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Composite carrier, pH response type compound drug-loading system and preparation method of composite carrier

A composite carrier and drug-carrying technology, which is applied in the direction of pharmaceutical formulations, medical preparations of non-active ingredients, etc., to achieve the effect of uniform size and good dispersion

Inactive Publication Date: 2015-04-29
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are still some limitations in the application of some larger protein drugs

Method used

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  • Composite carrier, pH response type compound drug-loading system and preparation method of composite carrier
  • Composite carrier, pH response type compound drug-loading system and preparation method of composite carrier
  • Composite carrier, pH response type compound drug-loading system and preparation method of composite carrier

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preparation example Construction

[0121] The preparation method of composite carrier of the present invention comprises the following steps:

[0122] (a) 3-glycidyl ether trimethoxysilane is connected to the molecular chain of the carboxymethyl chitosan to obtain a compound;

[0123] (b) The composite obtained in step a) reacts with mesoporous silica, and the carboxymethyl chitosan is grafted to the surface of the mesoporous silica through 3-glycidyl ether trimethoxysilane to obtain The composite carrier.

[0124] When preparing the composite drug-loading system of the present invention, the macromolecular protein drug is loaded on the mesoporous silica, and then reacts with the complex obtained in step a) to obtain a composite drug-loading system.

[0125] In a preferred embodiment, the preparation method comprises the steps of:

[0126] (i) carboxymethyl chitosan molecule is dispersed in water, and its surface is modified with 3-glycidyl ether trimethoxysilane;

[0127] (ii) The surface-modified carboxyme...

Embodiment 1

[0164] Synthesis of N,O-Carboxymethyl Chitosan (NOCC)

[0165] Weigh 10g chitosan (molecular weight 3×10 5 g / mol, degree of deacetylation 90%) powder, under stirring at room temperature, join in the 500ml three-necked flask that fills 100ml isopropanol, then 25ml concentration is that the NaOH of 10mol / L is divided into 5 parts equally, within 25min respectively Add it to the flask, and continue to stir for 30 minutes after the addition is complete.

[0166] After the stirring finishes, weigh 60g of monochloroacetic acid, divide it into 5 parts, and add a part to the flask every one minute.

[0167] After the addition, the temperature of the system was raised to 60° C., and the reaction was continued for 3 h.

[0168] The reaction was terminated, the obtained product was filtered, and the filtrate was washed with anhydrous methanol, and dried in vacuum at 60° C. to obtain a yellow solid (molecular weight 3×10 5 g / mol, degree of deacetylation 90%). Hereinafter marked as NOC...

Embodiment 2

[0172] Preparation of Large Mesoporous Silica Nanoparticles 1-MCF by Sol-Gel Method

[0173] Add 10ml of concentrated hydrochloric acid with a mass fraction of 37% and 65ml of ultrapure water into the reaction vessel, mix well, and keep in a 40°C water bath.

[0174] Then, 4 g of polyethylene oxide-polypropylene oxide-polyethylene oxide triblock copolymer (P123) was slowly added to the mixture and stirred vigorously for about 1 h until it was completely dissolved, and the solution was in a clear state.

[0175] After the dissolution was complete, 4 g of trimethylolpropane (TMP) was added to the mixture, and kept stirring in a water bath at 40° C. for 2 h. Afterwards, 9.2 ml of tetraethyl orthosilicate (TEOS) was added dropwise and stirred vigorously, and the stirring was continued for 5 minutes after the addition was completed.

[0176] The addition of the first stage was completed, and the system was aged in a water bath at 40° C. for 20 h. Then add 46mg NH 4 F, stir gentl...

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Abstract

The invention discloses a composite carrier, a pH response type compound drug-loading system and a preparation method of the composite carrier. The composite carrier disclosed by the invention comprises carboxymethyl chitosan and mesoporous silica, wherein the carboxymethyl chitosan is grafted on the surface of the mesoporous silica through 3-glycidyl ether trimethoxy silane; and the pH response type compound drug-loading system disclosed by the invention comprises the composite carrier and macromolecular protein medicines. The composite carrier disclosed by the invention has super-large aperture and pore volume, and a three-dimensional communication channel structure; the limitation of a traditional mesoporous silica-based carrier channel in size is overcome; the composite carrier can be used as an ideal carrier for bearing the macromolecular protein medicines; the activity of the loaded protein can also be effectively maintained; and a new choice is provided for loading and response type fixed-point release of large-size protein medicines.

Description

technical field [0001] The invention relates to a drug-carrying system, in particular to a compound drug-carrying system of carboxymethyl chitosan / large mesoporous silica material and a preparation method thereof. Background technique [0002] Traditional mesoporous materials such as mesoporous crystal materials (MCM) series have pore diameters in the range of 2-10nm, which are very effective for the loading and release of small molecule drugs, but there are obvious size limitations for large size macromolecular protein drugs. Studies have shown that many macromolecular protein drugs have irreplaceable curative effects in the treatment of cancer, tumors and other diseases. Therefore, it is necessary to design large-pore carriers for this type of drugs. [0003] There are many studies on the environment-responsive drug release carrier based on mesoporous silicon, which also involves various types of environmental stimuli, such as temperature, magnetic field, light radiation, ...

Claims

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Application Information

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IPC IPC(8): A61K47/36A61K47/04
Inventor 刘昌胜甘琪袁媛朱娇阳
Owner EAST CHINA UNIV OF SCI & TECH
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