Acid amide-grafted sodium alginate nanometer material, preparation method thereof and use thereof

A technology of sodium alginate and nanomaterials, applied in chemical instruments and methods, medical preparations of non-active ingredients, pharmaceutical formulations, etc., can solve the problems of dispersion, small diffusion performance, easy degradation, etc., and achieve improved delivery efficiency , solve the effect of low embedding rate and good biocompatibility

Inactive Publication Date: 2009-10-28
OCEAN UNIV OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, many excellent hydrophobic drugs such as paclitaxel, doxorubicin, itraconazole, etc. are very good drugs in the treatment of diseases, but their application is limited due to their small water solubility, and their extremely small solubility makes the absorption after taking the drugs difficult. For many years, a variety of research methods have been adopted in order to improve the utilization, such as the method of increasing the solubility by grinding to increase the total specific surface area, the particle crystallization method, the spray drying method, etc., but these methods have their own Disadvantages such as poor dispersion, poor stability, wide particle size distribution, etc.
Not only hydrophobic drugs, protein drugs also have short half-life in vivo, easy to degrade, easy to inactivate, difficult to be absorbed in the gastrointestinal tract, and need to be taken in large quantities to maintain drug efficacy. Moreover, because most proteins and peptides Drug-like drugs have a low partition coefficient and small diffusion properties, making them difficult to be taken up by lipophilic membranes, and it is difficult to pass through biological barriers so that their applications are limited

Method used

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  • Acid amide-grafted sodium alginate nanometer material, preparation method thereof and use thereof
  • Acid amide-grafted sodium alginate nanometer material, preparation method thereof and use thereof
  • Acid amide-grafted sodium alginate nanometer material, preparation method thereof and use thereof

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preparation example Construction

[0021] 3. Preparation of amide grafted sodium alginate material

[0022] (1) Dissolve an appropriate amount of the sample treated in step 2 in DMSO, add amide at a molar ratio of 1:7.5 to 1:18 (alginic acid monomer: amide), and use the molar ratio of sodium alginate monomer and crosslinking agent The ratio is 2:1 ~ 1:5, add cross-linking agent, and react in a sealed water bath at 50°C for 24 hours;

[0023] (2) Put the mixture of the above reaction into a dialysis bag with a molecular weight cut-off of 8-14KDa, dialyze with a sodium salt solution that can replace tetrabutyl cations for 48 hours, change the dialysate 8 times during this period, replace tetrabutyl cations with sodium ions Replaced;

[0024] (3) Take out the dialyzed substance, perform Soxhlet extraction in a water bath at 80° C. for 10 h, and remove unreacted amides;

[0025] (4) drying it at room temperature to get final product;

[0026] The cross-linking agent mentioned in the present invention is a reagen...

Embodiment 1

[0029] First, put 20 g of sodium alginate with a molecular weight of 32000, 12.5 ml (0.6 mol / L) of concentrated hydrochloric acid and ethanol with a total volume of 250 ml, stir for 3 hours, store at 0-4°C overnight, and filter and dry the next day to obtain alginic acid; Add 3 g of alginic acid to 50 ml of water, adjust the pH to neutral with tetrabutylammonium hydroxide, and then freeze-dry; then dissolve it in DMSO (dimethyl sulfoxide) at a weight-volume ratio of 2%, and add the Oleamide with a molar ratio of 10:1, and EDC and NHS with a molar ratio of 2:1 to sodium alginate monomer, sealed and reacted in a water bath at 50°C for 24 hours; In a dialysis bag, dialyze with 400 mg / L sodium nitride solution for 48 hours, and change the dialysate 8 times during the period; use methanol as the extraction solution for Soxhlet extraction for 10 hours to remove unreacted oleamide, and dry at room temperature to obtain amide-grafted seaweed Sodium acid material.

[0030] The hydroph...

Embodiment 2

[0032] First, put 20 g of sodium alginate with a molecular weight of 32000, 12.5 ml (0.6 mol / L) of concentrated hydrochloric acid and ethanol with a total volume of 250 ml, stir for 3 hours, store at 0-4°C overnight, and filter and dry the next day to obtain alginic acid; Add 3 g of alginic acid to 50 ml of water, adjust the pH to neutral with tetrabutylammonium hydroxide, and freeze-dry; then dissolve it in DMSO (dimethyl sulfoxide) at a weight-to-volume ratio of 2%, and add the Oleamide with a molar ratio of 15:1, and EDC and NHS with a molar ratio of 2:1 to sodium alginate monomer, sealed and reacted in a water bath at 50°C for 24 hours; In a dialysis bag, dialyze with 400 mg / L sodium nitride solution for 48 hours, and change the dialysate 8 times during the period; use methanol as the extraction solution for Soxhlet extraction for 10 hours to remove unreacted oleamide, and dry at room temperature to obtain amide-grafted seaweed Sodium acid material.

[0033] The degree of...

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Abstract

The invention relates to an acid amide-grafted sodium alginate nanometer material, a preparation method thereof and use thereof. The acid amide-grafted sodium alginate nanometer material comprises acid amide having an aliphatic chain and sodium alginate having a molecular weight of less than or equal to 50,000, and is characterized in that a carboxyl group of the sodium alginate is grated with hydrophobic acid amide by a chemical synthesis method for hydrophobic modification so as to form an amphipathic material, namely a modified sodium alginate nanometer material, having both hydrophobicity and hydrophilcity. The acid amide-grafted sodium alginate nanometer material performs self aggregation in deionized water to form nanoparticles, wherein the diameter of the nanoparticles is between 40 and 1,000 nanometers; under a condition of substituted ratio of 2 percent, the mean particle diameter of the nanoparticles is 596.2 nanometers; the medicament-loading rate is up to 40 percent; the medicament entrapment rate is up to 95.1 percent; and the medicament release time is as long as 6 days. The acid amide-grafted sodium alginate nanometer material can be used in a plurality of pharmaceutical fields as a slow release carrier of a plurality of medicaments, particularly hydrophobic medicaments, protein medicaments, polypeptides and vaccines.

Description

technical field [0001] The invention relates to an amide-grafted sodium alginate nanometer material and a preparation method and application thereof. Background technique [0002] Sodium alginate is a natural polymer polysaccharide existing in brown algae. Because of the large number of carboxyl groups in its molecular chain, it has good hydrophilicity, and has many excellent characteristics such as good gelation and stability. High, and has a high viscosity in aqueous solution, so it has a wide range of applications in the food industry, cosmetics industry and pharmaceutical industry. Among them, in the pharmaceutical industry, sodium alginate has been widely used as a drug carrier for many years to prepare various drug delivery systems such as pills, powders, and tablets. However, in terms of embedding hydrophobic drugs, the above-mentioned dosage forms have great defects in terms of sustained release effect, embedding rate, and increase in drug stability, resulting in a ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/04C07K17/04C07K17/10A61K47/36
Inventor 刘晨光王艳玲李倩
Owner OCEAN UNIV OF CHINA
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