Preparation method and application of hyaluronic acid-small molecule self-assembled nano-drug

A technology of hyaluronic acid and nano-drugs, which is applied in the direction of nano-drugs, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., and can solve problems such as low safety, complicated preparation process, and low drug loading , to achieve the effects of no waste of energy and materials, green and simple preparation process, and high drug loading capacity

Pending Publication Date: 2021-12-28
CHONGQING MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Through the self-assembly between HA and hydrophobic small-molecule drugs, nano-drugs with relatively uniform particle size can be formed to solve the problems of low safety, low drug-loading capacity and complicated preparation process of existing nano-drug loading systems

Method used

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  • Preparation method and application of hyaluronic acid-small molecule self-assembled nano-drug
  • Preparation method and application of hyaluronic acid-small molecule self-assembled nano-drug
  • Preparation method and application of hyaluronic acid-small molecule self-assembled nano-drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] This example provides a HA-small molecule self-assembled nano drug, the small molecule is tripterine. Concrete preparation steps are as follows:

[0040] Dissolve 10 mg of tripterine in 1 mL of dimethyl sulfoxide to obtain a 10 mg / mL solution of tripterine; dissolve 20 mg of HA with a molecular weight of 17 kDa in 2 mL of deionized water to obtain a 10 mg / mL HA solution. Then the HA solution was placed on a magnetic stirring table with a rotation speed of 300 rpm and a temperature of 25 °C. Take 20uL of tripterine solution and add it dropwise to the HA solution, and continue magnetic stirring for 30min. After stirring, the mixed solution was transferred to a snakeskin dialysis bag with a molecular weight cut-off of 10,000 Da, and dialyzed in 3L deionized water for 24 hours at room temperature, and the deionized water was replaced every 12 hours. During the dialysis period, avoid light. After dialysis, the mixed solution was transferred to a 5mL EP tube and stored at 4...

Embodiment 2

[0043] This example provides a HA-small molecule self-assembled nano drug, the small molecule is oleanolic acid. Concrete preparation steps are as follows:

[0044] Dissolve 10 mg of oleanolic acid in 1 mL of dimethyl sulfoxide to obtain a 10 mg / mL oleanolic acid solution; dissolve 20 mg of HA with a molecular weight of 17 kDa in 2 mL of deionized water to obtain a 10 mg / mL HA solution. Then the HA solution was placed on a magnetic stirring table with a rotation speed of 300 rpm and a temperature of 25 °C. 20 uL of oleanolic acid solution was added dropwise to the HA solution, and magnetic stirring was continued for 30 min. After stirring, the mixed solution was transferred to a snakeskin dialysis bag with a molecular weight cut-off of 10,000 Da, and dialyzed in 3L deionized water for 24 hours at room temperature, and the deionized water was replaced every 12 hours. During the dialysis period, avoid light. After dialysis, the mixed solution was transferred to a 5mL EP tube a...

Embodiment 3

[0047] This example provides a HA-small molecule self-assembled nano drug, the small molecule is oleanolic acid. Concrete preparation steps are as follows:

[0048] Dissolve 10 mg of oleanolic acid in 1 mL of dimethyl sulfoxide to obtain a 10 mg / mL oleanolic acid solution; dissolve 20 mg of HA with a molecular weight of 17 kDa in 2 mL of deionized water to obtain a 10 mg / mL HA solution . Then the HA solution was placed on a magnetic stirring table with a rotation speed of 300 rpm and a temperature of 25 °C. Take 20 uL of oleanolic acid solution and add it dropwise to the HA solution, and continue magnetic stirring for 30 min. After stirring, the mixed solution was transferred to a snakeskin dialysis bag with a molecular weight cut-off of 10,000 Da, and dialyzed in 3L deionized water for 24 hours at room temperature, and the deionized water was replaced every 12 hours. During the dialysis period, avoid light. After dialysis, the mixed solution was transferred to a 5mL EP tub...

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Abstract

The invention discloses a preparation method and an application of a hyaluronic acid-small molecule self-assembled nano-drug. According to the invention, hyaluronic acid and a hydrophobic small molecule drug are self-assembled through a simple dialysis method to form the nano-drug with a uniform morphology, so that the problem of low water solubility of a hydrophobic drug is solved, and the bioavailability of the drug is improved. Meanwhile, hyaluronic acid is used as a macromolecule widely existing in a human body, and has the characteristics of no toxicity, no immunogenicity and degradability, so that the hyaluronic acid-micromolecule self-assembled nano-drug disclosed by the invention has better biological safety. By utilizing the targeting capability of CD44 of the hyaluronic acid, the nano-drug disclosed by the invention can play a stronger curative effect in treatment of certain specific diseases such as cancers and inflammatory diseases. The preparation process is green and simple, the components of the nano-drug are clear, the quality is controllable, and large-scale industrial production is expected to be carried out.

Description

technical field [0001] The invention belongs to the field of nano-medicine preparation, and in particular relates to the preparation and application of a hyaluronic acid-small molecule self-assembled nano-medicine using hyaluronic acid as a template. Background technique [0002] Most small-molecule drugs have poor water solubility and can only be dissolved in organic solvents such as dichloromethane, acetone, and DMSO. However, these organic solvents are generally toxic and cannot be used in clinical treatment. Although hydrophobic drugs can be prepared into pharmaceutical preparations such as suspensions and emulsions through pharmaceutical preparation technology, the drug molecules will spontaneously aggregate into larger crystals in the body, reducing the bioavailability of the drug, thereby affecting the normal efficacy of the drug. With the widespread application of nanotechnology in the field of pharmaceutical preparations, the nanocarrier-assisted drug delivery syste...

Claims

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Application Information

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IPC IPC(8): A61K47/36A61K9/51A61K31/56A61P1/16B82Y5/00B82Y40/00
CPCA61K9/5161A61K31/56A61P1/16B82Y5/00B82Y40/00
Inventor 于超郑天野陈俊
Owner CHONGQING MEDICAL UNIVERSITY
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