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Degradable temperature sensitive physical aquagel and its preparation method

A hydrogel and temperature inversion technology, which is applied in the direction of medical preparations of non-active ingredients, drug delivery, and pharmaceutical formulations, can solve the problems of toxicity, non-degradability, and inability to achieve long-term drug delivery, and achieve good water absorption and operation Simple and convenient, the effect of mature reaction technology

Active Publication Date: 2008-10-22
FUDAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although poloxamers can be administered by injection, they can only exist in the body for a few days and are diluted by body fluids, which cannot achieve the effect of long-term administration. At the same time, they are more or less toxic to body organs and are not biodegradable. of

Method used

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  • Degradable temperature sensitive physical aquagel and its preparation method

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Add 10g of polyethylene glycol (1500) into a 250ml three-necked flask, then add 15.6g of DL-lactide and 3.13g of glycolide, heat it under vacuum to make it melt completely, add 20mg of stannous isooctanoate, and heat up the oil bath Reaction at 160°C for 24 hours. After the reaction is completed, the initial product is dissolved in dichloromethane solution, and methanol is precipitated. The yield is about 85%. Then, under an argon atmosphere, add 10 g of block copolymer to a 250 ml three-necked flask, dissolve 100 ml of dichloromethane solution, add anhydrous pyridine equimolar to acetyl chloride, and stir evenly; Add 30 ml of a mixed solution of acetyl chloride (the molar ratio of the same block copolymer is 4 / 1) and methylene chloride dropwise, and the addition is completed within a few hours; remove the ice-water bath and continue the reaction at room temperature for 8 hours. Finally, it is filtered and precipitated with a large amount of anhydrous methanol to obtai...

Embodiment 2

[0033] Add 10g of polyethylene glycol (1000) to a 250ml three-necked flask, then add 10.22g of DL-lactide and 4.84g of glycolide, heat it under vacuum to melt it completely, add 20mg of stannous isooctanoate, and heat up the oil bath Reaction at 160°C for 24 hours. After the reaction was completed, the initial product was dissolved in dichloromethane solution, and methanol was precipitated. The yield was about 81%. Then, under an argon atmosphere, add 10 g of block copolymer to a 250 ml three-necked flask, dissolve 100 ml of dichloromethane solution, add anhydrous pyridine equimolar to propionyl chloride, and stir evenly; Add 30 ml of a mixed solution of propionyl chloride (the molar ratio of the same block copolymer is 4 / 1) and methylene chloride dropwise, and the addition is completed within a few hours; remove the ice-water bath and continue the reaction at room temperature for 8 hours. Finally, it is filtered and precipitated with a large amount of anhydrous methanol to o...

Embodiment 3

[0035] Add 10g single-ended methoxypolyethylene glycol (5000) in a 250ml three-necked flask, then add ε-caprolactone 18.94g, after heating under vacuum to make it melt completely, add 20mg of stannous isooctanoate, and the oil bath is heated up to React at 160°C for 24 hours. After the reaction is completed, the initial product is dissolved in dichloromethane solution, and methanol is precipitated. The yield is about 82%. Then under argon atmosphere, in 250ml there-necked flask, add the block copolymer of 10g, after 100ml dichloromethane solution dissolves, add equimolar succinic anhydride and anhydrous pyridine (with block copolymer mol ratio is 4 / 1), reflux for 12 hours; after the reaction is completed, filter, add a large amount of anhydrous methanol for precipitation, and obtain a carboxyl-terminated block copolymer derivative with a yield of about 80%. pass 1 H-NMR and 13 C-NMR measures the relative molecular weight of copolymer composition and block; Measures the num...

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Abstract

A degradable temp-sensitive physically cross-linked hydrogel used as the slow-releasing carrier of injection is prepared from polyethylene glycol (PEG) as hydrophilic block, degradable polyester as hydrophobic block and the polymer terminated by functional radical through physical cross-linking.

Description

technical field [0001] The invention belongs to the technical field of polymer materials, and in particular relates to a reversible temperature-sensitive and degradable physical hydrogel with functional end groups and a preparation method thereof. Background technique [0002] The commercialization of peptide and protein drugs has been facilitated by the development of recombinant DNA technology and other technologies. However, peptide and protein drugs are easily degraded in the gastrointestinal environment, and their half-life is very short, which limits the application of peptide and protein drugs. In addition, the solubility of peptide and protein drugs and their stability in water are also difficulties faced by peptide and protein drugs. For these reasons, long-term sustained-release formulations allow slow release of active ingredients and provide high efficacy, safety, patient convenience, and compliance. [0003] Pharmaceutical polymer carriers and preparations hav...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/34A61K9/00A61K47/32
Inventor 丁建东俞麟
Owner FUDAN UNIV
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