Preparation and application of biological adhesion enhanced temperature-sensitive chitosan-based postoperative adhesion prevention hydrogel

A sensitive chitosan-based, bioadhesive technology, applied in the fields of medicine and health, can solve the problems of short retention time, insufficient bioadhesion, difficult burden on patients, etc., and achieves difficult displacement or falling off, suitable degradation speed, and convenient injection and use. Effect

Active Publication Date: 2021-07-27
PEKING UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Improved surgical techniques can reduce the incidence of postoperative adhesions to a certain extent, reduce the scale of postoperative adhesions, and reduce the incidence of postoperative adhesions, but cannot completely prevent the formation of adhesions; anti-adhesion drugs metabolize and absorb faster in the body, and remain The time is short and may affect the normal healing process of the wound; at present, the development and improvement of anti-adhesion physical barrier products are the focus of preventing postoperative adhesion
[0004] The anti-adhesion barrier products currently on the market have certain defects: poor biological safety, many reports of adverse reactions after clinical use; poor adhesion and coverage of postoperative wounds, especially irregular wounds; insufficient bioadhesion, It is easy to move or fall off from the action site, affecting the effect of the anti-adhesion barrier, or requiring additional sutures for fixation, which brings additional burden to the patient; the retention time of the action site is too short, and it will be degraded within 7 days of the critical period of postoperative adhesion formation; material price Expensive, unaffordable for patients, etc.

Method used

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  • Preparation and application of biological adhesion enhanced temperature-sensitive chitosan-based postoperative adhesion prevention hydrogel
  • Preparation and application of biological adhesion enhanced temperature-sensitive chitosan-based postoperative adhesion prevention hydrogel
  • Preparation and application of biological adhesion enhanced temperature-sensitive chitosan-based postoperative adhesion prevention hydrogel

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Experimental program
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Effect test

Embodiment 1

[0100] The synthesis of embodiment 1, hydroxybutyl chitosan

[0101] Alkalinization: Weigh 300mg of chitosan with molecular weights of 1000kD, 600kD, and 100kD respectively and place them in a 50mL conical flask, add 50% (w / v) potassium hydroxide aqueous solution, stir, fully swell for 2h, and then place at room temperature Stir and alkalinize for 24h.

[0102] Dispersion in isopropanol / water system: the alkalized chitosan was suction filtered to remove excess lye, and stood at 4°C for 12 hours. Take 10mL of isopropanol and 10mL of deionized water and mix them at a volume ratio of 1:1 to obtain an aqueous solution of isopropanol. Add chitosan after alkalization and standing to a 1:1 aqueous solution of isopropanol, and stir at room temperature for 24 hours until the alkali Chitosan was completely dispersed in isopropanol / water system.

[0103] Grafting reaction: Add 20mL 1,2-epoxybutane dropwise to the isopropanol / water system dispersed with alkalized chitosan, stir while ad...

Embodiment 2

[0106] Embodiment 2, hydroxybutyl chitosan infrared spectrometry

[0107] Weigh an appropriate amount of HBC and grind it with KBr powder at room temperature with a relative humidity -1 scan in range. Infrared spectra of HBC as figure 1 shown. 3400cm -1 The strong absorption peaks superimposed on the left and right -OH and -N-H vibrational absorption peaks are the characteristic peaks of chitosan, and the characteristic peaks of chitosan are retained after the introduction of hydroxybutyl. 2870cm -1 -2980cm -1 Between the three -C-H vibrational absorption peaks in the hydroxybutyl carbon chain and the 1463cm -1 The newly introduced -CH on the hydroxybutyl group near 3 The absorption peak of is the characteristic peak of HBC. Due to the newly introduced hydroxybutyl group, at 1155cm -1 Near-C 6 The characteristic band of -OH becomes weak and almost disappears. The infrared spectra of HBC prepared from chitosan with different molecular weights proved that the hydroxybu...

Embodiment 3

[0108] Embodiment 3, the use concentration of hydroxybutyl chitosan gel is determined

[0109] The determination of the HBC phase change time adopts the "test tube method", that is, take 1mL hydrogel and add it to a 10mL centrifuge tube, put it in a 37°C water bath, and observe whether the phase change occurs every 5s. The standard for the phase change is to place the centrifuge tube upside down. On the desktop, the HBC in the centrifuge tube does not flow down the tube wall within 30s, and the time that the centrifuge tube has been immersed in the water bath when it is taken out of the water bath is the temperature-sensitive gel phase transition time, accurate to 5s.

[0110] Prepare a 1.5%-5% (w / v) HBC aqueous solution, operate according to the aforementioned method, observe the phase change of HBC solutions with different concentrations in a 37°C water bath and record the phase change time, and plot the phase change time with the concentration change curve, such as figure...

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Abstract

The invention belongs to the technical field of medicine and sanitation, and particularly relates to preparation and application of biological adhesion enhanced temperature-sensitive chitosan-based postoperative adhesion prevention hydrogel. The preparation method comprises the following steps: 1, grafting hydroxybutyl groups on chitosan to prepare hydroxybutyl chitosan with temperature-sensitive performance; 2, grafting thioglycollic acid on the chitosan to prepare the thiolated chitosan with enhanced biological adhesion performance. and 3, physically mixing the hydroxybutyl chitosan solution and the sulfhydrylated chitosan solution according to a certain proportion to obtain the biological adhesion enhanced temperature-sensitive chitosan-based postoperative adhesion prevention hydrogel. The product has the following advantages: the product has reversible temperature-sensitive phase change ability, is a liquid with good fluidity at low temperature, is convenient to inject and use, can rapidly flow to fit and cover irregular wounds after being injected to the wounds, rapidly forms a hydrogel barrier at physiological temperature to isolate adjacent tissue or organ surfaces, and prevents postoperative adhesion.

Description

technical field [0001] The invention relates to the preparation of a bioadhesion-enhanced temperature-sensitive chitosan-based anti-adhesion hydrogel and its application in preventing post-surgical adhesion, belonging to the technical fields of medicine and hygiene. Background technique: [0002] Postoperative adhesion is a common postoperative complication of clinical surgery. Postoperative adhesion occurs after most abdominal, joint, and pelvic surgical operations, and the incidence rate varies from 50% to 97%. Adhesions after surgery often seriously endanger the health of patients, greatly reduce the quality of life of patients after surgery, and bring huge mental and emotional pressure and heavy economic burden to patients. Therefore, the prevention of adhesions after surgery is of great significance for patients undergoing surgery. [0003] At present, the prevention methods of postoperative adhesions are mainly divided into three categories: (1) improving surgical tec...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08L5/08C08B37/08A61L31/04A61L31/14
CPCC08J3/075C08B37/003A61L31/042A61L31/145A61L31/148A61L31/14A61L2400/06A61L2300/41C08J2305/08C08L5/08
Inventor 王学清王柏裕张强何冰张华代文兵
Owner PEKING UNIV
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