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A kind of preparation method of temperature-controlled drug release polymer microsphere material

A polymer and microsphere technology, which is applied in pharmaceutical formulations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc. The ball loses the slow release ability and other problems, so as to achieve the effect of retaining natural activity, protecting biological activity and fast curing speed.

Inactive Publication Date: 2019-01-18
NANJING UNIV OF SCI & TECH
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

Under physiological conditions, calcium ions will inevitably be replaced with other divalent ions, which makes the microspheres easily dissolve and lose the ability of sustained release
[0010] (2) The prepared polysaccharide microspheres rely on the degradation of the material itself to achieve the purpose of releasing drugs. This kind of slow release cannot achieve effective control, and it is difficult to achieve the purpose of intelligent delivery of drugs, resulting in poor drug delivery effect
[0011] (3) There are also microspheres that are cross-linked with chemical reagents such as glutaraldehyde or divinyl sulfone. These chemical cross-linking agents are cytotoxic. The cross-linking process leads to protein denaturation, and toxic residues will also produce toxic side effects, which are difficult for clinical use.

Method used

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  • A kind of preparation method of temperature-controlled drug release polymer microsphere material
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  • A kind of preparation method of temperature-controlled drug release polymer microsphere material

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preparation example Construction

[0031] The preparation method of the temperature-controlled drug release polymer microsphere material of the present invention specifically comprises the following steps:

[0032] Step 1, under room temperature, 0.5 gram of chitosan is dissolved in 40 milliliters of concentration and is the lactic acid solution of 5% (v / v), stirs 3 hours to form homogeneous solution, then adds the succinic anhydride of 1~4 times of chitosan quality, Stir at room temperature for 12 to 24 hours to react, dialyze and freeze-dry the reaction solution to obtain water-soluble succinyl chitosan;

[0033] Step 2. Dissolve 0.5 g of succinyl chitosan in 40 ml of phosphate buffer solution at room temperature, add 100 to 500 microliters of furfurylamine-2-methylfurylamine dropwise into the solution, and then add 1 / 5 Carbodiimide with ~1 / 2 times the mass of succinyl chitosan was stirred at room temperature for 12 to 24 hours to react, dialyzed and freeze-dried to obtain furanated chitosan;

[0034] Step 3...

Embodiment 1

[0043] (1) Add 0.5 gram of chitosan in 40 milliliters of 5% (v / v) lactic acid solution, stir at room temperature for 3 hours to form a uniform solution, then add 2 grams of succinic anhydride, stir at room temperature for 24 hours, then react The solution was dialyzed and freeze-dried to obtain succinyl chitosan;

[0044] (2) Dissolve 0.5 g of succinyl chitosan in 40 ml of buffer solution at room temperature, then add 500 microliters of furfurylamine-2-methylfurylamine dropwise, add 0.25 g of carbodiimide and stir at room temperature for 24 hours , dialyzed and freeze-dried to obtain furanated chitosan (the structure diagram is shown in figure 1 );

[0045] (3) Dissolve 1.0 g of sodium alginate in 100 ml of water at room temperature, then add 5 ml of sodium periodate solution with a concentration of 0.5 M dropwise, stir for 2 hours in the dark, dialyze and freeze-dry to obtain aldylated alginic acid sodium;

[0046] (4) Dissolve 1.0 g of alginate sodium alginate in 100 ml o...

Embodiment 2

[0054] (1) Add 0.5 gram of chitosan in 40 milliliters of 5% (v / v) lactic acid solution, stir at room temperature for 3 hours, form a uniform solution, then add 1.5 gram of succinic anhydride, stir at room temperature for 20 hours, then react The solution was dialyzed and freeze-dried to obtain succinyl chitosan;

[0055] (2) Dissolve 0.5 g of succinyl chitosan in 40 ml of buffer solution at room temperature, then add 400 microliters of furfurylamine-2-methylfurylamine dropwise, add 0.2 g of carbodiimide and stir at room temperature for 20 hours , dialysis and freeze-drying to obtain furanated chitosan;

[0056] (3) Dissolve 1.0 g of sodium alginate in 100 ml of water at room temperature, then add dropwise 4.5 ml of sodium periodate solution with a concentration of 0.5 M, stir for 3 hours in the dark, dialyze and freeze-dry to obtain alginic acid alginate sodium;

[0057] (4) Dissolve 1.0 gram of alginate sodium alginate in 100 milliliters of water at room temperature, then a...

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Abstract

The invention discloses a preparation method of a temperature controlled drug release polymer microsphere material. The steps consist of: dissolving chitosan in a lactic acid solution, adding succinic anhydride to carry out reaction so as to obtain water-soluble succinyl chitosan; dissolving the product in a buffer solution, and adding furfurylamine-2-furanomethylamine dropwise, then adding carbodiimide to carry out reaction so as to obtain furan chitosan; dissolving sodium alginate in water, and adding a sodium periodate solution dropwise to carry out reaction so as to obtain aldehyde sodium alginate; dissolving aldehyde sodium alginate in water, and adding 4-(4-N-maleimide phenyl)butyrate to carry out reaction so as to obtain maleimide sodium alginate; mixing a furan chitosan aqueous solution with a maleimide sodium alginate aqueous solution according to an equivoluminal ratio, then adding the mixture into paraffin oil containing an emulsifier span 80 to perform ultrasonic emulsification; subjecting the emulsion to stirring volatilization, then pouring the emulsion into isopropanol to precipitate polymer microspheres, and performing cleaning and freeze drying, thus obtaining the product. The invention significantly improves the use safety of the microsphere material, and the polymer microsphere material has important application value in the aspects of drug controlled release and gene therapy.

Description

technical field [0001] The invention belongs to the field of biomedical polymer materials, and in particular relates to a method for preparing a temperature-controlled drug release polymer microsphere material based on Diels-Alder reaction crosslinking. Background technique [0002] Microsphere materials with biodegradable properties can be used for the embedding and release of drugs, proteins or genes, and have been widely used in research in the fields of drug controlled release, tissue engineering and regenerative medicine. Selecting the appropriate microsphere system can realize the slow release of the drug in the body and achieve the ideal therapeutic effect. Natural polymers have excellent biocompatibility and tunable biodegradability, and are ideal matrix materials for preparing microspheres. Commonly used polysaccharides include: chitosan, sodium alginate, hyaluronic acid, cellulose, etc. [0003] In the field of tissue engineering and regenerative medicine, polysa...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/61A61K47/36A61K9/16A61K38/00
Inventor 谈华平范茗马烨张紫薇毛嘉慧
Owner NANJING UNIV OF SCI & TECH
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