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Temperature sensitive chitosan preparation and preparation and application thereof

A technology of chitosan and temperature sensitivity, which is applied in the direction of organic active ingredients, medical preparations containing active ingredients, surgical drugs, etc., can solve the problems affecting the biocompatibility and safety of materials, restrict the application of minimally invasive surgery, Restrict promotion and application and other issues to achieve good application prospects, prevent and prevent cerebrospinal fluid leakage, and achieve the effects of good physical isolation

Inactive Publication Date: 2009-11-18
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Polymer solutions mainly include sodium carboxymethylcellulose, sodium hyaluronate, water-soluble chitosan, etc. These materials have good fluidity and biocompatibility and can effectively prevent postoperative tissue adhesion, but good fluidity Can not completely cover the wound, fast degradation time is the main defect of this type of preparation; polymer gel is mainly divided into pre-crosslinked type and in situ crosslinked type, mainly including cross-linked sodium hyaluronate and cross-linked chitin Sugar gel, this type of material is cross-linked by chemical or physical methods on the basis of solution to increase the molecular weight and in vivo residence time of the material, but the use of cross-linking agents affects the biocompatibility and safety of the material, while the colloid Membrane materials restrict its application in minimally invasive surgery; membrane materials are mainly divided into degradable and non-degradable types, including polytetrafluoroethylene (PTFE), (Johnson's product, obtained by molecular assembly of relatively high molecular weight polyoxyethylene PEO and carboxymethyl cellulose CMC) and (Genzyme's product, made by blending hyaluronic acid and carboxymethyl cellulose), this type of material can effectively play a role in physical isolation, but it is difficult to fix during use and requires surgical sutures, which is inconvenient to operate. Limit the promotion and application of such materials

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  • Temperature sensitive chitosan preparation and preparation and application thereof
  • Temperature sensitive chitosan preparation and preparation and application thereof
  • Temperature sensitive chitosan preparation and preparation and application thereof

Examples

Experimental program
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Embodiment 1

[0027] Now, the present invention will be described in detail in conjunction with the embodiments, but the implementation of the present invention is not limited thereto. Embodiment 1: Preparation of thermosensitive chitosan

[0028] The first step, the preparation of chitosan

[0029] Take fresh shrimp shells, remove the head, feet and tail, wash them with water, soak them in 5% HCl and 10% NaOH respectively to remove calcium and protein, wash until neutral, dry, and grind to obtain powdered chitin. Take powdered chitin and deacetylate it in 50% NaOH solution above 100°C for more than 24 hours, then neutralize, wash with water for injection until neutral, dehydrate with alcohol, and finally vacuum-dry to obtain chitin with a deacetylation degree of 85-95%. Tetra sugar.

[0030] The second step, alkalization of chitosan

[0031] Get prepared chitosan, add 10 times the volume of 50% (wt / wt) KOH solution, fill with N 2 For protection, alkalization at 15°C for 24h.

[0032] ...

Embodiment 2

[0038] Example 2: Research on rheological properties of temperature-sensitive chitosan

[0039] A 2% temperature-sensitive chitosan solution was subjected to temperature scanning and time scanning with a rheometer. The temperature change frequency was 1°C / min and the vibration frequency was 1 rads. Gel time.

[0040] The storage modulus of 2% thermosensitive chitosan increases sharply with the increase of temperature during the gel formation process, showing typical gel characteristics, while the change of the loss modulus is not large. During the recovery process of the gel, the storage modulus drops sharply, and the loss modulus does not change much. Therefore, the temperature-sensitive chitosan prepared by the present invention has good temperature sensitivity and gel recovery. It was shown that the material can form a gel in figure 1 ).

Embodiment 3

[0041] Example 3: Biocompatibility study of thermosensitive chitosan

[0042] 48 Kunming mice were selected as experimental animals, and 2% thermosensitive chitosan was injected into the leg muscles of the mice, and the animals were sacrificed at the 1st, 2nd, 3rd, and 4th weeks respectively, and the muscles at the injection sites were injected for 10 % formalin was fixed, and HE staining was performed to observe its biocompatibility.

[0043] After 1 week of injection, there are a large number of inflammatory cells around the material, which is due to the normal reaction of the body caused by the entry of foreign matter, and the inflammatory cells are significantly reduced after 2 weeks, and there are no obvious inflammatory cells at the 3rd and 4th weeks , so the results show that the thermosensitive chitosan prepared by the present invention has good biocompatibility (see attached figure 2 ).

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Abstract

The invention relates to medical biomaterial technical field. The currently popular post operation tissue blocking preventing agent has the disadvantages that internal degradation time is fast, operation steps are cockamamie, and the agent is not applicable to minimally invasive surgery. The invention aims at providing an antiblocking material with favorable temperature responsivity, biocompatibility and biodegradability, namely a temperature sensitive chitosan preparation as well as the preparation method and application thereof. The invention, by carrying out hydroxyl butylation reaction on chitosan, controls reaction condition, attaches the chitosan with unique temperature responsivity and maintains other inherent biological characteristics of the chitosan. The temperature sensitive chitosan preparation of the invention has favorable temperature sensitive property and favorable gelatin recoverability, and is easy to operate in operation application; the favorable biocompatibility ensures the safety of the application of the temperature sensitive chitosan; the gelation time and internal residence time are controllable, thus meeting different application requirements; and animal experiments of the post operation tissue blocking and the cerebrospinal leakage prove that the invention has good clinical application prospect.

Description

technical field [0001] The invention relates to the technical field of medical biomaterials, in particular to a temperature-sensitive chitosan preparation and its preparation method and application. The preparation has good temperature responsiveness and can be used as a preparation for preventing postoperative tissue adhesion and preventing cerebrospinal fluid leakage to use. Background technique [0002] Surgical adhesions are common after surgical operations on the abdominal cavity and spine. Postoperative adhesions will not only affect the surgical effect, but also lead to serious postoperative complications, and even make the operation fail. According to foreign reports, the incidence rate of postoperative adhesion is as high as 80%. Severe cases can lead to abdominal pain, nerve compression and even death. Therefore, preventing postoperative adhesion is an urgent problem to be solved. [0003] The rapid development of biochemistry and materials science provides a var...

Claims

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Application Information

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IPC IPC(8): A61K31/722A61P41/00C08B37/08
Inventor 侯春林顾其胜魏长征
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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