Nano-carrier particle prepared from sugar-modified folic acid derivative and application of nano-carrier particle

A folic acid derivative and sugar modification technology, applied in the field of biomedicine, can solve the problems of affecting the therapeutic effect, uneven particle size of nanoparticles, immunogenicity reaction, etc. simple effect

Active Publication Date: 2020-09-29
北京和益源生物技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Firstly, most of the folic acid-modified polymers in these carriers are polymer macromolecules, resulting in a low proportion of folic acid in the molecules and low targeting efficiency; The efficiency of the drug is not high; again, the particles formed after the aggregation of these macromolecular polymers are likely to stimulate the immune system, causing immunogenic reactions and affecting the effect of treatment

Method used

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  • Nano-carrier particle prepared from sugar-modified folic acid derivative and application of nano-carrier particle
  • Nano-carrier particle prepared from sugar-modified folic acid derivative and application of nano-carrier particle
  • Nano-carrier particle prepared from sugar-modified folic acid derivative and application of nano-carrier particle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] This embodiment provides a nanocarrier particle FA-2-DG. FA-2-DG is formed by linking deoxyglucose and folic acid via aminoethanol, wherein the carboxyl group of folic acid is connected with the amino group of aminoethanol to form an amide bond, and the aminoethanol The hydroxyl group and the hydroxyl group of deoxyglucose are connected to form a glycosidic bond. The chemical structural formula of the FA-2-DG is as figure 2 shown.

[0044] Deoxyglucose has multiple hydroxyl groups. During the reaction, the hydroxyl groups have high reactivity, so they need to be protected with acetyl groups before the reaction. The acetyl-protected reaction proceeds from deoxyglucose and acetic anhydride in anhydrous pyridine. The amino group of aminoethanol will also have relatively high reactivity during the reaction process, so aminoethanol is not used directly in the reaction process, but 2-bromoethanol is used to react with acetyl deoxyglucose first, and this step requires trifl...

Embodiment 2

[0073] This embodiment provides a nanocarrier particle—glucose-modified folic acid derivative. The folic acid derivative is formed by linking glucose and folic acid through a linking arm of two carbon atoms, aminoethanol, and is a kind of nanocarrier particle. The 1-hydroxyl group of glucose and the hydroxyl group of aminoethanol form a glycosidic bond, and the carboxyl group of folic acid and the amino group of aminoethanol form an amide bond. The structure formed in this way can maintain good stability in vitro, and can be widely used in vivo by amidase and Hydrolyzed by glycosidase, quickly metabolized and excreted from the body, not easy to cause accumulation.

[0074] Such as Figure 6 As shown, taking glucose and connecting arm as an example of aminoethanol with 2 carbon atoms, the synthesis of the folic acid derivative comprises the following steps:

[0075] (1) Preparation of 6-(acetoxymethyl)-tetrahydro-2,3,4,5-tetraacetoxy-pyran (compound 2)

[0076] Dissolve 5.0 g...

Embodiment 3

[0095] In this example, the nano-carrier particles prepared in Example 1 were used to carry the anti-tumor drug cisplatin to obtain a targeted anti-tumor nano-particle, which was connected to the nano-carrier particles described in Example 1 and cisplatin through a coordination bond. To prepare the complex of FA-2-DG and cisplatin, mix the aqueous solution of cisplatin and FA-2-DG of the same concentration and stir at room temperature. After two hours, cisplatin and FA-2-DG are formed as Figure 8 The coordination compound (FA-2-DG-Pt) shown. The mixed solution was injected into HPLC-MS analysis, and the formation of the complex was confirmed. For mass spectrometry results, see Figure 9 .

[0096] The morphological characterization techniques of atomic force microscopy, transmission electron microscopy and scanning electron microscopy all confirmed that FA-2-DG itself can self-assemble to form nanoparticles, and form a coordination bond with cisplatin, and obtain FA-2-DG-Pt...

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Abstract

The invention discloses a nano-carrier particle prepared from a sugar-modified folic acid derivative and application of the nano-carrier particle; the nano-carrier particle is a novel nano-carrier particle formed by combining folic acid and sugar together by taking a carbon chain as a connecting bridge and utilizing a chemical bond mode; the sugar comprises, but not limited to, pentose and hexose,deoxyglucose, glucose, glucosamine, fructose, lactose and the like; the sugar and the folic acid are connected through a glycosidic bond or an ester bond; and furthermore, the length of a modified carbon chain between the sugar and the folic acid can be any number between 2 and 18 carbon atoms. The nano-carrier particle in the invention can be used for loading an anti-tumour drug; the molecular weight of the anti-tumour drug is 20-2000 Daltons; the nano-carrier particle not only solves the problem of poor water solubility of folic acid and is high in stability, but also has a self-assembly property; stable nano-particles are formed; and a variety of anti-tumour drugs can be efficiently carried in a targeted manner.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a nano-carrying particle prepared from a sugar-modified folic acid derivative and an application thereof. Background technique [0002] Folate receptors are highly expressed receptors on the surface of certain tumor cells in the human body. The development of anti-tumor therapeutic drugs targeting folic acid receptors has been going on for many years, but no mature therapeutic drugs have been introduced to the market so far. The existing folic acid-related anti-tumor drug development mostly uses folic acid to modify macromolecular PEG (polyethylene glycol) as a carrier, or as a part of a mixed carrier of various materials to carry anti-tumor drugs. Although this therapeutic strategy can achieve the function of targeting folate receptors, there are many shortcomings. Firstly, most of the folic acid-modified polymers in these carriers are polymer macromolecules, resulting in...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/54A61K47/69A61K45/00A61K33/243A61K31/7068A61K31/513A61K31/704A61K31/337A61P35/00A61P15/00A61P15/14C07H15/04C07H1/00
CPCA61K47/545A61K47/549A61K47/6929A61K45/00A61K33/243A61K31/7068A61K31/513A61K31/704A61K31/337A61P35/00A61P15/00A61P15/14C07H15/04C07H1/00Y02P20/55
Inventor 金绍明葛绍阳刘治麟王鹏杰杜仲尧
Owner 北京和益源生物技术有限公司
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