CN101401956B - Chitosan spherical honeycombed grain material, producing method and apparatus thereof - Google Patents
Chitosan spherical honeycombed grain material, producing method and apparatus thereof Download PDFInfo
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- CN101401956B CN101401956B CN2008102350729A CN200810235072A CN101401956B CN 101401956 B CN101401956 B CN 101401956B CN 2008102350729 A CN2008102350729 A CN 2008102350729A CN 200810235072 A CN200810235072 A CN 200810235072A CN 101401956 B CN101401956 B CN 101401956B
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Abstract
The invention relates to a chitosan spherical porous particle material, and a method and a device for preparing the same. The method comprises the following steps: step one, preparing a chitosan acetic acid solution by using an acetic acid solution, wherein the mass concentration of the acetic acid solution is between 1 and 5 percent, and the mass of the chitosan is between 5 and 25 percent of the total mass of the chitosan acetic acid solution; step two, adding the solution into a material storage tank from a feed opening, and controlling the pressure in the material storage tank between 0.08 and 0.5 Mpa through a pressure meter and a pressure control valve, wherein the chitosan acetic acid solution uniformly flows out of the material storage tank at a speed of between 10 and 60 drops per minute, and then is dripped into a condensate with a temperature between 10 and 20 DEG C below zero in a thermal insulation container to be condensed, so that a collagen spherical porous particle material with good sphericity and uniform particle diameter is formed; and step three, separating, freezing, drying, crosslinking and cleaning the collagen spherical porous particle material to obtain the chitosan spherical porous particle material. The spherical particle material has homogeneous particle diameter distribution, contains a large number of micropores communicated with one another therein, has higher specific surface area, and can be applied to tissue repair and medicament slow release.
Description
One, technical field
The invention belongs to a kind of technology of preparing that is applied to the spherical particle material of biomedical sector, be specifically related to a kind of method for preparing of natural copolymer chitosan spherical honeycombed grain material.
Two, background technology
Prior art: chitin extensively is present in the cell wall of arthropodan shell such as shrimp, Eriocheir sinensis and insecticide and rudimentary plants such as bacterium, algae, is one of the abundantest biopolymer of occurring in nature, is a kind of very abundant natural regenerated resources.Chitosan be chitin take off the acetyl product; Chitosan is nontoxic, good biocompatibility, biodegradable; In recent years, very noticeable as natural medical polymer materials in the research that can absorb aspects such as operation suture thread, hemostatic material, wound dressing material and artificial skin.Simultaneously, chitosan also is a kind of good hard tissue repairing material, can absorb in fracture also to be applied aspect immobilization material and the damaged packing material of bone.Except that being used for preparing the block body stephanoporate support, chitosan also can be used for preparing granule shape packing material.
Micro-sphere material has the unexistent excellent properties of a lot of irregular particles, as being difficult for causing stress concentration etc. after high flowability, high bulk density, difficult reunion, the filling.At present; Reparation, the alveolar ridge of frontal resorption increase due to the filling, periodontal disease of root canal and exodontia nest, the filling of jawbone bone blister cavities, atrophic rhinitis's filling, mastoid cavity filling, shaping (like the nasus incurvus beauty treatment) reach in the damaged filling of bone with other position of skeleton, and the microsphere particle packing material is used widely.The polymer-matrix microsphere particle has multiple method for preparing, and commonly used have emulsifying-chemical crosslink technique, emulsifying-solvent evaporated method and a spray drying method.The microsphere diameter distribution of using these method preparations is bigger, and packed density is big, and when being applied to tissue filling, intergranular hole is very few, is unfavorable for growing into of cambium.
Three, summary of the invention
The present invention is directed to above-mentioned technological deficiency, provide a kind of preparation to have the method for preparing of the chitosan spherical honeycombed grain material of homogeneous distributed granule diameter.
Technical scheme of the present invention is a kind of chitosan spherical honeycombed grain material; The spheroidal particle of described chitosan spherical honeycombed grain material; Particle diameter is φ 0.8～4mm; The granule body interior is the micropore of aperture less than 150 μ m, intercommunication between the micropore, and the porosity of chitosan spherical honeycombed grain material is 80～95%.
A kind of method for preparing for preparing described chitosan spherical honeycombed grain material, step is:
The first step is 5～25% the chitosan-acetic acid solution that the quality of 1～5% acetum preparing chitosan accounts for the chitosan-acetic acid solution gross mass with mass concentration, stirs chitosan is dissolved fully;
Second step; The chitosan-acetic acid solution that the first step is prepared adds storage tank from charge door; Pressure through in Pressure gauge and the pressure-control valve control storage tank is 0.08～0.5MPa, to guarantee that chitosan-acetic acid solution is the speed smooth outflow of the catheter of φ 0.5～3mm with 10～60/min from caliber.Behind the subsphaeroidal granule of about φ 0.8～4mm, drip greatly mouth of pipe director from the effusive chitosan-acetic acid solution of catheter; In dropping process; Because capillary effect forms spherical; The temperature that then splashes in the cool-bag is condensation in the-condensed fluid of (10～20) ℃, forms the collagen spherical honeycombed grain material of good sphericity, uniform particle diameter.
According to the surface tension formula:
mg＝2πrσ
In the formula: m is a drop mass; R is the extracapillary radius; σ is a surface tension; G is an acceleration of gravity.When the density and viscosity one timing of collagen solution, under the condition of no external interference, this method can be prepared the spheroidal particle of good sphericity, uniform particle diameter.
The 3rd step is with the condensed spherical particles separation of second step, lyophilization; It is 0.25～2.5% cross-linking agent crosslinking Treatment that spheroidal particle after the lyophilization is put into mass concentration, cleans with dehydrated alcohol then, obtains chitosan spherical honeycombed grain material.Described condensed fluid is dimethicone or vegetable oil.Described cross-linking agent is any one in formaldehyde, glutaraldehyde, the Biformyl.
The device of described chitosan spherical honeycombed grain material; Described device is made up of storage tank and cool-bag, is provided with charge door at the storage tank top, on storage tank, also is provided with Pressure gauge; Pressure gauge is connected with pressure-control valve; Bottom at storage tank is provided with catheter, on catheter, is provided with flow control valve, below catheter, is provided with cool-bag.
Beneficial effect: the chitosan spherical honeycombed grain material of the present invention's preparation::
(1) contain a large amount of intercommunication micropores in the granule body interior, form three-dimensional netted stereochemical structure, this granule has higher specific surface area, helps the flowing of adherent tissue fluid of cell;
(2) chitosan particle has the homogeneous particle diameter distribution, need not sieve the granular materials that processing can obtain having same particle size; Because according to the surface tension formula:
mg＝2πrσ
In the formula: m is a drop mass; R is the extracapillary radius; σ is a surface tension; G is an acceleration of gravity.When the density and viscosity one timing of collagen solution, under the condition of no external interference, this method can be prepared the spheroidal particle of good sphericity, uniform particle diameter.
(3) the uniform particle diameter property because of the chitosan sphere granular materials for preparing according to this method is good; And the spherical granular material of same particle size; The intergranular space rate is maximum after the filling, so help the migration growth of the mobile and cell of tissue fluid after the chitosan sphere granular materials of the present invention filling.
Four, Figure of description:
The device sketch map that Fig. 1 uses for the present invention.
Device mainly is made up of charge door 1, Pressure gauge 2, pressure-control valve 3, storage tank 4, flow control valve 5, catheter 6, condensed fluid 7 and cool-bag 8.
Fig. 2 is a chitosan spherical honeycombed grain.
Fig. 3 is the internal void photo of chitosan spherical honeycombed grain.
Four, specific embodiments:
Embodiment 1:
(1) is the chitosan-acetic acid solution that 1.5% acetum preparing chitosan quality accounts for whole chitosan-acetic acid solution quality 6% with mass concentration, stirs chitosan is dissolved fully;
(2) as shown in Figure 1; The chitosan-acetic acid solution for preparing is added storage tank 4 from charge door 1; Through the pressure in pressure-control valve and the Pressure gauge control storage tank 4 is that to make chitosan-acetic acid solution be the speed smooth outflow of the catheter 6 of φ 0.5mm with 10/min from caliber to 0.08MPa; Flow velocity drips behind the subsphaeroidal granule of about φ 0.8mm greatly mouth of pipe director from the effusive chitosan-acetic acid solution of catheter through flow control valve control, and the temperature that splashes in the cool-bag 8 is condensation in-10 ℃ the condensed fluid 7; Condensed fluid is a dimethicone, forms spherical granular material;
(3) condensed microsphere separates, and handles 8h-5 ℃ temperature lyophilization, and it is 0.25% glutaraldehyde solution crosslinking Treatment 3h that the spheroidal particle after the lyophilization is put into mass concentration earlier; The reuse dehydrated alcohol cleans; Obtain chitosan spherical honeycombed grain material, as shown in Figure 2, particle diameter is φ 0.8mm; Good sphericity, uniform particle diameter.As shown in Figure 3, the granule body interior is the micropore of aperture less than 150 μ m, intercommunication between the micropore, and the porosity of chitosan spherical honeycombed grain material is 80%.
Embodiment 2:
(1) is the chitosan-acetic acid solution that 3% acetum preparing chitosan quality accounts for whole chitosan-acetic acid solution quality 25% with mass concentration, stirs fully dissolving;
(2) chitosan-acetic acid solution for preparing is added storage tank 4 from charge door 1; Through the pressure of control in the storage tank 4 is that to make chitosan-acetic acid solution be the speed smooth outflow of the catheter 6 of φ 3mm with 60/min from caliber to 0.5MPa; Behind the subsphaeroidal granule of about φ 4mm, drip greatly mouth of pipe director from the effusive chitosan-acetic acid solution of catheter; The temperature that splashes in the cool-bag 8 is condensation in-20 ℃ the condensed fluid 7, forms spherical granular material; Condensed fluid is a vegetable oil.
(3) condensed microsphere separates, and handles 24h-10 ℃ temperature lyophilization, and it is 2.5% glyoxal solution crosslinking Treatment 24h that the spheroidal particle after the lyophilization is put into mass concentration earlier; The reuse dehydrated alcohol cleans; Obtain chitosan spherical honeycombed grain material, particle diameter is φ 4mm, and the granule body interior is the micropore of aperture less than 150 μ m; Intercommunication between the micropore, the porosity of chitosan spherical honeycombed grain material are 95%.
Embodiment 3:
(1) is the chitosan-acetic acid solution that 5% acetum preparing chitosan quality accounts for whole chitosan-acetic acid solution quality 15% with mass concentration, stirs fully dissolving;
(2) chitosan-acetic acid solution for preparing is added storage tank 4 from charge door 1; Through the pressure of control in the storage tank 4 is that to make chitosan-acetic acid solution be the speed smooth outflow of the catheter 6 of φ 1.5 with 30/min from caliber to 0.28MPa; Behind the subsphaeroidal granule of about φ 2mm, drip greatly mouth of pipe director from the effusive chitosan-acetic acid solution of catheter; The temperature that splashes in the cool-bag 8 is condensation in-15 ℃ the condensed fluid 7, forms spherical granular material;
(3) condensed microsphere separates, and handles 14h in the-temperature lyophilization of (5～10) ℃, and it is 1.25% formalin crosslinking Treatment 15h that the spheroidal particle after the lyophilization is put into mass concentration earlier; The reuse dehydrated alcohol cleans; Obtain chitosan spherical honeycombed grain material, particle diameter is φ 2mm, and the granule body interior is the micropore of aperture less than 150 μ m; Intercommunication between the micropore, the porosity of chitosan spherical honeycombed grain material are 88%.
Claims (4)
1. chitosan spherical honeycombed grain material; It is characterized in that described chitosan spherical honeycombed grain material, particle diameter is φ 0.8～4mm, and the granule body interior is the micropore of aperture less than 150 μ m; Intercommunication between the micropore, the porosity of chitosan spherical honeycombed grain material are 80～95%.
2. a method for preparing for preparing chitosan spherical honeycombed grain material as claimed in claim 1 is characterized in that, preparation process is:
The first step is 5～25% the chitosan-acetic acid solution that the quality of 1～5% acetum preparing chitosan accounts for the chitosan-acetic acid solution gross mass with mass concentration, stirs chitosan is dissolved fully;
In second step, the chitosan-acetic acid solution that the first step is prepared is the pipe of φ 0.5～3mm from caliber, with the speed smooth outflow of 10～60/min, splashes into temperature for condensation in the-condensed fluid of (10～20) ℃, forms spheroidal particle;
The 3rd step is with the condensed spherical particles separation of second step, lyophilization; It is 0.25～2.5% glutaraldehyde solution crosslinking Treatment that spheroidal particle after the lyophilization is put into mass concentration, cleans with dehydrated alcohol then, obtains chitosan spherical honeycombed grain material.
3. the method for preparing of chitosan spherical honeycombed grain material as claimed in claim 2 is characterized in that, described condensed fluid is dimethicone or vegetable oil.
4. prepare the device of chitosan spherical honeycombed grain material as claimed in claim 1, it is characterized in that, described device is made up of storage tank (4) and cool-bag (8); Be provided with charge door (1) at storage tank (4) top; On storage tank (4), also be provided with Pressure gauge (2), Pressure gauge (2) is connected with pressure-control valve (3), is provided with catheter (6) in the bottom of storage tank (4); On catheter (6), be provided with flow control valve (5), below catheter, be provided with cool-bag (8).
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US11833539B2 (en) | 2018-10-02 | 2023-12-05 | Boston Scientific Scimed, Inc. | Fluidization devices and methods of use |
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| CN117547720A (en) | 2018-10-02 | 2024-02-13 | 波士顿科学国际有限公司 | Device for fluidifying and delivering a powdered agent |
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| US11918780B2 (en) | 2019-12-03 | 2024-03-05 | Boston Scientific Scimed, Inc. | Agent administering medical device |
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Cited By (1)
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