CN101401960A - Glutin-hydroxyapatite composite spheroidal particle, producing method and apparatus thereof - Google Patents
Glutin-hydroxyapatite composite spheroidal particle, producing method and apparatus thereof Download PDFInfo
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- CN101401960A CN101401960A CNA2008102350663A CN200810235066A CN101401960A CN 101401960 A CN101401960 A CN 101401960A CN A2008102350663 A CNA2008102350663 A CN A2008102350663A CN 200810235066 A CN200810235066 A CN 200810235066A CN 101401960 A CN101401960 A CN 101401960A
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Abstract
The invention provides a gelatin-hydroxyapatite composite spherical particle with homogeneous particle diameter distribution, and a method and a device for preparing the same. The gelatin-hydroxyapatite composite spherical particle prepared by the method contains a plurality of micropores communicated with one another in a particle body, has higher specific surface area, and is advantageous to the flow of tissue fluid for adhering cells; the gelatin-hydroxyapatite composite spherical particle has homogeneous particle diameter distribution, and particle materials of the same particle diameter can be obtained without screening treatment; and the spherical particle materials with the same particle diameter can obtain the largest inter-particle porosity after being filled. The gelatin-hydroxyapatite composite spherical particle materials consist of gelatin and nano-hydroxyapatite, which not only has good degradability, but also has biological activity.
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 preparation method of glutin-hydroxyapatite composite spheroidal particle.
Two, background technology
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.
Hydroxyapatite (Hydroxyapatite is called for short HA) is the main inorganic composition in vertebrates skeleton and the tooth, and in sclerotin, hydroxyapatite accounts for 60% greatly.The hydroxyapatite of synthetic has the inorganic constituents similar to body bone tissue, contain necessary calcium of tissue and P elements, after implanting, under the effect of body fluid, calcium and the phosphorus material surface that can dissociate, absorbed by body tissue, and can combine the tissue that growth makes new advances with skeleton tissue formation chemical bond.Therefore, hydroxylapatite ceramic is the excellent biological compatibility that has of generally acknowledging at present, and has bone and lure guided bone, i.e. biological activity.But the hydroxyapatite of synthetic exists with Powdered usually, because it lacks adhesive, operation is inconvenient in application, and molding is not good, and material is implanted normal generation the in back and is shifted and spills, and makes its application be subjected to certain limitation.If with gelatin and the compound preparation composite of hydroxyapatite, 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-hydroxyapatite 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
Technical problem: the present invention is directed to above-mentioned technological deficiency, a kind of glutin-hydroxyapatite composite spheroidal particle material with homogeneous distributed granule diameter and preparation method thereof and device are provided.
Technical scheme: a kind of glutin-hydroxyapatite composite spheroidal particle, described composite particles is prepared through drop-condensation process by the glutin-hydroxyapatite suspension, 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 gelatin-hydroxyl lime stone composite spheroidal particle is 75～92%, and the mass ratio of hydroxyapatite and gelatin is (6～1): (1～5).
A kind of method for preparing glutin-hydroxyapatite composite spheroidal particle, preparation process is: gelatin is dissolved in 55～75 ℃ the distilled water to such an extent that mass percent is 5～25% gelatin solution, in gelatin solution, add nanometer hydroxyapatite again, fully stir and obtain glutin-hydroxyapatite suspension, described nanometer hydroxyapatite: the mass ratio of gelatin is (6～1): (1～5); The glutin-hydroxyapatite suspension that the last step was 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; To go up step condensed spherical particles separation, 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-hydroxyapatite composite spheroidal particle.
Described condensed fluid is dimethicone or vegetable oil.
Described cross-linking agent is any one in formaldehyde, glutaraldehyde or the Biformyl.
A kind of device for preparing the glutin-hydroxyapatite composite spherical honeycombed grain material, described device is made up of storage tank and cool-bag, be provided with charge door at the storage tank top, on storage tank, also be provided with Pressure gauge, Pressure gauge is connected with pressure-control valve, bottom at storage tank is provided with catheter, is provided with flow control valve on catheter, and cool-bag is located at the catheter below.
Beneficial effect: the present invention preparation obtain glutin-hydroxyapatite composite spheroidal particle:
(1) contain a large amount of intercommunication micropores in the granule body interior, this granule has higher specific surface area, helps the flowing of adherent tissue fluid of cell;
(2) glutin-hydroxyapatite composite spheroidal particle has the homogeneous particle diameter distribution, does not need to sieve the granular materials that processing can obtain having same particle size; 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 gelatin solution, under the condition of no external interference, this method can be prepared the spheroidal particle of good sphericity, uniform particle diameter.
(3) spherical granular material of same particle size can obtain largest inter-particle porosity after the filling.
(4) granular materials is made up of gelatin and nanometer hydroxyapatite, has both possessed good degradation capability, has possessed biological activity again.
Four, description of drawings
Fig. 1 is the principle schematic of device.Device mainly is made up of (1) charge door, (2) Pressure gauge, (3) pressure-control valve, (4) storage tank, (5) flow control valve, (6) catheter, (7) condensed fluid and (8) cool-bag among the figure.
Fig. 2 is the glutin-hydroxyapatite composite spherical honeycombed grain;
Fig. 3 is a glutin-hydroxyapatite composite spheroidal particle internal void photo.
Five, the specific embodiment
Embodiment 1:
(1) gelatin is dissolved in 55～75 ℃ the distilled water to such an extent that mass percent is 5% gelatin solution, in gelatin solution, add nanometer hydroxyapatite again, fully stir and obtain glutin-hydroxyapatite suspension, described nanometer hydroxyapatite: the mass ratio of gelatin is 2: 1;
(2) prepared suspension liquid adds storage tank 4 from charge door 1, by the pressure in the control storage tank 4 is 0.08～0.5MPa, to guarantee that the glutin-hydroxyapatite suspension is with the speed smooth outflow of 10～60/min the catheter 6 of φ 0.5～3mm from caliber, splash into condensation in the dimethicone condensed fluid 7 in the cool-bag 8, the temperature of condensed fluid is-(10～20) ℃, form spheroidal particle;
(3) condensed microsphere separates, and handle 8～24h in the-temperature lyophilization of (5～10) ℃, it is formalin 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-hydroxyapatite composite spheroidal particle, 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, porosity are 75～92%.
Embodiment 2:
(1) gelatin is dissolved in 55～75 ℃ the distilled water to such an extent that mass percent is 15% gelatin solution, in gelatin solution, add nanometer hydroxyapatite again, fully stir and obtain glutin-hydroxyapatite suspension, described nanometer hydroxyapatite: the mass ratio of gelatin is 6: 1;
(2) prepared suspension liquid adds storage tank 4 from charge door 1, by the pressure in the control storage tank 4 is 0.08～0.5MPa, to guarantee that the glutin-hydroxyapatite suspension is with the speed smooth outflow of 10～60/min the catheter 6 of φ 0.5～3mm from caliber, splash into condensation in the vegetable oil condensed fluid 7 in the cool-bag 8, the temperature of condensed fluid is-(10～20) ℃, form spheroidal particle;
(3) 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-hydroxyapatite composite spheroidal particle, 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, porosity are 75～92%.
Embodiment 3:
(1) gelatin is dissolved in 55～75 ℃ the distilled water to such an extent that mass percent is 25% gelatin solution, in gelatin solution, add nanometer hydroxyapatite again, fully stir and obtain glutin-hydroxyapatite suspension, described nanometer hydroxyapatite: the mass ratio of gelatin is 2: 5;
(2) prepared suspension liquid adds storage tank 4 from charge door 1, by the pressure in the control storage tank 4 is 0.08～0.5MPa, to guarantee that the glutin-hydroxyapatite suspension is with the speed smooth outflow of 10～60/min the catheter 6 of φ 0.5～3mm from caliber, splash into condensation in the dimethicone condensed fluid 7 in the cool-bag 8, the temperature of condensed fluid is-(10～20) ℃, form spheroidal particle;
(3) condensed microsphere separates, and handle 8～24h in the-temperature lyophilization of (5～10) ℃, it is glyoxal 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-hydroxyapatite composite spheroidal particle, 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, porosity are 75～92%.
A kind of device for preparing the glutin-hydroxyapatite composite spheroidal particle material, described device is made up of storage tank 4 and cool-bag 8, be provided with charge door 1 at storage tank 4 tops, on storage tank 4, also be provided with Pressure gauge 2, Pressure gauge 2 is connected with pressure-control valve 3, be provided with catheter 6 in the bottom of storage tank 4, be provided with flow control valve 5 on catheter 6, cool-bag 8 is located at catheter 6 belows.
Claims (5)
1. glutin-hydroxyapatite composite spheroidal particle, it is characterized in that described composite particles is prepared through drop-condensation process by the glutin-hydroxyapatite suspension, 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 gelatin-hydroxyl lime stone composite spheroidal particle is 75～92%, and the mass ratio of hydroxyapatite and gelatin is (6～1): (1～5).
2. method for preparing the described glutin-hydroxyapatite composite spheroidal particle of claim 1 is characterized in that preparation process is:
A. gelatin is dissolved in 55～75 ℃ the distilled water to such an extent that mass percent is 5～25% gelatin solution, in gelatin solution, add nanometer hydroxyapatite again, fully stir and obtain glutin-hydroxyapatite suspension, described nanometer hydroxyapatite: the mass ratio of gelatin is (6～1): (1～5);
B. will go up the glutin-hydroxyapatite suspension for preparing of step 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;
C. will go up step condensed spherical particles separation, 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-hydroxyapatite composite spheroidal particle.
3. the preparation method of glutin-hydroxyapatite 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-hydroxyapatite composite spheroidal particle as claimed in claim 2 is characterized in that, described cross-linking agent is any one in formaldehyde, glutaraldehyde or the Biformyl.
5. device for preparing the described glutin-hydroxyapatite composite spheroidal particle of 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), be provided with catheter (6) in the bottom of storage tank (4), be provided with flow control valve (5) on catheter (6), cool-bag (8) is located at catheter (6) below.
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| CN102885698A (en) * | 2012-04-20 | 2013-01-23 | 张晓金 | Ultra-micro colloidal powder with core- shell structure and preparation method and application thereof |
| CN103071158A (en) * | 2013-01-10 | 2013-05-01 | 天津科技大学 | Bone capsule shell with functions of supplying calcium and building strong bones and preparation method thereof |
| CN107233318A (en) * | 2017-06-02 | 2017-10-10 | 河南工程学院 | The preparation method of hydroxyapatite drug bearing microsphere with multistage slow controlled-release effect |
| JP2020528469A (en) * | 2017-07-12 | 2020-09-24 | マツクス−プランク−ゲゼルシヤフト ツール フエルデルング デル ヴイツセンシヤフテン エー フアウＭＡＸ−ＰＬＡＮＣＫ−ＧＥＳＥＬＬＳＣＨＡＦＴ ＺＵＲ ＦＯｅＲＤＥＲＵＮＧ ＤＥＲ ＷＩＳＳＥＮＳＣＨＡＦＴＥＮ Ｅ．Ｖ． | The use of hydroxyapatite / gelatin composites, and in particular as artificial ivory, and methods of making the composites. |
| CN115368589A (en) * | 2022-08-26 | 2022-11-22 | 诺一迈尔(山东)医学科技有限公司 | Hemostatic material for filling extracted tooth sockets and preparation method thereof |
| CN116891852A (en) * | 2023-07-14 | 2023-10-17 | 四川大学 | Specific nucleic acid aptamer, targeted antibacterial drug-loaded gelatin microsphere modified by specific nucleic acid aptamer and application of targeted antibacterial drug-loaded gelatin microsphere |
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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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| CN102885698A (en) * | 2012-04-20 | 2013-01-23 | 张晓金 | Ultra-micro colloidal powder with core- shell structure and preparation method and application thereof |
| CN103071158A (en) * | 2013-01-10 | 2013-05-01 | 天津科技大学 | Bone capsule shell with functions of supplying calcium and building strong bones and preparation method thereof |
| CN103071158B (en) * | 2013-01-10 | 2015-02-25 | 天津科技大学 | Bone capsule shell with functions of supplying calcium and building strong bones and preparation method thereof |
| CN107233318A (en) * | 2017-06-02 | 2017-10-10 | 河南工程学院 | The preparation method of hydroxyapatite drug bearing microsphere with multistage slow controlled-release effect |
| JP2020528469A (en) * | 2017-07-12 | 2020-09-24 | マツクス−プランク−ゲゼルシヤフト ツール フエルデルング デル ヴイツセンシヤフテン エー フアウＭＡＸ−ＰＬＡＮＣＫ−ＧＥＳＥＬＬＳＣＨＡＦＴ ＺＵＲ ＦＯｅＲＤＥＲＵＮＧ ＤＥＲ ＷＩＳＳＥＮＳＣＨＡＦＴＥＮ Ｅ．Ｖ． | The use of hydroxyapatite / gelatin composites, and in particular as artificial ivory, and methods of making the composites. |
| CN115368589A (en) * | 2022-08-26 | 2022-11-22 | 诺一迈尔(山东)医学科技有限公司 | Hemostatic material for filling extracted tooth sockets and preparation method thereof |
| CN116891852A (en) * | 2023-07-14 | 2023-10-17 | 四川大学 | Specific nucleic acid aptamer, targeted antibacterial drug-loaded gelatin microsphere modified by specific nucleic acid aptamer and application of targeted antibacterial drug-loaded gelatin microsphere |
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