Injection type pH sepsitive chitin quarternary ammonium salt aquagel and its preparation method

Abstract

The present invention discloses an injectable pH-sensitive chitosan quaternary ammonium salt hydrogel and a preparation method thereof, belonging to the medicine engineering pharmaceutic preparation field. The method adopts the chitosan hyamine and the glycerophosphate to prepare the injectable pH-sensitive chitosan quaternary ammonium salt hydrogel. The preparation method comprises the following steps: (1) the chitosan and the 2.3-epoxypropyl ammonium trimethylchloride are reacted at the reaction temperature, are deposited using acetone, washed, and dried to obtain chitosan hyamine; (2) the prepared chitosan hyamine is dissolved into an acid solution; (3) glycerophosphate is added dropwise into the chitosan hyamine acid solution to obtain uniform and clear mixed solution while stirring; (4) the temperature is rised to a gelatinization temperature, and an uniform and transparent chitosan hyamine hydrogel is obtained after keeping constant temperature. The hydrogel can happen gelatinization at a room temperature, and responds to the internal pH value variation to swelling, dissolve and realize intelligent release of the embedding drugs.

Description

technical field [0001] The invention relates to an injectable pH-sensitive chitosan quaternary ammonium hydrogel and a preparation method thereof, belonging to the field of pharmaceutical preparations of medical engineering. Background technique [0002] Chitosan is the product of N-deacetylation of chitin, and it is a linear polysaccharide composed of β(1→4)-bonded D-glucosamine residues and N-acetylglucosamine with different numbers and random distribution. . Chitosan has a wider range of uses than chitin because it has free amino groups on its molecular chain and can be dissolved in dilute acid solutions. As a natural cationic biopolymer, chitosan has a wide range of sources, non-toxic, odorless, antithrombotic, antistatic, alkali resistance, film forming, bioadhesion, biocompatibility and biodegradability, and its The degradation products are non-toxic, non-immunogenic and non-carcinogenic. These properties make chitosan a promising biomedical carrier [1] . Chitosan...

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Problems solved by technology

[0004] However, there are still many shortcomings in the smart hydrogels prepared so far, which limit their clinical application.

First of all, most of the currently prepared smart hydrogels are not injectable, and are usually shaped outside the body, and must be surgically implanted to enter the body, which brings economic burden and physical pain to patients as well as application problems. inconvenient

Second, most of the currently prepared smart hydrogels are not biodegradable or lack biocompatibility.

When the drug is released, it must be removed from the human body through surgery, which also limits the clinical application of hydrogel as a drug carrier

For example, polyacrylamide polymers and their derivatives are the most widely studied temperature-sensitive hydrogels, but polyacrylamide polymers are not biodegradable, and their monomers are toxic to the human body. There are great obstacles in the clinical application of gel

In addition, the pH responsiveness of the currently developed pH-sensitive hydrogels is not sensitive enough, and it is difficult to quickly respond to small changes in pH in the body to achieve "on-off" drug release.

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