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HPPE (hyperbranched polyphosphate ester) material of acetal bond skeleton as well as preparation method and application of HPPE material

A polyphosphate and acetal bond technology, which is applied to medical preparations without active ingredients, wave energy or particle radiation treatment materials, and medical preparations containing active ingredients, etc. It can achieve good biocompatibility and degradability, great potential for clinical application, and improve the efficacy of PDT.

Active Publication Date: 2018-11-06
AC PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the embedding of PS in the core of nanoparticles will limit the absorption of light energy by PS.
Afterwards, the process of transferring energy to oxygen results in a decrease in the production rate of ROS, resulting in a decrease in the efficacy of PDT
In addition, due to the extremely short diffusion distance (<20nm) and action time (<40ns) of ROS, the ROS produced by PS in nanoparticles has poor lethality.

Method used

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  • HPPE (hyperbranched polyphosphate ester) material of acetal bond skeleton as well as preparation method and application of HPPE material
  • HPPE (hyperbranched polyphosphate ester) material of acetal bond skeleton as well as preparation method and application of HPPE material
  • HPPE (hyperbranched polyphosphate ester) material of acetal bond skeleton as well as preparation method and application of HPPE material

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Embodiment 1, the synthesis and characterization of hyperbranched polyphosphate material

[0048] 1. Synthesis of acid-responsive hyperbranched polyphosphate S-hbPPE

[0049] Acid-responsive hyperbranched polyphosphate was obtained by polycondensation reaction of phosphorus oxychloride, 2,2'-(propane-2,2-diylbis(oxy))diethanol and mPEG-OH.

[0050] The synthetic route of S-hbPPE hyperbranched polyphosphate material is as follows figure 1 shown.

[0051] Preparation and pretreatment of required components

[0052] 1. Purification of phosphorus oxychloride and polyethylene glycol to remove water

[0053] Build a set of atmospheric distillation device to remove water vapor. Connect the condenser tube to circulating cooling water, and under the protection of nitrogen, add phosphorus oxychloride to the round bottom flask, place the round bottom flask in an oil bath, set the temperature of the oil bath to 110°C, and turn on the stirring. Collect the pre-distillation frac...

Embodiment 2

[0062] Embodiment 2, the nanoparticle formation and application of hyperbranched polyphosphate

[0063] 1. Preparation of hyperbranched drug-loaded nanoparticles

[0064] Acid-sensitive polymeric materials have been extensively studied as drug delivery vehicles. Among these sensitive nanomaterials, acid-sensitive hyperbranched polymers (HBPs) have specific advantages because of their highly branched topology and many sensitive chemical bonds with multiple triggers for rapid intracellular drug release. location. So far, only a few HBPs nanomaterials have been used as delivery vehicles for PSs.

[0065] Prepare the nanoparticles of hyperbranched polyphosphate by nano precipitation method (Nano precipitation method), the specific method is as follows:

[0066] S-hbPPE (10.0 mg) and photosensitizer Ce6 (1.0 mg) were weighed and dissolved in DMSO (1.0 mL), and then 10 mL of ultrapure water was gradually added to the above material mixture during stirring. Subsequently, after st...

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Abstract

The invention discloses an HPPE (hyperbranched polyphosphate ester) material of an acetal bond skeleton as well as a preparation method and an application of the HPPE material. The method comprises steps as follows: (1), diol containing acetal bonds and triethylamine are dissolved in a solvent, phosphorus oxychloride is added under the condition of ice bath, and stirring reaction is performed; (2), after the reaction, methoxy polyethylene glycol is added, the stirring reaction is performed, and the HPPE material of the acetal bond skeleton is obtained. The HPPE material has good biocompatibility and biodegradability; the HPPE material is self-assembled to form nanoparticles, each acetal bond is broken into two hydroxyls in the endosome / lysosome acid environment in tumor cells, phosphate ofparticle kernels is transformed from hydrophobicity to hydrophility, the particles are disintegrated, a photosensitizer drug is rapidly released, concentration of a free photosensitizer in the tumorcells is increased, a large amount of active oxygen is produced under excitation of a light source with specific wavelength kills the tumor cells, PDT curative effect is improved, and the HPPE material has great clinical application potential.

Description

technical field [0001] The invention relates to the field of polyphosphate materials, in particular to a hyperbranched polyphosphate material with an acetal bond skeleton and a preparation method and application thereof. Background technique [0002] At present, photodynamic therapy (photodynamic therapy, PDT) is a photosensitizer (Photosensitizer, PS) that absorbs light energy of an appropriate wavelength for energy transfer, and excites oxygen molecules to generate cytotoxic reactive oxygen species (Reactive Oxygen Species, ROS). A clinically approved treatment for a variety of localized and superficial cancers. PDT is a non-invasive treatment method, which can precisely control the treatment time and treatment site, and reduce the toxic and side effects on normal tissues. In the past decades of related research, it is mainly through increasing the content of PS in tumor cells to improve the therapeutic effect of PDT. [0003] In recent years, photodynamic therapy (PDT) ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G83/00C08G79/04A61K47/34A61K9/50A61K41/00A61P35/00
CPCA61K9/5031A61K41/0071A61P35/00C08G79/04C08G83/005C08G83/006
Inventor 杨显珠王均曹紫洋
Owner AC PHARMA CO LTD
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