CN101401963A - Glutin-beta-tricalcium phosphate composite spheroidal particle, producing method and apparatus thereof - Google Patents
Glutin-beta-tricalcium phosphate composite spheroidal particle, producing method and apparatus thereof Download PDFInfo
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- CN101401963A CN101401963A CNA2008102350790A CN200810235079A CN101401963A CN 101401963 A CN101401963 A CN 101401963A CN A2008102350790 A CNA2008102350790 A CN A2008102350790A CN 200810235079 A CN200810235079 A CN 200810235079A CN 101401963 A CN101401963 A CN 101401963A
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Abstract
The invention relates to a gelatin-beta-tricalcium phosphate composite spherical particle and a method for preparing the same. The method comprises the following steps: in the process of preparation, preparing a gelatin solution at first, and then adding beta-nano-tricalcium phosphate powder into the gelatin solution to prepare a suspension liquid, wherein the mass ratio of beta-tricalcium phosphate to the gelatin is (6-1) to (1-5). The prepared suspension liquid is added into a material storage tank (4) from a feed opening (1), is forced to flow out of a liquid guiding tube (6) evenly through controlling the pressure in the material storage tank (2), and is dripped into a condensate (7) in a thermal insulation container (8) to be condensed so as to form spherical particles. The condensed spherical particles are treated by freeze-drying at first, then are crosslinked by 2.5 percent of glutaraldehyde solution, and finally are washed by anhydrous ethanol to obtain the gelatin-beta-tricalcium phosphate composite 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 glutin-beta-tricalcium phosphate composite spheroidal particle and preparation method thereof and device.
Two, background technology
Prior art: gelatin is a kind of protein that the collagen triple-helix structure is converted into random chain and obtains, and is the soluble mixtures of polypeptides of a kind of hot water, thereby has biodegradability and excellent biological compatibility.Owing to have good film property, gelatin is used widely in the capsule of oral drug; Simultaneously, gelatin also has activated macrophage and anastalsis, can be used for making wound dressing, hemostatic material and artificial skin, and the hard tissue repair packing material.Single gelatin all is difficult to satisfy the needs of organizational project cell culture on intensity and the degradation speed, and gelatin and ceramic material is compound, is one of approach that improves its performance.
(β-TCP) is one of biodegradation or bio-absorbable type biological active ceramic material to bata-tricalcium phosphate, behind its implanted human body, Ca, P that degraded produces can enter the live body blood circulation, help new bone formation, it can be used as the desirable substitution material of human body hard tissue such as tooth and bone, has good biodegradable, biocompatibility and biological nontoxic.Therefore, bata-tricalcium phosphate is a kind of comparatively ideal hard tissue repairing material.The bata-tricalcium phosphate of synthetic exists with Powdered usually, if with gelatin and the compound preparation composite of bata-tricalcium phosphate, the good biocompatibility of existing natural macromolecular material and biodegradability have the good mechanical performance again, and the performance of material will obtain very big improvement.The glutin-beta-tricalcium phosphate composite also can be used for preparing the packing material of particle shape except that being used for preparing the block body stephanoporate support.
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 (as 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 preparation method, 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, a kind of glutin-beta-tricalcium phosphate composite spheroidal particle and preparation method thereof and device are provided, can prepare glutin-beta-tricalcium phosphate composite particles with homogeneous distributed granule diameter.
Technical scheme of the present invention is: a kind of glutin-beta-tricalcium phosphate composite spheroidal particle, the mass ratio that it is characterized in that bata-tricalcium phosphate and gelatin in the described glutin-beta-tricalcium phosphate composite spheroidal particle is (6～1): (1～5), the particle diameter of spheroidal particle is φ 0.8～4mm, the granule body interior is the micropore of aperture less than 150 μ m, intercommunication between the micropore, the porosity of glutin-beta-tricalcium phosphate composite spheroidal particle are 75～92%.
A kind of preparation method for preparing described glutin-beta-tricalcium phosphate composite spheroidal particle, preparation process is:
The first step is dissolved in the distilled water by taking by weighing the gelatin that accounts for solution gross mass 5～25%, and be (6～1) by the mass ratio of bata-tricalcium phosphate and gelatin: (1～5) takes by weighing the nanometer bata-tricalcium phosphate;
Second step added the nanometer bata-tricalcium phosphate in gelatin solution, fully stir and obtain the glutin-beta-tricalcium phosphate suspension;
The 3rd step was the pipe of φ 0.5～3mm with the second glutin-beta-tricalcium phosphate suspension that prepare of step from caliber, with the speed smooth outflow of 10～60/min, splashed into temperature for condensation in the-condensed fluid of (10～20) ℃, formed spheroidal particle; Described condensed fluid is dimethicone or vegetable oil.
The 4th step is with the condensed spherical particles separation of the 3rd step, lyophilization; It is cross-linking agent solution crosslinking Treatment 3～24h of 0.25～2.5% that spheroidal particle after the lyophilization is put into mass concentration, cleans with dehydrated alcohol then, obtains glutin-beta-tricalcium phosphate composite spheroidal particle.Described cross-linking agent is any one in formaldehyde, glutaraldehyde, the Biformyl.
Adopt drop-condensation method of the present invention to prepare microsphere particle, the preparation facilities of chitosan-beta-tricalcium phosphate composite spherical honeycombed grain material mainly is made up of charge door, Pressure gauge, pressure-control valve, storage tank, flow control valve, catheter, condensed fluid and cool-bag.
The slurry for preparing adds storage tank from charge door, by the pressure in Pressure gauge and the pressure-control valve control storage tank, to guarantee that slurry is from the catheter smooth outflow.Behind certain volume, drip greatly mouth of pipe director from the effusive slurry of catheter, in dropping process,, then enter the condensed fluid condensation in the cool-bag, form spheroidal particle because that capillary effect forms is spherical.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 chitosan solution, under the condition of no external interference, this method can be prepared the spheroidal particle of good sphericity, uniform particle diameter.
Beneficial effect: the present invention preparation obtain glutin-beta-tricalcium phosphate composite spheroidal particle:
(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) composite particles has the homogeneous particle diameter distribution, does not need to carry out follow-up screening during use and handles; The present invention be the slurry that will configure by splashing in the refrigerated in advance liquid, the surface tension of using liquid is condensed into a kind of process of spheroidal particle.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 slurry, under the condition of no external interference, this method can be prepared the microsphere particle of good sphericity, uniform particle diameter.
(3) because the narrow diameter distribution of the spheroidal particle of the present invention preparation, and the spherical granular material of same particle size can obtain largest inter-particle porosity after the filling, so when being applied to tissue filling, help growing into of cambium.
(4) granular materials is made up of gelatin and nanometer bata-tricalcium phosphate, has both possessed good degradation capability, when being used for the bone reparation, can provide Ca, P ion for new bone formation again.
Four, description of drawings:
Fig. 1 spheroidal particle forming device sketch map.
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.
The photo of Fig. 2 glutin-beta-tricalcium phosphate composite spherical honeycombed grain.
Fig. 3 is the internal void photo of glutin-beta-tricalcium phosphate composite spherical honeycombed grain.
Five, the specific embodiment:
Embodiment 1:
(1) taking by weighing the gelatin that accounts for solution gross mass 5% and be dissolved in 55～75 ℃ the distilled water, is to take by weighing the nanometer bata-tricalcium phosphate at 2: 1 by the mass ratio of bata-tricalcium phosphate and gelatin;
(2) the nanometer bata-tricalcium phosphate is added in the gelatin solution, fully stir and obtain the glutin-beta-tricalcium phosphate suspension;
(3) as shown in Figure 1, prepared suspension liquid adds storage tank 4 from charge door 1, by the pressure in Pressure gauge 2 and the pressure-control valve 3 control storage tanks 4 is 0.08MPa, to guarantee that the glutin-beta-tricalcium phosphate suspension is with the speed smooth outflow of 30/min the catheter 6 of φ 0.5mm from caliber, flow velocity can be controlled by flow control valve 5, and solution splashes into condensation in the condensed fluid 7 in the cool-bag 8, and the temperature of condensed fluid is-10 ℃, condensed fluid is a vegetable oil, forms spheroidal particle;
(4) condensed microsphere separates, and handle 8～24h in the-temperature lyophilization of (5～10) ℃, it is glutaraldehyde solution crosslinking Treatment 3～24h of 0.25～2.5% that spheroidal particle after the lyophilization is put into mass concentration earlier, the reuse dehydrated alcohol cleans, obtain glutin-beta-tricalcium phosphate composite spheroidal particle, as shown in Figure 2, particulate good sphericity, uniform particle diameter, particle diameter are φ 0.8～4mm, as shown in Figure 3, the granule body interior is the micropore of aperture less than 150 μ m, intercommunication between the micropore forms the 3 D stereo network structure, and porosity is 75～92%.
Embodiment 2:
(1) taking by weighing the gelatin that accounts for solution total amount 15% by mass percentage, is to take by weighing the nanometer bata-tricalcium phosphate at 6: 1 by the mass ratio of bata-tricalcium phosphate and gelatin;
(2) fully dissolving in the distilled water of 55～75 ℃ of gelatin addings, add the nanometer bata-tricalcium phosphate, fully stir and obtain suspension;
(3) prepared suspension liquid adds storage tank 4 from charge door 1, by the pressure in Pressure gauge 2 and the pressure-control valve 3 control storage tanks 4 is 0.5MPa, to guarantee that the glutin-beta-tricalcium phosphate suspension is with the speed smooth outflow of 60/min the catheter 6 of φ 1.5mm from caliber, flow velocity can be controlled by flow control valve 5, solution splashes into condensation in the condensed fluid 7 in the cool-bag 8, the temperature of condensed fluid is-20 ℃, and condensed fluid is a vegetable oil, forms spheroidal particle;
(4) condensed microsphere separates, and handle 14h-7 ℃ temperature lyophilization, it is 0.25% glyoxal solution crosslinking Treatment 14h that spheroidal particle after the lyophilization is put into mass concentration earlier, the reuse dehydrated alcohol cleans, obtain glutin-beta-tricalcium phosphate composite spheroidal particle, particle diameter is φ 2mm, and the granule body interior is the micropore of aperture less than 150 μ m, intercommunication between the micropore, porosity are 75%.
Embodiment 3:
(1) taking by weighing the gelatin that accounts for solution total amount 25% by mass percentage, is to take by weighing the nanometer bata-tricalcium phosphate at 2: 5 by the mass ratio of bata-tricalcium phosphate and gelatin;
(2) fully dissolving in the distilled water of 55～75 ℃ of gelatin addings, add the nanometer bata-tricalcium phosphate, fully stir and obtain suspension;
(3) prepared suspension liquid adds storage tank 4 from charge door 1, by the pressure in Pressure gauge 2 and the pressure-control valve 3 control storage tanks 4 is 0.18MPa, to guarantee that the glutin-beta-tricalcium phosphate suspension is with the speed smooth outflow of 10/min the catheter 6 of φ 3mm from caliber, flow velocity can be controlled by flow control valve 5, solution splashes into condensation in the condensed fluid 7 in the cool-bag 8, the temperature of condensed fluid is-10 ℃, and condensed fluid is a dimethicone, forms spheroidal particle;
(4) condensed microsphere separates, and handle 24h-5 ℃ temperature lyophilization, it is 2.5% formalin crosslinking Treatment 24h that spheroidal particle after the lyophilization is put into mass concentration earlier, the reuse dehydrated alcohol cleans, obtain glutin-beta-tricalcium phosphate composite spheroidal particle, particle diameter is φ 4mm, and the granule body interior is the micropore of aperture less than 150 μ m, intercommunication between the micropore, porosity are 92%.
Claims (5)
1. glutin-beta-tricalcium phosphate composite spheroidal particle, the mass ratio that it is characterized in that bata-tricalcium phosphate and gelatin in the described glutin-beta-tricalcium phosphate composite spheroidal particle is (6～1): (1～5), the particle diameter of spheroidal particle is φ 0.8～4mm, the granule body interior is the micropore of aperture less than 150 μ m, intercommunication between the micropore, the porosity of glutin-beta-tricalcium phosphate composite spheroidal particle are 75～92%.
2. preparation method for preparing the described glutin-beta-tricalcium phosphate composite spheroidal particle of claim 1 is characterized in that preparation process is:
The first step is dissolved in the distilled water by taking by weighing the gelatin that accounts for solution gross mass 5～25%, and be (6～1) by the mass ratio of bata-tricalcium phosphate and gelatin: (1～5) takes by weighing the nanometer bata-tricalcium phosphate;
Second step added the nanometer bata-tricalcium phosphate in gelatin solution, fully stir and obtain the glutin-beta-tricalcium phosphate suspension;
The 3rd step was the pipe of φ 0.5～3mm with the second glutin-beta-tricalcium phosphate suspension that prepare of step from caliber, with the speed smooth outflow of 10～60/min, splashed into temperature for condensation in the-condensed fluid of (10～20) ℃, formed spheroidal particle;
The 4th step is with the condensed spherical particles separation of the 3rd step, lyophilization; It is cross-linking agent solution crosslinking Treatment 3～24h of 0.25～2.5% that spheroidal particle after the lyophilization is put into mass concentration, cleans with dehydrated alcohol then, obtains glutin-beta-tricalcium phosphate composite spheroidal particle.
3. the preparation method of glutin-beta-tricalcium phosphate composite spheroidal particle as claimed in claim 2 is characterized in that, described condensed fluid is dimethicone or vegetable oil.
4. the preparation method of glutin-beta-tricalcium phosphate composite spheroidal particle as claimed in claim 2 is characterized in that, described cross-linking agent is any one in formaldehyde, glutaraldehyde, the Biformyl.
5. the device for preparing glutin-beta-tricalcium phosphate composite spheroidal particle 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, also be provided with Pressure gauge (2) on storage tank (4), 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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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105858629A (en) * | 2016-03-30 | 2016-08-17 | 武汉亚洲生物材料有限公司 | Preparation method for inorganic microspheres, inorganic microspheres prepared thereby, and application of inorganic microspheres |
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| US5560543A (en) * | 1994-09-19 | 1996-10-01 | Board Of Regents, The University Of Texas System | Heat-resistant broad-bandwidth liquid droplet generators |
| CN1106861C (en) * | 2000-05-19 | 2003-04-30 | 清华大学 | Preparation method of nanometer phase calcium-phosphorus salt/collagen/polylactic acid bone composite material |
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| CN1241657C (en) * | 2003-12-12 | 2006-02-15 | 清华大学 | Degradable material capable of guiding the regeneration and renovation process of hard tissue and its preparation |
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| RU2036095C1 (en) * | 1992-10-20 | 1995-05-27 | Институт пищевых веществ РАН | Apparatus for obtaining spherical pellets from water system-based material |
| CN1931378A (en) * | 2006-09-29 | 2007-03-21 | 清华大学 | Micro rack for bone tissue engineering and its prepn process and application |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105858629A (en) * | 2016-03-30 | 2016-08-17 | 武汉亚洲生物材料有限公司 | Preparation method for inorganic microspheres, inorganic microspheres prepared thereby, and application of inorganic microspheres |
| CN105858629B (en) * | 2016-03-30 | 2018-07-17 | 武汉亚洲生物材料有限公司 | A kind of preparation method of inorganic microsphere and thus obtained inorganic microsphere and application thereof |
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