who cannot or do not want to swallow tablets. Therefore change its dosage form to oral solution.

The metformin hydrochloride oral solution of the present invention is convenient for patients to take after changing the dosage form, has good taste, fast absorption, and still significant curative effect. The preparation process also has the advantages of simple, stable and easy-to-master preparation process, simple equipment, low investment, simple operation, short production cycle and the like.

Detailed ways

Metformin hydrochloride, the active component of the metformin hydrochloride oral solution of the present invention, has the functions of lowering blood sugar in treating diabetes, alleviating and gradually eliminating the symptoms of diabetes and the like. Confirmed through clinical research, add metformin hydrochloride oral solution (I) on the basis of original treatment (diet control and sulfonylurea hypoglycemic agent treatment) by 23 cases. Those whose fasting blood glucose is above 10mmol/L, 0.5g (calculated as metformin hydrochloride) 3 times/day, belong to group A; those whose fasting blood glucose is below 10mmol/L, receive 0.25g (calculated as metformin hydrochloride) 3 times/day, belong to group B, Measure hemoglobin (HbA, C), cholesterol (ch), triglyceride (TG), creatinine (Cr), blood urea nitrogen (BUN), and ALT at 2 hours before and after taking (I) respectively. and body weight, blood pressure. Observations show that: it has a lowering effect on blood sugar and blood lipids in patients with type I diabetes, especially on postprandial blood sugar, which is obvious in larger doses.

Toxicity research of metformin hydrochloride oral solution: Through clinical observation of 64 patients, different doses of metformin hydrochloride oral solution were selected according to the level of blood sugar. , insulin release assay. Results _P < 0.001 after treatment compared with before treatment. There was no significant change in insulin level before and after treatment; no obvious side effects. Combined with the previous long-term toxicity test of metformin hydrochloride tablets in animals: 50 times, 30 times and 10 times of the clinical dose, the test animals in each dose group had no abnormal performance, and there was no significant difference compared with the blank group (P<0.05), and the drug was withdrawn for 2 weeks , no delayed toxic reaction was found, indicating that the metformin hydrochloride oral solution has low clinical maximum daily dose toxicity and is safe in clinical application.

The clinical application of metformin hydrochloride oral solution to the clinical trials of treating hyperinsulinemia anovulation: 29 patients with hyperinsulinemia were treated with metformin hydrochloride oral solution for 12 weeks, and 19 of them received chlorine before and after treatment with metformin hydrochloride oral solution. Clomid treatment for 1 cycle. Observe the changes of blood testosterone level and ovulation function before and after treatment. Results: The blood testosterone level before treatment with Metformin Hydrochloride Oral Solution was (2.7±1.0) nmol/L. After 4 weeks of treatment, it was (1.9±1.0) nmol/L. The difference was significant (P<0.05) ). Spontaneous ovulation, there were 3 cases before treatment with metformin hydrochloride oral solution, and there were 10 cases after treatment (8 cases were former anovulators) (P＜0.05); 19 cases had taken clomiphene before and after treatment with metformin hydrochloride oral solution There were 8 cases of successful ovulation induction before metformin hydrochloride treatment, and 15 cases after treatment (P<0.05). Conclusion: Hyperinsulinemia can lead to a decrease in blood testosterone level and improve ovulation function.

The following examples can further illustrate the preparation method of the present invention:

Example 1: Weigh 100 kg of metformin hydrochloride, add 120 L of water, place at 50° C. and stir for 20 minutes to dissolve metformin hydrochloride, then add 1.3 kg of stevia and stir for 15 minutes to dissolve, add 5 L of orange essence and 5 L of coconut essence, and stir for 1 0 Minutes, finally add 5kg of sodium benzoate and stir for 10 minutes to dissolve, add water to make up 4000L, stir for 30 minutes, filter, fill, sterilize with damp heat for 0.5 hours, sterilization temperature 100±2°C, add outer packaging, you can get metformin hydrochloride for oral administration solution product.

Claims (3)

1. A metformin hydrochloride oral solution is characterized in that its formula is: metformin hydrochloride by 25.0～100g, stevia 0.4～1.6g, orange essence 1.25～5.00ml, coconut essence 1.25～5.00ml, sodium benzoate 2.0～8.0g Add appropriate amount of purified water to make an oral solution of 1000-3000ml; The preparation method is to add metformin hydrochloride in an appropriate amount of water, stir for 10 minutes to dissolve, then add stevia and stir for 10 to 20 minutes to dissolve, add orange essence and coconut essence and stir for 10 to 20 minutes, and finally add sodium benzoate and stir for 10 to 20 minutes. After dissolving in 20 minutes, add water to make up 1000-3000ml, stir for 30 minutes, filter, fill, and sterilize with damp heat for 0.5 hours at a sterilization temperature of 100±2°C, add outer packaging, and you can get metformin hydrochloride oral solution product. 2. The metformin hydrochloride oral solution according to claim 1 is characterized in that its formula is: according to the compounding ratio of metformin hydrochloride 25.0g, stevioside 0.4g, orange essence 1.25ml, coconut essence 1.25ml, sodium benzoate 2.0g, add Appropriate amount of purified water is prepared to 1000ml oral solution. 3. The preparation method of metformin hydrochloride oral solution according to claim 1, characterized in that take 25.0g of metformin hydrochloride, add 100ml of water, heat to 50°C to completely dissolve metformin hydrochloride, then add 0.4g of stevia, and stir for 10 minutes Dissolve, add 1.25ml of orange essence and 1.25ml of coconut essence, stir for 10 minutes, finally add 2.0g of sodium benzoate, stir for 10 minutes to dissolve, add water to make up 1000ml, stir for 30 minutes, filter, fill, sterilize with moist heat for 0.5 hours, sterilize The bacterial temperature is 100±2°C, and the outer packaging is added to obtain the metformin hydrochloride oral liquid product.