A potassium chloride oral solution and preparation method thereof

Abstract

The present invention belongs to the technical field of pharmaceutical preparations, and specifically relates to a potassium chloride oral solution and a preparation method thereof. The raw materials of the potassium chloride oral solution include: potassium chloride, an antibacterial agent, a pH regulator, a flavoring agent, a stabilizer, a sweetener, an essence, a pigment and water; the stabilizer is a mixture of xanthan gum, gallic acid and hydroxyethyl cellulose. The present invention further improves the stability and taste of the potassium chloride solution, and the preparation of the present invention has a good antibacterial effect and can be stored for a long time.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a potassium chloride oral solution and a preparation method thereof. Background Art

[0002] Potassium chloride is an electrolyte supplement. Potassium is the main cation in cells and an important component for maintaining intracellular osmotic pressure. The intracellular concentration is about 150-160mmol / L, and the concentration in the extracellular fluid is lower, only 3.5-5.0mmol / L. The body mainly relies on Na on the cell membrane. + , K + , and ATPase to maintain K inside and outside the cell + 、Na + Concentration difference.

[0003] Hypokalemia is a common electrolyte disorder in clinical practice. Oral potassium supplementation is the safest. Existing oral potassium supplementation preparations mainly include oral liquid, sustained-release tablets, sustained-release capsules, granules, powders, etc. Compared with solid preparations, liquid preparation drugs are dispersed in the medium as particles or molecules, with large dispersion and fast absorption, and can exert drug effects more quickly. Since the drug in the solution exists in a molecular state, it can be absorbed without dissolving, while the drug in the suspension exists in the form of particles and needs to be further dissolved by body fluids after entering the human body, so the absorption rate is slower than that of the solution. Potassium chloride liquid itself is colorless and has no volatile odor, but it tastes salty and astringent. Using traditional methods of taking it, the taste is poor, causing nausea and loss of appetite. In order to improve patient compliance, doctors often mix 10% potassium chloride injection into orange juice (beverage) or honey for patients to take, which is inconvenient in clinical applications and has problems such as poor patient experience.

[0004] In addition, since the 10% potassium chloride oral solution prepared by hospital preparations is a non-terminally sterilized preparation and is easily contaminated by microorganisms and deteriorates, the 10% potassium chloride solution prescription included in the Chinese Hospital Preparation Standards (Western Medicine Preparations) contains 10 mL (1000 mL) of a preservative 5% ethylparaben solution. -1 , the content of ethylparaben is 0.05% to ensure the quality of the preparation. However, it is found that the 10% potassium chloride oral solution is not stable enough during storage and application, especially many small crystals are easily precipitated below 20°C, making the preparation properties unqualified. It is found that the 10% potassium chloride oral solution is not stable enough during storage and application, especially many small crystals are easily precipitated below 20°C, making the preparation properties unqualified.

[0005] Chinese invention patent application CN115969783A discloses a potassium chloride oral solution and a preparation method thereof. The invention uses potassium chloride as an active ingredient, sodium benzoate as an antibacterial agent, glycerin as a humectant, anhydrous citric acid and sodium citrate as buffers, polyethylene glycol 400 as a stabilizer, and adds sweeteners and flavoring agents to prepare a potassium chloride oral solution, which solves the problems of poor taste and low patient compliance of the existing potassium chloride oral solution, and ensures the stability of the properties of the potassium chloride oral solution during storage and transportation under low temperature (-10°C), but the taste needs to be further improved.

[0006] Therefore, it is very necessary to develop a potassium chloride oral preparation and a preparation method thereof that can solve the above-mentioned technical problems. Summary of the invention

[0007] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a potassium chloride oral preparation with good taste, no aftertaste and high stability and a preparation method thereof.

[0008] The present invention is achieved through the following technical solutions:

[0009] A potassium chloride oral solution, the raw materials of which include potassium chloride, an antibacterial agent, a pH regulator, a flavoring agent, a stabilizer, a sweetener, an essence, a pigment and water;

[0010] The stabilizer is a mixture of xanthan gum, gallic acid and hydroxyethyl cellulose.

[0011] Preferably, in terms of weight volume percentage concentration, the raw materials of the potassium chloride oral solution include: 8%-12% potassium chloride, 0.05%-0.2% antibacterial agent, 0.8%-1.2% pH regulator, 2%-6% flavoring agent, 1.5%-3.0% stabilizer, 0.4%-0.8% sweetener, 0.1%-0.3% flavor, 0.005%-0.02% pigment and the balance water.

[0012] Preferably, the mass ratio of xanthan gum, gallic acid and hydroxyethyl cellulose is 5-7:2-4:1.

[0013] Preferably, the flavoring agent is selected from one or more of glycerol, sorbitol, ethyl maltol and mannitol, and the pH adjuster is selected from one or more of acetic acid, malic acid, lactic acid, citric acid, sodium bicarbonate, potassium bicarbonate, sodium citrate, sodium dihydrogen phosphate and disodium hydrogen phosphate.

[0014] Further preferably, the flavoring agent is a mixture of glycerol and ethyl maltol, and the mass ratio of the glycerol to ethyl maltol is 2-4:1.

[0015] Further preferably, the pH adjuster is a mixture of citric acid and sodium citrate, and the mass ratio of citric acid to sodium citrate is 1:1-1:2.

[0016] Preferably, the antibacterial agent is selected from at least one of sodium benzoate, methylparaben, sodium methylparaben, ethylparaben and potassium sorbate.

[0017] Preferably, the sweetener comprises one or more of aspartame, sucrose, sucralose and saccharin sodium, the flavor is selected from one or more of sweet orange flavor, strawberry flavor, tangerine flavor, pineapple flavor, apple flavor, and lemon flavor, and the pigment is selected from one or more of sunset yellow, beetroot red, turmeric and lemon yellow.

[0018] The present invention also relates to a method for preparing the potassium chloride oral solution, comprising the following steps:

[0019] (1) mixing 60% to 80% of the prescribed amount of water with a pH adjuster and a stabilizer, and stirring to obtain a mixture 1;

[0020] (2) adding potassium chloride, a flavoring agent and an antibacterial agent to the mixture 1 and stirring to obtain a mixture 2;

[0021] (3) Add the sweetener, flavor and pigment to the mixture 2, continue to stir evenly, and then use a 500 ml volumetric flask to make up to the mark and shake evenly to prepare a potassium chloride oral solution.

[0022] Preferably, the stirring time in step (1) and step (2) is 15-25 min.

[0023] The beneficial effects of the present invention are:

[0024] The potassium chloride oral preparation of the present invention further improves the stability and taste of the solution by adding a mixture of xanthan gum, gallic acid and hydroxyethyl cellulose as a stabilizer and a mixture of glycerol and ethyl maltol as a flavoring agent. The preparation of the present invention has excellent stability and good antibacterial effect, and can meet the requirements of low-temperature transportation and long-term storage. DETAILED DESCRIPTION

[0025] The present invention will be further described below in conjunction with specific embodiments, and the advantages and features of the present invention will become clearer as the description proceeds. However, these embodiments are exemplary only and do not constitute any limitation to the scope of the present invention. It should be understood by those skilled in the art that the details and forms of the technical solution of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, but these modifications and replacements all fall within the scope of protection of the present invention. Active ingredient potassium chloride and other medical adjuvants can be obtained commercially.

[0026] Example 1

[0027] A potassium chloride oral solution, the raw materials and dosage are shown in Table 1.

[0028] Table 1 Raw materials and dosage

[0029]

[0030] The preparation method of above-mentioned potassium chloride solution is:

[0031] (1) Mix 70% of the prescribed amount of purified water with a pH adjuster and a stabilizer, and stir for 20 minutes to obtain a mixture 1;

[0032] (2) adding potassium chloride, flavoring agent and antibacterial agent to mixture 1 and stirring for 20 minutes to obtain mixture 2;

[0033] (3) Add the sweetener, flavor and pigment to the mixture 2, continue to stir evenly, and then use a 500 ml volumetric flask to make up to the mark and shake evenly to prepare a potassium chloride oral solution.

[0034] Example 2

[0035] A potassium chloride oral solution, the raw materials and dosage are shown in Table 2.

[0036] Table 2 Raw materials and dosage

[0037]

[0038] The preparation method of the above potassium chloride oral solution is consistent with that of Example 1.

[0039] Example 3

[0040] A potassium chloride oral solution, the raw materials and dosage are shown in Table 3.

[0041] Table 3 Raw materials and dosage

[0042]

[0043] The preparation method of the above potassium chloride oral solution is consistent with that of Example 1.

[0044] Example 4

[0045] A potassium chloride oral solution, the raw materials and dosage are shown in Table 4.

[0046] Table 4 Raw materials and dosage

[0047]

[0048] The preparation method of the above potassium chloride oral solution is consistent with that of Example 1.

[0049] Comparative Example 1

[0050] A potassium chloride oral solution, which differs from Example 1 only in that the stabilizer composition is different. The raw materials and amounts are shown in Table 5.

[0051] Table 5 Raw materials and dosage

[0052]

[0053] The preparation method of the above potassium chloride solution is consistent with that of Example 1.

[0054] Comparative Example 2

[0055] A potassium chloride oral solution, which differs from Example 1 only in that the stabilizer composition is different. The raw materials and amounts are shown in Table 6.

[0056] Table 6 Raw materials and dosage

[0057]

[0058] The preparation method of the above potassium chloride solution is consistent with that of Example 1.

[0059] Comparative Example 3

[0060] A potassium chloride oral solution, which differs from Example 1 only in that the stabilizer composition is different. The raw materials and amounts are shown in Table 7.

[0061] Table 7 Raw materials and dosage

[0062]

[0063]

[0064] The preparation method of the above potassium chloride solution is consistent with that of Example 1.

[0065] Comparative Example 4

[0066] A potassium chloride oral solution, which differs from Example 1 only in that the stabilizer composition is different. The raw materials and amounts are shown in Table 8.

[0067] Table 8 Raw materials and dosage

[0068] The preparation method of the above potassium chloride solution is consistent with that of Example 1.

[0069] Comparative Example 5

[0070] A potassium chloride oral solution, which is different from Example 1 only in that the flavoring agent composition is different. The raw materials and amounts are shown in Table 9.

[0071] Table 9 Raw materials and dosage

[0072]

[0073]

[0074]

[0075] The preparation method of the above potassium chloride solution is consistent with that of Example 1.

[0076] Comparative Example 6

[0077] A potassium chloride oral solution, which differs from Example 1 only in that the flavoring agent composition is different. The raw materials and amounts are shown in Table 10.

[0078] Table 10 Raw materials and dosage

[0079]

[0080] The preparation method of the above potassium chloride solution is consistent with that of Example 1.

[0081] Effect test

[0082] 1. Taste test

[0083] The taste scores of Examples 1-4 and Comparative Examples 1-6 were evaluated as shown in Table 11.

[0084] Table 11 Taste test scores

[0085]

[0086]

[0087] Note: Excellent: excellent taste, no aftertaste; Fair: average taste, slightly bitter; Poor: poor taste, with a strong aftertaste.

[0088] 2. Stability test

[0089] The potassium chloride oral solutions of Examples 1-4 and Comparative Examples 1-6 were respectively packaged into sealed glass bottles, 20 bottles in each group, 10 bottles were stored at 20°C as controls, and 10 bottles were placed at 60°C for 30 days. Samples were taken on the 10th, 20th, and 30th days, and tested according to the key stability inspection items. The results are shown in Tables 12 and 13.

[0090] Table 12 Test results of properties stability of Examples 1-4 and Comparative Examples 1-6

[0091] 10 days 20 days 30 days Example 1 No change No change No change Example 2 No change No change No change Example 3 No change No change No change Example 4 No change No change No change Comparative Example 1 A small amount of precipitation A small amount of precipitation There is a lot of precipitation Comparative Example 2 A small amount of precipitation A small amount of precipitation There is a lot of precipitation Comparative Example 3 A small amount of precipitation A small amount of precipitation There is a lot of precipitation Comparative Example 4 A small amount of precipitation A small amount of precipitation There is a lot of precipitation Comparative Example 5 No change No change A small amount of precipitation Comparative Example 6 No change No change A small amount of precipitation

[0092] Table 13 Content and impurity detection results of Examples 1-4 and Comparative Examples 1-4

[0093]

[0094]

[0095] The potassium chloride oral solutions of Examples 1-4 and Comparative Examples 1-4 were respectively packaged into sealed glass bottles, 20 bottles in each group, 10 bottles were stored at 20°C as a control, and 10 bottles were placed at -10°C for 2 days. Samples were taken on the first and second days to test the product stability. The results are shown in Table 14 (freezing test, testing needs to be performed after thawing).

[0096] Table 14 Stability test results

[0097] Example 1 Example 2 Example 3 Example 4 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 0d Stablize Stablize Stablize Stablize Stablize Stablize Stablize Stablize 1d Stablize Stablize Stablize Stablize Stablize Unstable Stablize Unstable 2d Stablize Stablize Stablize Stablize Unstable Unstable Unstable Unstable

[0098] Note: No stratification, water precipitation or crystallization indicates stability.

[0099] In addition, the inventors conducted a long-term stability test of potassium chloride oral solution. The potassium chloride oral solution of Examples 1-4 was subjected to 3-month accelerated and 6-month long-term stability tests. The assessment item indicators were compared with those of 0 month, and there was no significant change in properties, identification, pH value, relative density, content determination, microbial limit test, etc. This shows that the quality of the potassium chloride oral solution samples is stable.

[0100] The above detailed description is a specific description of one feasible embodiment of the present invention. The embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or modification that does not deviate from the present invention should be included in the scope of the technical solution of the present invention.

Claims

1. A potassium chloride oral solution, characterized in that According to the weight volume percentage concentration, the raw materials of the potassium chloride oral solution include: potassium chloride 8%-12%, antibacterial agent 0.05%-0.2%, pH regulator 0.8%-1.2%, flavoring agent 2%-6%, stabilizer 1.5%-3.0%, sweetener 0.4%-0.8%, flavor 0.1%-0.3%, pigment 0.005%-0.02% and the balance water; The stabilizer is a mixture of xanthan gum, gallic acid and hydroxyethyl cellulose; The flavoring agent is a mixture of glycerol and ethyl maltol.

2. The potassium chloride oral solution according to claim 1, characterized in that The mass ratio of the xanthan gum, gallic acid and hydroxyethyl cellulose is 5-7:2-4:

1.

3. The potassium chloride oral solution according to claim 1, characterized in that The pH regulator is selected from one or more of acetic acid, malic acid, lactic acid, citric acid, sodium bicarbonate, potassium bicarbonate, sodium citrate, sodium dihydrogen phosphate and disodium hydrogen phosphate.

4. The potassium chloride oral solution according to claim 1, characterized in that The mass ratio of the glycerol to ethyl maltol is 2-4:

1.

5. The potassium chloride oral solution according to claim 3, characterized in that The pH regulator is a mixture of citric acid and sodium citrate, and the mass ratio of the citric acid to the sodium citrate is 1:1-1:

2.

6. The potassium chloride oral solution according to claim 1, characterized in that The antibacterial agent is selected from at least one of sodium benzoate, methylparaben, sodium methylparaben, ethylparaben and potassium sorbate.

7. The potassium chloride oral solution according to claim 1, characterized in that The sweetener comprises one or more of aspartame, sucrose, sucralose and sodium saccharin; the flavor is selected from one or more of sweet orange flavor, strawberry flavor, tangerine flavor, pineapple flavor, apple flavor and lemon flavor; and the pigment is selected from one or more of sunset yellow, beetroot red, turmeric and lemon yellow.

8. A method for preparing the potassium chloride oral solution according to any one of claims 1 to 7, characterized in that: The steps include: (1) mixing 60% to 80% of the prescribed amount of water with a pH adjuster and a stabilizer, and stirring to obtain a mixture 1; (2) adding potassium chloride, a flavoring agent and an antibacterial agent to the mixture 1 and stirring to obtain a mixture 2; (3) Add the sweetener, flavor and pigment to the mixture 2, continue to stir evenly, and then use a 500 ml volumetric flask to make up to the mark and shake evenly to prepare a potassium chloride oral solution.

9. The preparation method according to claim 8, characterized in that: The stirring time in step (1) and step (2) is 15-25 minutes.

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