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Hyaluronic acid-cationic drug ion pair particle

A technology of cationic drugs and hyaluronic acid, which is applied in the field of medicine and nanomaterials, can solve the problems of reducing the drug loading of particles and complex particle technology, and achieve the effect of large drug loading, simple preparation process, and good water solubility

Active Publication Date: 2015-12-09
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0012] In addition, the preparation process of traditional microparticles is not only complicated, but also needs to add a large amount of auxiliary materials in the preparation process to ensure the roundness, suitable particle size and uniform dispersion of the microparticles.
The use of excipients will not only reduce the drug loading of the microparticles, but also cause certain toxicity

Method used

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Examples

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Effect test

Embodiment 1

[0060] Hyaluronic acid (HA) with a molecular weight of 100,000Da is dissolved in deionized water, and doxorubicin (DOX) is dissolved in deionized water. At 25°C, slowly add the doxorubicin solution dropwise to the hyaluronic acid solution, feed the material according to the molar ratio of the number of carboxylic acids of hyaluronic acid to doxorubicin at 1:1, stir and react for 30 minutes, and ultrasonically obtain the hyaluronic acid- Doxorubicin ion-pair microparticles, with a particle size of 180nm, are used for tumor targeting by intravenous injection.

Embodiment 2

[0062] Hyaluronic acid with a molecular weight of 5,000 Da and 0.5% (m / v) polyethylene glycol-15-hydroxystearate (SolutolHS15) were dissolved in deionized water, and carboplatin was dissolved in deionized water. At 20°C, slowly add the carboplatin solution to the hyaluronic acid solution dropwise, feed according to the molar ratio of the number of carboxylic acids of hyaluronic acid to carboplatin at 1:5, stir for 5 minutes, probe ultrasonically, and homogenize under high pressure to obtain hyaluronic acid Acid-carboplatin ion-pair microparticles, with a particle size of 20nm, are used for tumor targeting by intravenous injection.

Embodiment 3

[0064] Hyaluronic acid with a molecular weight of 1000,000Da and 1% (m / v) F68 were dissolved in deionized water, and pirarubicin was dissolved in absolute ethanol. At 50°C, slowly add the pirarubicin solution dropwise to the hyaluronic acid solution, feed in a molar ratio of 20:1 between the number of carboxylic acids of hyaluronic acid and pirarubicin, stir for 72 hours, and remove ethanol by rotary evaporation, that is Hyaluronic acid-pirarubicin ion-pair microparticles with a particle size of 100 μm are obtained, and the drug can be released slowly through intramuscular or subcutaneous injection to achieve a long-term anti-tumor effect.

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Abstract

The invention provides a hyaluronic acid-cationic drug ion pair particle as well as a preparation method and application thereof. A positively charged cationic drug serves as a hydrophobic core and negatively charged hyaluronic acid functions as a hydrophilic shell, so that the ion pair particle has double targeting properties, namely active targeting and passive targeting.

Description

technical field [0001] The present invention relates to a novel hyaluronic acid-cation drug ion-pair particle and its preparation method and application, in particular to a particle with a shell-core structure formed by negatively charged hyaluronic acid and a positively charged drug, which belongs to the field of medicine and nanotechnology. field of materials technology. Background technique [0002] Hyaluronic acid is an acidic polymucopolysaccharide, which is formed by repeated cross-linking of N-acetylglucosamine and glucuronic acid (as shown in formula 1), and is widely distributed in the extracellular matrix of soft connective tissue. Hyaluronic acid has the common properties of many natural mucopolysaccharides: white, odorless, tasteless, amorphous solid, soluble in water, and strongly hygroscopic. [0003] [0004] Formula 1: Structure of hyaluronic acid [0005] Currently, hyaluronic acid is mainly used in the fields of cosmetics and medicine. Hyaluronic acid...

Claims

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Application Information

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IPC IPC(8): A61K9/50A61K45/00A61K47/48A61P35/00
Inventor 龚涛张志荣李文浩
Owner SICHUAN UNIV
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