Colon-targeted sinomenine hydrochloride slow-release nanofiber membrane and preparation method and application thereof

[0033] Example 1

[0034] A preparation method of colon-targeted sinomenine hydrochloride sustained-release nanofiber membrane, comprising:

[0035] (1) Weigh 2.2508g of polyacrylic acid resin Eudragit S100 with an analytical balance, add it to a mixed solution of 3.6430g N,N-dimethylacetamide and 9.110g absolute ethanol, heat and stir to obtain a shell layer spinning solution . Among them, the concentration of absolute ethanol is ≥99.7%, the concentration of N,N-dimethylacetamide is ≥99.5%, the heating temperature is 50°C, and the stirring time is 8h;

[0036] (2) Weigh 0.2503g of polyacrylic resin Eudragit RS100 and 0.3003g of sinomenine hydrochloride with an analytical balance, add them to a mixed solution of 1.2720g of chloroform and 3.1781g of absolute ethanol, and stir at room temperature to obtain a core layer spinning solution. Among them, the concentration of absolute ethanol is greater than or equal to 99.7%, and the concentration of chloroform is greater than or equal to 99.0%; the stirring time is 4h;

[0037] (3) spinning the spinning solution obtained in step (1) and step (2) by coaxial electrospinning to obtain a drug-loaded nanofiber membrane, and placing it in a vacuum drying oven for drying. The drug loading of the fiber membrane is 10% to 20%. Among them, the electrospinning process parameters are: the voltage of the positive electrode is +13KV, the negative electrode is -1KV, the flow rate of the shell layer is 1.2mL/h, the flow rate of the core layer is 0.3mL/h, the receiving distance is 15cm, and the ambient temperature is 25°C. The humidity is 40%~60%, the spinning time is 4~6h, and the coaxial electrospinning equipment is used for spinning. The electrospinning needles are 25G+18G needles. 0.85mm.

[0038] The in vitro release measurement of the coaxial drug-loaded sustained-release nanofiber membrane of the present embodiment 1 is as follows:

[0039](1) Weigh 50.2 mg of the drug-loaded nanofiber membrane prepared above with an analytical balance, first immerse it in 50 mL of pH=1.2 hydrochloric acid buffer (simulating gastric release), place it on a constant temperature shaker, and set the parameters to 37° C. It is 100 times/min, the release time is 120min, 5mL of release medium is taken out every 30min, and the same volume of hydrochloric acid buffer is added at the same time, and the absorbance of the release medium at 265nm is measured by UV-1800 UV-Vis spectrophotometer, and the drug is calculated. cumulative release;

[0040] (2) The drug-loaded nanofiber membrane released for 120min was transferred and immersed in 50mL pH=6.8 phosphate buffer (simulating intestinal release), placed on a constant temperature shaker, the parameters were set to 37°C, the speed was 100 times/min, and the interval was Time to take out 5 mL of release medium, and add the same volume of phosphate buffer at the same time, use UV-1800 UV-Vis spectrophotometer to measure the absorbance of the release medium at 265 nm, and calculate the cumulative drug release;

[0041] (3) The drug-loaded nanofiber membrane released for 240min was transferred and immersed in 50mL pH=7.6 phosphate buffer (simulated colon release), placed on a constant temperature shaker, the parameter was set to 37°C, the speed was 100 times/min, and the interval was set to 100 times/min. 5 mL of release medium was taken out, and the same volume of phosphate buffer was added at the same time. The absorbance of the release medium at 265 nm was measured with a UV-1800 UV-Vis spectrophotometer, and the cumulative drug release was calculated.

[0042] like figure 1 Shown is the high performance liquid chromatogram of the sinomenine hydrochloride used in Example 1 of the present invention. As can be seen from the figure, the retention time of the sinomenine hydrochloride is 11 min, and the content reaches a maximum of 76%.

[0043] like figure 2 As shown in the figure, it is a microscopic picture of the nanofiber membrane obtained by electrospinning in Example 1 of the present invention. It can be seen from the figure that a continuous nanofiber membrane is prepared by electrospinning technology, and sinomenine hydrochloride is large Parts are encased in a fibrous membrane.

[0044] like image 3 As shown in the figure, the nanofiber membrane prepared in Example 1 of the present invention is released in the hydrochloric acid buffer with pH of 1.2 and the phosphate buffer with pH of 6.8 and 7.6. It can be seen from the figure that the nanofiber membrane has a pH of 1.2. In the simulated gastric environment, only 5% was released in two hours, and in the simulated intestinal environment with pH 6.8, only 4% was released in two hours, and in the simulated colon environment with pH 7.4, 24 hours were achieved. The slow release rate of sinomenine hydrochloride reaches about 80%. This figure fully proves that sinomenine hydrochloride is encapsulated in the nanofiber membrane and hardly released in the gastrointestinal tract, but achieves the effect of targeted sustained release in the colon.

[0045] Example 2

[0046] A preparation method of colon-targeted sinomenine hydrochloride sustained-release nanofibrous membrane is basically the same as the method in Example 1, and the difference is:

[0047] In step (1), the amount of polyacrylic resin Eudragit S100 is 2.2501g; the solution is 6.3750g of N,N-dimethylacetamide mixed with 6.3750g of absolute ethanol. The rest of the steps are the same.

[0048] In step (3), in the electrospinning process, the voltage of the positive electrode is +17KV, and the ambient temperature is 26°C, and the drug-loading amount of the obtained drug-loaded nanofiber membrane is 20%-30%.

[0049] The in vitro release amount of the coaxial drug-loaded sustained-release nanofiber membrane in Example 2 was determined by the same method as in Example 1. The nanofiber membrane prepared in Example 2 of the present invention released only about 5% in two hours in a simulated stomach environment with pH 1.2, and only released about 4% in two hours when transferred to a simulated intestinal environment with pH 6.8 , transferred to a simulated colon environment with pH 7.4, and achieved a slow release for 24 hours, with a release rate of about 80%, which fully proves that sinomenine hydrochloride is encapsulated in the nanofibrous membrane and hardly released in the gastrointestinal tract, while The effect of targeted sustained release at the colonic site is achieved.

[0050] Example 3

[0051] A preparation method of colon-targeted sinomenine hydrochloride sustained-release nanofibrous membrane is basically the same as the method in Example 1, and the difference is:

[0052] In step (1), the amount of polyacrylic resin Eudragit S100 is 2.2498g; the solution is 6.3750g of N,N-dimethylacetamide mixed with 6.3750g of absolute ethanol. The rest of the steps are the same.

[0053] In step (2), weigh 0.2503g of polyacrylic acid resin Eudragit RS100 and 0.3003g of sinomenine hydrochloride; add them to a mixed solution of 1.0556g of chloroform and 3.6944g of absolute ethanol, and stir at room temperature to obtain a core layer spinning solution . Among them, the concentration of absolute ethanol is greater than or equal to 99.7%, and the concentration of chloroform is greater than or equal to 99.0%; the stirring time is 4h;

[0054] In step (3), in the electrospinning process, the voltage of the positive electrode is +17KV, and the ambient temperature is 26°C, and the drug-loading amount of the obtained drug-loaded nanofiber membrane is 20%-30%.

[0055] The in vitro release amount of the coaxial drug-loaded sustained-release nanofiber membrane of Example 3 was determined by the same method as in Example 1. The nanofiber membrane prepared in Example 3 of the present invention released only about 5% in two hours in a simulated stomach environment with pH 1.2, and only released about 4% in two hours when transferred to a simulated intestinal environment with pH 6.8 , transferred into a simulated colon environment with pH 7.4, and achieved a slow release of 24 hours, with a release rate of about 80%, which fully proves that sinomenine hydrochloride is encapsulated in the nanofibrous membrane and hardly released in the gastrointestinal tract. The effect of targeted sustained release in the colonic site.