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Preparation and application of composite polysaccharide gel based on folic acid targeting

A compound polysaccharide and folic acid targeting technology, which can be used in medical preparations with non-active ingredients, medical preparations containing active ingredients, and drug combinations, etc., can solve problems such as limiting the development of folic acid-polysaccharide complex systems and difficulties in covalent bonding.

Active Publication Date: 2018-05-25
NORTHWEST NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the coupling of natural polymer polysaccharides and folic acid generally adopts the amidation reaction of the amino group of chitosan and the carboxyl group of folic acid. However, it is difficult to covalently combine neutral polysaccharides, especially acidic polysaccharides and folic acid. Great restrictions on the preparation of folic acid-polysaccharide complex system and the development of related materials

Method used

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  • Preparation and application of composite polysaccharide gel based on folic acid targeting
  • Preparation and application of composite polysaccharide gel based on folic acid targeting
  • Preparation and application of composite polysaccharide gel based on folic acid targeting

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] A preparation based on folic acid-targeted complex polysaccharide gel, comprising:

[0057] (1) Preparation of aminated alginic acid:

[0058] Add 0.2 g of sodium alginate to 50 mL of anhydrous formamide, add 2 mL of 0.5 mol / L hydrochloric acid, stir at 70°C until completely dissolved, add 0.2 g of EDC, stir for 30 min, and cool to room temperature. Then, drop this mixed solution into 1 mL of ethylenediamine at a rate of 40 drops / min, and react at 30°C for 20 hours. After the reaction, wash with 53 mL of acetone for 7 times, and filter with suction. Vacuum drying at ~0.08 MPa for 8-12 h yielded aminated alginic acid with a nitrogen content of 6.27%.

[0059] (2) Coupling of aminated alginic acid and folic acid:

[0060] Stir 0.1 g of aminated alginic acid at 60 °C until completely dissolved in 40 mL of anhydrous formamide. Add 0.22g of folic acid into 20mL of DMSO, and stir until completely dissolved at room temperature in the dark, add 0.382g of EDC and 0.232g of NH...

Embodiment 2

[0064] A preparation based on folic acid-targeted complex polysaccharide gel, comprising:

[0065] (1) Preparation of aminated alginic acid:

[0066] Add 0.2 g of sodium alginate to 40 mL of anhydrous formamide, add 2 mL of 0.5 mol / L hydrochloric acid, stir at 80°C until completely dissolved, add 0.25 g of EDC, stir for 20 min, and cool to room temperature. Then, drop this mixed solution into 2 mL of ethylenediamine at a rate of 30 drops / min, and react at 25°C for 18 hours. After the reaction, wash with 66 mL of acetone for 5 times, filter with suction, and filter the cake at 50°C and 0.08 MPa. Vacuum-dried for 8 h to obtain aminated alginic acid with a nitrogen content of 8.03%.

[0067] (2) Coupling of aminated alginic acid and folic acid:

[0068] Stir 0.1 g of aminated alginic acid at 40 °C until completely dissolved in 50 mL of anhydrous formamide. Add 0.22g of folic acid into 22mL of DMSO, and stir until completely dissolved at room temperature in the dark, add 0.382g...

Embodiment 3

[0072] A preparation based on folic acid-targeted complex polysaccharide gel, comprising:

[0073] (1) Preparation of aminated alginic acid:

[0074] Add 0.2g of sodium alginate to 50mL of anhydrous formamide, add 2mL of 0.5mol / L hydrochloric acid, stir at 75°C until completely dissolved, add 0.25g of EDC, stir for 25min, and cool to room temperature. Then, drop this mixed solution into 2 mL of ethylenediamine at a rate of 50 drops / min, and react at 30°C for 24 hours. After the reaction, wash with 106 mL of acetone for 8 times, filter with suction, and filter the cake at 55°C and 0.06 MPa. Vacuum drying for 10 h yielded aminated alginic acid with a nitrogen content of 8.46%.

[0075] (2) Coupling of aminated alginic acid and folic acid:

[0076] Stir 0.1 g of aminated alginic acid at 50 °C until completely dissolved in 33 mL of anhydrous formamide. Add 0.22g of folic acid into 20mL of DMSO, and stir until completely dissolved at room temperature in the dark, add 0.382g of E...

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Abstract

The invention discloses a preparation method of a composite polysaccharide gel based on folic acid targeting, and belongs to the technical field of biology macromolecules. The preparation method comprises the following steps of enabling a coupling agent to modify acid polysaccharide, coupling with the folic acid, and performing in-situ releasing, so as to prepare a three-component composite polysaccharide gel with an interpenetration crosslinking network structure and high mechanical strength. The composite polysaccharide gel has the in-vitro drug-release targeting property based on the identification of folic acid receptor at the surface of tumor cell. The preparation method has the advantages that the coupling effect is good, and the conversion rate is high; the composite polysaccharidegel can load various anti-tumor drugs, and the application range of the natural macromolecules is widened.

Description

technical field [0001] The invention belongs to the technical field of biological macromolecules, and relates to the preparation and application of a folic acid-functionalized polysaccharide composite gel, in particular to the folic acid-targeted composite polysaccharide gel-loaded antitumor drug and its application. Background technique [0002] Polysaccharide is a natural polymer compound with good viscosity and sol-gel transition ability. The polysaccharide molecular chain contains a variety of functional groups, such as hydroxyl, carboxyl and amino groups, which can interact with functional groups on other compounds. Reaction, as a drug-loaded carrier applied to the drug delivery system. Sodium alginate is widely used in the field of drug release, but the mechanical strength of sodium alginate hydrogel is low and easy to degrade, which seriously limits the application range in the field of drug release, so it forms a composite gel with other polymers The mechanical st...

Claims

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Application Information

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IPC IPC(8): A61K9/06A61K47/36A61K47/22A61K31/519A61P35/00
CPCA61K9/06A61K31/519A61K47/22A61K47/36
Inventor 王俊龙李瑞秦晓洁杨婷包爱娟郭淑娟张会孔维宝梁俊玉姚健张继
Owner NORTHWEST NORMAL UNIVERSITY
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