Liquid composition containing ceftizoxime sodium microcapsules as well as preparation method and application of liquid composition

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a liquid composition containing ceftizoxime sodium microcapsules as well as a preparation method and application of the liquid composition. The liquid composition containing the ceftizoxime sodium micro-capsule, provided by the invention, comprises the ceftizoxime sodium micro-capsule, sodium carboxymethyl cellulose and a buffering agent, the pH value of the liquid composition is 7-9; the ceftizoxime sodium micro-capsule comprises a capsule core and a capsule wall material wrapping the capsule core, and the capsule core comprises ceftizoxime sodium. The liquid composition containing the ceftizoxime sodium micro-capsules is stable in property, long in storage period after being prepared, capable of being used at any time, free of fresh preparation and quite convenient to use clinically.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to a liquid composition containing cefuroxime sodium microcapsules, a preparation method and an application thereof. Background Art

[0002] Cefuroxime sodium, chemical name: (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-8-oxo-5-thia-1-aminobicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt, is a semi-synthetic third-generation cephalosporin with a broad antibacterial spectrum, similar to cefotaxime. It has moderate antibacterial effects on some Gram-positive bacteria; it has stronger antibacterial effects on Gram-negative bacteria; some Gram-negative bacteria resistant to first-generation cephalosporins and gentamicin may also be sensitive to Cefuroxime sodium; but fecal streptococci and methicillin-resistant Staphylococci are not sensitive to Cefuroxime sodium. Cefuroxime sodium is mainly used to treat various infections caused by sensitive bacteria, including sepsis, respiratory system infections, urinary and reproductive system infections, pleurisy, peritonitis, cholecystitis, intrauterine infection, adnexitis, meningitis, and secondary infections such as trauma and burns; in addition, because cefuroxime sodium is mainly excreted through the kidneys, it is particularly effective in treating pyelonephritis and urinary tract infections.

[0003] The ceftizoxime sodium preparations in the prior art are all lyophilized powders, which are extremely unstable after being prepared into liquid compositions. They should not be placed at room temperature for more than 7 hours, and should not be placed in a refrigerator for more than 48 hours. They have poor stability. When using the ceftizoxime sodium liquid composition, it needs to be freshly prepared, and the steps are cumbersome. At the same time, the existing ceftizoxime sodium preparations have a poor dissolution rate and dissolve slowly, which brings many inconveniences to clinical use. Summary of the invention

[0004] Therefore, the technical problem to be solved by the present invention is to overcome the defects of the prior art that ceftizoxime sodium is extremely unstable as a liquid preparation, ceftizoxime sodium will degrade, has a short storage time, needs to be prepared immediately before use, causing inconvenience in use, etc., thereby providing a liquid composition containing ceftizoxime sodium microcapsules and a preparation method and application thereof.

[0005] To this end, the present invention provides the following technical solutions.

[0006] The invention provides a liquid composition containing ceftizoxime sodium microcapsules, comprising ceftizoxime sodium microcapsules, sodium carboxymethyl cellulose and a buffer; the pH value of the liquid composition is 7-9; the ceftizoxime sodium microcapsules comprise a capsule core and a capsule material wrapping the capsule core, and the capsule core comprises ceftizoxime sodium.

[0007] In an optional embodiment, the pH of the liquid composition is 7-8;

[0008] In an optional embodiment, the liquid composition further comprises a pH adjuster; the pH adjuster comprises at least one of hydrochloric acid, sodium hydroxide, phosphoric acid, citric acid and acetic acid.

[0009] In an optional embodiment, the mass ratio of the cefuroxime sodium microcapsules to sodium carboxymethyl cellulose is (12-36):(1.5-3).

[0010] In an optional embodiment, the buffer comprises at least one of a phosphate-phosphate buffer, a citric acid-citrate buffer, and an acetic acid-acetate buffer;

[0011] In an optional embodiment, the mass ratio of the cefuroxime sodium microcapsules to the buffer is (12-36):(3.28-15.48).

[0012] In an optional embodiment, the capsule material comprises an inner coating and an outer coating, wherein the inner coating wraps the capsule core; the inner coating comprises carboxymethyl dextran; and the outer coating comprises monolinoleyl glycerol;

[0013] Preferably, the mass ratio of cefuroxime sodium, carboxymethyl dextran and monolinoleyl glycerol is (1-3):(0.5-1.5):(0.5-1.5);

[0014] Preferably, the particle size of the cefuroxime sodium is 80-120 μm;

[0015] Preferably, the monolinoleic acid glyceride includes at least one of monolinoleic acid glyceride, monolinoleic acid diglyceride and monolinoleic acid triglyceride;

[0016] Preferably, the carboxymethyl glucan is carboxymethylated yeast glucan;

[0017] Preferably, the outer coating further comprises at least one of an antioxidant and a suspending agent.

[0018] In an optional embodiment, the monolinoleylglycerol comprises monolinoleylglycerol, monolinoleylglycerol dilinoleylglycerol and monolinoleylglycerol trilinoleylglycerol in a volume ratio of (2-2.5):(1-1.5):(1-1.5);

[0019] In an optional embodiment, the mass ratio of the monolinoleyl glyceride, the antioxidant and the suspending agent is (0.5-1.5):(0.2-0.6):(0.2-0.6);

[0020] In an optional embodiment, the antioxidant includes at least one of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butylhydroquinone (TBHQ) and vitamin E;

[0021] Preferably, the antioxidant is vitamin E;

[0022] In an optional embodiment, the suspending agent includes at least one of sodium carboxymethylcellulose, dimethicone, carbomer and Tween 80;

[0023] Preferably, the suspending agent is Tween 80.

[0024] The present invention also provides a method for preparing a liquid composition containing cefuroxime sodium microcapsules, comprising the following steps:

[0025] Cefuroxime sodium microcapsules and a buffer are prepared into a solution A; sodium carboxymethyl cellulose is prepared into a solution B; the solution A and the solution B are mixed and the pH is adjusted to 7-9.

[0026] In an optional embodiment, the pH is 7-8.

[0027] In an optional embodiment, the pH of solution A is 6-9.

[0028] The preparation method of the cefuroxime sodium microcapsules comprises the following steps:

[0029] (1) preparing a carboxymethyl dextran solution, and spraying the carboxymethyl dextran solution on cefuroxime sodium by a spraying method to obtain a pre-microcapsule product;

[0030] (2) preparing a monolinoleic acid glyceryl solution, and spraying the monolinoleic acid glyceryl solution on the pre-microcapsule product by a spraying method to obtain cefuroxime sodium microcapsules.

[0031] In an optional embodiment, the step (1) further comprises suspending and fluidizing the cefuroxime sodium at 30-55° C. before the spraying;

[0032] In an optional embodiment, the suspension fluidization of cefuroxime sodium is carried out under hot air;

[0033] In an optional embodiment, in step (1), the concentration of the carboxymethyl dextran solution is 10-20wt%;

[0034] The solvent of the solution is a well-known solvent in the art, such as an organic solvent and water. Considering the safety to the human body, the solvent is preferably water;

[0035] In an optional embodiment, in step (2), the concentration of the monolinoleylglycerol solution is 5-15wt%;

[0036] In an optional embodiment, in the step (1), based on the mass of the ceftizoxime sodium, the mass of the carboxymethyl dextran added per minute is 0.1-0.2 wt %;

[0037] In an optional embodiment, in step (2), based on the mass of the pre-microcapsule product, the mass of the dispersed phase in the monolinoleic acid glyceryl solution added per minute is 0.1-0.2 wt %. It should be noted that the monolinoleic acid glyceryl solution is a dispersion, which includes a dispersed phase and a dispersion medium, and the dispersed phase includes monolinoleic acid glyceryl.

[0038] The dispersion medium of the dispersion is a solvent known in the art, such as an organic solvent and water. Considering the safety to the human body, the dispersion medium is preferably water;

[0039] In an optional embodiment, the monolinoleylglycerol solution further comprises at least one of an antioxidant and a suspending agent. It should be noted that the dispersed phase further comprises at least one of an antioxidant and a suspending agent.

[0040] In an optional embodiment, the step (1) further comprises a first drying step after the spraying;

[0041] In an optional embodiment, the first drying temperature is 30-55°C;

[0042] In an optional embodiment, the first drying time is 30-60s;

[0043] In an optional embodiment, the step (2) further comprises a second drying step after the spraying;

[0044] In an optional embodiment, the second drying temperature is 30-55°C;

[0045] In an optional embodiment, the second drying time is 30-60 seconds.

[0046] The present invention also provides a preparation comprising a liquid composition containing ceftizoxime sodium microcapsules, wherein the preparation comprises the above-mentioned liquid composition containing ceftizoxime sodium microcapsules or the liquid composition containing ceftizoxime sodium microcapsules prepared by the above-mentioned preparation method. Preferably, the dosage form of the preparation is selected from injection.

[0047] The technical solution of the present invention has the following advantages:

[0048] 1. The liquid composition containing sodium cefuroxime microcapsules provided by the present invention comprises sodium cefuroxime microcapsules, sodium carboxymethyl cellulose, and a buffer; the pH of the liquid composition is 7-9; the sodium cefuroxime microcapsules comprise a capsule core and a capsule material wrapping the capsule core, and the capsule core comprises sodium cefuroxime. The liquid composition containing sodium cefuroxime microcapsules provided by the present invention has stable properties, a long storage period after preparation, and can be used at any time without fresh preparation, which is very convenient for clinical use. The liquid composition of the present invention comprises sodium cefuroxime microcapsules, sodium carboxymethyl cellulose, and a buffer, and the pH is 7-9. Sodium carboxymethyl cellulose is a high-viscosity liquid within the above pH range and does not precipitate when encountering salt. After sodium cefuroxime is made into a liquid composition, it has high stability, does not need to be prepared immediately, and the liquid composition has good storage stability. The sodium carboxymethyl cellulose in the microcapsule of the present invention can be combined with the sodium cefuroxime microcapsules to form mixed micelles in the human body, ensuring that the drug is stable in the body and better exerting its efficacy. In the prior art, when ceftizoxime sodium is made into a liquid preparation, the stability is greatly reduced, the performance of ceftizoxime sodium itself cannot be brought into play, and the drug utilization rate is low. The present invention can solve the problem of greatly reduced stability when ceftizoxime sodium is made into a liquid preparation in the prior art, and can be used at any time without fresh preparation, which can ensure that the liquid preparation will not have problems such as sedimentation and precipitation, and can fully utilize the drug properties.

[0049] 2. The preparation method of the liquid composition containing ceftizoxime sodium microcapsules provided by the present invention, the ceftizoxime sodium microcapsules and the buffer are made into solution A, and the sodium carboxymethyl cellulose is made into solution B; then the solution A and the solution B are mixed, the stability is better, and the direct mixing of the sodium carboxymethyl cellulose and the ceftizoxime sodium microcapsules to avoid destroying the microcapsule structure; the pH value of the solution A is further preferably 6-9, and the mixing effect is better when it is subsequently mixed with sodium carboxymethyl cellulose. The pH of the liquid composition provided by the present invention is 7-9, and within this range, at least one of sodium carboxymethyl cellulose, dimethicone, carbomer and Tween 80 can be used as a suspending agent, which has a wide range of applications and is easy to prepare. DETAILED DESCRIPTION

[0050] The following examples are provided for a better understanding of the present invention, but are not intended to limit the best mode of implementation, nor to limit the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior arts shall fall within the protection scope of the present invention.

[0051] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in the field can be used. If no manufacturer is specified for the reagents or instruments used, they are all conventional reagent products that can be obtained commercially.

[0052] The cefuroxime sodium microcapsules used in the following examples were prepared by the following method:

[0053] (1) 125 g of cefuroxime sodium is placed in a bottom-spray fluidized bed, hot air is introduced, and the hot air temperature is controlled to be 30° C. to suspend and fluidize the cefuroxime sodium; 125 g of carboxymethyl dextran is mixed with 500 mL of water, atomized through the nozzle of the bottom-spray fluidized bed, and continuously added to the fluidized bed. The mass of carboxymethyl dextran sprayed per minute is 0.1 to 0.2 wt % based on the mass of cefuroxime sodium; after spraying, hot air drying is performed at 30° C. for 30 to 60 s to obtain a pre-microcapsule product.

[0054] (2) 125 g of monolinoleyl glycerol, 50 g of Tween 80, 50 g of vitamin E and 200 mL of water were mixed into a solution, atomized through a nozzle of a bottom spray fluidized bed, and continuously added into the fluidized bed. The total mass of monolinoleyl glycerol, Tween 80 and vitamin E in the solution sprayed per minute was 0.1-0.2 wt % based on the mass of the previous microcapsule product. After the spraying was completed, hot air drying was used at 30° C. for 30-60 s, and the material was cooled to obtain cefuroxime sodium microcapsules.

[0055] Example 1

[0056] This embodiment provides a method for preparing a liquid composition containing ceftizoxime sodium microcapsules. The raw materials and dosage of the liquid composition containing ceftizoxime sodium microcapsules are shown in Table 1.

[0057] Table 1

[0058] composition Dosage Cefuroxime Sodium Microcapsules 60g Sodium acetate 32.8g Sodium Carboxymethyl Cellulose 7.5g Acetic acid / sodium hydroxide Moderate water Add to 500ml

[0059] The preparation method is as follows: (1) dissolving sodium acetate in 50% of the prescribed amount of water, and adjusting the pH to 6.0-9.0 using acetic acid and sodium hydroxide;

[0060] (2) dissolving the cefuroxime sodium microcapsules in the solution obtained in step (1);

[0061] (3) dissolving sodium carboxymethyl cellulose in 30% of the prescribed amount of water;

[0062] (4) Mixing the solution obtained in step (2) with the solution obtained in step (3); adjusting the pH to 7.0-8.0, and making up to volume with 20% of the prescribed amount of water.

[0063] Example 2

[0064] This embodiment provides a method for preparing a liquid composition containing ceftizoxime sodium microcapsules. Compared with Example 1, the only difference is that the amount of raw materials used is different. The amount of raw materials used is shown in Table 2.

[0065] Table 2

[0066] composition Dosage Cefuroxime Sodium Microcapsules 180g Sodium acetate 49.2g Sodium Carboxymethyl Cellulose 15g Acetic acid / sodium hydroxide Moderate water Add to 500ml

[0067] Example 3

[0068] This embodiment provides a method for preparing a liquid composition containing ceftizoxime sodium microcapsules. Compared with Example 1, the only difference is that the amount of raw materials used is different. The amount of raw materials used is shown in Table 3.

[0069] Table 3

[0070] composition Dosage Cefuroxime Sodium Microcapsules 60g Sodium Citrate 51.6g Sodium Carboxymethyl Cellulose 7.5g Citric Acid / Sodium Hydroxide Moderate water Add to 500ml

[0071] Example 4

[0072] This embodiment provides a method for preparing a liquid composition containing ceftizoxime sodium microcapsules. Compared with Example 1, the only difference is that the amount of raw materials used is different. The amount of raw materials used is shown in Table 4.

[0073] Table 4

[0074] composition Dosage Cefuroxime Sodium Microcapsules 60g Sodium acetate 4.1g Sodium Carboxymethyl Cellulose 7.5g Acetic acid / sodium hydroxide Moderate water Add to 500ml

[0075] Example 5

[0076] This embodiment provides a method for preparing a liquid composition containing ceftizoxime sodium microcapsules. Compared with Example 1, the only difference is that the amount of raw materials used is different. The amount of raw materials used is shown in Table 5.

[0077] Table 5

[0078] composition Dosage Cefuroxime Sodium Microcapsules 60g Sodium acetate 123g Sodium Carboxymethyl Cellulose 7.5g Acetic acid / sodium hydroxide Moderate water Add to 500ml

[0079] Example 6

[0080] This embodiment provides a method for preparing a liquid composition containing ceftizoxime sodium microcapsules. Compared with Example 1, the only difference is that the amount of raw materials used is different. The amount of raw materials used is shown in Table 6.

[0081] Table 6

[0082] composition Dosage Cefuroxime Sodium Microcapsules 60g Sodium acetate 4.1g Sodium Carboxymethyl Cellulose 5g Acetic acid / sodium hydroxide Moderate water Add to 500ml

[0083] Example 7

[0084] This embodiment provides a method for preparing a liquid composition containing ceftizoxime sodium microcapsules. Compared with Example 1, the only difference is that the amount of raw materials used is different. The amount of raw materials used is shown in Table 7.

[0085] Table 7

[0086] composition Dosage Cefuroxime Sodium Microcapsules 60g Sodium acetate 4.1g Sodium Carboxymethyl Cellulose 20g Acetic acid / sodium hydroxide Moderate water Add to 500ml

[0087] Comparative Example 1

[0088] This comparative example provides a method for preparing a liquid composition containing ceftizoxime sodium microcapsules. Compared with Example 1, the only difference is that step (4) is different, and the pH is adjusted to 6.0 instead of adjusting the pH to 7.0-8.0 in Example 1.

[0089] Table 8

[0090] composition Dosage Cefuroxime Sodium Microcapsules 60g Sodium acetate 32.8g Sodium Carboxymethyl Cellulose 7.5g Acetic acid / sodium hydroxide Moderate water Add to 500ml

[0091] Comparative Example 2

[0092] This comparative example provides a method for preparing a liquid composition containing ceftizoxime sodium microcapsules. Compared with Example 1, the only difference is that step (4) is different, and the pH is adjusted to 10 instead of adjusting the pH to 7.0-8.0 in Example 1.

[0093] Table 9

[0094] composition Dosage Cefuroxime Sodium Microcapsules 60g Sodium acetate 32.8g Sodium Carboxymethyl Cellulose 7.5g Acetic acid / sodium hydroxide Moderate water Add to 500ml

[0095] Comparative Example 3

[0096] This comparative example provides a method for preparing a liquid composition containing ceftizoxime sodium microcapsules. Compared with Example 1, the only difference is that glycerol is used instead of sodium carboxymethyl cellulose.

[0097] Table 10

[0098]

[0099]

[0100] Comparative Example 4

[0101] This comparative example provides a method for preparing a liquid composition containing ceftizoxime sodium microcapsules. Compared with Example 1, the only difference is that gum arabic is used instead of sodium carboxymethyl cellulose.

[0102] Table 11

[0103] composition Dosage Cefuroxime Sodium Microcapsules 60g Sodium acetate 32.8g Gum Arabic 7.5g Acetic acid / sodium hydroxide Moderate water Add to 500ml

[0104] Note: In Table 1-11, “ / ” means “and”.

[0105] Experimental Example 1

[0106] In this experimental example, the liquid composition containing cefuroxime sodium microcapsules prepared in Examples 1-7 and Comparative Examples 1-4 was subjected to a sedimentation volume ratio test and a redispersibility test, as follows.

[0107] Sedimentation volume ratio inspection: record the height of the suspension before the liquid composition settles as H0, let it stand for 3 hours, and then record the height of the sedimentation surface after the liquid composition settles as H, and calculate the sedimentation volume ratio F, the formula is as follows:

[0108] F = (H / H0) × 100%;

[0109] The calculated F of Examples 1-7 is 99.5%, 99%, 98%, 96%, 96.5%, 93%, and 97%, respectively, which meets the requirement of the Chinese Pharmacopoeia that the sedimentation volume ratio should be 90% when the sedimentation time is 3 hours. The F of Comparative Examples 1-4 is 72%, 73%, 66%, and 64%, respectively.

[0110] Redispersibility test: Add the liquid composition into a 100 ml stoppered measuring cylinder, stopper it tightly, and place it for 14 days for flocculation. Then, invert the measuring cylinder and turn it over (shake evenly, one inversion and one forward rotation counts as one time). Observe whether there is precipitation at the bottom of the measuring cylinder, and record the number of inversions required for complete suspension.

[0111] After the samples were allowed to settle for 14 days, Examples 1-7 required inverting the barrel for remixing 2 times, 2 times, 3 times, 6 times, 5 times, 5 times, and 4 times, respectively; while Comparative Examples 1-4 required inverting the barrel for remixing 12 times, 10 times, 10 times, and 7 times, respectively.

[0112] In summary, the present invention regulates the pH of the liquid composition to 7-9, which helps the ceftizoxime sodium liquid preparation to be placed for a long time without precipitation and other problems. Regulating the mass ratio of ceftizoxime sodium microcapsules to sodium carboxymethyl cellulose to (12-36): (1.5-3) and the mass ratio of the ceftizoxime sodium microcapsules to the buffer to (12-36): (3.28-15.48) helps to further improve the storage stability of the liquid preparation and reduce the precipitation, sedimentation and other problems of the liquid preparation.

[0113] Experimental Example 2

[0114] In this experimental example, the particle size of the liquid composition containing cefuroxime sodium microcapsules prepared in Examples 1-7 and Comparative Examples 1-4 was measured using a microscopic image analyzer. The results are shown in Table 12.

[0115] Table 12

[0116]

[0117] It can be seen from Table 12 that the liquid composition containing cefuroxime sodium microcapsules prepared in the present invention has a small particle size and good injectability.

[0118] Experimental Example 3

[0119] In this experimental example, an accelerated stability test was conducted on the liquid composition containing cefuroxime sodium microcapsules prepared in Examples 1-7 and Comparative Examples 1-4, as follows.

[0120] (1) The liquid composition containing ceftizoxime sodium microcapsules prepared in Examples 1-7 and Comparative Examples 1-4 and the commercially available preparation (manufacturer: Southwest Pharmaceutical Co., Ltd.) were placed in vials and placed in an acceleration box (40°C, 75% humidity). The samples were subjected to product stability tests for 1 month, 2 months, and 3 months. After the expiration, the ceftizoxime sodium content in the samples was detected by the parameters in Table 13 of the high performance liquid chromatography method; the impurity content in the samples was detected by the parameters in Table 14 of the high performance liquid chromatography method; and the retention rates of ceftizoxime sodium and impurities were calculated. The results are shown in Tables 16-17.

[0121] Table 13 HPLC parameters 1 Note: This table is used to detect the content of cefuroxime sodium.

[0122] Table 14 HPLC parameters 2

[0123]

[0124]

[0125] Note: This table is used to detect the content of impurities.

[0126] Table 15

[0127] Time (minutes) Mobile phase A (%) Mobile phase B (%) 0 97 3 10 85 15 20 40 60 25 40 60 26 97 3 35 97 3

[0128] The retention rate of cefuroxime sodium = the content of cefuroxime sodium in each time period of the sample / the detection content in the sample at month 0; the sample at month 0 is the sample just prepared, and the retention rate at month 0 is regarded as 100%.

[0129] Table 16 Retention rate of cefuroxime sodium

[0130] Sample name 1M 2M 3M Example 1 99.1％ 95.7％ 94.9％ Example 2 98.9％ 97.2％ 94.2％ Example 3 99.5％ 97.8％ 95.1％ Example 4 99.4％ 96.6％ 94.1％ Example 5 97.2％ 95.3％ 94.0％ Example 6 96.0％ 95.8％ 93.2％ Example 7 98.7％ 96.4％ 93.8％ Comparative Example 1 85.5％ 66.3％ 46.6％ Comparative Example 2 83.9％ 64.1％ 43.8％ Comparative Example 3 75.2％ 49.3％ 35.6％ Comparative Example 4 82.9％ 71.2％ 60.4％ Commercially available samples 98.5％ 96.8％ 93.2％

[0131] Note: 1M, 2M and 3M correspond to the test results after the samples have been stored for 1 month, 2 months and 3 months respectively.

[0132] Table 17 Retention rate of impurities

[0133] Sample name 1M 2M 3M Example 1 0.11％ 0.26％ 0.38％ Example 2 0.14％ 0.19％ 0.41％ Example 3 0.09％ 0.20％ 0.32％ Example 4 0.06％ 0.24％ 0.48％ Example 5 0.16％ 0.20％ 0.39％ Example 6 0.20％ 0.32％ 0.58％ Example 7 0.13％ 0.36％ 0.60％ Comparative Example 1 3.15％ 9.33％ 12.55％ Comparative Example 2 4.07％ 11.80％ 14.97％ Comparative Example 3 2.01％ 2.64％ 4.15％ Comparative Example 4 2.12％ 2.25％ 3.39％ Commercially available samples 0.21％ 0.34％ 0.65％

[0134] Note: 1M, 2M and 3M correspond to the test results after the samples have been placed for 1 month, 2 months and 3 months respectively.

[0135] As can be seen from Tables 16-17, the liquid composition containing ceftizoxime sodium microcapsules prepared by the method for preparing the liquid composition containing ceftizoxime sodium microcapsules provided by the present invention has good retention rate and stability. At the same time, it contains fewer impurities, which can reduce the probability of adverse reactions and allergic reactions.

[0136] It can be seen from the examples and comparative examples 3-4 that the liquid composition containing ceftizoxime sodium microcapsules prepared by using sodium carboxymethyl cellulose as a suspending agent has better stability, while the retention rate of ceftizoxime sodium is greatly reduced in the liquid composition prepared by using glycerol or gum arabic.

[0137] It can be seen from the examples and comparative examples 1-2 that the liquid composition containing ceftizoxime sodium microcapsules prepared by the present invention has better stability at a pH value of 7-9. When the pH value of the comparative example is 6 or 10, the stability of the liquid composition is significantly reduced.

[0138] In summary, the liquid composition containing ceftizoxime sodium microcapsules prepared by the present invention has a small particle size for easy injection and also ensures stability, and the retention rate of ceftizoxime sodium is significantly improved.

[0139] Obviously, the above embodiments are merely examples for the purpose of clear explanation, and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived from these are still within the scope of protection of the invention.

Claims

1. A liquid composition containing cefuroxime sodium microcapsules, characterized in that: The invention comprises ceftizoxime sodium microcapsules, sodium carboxymethyl cellulose and a buffer; the pH value of the liquid composition is 7-9; the ceftizoxime sodium microcapsules comprise a capsule core and a capsule material wrapping the capsule core, and the capsule core comprises ceftizoxime sodium.

2. The liquid composition according to claim 1, characterized in that The pH of the liquid composition is 7-8; and / or, The liquid composition further comprises a pH adjuster; the pH adjuster comprises at least one of hydrochloric acid, sodium hydroxide, phosphoric acid, citric acid and acetic acid.

3. The liquid composition according to claim 1, characterized in that The mass ratio of the cefuroxime sodium microcapsules to sodium carboxymethyl cellulose is (12-36):(1.5-3).

4. The liquid composition according to claim 1, characterized in that The buffer comprises at least one of a phosphate-phosphate buffer, a citric acid-citrate buffer and an acetic acid-acetate buffer; and / or, The mass ratio of the cefuroxime sodium microcapsules to the buffer is (12-36):(3.28-15.48).

5. The liquid composition according to any one of claims 1 to 4, characterized in that The capsule material comprises an inner coating and an outer coating, wherein the inner coating wraps the capsule core; the inner coating comprises carboxymethyl dextran; and the outer coating comprises monolinoleyl glycerol; Preferably, the mass ratio of cefuroxime sodium, carboxymethyl dextran and monolinoleyl glycerol is (1-3):(0.5-1.5):(0.5-1.5); Preferably, the particle size of the cefuroxime sodium is 80-120 μm; Preferably, the monolinoleic acid glyceride includes at least one of monolinoleic acid glyceride, monolinoleic acid diglyceride and monolinoleic acid triglyceride; Preferably, the carboxymethyl glucan is carboxymethylated yeast glucan; Preferably, the outer coating further comprises at least one of an antioxidant and a suspending agent.

6. The liquid composition according to claim 5, characterized in that The monolinoleic acid glyceride comprises monolinoleic acid glyceride, monolinoleic acid diglyceride and monolinoleic acid triglyceride in a volume ratio of (2-2.5):(1-1.5):(1-1.5); and / or, The mass ratio of the monolinoleylglycerol, the antioxidant and the suspending agent is (0.5-1.5):(0.2-0.6):(0.2-0.6); and / or, The antioxidant comprises at least one of butylated hydroxyanisole, butylated hydroxytoluene, tert-butylhydroquinone and vitamin E; and / or, The suspending agent includes at least one of sodium carboxymethylcellulose, dimethicone, carbomer and Tween 80.

7. A method for preparing a liquid composition containing ceftizoxime sodium microcapsules, characterized in that: The steps include: Cefuroxime sodium microcapsules and a buffer are prepared into a solution A; sodium carboxymethyl cellulose is prepared into a solution B; the solution A and the solution B are mixed and the pH value is adjusted to 7-9.

8. The preparation method according to claim 7, characterized in that: The pH is 7-8.

9. The preparation method according to claim 8, characterized in that: The pH of the solution A is 6-9.

10. A preparation comprising a liquid composition containing cefuroxime sodium microcapsules, characterized in that: The preparation comprises the liquid composition containing ceftizoxime sodium microcapsules according to any one of claims 1 to 6 or the liquid composition containing ceftizoxime sodium microcapsules prepared by the preparation method according to any one of claims 7 to 9. Preferably, the dosage form of the preparation is selected from injection.

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