Oral solution for treating constipation and preparation method thereof

Abstract

The invention discloses an oral solution for treating constipation and a preparation method thereof. The prescription comprehensively considers the advantages and disadvantages of the lactulose and the magnesium sulfate which are diarrhea-inducing components, and the lactulose and the magnesium sulfate are mixed to prepare an oral solution. The risk of hypokalemia caused by long-term taking of lactulose is avoided, and the defect that the mouth feel is poor when a magnesium sodium potassium sulfate oral solution is taken is also avoided. The prepared oral solution has the characteristics of being beneficial to swallowing, convenient to take and good in mouth feel, so that the medication compliance of a patient is greatly improved.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations and relates to a medicine for treating chronic functional constipation, and specifically relates to an oral solution for treating constipation and a preparation method thereof. Background Art

[0002] The drugs currently used to treat constipation include lactulose oral solution, magnesium sulfate powder, polyethylene glycol 4000 powder, etc. Among them, lactulose is a synthetic disaccharide that is not absorbed in the intestine. After being decomposed by colon bacteria, it lowers the intestinal pH to block the absorption of ammonia. The high permeability of disaccharides can also be used to treat constipation. It has no intestinal irritation and is safe to use. Lactulose oral solution was developed by Abbott and launched in Germany in 1982 (trade name: Duphalac). It is suitable for the treatment of chronic functional constipation, hyperammonemia and diseases caused by elevated blood ammonia.

[0003] Subsequently, the original company's lactulose oral solution was approved for import and listing in my country, with the trade name Dumik. Generally, 50% sugar solution can inhibit the growth of yeast, 65% can inhibit the growth of bacteria, and 80% can inhibit the growth of mold. The lactulose oral solution uses a lactulose concentration of about 67%. However, at this concentration, the solution viscosity is relatively large, and it is difficult to filter through a 0.22um filter membrane. Although it improves after heating, the temperature will affect the stability of lactulose when it exceeds 60°C, and colored impurities will be produced, posing certain safety risks. Therefore, most manufacturers have cancelled the sterilization filtration step and replaced it with a 0.8um filter element filter. At the same time, long-term use of lactulose oral solution may also lead to electrolyte disorders and cause hypokalemia.

[0004] Magnesium sulfate can also be used to treat constipation. Its similar product, magnesium sodium potassium sulfate oral solution, is mainly used for intestinal cleansing. They both have the characteristics of bad taste and obvious side effects.

[0005] We have learned through understanding and research that lactulose oral solution and magnesium sulfate are both osmotic laxatives. Osmotic laxatives are slowly absorbed in the intestine, so they can maintain high osmotic pressure in the intestinal cavity, prevent the absorption of salt and water in the intestine, thereby expanding the intestinal cavity, stimulating intestinal peristalsis, and relieving constipation. A newly developed oral solution for treating constipation combines the characteristics of lactulose and magnesium sulfate, reducing their dosages while maintaining their osmotic pressure unchanged, thus achieving a therapeutic effect, while also reducing the dosage of magnesium sulfate and the occurrence of side effects. In addition, lactulose not only acts as a laxative, but also as a sweetener to improve the taste of the oral solution, and medication compliance is better.

[0006] In the preparation method, although the reduction of lactulose concentration is beneficial to the sterilization filtration operation, the antibacterial ability of the oral solution is reduced. We added the preservative sodium benzoate to ensure the microbiological properties of the product. Summary of the invention

[0007] The present invention provides an oral solution for treating constipation, which is composed of the following prescription in a 90 ml preparation unit: milk

[0008] Concentrated fructose solution (relative density 1.33, lactulose content 0.667 g / ml) 10 g

[0009] Magnesium sulfate 0.8g

[0010] Sodium sulfate 8.75g

[0011] Potassium sulfate 1.6g

[0012] Sodium benzoate 0.05g

[0013] Add purified water to 90 ml.

[0014] The oral solution for treating constipation prepared by this product has good process stability and is suitable for large-scale industrial production.

[0015] The present invention further provides a method for preparing an oral solution for treating constipation, comprising the following main steps: 1) preparing ingredients: adding a prescribed amount of magnesium sulfate, sodium sulfate, potassium sulfate, and sodium benzoate into a liquid preparation tank, adding 1 / 2 of the prescribed amount of pure water, heating to 40° C. to 50° C., and stirring to dissolve;

[0016] 2) Mixing: Slowly add the prescribed amount of lactulose concentrated solution into the preparation tank and stir to dissolve.

[0017] 3) Make up the volume: Add purified water to make up the volume to the prescribed amount and conduct intermediate testing;

[0018] 4) Sterilization: Filter and sterilize using a cartridge filter + 0.22μm filter element;

[0019] 5) Filling: After the intermediates are inspected and qualified, filling and packaging are carried out.

[0020] The beneficial technical effects of the present invention are: the formula combines the cathartic effects of lactulose and magnesium sulfate, but the amount of magnesium sulfate used is greatly reduced, and the product is easy to take and has a good taste; a certain amount of sodium and potassium are added to the formula to prevent hyponatremia and potassiumemia caused by long-term use of cathartic drugs. In terms of process, the viscosity of the oral solution is greatly reduced, and it is easy to filter, which ensures the microbial properties of the product and greatly improves its safety. DETAILED DESCRIPTION

[0021] The present invention will be further described below in conjunction with specific embodiments, but this should not be understood as the scope of the above-mentioned subject matter of the present invention being limited to the following embodiments. All technologies realized based on the above-mentioned content of the present invention belong to the scope of the present invention. The adjuvants in the following embodiments can be replaced with pharmaceutically acceptable similar adjuvants, or reduced or increased.

[0022] Example

[0023] 1. Prescription:

[0024] Lactulose concentrated solution (relative density 1.33, lactulose content 0.667g / ml) 10g

[0025] Magnesium sulfate 0.8g

[0026] Sodium sulfate 8.75g

[0027] Potassium sulfate 1.6g

[0028] Sodium benzoate 0.05g

[0029] Add purified water to 90 ml.

[0030] 2. Preparation method

[0031] The present invention further provides a method for preparing an oral solution for treating constipation, comprising the following main steps: 1) preparing ingredients: adding a prescribed amount of magnesium sulfate, sodium sulfate, potassium sulfate, and sodium benzoate into a liquid preparation tank, adding 1 / 2 of the prescribed amount of pure water, heating to 40° C. to 50° C., and stirring to dissolve;

[0032] 2) Mixing: Slowly add the prescribed amount of lactulose concentrated solution into the preparation tank and stir to dissolve.

[0033] 3) Make up the volume: Add purified water to make up the volume to the prescribed amount and conduct intermediate testing;

[0034] 4) Sterilization: Filter and sterilize using a cartridge filter + 0.22μm PES filter element;

[0035] 5) Filling: After the intermediates are inspected and qualified, filling and packaging are carried out.

[0036] 3. Quality inspection

[0037] The key quality indicators of oral solutions are tested in accordance with the relevant provisions of the 2020 edition of the Pharmacopoeia.

[0038] Key quality index test results of oral solution

[0039]

Claims

1. An oral solution for treating constipation, characterized in that: In a 90 ml preparation unit, the prescription composition is as follows: lactulose concentrated solution (relative density 1.33, lactulose content 0.667 g / ml), magnesium sulfate, sodium sulfate, potassium sulfate, a preservative, and the balance is water.

2. An oral solution for treating constipation according to claim 1, characterized in that: The dosage of the lactulose concentrated solution is 5 to 20 g, more preferably 10 g.

3. An oral solution for treating constipation according to claim 1, characterized in that: The amount of magnesium sulfate is 0.2-0.8 g, the amount of sodium sulfate is 2.2-8.75 g, and the amount of potassium sulfate is 0.4-1.6 g; more preferably, the amount of magnesium sulfate is 0.4 g, the amount of sodium sulfate is 4.4 g, and the amount of potassium sulfate is 0.8 g.

4. An oral solution for treating constipation according to claim 1, characterized in that: The preservative is sodium benzoate, and the dosage is 45mg to 180mg, more preferably 90mg.

5. An oral solution for treating constipation according to claims 1 to 4, wherein the preparation method comprises the following steps: 1) Ingredients: Put the prescribed amount of magnesium sulfate, sodium sulfate, potassium sulfate, and sodium benzoate into the liquid preparation tank, add 1 / 2 of the prescribed amount of pure water, heat to 40°C to 50°C, and stir to dissolve; 2) Mixing: Slowly add the prescribed amount of lactulose concentrated solution into the preparation tank and stir to dissolve. 3) Make up the volume: Add purified water to make up the volume to the prescribed amount and conduct intermediate testing; 4) Sterilization: Filter and sterilize using a cartridge filter + 0.22μm filter element; 5) Filling: After the intermediates are inspected and qualified, filling and packaging are carried out.

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