CN102604138B - Method for preparing chitosan substrate film by self-deposition of micron gel - Google Patents

Abstract

The invention discloses a method for preparing a chitosan substrate film by self-deposition of micron gel. The method comprises the following steps: dissolving chitosan into a diluted acid aqueous solution to prepare a chitosan acid solution; carrying out ultrasonic oscillation, and simultaneously dropwise adding a chitosan precipitating agent so as to separate out chitosan hydrogel; washing the chitosan hydrogel with deionized water until pH value is 7.4; and filtering to obtain chitosan micron hydrogel; and soaking the chitosan micron hydrogel into a glycerol aqueous solution or a glycerol aqueous solution containing a thrombin medicament or an antibacterial active matter, filtering, centrifuging, injecting into a mould, and drying under a vacuum condition. The method disclosed by the invention is simple in preparation process; the prepared chitosan film is loose in structure and has high water permeability and high compliance, and does not curl when contacting water; and various hemostatic or antibacterial medicament active components can be conveniently loaded in chitosan, and the prepared chitosan film is a good medicament carrier.

Description

A method for preparing chitosan matrix film by self-deposition of micro-gel

technical field

The invention relates to a preparation method of a chitosan matrix film, in particular to a method for preparing a chitosan matrix film by micro-gel self-deposition.

Background technique

Chitosan (Chitosan), scientific name (1,4)-2-amino-2-deoxy-β-D-glucose, is composed of chitin (N-acetyl-2-acetylamino-D-glucose with 1-4 glycoside bonded) a biopolymer obtained after deacetylation reaction, its molecular chain usually contains two structural units of N-acetylglucose and N-glucosamine, the ratio of which varies with the degree of deacetylation different from each other.

Chitin is derived from marine shellfish and algae, and chitosan is the deacetylation product of chitin. Chitosan is a natural weakly alkaline biomass sugar with excellent biocompatibility, non-toxic, antibacterial, hemostatic, and wound healing functions . At present, chitosan is widely used, including medical, agricultural, cosmetic and other fields. Among them, the application in the medical field has attracted people's attention in recent years. For example, the chitosan hemostatic bandage (Chitosan Bandages) of Hemcon Company in the United States is mainly used for on-site hemostatic treatment of acute traumatic bleeding and gunshot wounds. Passed the FDA certification of the United States and the CE certification of the European Union; in 2010, it was certified by the China Food and Drug Administration).

Chitosan has a compact structure, high crystallinity, no melting point, and it is difficult to be prepared by conventional methods such as melt injection molding. It is an effective way to expand the application field of chitosan to break through the problem of chitosan processing and molding. At present, chitosan molding methods include electrospinning, solution stretching and spinning, and the preparation of chitosan film is currently mainly using the solution casting method, that is, chitosan is pre-dissolved in acid or alkali solvent, poured into the mold and then dried. forming. There are mainly the following types: Method 1, the solution is injected into the mold and dried directly to form a film; Method 2, the solution is injected into the mold and dried to form a film, then neutralized with alkali or acid, washed with water until neutral, and then dried to form a film; Method 3, The solution is injected into the mold, gradually neutralized with lye or acid solution to obtain a plate-shaped gel, washed with water until neutral, and then dried to form a film. The first method obtains a film containing acid or alkali, which is not conducive to long-term storage; the latter two methods obtain a neutral film. The final result of these three methods is a dense film, which will swell and curl when absorbing water, which is not conducive to application. The curling of the film is easily caused during the preparation process of the second method. Method 3 is similar to the in-situ precipitation method. During the gradual neutralization process, the chitosan gel will form layers, and the gel will deform or even curl during the drying process. Therefore, the preparation technology of chitosan film still needs to be improved.

Contents of the invention

The purpose of the present invention is to provide a method for preparing a chitosan matrix film by self-deposition of micro-gel with simple preparation process, so as to obtain a film that is loose and does not curl when exposed to water.

In order to achieve the above object, the method for preparing the chitosan matrix film from microgel self-deposition of the present invention may further comprise the steps:

first step:

Dissolve chitosan in dilute acid aqueous solution to prepare a chitosan acid solution with a mass concentration of 2%, filter to remove insoluble matter, and ultrasonically oscillate, while adding chitosan precipitant drop by drop to the solution to precipitate chitosan Gel, ultrasonic vibration control chitosan gel particle size between 100 ~ 500 μm, prepared chitosan micron hydrogel suspension;

Step two:

The chitosan micron hydrogel suspension prepared in the first step is washed with deionized water to a pH value of 7.4, and filtered to obtain chitosan micron hydrogel;

third step:

Immerse the chitosan micron hydrogel prepared in the second step in a glycerol aqueous solution with a mass concentration of 0.5% to 10% for 30-60 minutes, and then filter to obtain a glycerin-plasticized chitosan micron hydrogel ;

the fourth step:

The chitosan micro-hydrogel plasticized by glycerol is centrifuged, and the water content of the chitosan micro-hydrogel plasticized by glycerol is controlled to be 100% to 500% of the chitosan quality; The molded chitosan micron hydrogel is injected into a mould, and dried at 45-80° C. under vacuum or normal pressure conditions to obtain a chitosan matrix film.

In the present invention, the degree of deacetylation of the chitosan is 50%-100%, and the molecular weight is 100000-500000. The calculation method of the degree of deacetylation is as follows: "Determination of the degree of deacetylation of chitosan by acid-base conductometric titration" written by Jia Zhishen and Li Xiuling in "Analytical Chemistry Research Bulletin" No. 7, 2002, pages 846-848.

In order to endow the chitosan base film with hemostatic or antibacterial function, three seven elements, CaCl ₂ or tranexamic acid coagulation drugs can be added to the glycerol aqueous solution, or oxytetracycline or nano silver antibacterial active substances can be added. The addition amount of medicine is selected according to need.

Among the present invention, used mold can be the vessel such as petri dish etc. that has opening, and other positions are sealed; It can also be the similar opening such as sample sieve, the utensil that has porous gauze at the bottom.

In the present invention, the dilute acid is an aqueous formic acid solution with a mass concentration of 1% to 5%, an aqueous acetic acid solution with a mass concentration of 1% to 5%, or an aqueous hydrochloric acid solution with a mass concentration of 1% to 5%.

In the present invention, described chitosan precipitating agent can be the NaOH aqueous solution that mass concentration is 5%, the KOH aqueous solution that mass concentration is 5%, the NaOH ethanol solution that mass concentration is 5% or that mass concentration is 5% KOH ethanol solution.

The present invention has following advantage and effect:

1. The present invention utilizes the capillary force and van der Waals force between chitosan micron hydrogel particles to connect each other, dry and shape, no need to add cross-linking agent, only need to wash once, which greatly simplifies the preparation process, and can be quickly prepared Flat, regular chitosan film.

2. The chitosan film prepared by the present invention has a loose structure, high water permeability, does not curl when exposed to water, has high compliance, and can be easily attached to various surfaces.

3. The present invention uses neutral chitosan micron hydrogel, which can conveniently load various hemostatic or antibacterial drug active ingredients in chitosan, and is a good drug carrier.

Detailed ways

The present invention will be further described below in conjunction with embodiment:

Example 1:

(1) Take 2g of chitosan with a deacetylation degree of 95% and a molecular weight of 100,000, add 200ml of 2% acetic acid aqueous solution, stir at room temperature until completely dissolved, and prepare a 1% (m/v) chitosan acetic acid aqueous solution. Stand still for defoaming; filter the above solution, ultrasonically vibrate in an ultrasonic disperser, and simultaneously add 5% aqueous sodium hydroxide solution dropwise to the solution until it completely precipitates to obtain a chitosan micron hydrogel suspension. The particle size of chitosan microgel is between 300 and 500 μm;

(2) Rinse the chitosan micron hydrogel suspension with deionized water to neutral pH=7.4, filter to obtain chitosan micron hydrogel;

(3) Immerse the prepared chitosan micron hydrogel in a glycerol solution with a mass concentration of 1%, and filter after 30 minutes to obtain a chitosan micron hydrogel plasticized with glycerol;

(4) Centrifuge the chitosan micro-hydrogel plasticized with glycerol to remove excess water, and control the moisture content of the chitosan micro-hydrogel plasticized with glycerol to be 100% of the chitosan quality, Then inject the chitosan micron hydrogel plasticized by glycerol into the mould, and dry at 60° C. under normal pressure to obtain the chitosan matrix film. The chitosan film has high water permeability and does not curl when exposed to water.

Example 2:

(1) Take 2g of chitosan with a deacetylation degree of 85% and a molecular weight of 200,000, add 200ml of a 2% hydrochloric acid aqueous solution, stir at room temperature until completely dissolved, and prepare a 1% (m/v) chitosan hydrochloric acid aqueous solution, Stand still for defoaming; filter the above solution, ultrasonically vibrate in an ultrasonic disperser, and simultaneously add 5% potassium hydroxide aqueous solution dropwise to the solution until it completely precipitates to obtain a micron hydrogel suspension of chitosan. The particle size of chitosan microgel is between 100 and 300 μm;

(2) Rinse chitosan micron hydrogel with deionized water to neutral pH=7.4, filter to obtain chitosan micron hydrogel;

(3) Immerse the prepared chitosan micron hydrogel in a solution containing 1% glycerol, 0.5% CaCl _and 1% notoginseng, and filter after 30 minutes to obtain _CaCl and notoginsin Glycerol plasticized chitosan micron hydrogel;

(4) Centrifuge the glycerol-plasticized chitosan micron hydrogel containing _CaCl2 and notoginsin in step (3) to remove excess water, and control the water content of the chitosan micron hydrogel to the shell 100% polysaccharide quality, then inject the glycerol plasticized chitosan micron hydrogel containing CaCl ₂ and notoginseng into the mold, and dry it at 45°C under vacuum to obtain CaCl ₂ and notoginseng Glycerin-plasticized chitosan film, which can be used for rapid hemostasis.

Example 3:

(1) Take 2g of chitosan with a deacetylation degree of 75% and a molecular weight of 500,000, add 200ml of 2% acetic acid aqueous solution, stir at room temperature until completely dissolved, and prepare a 1% (m/v) chitosan acetic acid aqueous solution. Stand still for defoaming; filter the above solution, ultrasonically vibrate in an ultrasonic disperser, and simultaneously add 5% aqueous sodium hydroxide solution dropwise to the solution until it completely precipitates to obtain a chitosan micron hydrogel suspension. The particle size of chitosan microgel is between 100 and 300 μm;

(2) Rinse chitosan micron hydrogel with deionized water to neutral pH=7.4, filter to obtain chitosan micron hydrogel;

(3) Immerse the prepared chitosan micron hydrogel in an aqueous solution containing mass concentrations of 1% glycerin, 1% notoginsin and 0.5% nano-silver. After 30 minutes, filter to obtain Silver glycerol plasticized chitosan micron hydrogel;

(4) Centrifuge the glycerin-plasticized chitosan micron hydrogel containing notoginseng and nano-silver to remove excess water, and control the water content of the chitosan micron hydrogel to 200% of the mass of chitosan %, and then inject the plasticized chitosan micron hydrogel containing notoginseng and nano-silver into the mold, and dry at 80°C under vacuum to obtain chitosan containing notoginseng and nano-silver sugar film. This chitosan film has the function of antibacterial and hemostatic.

The above-mentioned embodiments are only for those skilled in the art to understand the content of the present invention and implement it accordingly, and shall not limit the protection scope of the present invention. All equivalent changes or modifications made according to the spirit of the present invention shall fall within the protection scope of the present invention.

Claims (3)

1. a kind of micron gel self-deposition prepares the method for chitosan matrix membrane, it is characterized in that comprising the following steps: first step: Dissolve chitosan in dilute acid aqueous solution to prepare a chitosan acid solution with a mass concentration of 2%, filter to remove insoluble matter, and ultrasonically oscillate, while adding chitosan precipitant drop by drop to the solution to precipitate chitosan water Gel, ultrasonic vibration controls the particle size of chitosan gel between 100 and 500 μm, and prepares chitosan micron hydrogel suspension. The above-mentioned dilute acid is formic acid aqueous solution with a mass concentration of 1% to 5%. Acetic acid aqueous solution with a concentration of 1% to 5% or an aqueous hydrochloric acid solution with a mass concentration of 1% to 5%, the chitosan precipitating agent is a NaOH aqueous solution with a mass concentration of 5%, and a KOH aqueous solution with a mass concentration of 5%. , a NaOH ethanol solution with a mass concentration of 5% or a KOH ethanol solution with a mass concentration of 5%; Step two: The chitosan micron hydrogel suspension prepared in the first step is washed with deionized water to a pH value of 7.4, and filtered to obtain chitosan micron hydrogel; third step: Immerse the chitosan micron hydrogel prepared in the second step in a glycerol aqueous solution with a mass concentration of 0.5% to 10% for 30-60 minutes, and then filter to obtain a glycerin-plasticized chitosan micron hydrogel ; the fourth step: The chitosan micro-hydrogel plasticized by glycerol is centrifuged, and the water content of the chitosan micro-hydrogel plasticized by glycerol is controlled to be 100% to 500% of the chitosan quality; The molded chitosan micron hydrogel is injected into a mould, and dried at 45-80° C. under vacuum or normal pressure conditions to obtain a chitosan matrix film. 2. The method for preparing chitosan matrix film by self-deposition of microgel according to claim 1, characterized in that: the degree of deacetylation of the chitosan is 50% to 100%, and the molecular weight is 100,000 to 500,000. 3. micron gel self-deposition according to claim 1 prepares the method for chitosan matrix film, it is characterized in that: the 3rd step adds notoginseng, _CaCl or tranexamic acid blood coagulation medicine in glycerol aqueous solution , or add oxytetracycline or nano silver antibacterial active substances.