CN103937009A - Preparing method of chitosan hydrogel - Google Patents

Abstract

The invention discloses a preparing method of chitosan hydrogel. According to the method, chitosan is used as a raw material, glutaraldehyde is used as a crosslinking agent, and the chitosan hydrogel is synthesized in an acetic acid solution. Process conditions for preparing the chitosan hydrogel are optimized through orthogonal experiments. Experiment results show that: when the concentration of the chitosan is 3%, the concentration of the glutaraldehyde is 3% and the gelation temperature is 55 DEG C, the hardness of the prepared chitosan hydrogel is the maximum; and when the concentration of the chitosan is 2%, the concentration of the glutaraldehyde is 1% and the gelation temperature is 45 DEG C, the swelling degree of the prepared chitosan hydrogel is the maximum. The chitosan hydrogel has good biological compatibility, and therefore the chitosan hydrogel has broad application prospects in the fields of drug release systems, biomimetic materials, chemical mechanical systems, and the like.

Description

A kind of preparation method of chitosan hydrogel

1, technical field

The present invention belongs to chemistry by International Patent Classification (IPC) (IPC); Ministry of Metallurgical Industry, chemical branch, organic high molecular compound; Its preparation or chemical process; The large class of composition taking it as base-material, polyose; Its derivative group, chitin; Chondroitin sulfate; Hyaluronic acid; The technical field of their derivative group.

2, background technology

Hydrogel is a kind of high molecular polymer with three-dimensional structure, forms by hydrophilic macromolecular compound is crosslinked, can be in water swelling and keep large quantity of moisture and don't dissolving.Meanwhile, there is good biocompatibility, thereby have broad application prospects in fields such as drug delivery system, biomimetic material, chemical machinery systems.

Chitosan wide material sources, cheap and easy to get, and there is good biocompatibility, security and biological degradability, be the ideal material of preparing hydrogel.In the time thering is the cross-linked polymer of tridimensional network and solvent phase mutual effect, occur swellingly, owing to thering is crosslinking structure, its swelling behavior is restricted.Swelling degree is decided by cross-linking density, and cross-linking density is higher, and swelling capacity is less.Chitosan, because of its characteristic that has softness intensity difference, is unable to undergo weight.In addition, it also has the shortcomings such as character volatile, gel is very unstable compared with the mechanically resistant materials such as metal.Therefore, hardness and the swelling capacity of research chitosan, be the widespread use of chitosan gel, and synthesized high-performance chitosan based aquagel is laid a good foundation.

3, summary of the invention

3.1 experimental section

3.1.1 instrument and medicine

HHS type electric-heated thermostatic water bath, JA5003 type electronic balance, 10222A type digital display electric drying oven with forced convection, QTS225Texture Aualyser (Britain), FUHUA HZ22C constant incubator, microscope, blood counting chamber; Chitosan (biochemical reagents), glutaraldehyde (AR), Glacial acetic acid (AR), potato, glucose, agar, candiyeast.

3.1.2 the preparation of chitosan hydrogel

Accurately take 1.0g chitosan in clean beaker, add 40mL2% acetum, stirring and dissolving; Add 16mL2% glutaraldehyde, stir, 50 DEG C of constant temperature 1h obtain yellow transparent chitosan hydrogel; Room temperature is placed 48h and is obtained yellow transparent chitosan hydrogel.

3.1.3 the mensuration of sewlling ration

Accurately take 2g left and right gel, be dipped to swelling equilibrium in distilled water, elimination excessive moisture, blots its surface-moisture with filter paper, weighs, with following formula calculation sample sewlling ration.

$\mathrm{SR}=\frac{\mathrm{Ws}-\mathrm{Wd}}{\mathrm{Wd}}\×100\%$

In formula: the sewlling ration (%) that SR is hydrogel; Ws is the quality (g) of gel reach swelling equilibrium in distilled water time; Wd is gel quality (g) while not soaking.

3.1.4 gel hardness test

Cylindrical probe (diameter is 10mm) on QTS225TextureAualyser declines with the speed of 15cm/s, when from gel surface when pressing down 6mm, record gel hardness (g).Sample test 3 times, gets its mean value.

3.1.5 the mensuration of gel biological compatibility

In chitosan solution, add 1.0mL7.68 × 10 ⁸individual yeast/mL candiyeast bacteria suspension, add glutaraldehyde solution again, gel under room temperature, with sterilized water soaks after placing 24h in 28 DEG C of constant incubators, shakes 1h in constant-temperature table; Get supernatant liquor 1mL and be inoculated on yeast solid substratum, in 28 DEG C of constant incubators, carry out microorganism culturing, observe its colony growth situation.

4, brief description of the drawings

Accompanying drawing has mainly been narrated the concentration of chitosan, concentration and the impact of temperature on hydrogel hardness and swelling capacity of glutaraldehyde, with and biocompatibility:

Fig. 1: the impact of chitosan concentration on gel hardness and swelling capacity;

Fig. 2: the impact of glutaraldehyde concentration on gel hardness and swelling capacity;

Fig. 3: the impact of gelling temp on hardness and swelling capacity;

Fig. 4: candiyeast colony growth situation.

5, Analysis of conclusion

Below in conjunction with above-mentioned accompanying drawing, chitosan hydrogel preparation method of the present invention is described further:

5.1 chitosan concentration

The concentration of glutaraldehyde is 2%, gelling temp is 50 DEG C, and preparation chitosan concentration is respectively 1%, 2%, 3%, 4%, 5%, 6% chitosan solution 40mL, adds 2% glutaraldehyde 16mL, 1h in 50 DEG C of constant temperature water baths, measures gel hardness after placing 24h under room temperature; Take the each 2g of the chitosan hydrogel of preparing under similarity condition left and right simultaneously, be soaked in distilled water to swelling equilibrium, measure its equilibrium swelling degree, chitosan concentration on the impact of gel hardness and swelling capacity as shown in Figure 1.

As shown in Figure 1, hydrogel hardness increases maximum in the time that chitosan concentration is 6% along with the increase of chitosan concentration; And swelling capacity is to reduce along with the increase of chitosan concentration.Reason is the increase along with chitosan concentration, and chitosan interchain has formed cohesion tangled structure, and this tangled structure causes by the hydrogen bond association structure forming between the light side group of chitosan interchain, and its effect is similar to the cross-linking set in cross-linked network structure.In the time that chitosan concentration increases, the interior chitosan molecule number of unit volume increases, and form interchain hydrogen bond and condense the increase of counting out of tangling, that is degree of crosslinking increase, therefore swelling capacity reduces.

5.2 glutaraldehyde concentration

Prepare 3% chitosan solution 40mL, add respectively concentration to be respectively 0.5%, 1.0%, 1.5%, 2%, 2.5%, 3% glutaraldehyde solution 16mL, 1h in 50 DEG C of constant temperature water baths, measures gel hardness after placing 24h under room temperature; Take the each 2g of the chitosan hydrogel of preparing under similarity condition left and right simultaneously, be soaked in distilled water to swelling equilibrium, measure its equilibrium swelling degree, glutaraldehyde concentration on the impact of gel hardness and swelling capacity as shown in Figure 2.

As shown in Figure 2, the hardness of hydrogel is along with crosslinker concentration increases and increases.Reason is that this deacetylation of testing raw material chitosan used is 92.67%, therefore there is a large amount of amino on chitosan molecular chain, increase linking agent glutaraldehyde concentration, make the crosslinked aggravation between chitosan molecular chain, it is finer and close that network structure becomes, thereby gel hardness is along with linking agent glutaraldehyde concentration increases and increases; And network structure becomes the more fine and close resistance increasing that also can make water molecules enter gel structure, hydrophilic radical on chitosan molecular chain is difficult to contact with water molecules, the stretching, extension of gel macromolecule network is restricted, thereby causes swelling capacity to reduce along with the increase of glutaraldehyde concentration.

5.3 gelling temp

Prepare 3% chitosan solution 40mL, adding concentration is 2% glutaraldehyde solution 16mL, stirs and is placed in 30 DEG C, 35 DEG C, 40.℃、45℃、50。DEG C and the constant temperature water bath of 55 DEG C in 1h, under room temperature, place 24h, measure gel hardness and swelling capacity, to study the impact of gelling temp on hardness and swelling capacity, experimental result is as shown in Figure 3.

As seen from Figure 3, hydrogel hardness is first to reduce along with the rising of gelling temp, then increases, hardness maximum 55 DEG C time; And swelling capacity first increases along with the rising of gelling temp, then reduce, 40 DEG C time, swelling behavior degree is the highest; But gelling temp is little to hardness, swelling capacity influence degree.

5.4 biocompatibility

The chitosan hydrogel of embedding candiyeast is immersed in sterilized water, gets 1mL supernatant liquor and be inoculated in yeast culture base, cultivate 2～3d in 28 DEG C of constant incubators, media surface grows shallow milk yellow candiyeast bacterium colony, and experimental result as shown in Figure 4.This result shows, chitosan hydrogel has good biocompatibility, and microorganism cells is not had to toxic action.

Claims (2)

1. the preparation method of chitosan hydrogel of the present invention, is taking chitosan as raw material, as linking agent, synthesizes chitosan hydrogel by glutaraldehyde in acetum.

2. according to claim 1, the processing condition of chitosan hydrogel of preparation highest hardness are: chitosan concentration is 3%, glutaraldehyde concentration is 3%, gelling temp is 55 DEG C; The processing condition of preparing the chitosan hydrogel of maximum swelling degree are: chitosan concentration is 2%, glutaraldehyde concentration is 1%, gelling temp is 45 DEG C.