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Poly n-(2-hydroxypropyl) methacrylamide-lonidamine macromolecular prodrug and preparation method thereof

A technology of methacrylamide and hydroxypropyl, which is applied in the field of drug synthesis, can solve the problems of low bioavailability, low water solubility of lonidamine, and reduced therapeutic index, and achieve good biocompatibility and increase water solubility And the effect of half-life and high rate of receiving medicine

Inactive Publication Date: 2017-02-01
NORTHWEST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, lonidamine has low water solubility, low bioavailability, and no targeting, which reduces its therapeutic index.

Method used

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  • Poly n-(2-hydroxypropyl) methacrylamide-lonidamine macromolecular prodrug and preparation method thereof
  • Poly n-(2-hydroxypropyl) methacrylamide-lonidamine macromolecular prodrug and preparation method thereof
  • Poly n-(2-hydroxypropyl) methacrylamide-lonidamine macromolecular prodrug and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1: the synthesis of PHPMA

[0024] In a 100 mL three-neck flask, add 55 mL ethanol, 8.0 gHPMA, and 1.3 g AIBN in sequence, pass nitrogen gas under the liquid surface for 5 mins (exhaust the air), seal it, slowly raise the temperature to 55 °C and keep it for 24 h, after the reaction is complete, reduce the pressure Distill about 50 mL of ethanol, add 40 mL of ether, and stir vigorously. A large amount of white solid is formed. After suction filtration, the obtained solid is soaked in acetone for 5 h, filtered to obtain a white powder, weighing 6.8 g. Its average molecular weight is 17000 measured by viscosity method.

Embodiment 2

[0025] Embodiment 2: the synthesis of PHPMA-LND

[0026] Such as figure 1 As indicated, add 10.0 g PHPMA and 0.7 g DCC into a 100 mL round-bottomed flask, add 20 mL of freshly steamed DMF, stir and dissolve, add 1.0 g LND and 0.1 g DMAP, heat the oil bath to 50°C, and continue the reaction After 12 h, distill under reduced pressure, remove DMF, add 40 mL of acetone, a large amount of solid precipitates, filter with suction to obtain a white solid, wash with a small amount of cold isopropanol, absolute ethanol, absolute ether and acetone for several times , dried, and weighed to obtain 10.2 g of white solid, whose drug loading was determined to be 4.9% by UV.

[0027] The synthesized PHPMA-LND prodrug was analyzed by IR and DSC, the results are as follows:

[0028] From figure 2 The IR spectra of PHPMA and PHPMA-LND can be seen, 3340cm -1 It is the stretching vibration absorption peak of the hydroxyl group in the polymer carrier PHPMA molecular chain, 2950 cm -1 It is th...

Embodiment 3

[0031] Embodiment 3: In vitro hydrolysis release experiment of PHPMA-LND

[0032] Put PHPMA-LND into 4cm-long dialysis bags (molecular weight cut-off 10000) and seal them respectively, and put them into 40mL of pH=1.1 (KCl-glycine / HCl), pH=7.4 (Na 2 HPO 4 / KH 2 PO 4 ), pH=8.0 (tris / CaCl 2 ), pH=10.0 (Na 2 CO 3 / NaHCO 3 ) in a buffer solution at a constant temperature of 37°C for release experiments. Sampling 5.0 mL at a certain time interval for UV testing, quantitatively determine the amount of drug released at this time interval, and at the same time replenish 5.0 mL of fresh buffer solution to the release system to maintain the solution of the release system at 40 mL. The cumulative release amount of the drug was calculated according to the following formula.

[0033] Cumulative Release (%)=100×(40.0C n + 5.0∑C(n-1)) / W 0

[0034] Where: W 0 — the mass of LND in the macromolecule prodrug to be tested (mg);

[0035] C n —Concentration (mg / mL) of LND in the relea...

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Abstract

Poly-N-(2-hydroxypropyl)methacrylamide-lonidamine macromolecule prodrug and preparation method thereof. The invention discloses a compound represented by the general structural formula (I), wherein m=10-500 and n=10-500. The PHPMA-LND macromolecular prodrug synthesized by the present invention can not only increase the water solubility and half-life of the small molecule drug LND, and has a high drug delivery rate, but also can effectively control the release of its drug in the human body, reduce the number of times patients take medicine, and reduce its side effects.

Description

technical field [0001] The invention relates to a prodrug of lonidamine with poly N-(2-hydroxypropyl)methacrylamide as a carrier and a synthesis method thereof, belonging to the technical field of drug synthesis. Background technique [0002] Although the small-molecule drugs that people use daily have high efficacy and are convenient to use, many of them have serious side effects. Generally, small molecule drugs enter the human body through oral administration or injection. Within a short period of time after taking the drug, the concentration of the drug in the blood far exceeds the concentration required for treatment. Too high a concentration may cause poisoning and allergies. At the same time, they have a fast metabolism in the organism, a short half-life, and are easy to excrete. Therefore, as time goes by, the concentration of the drug will decrease rapidly and affect the curative effect. On the other hand, small-molecule drugs also lack selectivity for entering desi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08F8/30C08F120/58A61K47/48
Inventor 张娟张亚洲邢晓虎
Owner NORTHWEST UNIV
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