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Azo high polymer for transporting medicine to intestinal tracts and releasing medicine as well as preparation method and application of azo high polymer

A polymer and azo technology, applied in the field of medicine, can solve problems such as reducing transportation efficiency

Active Publication Date: 2021-08-20
NANJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these materials usually contain easily degradable cross-linking groups, such as amide bonds, ether-ester bonds, etc., which make them partially degrade before reaching the colon and reduce the transport efficiency

Method used

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  • Azo high polymer for transporting medicine to intestinal tracts and releasing medicine as well as preparation method and application of azo high polymer
  • Azo high polymer for transporting medicine to intestinal tracts and releasing medicine as well as preparation method and application of azo high polymer
  • Azo high polymer for transporting medicine to intestinal tracts and releasing medicine as well as preparation method and application of azo high polymer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] The synthetic method of embodiment 1 azo high polymer polymer-DE is as follows:

[0035]① Add 4-nitroaniline (2.0 g, 14.48 mmol) into ultrapure water (15 mL), and add concentrated HCl (3.7 mL). Stir at room temperature for 30 minutes at 600 rpm. The solution was then cooled to 0~5°C, and a solution of sodium nitrite (1.0 g, 14.49 mmol) in water (15 mL) was added slowly. The resulting mixture was stirred at 0~5°C for 1 hour, then added to a solution of 3-hydroxybenzoic acid (2.0 g, 14.48 mmol) and NaOH (1.16 g, 28.96 mmol). Add dropwise (15 mL) via addition funnel at 0°C. The resulting suspension was stirred for another hour. The orange precipitate was then filtered and washed well with water. After vacuum freeze-drying, an orange solid compound A (3.3363 g, 11.62 mmol) was obtained with a yield of 80.22%.

[0036] Detection shows that the prepared compound A nuclear magnetic characterization is as follows: 1 H NMR (400MHz, CD 3 OD) δ8.38(d, J=9.1Hz, 2H), 7.99(d, ...

Embodiment 2

[0049] Degradation experiment of embodiment 2 azo high polymer polymer-D'1E'1:

[0050] ①Cultivate Escherichia coli BL21 in 100mL LB liquid medium to OD 600nm After =0.6~0.8, centrifuge for 5min at a speed of 8000rpm, and remove the supernatant;

[0051] ②Add 7.5mL buffer solution (Tris(20mM), NaCl(300mM),pH=7.00), freeze-thaw and ultrasonically lyse 6 times, then centrifuge at 8000rpm for 5min each time, and keep the supernatant;

[0052] ③ Add 75 μL each of kanamycin (5 mg / mL) and ampicillin sodium (5 mg / mL), 300 μL of NADH (15 mM), and 75 μL of polymer-D’1E’1 in DMSO (5 mg / mL). Incubate for 14 hours in a shaker at 37°C with a rotation speed of 180 rpm;

[0053] ④Centrifuge the cultured mixed solution for 5min at 8000rpm, remove the supernatant, add 7.5mL DMSO to the precipitate to completely dissolve polymer-D'1E'1;

[0054] ⑤Centrifuge again, measure the ultraviolet absorbance of the supernatant, and compare it with the DMSO solution of polymer-D'1E'1 with the same init...

Embodiment 3

[0056] The degradation experiment of embodiment 3 azo high polymer polymer-D'3E'1:

[0057] ①Cultivate Escherichia coli BL21 in 100mL LB liquid medium to OD 600nmAfter =0.6~0.8, centrifuge for 5min at a speed of 8000rpm, and remove the supernatant;

[0058] ②Add 7.5mL buffer solution (Tris(20mM), NaCl(300mM),pH=7.00), freeze-thaw and ultrasonically lyse 6 times, then centrifuge at 8000rpm for 5min each time, and keep the supernatant;

[0059] ③ Add 75 μL each of kanamycin (5 mg / mL) and ampicillin sodium (5 mg / mL), 300 μL of NADH (15 mM), and 75 μL of polymer-D’3E’1 in DMSO (5 mg / mL). Incubate for 14 hours in a shaker at 37°C with a rotation speed of 180 rpm;

[0060] ④Centrifuge the cultured mixed solution for 5min at 8000rpm, remove the supernatant, add 7.5mL DMSO to the precipitate to completely dissolve polymer-D'3E'1;

[0061] ⑤Centrifuge again, measure the ultraviolet absorbance of the supernatant, and compare it with the DMSO solution of the same initial concentration...

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Abstract

The invention discloses an azo high polymer for transporting medicine to intestinal tracts and releasing the medicine as well as a preparation method and application of the azo high polymer. The azo high polymer is synthesized by taking dibromoalkane with two brominated ends, oligomeric glycol, paranitroaniline and m-hydroxybenzoic acid as main raw materials. The final structure of the azo high polymer is shown in a formula described in the specifications of the invention; in the formula, x is equal to the sum of y and z, n is equal to 2, 3, 4, 5..., m is equal to 2, 3, 4, 5...; the high polymer can wrap the medicine to form particles through a double emulsification method, the particles reach the intestinal tracts through oral administration, then azo bonds are cut off by bacteria living in the intestinal tracts, the medicine is released, and therefore the effect of treating intestinal diseases is achieved.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to an azo high polymer used for transporting and releasing medicine to the intestinal tract and its preparation method and application. Background technique [0002] There are various types of microorganisms in the human body, and the intestinal flora accounts for the vast majority. These bacteria participate in digestion and metabolism by secreting enzymes with different properties, and affect many key functional systems of the human body, such as the nervous system and immune system. The imbalance of intestinal flora and changes in the microenvironment may be accompanied by corresponding intestinal diseases, such as: inflammatory reactive bowel disease, human colorectal cancer, etc. [0003] Researchers often use enzymes secreted by intestinal flora to catalyze the decomposition of molecules and release small molecular substances such as aminosalicylic acid to achieve anti-inf...

Claims

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Application Information

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IPC IPC(8): C07D249/04A61K47/22
CPCC07D249/04A61K47/22Y02A50/30
Inventor 王晓剑朱世玉王益万邹娟
Owner NANJING UNIV OF TECH