Preparation method of compound gentamicin sulfate slow-release injection based on micro-capsule technology

Abstract

The invention relates to the field of slow-release injection preparation, in particular to a preparation method of a compound gentamicin sulfate slow-release injection based on a micro-capsule technology. The compound gentamicin sulfate sustained-release injection is prepared through a double emulsion method, the modified starch, the polyvinyl alcohol and the sodium stearate are adopted as micro-capsule shells, the micro-capsule shells and the compound gentamicin sulfate form the sustained-release injection, sustained release of drugs can be successfully achieved, drug release is not uniform, and the stability of the drugs is improved.

Description

Technical Field

[0001] The invention relates to the field of sustained-release injection preparation, and in particular to a method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology. Background Art

[0002] Gentomycin sulfate, as an antibiotic widely used in the medical field, has shown remarkable effects in combating Gram-negative and some Gram-positive bacterial infections due to its strong antibacterial ability. However, this drug is not perfect. Its short half-life means that its effective action time in the body is limited, and its high toxicity has become a key factor limiting its long-term use. Long-term or improper use of gentamicin sulfate may not only lead to bacterial resistance, but also cause severe kidney damage, posing a potential threat to the patient's health.

[0003] In order to overcome these defects, researchers are actively exploring new ways to improve the efficacy and safety of gentamicin sulfate, among which the research and development of sustained-release preparations has become an important direction. Although traditional sustained-release preparations can prolong the duration of drug action to a certain extent, they often face problems such as uneven drug release, difficulty in maintaining stable drug efficacy, and poor patient compliance due to the need to take medication frequently. These problems not only affect the treatment effect, but also reduce the patient's medication experience.

[0004] Therefore, it is necessary to develop an innovative sustained-release technology to achieve slow and uniform release of drugs. Summary of the invention

[0005] In view of the existing technical problems, the present invention aims to provide a method for preparing a compound gentamicin sulfate sustained-release injection based on microencapsulation technology. The compound gentamicin sulfate sustained-release injection prepared by this preparation method has good sustained-release properties and effectively realizes the slow and uniform release of the drug.

[0006] The present invention discloses a method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology, and the preparation method comprises the following steps:

[0007] S1 internal phase emulsification: dissolve gentamicin sulfate and antibiotics in water to form a drug-containing aqueous phase; add modified starch and sodium stearate to the drug-containing aqueous phase, stir until uniform, and then use a high-shear emulsification equipment to emulsify the internal phase emulsion to obtain a microemulsion with uniform particle size distribution;

[0008] S2 external phase emulsification: dissolving polyvinyl alcohol in dichloromethane to obtain an external phase solution, slowly dropping the microemulsion prepared in step S1 into the external phase solution for secondary emulsification, and stirring evenly to obtain an O / W / O double emulsion;

[0009] S3 volatilization curing: the O / W / O double emulsion obtained in step S2 is concentrated under reduced pressure, and then coumarin is slowly added dropwise to the concentrated solution. After the addition is completed, the solution is placed in an ultraviolet irradiation device to cause a cross-linking reaction to achieve curing, thereby obtaining a cured microcapsule reaction solution;

[0010] S4 washing, freeze drying and drying: centrifuging the microcapsule reaction solution obtained in step S3 and collecting the microcapsules, washing them with physiological saline for 3 to 5 times, and freeze drying them after washing to obtain composite gentamicin sulfate sustained-release microcapsules;

[0011] S5: Mixing the final microcapsule preparation: Mix the compound gentamicin sulfate sustained-release microcapsules obtained in step S4 with physiological saline, filter after mixing evenly, and collect the filtrate to obtain the compound gentamicin sulfate sustained-release injection.

[0012] Preferably, in the S1 internal phase emulsification step, the concentration of the modified starch is 2-5% g / ml.

[0013] Preferably, in the S1 internal phase emulsification step, the concentration of sodium stearate is 0.1-0.5% g / ml.

[0014] Preferably, in the S1 internal phase emulsification step, the concentration of gentamicin sulfate is 10-20 mg / ml.

[0015] Preferably, in the S1 internal phase emulsification step, the mass ratio of gentamicin sulfate to antibiotic is 1:(0.3-0.8).

[0016] Preferably, in the internal phase emulsification step S1, the internal phase emulsion is emulsified for 50 to 70 minutes.

[0017] Preferably, in the S2 external phase emulsification step, the concentration of the polyvinyl alcohol is 0.8-1.2% g / ml.

[0018] Preferably, in the S2 external phase emulsification step, the secondary emulsification time is 20 to 40 minutes.

[0019] Preferably, in the volatilization and curing step S3, the concentration of the coumarin is 0.005-0.01% g / ml.

[0020] Preferably, in the volatilization and curing step S3, the ultraviolet wavelength of the ultraviolet irradiation equipment is 300 to 500 nm; and the ultraviolet irradiation time is 15 to 30 minutes.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] The invention provides a method for preparing a compound gentamicin sulfate sustained-release injection. Modified starch, polyvinyl alcohol and sodium stearate are used as shell materials for preparing microcapsules, and the shell materials are used to prepare compound gentamicin sulfate sustained-release microcapsules by using a double emulsion method. Ultraviolet curing is then used in the microcapsule curing process, and the microcapsules are finally mixed with physiological saline to form the compound gentamicin sulfate sustained-release injection.

[0023] Modified starch is used as the shell material of the microcapsule, so that the final prepared injection has better biodegradability and sustained release effect; polyvinyl alcohol is used as an emulsifier to help stabilize the formation of the emulsion; sodium stearate is used as an emulsifier to help stabilize the emulsion to form a fat layer; ultraviolet irradiation will trigger a cross-linking reaction to solidify the microcapsule shell and improve its mechanical strength.

[0024] The compound gentamicin sulfate sustained-release injection prepared by the preparation method provided by the invention has good sustained-release performance and realizes slow and uniform release of the drug. DETAILED DESCRIPTION

[0025] 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.

[0026] 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.

[0027] Example 1: A method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology, comprising the following steps:

[0028] S1 internal phase emulsification: dissolve gentamicin sulfate and antibiotics in water to form a drug-containing aqueous phase; wherein the concentration of gentamicin sulfate is 10 mg / ml, and the mass ratio of gentamicin sulfate to antibiotics is 1:0.3; add modified starch and sodium stearate to the drug-containing aqueous phase, the concentration of modified starch is 2% g / ml, and the concentration of sodium stearate is 0.1% g / ml; stir until uniform, and then use a high-shear emulsification equipment to emulsify the internal phase emulsion, and the internal emulsification time is 50 minutes; obtain a microemulsion with uniform particle size distribution.

[0029] S2 external phase emulsification: dissolve polyvinyl alcohol in dichloromethane to obtain an external phase solution, the concentration of polyvinyl alcohol is 0.8% g / ml; slowly add the microemulsion prepared in step S1 dropwise to the external phase solution for secondary emulsification, the stirring speed of the secondary emulsification is 5000 rpm, and the emulsification time is 30 minutes; after the second emulsification, an O / W / O double emulsion is obtained.

[0030] S3 volatilization curing: the O / W / O double emulsion obtained in step S2 is concentrated under reduced pressure, and then coumarin is slowly added dropwise to the concentrate, and the concentration of the added coumarin is 0.005% g / ml; after the dropwise addition is completed, it is placed in an ultraviolet irradiation device, and the ultraviolet wavelength of the ultraviolet irradiation device is set to 300nm; the ultraviolet irradiation time is 15min, and ultraviolet irradiation is performed to cause a cross-linking reaction to achieve curing, and a cured microcapsule reaction liquid is obtained;

[0031] S4 washing, freeze drying and drying: centrifuging the microcapsule reaction solution obtained in step S3 and collecting the microcapsules, washing them with physiological saline for 3 to 5 times, and freeze drying them after washing, the freeze drying temperature is -40°C, and the freeze drying time is 10 hours; obtaining the composite gentamicin sulfate sustained-release microcapsules;

[0032] S5: Mixing of the final microcapsule preparation: The compound gentamicin sulfate sustained-release microcapsules obtained in step S4 are mixed with physiological saline, and after being evenly mixed, the mixture is filtered to collect the filtrate, which is the compound gentamicin sulfate sustained-release injection, and the concentration of the injection is 10 mg / mL.

[0033] Example 2: A method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology, comprising the following steps:

[0034] S1 internal phase emulsification: dissolve gentamicin sulfate and antibiotics in water to form a drug-containing aqueous phase; wherein the concentration of gentamicin sulfate is 12 mg / ml, and the mass ratio of gentamicin sulfate to antibiotics is 1:0.4; add modified starch and sodium stearate to the drug-containing aqueous phase, the concentration of modified starch is 2.5% g / ml, and the concentration of sodium stearate is 0.12% g / ml; stir until uniform, and then use a high-shear emulsification equipment to emulsify the internal phase emulsion, and the internal emulsification time is 55 minutes; obtain a microemulsion with uniform particle size distribution.

[0035] S2 external phase emulsification: dissolve polyvinyl alcohol in dichloromethane to obtain an external phase solution, the concentration of polyvinyl alcohol is 0.9% g / ml; slowly add the microemulsion prepared in step S1 dropwise to the external phase solution for secondary emulsification, the stirring speed of the secondary emulsification is 6000 rpm, and the emulsification time is 25 minutes; after the second emulsification, an O / W / O double emulsion is obtained.

[0036] S3 volatilization curing: the O / W / O double emulsion obtained in step S2 is concentrated under reduced pressure, and then coumarin is slowly added dropwise to the concentrate, and the concentration of the added coumarin is 0.006% g / ml; after the dropwise addition is completed, it is placed in an ultraviolet irradiation device, and the ultraviolet wavelength of the ultraviolet irradiation device is set to 350nm; the ultraviolet irradiation time is 20min, and ultraviolet irradiation is performed to cause a cross-linking reaction to achieve curing, and a cured microcapsule reaction liquid is obtained;

[0037] S4 washing, freeze drying and drying: centrifuging the microcapsule reaction solution obtained in step S3 and collecting the microcapsules, washing them with physiological saline for 3 to 5 times, and freeze drying them after washing, the freeze drying temperature is -45°C, and the freeze drying time is 10 hours; obtaining the composite gentamicin sulfate sustained-release microcapsules;

[0038] S5: Mixing of the final microcapsule preparation: The compound gentamicin sulfate sustained-release microcapsules obtained in step S4 are mixed with physiological saline, and after being evenly mixed, the mixture is filtered to collect the filtrate, which is the compound gentamicin sulfate sustained-release injection, and the concentration of the injection is 10 mg / mL.

[0039] Example 3: A method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology, comprising the following steps:

[0040] S1 internal phase emulsification: dissolve gentamicin sulfate and antibiotics in water to form a drug-containing aqueous phase; wherein the concentration of gentamicin sulfate is 15 mg / ml, and the mass ratio of gentamicin sulfate to antibiotics is 1:0.5; add modified starch and sodium stearate to the drug-containing aqueous phase, the concentration of modified starch is 3% g / ml, and the concentration of sodium stearate is 0.15% g / ml; stir until uniform, and then use a high-shear emulsification equipment to emulsify the internal phase emulsion, and the internal emulsification time is 60 minutes; obtain a microemulsion with uniform particle size distribution.

[0041] S2 external phase emulsification: dissolve polyvinyl alcohol in dichloromethane to obtain an external phase solution, the concentration of polyvinyl alcohol is 1.0% g / ml; slowly add the microemulsion prepared in step S1 dropwise to the external phase solution for secondary emulsification, the stirring speed of the secondary emulsification is 7000 rpm, and the emulsification time is 20 minutes; after the second emulsification, an O / W / O double emulsion is obtained.

[0042] S3 volatilization curing: the O / W / O double emulsion obtained in step S2 is concentrated under reduced pressure, and then coumarin is slowly added dropwise to the concentrate, and the concentration of the added coumarin is 0.008% g / ml; after the dropwise addition is completed, it is placed in an ultraviolet irradiation device, and the ultraviolet wavelength of the ultraviolet irradiation device is set to 400nm; the ultraviolet irradiation time is 25min, and ultraviolet irradiation is performed to cause a cross-linking reaction to achieve curing, and a cured microcapsule reaction liquid is obtained;

[0043] S4 washing, freeze drying and drying: centrifuging the microcapsule reaction solution obtained in step S3 and collecting the microcapsules, washing them with physiological saline for 3 to 5 times, and freeze drying them after washing, the freeze drying temperature is -50°C, and the freeze drying time is 10 hours; obtaining the composite gentamicin sulfate sustained-release microcapsules;

[0044] S5: Mixing of the final microcapsule preparation: The compound gentamicin sulfate sustained-release microcapsules obtained in step S4 are mixed with physiological saline, and after being evenly mixed, the mixture is filtered to collect the filtrate, which is the compound gentamicin sulfate sustained-release injection, and the concentration of the injection is 10 mg / mL.

[0045] Example 4: A method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology, comprising the following steps:

[0046] S1 internal phase emulsification: dissolve gentamicin sulfate and antibiotics in water to form a drug-containing aqueous phase; wherein the concentration of gentamicin sulfate is 17 mg / ml, and the mass ratio of gentamicin sulfate to antibiotics is 1:0.7; add modified starch and sodium stearate to the drug-containing aqueous phase, the concentration of modified starch is 4% g / ml, and the concentration of sodium stearate is 0.17% g / ml; stir until uniform, and then use a high-shear emulsification equipment to emulsify the internal phase emulsion, and the internal emulsification time is 65 minutes; obtain a microemulsion with uniform particle size distribution.

[0047] S2 external phase emulsification: dissolve polyvinyl alcohol in dichloromethane to obtain an external phase solution, the concentration of polyvinyl alcohol is 1.1% g / ml; slowly add the microemulsion prepared in step S1 dropwise to the external phase solution for secondary emulsification, the stirring speed of the secondary emulsification is 8000 rpm, and the emulsification time is 15 minutes; after the second emulsification, an O / W / O double emulsion is obtained.

[0048] S3 volatilization curing: the O / W / O double emulsion obtained in step S2 is concentrated under reduced pressure, and then coumarin is slowly added dropwise to the concentrate, and the concentration of the added coumarin is 0.009% g / ml; after the dropwise addition is completed, it is placed in an ultraviolet irradiation device, and the ultraviolet wavelength of the ultraviolet irradiation device is set to 450nm; the ultraviolet irradiation time is 30min, and ultraviolet irradiation is performed to cause a cross-linking reaction to achieve curing, and a cured microcapsule reaction liquid is obtained;

[0049] S4 washing, freeze drying and drying: centrifuging the microcapsule reaction solution obtained in step S3 and collecting the microcapsules, washing them with physiological saline for 3 to 5 times, and freeze drying them after washing, the freeze drying temperature is -60°C, and the freeze drying time is 10 hours; obtaining the composite gentamicin sulfate sustained-release microcapsules;

[0050] S5: Mixing of the final microcapsule preparation: The compound gentamicin sulfate sustained-release microcapsules obtained in step S4 are mixed with physiological saline, and after being evenly mixed, the mixture is filtered to collect the filtrate, which is the compound gentamicin sulfate sustained-release injection, and the concentration of the injection is 10 mg / mL.

[0051] Example 5: A method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology, comprising the following steps:

[0052] S1 internal phase emulsification: dissolve gentamicin sulfate and antibiotics in water to form a drug-containing aqueous phase; wherein the concentration of gentamicin sulfate is 20 mg / ml, and the mass ratio of gentamicin sulfate to antibiotics is 1:0.8; add modified starch and sodium stearate to the drug-containing aqueous phase, the concentration of modified starch is 5% g / ml, and the concentration of sodium stearate is 0.2% g / ml; stir until uniform, and then use a high-shear emulsification equipment to emulsify the internal phase emulsion, and the internal emulsification time is 70 minutes; obtain a microemulsion with uniform particle size distribution.

[0053] S2 external phase emulsification: dissolve polyvinyl alcohol in dichloromethane to obtain an external phase solution, the concentration of polyvinyl alcohol is 1.2% g / ml; slowly add the microemulsion prepared in step S1 dropwise to the external phase solution for secondary emulsification, the stirring speed of the secondary emulsification is 9000 rpm, and the emulsification time is 15 minutes; after the second emulsification, an O / W / O double emulsion is obtained.

[0054] S3 volatilization curing: the O / W / O double emulsion obtained in step S2 is concentrated under reduced pressure, and then coumarin is slowly added dropwise to the concentrate, and the concentration of the added coumarin is 0.01% g / ml; after the dropwise addition is completed, it is placed in an ultraviolet irradiation device, and the ultraviolet wavelength of the ultraviolet irradiation device is set to 500nm; the ultraviolet irradiation time is 30min, and ultraviolet irradiation is performed to cause a cross-linking reaction to achieve curing, and a cured microcapsule reaction liquid is obtained;

[0055] S4 washing, freeze drying and drying: centrifuging the microcapsule reaction solution obtained in step S3 and collecting the microcapsules, washing them with physiological saline for 3 to 5 times, and freeze drying them after washing, the freeze drying temperature is -80°C, and the freeze drying time is 10 hours; obtaining the composite gentamicin sulfate sustained-release microcapsules;

[0056] S5: Mixing of the final microcapsule preparation: The compound gentamicin sulfate sustained-release microcapsules obtained in step S4 are mixed with physiological saline, and after being evenly mixed, the mixture is filtered to collect the filtrate, which is the compound gentamicin sulfate sustained-release injection, and the concentration of the injection is 10 mg / mL.

[0057] The sustained-release properties of the compound gentamicin sulfate sustained-release injection prepared in Examples 1 to 5 were tested, and the experimental settings were as follows: a phosphate buffer solution with a pH of 6.8, a temperature of 37°C, and a rotation speed of 50 rpm were set, the compound gentamicin sulfate sustained-release injection was loaded into a dialysis bag or wrapped with a film, the dialysis bag containing the drug was immersed in the phosphate buffer solution, and samples were taken at 1h, 2h, 4h, 6h, 8h, 12h, 24h, and 48h to detect the release of the compound gentamicin sulfate in the sample. The experimental results are shown in Table 1 below:

[0058] Table 1

[0059]

[0060] From the data in Table 1 above, it can be seen that the release pattern of the compound gentamicin sulfate sustained-release injection meets the requirements of the sustained-release dosage form, that is, the release rate of the drug is relatively fast in the first few hours, but as time goes on, the release rate of the drug gradually decreases and eventually stabilizes. In addition, the stability of the drugs in Examples 4 and 5 is good, there is no significant degradation phenomenon, the release characteristics of the drugs are stable, and the fluctuation of the release amount is small.

[0061] The compound gentamicin sulfate sustained-release injection prepared in Example 4 was tested for the effect of pH value on the in vitro drug release process. The drug release was carried out under the conditions of pH values ​​of 1.2, 6.8, and 7.4. Samples were taken at different time points (1h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, and 72h). The drug concentrations at different time points under different pH conditions were recorded. The experimental data are shown in Table 2 below:

[0062] Table 2

[0063] Sampling time (h) pH=1.2 Release amount (mg) pH=6.8 Release amount (mg) pH=7.4 Release amount (mg) 0 0 0 0 1 1.2 1.2 0.8 2 2.5 2.3 2.0 4 4.0 3.5 3.5 6 6.0 6.0 4.8 8 8.5 8.0 5.7 12 9.5 9.0 6.5 24 10.0 9.6 8.0 48 10.0 10.0 9.2 72 10.0 10.0 10.0

[0064] From the experimental data in Table 2 above, it can be seen that in the simulated solution of pH = 1.2, the drug release rate is relatively fast and the entire release is completed earliest. This is because the strong acid environment promotes the dissolution of the sustained-release matrix or the release of the drug. In the simulated solution of pH = 6.8, the drug release rate is relatively slow and stable. This is because the pH value is close to neutral, which is suitable for the gradual release of sustained-release drugs. In the simulated solution of pH = 7.4, the drug release is the slowest and lasts for a long time, indicating that the drug release rate slows down with the increase of pH value.

[0065] The release rate of compound gentamicin sulfate sustained-release injection under different pH conditions is significantly different. The drug release is faster in pH = 1.2 (simulated gastric fluid), while the drug release is slower and more stable in pH = 6.8 (simulated intestinal fluid) and pH = 7.4 (normal saline). The drug release process is affected by pH. A lower pH value may accelerate the release of the drug, while a neutral or near-neutral environment is conducive to the smooth release of sustained-release drugs.

[0066] 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 method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology, characterized in that: The following steps are involved: S1 internal phase emulsification: dissolve gentamicin sulfate and antibiotics in water to form a drug-containing aqueous phase; add modified starch and sodium stearate to the drug-containing aqueous phase, stir until uniform, and then use a high-shear emulsification equipment to emulsify the internal phase emulsion to obtain a microemulsion with uniform particle size distribution; S2 external phase emulsification: dissolving polyvinyl alcohol in dichloromethane to obtain an external phase solution, slowly dropping the microemulsion prepared in step S1 into the external phase solution for secondary emulsification, and stirring evenly to obtain an O / W / O double emulsion; S3 volatilization curing: the O / W / O double emulsion obtained in step S2 is concentrated under reduced pressure, and then coumarin is slowly added dropwise to the concentrated solution. After the addition is completed, the solution is placed in an ultraviolet irradiation device to cause a cross-linking reaction to achieve curing, thereby obtaining a cured microcapsule reaction solution; S4 washing, freeze drying and drying: centrifuging the microcapsule reaction solution obtained in step S3 and collecting the microcapsules, washing them with physiological saline for 3 to 5 times, and freeze drying them after washing to obtain composite gentamicin sulfate sustained-release microcapsules; S5: Mixing the final microcapsule preparation: Mix the compound gentamicin sulfate sustained-release microcapsules obtained in step S4 with physiological saline, filter after mixing evenly, and collect the filtrate to obtain the compound gentamicin sulfate sustained-release injection.

2. The method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology according to claim 1, characterized in that: In the S1 internal phase emulsification step, the concentration of the modified starch is 2-5% g / ml.

3. The method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology according to claim 1, characterized in that: In the S1 internal phase emulsification step, the concentration of sodium stearate is 0.1-0.5% g / ml.

4. The method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology according to claim 1, characterized in that: In the S1 internal phase emulsification step, the concentration of gentamicin sulfate is 10-20 mg / ml.

5. The method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology according to claim 1, characterized in that: In the S1 internal phase emulsification step, the mass ratio of gentamicin sulfate to antibiotic is 1:(0.3-0.8).

6. The method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology according to claim 1, characterized in that: In the internal phase emulsification step S1, the internal phase emulsion is emulsified for 50 to 70 minutes.

7. The method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology according to claim 1, characterized in that: In the S2 external phase emulsification step, the concentration of the polyvinyl alcohol is 0.8-1.2% g / ml.

8. The method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology according to claim 1, characterized in that: In the S2 external phase emulsification step, the secondary emulsification time is 20 to 40 minutes.

9. The method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology according to claim 1, characterized in that: In the volatilization and curing step S3, the concentration of the coumarin is 0.005-0.01% g / ml.

10. The method for preparing a compound gentamicin sulfate sustained-release injection based on microcapsule technology according to claim 1, characterized in that: In the volatilization and curing step S3, the ultraviolet wavelength of the ultraviolet irradiation equipment is 300 to 500 nm; the ultraviolet irradiation time is 15 to 30 minutes.

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