CN101401960B - Glutin-hydroxyapatite composite spheroidal particle, producing method and apparatus thereof - Google Patents

Glutin-hydroxyapatite composite spheroidal particle, producing method and apparatus thereof Download PDF

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Publication number
CN101401960B
CN101401960B CN2008102350663A CN200810235066A CN101401960B CN 101401960 B CN101401960 B CN 101401960B CN 2008102350663 A CN2008102350663 A CN 2008102350663A CN 200810235066 A CN200810235066 A CN 200810235066A CN 101401960 B CN101401960 B CN 101401960B
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hydroxyapatite
glutin
spheroidal particle
gelatin
particle
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CN101401960A (en
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董寅生
张艳
盛晓波
储成林
郭超
林萍华
浦跃朴
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Haian Shen county gelatin Co., Ltd.
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Southeast University
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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

The preparation method of glutin-hydroxyapatite composite spheroidal particle
One, technical field
The invention belongs to a kind of spherical particle material preparation technology that is applied to 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 good biocompatibility.Owing to having 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 greatly 60%.The hydroxyapatite of synthetic has the inorganic constituents similar to body bone tissue, contain the 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 form chemical bonds with the skeleton tissue, the tissue that growth makes new advances.Therefore, hydroxylapatite ceramic is the good biocompatibility 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 normal the generation was shifted and spills after material was implanted, and made its application be subject to certain limitation.If with gelatin and the compound preparation composite of hydroxyapatite, the good biocompatibility of existing natural macromolecular material and biodegradability have again good mechanical property, the performance of material will be very significantly improved.The glutin-hydroxyapatite composite also can be used for preparing the packing material of particle shape except 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 jaw bones blister cavities, atrophic rhinitis's filling, mastoid cavity filling, shaping (such 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, emulsion solvent evaporation technique and a spray drying method.The microsphere diameter distribution of using these method preparations is larger, and packed density is large, 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 that the aperture is less than the micropore of 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 upper step was prepared is the pipe of φ 0.5~3mm from caliber, evenly flows out with the speed of 10~60/min, splashes into temperature for condensation in the-condensed fluid of (10~20) ℃, forms spheroidal particle; With the condensed spheroidal particle separation of upper 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, then cleans with dehydrated alcohol, 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 comprised 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 at 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, is conducive to the Flow of tissue fluid of the adhesion of cell;
(2) glutin-hydroxyapatite composite spheroidal particle has the particle size distribution of homogeneous, 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 drop mass; R is the extracapillary radius; σ is surface tension; G is acceleration of gravity.When density and viscosity one timing of gelatin solution, under the condition without 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 maximum interparticle porosity after the filling.
(4) granular materials is comprised of gelatin and nanometer hydroxyapatite, has both possessed good degradation capability, has possessed again biological activity.
Four, description of drawings
Fig. 1 is the principle schematic of device.Device mainly is comprised 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 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) suspension for preparing adds storage tank 4 from charge door 1, be 0.08~0.5MPa by the pressure of control in the storage tank 4, to guarantee that the speed with 10~60/min evenly flows out the catheter 6 of glutin-hydroxyapatite suspension from caliber as φ 0.5~3mm, 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 process 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 first mass concentration, clean with dehydrated alcohol again, obtain glutin-hydroxyapatite composite spheroidal particle, particle diameter is φ 0.8~4mm, and the granule body interior is that the aperture is less than the micropore of 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) suspension for preparing adds storage tank 4 from charge door 1, be 0.08~0.5MPa by the pressure of control in the storage tank 4, to guarantee that the speed with 10~60/min evenly flows out the catheter 6 of glutin-hydroxyapatite suspension from caliber as φ 0.5~3mm, 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 process 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 first mass concentration, clean with dehydrated alcohol again, obtain glutin-hydroxyapatite composite spheroidal particle, particle diameter is φ 0.8~4mm, and the granule body interior is that the aperture is less than the micropore of 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) suspension for preparing adds storage tank 4 from charge door 1, be 0.08~0.5MPa by the pressure of control in the storage tank 4, to guarantee that the speed with 10~60/min evenly flows out the catheter 6 of glutin-hydroxyapatite suspension from caliber as φ 0.5~3mm, 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 process 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 first mass concentration, clean with dehydrated alcohol again, obtain glutin-hydroxyapatite composite spheroidal particle, particle diameter is φ 0.8~4mm, and the granule body interior is that the aperture is less than the micropore of 150 μ m, intercommunication between the micropore, porosity are 75~92%.
Embodiment 4
A kind of device for preparing the glutin-hydroxyapatite composite spheroidal particle material, described device is comprised 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 at catheter 6, cool-bag 8 is located at catheter 6 belows.

Claims (1)

1. method for preparing 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 that the aperture is less than the micropore of 150 μ m, intercommunication between the micropore, the porosity of glutin-hydroxyapatite composite spheroidal particle is 75~92%, used preparation facilities is comprised 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) at catheter (6), cool-bag (8) is located at catheter (6) below, and 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. the glutin-hydroxyapatite suspension that the upper step was prepared is the pipe of φ 0.5~3mm from caliber, evenly flows out with the speed of 10~60/min, splashes into temperature for condensation in the-condensed fluid of (10~20) ℃, forms spheroidal particle; Described condensed fluid is dimethicone or vegetable oil;
C. with the condensed spheroidal particle separation of upper 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, then clean with dehydrated alcohol, obtain glutin-hydroxyapatite composite spheroidal particle, described cross-linking agent is any one in formaldehyde, glutaraldehyde or the Biformyl.
CN2008102350663A 2008-11-07 2008-11-07 Glutin-hydroxyapatite composite spheroidal particle, producing method and apparatus thereof Expired - Fee Related CN101401960B (en)

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CN102885698B (en) * 2012-04-20 2016-12-21 张晓金 A kind of ultra micro hydrocolloid powder possessing core, shell structure and its production and use
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
DE102017115672B4 (en) * 2017-07-12 2020-08-27 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Isotropic hydroxyapatite / gelatin composite material, process for its production and its use
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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CN1272383A (en) * 2000-05-19 2000-11-08 清华大学 Preparation method of nanometer phase calcium-phosphorus salt/collagen/polylactic acid bone composite material
CN1607033A (en) * 2003-10-15 2005-04-20 中国科学院过程工程研究所 Chitose microsphere and microcapsule with uniform size and its preparation method
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