A kind of prodrug and its preparation method and application

A prodrug and reaction technology, used in pharmaceutical formulations, drug combinations, drug delivery, etc., can solve problems such as large toxic side effects, poor targeting, and poor water solubility.

Active Publication Date: 2020-12-15
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in clinical application, there are disadvantages of poor water solubility, high toxicity and side effects, and poor targeting.

Method used

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  • A kind of prodrug and its preparation method and application
  • A kind of prodrug and its preparation method and application
  • A kind of prodrug and its preparation method and application

Examples

Experimental program
Comparison scheme
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preparation example Construction

[0075] (1) Preparation of succinylated paclitaxel: Suspend succinic anhydride in dichloromethane, add paclitaxel, stir, add anhydrous pyridine, stir and react for 24-48 hours; after reaction, distill under reduced pressure, add water to wash, centrifuge to collect the precipitate, and vacuum dry. to obtain succinyl paclitaxel;

[0076] Wherein, the mass ratio of succinyl to paclitaxel is 1:1-1:10, further 1:3-1:5, and the amount of pyridine is 0.1-0.3% (v / v) of the reaction system.

[0077] (2) Preparation of hyaluronic acid-cystamine: dissolve hyaluronic acid in PBS solution with pH 7.4, add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in sequence Salt (EDC·HCl), N-hydroxysuccinimide (NHS), stir at room temperature to activate the carboxyl group of HA for a period of time, add cystamine, continue stirring to obtain a crude product, which is purified by dialysis and freeze-dried to obtain HA-cys polymerization thing;

[0078] Wherein, the feeding of hyaluronic a...

Embodiment 1

[0089] Example 1 Synthesis of paclitaxel-hyaluronic acid-chlorin e6 polymer

[0090] (1) Weigh 20mg of succinic anhydride, add 8mL of dichloromethane, magnetically stir to dissolve, add 60mg of PTX, magnetically stir to dissolve, add 60μL of anhydrous pyridine, and stir for 24 hours after the reaction system is clarified. Distill under reduced pressure, add 10 mL of water, stir for 15 min, collect the precipitate after centrifugation, wash the precipitate with 30 mL of water again, and dry in vacuo to obtain succinylated paclitaxel (compound of formula 1).

[0091] (2) Weigh 0.2g hyaluronic acid, dissolve it in 50mL PBS (pH=7.4), add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC· HCl) 78.2mg, N-hydroxysuccinimide (NHS) 47.0mg, stirred at room temperature to activate the carboxyl group of HA for 30min, added 1.12g of cystamine, and continued to stir for 24h to obtain a crude product, which was purified by water dialysis and freeze-dried to obtain hyaluronic...

Embodiment 2

[0096] Weigh 5mg of the paclitaxel-hyaluronic acid-chlorin e6 polymer obtained in Example 1, dissolve it in 3mL of water, ultrasonicate the probe for 4min, the power is 40w, the ultrasonic pulse is turned on for 2s and turned off for 4s, and the obtained colloidal solution is passed through 0.45μm Microporous membrane to obtain green paclitaxel-hyaluronic acid-chlorin e6 polymer self-assembled nanoparticle solution, transmission electron microscope to investigate the shape of nanoparticles, see figure 2 .

[0097] To investigate the reduction sensitivity of self-assembled nanoparticles, incubate nanoparticles with high concentration (20mM) dithiothreitol (DTT) for 4h, compare the particle size and particle size distribution in DTT environment and water, see Figure 3-4 , the result is as follows:

[0098]

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Abstract

The invention provides a prodrug and a preparation method and application thereof. The prodrug is basically composed of compounds shown in formulas 1 and 2 and a polymer monomer structure shown in formula 3, wherein the compounds shown in the formulas 1 and 2 are connected with cystamine of the monomer structure shown in the formula 3; according to the prodrug, the solubility of the loaded drug isimproved, in-vivo distribution is improved, chemical therapy and photodynamic therapy are combined, and the higher anti-tumor effect is achieved.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a prodrug and its preparation method and application. Background technique [0002] The information disclosed in this background section is only intended to increase the understanding of the general background of the present invention, and is not necessarily taken as an acknowledgment or any form of suggestion that the information constitutes the prior art already known to those skilled in the art. [0003] Paclitaxel, also known as paclitaxel, taxol, porphyrin, and special element, is the best natural anticancer drug that has been discovered so far. It has been widely used in the treatment of breast cancer, ovarian cancer, some head and neck cancers and lung cancer in clinical practice. However, in clinical application, there are disadvantages of poor water solubility, high toxicity and side effects, and poor targeting. [0004] Amphiphilic polysaccharide po...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/61A61K31/337A61K41/00A61P35/00
CPCA61K31/337A61K41/0071A61K47/6939A61P35/00A61K2300/00
Inventor 翟光喜付曼菲王汝娟
Owner SHANDONG UNIV
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