A light-responsive drug gel carrier and a preparation method thereof

Abstract

The present application relates to the technical field of biological materials, in particular to a light-responsive drug gel carrier and a preparation method thereof, in order to improve the controlled release function of the hydrogel material, the methyl methacrylate nitrobenzene compound containing nitrobenzene structure, hydantoin structure and propylene structure is prepared first, under the action of a photoinitiator, the double bond is crosslinked with methyl methacrylate and ethylene glycol methacrylate to form a hydrophilic gel network, so that the drug gel carrier is obtained; wherein the nitrobenzene structure has photosensitivity, and the crosslinking structure will be broken under ultraviolet irradiation, thereby reducing the stability of the gel material, destroying the rearrangement of the gel micelle structure, and realizing the release of the loaded drug; and the hydantoin structure introduced in the methyl methacrylate nitrobenzene compound also has good antibacterial performance, which can effectively avoid wound infection and improve wound recovery.

Description

Technical Field

[0001] This invention relates to the field of biomaterials technology, specifically to a photoresponsive drug gel carrier and its preparation method. Background Technology

[0002] When human skin is injured, it loses its protective function. During the skin's repair process, the wound requires multiple applications of medication and sterilization, often resulting in repeated dressing removals, which severely affects wound healing and causes pain for the patient. Hydrogel materials are highly hydrophilic and biocompatible gel materials with good softness, making them suitable as filler and excipient materials for human tissues. However, hydrogel materials have poor drug loading capacity and cannot achieve intermittent drug release. Drugs such as vascular endothelial growth factor have short half-lives in vivo, and overdose can easily lead to decreased wound clotting function and further bleeding. Therefore, it is necessary to develop a controlled-release hydrogel material to address this deficiency of hydrogels. Summary of the Invention

[0003] The purpose of this invention is to provide a photoresponsive drug gel carrier and its preparation method to solve the problems raised in the prior art.

[0004] To achieve the above objectives, the present invention provides the following technical solution: a method for preparing a photoresponsive drug gel carrier, comprising the following steps:

[0005] S1. Preparation of methylpropene nitrobenzene compounds;

[0006] S11. Under nitrogen atmosphere protection, sodium hydroxide and deionized water were mixed, and 2,6-dimethylnitrobenzene was added to the mixture. After mixing evenly, the mixture was heated, and a saturated aqueous solution of potassium permanganate was added dropwise. After the addition was completed, the mixture was kept at the temperature and refluxed for 24-48 hours. The mixture was then filtered, and hydrochloric acid was added dropwise to the filtrate to adjust the pH to 1.8-2. The precipitate formed in the filtrate was collected and dried under vacuum to constant weight to obtain nitrobenzene dibenzoate compound.

[0007] S12. Disperse 1,3-dihydroxyethyl-5,5-dimethylhydantoin in THF and stir until evenly dispersed, then add... A THF solution containing dibenzoic acid nitrobenzene compound was added dropwise, the mixture was heated, and stirred under reflux for 12-24 hours. Excess solvent was removed by rotary evaporation, and the mixture was washed with deionized water at 0-4℃. The mixture was then vacuum evaporated to constant weight to obtain dihydroxynitrobenzene compound.

[0008] S13. The dihydroxynitrobenzene compound was dispersed in THF under a nitrogen atmosphere and cooled to a constant temperature in an ice-water bath. Triethylamine was added and mixed evenly. Methacryl chloride was added dropwise. After the addition was complete, the reaction was stirred for 1-4 hours. Sodium carbonate was added and the reaction was stirred for 3-5 minutes. The mixture was then extracted with ethyl acetate, the organic phase was collected, and the mixture was evaporated under vacuum to a constant weight to obtain the methacrylnitrobenzene compound.

[0009] S2. Methyl methacrylate, ethylene glycol methacrylate, and methacrylic nitrobenzene compound were mixed, diluted with DMF, and mixed evenly. Under nitrogen atmosphere protection, azobisisobutyronitrile was added, the mixture was heated, stirred and reacted for 12-24 hours, and excess solvent was removed by rotary evaporation. The resulting product was dialyzed for 2-4 days, lyophilized, and then placed in water to stand, thus obtaining a photoresponsive drug gel carrier.

[0010] Furthermore, in step S11, by weight, the amount of each component added is 3-4.5 parts sodium hydroxide, 10 parts 2,6-dimethylnitrobenzene, and 10-50 parts potassium permanganate.

[0011] Furthermore, in step S11, the temperature during heating is 95~99℃.

[0012] Furthermore, in step S12, by weight, the amount of each component added is 20-28 parts of 1,3-dihydroxyethyl-5,5-dimethylhydantoin and 0.12-0.15 parts of... 10 parts of dibenzoic acid nitrobenzene compound.

[0013] Furthermore, in step S12, the heating temperature is 64~66℃.

[0014] Furthermore, in step S13, by weight, the amounts of each component added are 10 parts of dihydroxynitrobenzene compound, 2-3 parts of triethylamine, 2-4 parts of methacryloyl chloride, and 0.18-0.3 parts of sodium carbonate.

[0015] Furthermore, by weight, in step S2, the amounts of each component added are 3-5 parts methyl methacrylate, 6-8 parts ethylene glycol methacrylate and 3-8 parts methacrylate nitrobenzene compound, and 0.1-0.15 parts azobisisobutyronitrile.

[0016] Furthermore, in step S2, the heating temperature is 85~95℃.

[0017] Furthermore, in step S2, during dialysis, the dialysis bag has a capacity of 10~20 kDa.

[0018] Furthermore, a photoresponsive drug gel carrier is prepared by the above method.

[0019] Compared with the prior art, the beneficial effects of the present invention are:

[0020] To enhance the controlled-release function of hydrogel materials, this invention first uses 2,6-dimethylnitrobenzene containing a nitrobenzene structure as a raw material. This raw material is mixed with sodium hydroxide and potassium permanganate, and the methyl group is oxidized to generate a carboxylic acid group. Then, 1,3-dihydroxyethyl-5,5-dimethylhydantoin containing a hydroxyethyl group is used for further reaction. Through esterification between the carboxyl and hydroxyl groups, a dihydroxynitrobenzene compound containing a hydroxyl group, hydantoin, and a nitrobenzene structure is generated. Further reaction with methacryloyl chloride introduces a propylene group with a double bond. Under the action of a photoinitiator, the double bond cross-links with methyl methacrylate and ethylene glycol methacrylate to form a hydrophilic gel network, thus obtaining a drug gel carrier.

[0021] The nitrobenzene structure is photosensitive and will break under ultraviolet irradiation, thereby reducing the stability of the gel material and disrupting the rearrangement of the gel micelle structure, thus realizing the release of the loaded drug; in addition, the hydantoin structure introduced into the methacrylic nitrobenzene compound in this invention also has good antibacterial properties, which can effectively prevent wound infection and improve wound healing. Detailed Implementation

[0022] Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0023] Example 1. A method for preparing a photoresponsive drug gel carrier, comprising the following steps:

[0024] S1. Preparation of methylpropene nitrobenzene compounds;

[0025] S11. Under nitrogen atmosphere protection, 3 parts by weight of sodium hydroxide and deionized water were mixed, and 10 parts by weight of 2,6-dimethylnitrobenzene were added to the mixture. After mixing evenly, the mixture was heated to 95°C, and a saturated aqueous solution of potassium permanganate containing 10 parts by weight of potassium permanganate was added dropwise. After the addition was completed, the mixture was kept at the temperature and refluxed for 24 hours. The mixture was then filtered, and hydrochloric acid was added dropwise to the filtrate to adjust the pH to 2. The precipitate formed in the filtrate was collected and dried under vacuum to constant weight to obtain nitrobenzene dibenzoate compound.

[0026] S12. By weight, disperse 20 parts of 1,3-dihydroxyethyl-5,5-dimethylhydantoin in THF and stir until evenly dispersed. Then add 0.12 parts of... A THF solution containing 10 parts of dibenzoic acid nitrobenzene compound was added dropwise, the temperature was raised to 64°C, and the mixture was refluxed and stirred for 12 hours. Excess solvent was removed by rotary evaporation, and the mixture was washed with deionized water at 0~4°C. The mixture was then vacuum evaporated to constant weight to obtain dihydroxynitrobenzene compound.

[0027] S13. By weight, 10 parts of dihydroxynitrobenzene compound were dispersed in THF. Under nitrogen atmosphere protection, the mixture was cooled to constant temperature in an ice-water bath. Then, 2 parts of triethylamine were added and mixed evenly. Next, 2 parts of methacrylamide chloride were added dropwise. After the addition was completed, the mixture was stirred for 1 hour. Then, 0.18 parts of sodium carbonate were added and the mixture was stirred for 5 minutes. The mixture was then extracted with ethyl acetate, the organic phase was collected, and the mixture was evaporated under vacuum to constant weight to obtain methacrylamide nitrobenzene compound.

[0028] S2. By weight, 3 parts of methyl methacrylate, 6 parts of ethylene glycol methacrylate and 3 parts of methacrylic nitrobenzene compound were mixed, diluted with DMF and mixed evenly. Under nitrogen atmosphere, 0.1 parts of azobisisobutyronitrile were added, the mixture was heated and stirred for 12 hours. Excess solvent was removed by rotary evaporation. The product was dialyzed for 2 days using a 10 kDa dialysis bag, then lyophilized. The product was placed in water and allowed to stand to obtain a photoresponsive drug gel carrier.

[0029] Example 2. A method for preparing a photoresponsive drug gel carrier, comprising the following steps:

[0030] S1. Preparation of methylpropene nitrobenzene compounds;

[0031] S11. Under nitrogen atmosphere protection, 3 parts by weight of sodium hydroxide and deionized water were mixed, and 10 parts by weight of 2,6-dimethylnitrobenzene were added to the mixture. After mixing evenly, the mixture was heated to 99°C, and a saturated aqueous solution of potassium permanganate containing 10 parts by weight of potassium permanganate was added dropwise. After the addition was completed, the mixture was kept at the temperature and refluxed for 48 hours. The mixture was then filtered, and hydrochloric acid was added dropwise to the filtrate to adjust the pH to 2. The precipitate formed in the filtrate was collected and dried under vacuum to constant weight to obtain nitrobenzene dibenzoate compound.

[0032] S12. By weight, disperse 20 parts of 1,3-dihydroxyethyl-5,5-dimethylhydantoin in THF and stir until evenly dispersed. Then add 0.15 parts of... A THF solution containing 10 parts of dibenzoic acid nitrobenzene compound was added dropwise, the temperature was raised to 66°C, and the mixture was refluxed and stirred for 24 hours. Excess solvent was removed by rotary evaporation, and the mixture was washed with deionized water at 0~4°C and then vacuum evaporated to constant weight to obtain dihydroxynitrobenzene compound.

[0033] S13. By weight, 10 parts of dihydroxynitrobenzene compound were dispersed in THF, protected under a nitrogen atmosphere, and cooled to a constant temperature in an ice-water bath. Then, 3 parts of triethylamine were added and mixed evenly. Next, 2 parts of methacrylamide chloride were added dropwise. After the addition was complete, the reaction was stirred for 1 hour. Then, 0.3 parts of sodium carbonate were added and the reaction was stirred for 5 minutes. The mixture was then extracted with ethyl acetate, the organic phase was collected, and the mixture was evaporated under vacuum to a constant weight to obtain the methacrylamide nitrobenzene compound.

[0034] S2. By weight, 3 parts of methyl methacrylate, 6 parts of ethylene glycol methacrylate and 3 parts of methacrylic nitrobenzene compound were mixed, diluted with DMF and mixed evenly. Under nitrogen atmosphere, 0.1 parts of azobisisobutyronitrile were added, the mixture was heated and stirred for 24 hours. Excess solvent was removed by rotary evaporation. The product was dialyzed for 2 days using a 20 kDa dialysis bag, then lyophilized. The product was placed in water and allowed to stand to obtain a photoresponsive drug gel carrier.

[0035] Example 3. A method for preparing a photoresponsive drug gel carrier, comprising the following steps:

[0036] Compared with Example 2, this example increases the amount of sodium hydroxide and potassium permanganate added in step S11;

[0037] S1. Preparation of methylpropene nitrobenzene compounds;

[0038] S11. Under nitrogen atmosphere protection, 4.5 parts by weight of sodium hydroxide and deionized water were mixed, and 10 parts of 2,6-dimethylnitrobenzene were added to the mixture. After mixing evenly, the mixture was heated to 99°C, and a saturated aqueous solution of potassium permanganate containing 50 parts of potassium permanganate was added dropwise. After the addition was completed, the mixture was kept at the temperature and refluxed for 48 hours. The mixture was then filtered, and hydrochloric acid was added dropwise to the filtrate to adjust the pH to 2. The precipitate formed in the filtrate was collected and dried under vacuum to constant weight to obtain nitrobenzene dibenzoate compound.

[0039] S12. By weight, disperse 20 parts of 1,3-dihydroxyethyl-5,5-dimethylhydantoin in THF and stir until evenly dispersed. Then add 0.15 parts of... 3. Add a THF solution containing 10 parts of dibenzoic acid nitrobenzene compound dropwise, heat to 66°C, reflux and stir for 24 hours, remove excess solvent by rotary evaporation, wash with deionized water at 0~4°C, and then evaporate under vacuum to constant weight to obtain dihydroxynitrobenzene compound.

[0040] S13. By weight, 10 parts of dihydroxynitrobenzene compound were dispersed in THF, protected under a nitrogen atmosphere, and cooled to a constant temperature in an ice-water bath. Then, 3 parts of triethylamine were added and mixed evenly. Next, 2 parts of methacrylamide chloride were added dropwise. After the addition was complete, the reaction was stirred for 1 hour. Then, 0.3 parts of sodium carbonate were added and the reaction was stirred for 5 minutes. The mixture was then extracted with ethyl acetate, the organic phase was collected, and the mixture was evaporated under vacuum to a constant weight to obtain the methacrylamide nitrobenzene compound.

[0041] S2. By weight, 3 parts of methyl methacrylate, 6 parts of ethylene glycol methacrylate and 3 parts of methacrylic nitrobenzene compound were mixed, diluted with DMF and mixed evenly. Under nitrogen atmosphere, 0.1 parts of azobisisobutyronitrile were added, the mixture was heated and stirred for 24 hours. Excess solvent was removed by rotary evaporation. The product was dialyzed for 2 days using a 20 kDa dialysis bag, then lyophilized. The product was placed in water and allowed to stand to obtain a photoresponsive drug gel carrier.

[0042] Example 4. A method for preparing a photoresponsive drug gel carrier, comprising the following steps:

[0043] Compared with Example 3, this example increases the amount of 1,3-dihydroxyethyl-5,5-dimethylhydantoin added in step S12;

[0044] S1. Preparation of methylpropene nitrobenzene compounds;

[0045] S11. Under nitrogen atmosphere protection, 4.5 parts by weight of sodium hydroxide and deionized water were mixed, and 10 parts of 2,6-dimethylnitrobenzene were added to the mixture. After mixing evenly, the mixture was heated to 99°C, and a saturated aqueous solution of potassium permanganate containing 50 parts of potassium permanganate was added dropwise. After the addition was completed, the mixture was kept at the temperature and refluxed for 48 hours. The mixture was then filtered, and hydrochloric acid was added dropwise to the filtrate to adjust the pH to 2. The precipitate formed in the filtrate was collected and dried under vacuum to constant weight to obtain nitrobenzene dibenzoate compound.

[0046] S12. By weight, disperse 28 parts of 1,3-dihydroxyethyl-5,5-dimethylhydantoin in THF and stir until evenly dispersed. Then add 0.15 parts of... A THF solution containing 10 parts of dibenzoic acid nitrobenzene compound was added dropwise, the temperature was raised to 66°C, and the mixture was refluxed and stirred for 24 hours. Excess solvent was removed by rotary evaporation, and the mixture was washed with deionized water at 0~4°C and then vacuum evaporated to constant weight to obtain dihydroxynitrobenzene compound.

[0047] S13. By weight, 10 parts of dihydroxynitrobenzene compound were dispersed in THF, protected under a nitrogen atmosphere, and cooled to a constant temperature in an ice-water bath. Then, 3 parts of triethylamine were added and mixed evenly. Next, 2 parts of methacrylamide chloride were added dropwise. After the addition was complete, the reaction was stirred for 1 hour. Then, 0.3 parts of sodium carbonate were added and the reaction was stirred for 5 minutes. The mixture was then extracted with ethyl acetate, the organic phase was collected, and the mixture was evaporated under vacuum to a constant weight to obtain the methacrylamide nitrobenzene compound.

[0048] S2. By weight, 3 parts of methyl methacrylate, 6 parts of ethylene glycol methacrylate and 3 parts of methacrylic nitrobenzene compound were mixed, diluted with DMF and mixed evenly. Under nitrogen atmosphere, 0.1 parts of azobisisobutyronitrile were added, the mixture was heated and stirred for 24 hours. Excess solvent was removed by rotary evaporation. The product was dialyzed for 2 days using a 20 kDa dialysis bag, then lyophilized. The product was placed in water and allowed to stand to obtain a photoresponsive drug gel carrier.

[0049] Example 5. A method for preparing a photoresponsive drug gel carrier, comprising the following steps:

[0050] Compared with Example 4, this example increases the amount of methacrylamide chloride added in step S13;

[0051] S1. Preparation of methylpropene nitrobenzene compounds;

[0052] S11. Under nitrogen atmosphere protection, 4.5 parts by weight of sodium hydroxide and deionized water were mixed, and 10 parts of 2,6-dimethylnitrobenzene were added to the mixture. After mixing evenly, the mixture was heated to 99°C, and a saturated aqueous solution of potassium permanganate containing 50 parts of potassium permanganate was added dropwise. After the addition was completed, the mixture was kept at the temperature and refluxed for 48 hours. The mixture was then filtered, and hydrochloric acid was added dropwise to the filtrate to adjust the pH to 2. The precipitate formed in the filtrate was collected and dried under vacuum to constant weight to obtain nitrobenzene dibenzoate compound.

[0053] S12. By weight, disperse 28 parts of 1,3-dihydroxyethyl-5,5-dimethylhydantoin in THF and stir until evenly dispersed. Then add 0.15 parts of... A THF solution containing 10 parts of dibenzoic acid nitrobenzene compound was added dropwise, the temperature was raised to 66°C, and the mixture was refluxed and stirred for 24 hours. Excess solvent was removed by rotary evaporation, and the mixture was washed with deionized water at 0~4°C and then vacuum evaporated to constant weight to obtain dihydroxynitrobenzene compound.

[0054] S13. By weight, 10 parts of dihydroxynitrobenzene compound were dispersed in THF, protected under a nitrogen atmosphere, and cooled to a constant temperature in an ice-water bath. Then, 3 parts of triethylamine were added and mixed evenly. Next, 4 parts of methacrylamide chloride were added dropwise. After the addition was complete, the reaction was stirred for 1 hour. Then, 0.3 parts of sodium carbonate were added and the reaction was stirred for 5 minutes. The mixture was then extracted with ethyl acetate, the organic phase was collected, and the mixture was evaporated under vacuum to a constant weight to obtain the methacrylamide nitrobenzene compound.

[0055] S2. By weight, 3 parts of methyl methacrylate, 6 parts of ethylene glycol methacrylate and 3 parts of methacrylic nitrobenzene compound were mixed, diluted with DMF and mixed evenly. Under nitrogen atmosphere, 0.1 parts of azobisisobutyronitrile were added, the mixture was heated and stirred for 24 hours. Excess solvent was removed by rotary evaporation. The product was dialyzed for 2 days using a 20 kDa dialysis bag, then lyophilized. The product was placed in water and allowed to stand to obtain a photoresponsive drug gel carrier.

[0056] Example 6. A method for preparing a photoresponsive drug gel carrier, comprising the following steps:

[0057] Compared with Example 5, this example increases the amount of methpropylene nitrobenzene compound added in step S2;

[0058] S1. Preparation of methylpropene nitrobenzene compounds;

[0059] S11. Under nitrogen atmosphere protection, 4.5 parts by weight of sodium hydroxide and deionized water were mixed, and 10 parts of 2,6-dimethylnitrobenzene were added to the mixture. After mixing evenly, the mixture was heated to 99°C, and a saturated aqueous solution of potassium permanganate containing 50 parts of potassium permanganate was added dropwise. After the addition was completed, the mixture was kept at the temperature and refluxed for 48 hours. The mixture was then filtered, and hydrochloric acid was added dropwise to the filtrate to adjust the pH to 2. The precipitate formed in the filtrate was collected and dried under vacuum to constant weight to obtain nitrobenzene dibenzoate compound.

[0060] S12. By weight, disperse 28 parts of 1,3-dihydroxyethyl-5,5-dimethylhydantoin in THF and stir until evenly dispersed. Then add 0.15 parts of... A THF solution containing 10 parts of dibenzoic acid nitrobenzene compound was added dropwise, the temperature was raised to 66°C, and the mixture was refluxed and stirred for 24 hours. Excess solvent was removed by rotary evaporation, and the mixture was washed with deionized water at 0~4°C and then vacuum evaporated to constant weight to obtain dihydroxynitrobenzene compound.

[0061] S13. By weight, 10 parts of dihydroxynitrobenzene compound were dispersed in THF, protected under a nitrogen atmosphere, and cooled to a constant temperature in an ice-water bath. Then, 3 parts of triethylamine were added and mixed evenly. Next, 4 parts of methacrylamide chloride were added dropwise. After the addition was complete, the reaction was stirred for 1 hour. Then, 0.3 parts of sodium carbonate were added and the reaction was stirred for 5 minutes. The mixture was then extracted with ethyl acetate, the organic phase was collected, and the mixture was evaporated under vacuum to a constant weight to obtain the methacrylamide nitrobenzene compound.

[0062] S2. By weight, 3 parts of methyl methacrylate, 6 parts of ethylene glycol methacrylate and 8 parts of methacrylic nitrobenzene compound were mixed, diluted with DMF and mixed evenly. Under nitrogen atmosphere, 0.1 parts of azobisisobutyronitrile were added, the mixture was heated and stirred for 24 hours, and excess solvent was removed by rotary evaporation. The product was dialyzed for 2 days using a 20 kDa dialysis bag, then lyophilized and placed in water to stand, thus obtaining a photoresponsive drug gel carrier.

[0063] Example 7. A method for preparing a photoresponsive drug gel carrier, comprising the following steps:

[0064] Compared with Example 6, this example increases the amount of methyl methacrylate and ethylene glycol methacrylate added in step S2;

[0065] S1. Preparation of methylpropene nitrobenzene compounds;

[0066] S11. Under nitrogen atmosphere protection, 4.5 parts by weight of sodium hydroxide and deionized water were mixed, and 10 parts of 2,6-dimethylnitrobenzene were added to the mixture. After mixing evenly, the mixture was heated to 99°C, and a saturated aqueous solution of potassium permanganate containing 50 parts of potassium permanganate was added dropwise. After the addition was completed, the mixture was kept at the temperature and refluxed for 48 hours. The mixture was then filtered, and hydrochloric acid was added dropwise to the filtrate to adjust the pH to 2. The precipitate formed in the filtrate was collected and dried under vacuum to constant weight to obtain nitrobenzene dibenzoate compound.

[0067] S12. By weight, disperse 28 parts of 1,3-dihydroxyethyl-5,5-dimethylhydantoin in THF and stir until evenly dispersed. Then add 0.15 parts of... A THF solution containing 10 parts of dibenzoic acid nitrobenzene compound was added dropwise, the temperature was raised to 66°C, and the mixture was refluxed and stirred for 24 hours. Excess solvent was removed by rotary evaporation, and the mixture was washed with deionized water at 0~4°C and then vacuum evaporated to constant weight to obtain dihydroxynitrobenzene compound.

[0068] S13. By weight, 10 parts of dihydroxynitrobenzene compound were dispersed in THF, protected under a nitrogen atmosphere, and cooled to a constant temperature in an ice-water bath. Then, 3 parts of triethylamine were added and mixed evenly. Next, 4 parts of methacrylamide chloride were added dropwise. After the addition was complete, the reaction was stirred for 1 hour. Then, 0.3 parts of sodium carbonate were added and the reaction was stirred for 5 minutes. The mixture was then extracted with ethyl acetate, the organic phase was collected, and the mixture was evaporated under vacuum to a constant weight to obtain the methacrylamide nitrobenzene compound.

[0069] S2. By weight, 5 parts of methyl methacrylate, 8 parts of ethylene glycol methacrylate and 8 parts of methacrylic nitrobenzene compound were mixed, diluted with DMF and mixed evenly. Under nitrogen atmosphere protection, 0.1 parts of azobisisobutyronitrile were added, the mixture was heated and stirred for 24 hours. Excess solvent was removed by rotary evaporation. The product was dialyzed for 2 days using a 20 kDa dialysis bag, then lyophilized. The product was placed in water and allowed to stand to obtain a photoresponsive drug gel carrier.

[0070] Comparative Example 1. A method for preparing a photoresponsive drug gel carrier, comprising the following steps:

[0071] Compared with Example 2, this comparative example did not prepare a compound containing added methylpropene nitrobenzene;

[0072] By weight, 3 parts of methyl methacrylate and 6 parts of ethylene glycol methacrylate were mixed, diluted with DMF and mixed evenly. Under nitrogen atmosphere protection, 0.1 parts of azobisisobutyronitrile were added, the mixture was heated and stirred for 24 hours. Excess solvent was removed by rotary evaporation. The product was dialyzed for 2 days using a 20 kDa dialysis bag, then lyophilized. The product was then placed in water and allowed to stand to obtain a photoresponsive drug gel carrier.

[0073] Detection: The photoresponsive drug gel carriers prepared in Examples 1-7 and Comparative Example 1 were dispersed in THF, dissolved by sonication, mixed with doxorubicin hydrochloride, stirred and mixed evenly, the mixture was dialyzed to remove THF, lyophilized, and then placed in PBS buffer for 24 h to obtain the photoresponsive drug gel carrier loaded with doxorubicin hydrochloride.

[0074] The photoresponsive drug gel carrier loaded with doxorubicin hydrochloride prepared above was placed in a dialysis bag, and PBS buffer was used as the dialysis solution. It was incubated at 37°C. Ultraviolet irradiation group and no irradiation group were set up in the dark. At each time interval, 1 mL of the outer PBS solution was taken to measure the ultraviolet absorption and test the drug release percentage.

[0075] The antibacterial properties of the photoresponsive drug gel carriers prepared in Examples 1-7 and Comparative Example 1 were tested according to QB / T 2591-2003. The test results are shown in the table below.

[0076]

[0077] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a photoresponsive drug gel carrier, characterized in that, Includes the following steps: S1. Preparation of methylpropene nitrobenzene compounds; S11. Under nitrogen atmosphere protection, sodium hydroxide and deionized water were mixed, and 2,6-dimethylnitrobenzene was added to the mixture. After mixing evenly, the mixture was heated, and a saturated aqueous solution of potassium permanganate was added dropwise. After the addition was completed, the mixture was kept at the temperature and refluxed for 24-48 hours. The mixture was then filtered, and hydrochloric acid was added dropwise to the filtrate to adjust the pH to 1.8-2. The precipitate formed in the filtrate was collected and dried under vacuum to constant weight to obtain nitrobenzene dibenzoate compound. The components added, by weight, are 3-4.5 parts sodium hydroxide, 10 parts 2,6-dimethylnitrobenzene, and 10-50 parts potassium permanganate. S12. 1,3-Dihydroxyethyl-5,5-dimethylhydantoin was dispersed in THF and stirred until evenly dispersed. Fe(OTf)3 was added, and a THF solution containing nitrobenzene dibenzoic acid was added dropwise. The mixture was heated to 64-66°C and stirred under reflux for 12-24 hours. Excess solvent was removed by rotary evaporation, and the mixture was washed with deionized water at 0-4°C. The mixture was then evaporated under vacuum to constant weight to obtain the dihydroxynitrobenzene compound. The components added, by weight, are 20-28 parts of 1,3-dihydroxyethyl-5,5-dimethylhydantoin, 0.12-0.15 parts of Fe(OTf)3, and 10 parts of nitrobenzene dibenzoate compound. S13. The dihydroxynitrobenzene compound was dispersed in THF under a nitrogen atmosphere and cooled to a constant temperature in an ice-water bath. Triethylamine was added and mixed evenly. Methacryl chloride was added dropwise. After the addition was complete, the reaction was stirred for 1-4 hours. Sodium carbonate was added and the reaction was stirred for 3-5 minutes. The mixture was then extracted with ethyl acetate, the organic phase was collected, and the mixture was evaporated under vacuum to a constant weight to obtain the methacrylnitrobenzene compound. The components, by weight, are 10 parts dihydroxynitrobenzene compound, 2-3 parts triethylamine, 2-4 parts methacryloyl chloride, and 0.18-0.3 parts sodium carbonate. S2. Methyl methacrylate, ethylene glycol methacrylate, and methacrylic nitrobenzene compound were mixed, diluted with DMF, and mixed evenly. Under nitrogen atmosphere protection, azobisisobutyronitrile was added, the mixture was heated, stirred and reacted for 12-24 hours, and excess solvent was removed by rotary evaporation. The resulting product was dialyzed for 2-4 days, lyophilized, and then placed in water to stand, thus obtaining a photoresponsive drug gel carrier.

2. The method for preparing a photoresponsive drug gel carrier according to claim 1, characterized in that: In step S11, the temperature during heating is 95~99℃.

3. The method for preparing a photoresponsive drug gel carrier according to claim 1, characterized in that: By weight, in step S2, the amounts of each component added are 3-5 parts methyl methacrylate, 6-8 parts ethylene glycol methacrylate and 3-8 parts methacrylate nitrobenzene compound, and 0.1-0.15 parts azobisisobutyronitrile.

4. The method for preparing a photoresponsive drug gel carrier according to claim 1, characterized in that: In step S2, the heating temperature is 85~95℃.

5. The method for preparing a photoresponsive drug gel carrier according to claim 1, characterized in that: In step S2, during dialysis, the dialysis bag has a capacity of 10~20 kDa.

6. A photoresponsive drug gel carrier prepared by the preparation method according to any one of claims 1 to 5.

Images