Bromhexine hydrochloride composition and preparation method thereof

Abstract

The invention provides a bromhexine hydrochloride composition and a preparation method thereof, and particularly relates to the field of medicines. The bromhexine hydrochloride injection comprises 3-5 mg of bromhexine hydrochloride, 4-6 g of glucose, 0.8-1 g of sodium chloride, a proper amount of a pH regulator and water for injection, the volume is fixed to 100 ml, and the pH is 4-5. Adding 70% of water for injection into the mixing tank, wherein the temperature of the water for injection is less than 40 DEG C; the preparation method comprises the following steps: weighing bromhexine hydrochloride according to a prescription amount, adding the bromhexine hydrochloride into a mixing tank, controlling the temperature at 30-40 DEG C, and mixing and stirring for 20-30 minutes to obtain a mixed solution; weighing the glucose and the sodium chloride according to the prescription amount, sequentially adding the glucose and the sodium chloride into the mixed solution, controlling the temperature to be 30-40 DEG C, and mixing and stirring for 20-30 minutes; adding a pH regulator to regulate the pH value to a target value; fixing the total volume to 100% by using water for injection, and then mixing and stirring for 20-30 minutes; and sterilizing and filtering to obtain a target product. The bromhexine hydrochloride for oral administration or injection is prepared by reducing auxiliary materials, and the composition is good in stability.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of medicine, and particularly relates to a bromhexine hydrochloride composition and a preparation method thereof. BACKGROUND

[0002] Bromhexine hydrochloride can directly act on bronchial glands, promote lysosomes of mucus secretion cells to release, make mucopolysaccharide fibers in sputum differentiate and split, and also can inhibit synthesis of acid glycoprotein in mucus glands and goblet cells, so that small molecule glycoprotein with low viscosity is secreted, thereby reducing the viscosity of sputum and making it easy to be coughed out.

[0003] The existing bromhexine hydrochloride composition such as injection or oral solution has more adjuvants, has a larger probability of causing adverse reactions, and can increase production cost. A patent with the application number CN202210555366.X discloses a bromhexine hydrochloride injection and a preparation method and application thereof, which contains bromhexine hydrochloride, methyl paraben, propyl paraben, tartaric acid, a pH regulator and water for injection. The application guarantees the stability of the bromhexine hydrochloride injection, but has the problem of more adjuvants.

[0004] In view of the prior art condition, a bromhexine hydrochloride composition and a preparation method thereof are needed, which can prepare bromhexine hydrochloride for oral administration or injection by reducing adjuvants, and the composition has good stability. SUMMARY

[0005] The application aims to provide a bromhexine hydrochloride composition and a preparation method thereof, which can reduce the degradation of related substances of the drug solution by controlling the production process of the drug solution, and obtain a more stable bromhexine hydrochloride composition.

[0006] The application provides the following technical scheme:

[0007] A bromhexine hydrochloride composition contains 3-5 mg of bromhexine hydrochloride, 4-6 g of glucose, 0.8-1 g of sodium chloride, an appropriate amount of a pH regulator, water for injection, and is constant volume to 100 ml, and the pH is 4-5.

[0008] Preferably, the composition contains 4 mg of bromhexine hydrochloride, 5 g of glucose and 0.9 g of sodium chloride.

[0009] Preferably, the pH is 4.5.

[0010] Preferably, the pH regulator is sodium hydroxide or hydrochloric acid.

[0011] A preparation method of a bromhexine hydrochloride composition, characterized in that the method comprises the following steps:

[0012] Step one, 70% of water for injection is added into a mixing tank, and the temperature of the water for injection is less than 40 DEG C;

[0013] Step two, take the prescription amount of bromhexine hydrochloride, add to the mixing tank, control the temperature at 30-40℃, mixed stirring 20-30min to obtain the mixed solution;

[0014] Step three, take the prescription amount of glucose, sodium chloride in turn into the mixed solution, control the temperature at 30-40℃, mixed stirring 20-30min;

[0015] Step four, add pH regulator, adjust the pH to the target value;

[0016] Step five, use water for injection to set the total volume to 100%, then mixed stirring 20-30min;

[0017] Step six, sterilization filtration to obtain the target product;

[0018] Preferably, in step two, take the prescription amount of bromhexine hydrochloride, add to the mixing tank, control the temperature at 35℃, mixed stirring 25min to obtain the mixed solution.

[0019] Preferably, in step three, take the prescription amount of glucose, sodium chloride in turn into the mixed solution, control the temperature at 35℃, mixed stirring 25min;

[0020] Preferably, in step four, the pH regulator is 0.05mol / L; the pH regulator is sodium hydroxide or hydrochloric acid.

[0021] Preferably, in step six, sterilization at 121℃ for 12min, filter with 0.22μm PES filter membrane to obtain the target product.

[0022] Advantages of the present application

[0023] Unlike the existing injection of bromhexine hydrochloride composition, by adding a large amount of auxiliary materials, to improve the composition stability, the present application by reducing the auxiliary materials, preparation of bromhexine hydrochloride for oral or injection, and the composition stability is good. DETAILED DESCRIPTION

[0024] Example 1

[0025] A bromhexine hydrochloride composition, comprising bromhexine hydrochloride 3mg, glucose 4g and sodium chloride 0.8g, appropriate amount of pH regulator, water for injection to 100ml, and pH is 4; the pH regulator is sodium hydroxide or hydrochloric acid.

[0026] A bromhexine hydrochloride composition preparation method, the steps are as follows: comprising the following steps:

[0027] The total amount of 70% of water for injection is added to the mixing tank, and the temperature of the water for injection is less than 40 DEG C; the prescription amount of bromhexine hydrochloride is weighed and added to the mixing tank, and the temperature is controlled at 30 DEG C, and mixed and stirred for 20 min to obtain a mixed solution; the prescription amount of glucose and sodium chloride is weighed and added to the mixed solution in turn, and the temperature is controlled at 30 DEG C, and mixed and stirred for 20 min; the pH regulator is 0.05 mol / L; the pH regulator is sodium hydroxide or hydrochloric acid, and the pH is adjusted to 4; the total capacity is set to 100% with water for injection, and then mixed and stirred for 20 min; sterilized at 121 DEG C for 12 min, filtered with a 0.22 mu PES filter membrane to obtain the target product;

[0028] Example 2

[0029] A bromhexine hydrochloride composition, comprising bromhexine hydrochloride 4 mg, glucose 5 g and sodium chloride 0.9 g, an appropriate amount of pH regulator, water for injection is set to 100 ml, and the pH is 4.5; the pH regulator is sodium hydroxide or hydrochloric acid.

[0030] A method for preparing a bromhexine hydrochloride composition, comprising the following steps: the total amount of 70% of water for injection is added to the mixing tank, and the temperature of the water for injection is less than 40 DEG C; the prescription amount of bromhexine hydrochloride is weighed and added to the mixing tank, and the temperature is controlled at 35 DEG C, and mixed and stirred for 25 min to obtain a mixed solution; the prescription amount of glucose and sodium chloride is weighed and added to the mixed solution in turn, and the temperature is controlled at 35 DEG C, and mixed and stirred for 25 min; the pH regulator is 0.05 mol / L; the pH regulator is sodium hydroxide or hydrochloric acid, and the pH is adjusted to 4.5; the total capacity is set to 100% with water for injection, and then mixed and stirred for 20-30 min; sterilized at 121 DEG C for 12 min, filtered with a 0.22 mu PES filter membrane to obtain the target product;

[0031] Example 3

[0032] A bromhexine hydrochloride composition, comprising bromhexine hydrochloride 5 mg, glucose 6 g and sodium chloride 1 g, an appropriate amount of pH regulator, water for injection is set to 100 ml, and the pH is 5.

[0033] A preparation method of a bromhexine hydrochloride composition, steps are as follows: 70% of total amount of water for injection is added into a mixing tank, and the temperature of the water for injection is less than 40 DEG C; the prescription amount of bromhexine hydrochloride is weighed and added into the mixing tank, the temperature is controlled at 40 DEG C, and mixing and stirring are carried out for 30 min to obtain a mixed solution; the prescription amount of glucose and sodium chloride is weighed and added into the mixed solution in sequence, the temperature is controlled at 40 DEG C, and mixing and stirring are carried out for 30 min; 0.05 mol / L of pH regulator is added; the pH regulator is sodium hydroxide or hydrochloric acid, and the pH is adjusted to 5; the total capacity is set to 100% using water for injection, and then mixing and stirring are carried out for 30 min; sterilization is carried out at 121 DEG C for 12 min, 0.22 mu PES filter membrane is used for filtration to obtain a target product;

[0034] The products prepared in examples 1 to 3 are each taken 10ml, and are numbered 1a, 1b, 1c respectively, and high temperature experiments are carried out at 60 DEG C, and specific data are as follows:

[0035]

[0036] The products prepared in examples 1 to 3 are each taken 10ml, and are numbered 2a, 2b, 2c respectively, and light experiments are carried out at room temperature, and specific data are as follows:

[0037]

[0038] From the above data, it can be seen that the products prepared in examples 1 to 3 have good composition stability, and the product prepared under the condition of example 2 has the best comprehensive stability.

[0039] The above only is the preferred embodiment of the present application, and does not limit the present application, although the present application is described in detail with reference to the foregoing embodiments, and for those skilled in the art, the technical solutions recorded in the foregoing embodiments can be modified, or some technical features can be replaced equivalently. Any modification, equivalent replacement, improvement, etc. within the spirit and principle of the present application should be included in the protection scope of the present application.

Claims

1. A bromhexine hydrochloride composition, characterized in that: It contains 3-5 mg of bromhexine hydrochloride, 4-6 g of glucose, and 0.8-1 g of sodium chloride, with an appropriate amount of pH adjuster, and is diluted to 100 ml with water for injection, and the pH is 4-5.

2. The bromhexine hydrochloride composition according to claim 1, characterized in that: It contains 4 mg of bromhexine hydrochloride, 5 g of glucose, and 0.9 g of sodium chloride.

3. The bromhexine hydrochloride composition according to claim 1, characterized in that: The pH is 4.

5.

4. The bromhexine hydrochloride composition according to claim 1, characterized in that: The pH adjuster is sodium hydroxide or hydrochloric acid.

5. The bromhexine hydrochloride composition according to claim 1, characterized in that its preparation method comprises the following steps: Step 1: Add 70% of the total amount of water for injection into the mixing vessel, and ensure that the temperature of the water for injection is less than 40°C. Step 2: Weigh out the prescribed amount of bromhexine hydrochloride, add it to a mixing tank, control the temperature at 30℃-40℃, and mix and stir for 20-30 minutes to obtain a mixture. Step 3: Weigh the prescribed amounts of glucose and sodium chloride and add them to the mixture in sequence. Control the temperature at 30℃-40℃ and mix for 20-30 minutes. Step 4: Add pH adjuster to adjust the pH to the target value; Step 5: Use water for injection to bring the total volume to 100%, then mix and stir for 20-30 minutes; Step 6: Sterilization filtration yields the target product.

6. The method for preparing a bromhexine hydrochloride composition according to claim 5, characterized in that: In step two, weigh out the prescribed amount of bromhexine hydrochloride, add it to a mixing tank, control the temperature at 35°C, and mix and stir for 25 minutes to obtain a mixture.

7. The method for preparing a bromhexine hydrochloride composition according to claim 5, characterized in that: In step three, weigh out the prescribed amounts of glucose and sodium chloride and add them to the mixture in sequence, control the temperature at 35℃, and mix and stir for 25 minutes.

8. The method for preparing a bromhexine hydrochloride composition according to claim 5, characterized in that: In step four, the pH adjuster is 0.05 mol / L; the pH adjuster is sodium hydroxide or hydrochloric acid.

9. The method for preparing a bromhexine hydrochloride composition according to claim 5, characterized in that: In step six, sterilize at 121℃ for 12 minutes, and then filter with a 0.22μm PES membrane to obtain the target product.

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