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Preparation and application of biodegradable thermosensitive in-situ hydrogel

A hydrogel and temperature-sensitive technology, applied in the field of medicine, can solve the problems of short drug release time, high triglycerides, and low hydrogel strength, and achieve adjustable drug release rate, adjustable structure, The effect of the simple preparation process

Inactive Publication Date: 2013-11-27
FANTAI INST OF CHEM MEDICINES NANJING
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although PEO-PPO-PEO block copolymers have been applied in many fields, due to their low hydrogel strength and fast erosion in vivo, the sustained release time of drugs is short
More importantly, the above two materials are non-biodegradable materials, and the hydrogel prepared by them may have safety problems during use, such as residues that may be caused when the PNIPAAm gel is surgically removed, and long-term application PEO-PPO-PEO can cause hypercholesterolemia and hypertriglyceridemia, limiting their widespread use to some extent

Method used

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  • Preparation and application of biodegradable thermosensitive in-situ hydrogel
  • Preparation and application of biodegradable thermosensitive in-situ hydrogel
  • Preparation and application of biodegradable thermosensitive in-situ hydrogel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Firstly, the reactants were purified as follows: PEG and lactide (LA) were dried under reduced pressure at room temperature, and β-butyrolactone (β-BL) was heated to reflux with calcium hydride for 1 hour, and then distilled under reduced pressure.

[0037] The specific synthesis steps are: weigh PEG respectively 1500 4.0g and LA9.0g were placed in a dry three-necked flask, heated to 130°C in an oil bath to melt, and continuously vacuumed under magnetic stirring to remove the residual moisture in it. After 2h, under the protection of nitrogen, add β- BL1.0g and 0.3% (w / w, relative to monomer mass) of Sn(Oct) 2 , after repeated vacuum-filling with nitrogen, the temperature was raised to 150° C. for 6 h under the protection of nitrogen. After the reaction is completed, let it cool to room temperature, add an appropriate amount of distilled water, wash repeatedly in a water bath at about 75°C to remove unreacted monomers or low molecular weight products, freeze-dry, and s...

Embodiment 2

[0039] Take by weighing an appropriate amount of polymer synthesized in Example 1, add distilled water, and magnetically stir at room temperature to dissolve, and prepare respectively a polymer solution with a concentration of 10, 15, 20, 25 and 30%, and use the vial inversion method to measure its phase transition temperature. and draw a phase diagram.

Embodiment 3

[0041] Get the polymkeric substance synthesized in the example 1, preparation concentration is the polymer aqueous solution of 0.5%. The particle size of micelles at different temperatures was determined by dynamic light scattering.

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Abstract

The invention relates to preparation and an application of a biodegradable thermosensitive in-situ hydrogel. The hydrogel is prepared by the following steps: by taking a water soluble amphiphilic thermosensitive block polymer polybutyrolactone lactide-polyethylene glycol-polymer polybutyrolactone lactide as a carrier material, dispersing or dissolving the medicine in aqueous liquor thereof; or dispersing particles such microballoon, lipidosome and emulsion droplets which load the medicine in the aqueous liquor. When the temperature is lower than the phase inversion temperature, the hydrogel exists in form of a liquid which can be delivered by way of injection and the like. When temperature at the delivery part is raised to body temperature, the hydrogel gelates and the medicine is slowly released by way of diffusion or / and corrosion, and the release rate of the medicine can be adjusted by changing concentration, molecular weight, proportion of hydrophilic blocks and hydrophobic blocks or block constitution of the polymer. The hydrogel can be delivered by way of eyes, transdermal delivery, vagina, urethra, rectum, nasal cavity and ears.

Description

Technical field: [0001] The invention belongs to the technical field of medicine, and specifically relates to the synthesis and characterization of a temperature-sensitive block polymer, and the specific application of an in-situ hydrogel with slow-release function prepared by using it as a carrier material. technical background: [0002] Hydrogel is a kind of aqueous system with three-dimensional network structure formed by natural or synthetic polymer materials through physical or chemical cross-linking. Since Wichterle and Lim first used poly 2-hydroxyethyl methacrylate (pHEMA) as a gel material for contact lenses in 1960, due to the superior ecology of hydrogels, it has been widely used in drug delivery systems, tissue engineering, etc. and regenerative medicine and other fields have received great attention. In particular, stimulus-sensitive hydrogels or environment-sensitive hydrogels can respond to small changes in the external environment such as physical (temperatu...

Claims

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Application Information

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IPC IPC(8): A61K47/34C08G63/664
Inventor 吴建梅涂家生
Owner FANTAI INST OF CHEM MEDICINES NANJING
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