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Polysaccharide sulfate antitumor nano preparation and preparation method

A technology of sodium alginate diester and nano preparations, which is applied in the direction of antineoplastic drugs, pharmaceutical formulas, medical preparations of non-active ingredients, etc., can solve problems such as the instability of nano-suspensions, achieve significant crystal-inhibiting properties, and improve Stable, low-cost effect

Active Publication Date: 2019-03-29
TIANJIN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In order to avoid the instability of nanosuspensions, the most common solution is to add stabilizers (surfactants and crystal inhibitors used alone or in combination) during the preparation process. However, it is found and selected with excellent properties and matching parameters The stabilizer is a painstaking and complicated process

Method used

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  • Polysaccharide sulfate antitumor nano preparation and preparation method
  • Polysaccharide sulfate antitumor nano preparation and preparation method
  • Polysaccharide sulfate antitumor nano preparation and preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] 1. Preparation of doxorubicin / celecoxib sodium alginate diester nanosuspension

[0056] Weigh 25 mg of sodium alginate diester (School of Medicine, Ocean University of China) and 5 mg of polyvinylpyrrolidone (PVPK30, purchased from Sigma-Aldrich), dissolve them in 15 mL of distilled water, and stir to fully dissolve them. Doxorubicin hydrochloride (purchased from Dalian Meilun Biotechnology Co., Ltd.) was dissolved in dimethyl sulfoxide at a concentration of 8 mg / mL, and 3 times the molar equivalent of triethylamine was added. Stir at room temperature for 12 h in the dark for desalination; dissolve celecoxib (Dalian Meilun Biotechnology Co., Ltd.) in dimethyl sulfoxide at a concentration of 80 mg / mL; Equal volumes of the coxib solution were mixed and stirred for 24 h in the dark. Then 2 mL of the drug solution was slowly added dropwise to the above-mentioned sodium alginate diester solution, stirring was continued at room temperature for 30 min, and the rotation speed w...

Embodiment 2

[0088] 1. Preparation of doxorubicin / celecoxib sodium alginate diester nanopowder injection

[0089] Add about 2% mannose to the doxorubicin / celecoxib sodium alginate nanosuspension prepared in Example 1, and then freeze-dry to obtain a reddish-brown flocculent powder, which is its Nano powder injection.

[0090] 2. Determination of drug content in doxorubicin / celecoxib diester sodium alginate nanopowder injection

[0091] The same HPLC method as in Example 1 was used to detect the contents of doxorubicin and celecoxib in the nanopowder injection. Sample processing and determination of drug content: When detecting the content of doxorubicin, accurately weigh 5 mg of nanopowder injection and disperse it in 5 mL of 0.1 mol / L hydrochloric acid solution, vortex for 3 h and then filter. In Example 1, the concentration of doxorubicin was determined by sample injection under high performance liquid chromatography conditions, and the content of doxorubicin in the nano powder inject...

Embodiment 3

[0096] 1. Preparation of norcantharidin nanosuspension

[0097] Weigh 25 mg of sodium alginate diester and 5 mg of polyvinylpyrrolidone, dissolve them in 15 mL of distilled water, stir to dissolve them fully; weigh 30 mg of norcantharidin (purchased from Dalian Meilun Biotechnology Co., Ltd.) In 1.5 mL of acetone, slowly add dropwise to the above-mentioned sodium alginate diester solution, continue to stir at room temperature for 30 min, and control the rotation speed at 600-800 rpm to obtain a white milky suspension, and then rotary evaporate at room temperature to remove the acetone. Obtain norcantharidin nanosuspension.

[0098] 2. Determination of Drug Content in Norcantharidin Nanosuspension

[0099]The drug content of norcantharidin in the nanosuspension was detected by high performance liquid chromatography (HPLC). The chromatographic conditions are as follows: Waters C18 column (4.6×250 mm, 5 μm); mobile phase pH 3.1 phosphoric acid aqueous solution-methanol (70 / 30...

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Abstract

The invention relates to a polysaccharide sulfate antitumor nano preparation and a preparation method. The nano preparation comprises 15%-50% by mass of polysaccharide sulfate, 40%-80% by mass of doxorubicin hydrochloride and celecoxib and the balance of water, wherein the mass ratio of the polysaccharide sulfate to polyvinylpyrrolidone is (2-5):1, the characteristic viscosity of the polysaccharide sulfate is 9.0-14.0, the content of organic sulfur is 9.0%-13.0%, and the mass ratio of the doxorubicin hydrochloride to the celecoxib is 1 / 10-1 / 2. The polysaccharide sulfate is applied to preparation of the nano preparation of a hydrophobic or amphipathic antitumor drug as a stabilizer due to surface activity and crystallization inhibition performance, so that the solubility of the drug is improved, the bioavailability of the drug is increased, the efficacy of the drug is enhanced, toxic and side effects of the drug are reduced, and the drug is better applied to clinical tumor tretament. The nano preparation can significantly inhibit growth and transfer of tumor in vivo and vitro, and the scientific basis is provided for application development of the polysaccharide sulfate in aspects of new dosage forms of the antitumor drug.

Description

technical field [0001] The invention relates to an anti-tumor nano-preparation of sodium alginate and its preparation method. Specifically, it uses the surface activity and crystal-inhibiting properties of sodium alginate as a stabilizer for the preparation of hydrophobic or amphiphilic anti-tumor agents. The nano-preparation of tumor drugs can improve the solubility of drugs, improve the bioavailability of drugs, enhance the efficacy of drugs, reduce the side effects of drugs, and then be better used in the clinical application of tumor treatment. Background technique [0002] Tumor is a new organism formed by the body under the action of various tumorigenic factors, the cells of local tissues lose the normal regulation of their growth at the gene level, resulting in abnormal clonal proliferation. According to the degree of harm to the human body, tumors can be divided into two categories: benign tumors and malignant tumors. Among them, malignant tumors have always been on...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/704A61K31/635A61K31/734A61K31/34A61K9/10A61K9/19A61K47/36A61P35/00
CPCA61K9/0019A61K9/10A61K9/19A61K31/34A61K31/635A61K31/704A61K31/734A61K47/36A61P35/00A61K2300/00
Inventor 王银松张韬李春雨刘慧
Owner TIANJIN MEDICAL UNIV
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