Compound sodium picosulfate oral solution and preparation method thereof

Abstract

The present invention relates to the field of pharmaceutical technology, and more particularly to a compound sodium picosulfate oral solution and a preparation method thereof. The oral solution comprises the following components: sodium picosulfate, anhydrous citric acid, magnesium oxide, a stabilizer, an antibacterial agent, and a pH adjuster, wherein the antibacterial agent comprises methylparaben and propylparaben in a mass ratio of 15:1-6:1. The present invention has the advantages of high stability and good antibacterial efficacy.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceuticals, and in particular to a compound sodium picosulfate oral solution and a preparation method thereof. Background Art

[0002] Sodium picosulfate is a laxative synthesized by the Italian company De Angeli in 1964. The efficacy of phenolic laxatives is primarily based on free hydroxyl groups. Therefore, the synthesis of these compounds is achieved by adding other groups to the hydroxyl groups. The efficacy of a large number of these compounds has been evaluated, and studies have shown that these compounds rarely experience gastrointestinal side effects. Their laxative effect is exerted by hydrolytic enzymes produced by colonic flora, producing diphenols. Sodium picosulfate exhibits excellent laxative effects.

[0003] Sodium picosulfate acts in the colon. Hydrolyzed by enzymes produced by colonic flora, it produces diphenolic compounds, its active ingredient. These compounds directly stimulate the intestinal mucosa, promote intestinal motility, and inhibit water absorption in the intestine, resulting in a cathartic effect. Urinary excretion indicates that sodium picosulfate is virtually not absorbed in the gastrointestinal tract, resulting in minimal systemic effects. Its efficacy is unrelated to the plasma concentration of the active ingredient.

[0004] Currently, the marketed products of sodium picosulfate include solutions, tablets, and granules, all of which are gastric-soluble preparations. Sodium picosulfate is extremely unstable to acid and degrades by approximately 29% in 24 hours in artificial simulated gastric fluid at pH 1.2 at 37°C. The main degradation products are diphenols (impurity B in the European Pharmacopoeia). Although diphenols are active ingredients, they are irritating to the gastrointestinal mucosa above the colon. The onset of action of sodium picosulfate is 6-12 hours after administration. Premature release of the active ingredient can cause adverse reactions such as nausea, vomiting, abdominal borborygmus, abdominal distension, and abdominal pain. Therefore, it is necessary to improve the common gastric-soluble preparations of sodium picosulfate.

[0005] Several batches of existing overseas marketed reference preparations (trade name: Clenpiq, manufacturer: Ferring Pharmaceuticals Inc.) show a pH of around 4.9-5.4. The antibacterial efficacy study, in accordance with the requirements of the Chinese Pharmacopoeia, has certain risks, and the 28-day test results are at the lower limit. Therefore, there is also a certain risk in stability.

[0006] Chinese patent CN106456534B discloses a physically and chemically stable liquid pharmaceutical composition comprising sodium picosulfate, magnesium oxide, citric acid, and malic acid. The composition is actually a compound sodium picosulfate oral solution with a pH range of 4.1 to 5.4. However, the patent does not study the types of antibacterial agents, nor does it study the effects of the raw material dosage ratio on the antibacterial efficacy and stability.

[0007] Chinese patent application CN105456264A discloses a dual-action laxative pharmaceutical composition and its preparation method. The composition comprises the following components: sodium picosulfate, anhydrous magnesium citrate, anhydrous citric acid, potassium bicarbonate, and a flavoring agent. Therefore, the composition does not contain magnesium oxide as an active ingredient, and the effects of pH range and antibacterial agent type on stability and antibacterial efficacy have not been studied.

[0008] Therefore, it is very necessary to develop a compound sodium picosulfate oral solution and a preparation method thereof that can solve the above-mentioned technical problems. Summary of the Invention

[0009] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a compound sodium picosulfate oral solution with high stability and good antibacterial efficacy and a preparation method thereof.

[0010] To address the problems existing in the prior art, the inventors unexpectedly discovered, after extensive research, that sodium picosulfate compound oral solution uses the antibacterial agents methylparaben and propylparaben, adjusts the pH to a range of 5.5-7.0 according to a certain weight ratio, and simultaneously controls the weight ratio of magnesium oxide, stabilizer, and antibacterial agent. This not only improves the stability of the relevant substances in the product, but also significantly enhances the antibacterial efficacy and achieves excellent property stability.

[0011] Specifically, the present invention is achieved through the following technical solutions:

[0012] A compound sodium picosulfate oral solution comprises the following components: sodium picosulfate, anhydrous citric acid, magnesium oxide, a stabilizer, an antibacterial agent and a pH regulator, wherein the antibacterial agent comprises methylparaben and propylparaben, and the mass ratio of the two is 15:1-6:1.

[0013] Preferably, the pH range of the compound sodium picosulfate oral solution is 5.5-7.0.

[0014] Preferably, the weight ratio of magnesium oxide:stabilizer:bacteriostatic agent is 21.875:35:1.3-21.875:72:3.2.

[0015] More preferably, each 100 mL of oral solution contains: 0.0063 g of sodium picosulfate, 2.1875 g of anhydrous citric acid, 7.5 g of magnesium oxide, 3.5-7.2 g of stabilizer, 0.08-0.26 g of chelating agent, 0.12-0.28 g of antibacterial agent, and 0.12-0.25 g of antioxidant.

[0016] Preferably, the stabilizer is at least one of L-malic acid and L-tartaric acid.

[0017] Preferably, the pH regulator is at least one of sodium hydroxide and potassium hydroxide.

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

[0019] (1) Preparation 1: Add magnesium oxide and anhydrous citric acid to purified water and stir to dissolve completely, then add stabilizer and antibacterial agent in sequence. After the addition is completed, add pH regulator to adjust the pH to obtain Preparation 1;

[0020] (2) Preparation 2: Add sodium picosulfate to preparation 1, stir to dissolve evenly, then adjust to volume and filter to obtain the product.

[0021] Preferably, the temperature of the purified water in step (1) is 55-65°C; after the addition is completed, the temperature is maintained at 80-90°C for 10-45 minutes, and then cooled to below 40°C, and a pH regulator is added to adjust the pH.

[0022] Preferably, the filtration in step (2) is followed by filling, with a filling volume of about 160 mL / bottle.

[0023] Preferably, the compound sodium picosulfate oral solution further comprises the following components: at least one of a chelating agent, an antioxidant, a sweetener, a flavoring agent, and an aromatic agent as an inactive ingredient.

[0024] The compound sodium picosulfate oral solution of the present invention is not limited to adding the above-mentioned several types of inactive ingredients.

[0025] More preferably, the compound sodium picosulfate oral solution further comprises the following components: a chelating agent and an antioxidant.

[0026] More preferably, when the compound sodium picosulfate oral solution further comprises a chelating agent, each 100 mL of the oral solution contains: 0.08-0.26 g of the chelating agent.

[0027] More preferably, when the compound sodium picosulfate oral solution further comprises an antioxidant, each 100 mL of the oral solution contains: 0.12-0.25 g of the antioxidant.

[0028] More preferably, the chelating agent is at least one of ethylenediaminetetraacetic acid, disodium edetate, and calcium disodium edetate.

[0029] More preferably, the antioxidant is at least one of sodium metabisulfite, sodium sulfite, sodium bisulfite, and sodium thiosulfate.

[0030] The present invention also relates to a method for preparing the compound sodium picosulfate oral solution, comprising the following steps:

[0031] (1) Preparation 1: Add magnesium oxide and anhydrous citric acid to purified water and stir to dissolve completely, then add stabilizer, antibacterial agent, and chelating agent in sequence. After the addition is completed, add pH regulator to adjust the pH to obtain Preparation 1;

[0032] (2) Preparation 2: Add antioxidant to Preparation 1 and stir to dissolve evenly, then add sodium picosulfate, stir to dissolve evenly, then adjust the volume and filter to obtain the product.

[0033] More preferably, the compound sodium picosulfate oral solution further comprises the following components: at least one of a sweetener, a flavoring agent, and an aromatic agent.

[0034] The present invention also relates to a method for preparing the compound sodium picosulfate oral solution, comprising the following steps:

[0035] (1) Preparation 1: Magnesium oxide and anhydrous citric acid are added to purified water and stirred to dissolve completely, and then a stabilizer, an antibacterial agent, a chelating agent, and a sweetener and / or a flavoring agent, and / or an aromatic agent are added in sequence. After the addition is completed, a pH regulator is added to adjust the pH to obtain Preparation 1;

[0036] (2) Preparation 2: Add antioxidant to preparation 1, stir and dissolve evenly, then add sodium picosulfate, stir and dissolve evenly, then adjust the volume and filter to obtain the product.

[0037] The present invention also relates to a method for preparing the compound sodium picosulfate oral solution, comprising the following steps:

[0038] (1) Preparation 1: Add magnesium oxide and anhydrous citric acid to purified water and stir to dissolve completely, then add stabilizer, antibacterial agent, and chelating agent in sequence. After the addition is completed, add pH regulator to adjust the pH to obtain Preparation 1;

[0039] (2) Liquid 2: Add antioxidant, sweetener and / or flavoring agent, and / or aromatic agent to liquid 1, stir and dissolve evenly, then add sodium picosulfate, stir and dissolve evenly, then adjust the volume and filter to obtain the product.

[0040] Sweeteners and / or flavoring agents and / or aromatics may be added to the preparation liquid 1 or the preparation liquid 2.

[0041] Preferably, the temperature of the purified water in step (1) is 55-65°C; after the addition is completed, the temperature is maintained at 80-90°C for 10-45 minutes, and then cooled to below 40°C, and a pH regulator is added to adjust the pH.

[0042] Preferably, the filtration in step (2) is followed by filling, with a filling volume of about 160 mL / bottle.

[0043] The beneficial effects of the present invention are:

[0044] (1) The present invention significantly improves the stability of related substances by controlling the pH range of the compound sodium picosulfate oral solution to 5.5-7.0;

[0045] (2) The present invention significantly improves the antibacterial efficacy and stability by controlling the weight ratio of magnesium oxide, stabilizer, and antibacterial agent (methylparaben, propylparaben), as well as the weight ratio of methylparaben and propylparaben in the antibacterial agent;

[0046] (3) The compound sodium picosulfate oral solution of the present invention has higher stability. Its properties and related substances remain stable after being placed at a high temperature of 60°C for 30 days, which is of great significance for improving clinical safety. DETAILED DESCRIPTION

[0047] The present invention will be further described below with reference to specific embodiments, and the advantages and features of the present invention will become clearer as the description proceeds. However, these embodiments are merely exemplary 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 solutions of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, and such modifications and replacements fall within the scope of protection of the present invention.

[0048] The raw material and auxiliary material manufacturers used in the embodiments of the present invention are shown in Table 1.

[0049] Table 1 Information on raw and auxiliary materials used in the examples

[0050] Name of raw materials factory magnesium oxide Hebei Xingtai Metallurgical Magnesium Industry Co., Ltd. Anhydrous citric acid Hunan Huari Pharmaceutical Co., Ltd. L-Malic acid Jiangxi Alpha Hi-Tech Pharmaceutical Co., Ltd. L-Tartaric acid Chengdu Huayi Pharmaceutical Excipients Manufacturing Co., Ltd. Sodium hydroxide Hunan Erkang Pharmaceutical Co., Ltd. Acesulfame potassium Anhui Weiduo Food Ingredients Co., Ltd. Edetate disodium Hunan Erkang Pharmaceutical Co., Ltd. Sodium hydroxide Nanjing Chemical Reagent Co., Ltd. potassium hydroxide Nanjing Chemical Reagent Co., Ltd. Methylparaben Hubei Gedian Renfu Pharmaceutical Excipients Co., Ltd. Propylparaben Hubei Gedian Renfu Pharmaceutical Excipients Co., Ltd. Benzyl alcohol Chengdu Huayi Pharmaceutical Excipients Manufacturing Co., Ltd. Sodium thiosulfate Heilan Chemical Industry Co., Ltd. Sodium metabisulfite Sichuan Jinshan Pharmaceutical Co., Ltd. Sucralose Jiangxi Alpha Hi-Tech Pharmaceutical Co., Ltd. Sodium picosulfate Kreative Organics Private Limited Cranberry flavor Tianning Flavors (Jiangsu) Co., Ltd. Strawberry flavor Tianning Flavors (Jiangsu) Co., Ltd.

[0051] Example 1

[0052] Table 2

[0053]

[0054]

[0055] Preparation method: (1) Preparation 1: Add magnesium oxide and anhydrous citric acid to purified water at about 55-65°C and stir to dissolve completely. Then add stabilizer, antibacterial agent, chelating agent, sweetener, and fragrance in sequence. After adding, maintain 80-90°C for 11 minutes. Adjust pH: After the liquid is cooled to below 40°C, add sodium hydroxide aqueous solution to adjust the solution pH to 5.8. (2) Preparation 2: Add antioxidant. After adding, stir to dissolve evenly. Then add sodium picosulfate and stir to dissolve evenly. Then adjust to volume. (3) Filter. (4) Fill. The filling volume is about 160mL / bottle. The specific formula is shown in Table 2.

[0056] Example 2

[0057] Table 3

[0058]

[0059]

[0060] Preparation method: (1) Solution 1: Add magnesium oxide and anhydrous citric acid to purified water at about 55-65°C and stir to dissolve completely. Then add stabilizer, antibacterial agent, chelating agent, sweetener, and fragrance in sequence. After adding, maintain the temperature at 80-90°C for 45 minutes. Adjust pH: After the solution cools to below 40°C, add sodium hydroxide aqueous solution to adjust the solution pH to 5.5. (2) Solution 2: Add antioxidant. After adding, stir to dissolve uniformly. Then add sodium picosulfate and stir to dissolve uniformly. Then adjust to volume. (3) Filter. (4) Fill. The filling volume is about 160 mL / bottle. The specific formula is shown in Table 3.

[0061] Example 3

[0062] Table 4

[0063]

[0064] Preparation method: (1) Preparation: Add magnesium oxide and anhydrous citric acid to purified water at about 55-65°C and stir to dissolve completely. Then add stabilizer, antibacterial agent, chelating agent, sweetener, and fragrance in sequence. After adding, maintain the temperature at 80-90°C for 30 minutes. Adjust pH: After the liquid is cooled to below 40°C, add sodium hydroxide aqueous solution to adjust the solution pH to 6.5. (2) Preparation 2: Add antioxidant. After adding, stir to dissolve evenly. Then add sodium picosulfate and stir to dissolve evenly. Then adjust the volume. (3) Filter. (4) Fill. The filling volume is about 160 mL / bottle. The specific formula is shown in Table 4.

[0065] Example 4

[0066] Table 5

[0067]

[0068] Preparation method: (1) Preparation: Add magnesium oxide and anhydrous citric acid to purified water at about 55-65°C and stir to dissolve completely. Then add stabilizer, antibacterial agent, chelating agent, sweetener, and fragrance in sequence. After adding, maintain the temperature at 80-90°C for 30 minutes. Adjust pH: After the liquid is cooled to below 40°C, add sodium hydroxide aqueous solution to adjust the pH of the solution to 5.5. (2) Preparation 2: Add antioxidant. After adding, stir to dissolve evenly. Then add sodium picosulfate and stir to dissolve evenly. Then adjust the volume. (3) Filter. (4) Fill. The filling volume is about 160mL / bottle. The specific formula is shown in Table 5.

[0069] Example 5

[0070] Table 6

[0071]

[0072] Preparation method: (1) Preparation: Add magnesium oxide and anhydrous citric acid to purified water at about 55-65°C and stir to dissolve completely. Then add stabilizer, antibacterial agent, chelating agent, sweetener, and fragrance in sequence. After adding, maintain the temperature at 80-90°C for 30 minutes. Adjust pH: After the liquid is cooled to below 40°C, add potassium hydroxide aqueous solution to adjust the pH of the solution to 5.9. (2) Preparation 2: Add antioxidant. After adding, stir to dissolve evenly. Then add sodium picosulfate and stir to dissolve evenly. Then adjust the volume. (3) Filter. (4) Fill. The filling volume is about 160 mL / bottle. The specific formula is shown in Table 6.

[0073] Example 6

[0074] Table 7

[0075]

[0076] Preparation method: (1) Preparation: Add magnesium oxide and anhydrous citric acid to purified water at about 55-65°C and stir to dissolve completely. Then add stabilizer, antibacterial agent, chelating agent, sweetener, and fragrance in sequence. After adding, maintain the temperature at 80-90°C for 20 minutes. Adjust pH: After the liquid is cooled to below 40°C, add potassium hydroxide aqueous solution to adjust the pH of the solution to 5.8. (2) Preparation 2: Add antioxidant. After adding, stir to dissolve evenly. Then add sodium picosulfate and stir to dissolve evenly. Then adjust the volume. (3) Filter. (4) Fill. The filling volume is about 160 mL / bottle. The specific formula is shown in Table 7.

[0077] Example 7

[0078] Table 8

[0079]

[0080] Preparation method: (1) Preparation: Add magnesium oxide and anhydrous citric acid to purified water at about 55-65°C and stir to dissolve completely. Then add stabilizer, antibacterial agent, chelating agent, sweetener, and fragrance in sequence. After adding, maintain the temperature at 80-90°C for 30 minutes. Adjust pH: After the liquid is cooled to below 40°C, add potassium hydroxide aqueous solution to adjust the pH of the solution to 6.2. (2) Preparation 2: Add antioxidant. After adding, stir to dissolve evenly. Then add sodium picosulfate and stir to dissolve evenly. Then adjust the volume. (3) Filter. (4) Fill. The filling volume is about 160 mL / bottle. The specific formula is shown in Table 8.

[0081] Example 8

[0082] Table 9

[0083]

[0084] Preparation method: (1) Preparation: Add magnesium oxide and anhydrous citric acid to purified water at about 55-65°C and stir to dissolve completely. Then add stabilizer, antibacterial agent, chelating agent, sweetener, and fragrance in sequence. After adding, maintain the temperature at 80-90°C for 30 minutes. Adjust pH: After the liquid is cooled to below 40°C, add sodium hydroxide aqueous solution to adjust the pH of the solution to 6.9. (2) Preparation 2: Add antioxidant. After adding, stir to dissolve evenly. Then add sodium picosulfate and stir to dissolve evenly. Then adjust the volume. (3) Filter. (4) Fill. The filling volume is about 160 mL / bottle. The specific formula is shown in Table 9.

[0085] Comparative Example 1

[0086] The only difference from Example 1 is that methylparaben and propylparaben are replaced by 1.4 g of sodium benzoate.

[0087] Comparative Example 2

[0088] The only difference from Example 1 is that the pH value is 5.4.

[0089] Comparative Example 3

[0090] The only difference from Example 1 is that the pH value is 7.1.

[0091] Comparative Example 4

[0092] The only difference from Example 1 is that the amounts of methylparaben and propylparaben are 1.6 g and 0.1 g, respectively, with a weight ratio of 16:1.

[0093] Comparative Example 5

[0094] The only difference from Example 1 is that the amounts of methylparaben and propylparaben are 1.18 g and 0.22 g, respectively, with a weight ratio of 5.5:1.

[0095] Comparative Example 6

[0096] The only difference from Example 4 is that the amount of magnesium oxide is 21.875 g, the amount of stabilizer is 35 g, the amount of antibacterial agent is 1.28 (1.2 g of methylparaben and 0.08 g of propylparaben), and the weight ratio of magnesium oxide, stabilizer and antibacterial agent is 21.875:35:1.28.

[0097] Comparative Example 7

[0098] The only difference from Example 4 is that the amount of magnesium oxide is 21.875 g, the amount of stabilizer is 35 g, the amount of antibacterial agent is 1.28 g (1.22 g of methylparaben and 0.1 g of propylparaben), and the weight ratio of magnesium oxide, stabilizer and antibacterial agent is 21.875:35:1.32.

[0099] Comparative Example 8

[0100] The only difference from Example 4 is that the amount of magnesium oxide is 21.875 g, the amount of L-tartaric acid is 34 g, the amount of antibacterial agent is 1.3 g (1.22 g of methylparaben and 0.08 g of propylparaben), and the weight ratio of magnesium oxide, stabilizer, and antibacterial agent is 21.875:34:1.3.

[0101] Comparative Example 9

[0102] The only difference from Example 4 is that the amount of magnesium oxide is 21.875 g, the stabilizer is L-malic acid, the amount is 34 g, the amount of antibacterial agent is 1.3 g (1.22 g of methylparaben and 0.08 g of propylparaben), and the weight ratio of magnesium oxide, stabilizer and antibacterial agent is 21.875:34:1.3.

[0103] Comparative Example 10

[0104] The only difference from Example 7 is that the stabilizer is L-malic acid in an amount of 73 g, and the weight ratio of magnesium oxide, stabilizer, and antibacterial agent is 21.875:73:3.2.

[0105] Comparative Example 11

[0106] The only difference from Example 7 is that the amount of the antibacterial agent is 3.25 g (3 g of methylparaben, 0.25 g of propylparaben), and the weight ratio of magnesium oxide, stabilizer, and antibacterial agent is 21.875:72:3.25.

[0107] Comparative Example 12

[0108] The only difference from Example 7 is that the amount of the antibacterial agent is 3.45 g (3.25 g of methylparaben and 0.2 g of propylparaben), and the weight ratio of magnesium oxide, stabilizer, and antibacterial agent is 21.875:72:3.45.

[0109] Comparative Example 13

[0110] The only difference from Example 1 is that the amount of chelating agent used is 0.7 g, accounting for 0.07%.

[0111] Comparative Example 14

[0112] The only difference from Example 1 is that the amount of chelating agent used is 2.7 g, accounting for 0.27%.

[0113] Comparative Example 15

[0114] The only difference from Example 1 is that the amount of antioxidant used is 2.6 g, accounting for 0.26%.

[0115] Comparative Example 16

[0116] The only difference from Example 1 is that the amount of antioxidant used is 1.1 g, accounting for 0.11%.

[0117] Comparative Example 17

[0118] The only difference with Example 1 is that the antibacterial agent is 1.4g methylparaben.

[0119] Comparative Example 18

[0120] The only difference from Example 1 is that the antibacterial agent is 1.4 g of propylparaben.

[0121] Evaluation of the results of each embodiment and comparative example

[0122] The oral liquids obtained in Examples 1 to 8 and Comparative Examples 1 to 18 were compared with a marketed control preparation (Batch No.: U04004AA, Manufacturer: Ferring Pharmaceuticals Inc) for related substances, property stability, and antibacterial efficacy. Specific standards are shown in Table 10, and the results are shown in Tables 11 to 14.

[0123] The stability testing method of the compound picocyanate oral solution provided by the present invention is as follows: samples of the reference preparation, each embodiment, and each comparative example are placed at a high temperature of 60° C. for 10 days, 20 days, and 30 days to detect changes in properties and related substances.

[0124] The antibacterial efficacy detection method of the compound Pico oral solution provided by the present invention is as follows: the reference preparation, each embodiment, and each comparative example are subjected to bacterial culture and detection for 0 days, 14 days, and 28 days, with reference to the Chinese Pharmacopoeia 2020 edition, and the judgment criteria are as follows:

[0125] Table 10 Criteria for judging the antibacterial efficacy of oral liquids

[0126]

[0127] Table 11 High temperature 60°C stability results of Examples 1-8

[0128]

[0129]

[0130] Table 12 High temperature 60°C stability results of reference preparations and comparative examples 1-18

[0131]

[0132]

[0133]

[0134] Table 13 Antibacterial efficacy results of Examples 1 to 8

[0135]

[0136]

[0137] *Note: All results meet the requirements.

[0138] Table 14 Antibacterial efficacy results of reference preparations and comparative examples 1 to 18

[0139]

[0140]

[0141] *Note: To save costs, the antibacterial efficacy of comparative examples 14, 15, and 16, which obviously did not meet the requirements, was not tested.

[0142] Among Examples 1-8, Example 1 is the best example.

[0143] The stability of the reference preparation meets the requirements, and its antibacterial efficacy also meets the requirements, but is at the lower limit;

[0144] In Comparative Example 1, the antibacterial agent is an example of another commonly used antibacterial agent. The antibacterial efficacy of the obtained preparation sample did not meet the requirements and the properties were also defective;

[0145] Comparative Examples 2-3 are examples outside the pH range of 5.5-7.0. The antibacterial efficacy or stability of related substances of the obtained preparation samples did not meet the requirements to varying degrees.

[0146] Comparative Examples 4-5 are examples where the weight ratio of the antibacterial agents methylparaben:propylparaben is outside the range, and at least one of the antibacterial efficacy and property stability of the obtained preparation samples does not meet the requirements.

[0147] Comparative Examples 6-12 are examples where the weight ratio of magnesium oxide:stabilizer:antibacterial agent is outside the range, and at least one of the antibacterial efficacy and stability of the obtained preparation samples is poor.

[0148] Examples 13-14 are examples where the chelating agent dosage is outside the range, and Comparative Examples 15-16 are examples where the oxidant dosage is outside the range. The resulting preparation samples have at least one of poor antibacterial efficacy and stability.

[0149] The antibacterial agents in Comparative Examples 17-18 are methylparaben and propylparaben, which are used alone, and the antibacterial efficacy does not meet the requirements.

[0150] The above detailed description is a specific description of one feasible embodiment of the present invention. This embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or modification that does not depart from the present invention should be included in the scope of the technical solution of the present invention.

Claims

1. A compound sodium picosulfate oral solution, characterized in that: The invention comprises the following components: sodium picosulfate, anhydrous citric acid, magnesium oxide, a stabilizer, an antibacterial agent, a pH regulator, a chelating agent and an antioxidant, wherein the antibacterial agent comprises methylparaben and propylparaben, and the mass ratio of the two is 6:1-15:1; The weight ratio of magnesium oxide: stabilizer: antibacterial agent is 21.875:35:1.3-21.875:72:3.2; Each 100 mL of oral solution contains: chelating agent 0.08-0.26 g, antioxidant 0.12-0.25 g; The pH range of the compound sodium picosulfate oral solution is 5.5-7.

0.

2. The compound sodium picosulfate oral solution according to claim 1, characterized in that Each 100 mL of oral solution contains: sodium picosulfate 0.0063 g, anhydrous citric acid 2.1875 g, magnesium oxide 7.5 g, stabilizer 3.5-7.2 g, chelating agent 0.08-0.26 g, antibacterial agent 0.12-0.28 g, and antioxidant 0.12-0.25 g.

3. The compound sodium picosulfate oral solution according to any one of claims 1-2, characterized in that The stabilizer is at least one of L-malic acid and L-tartaric acid, and the pH adjuster is at least one of sodium hydroxide and potassium hydroxide.

4. The compound sodium picosulfate oral solution according to any one of claims 1-2, characterized in that The compound sodium picosulfate oral solution further comprises the following components: at least one of a sweetener, a flavoring agent and an aromatic agent.

5. The compound sodium picosulfate oral solution according to claim 1, characterized in that The chelating agent is at least one of ethylenediaminetetraacetic acid, disodium edetate, and calcium disodium edetate; and the antioxidant is at least one of sodium metabisulfite, sodium sulfite, sodium bisulfite, and sodium thiosulfate.

6. The method for preparing the compound sodium picosulfate oral solution according to any one of claims 1 to 3, characterized in that: The steps include: (1) Preparation 1: Add magnesium oxide and anhydrous citric acid to purified water and stir to dissolve completely, then add stabilizer, antibacterial agent, and chelating agent in sequence. After the addition is completed, add pH regulator to adjust the pH to obtain Preparation 1; (2) Liquid 2: Add antioxidant to liquid 1 and stir to dissolve evenly. Then add sodium picosulfate and stir to dissolve evenly. Then adjust the volume and filter to obtain the product.

7. The preparation method according to claim 6, characterized in that The temperature of the purified water in step (1) is 55-65°C. After the addition is completed, the temperature is maintained at 80-90°C for 10-45 minutes, and then cooled to below 40°C. A pH regulator is added to adjust the pH.

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