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Preparation of composite drug-loaded nanoparticles of carboxyl-chitosan and chitosan modified by glycyrrhizanates

A technology of carboxylated chitosan and glycyrrhizinate, which is applied in the field of medicine, can solve problems not related to the active targeting function of drug-loaded nanoparticles, and achieve the effect of a safe and reliable treatment plan

Inactive Publication Date: 2008-12-31
GUANGDONG HOSPITAL OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Chinese patent CN1586488A prepared glycyrrhizic acid chitosan nanoparticles, which improved the gastrointestinal absorption of glycyrrhizic acid, but did not involve the use of glycyrrhizic acid as a molecular targeting ligand to improve the active targeting function of drug-loaded nanoparticles
This technology has not yet been reported in the literature

Method used

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  • Preparation of composite drug-loaded nanoparticles of carboxyl-chitosan and chitosan modified by glycyrrhizanates
  • Preparation of composite drug-loaded nanoparticles of carboxyl-chitosan and chitosan modified by glycyrrhizanates
  • Preparation of composite drug-loaded nanoparticles of carboxyl-chitosan and chitosan modified by glycyrrhizanates

Examples

Experimental program
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Effect test

Embodiment 1

[0021] Example 1: Preparation of Glycyrrhizic Acid Monoamine Salt Modified Chitosan / Carboxylated Chitosan Composite Blank Nanoparticles

[0022] (1) Configuration of chitosan acidic aqueous solution: get chitosan (molecular weight 40k, degree of deacetylation > 90%, Zhejiang Jinke Biochemical Co., Ltd.), and configure 5mg / mL chitosan with 0.3% acetic acid solution solution, adjusted to pH 6.0 with ammonia water, and filtered for later use.

[0023] (2) Configuration of carboxylated chitosan aqueous solution: take carboxypropyl chitosan (purchased from Zhejiang Jinke Biochemical Co., Ltd.), add distilled water to configure a 4mg / mL solution, add glycyrrhizic acid monoamine salt, adjust the final The concentration is 0.3mg / mL, adjusted to pH 8.5 with ammonia water, and filtered for later use.

[0024] (3) Preparation of composite nanoparticles: Take 10mL of the solution in (2), slowly add 4mL of the solution in (1) under stirring at room temperature (rotating speed is 1000r / min...

Embodiment 2

[0025] Example 2 Glycyrrhizinate Modified Chitosan / Carboxylated Chitosan Composite Blank Nanoparticles Binding Effect on Liver Parenchymal Cells

[0026](1) Fluorescent labeling of chitosan: get 100mL of 2.5% chitosan solution, adjust the pH to 8.5 with 1mol / L NaOH solution, add 1mg / mL of fluorescent dye rhodamine B isothiocyanate (rhodamine B isothiocyanate, RBITC, sigma) 100uL, reacted in the dark for 1h, free RBITC was removed by dialysis with a dialysis bag in the dark, and RBITC-labeled chitosan solution (RBITC-CS) was obtained. Take an appropriate amount and configure it to 5mg·mL -1 RBITC-CS solution.

[0027] (2) The operation steps are the same as those in Example 1 to obtain fluorescently labeled glycyrrhizic acid monoamine salt modified chitosan / carboxylated chitosan composite blank nanoparticles, constant volume 20mL (referred to as GL-RBITC-CS / CCS-NPs group) Operation steps are the same as example 1, only do not add glycyrrhizic acid monoamine salt in carboxylat...

Embodiment 3

[0030] Example 3 Preparation of Glycyrrhizic Acid Diamine Salt Modified Chitosan / Carboxylated Chitosan Composite Adriamycin Nanoparticles

[0031] (1) Configuration of chitosan acidic aqueous solution: get chitosan (molecular weight 100k, degree of deacetylation > 90%, Zhejiang Jinke Biochemical Co., Ltd.), and configure 2mg / mL chitosan with 0.5% acetic acid solution Add an appropriate amount of doxorubicin hydrochloride to the solution so that the final concentration is 4 mg / mL, adjust the pH to 6.5 with ammonia water, and filter for later use.

[0032] (2) Configuration of carboxylated chitosan aqueous solution: take carboxypropyl chitosan (Zhejiang Jinke Biochemical Co., Ltd.), add distilled water to configure a 2mg / mL solution, add diamine glycyrrhizinate, and the final concentration is 1mg / mL, adjusted to pH 8.5 with ammonia water, and filtered for later use.

[0033] (3) Preparation of composite drug-loaded nanoparticles: Take 10 mL of the solution in (2), slowly add 4...

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Abstract

The invention relates to a new type of liver targeted drug carrier- glycyrrhetate modified chitosan / carboxylated chitosan compound drug carrier nanometer particle as well as its preparing method. The preparing procedure includes the following steps: dissolving the glycyrrhetate into carboxylated chitosan of a certain density; adding certain amount of chitosan solution which contains drug into the carboxylated chitosan while stirring; nanometer particles form automatically because of the electrostatic interaction among different molecules. The invention has simple preparing procedures, mile operating conditions and it has no poisoning or side effects of the organic solvents. Since the glycyrrhizin has characteristic of targeting at the liver, the product in the invention has the function of active targeting which leads to high effect liver targeting capabilities. The invention is applicable to the entrapment of medicine that contains electrical group (such as doxorubicin hydrochloride), protein drugs and medicine that has certain water-solubility in neutral pH conditions.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a preparation method of glycyrrhizinate-modified chitosan / carboxylated chitosan composite drug-loaded nanoparticles. Background technique [0002] Nanoparticles (NPs) are solid colloidal particles with a particle size between 10-1000nm that can adsorb and embed various drug molecules. After intravascular injection of nanoparticles, at least 80-85% of NPs were phagocytized by the reticuloendothelial system (RES). They are Kupffer cells, so NPs can accumulate in the liver and have a passive targeting function. The liver is composed of parenchymal cells and non-parenchymal cells (endothelial cells, Kupffer cells, etc.). It contains hundreds of enzymes, and most of the lesions related to the liver, such as liver cancer, hepatitis, and cirrhosis, mostly occur in parenchymal cells. After nanoparticles enter the blood circulation, they are quickly recognized and eliminated by the reticuloendo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K47/36A61K47/06A61P1/16
Inventor 刘奕明林爱华
Owner GUANGDONG HOSPITAL OF TRADITIONAL CHINESE MEDICINE
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