A kind of temperature-sensitive gel containing organosilicon quaternary ammonium salt and preparation method thereof

Abstract

The invention provides a thermosensitive gel containing organosilicon quaternary ammonium salt and a preparation method thereof, and belongs to the field of medicine. The method first synthesizes hydroxypropyl chitosan (HPCH), then dissolves HPCH in water to obtain a thermosensitive precursor solution, adds organosilicon quaternary ammonium salt to the thermosensitive gel precursor solution, and stirs at low temperature for a certain time to obtain a clear transparent solution. Finally, the transparent solution obtained in the previous step is placed at an appropriate temperature for a certain time to form a thermosensitive inclusion organosilicon quaternary ammonium salt gel. The thermosensitive inclusion organosilicon quaternary ammonium salt gel of the invention can form a hydrogel in situ, so that the diffusion degree of the quaternary ammonium salt is reduced, and the local quaternary ammonium salt concentration is increased, and the gel has a long-term antibacterial ability.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a method for preparing a temperature-sensitive gel containing a quaternary ammonium salt of organic silicon. Background Art

[0002] Quaternary ammonium salts have excellent antibacterial properties and low overall cost, and are widely used in disinfection of public places, sterilization of circulating water, and antibacterial finishing agents, etc. However, small molecule quaternary ammonium salts are easy to diffuse in water, and the concentration decreases, and the antibacterial properties are lost. Summary of the invention

[0003] The present invention aims at solving the above-mentioned technical problems and provides a method for preparing a temperature-sensitive quaternary ammonium salt inclusion gel.

[0004] The purpose of the present invention can be achieved through the following technical solutions:

[0005] A method for preparing a temperature-sensitive gel containing a quaternary ammonium salt of organic silicon, the method comprising the following steps:

[0006] (1) Synthesis of hydroxypropyl chitosan (HPCH).

[0007] Mix NaOH, urea and water and pre-cool to -30 to -10°C, at which point the solution is in a semi-frozen state, crush the ice, disperse the chitosan powder in it, and then freeze it. Stir during the freezing process to ensure that the chitosan powder is evenly dispersed; take it out after 40 to 60 hours, and obtain a clear and transparent chitosan solution after thawing;

[0008] Add 1,2-propylene oxide to the chitosan solution at 1-5°C, react at 1-5°C for 20-30h, then raise the temperature to 10-20°C, react for 3-9h, adjust the reaction system to neutrality, and terminate the reaction; dialyze, freeze-dry, and obtain white sponge-like hydroxypropyl chitosan;

[0009] (2) dissolving white sponge-like hydroxypropyl chitosan in deionized water to obtain a thermosensitive gel precursor solution;

[0010] (3) adding the organosilicon quaternary ammonium salt to the above-mentioned temperature-sensitive gel precursor solution, and stirring at low temperature to obtain a clear and transparent solution;

[0011] (4) The clear and transparent solution of step (3) is allowed to stand to form a temperature-sensitive gel containing a quaternary ammonium salt of organic silicon.

[0012] In the technical solution of the present invention, in step (1), the mass ratio of chitosan powder: NaOH: urea: water is 1-5: 8-15: 1-8: 75-90.

[0013] In the technical solution of the present invention, the mass ratio of the chitosan solution to 1,2-propylene oxide in step (1) is 100:7-20.

[0014] In the technical solution of the present invention, the solid content of the precursor solution obtained in step (2) is in the range of 1-5%.

[0015] In the technical solution of the present invention, the organosilicon quaternary ammonium salt described in step (3) is one or more of trimethyl [3- (trimethoxysilyl) propyl] ammonium chloride (CAS: 35141-36-7) and dimethyl octadecyl [3- (trimethoxysilyl) propyl] ammonium chloride (CAS: 27668-52-6).

[0016] In the technical solution of the present invention, the mass ratio of the organosilicon quaternary ammonium salt added in step (3) to the thermosensitive gel precursor solution is 0.05 to 1:1.

[0017] In the technical solution of the present invention, the low temperature range in step (3) is 4-15°C.

[0018] In the technical solution of the present invention, the standing temperature in step (4) is 25-37° C., and the standing time is 1 to 3 minutes.

[0019] The thermosensitive gel containing organosilicon quaternary ammonium salt is prepared by the above-mentioned method.

[0020] Beneficial effects of the present invention:

[0021] 1. It can form hydrogel in situ, which reduces the diffusion of quaternary ammonium salt;

[0022] 2. It increases the local concentration of quaternary ammonium salts and has long-lasting antibacterial ability. DETAILED DESCRIPTION

[0023] The present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited thereto:

[0024] Example 1

[0025] (1) Synthesis of hydroxypropyl chitosan (HPCH).

[0026] Weigh 11g NaOH and 5g urea into a beaker, add 83g water, dissolve, precool to -18℃, weigh 2g chitosan powder and disperse it, place in the freezer of the refrigerator and freeze. Stir in time during the freezing process to ensure that the chitosan is evenly dispersed. Take out after 48h and thaw to form a clear and transparent aqueous solution. Add 12g 1,2-propylene oxide to 100g 2wt% chitosan solution at 2℃, heat to 5℃ and react for 24h, then heat to 15℃ and react for 6h. Adjust the pH of the reaction system to 7 with HCl to terminate the reaction. Dialyze and freeze-dry to obtain white spongy hydroxypropyl chitosan (HPCH).

[0027] (2) Dissolve sponge-like HPCH in deionized water at 4°C to obtain a 1% thermosensitive gel precursor solution.

[0028] (3) Add trimethyl[3-(trimethoxysilyl)propyl]ammonium chloride to the above-mentioned thermosensitive gel precursor solution so that the mass ratio of organosilicon quaternary ammonium salt to 1% thermosensitive gel precursor solution is 0.05:1, and stir at 4°C for a certain period of time to obtain a clear and transparent solution.

[0029] (4) The transparent solution obtained in the previous step is placed at 37°C for 2 min to form a thermosensitive quaternary ammonium salt inclusion gel.

[0030] Example 2

[0031] 1) Synthesis of hydroxypropyl chitosan (HPCH).

[0032] Weigh 11g NaOH and 2g urea into a beaker, add 83g water, dissolve, precool to -20℃, weigh 2g chitosan powder and disperse it, place in the freezer of the refrigerator and freeze. Stir in time during the freezing process to ensure that the chitosan is evenly dispersed. Take out after 52h and thaw to form a clear and transparent aqueous solution. Add 15g 1,2-propylene oxide to 100g 2wt% chitosan solution at 2℃, heat to 5℃ and react for 24h, then heat to 15℃ and react for 6h. Adjust the pH of the reaction system to 7 with HCl to terminate the reaction. Dialyze and freeze-dry to obtain white spongy hydroxypropyl chitosan (HPCH).

[0033] (2) Dissolve sponge-like HPCH in deionized water at 4°C to obtain a 2% thermosensitive gel precursor solution.

[0034] (3) Add dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride to the above-mentioned thermosensitive gel precursor solution so that the mass ratio of organosilicon quaternary ammonium salt to 2% thermosensitive gel precursor solution is 0.25:1, and stir at 8°C for a certain period of time to obtain a clear and transparent solution.

[0035] (4) The transparent solution obtained in the previous step is placed at 30°C for 2 min to form a thermosensitive quaternary ammonium salt inclusion gel.

[0036] Example 3

[0037] 1) Synthesis of hydroxypropyl chitosan (HPCH).

[0038] Weigh 11g NaOH and 4g urea into a beaker, add 83g water, dissolve, precool to -25℃, weigh 2g chitosan powder and disperse it, place in the freezer of the refrigerator and freeze. Stir in time during the freezing process to ensure that the chitosan is evenly dispersed. Take out after 54h and thaw to form a clear and transparent aqueous solution. Add 10g 1,2-propylene oxide to 100g 2wt% chitosan solution at 2℃, heat to 5℃ and react for 24h, then heat to 15℃ and react for 6h. Adjust the pH of the reaction system to 7 with HCl to terminate the reaction. Dialyze and freeze-dry to obtain white spongy hydroxypropyl chitosan (HPCH).

[0039] (2) Dissolve sponge-like HPCH in deionized water at 4°C to obtain a 3% thermosensitive gel precursor solution.

[0040] (3) Add dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride to the above-mentioned thermosensitive gel precursor solution so that the mass ratio of organosilicon quaternary ammonium salt to 3% thermosensitive gel precursor solution is 0.75:1, and stir at 12°C for a certain period of time to obtain a clear and transparent solution.

[0041] (4) The transparent solution obtained in the previous step is placed at 28°C for 1 min to form a thermosensitive quaternary ammonium salt inclusion gel.

[0042] Example 4

[0043] 1) Synthesis of hydroxypropyl chitosan (HPCH).

[0044] Weigh 11g NaOH and 3g urea into a beaker, add 83g water, dissolve, precool to -18℃, weigh 2g chitosan powder and disperse it, place in the freezer of the refrigerator and freeze. Stir in time during the freezing process to ensure that the chitosan is evenly dispersed. Take out after 56h and thaw to form a clear and transparent aqueous solution. Add 12g 1,2-propylene oxide to 100g 2wt% chitosan solution at 2℃, heat to 5℃ and react for 24h, then heat to 15℃ and react for 6h. Adjust the pH of the reaction system to 7 with HCl to terminate the reaction. Dialyze and freeze-dry to obtain white spongy hydroxypropyl chitosan (HPCH).

[0045] (2) Dissolve sponge-like HPCH in deionized water at 4°C to obtain a 5% thermosensitive gel precursor solution.

[0046] (3) Add dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride to the above-mentioned thermosensitive gel precursor solution, with the mass ratio of organosilicon quaternary ammonium salt to 5% thermosensitive gel precursor solution being 1:1, and stir at 15°C for a certain period of time to obtain a clear and transparent solution.

[0047] (4) The transparent solution obtained in the previous step is placed at 25°C for 1 min to form a thermosensitive quaternary ammonium salt inclusion gel.

[0048] Gel transition temperature:

[0049] The gel transition temperatures obtained for all examples were measured:

[0050] Table 1 Gel transition temperature

[0051] sample Example 1 Example 2 Example 3 Example 4 Gel transition temperature 37℃ 30℃ 28℃ 25℃

[0052] Conclusion: It can be seen from Table 1 that the transition temperature of the thermosensitive quaternary ammonium salt inclusion gel obtained in the examples is 25-37°C, and gel can be formed at a relatively low temperature.

[0053] Antibacterial experiment:

[0054] Preparation of E.coil and S.aureus bacterial suspension 10 4 CFU / mL, take 4 ml into a vial, add 0.3 ml of the gel in the example, and place it on a shaker at 150 r / min, 37°C. Pay attention to the turbidity of the solution to judge the bacterial growth.

[0055] Table 2 Gel antibacterial ability (E.coil)

[0056] sample Example 1 Example 2 Example 3 Example 4 Solution turbidity time 72h 96h >7d >7d

[0057] Table 3 Antibacterial ability of gel (S. aureus)

[0058] sample Example 1 Example 2 Example 3 Example 4 Solution turbidity time >7d >7d >7d >7d

[0059] Conclusion: It can be seen from Table 2 and Table 3 that the temperature-sensitive quaternary ammonium salt inclusion gel obtained in the examples has antibacterial ability, and the higher the concentration of the added quaternary ammonium salt, the stronger the antibacterial ability. The concentrations added in this example can have a long-term antibacterial ability against Staphylococcus aureus.

Claims

1. A method for preparing a temperature-sensitive gel containing a quaternary ammonium salt of organosilicon, characterized in that: The method comprises the following steps: (1) Synthetic hydroxypropyl chitosan (HPCH) Mix NaOH, urea and water and pre-cool to -30~-10℃. At this time, the solution is in a semi-frozen state. Crush the ice cubes and disperse the chitosan powder in it. Then freeze it. Stir during the freezing process to ensure that the chitosan powder is evenly dispersed. Take it out after 40~60h and get a clear and transparent chitosan solution after thawing. Add 1,2-propylene oxide to the chitosan solution at 1-5°C, react at 1-5°C for 20-30 hours, then raise the temperature to 10-20°C, react for 3-9 hours, adjust the reaction system to neutrality, and terminate the reaction; dialyze, freeze-dry, and obtain white sponge-like hydroxypropyl chitosan; (2) dissolving white sponge-like hydroxypropyl chitosan in deionized water to obtain a thermosensitive gel precursor solution; (3) adding the organosilicon quaternary ammonium salt to the above-mentioned thermosensitive gel precursor solution, and stirring at low temperature to obtain a clear and transparent solution; (4) allowing the clear transparent solution of step (3) to stand to form a temperature-sensitive gel containing a silicone quaternary ammonium salt; Wherein, the solid content of the precursor solution obtained in step (2) is in the range of 1-5%; The organosilicon quaternary ammonium salt described in step (3) is one or more of trimethyl [3- (trimethoxysilyl) propyl] ammonium chloride and dimethyl octadecyl [3- (trimethoxysilyl) propyl] ammonium chloride; the low temperature range in step (3) is 4-15° C.; The mass ratio of the organosilicon quaternary ammonium salt added in step (3) to the thermosensitive gel precursor solution is 0.05~1:

1.

2. The preparation method according to claim 1, characterized in that: In step (1), the mass ratio of chitosan powder: NaOH: urea: water is 1-5: 8-15: 1-8: 75-90.

3. The preparation method according to claim 1, characterized in that: In step (1), the mass ratio of the chitosan solution to 1,2-propylene oxide is 100:7-20.

4. The preparation method according to claim 1, characterized in that: The standing temperature in step (4) is 25-37° C., and the standing time is 1-3 min.

5. A thermosensitive gel containing a quaternary ammonium salt of organic silicon, characterized in that: The method is prepared by any one of claims 1 to 4.