Amifostine-metal ion-hyaluronic acid nanocomposite

A nanocomposite and hyaluronic acid technology, which is applied in the direction of drug combinations, anti-toxic agents, and medical preparations of non-active ingredients, etc., can solve the problems of low drug loading, short half-life, and low encapsulation efficiency, and achieve easy industrialization The effect of production, extended half-life in vivo, and simple preparation method

Pending Publication Date: 2021-07-02
SOUTHWEST UNIVERSITY
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  • Abstract
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Problems solved by technology

[0004] However, the study found that amifostine was almost completely cleared within 2 hours after the patient's first injection, and multiple doses also increased the frequency and severity of side effects in patients
Since amifostine is a water-soluble drug, it is difficult to make it into a nano-preparation using conventional preparation methods, and there are problems such as low encapsulation efficiency, low drug loading and short half-life.

Method used

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  • Amifostine-metal ion-hyaluronic acid nanocomposite

Examples

Experimental program
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Effect test

Embodiment 1

[0018] Weigh 10 mg of amifostine and 40 mg of hyaluronic acid and dissolve them in 5 ml of ultrapure water, add 200 μl of zinc chloride solution (50 mg / ml) dropwise while stirring, stir and react at room temperature for 24 hours, and then use a dialysis bag (molecular weight cut-off 8000–14000 ) was dialyzed and purified in pure water for 12 hours to obtain the amifostine-zinc ion-hyaluronic acid nanocomposite. The average particle diameter of the nanocomposite measured by laser particle size analyzer is 35.2nm. The encapsulation efficiency of the nanocomposite was measured by Sephadex G50 dextran gel chromatography column to be 93.1%, and the drug loading capacity was 18.6%.

Embodiment 2

[0020] Weigh 15 mg of amifostine and 40 mg of hyaluronic acid and dissolve them in 5 ml of ultrapure water, add 200 μl of ferric chloride solution (40 mg / ml) dropwise while stirring, stir and react at room temperature for 24 hours, and then use a dialysis bag (molecular weight cut off 8000–14000 ) was dialyzed and purified in pure water for 12 hours to obtain the amifostine-iron ion-hyaluronic acid nanocomposite. The average particle size of the nanocomposite measured by laser particle size analyzer is 39.1nm. The encapsulation efficiency of the nanocomposite was measured by Sephadex G50 dextran gel chromatography column to be 92.3%, and the drug loading capacity was 25.2%.

Embodiment 3

[0022] Weigh 9 mg of amifostine and 40 mg of hyaluronic acid-polyethylene glycol and dissolve them in 5 ml of ultrapure water, add dropwise 200 μl of magnesium chloride solution (55 mg / ml) while stirring, stir and react at room temperature for 24 h, then use a dialysis bag (MWCO 8000–14000) in pure water for 12 hours to obtain the amifostine-magnesium ion-hyaluronic acid nanocomposite. The average particle size of the nanocomposite measured by laser particle size analyzer is 27.4nm. The encapsulation efficiency of the nanocomposite was measured by Sephadex G50 dextran gel chromatography column to be 91.5%, and the drug loading capacity was 16.8%.

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Abstract

The invention discloses a nanocomposite which takes metal ions as coordination centers and hyaluronic acid and derivatives thereof as carrier materials and entraps a hydrophilic drug, namely amifostine, belonging to the technical field of pharmaceutical preparations. The nanocomposite is simple to prepare and good in biocompatibility, and can solve the problems of low encapsulation efficiency, low drug loading capacity and a short in-vivo half-life period of an amifostine nanopreparation.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and specifically relates to a nanocomposite that uses metal ions as coordination centers, hyaluronic acid and its derivatives as carrier materials, and contains hydrophilic drug amifostine. Background technique [0002] At present, radiotherapy has become an important method for the comprehensive treatment of many malignant tumors. However, while ionizing radiation inhibits tumor cells, it can also cause radiation damage to normal tissues, resulting in serious toxic and side effects. Amifostine (AMI, WR-2721) is currently the most widely used anti-radiation drug with the clearest effect on the market. It has a selective protective effect on normal tissues and is widely used in tumor radiotherapy and chemotherapy. [0003] Amifostine is a prodrug containing phosphorothioate, and its active metabolite is called WR-1065, which is a sulfur-terminal compound released after the phos...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K31/661A61P39/00A61P35/00
CPCA61K31/661A61K47/6949A61P35/00A61P39/00
Inventor 于洋
Owner SOUTHWEST UNIVERSITY
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