A kind of multiple nano delivery system and its preparation method

A delivery system, a certain amount of technology, applied in the direction of pharmaceutical formulations, medical preparations of non-active ingredients, active ingredients of amines, etc., can solve the problem of single function of materials

Active Publication Date: 2021-08-17
GUANGZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the relatively single function of the material, the traditional nano-drug delivery system can only achieve single delivery of drugs or genes.

Method used

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  • A kind of multiple nano delivery system and its preparation method
  • A kind of multiple nano delivery system and its preparation method
  • A kind of multiple nano delivery system and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] In this embodiment, a multiple nano-delivery system and a preparation method thereof comprise the following steps:

[0058] (1) Accurately weigh 5.3mmol β-cyclodextrin and 34.1mmol 18-crown-6 under inert gas protection conditions, dissolve in 30mL anhydrous DMF, then add 42.0mmol KH and keep stirring to make it mix with cyclodextrin Hydroxyl fully reacted. Control the temperature at 50°C, and slowly add 13.4mL of glycidol dissolved in 10mL of anhydrous DMF into the above solution dropwise, and the dripping is completed in about 24 hours. Control the temperature at 80°C and continue the reaction for 16h to end. After the temperature of the system dropped to room temperature, a small amount of water was added to terminate the reaction, dialyzed against water (MWCO=1000), and freeze-dried to obtain a pale yellow β-CD-HPG solid.

[0059] (2) 8 mmol CDI dissolved in 10 mL of anhydrous DMF was slowly added dropwise into the solution of 4 mmol β-CD-HPG (dissolved in anhydrous ...

Embodiment 2

[0064] In this embodiment, a multiple nano-delivery system and a preparation method thereof comprise the following steps:

[0065] (1) Accurately weigh 5.3mmol β-cyclodextrin and 34.1mmol 18-crown-6 under inert gas protection conditions, dissolve in 30mL anhydrous DMF, then add 42.0mmol KH and keep stirring to make it mix with cyclodextrin Hydroxyl fully reacted. Control the temperature at 50°C, and slowly add 26.8 mL of glycidol dissolved in 20 mL of anhydrous DMF into the above solution dropwise, and the drop will be completed in about 24 hours. Control the temperature at 80°C and continue the reaction for 16h to end. After the temperature of the system dropped to room temperature, a small amount of water was added to terminate the reaction, dialyzed against water (MWCO=1000), and freeze-dried to obtain the host molecule β-CD-HPG solid with a higher degree of polymerization.

[0066] Steps (2)-(5) are the same as in Example 1.

Embodiment 3

[0068] In this embodiment, a multiple nano-delivery system and a preparation method thereof comprise the following steps:

[0069] Steps (1), (2), (4), and (5) in Example 1 are retained, and the step of targeting the mannose-modified host molecule is removed to obtain a non-targeting multiple nano-delivery system.

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Abstract

The invention discloses a multi-nano delivery system, which is obtained by dissolving host molecules and guest molecules in water at an equimolar ratio, fully stirring and reacting, dialysis and freeze-drying. The guest molecule is obtained by coupling amantadine hydrochloride through DSPE‑PEG‑NHS under basic conditions. The preparation method of the main molecule is as follows: firstly, using β-cyclodextrin as a starting material, ring-opening glycidol under alkaline conditions to obtain β-cyclodextrin grafted hyperbranched polyglycerol β-CD-HPG; Dicarbonylimidazole is used as a coupling reagent, and tris(2-aminoethyl)amine is linked to the hydroxyl group of β-CD-HPG to obtain β-cyclodextrin grafted hyperbranched polyglycerol grafted tris(2-aminoethyl) ) amine β-CD-HPG-TAEA; then using a targeting reagent to carry out targeted modification on β-CD-HPG-TAEA to obtain the host molecule. The multiple nano-delivery system can not only simultaneously load small molecule drugs and nucleic acid fragments, but the loaded small molecule drugs and nucleic acid fragments can be flexibly adjusted according to usage requirements.

Description

technical field [0001] The invention relates to a nano drug carrier, in particular to a multiple nano delivery system and a preparation method thereof. Background technique [0002] The nano-drug delivery system based on amphiphilic polymers can overcome the low bioavailability, poor stability and pharmacological effects of existing pharmaceutical preparations by combining their advantages such as long circulation, targeting, controlled release, transmucosal, transdermal and physicochemical responses. Short time, serious adverse reactions and other defects have attracted extensive attention of researchers in recent years. [0003] Tumor tissue structure is complex and proliferates rapidly, resulting in heterogeneity of tumor tissue structure and complex tumor microenvironment. Single drug therapy has limited effect, and long-term use will also cause drug resistance problems. The combination therapy of drugs and genes is a new and effective method for the treatment of tumors...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08G65/28C08G65/333C08G65/332C08G65/334C08B37/16A61K47/60A61K31/13A61K47/69
CPCA61K31/13A61K47/60A61K47/6951C08B37/0012C08G65/2606C08G65/2609C08G65/3324C08G65/3328C08G65/33306C08G65/3331C08G65/33396C08G65/3348
Inventor 杨斌尚同祎郑国栋陈晓明
Owner GUANGZHOU MEDICAL UNIV
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