CN101401956B - Chitosan spherical honeycombed grain material, producing method and apparatus thereof - Google Patents

Abstract

The invention relates to a chitosan spherical porous granular material and a preparation method and device thereof. The steps are as follows: the first step is to prepare a chitosan acetic acid solution whose quality of chitosan accounts for 5% to 25% of the total mass of the chitosan acetic acid solution with a mass concentration of 1 to 5% acetic acid solution; the second step is to prepare the solution Fill the storage tank from the feeding port, control the pressure in the storage tank to 0.08-0.5MPa through the pressure gauge and the pressure control valve, and flow out evenly at a speed of 10-60 drops/min. Then drop it into the condensate at the temperature of -(10-20)°C in the heat preservation container to condense to form a collagen spherical porous particle material with good sphericity and uniform particle size. The third step is separation and freeze-drying; cross-linking treatment and washing to obtain chitosan spherical porous particle material. The spherical particle material has a uniform particle size distribution, contains a large number of interconnected micropores inside, and has a high specific surface area, and can be applied in tissue repair and drug sustained release.

Description

Chitosan spherical porous particle material and its preparation method and device

1. Technical field

The invention belongs to a preparation technology of a spherical granular material applied in the field of biomedicine, and in particular relates to a preparation method of a natural polymer chitosan spherical porous granular material.

2. Background technology

Existing technology: Chitin widely exists in the shells of arthropods such as shrimps, crabs and insects, and in the cell walls of lower plants such as bacteria and algae. It is one of the most abundant biopolymers in nature and is an extremely rich natural compound. recycled resources. Chitosan is the deacetylation product of chitin. Chitosan is non-toxic, biocompatible and biodegradable. In recent years, it has been used as a natural medical polymer material in absorbable surgical sutures, hemostatic materials, wound dressing materials and Research on artificial skin and other aspects is very eye-catching. At the same time, chitosan is also an excellent hard tissue repair material, and it is also used in absorbable fixation materials for fractures and bone defect filling materials. In addition to being used to prepare bulk porous scaffolds, chitosan can also be used to prepare granular filling materials.

Microsphere materials have excellent properties that many irregular particles do not have, such as high fluidity, high bulk density, not easy to agglomerate, and not easy to cause stress concentration after filling. At present, it is used in the filling of root canals and extraction sockets, the restoration of alveolar bone absorption caused by periodontal disease, the increase of alveolar ridges, the filling of mandibular bone cysts, the filling of atrophic rhinitis, the filling of mastoid cavity, and plastic surgery (such as saddle bone filling). Nose beauty) and bone defect filling in other parts of the human skeleton, microsphere particle filling materials are widely used. There are many preparation methods for polymer-based microsphere particles, and the commonly used methods are emulsification-chemical cross-linking method, emulsification-solvent evaporation method and spray drying method. The microspheres prepared by these methods have a large diameter distribution range and a high packing density. When applied to tissue filling, the pores between the particles are too small, which is not conducive to the growth of new tissues.

3. Contents of the invention

Aiming at the above-mentioned technical defects, the present invention provides a preparation method for preparing chitosan spherical porous particle material with uniformly distributed particle diameters.

The technical solution of the present invention is a chitosan spherical porous particle material, the spherical particle of the chitosan spherical porous particle material has a particle diameter of φ0.8-4 mm, and the inside of the particle body is a micropore with a pore diameter less than 150 μm. The micropores communicate with each other, and the porosity of the chitosan spherical porous particle material is 80-95%.

A kind of preparation method of preparing described chitosan spherical porous particle material, the steps are:

The first step, the mass concentration is 1～5% acetic acid solution preparation chitosan quality accounts for 5～25% chitosan acetic acid solution total mass of chitosan acetic acid solution, stirring makes chitosan dissolve completely;

In the second step, the chitosan acetic acid solution prepared in the first step is added to the storage tank from the feeding port, and the pressure in the storage tank is controlled by a pressure gauge and a pressure control valve to be 0.08～0.5MPa to ensure that the chitosan acetic acid The solution flows out uniformly at a rate of 10-60 drops/min from a catheter with a diameter of φ0.5-3 mm. The chitosan acetic acid solution flowing out of the catheter grows to a nearly spherical particle of about φ0.8-4mm at the mouth of the catheter and then drips. During the falling process, it forms a spherical shape due to the effect of surface tension, and then drips into the heat preservation container. Condensate in the condensate at a temperature of - (10-20) ° C to form a collagen spherical porous particle material with good sphericity and uniform particle size.

According to the surface tension formula:

mg=2πrσ

In the formula: m is the mass of the droplet; r is the outer radius of the capillary; σ is the surface tension; g is the acceleration of gravity. When the density and viscosity of the collagen solution are constant, under the condition of no external interference, this method can prepare spherical particles with good sphericity and uniform particle size.

In the third step, the spherical particles condensed in the second step are separated and freeze-dried; the freeze-dried spherical particles are put into a cross-linking agent with a mass concentration of 0.25% to 2.5% for cross-linking treatment, and then washed with absolute ethanol to obtain Chitosan spherical porous particle material. The condensate is simethicone or vegetable oil. Described cross-linking agent is any one in formaldehyde, glutaraldehyde, glyoxal.

The device of the chitosan spherical porous granular material, the device is composed of a storage tank and a thermal insulation container, the top of the storage tank is provided with a feeding port, the storage tank is also provided with a pressure gauge, the pressure gauge and The pressure control valve is connected, the bottom of the material storage tank is provided with a guide tube, the guide tube is provided with a flow control valve, and a thermal insulation container is arranged under the guide tube.

Beneficial effect: the chitosan spherical porous particle material prepared by the present invention::

(1) There are a large number of intercommunicating micropores inside the particle body, forming a three-dimensional network structure. This particle has a high specific surface area, which is conducive to the flow of interstitial fluid for cell adhesion;

(2) Chitosan particles have a uniform particle size distribution, and the granular material with the same particle size can be obtained without sieving; because according to the surface tension formula:

mg=2πrσ

In the formula: m is the mass of the droplet; r is the outer radius of the capillary; σ is the surface tension; g is the acceleration of gravity. When the density and viscosity of the collagen solution are constant, under the condition of no external interference, this method can prepare spherical particles with good sphericity and uniform particle size.

(3) Because the particle size uniformity of the chitosan spherical granular material prepared according to the present method is good, and the spherical granular material of the same particle diameter has the largest void ratio after filling, so the chitosan spherical granular material of the present invention is filled It is beneficial to the flow of tissue fluid and the migration and growth of cells.

4. Attached drawings:

Figure 1 is a schematic diagram of the device used in the present invention.

The device is mainly composed of feeding port 1, pressure gauge 2, pressure control valve 3, storage tank 4, flow control valve 5, catheter 6, condensate 7 and heat preservation container 8.

Figure 2 is chitosan spherical porous particles.

Figure 3 is a photograph of the internal pores of chitosan spherical porous particles.

Fourth, the specific implementation plan:

Example 1:

(1) be that the acetic acid solution preparation chitosan quality of 1.5% with mass concentration accounts for the chitosan acetic acid solution of whole chitosan acetic acid solution quality 6%, stirring fully makes chitosan dissolve completely;

(2) as shown in Figure 1, the prepared chitosan acetic acid solution is added to the storage tank 4 from the feed port 1, and the pressure in the storage tank 4 is controlled by a pressure control valve and a pressure gauge to be 0.08MPa to make the chitosan The acetic acid solution flows out evenly from the catheter tube 6 with a pipe diameter of φ0.5mm at a rate of 10 drops/min. The flow rate is controlled by the flow control valve, and the chitosan acetate solution flowing out from the catheter tube grows to about The nearly spherical particles with a diameter of φ0.8 mm are dripped and condensed into the condensate 7 at a temperature of -10°C in the heat preservation container 8, and the condensate is dimethyl silicone oil to form a spherical particle material;

(3) The condensed microspheres were separated, and freeze-dried at a temperature of -5°C for 8 hours. The spherical particles after freeze-drying were first put into a glutaraldehyde solution with a mass concentration of 0.25% for cross-linking treatment for 3 hours, and then dried with anhydrous Wash with ethanol to obtain chitosan spherical porous particle material, as shown in Figure 2, the particle diameter is φ0.8mm, the sphericity is good, and the particle diameter is uniform. As shown in Figure 3, inside the particle body are micropores with a pore size less than 150 μm, and the micropores are interconnected, and the porosity of the chitosan spherical porous particle material is 80%.

Example 2:

(1) be that the acetic acid solution preparation chitosan quality of 3% with mass concentration accounts for the chitosan acetic acid solution of whole chitosan acetic acid solution quality 25%, stirring fully dissolves;

(2) the prepared chitosan acetic acid solution is added to the storage tank 4 from the feeding port 1, and the pressure in the control storage tank 4 is 0.5MPa to make the chitosan acetic acid solution from the pipe diameter be the catheter tube 6 of φ 3mm Flow out evenly at a speed of 60 drops/min, and the chitosan acetic acid solution flowing out from the catheter grows to a nearly spherical particle of about φ4mm at the mouth of the tube and then drips. The condensate 7 is condensed to form a spherical particle material; the condensate is vegetable oil.

(3) The condensed microspheres are separated, and freeze-dried at a temperature of -10°C for 24 hours. The spherical particles after the freeze-drying are first put into a glyoxal solution with a mass concentration of 2.5% for cross-linking treatment for 24 hours, and then dried with anhydrous Wash with ethanol to obtain the chitosan spherical porous particle material, the particle diameter is φ4mm, the interior of the particle body is micropores with a diameter less than 150 μm, and the micropores communicate with each other. The porosity of the chitosan spherical porous particle material is 95%.

Example 3:

(1) be that the acetic acid solution preparation chitosan quality of 5% with mass concentration accounts for the chitosan acetic acid solution of whole chitosan acetic acid solution quality 15%, stirring fully dissolves;

(2) the prepared chitosan acetic acid solution is added to the storage tank 4 from the feed port 1, and the pressure in the control storage tank 4 is 0.28MPa to make the chitosan acetic acid solution from the pipe diameter to be φ 1.5. Tube 6 flows out evenly with the speed of 30 drops/min, and the chitosan acetic acid solution that flows out from catheter tube grows to the subspherical particle of about φ 2mm at the mouth of the pipe and then drips, and the temperature that drips in the heat preservation container 8 is- Condensation in the condensate 7 at 15°C to form spherical granular materials;

(3) The condensed microspheres are separated, and freeze-dried at a temperature of - (5 ~ 10) ° C for 14 hours. The spherical particles after freeze-drying are first put into a formaldehyde solution with a mass concentration of 1.25% for cross-linking treatment for 15 hours, and then used After cleaning with absolute ethanol, the chitosan spherical porous particle material is obtained, and the particle diameter is φ2mm. The inside of the particle body is a micropore with a diameter less than 150 μm, and the micropores communicate with each other. The porosity of the chitosan spherical porous particle material is 88%.

Claims (4)

1. A chitosan spherical porous particle material is characterized in that the chitosan spherical porous particle material has a particle diameter of φ0.8～4mm, and the inside of the particle body is a micropore with an aperture less than 150 μm, between the micropores Interconnection, the porosity of the chitosan spherical porous particle material is 80-95%. 2. a preparation method preparing chitosan spherical porous granular material as claimed in claim 1, is characterized in that, preparation step is: The first step, the mass concentration is 1～5% acetic acid solution preparation chitosan quality accounts for 5～25% chitosan acetic acid solution total mass of chitosan acetic acid solution, stirring makes chitosan dissolve completely; In the second step, the chitosan acetic acid solution prepared in the first step is uniformly flowed out from a pipe with a diameter of 0.5 to 3mm at a rate of 10 to 60 drops/min, and the dropping temperature is - (10 to 20) Condensate in the condensate at ℃ to form spherical particles; In the third step, the spherical particles condensed in the second step are separated and freeze-dried; the freeze-dried spherical particles are cross-linked in a glutaraldehyde solution with a mass concentration of 0.25-2.5%, and then washed with absolute ethanol. The chitosan spherical porous particle material is obtained. 3. the preparation method of chitosan spherical porous granular material as claimed in claim 2, is characterized in that, described condensate is simethicone or vegetable oil. 4. prepare the device of chitosan spherical porous granular material as claimed in claim 1, it is characterized in that, described device is made up of storage tank (4) and insulation container (8), in storage tank (4) A feeding port (1) is provided on the top, and a pressure gauge (2) is also provided on the storage tank (4). The pressure gauge (2) is connected with the pressure control valve (3), and a A catheter (6) is provided, a flow control valve (5) is arranged on the catheter (6), and a thermal insulation container (8) is arranged below the catheter.

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