Highly bioadhesive and thermosensitive hydrogel, and preparation method and application thereof

A temperature-sensitive hydrogel and bioadhesion technology, which is applied in the directions of pharmaceutical formulation, drug combination, drug delivery, etc., can solve the problems that affect the application prospect of drug carriers, cannot solve the problem of gel precipitation, and cannot guarantee the stability of drugs, etc., to achieve convenience Clinical application, improving patient compliance, and reducing the effect of dosing frequency

Active Publication Date: 2010-06-09
WUHAN WORLDNER UNITED PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, chitosan (chitosa)-sodium glycerophosphate (GP) is actually a pseudo-temperature-controlled hydrogel, that is, it also gels at low temperatures, but the gelation time is longer, up to 3 months. This feature seriously affects its application prospects as a drug carrier because it cannot guarantee the stability of the drug during storage.
[0005] Poloxamer (poloxamer) is currently the most intensively studied polymer material for preparing temperature-sensitive in situ gels. Prescriptions containing poloxamer can increase the residence time of drugs at the site of action, improve bioavailability and Drug efficacy, and has an appropriate gelling temperature, the disadvantage is that the gelling mechanical strength is low, and the dissolution rate is fast
Therefore, although the combined application of poloxamer and chitosan solves the mechanical strength of the gel, it cannot solve the problem of gel precipitation under normal physiological pH conditions (except vagina, stomach), which limits its use as an injectable drug. Application of drug and mucosal drug delivery

Method used

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  • Highly bioadhesive and thermosensitive hydrogel, and preparation method and application thereof
  • Highly bioadhesive and thermosensitive hydrogel, and preparation method and application thereof
  • Highly bioadhesive and thermosensitive hydrogel, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 1: High bioadhesive thermosensitive hydrogel, composed of 18wt% poloxamer 407, 15wt% poloxamer 188, 0.3wt% carboxymethyl chitosan and the rest of water. Mix poloxamer 407 and poloxamer 188, add water and stir evenly, add carboxymethyl chitosan, stir evenly, and obtain high bioadhesion thermosensitive hydrogel. The gelation temperature was measured by the magnetic stirring method, and the gelation temperature of the gel was 35° C., and the gelation time was 5 minutes. (pH7.4 value).

[0019] Determination of gel strength: Take 20g of sample, put it in a cylinder with 50ml scale, and then put it in a constant temperature water bath at 37°C to make the sample gel, put a 100g weight on the pressure push rod, and connect the other end of the push rod to a The disc is in close contact with the inner wall of the cylinder and drilled with 6 round holes with a diameter of 2 mm. The gel strength is expressed by the time required for the disc to drop 2 cm under pressure. ...

Embodiment 2

[0022] Example 2: High bioadhesive thermosensitive hydrogel, composed of 18wt% poloxamer 407, 15wt% poloxamer 188, 5wt% carboxymethyl chitosan and the rest of water. Add water to poloxamer 407 and stir evenly, add carboxymethyl chitosan, stir evenly, and obtain high bioadhesive thermosensitive hydrogel. The gelation temperature was measured by magnetic stirring method, the gelation temperature of the gel was 35°C, and the gelation time was 1min. (pH9.0)

Embodiment 3

[0023] Example 3: High bioadhesive thermosensitive hydrogel, composed of 7wt% poloxamer 407, 5wt% poloxamer 188, 10wt% carboxymethyl chitosan and the rest of water. Add water to poloxamer 407 and stir evenly, add carboxymethyl chitosan, stir evenly, and obtain high bioadhesive thermosensitive hydrogel. The gelation temperature was measured by the magnetic stirring method, and the gelation temperature of the gel was 35° C., and the gelation time was 30 minutes. (pH 8.0)

[0024] Using the high bioadhesion temperature-sensitive hydrogel of the above-mentioned Example 1 or 2 or 3 as a blank gel, add diammonium glycyrrhizinate, stir evenly, prepare a temperature-sensitive hydrogel containing 0.5% diammonium glycyrrhizinate, and use the magnetic stirring method The gelling temperature was measured, and the gelling temperature of the gel was 35.5° C., and the gelling time was 5 minutes.

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Abstract

The invention relates to a temperature sensitive hydrogel with high bioadhesion, the components of which includes: 10 percent to 40 percent of poloxamer, 0.1 percent to 10 percent of carboxymethyl chitosan and 50 percent to 99.8 percent of water while the percentages are weight percentages. The invention also provides a preparation method of the temperature sensitive hydrogel: the poloxamer is added with water to be evenly stirred, and added with the carboxymethyl chitosan to be evenly stirred to obtain the temperature sensitive hydrogel with high bioadhesion. The temperature sensitive hydrogel can be used as a drug carrier after being defoamed. The preparation method of the invention can be used for the preparation of mucosal drug delivery preparations and injection drug delivery preparations and obtain an intelligent drug slow-release preparation, the hydrogel property of which meets the application requirements in the conditions of pathological mechanism and physiology, thus being convenient for clinical application, being capable of reducing the frequency of the drug delivery and improving the adaptability of patients; enhancing treatment effect and reducing toxic and side effects. Compared with the pure poloxamer hydrogel, the temperature sensitive hydrogel of the invention can obviously enhance the mechanical strength and the mucosa bioadhesion and obviously prolong the detention time in vivo under the condition of ensuring excellent fluidity and favorable hydrogel temperature condition.

Description

technical field [0001] The invention relates to a bioadhesive temperature-sensitive hydrogel, a preparation method and its application in mucosal drug delivery preparations and injection slow-release preparations. Background technique [0002] For a long time, the medical community has been looking forward to finding a way to inject the required amount of drugs into human organs when needed. The use of smart gels to automatically sense the state of the body and control the release of drugs has attracted more and more attention. .A new type of drug delivery system—the intelligent drug delivery system came into being. The intelligent drug delivery system can respond to a certain external stimulus signal, and adjust the release of drugs according to the nature and strength of the stimulus signal. According to the stimulus signal Intelligent drug delivery systems can be divided into physical stimulus-responsive drug release systems, chemical stimulus-responsive drug release syst...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/36A61K9/08A61K9/00A61K31/56A61P1/00
Inventor 丁虹陈竹
Owner WUHAN WORLDNER UNITED PHARMA
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