Preparation and application of a dextran-protoporphyrin prodrug nanomicelle

A nano-micelle and protoporphyrin technology, which is applied in the field of preparation of dextran-protoporphyrin prodrug nano-micelle, can solve problems such as instability and poor water solubility of photosensitizers, and achieve enhanced stability and low toxicity and side effects , high biological safety effect

Active Publication Date: 2022-03-11
SOUTHWEST UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The technical problem solved by the present invention provides a method for preparing a small molecule prodrug co-delivered by a photosensitizer and carbohydrates, which fundamentally solves the problem of poor water solubility and instability of the photosensitizer

Method used

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  • Preparation and application of a dextran-protoporphyrin prodrug nanomicelle
  • Preparation and application of a dextran-protoporphyrin prodrug nanomicelle
  • Preparation and application of a dextran-protoporphyrin prodrug nanomicelle

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Embodiment 1

[0031] Example 1 Preparation of a dextran-protoporphyrin prodrug

[0032] A kind of general synthetic schematic diagram of dextran-protoporphyrin prodrug is as figure 1 As shown, it mainly includes the following steps:

[0033] (1) The entire reaction process is carried out in an argon environment, and argon is used as a protective gas to prevent the presence of oxygen or hydrogen from affecting the reaction; at the same time, due to the presence of the photosensitizer protoporphyrin during the entire preparation process, it should be protected from light ; Protoporphyrin (PpIX) (57 mg, 0.1 mmol) was dissolved in 5 mL of anhydrous dichloromethane DCM to obtain a protoporphyrin solution, followed by addition of N-(3-dimethylaminopropyl)-N '-Ethylcarbodiimide hydrochloride EDC (75mg, 0.4mmol) and N-hydroxysuccinimide NHS (46mg, 0.4mmol) were stirred continuously to dissolve them. After dissolution, continue to stir in an ice bath for 30min, and then add hydrazine (1.2 mmol), r...

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Abstract

The invention discloses the preparation and application of a dextran-protoporphyrin prodrug nano-micelle. The preparation method comprises the following steps: (1) aminated protoporphyrin (PpIX-NH 2 ) preparation; (2) preparation of aldylated dextran (DEX‑CHO); (3) DEX‑CHO‑PpIX‑NH 2 and the preparation of DEX‑PpIX micelles. The prepared micelles have the advantages of stable particle size, uniform dispersion, high drug loading capacity, low toxicity and side effects, good biological safety, and good drug controlled release, which fundamentally improves the problem of poor water solubility of protoporphyrin. The modification of protoporphyrin by dextran greatly reduces the toxic and side effects of photosensitizers on normal cells. At the same time, the small molecule prodrug is released in a controlled manner in cancer cells, resulting in the effective enrichment of protoporphyrin in the tumor site. Through laser irradiation, Killing cancer cells to achieve precise diagnosis and treatment provides a new strategy and systematic theoretical support for the development of small molecule phototherapeutic prodrug delivery systems.

Description

technical field [0001] The invention relates to the fields of macromolecule chemical medicine and some biology, in particular to a preparation method and application of a dextran-protoporphyrin prodrug nano-micelle. Background technique [0002] Cancer is one of the major public health problems worldwide and has become a major killer threatening the health of our people. The World Health Organization's International Agency for Research on Cancer (IARC) recently released the latest global cancer burden data for 2020. According to statistics, in 2020, there will be about 19.29 million new cases of cancer and about 9.96 million deaths in the world. Among them, about 4.57 million new cancer cases will be reported in China, accounting for 23.7% of the world's total, and the number of deaths will be about 3 million, accounting for about 3 million of the global cancer deaths. about 30% of the population. Therefore, it is a general trend to find a new method and new strategy to im...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/61A61K41/00A61P35/00A61K49/00A61K49/22
CPCA61K47/61A61K41/0071A61P35/00A61K49/0054A61K49/0036A61K49/221A61K49/0002
Inventor 许志刚叶孟婕贾蝶康跃军
Owner SOUTHWEST UNIV
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