CN104069499B - The preparation of the hydroxyapatite microcapsule bioabsorbable carrier material of a kind of modification and application - Google Patents
The preparation of the hydroxyapatite microcapsule bioabsorbable carrier material of a kind of modification and application Download PDFInfo
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Abstract
The invention belongs to preparation and the applied technical field of biological compatibility carrier material, specifically disclose preparation and the application of the hydroxyapatite microcapsule bioabsorbable carrier material of a kind of modification.Hydroxyapatite nanoparticle and dibutylphosphoric acid ester are placed in acetone, normal-butyl is made to modify to nano grain surface, nano grain surface has oh group and n-butyl group simultaneously, thus obtains having the nano-particle after the amphipathic surface of hydrophilic/hydrophobic is modified；Being placed in aqueous phase or oil phase by this nano-particle, add oil phase or aqueous phase as core, acutely shake, after obtaining modifying using surface by self assembly, nano-particle is as the microencapsulation material with water/oil interface stability of film material.This microencapsulation material has bigger load-carry duty, effective ingredient buffer action and has appointment releasability etc., simple water solublity or fat-soluble biological material are dissolved in core, advantageously this microcapsule carrier material can be carried out actual application as the efficient carrier of biomaterial.
Description
Technical field
The present invention relates to preparation and the applied technical field of biological compatibility carrier material, be specifically related to a kind of modification
The preparation of hydroxyapatite microcapsule bioabsorbable carrier material and application.
Background technology
In the last few years, biomaterial field achieves and develops rapidly, the research of lithotroph medical material and
Applying the most active, wherein receive much concern is hydroxyapatite (hydroxyapatite is called for short HA or HAP)
The studies and clinical application of electro-active ceramic materials.Hydroxyapatite metal surface active material, it and hard group of organism
It is woven with similar chemical composition and structure, thus there is good biological activity and the compatibility.Use in the world not
Same process, have developed multiple hydroxyapatite composite material, coating material and nano material, it is thus achieved that
Breakthrough progress, develops having a extensive future of functional hydroxy apatite composite material.But hydroxy-apatite
After stone nano-particle carries out the modification of organic group surface, it is utilized to modify the water oil amphiphilic character system obtained
There is not been reported as the application of a kind of carrier material to become capsule of nano.
Microcapsule has Protective substances from environmental effect, shields taste, color, abnormal smells from the patient, change substance weight,
Volume, state or surface property, isolate active component, reduces volatility and toxicity, controls sustainable release etc.
Multiple effect, be widely used in medical science, food, pesticide, cosmetics, metal cutting, coating, ink,
Multiple field such as additive.First the preparation of microcapsule is to divide carefully by liquid, solid or gas core material, so
After with these microdroplets (grain) as core, make filmogen (wall material) deposit thereon, coating, formed one layer thin
Film, is coated with capsule heart microdroplet (grain).This process is referred to as micro encapsulation.
In the preparation of microencapsulation material, membrane material plays particularly important effect.Due to hydroxyapatite nano
Granule has good biocompatibility and a biological activity, the most common directly applies to bioabsorbable carrier material, bone
The aspects such as bone reparation.But nano-particle is directly used in load biomaterial, exist bearing capacity relatively fewer, load
Biomaterial be directly exposed in environment shortcomings such as easily dissipating, release process is wayward.And microencapsulation material
There is in water/oil phase median surface the abilities such as stable, isolation, controllable release, thus use organic group surface is repaiied
Nano-particle after decorations is formed has the microencapsulation material of water/oil interface stability as more efficiently carrier material
Material is the most necessary.
Summary of the invention
For the deficiencies in the prior art, object of the present invention is to provide the hydroxy-apatite of a kind of modification
The preparation of stone microcapsule bioabsorbable carrier material and application, a kind of novel have water/oil interface stability
The preparation method and application of hydroxyapatite microcapsule bioabsorbable carrier material modified of organic group surface.
Micro-glue that the hydroxyapatite nanoparticle modified with organic group surface provided by the present invention is film material
Capsule material is that one is by hydroxyapatite nanoparticle (Nano-HAP) and dressing agent (dibutylphosphoric acid ester, DBP)
It is placed in acetone soln, under the conditions of 57 DEG C, makes the phosphate of dibutylphosphoric acid ester and hydroxyapatite surface send out
Raw reaction, makes normal-butyl modify to nano grain surface, and nano grain surface has hydrophilic hydroxyl (OH-) simultaneously
Group and hydrophobic normal-butyl (-CH2CH2CH2CH3) group, thus it is amphipathic to obtain having hydrophilic/hydrophobic
Surface modify after nano-particle.Again this nano-particle having hydrophilic/hydrophobic amphipathic is placed in aqueous phase
Or in oil phase, add oil phase or aqueous phase as core, acutely shake, obtained with surface by self assembling process
After modification, nano-particle is as the microencapsulation material with water/oil interface stability of film material.This microencapsulation material
There is bigger load-carry duty, effective ingredient buffer action and there is the features such as appointment releasability, will be the most water-soluble
Property or fat-soluble biological material (biomacromolecule, drug molecule) are dissolved in core, it is possible to advantageously by this
Kind microcapsule carrier material carries out reality as the efficient carrier of biomaterial (biomacromolecule, drug molecule)
Application.
In order to realize above-mentioned technical purpose, this invention takes following technical measures:
A kind of hydroxyapatite microcapsule bioabsorbable carrier material of modification, the step of its preparation method is as follows:
(1) modification of hydroxyapatite nanoparticle:
Hydroxyapatite nanoparticle is placed in container, then dibutylphosphoric acid ester is added in this container, then add
Enter acetone dispersion and form reaction system, under the conditions of 57 DEG C, be stirred at reflux 4-6 hour；After backflow terminates, with
Acetone is that solvent is by product washes clean；By the product collection after washing, it is dried, obtains the hydroxy-apatite after modification
Stone nano-particle.
In described reaction system, the amount of hydroxyapatite material with acetone magnitude relation is: 1mmol:40-200ml；
In described reaction system, dibutylphosphoric acid ester concentration is 0.01-0.10mol/l；
(2) preparation of the hydroxyapatite microcapsule bioabsorbable carrier material modified:
Hydroxyapatite nanoparticle after the modification obtain step (1) is placed in container, adds A phase,
Fully dispersed, then B is added to, acutely shakes, to obtain final product.
Described A phase is oil phase or aqueous phase, and described B phase is oil phase or aqueous phase；
Oil phase is selected from having the liquid vegetable oil fat that biocompatibility can be absorbed naturally by organism；
Aqueous phase selected from having the aqueous solution of biocompatibility, such as distilled water, normal saline, Xylitol injection,
Glucose injection.
When A phase is oil phase, B phase is aqueous phase；When A phase is aqueous phase, B phase is oil phase；
Hydroxyapatite nanoparticle after described modification is 20mg:(1-5 with the ratio of A phase) ml；
Hydroxyapatite nanoparticle after described modification is 20mg:(20-100 with the ratio of B phase) μ l.
The hydroxyapatite microcapsule bioabsorbable carrier material of the above-mentioned modification prepared can be applied to as carrier
The carrying of biomaterial (biomacromolecule, drug molecule).
In above-mentioned application, biomaterial is carried on the hydroxyl of modification by the way of being directly dissolved in B phase
In apatite microcapsule bioabsorbable carrier material.
Compared with prior art, advantages of the present invention and having the beneficial effect that:
The preparation method of the hydroxyapatite microcapsule bioabsorbable carrier material of the modification of the present invention is simple, required
Reaction reagent kind and consumption are the most less, advantage of lower cost.In the application as a kind of bioabsorbable carrier material,
There is bigger bearing capacity, effective ingredient isolation and there is the effect of controlled release capability.
Accompanying drawing explanation
Fig. 1 is the chemical equation of the modification of step (1) hydroxyapatite nanoparticle of preparation method of the present invention.
R representative-CH in figure2CH2CH2CH3。
Fig. 2 is the hydroxyapatite microcapsule bioabsorbable carrier material that the step (2) of preparation method of the present invention is modified
The ideograph of preparation.Light color ball represents the hydroxyapatite nanoparticle after modifying, and dark ball is core,
I.e. B phase, core can be that oil phase or aqueous phase select aqueous phase or oil phase, the hydroxyl after modification according to external environment (A phase)
Base apatite nano-particle in water oil phase hybird environment with core generation self assembly, define and there is water/oil circle
The hydroxyapatite microcapsule bioabsorbable carrier material of the modification of face stability.
It is red that Fig. 3 is that embodiment 1 step (1) modifies the Fourier transformation of forward and backward hydroxyapatite nanoparticle
External spectrum collection of illustrative plates (FTIR), the infrared spectrum characteristic peak before modifying and after modification is typical hydroxyapatite
Standard diagram characteristic peak.Observe 3000cm-1Left and right wave number, it is seen that the hydroapatite particles after modification 2855,
2931、2945cm-1There is characteristic peak in place, shows that it is saturated hydrocarbyl C-CH3、C-CH2The structure of-C, card
Understand that organic group is successfully modified to hydroxyapatite surface.
Fig. 4 is the XRD spectra that embodiment 1 step (1) modifies forward and backward hydroxyapatite nanoparticle, repaiies
The XRD spectra of the nano-particle before decorations and after modification is illustrated as typical hydroxyapatite, with JCPDS
After 09-0423 standard PDF card comparison completely the same.Modify before with modify after, XRD spectra does not show
Writing change, before and after showing to modify, hydroapatite particles crystal structure and chemical property do not change, and modify
Occur only at surface.
Fig. 5 is (left figure) before embodiment 1 step (1) is modified, the hydroxyapatite nanoparticle of rear (right figure)
Transmission electron microscope pattern.Can be observed from transmission electron microscope pattern, modify forward and backward hydroapatite particles pattern,
The most there is not significant change in particle diameter, amphipathic the changing of provable nano-particle is not by nano-particle shape
Looks change and cause, but are caused by organic group the Surface Modification Effect.
Fig. 6 is the optical microscope of the hydroxyapatite microcapsule bioabsorbable carrier material of the modification of embodiment 1 preparation
Figure, external environment is oil phase, wherein visible in oil phase environment distribution spherical, modify with organic group surface
Hydroxyapatite nanoparticle is microcapsule bioabsorbable carrier material prepared by film material, with aqueous phase as core.
Fig. 7 is the optical microscope of the hydroxyapatite microcapsule bioabsorbable carrier material of the modification of embodiment 2 preparation
Figure, external environment is aqueous phase, wherein visible in aqueous environment distribution spherical, modify with organic group surface
Hydroxyapatite nanoparticle is microcapsule bioabsorbable carrier material prepared by film material, with oil phase as core.
Fig. 8 is the shows fluorescent microscopy images of the microcapsule of embodiment 3 preparation, and left figure is micro-glue of microscope direct observing
Scrotiform looks, right figure is the microcapsule pattern using blue light to excite Fluirescence observation.At oil phase external environment seen from left figure
That the hydroxyapatite nanoparticle spherical, that modify with organic group surface of middle distribution is prepared for film material, with water
It is the microencapsulation material of core mutually；At right figure, in core, the calcein solution of carrying is stimulated by blue light, and launches
Going out significant green fluorescence, picture display calcein is completely wrapped in prepared microcapsule so that it is with
The external environment of periphery is adequately isolated.
Fig. 9 is the optical microscope of the microcapsule of embodiment 4 preparation.In the picture of observation by light microscope visible
In aqueous phase external environment, the hydroxyapatite nanoparticle spherical, that modify with organic group surface of distribution is for film material
Microcapsule bioabsorbable carrier material that prepare, with oil-phase solution as core.
Figure 10 is the hydroxyapatite nanoparticle unit that in embodiment 1,5,6 step (1), the surface of preparation is modified
Element analyser C element content analysis block diagram.Embodiment 1 be can be observed in figure, in step (1) preparation
Grain, C content accounts for the 0.543% of gross mass；Embodiment 6, the granule of preparation in step (1), C content accounts for always
The 0.474% of quality；Embodiment 5, the granule of preparation in step (1), C content accounts for the 0.486% of gross mass.
Before modifying, the BET specific surface area of hydroxyapatite nanoparticle is 9.74m2/ g, according to document[1-2]Described method,
Calculate the amount of the material of normal-butyl contained by every square nanometers, then be translated into the absolute quantity of normal-butyl, calculate
The quantity of the normal-butyl that the surface that every square nanometers hydroxyapatite surface is accommodated is modified.Wherein embodiment 1,
The granule of preparation, every nm in step (1)2It is distributed 5.42 n-butyl group；Embodiment 6, in step (1)
The granule of preparation, every nm2It is distributed 4.69 n-butyl group；Embodiment 5, the granule of preparation in step (1),
Every nm2It is distributed 4.53 n-butyl group.All close to the every nm of the theory amount of being completely covered2There are 5 normal-butyl bases
Group, it can be verified that in the reaction system of embodiment 1,5,6, for the surface of hydroxyapatite nanoparticle
All can accomplish that the modification completely of normal-butyl covers.
Its computing formula is as follows:
In described formula: naFor every nm2The quantity of the normal-butyl covered；C% receives for hydroxyapatite before modifying
The C element of rice grain accounts for the percent of gross mass；CB% is the C element modifying front hydroxyapatite nanoparticle
Account for the percent of gross mass；NR=48g/mol；SBETTable is compared for the BET of hydroxyapatite nanoparticle before modifying
Area, this place is 9.74m2/g；NA is Avogadro's number.
Quote document
[1]Tanaka H,Yasukawa A,Kandori K,et al.Surface modification of calcium
hydroxyapatite with hexyl and decyl phosphates[J].Colloids and Surfaces A:
Physicochemical and Engineering Aspects,1997,125(1):53-62.
[2]Ishikawa T,Tanaka H,Yasukawa A,et al.Modification of calcium
hydroxyapatite using ethyl phosphates[J].J.Mater.Chem.,1995,5(11):1963-1967.
Figure 11 is the optical microscope of the hydroxyapatite microcapsule bioabsorbable carrier material of the modification of embodiment 5 preparation
Figure, external environment is oil phase, wherein visible in oil phase environment distribution spherical, modify with organic group surface
Hydroxyapatite nanoparticle is microcapsule bioabsorbable carrier material prepared by film material, with aqueous phase as core.
Figure 12 is the optical microscope of the hydroxyapatite microcapsule bioabsorbable carrier material of the modification of embodiment 6 preparation
Figure, external environment is oil phase, wherein visible in oil phase environment distribution spherical, modify with organic group surface
Hydroxyapatite nanoparticle is microcapsule bioabsorbable carrier material prepared by film material, with aqueous phase as core.
Detailed description of the invention
Preparation process and application process to product of the present invention in conjunction with specific embodiments is done in detail by applicant below
Describe in detail bright, it is simple to those skilled in the art are expressly understood the present invention.It is to be understood that following example should not
It is interpreted the application claims are claimed the restriction of scope by any way.
Material employed in following embodiment is described below with reagent:
Hydroxyapatite nanoparticle (Nano-HAP) is the nanometer hydroxyl that Aladdin (Aladdin) company produces
Base apatite, content>=97%, particle size<100nm (BET)；
Xylitol injection and glucose injection specification are 250ml:12.5g；
Edible oil used in embodiment 1-4 is that COFCO manufactures, good fortune board non-transgenic near the house squeezing sunflower
Seed oil；
Edible oil used in embodiment 5-7 is that benefit Hai Jiali produces, and gold dragon fish board golden ratio is edible to be in harmonious proportion
Oil, it is mainly composed of Oleum Brassicae campestris, soybean oil, Semen Maydis oil, Oleum Helianthi, Oleum Arachidis hypogaeae semen, Oleum sesami, Caulis et Folium Lini
Seed oil, safflower oil；
Other reagent are conventional commercial chemical reagent.
Embodiment 1 (prepared by product):
A kind of hydroxyapatite microcapsule bioabsorbable carrier material of modification, its preparation process is as follows:
(1) modification of hydroxyapatite nanoparticle:
By 0.500g (4.98 × 10-4Mol), during hydroxyapatite nanoparticle is placed in round-bottomed flask, it is subsequently adding
0.5mmol dibutylphosphoric acid ester, adds the dispersion of 50ml acetone and forms reaction system, di(2-ethylhexyl)phosphate fourth in reaction system
Ester concentration is 0.01mol/L.Under 57 DEG C of water bath condition, it is stirred at reflux 5 hours；After backflow terminates, sucking filtration
Separate product, then with acetone with suction method washed product 8 times；By the product nano powder collection after washing, put
60 DEG C of vacuum drying oven is dried 24 hours.
(2) preparation of the hydroxyapatite microcapsule bioabsorbable carrier material modified:
Dried product nano granule 20mg step (1) obtained is placed in test tube, adds 2ml food
With oil, abundant ultrasonic disperse；Then in test tube, add 100 μ l distilled water, acutely shake 5min, formed
The hydroxyapatite microcapsule bioabsorbable carrier material modified, its pattern is shown in Fig. 6, stands 7, non-water breakthrough oil phase
Lamination, it was demonstrated that distilled water is wrapped in microcapsule bioabsorbable carrier material completely as core.
Embodiment 2 (prepared by product):
A kind of hydroxyapatite microcapsule bioabsorbable carrier material of modification, its preparation process is as follows:
(1) modification of hydroxyapatite nanoparticle:
By 0.500g (4.98 × 10-4Mol), during hydroxyapatite nanoparticle is placed in round-bottomed flask, it is subsequently adding
0.5mmol dibutylphosphoric acid ester, adds the dispersion of 50ml acetone and forms reaction system, di(2-ethylhexyl)phosphate fourth in reaction system
Ester concentration is 0.01mol/L.Under 57 DEG C of water bath condition, it is stirred at reflux 5 hours；After backflow terminates, sucking filtration
Separate product, then with acetone with suction method washed product 8 times.By the product nano powder collection after washing, put
60 DEG C of vacuum drying oven is dried 24 hours.
(2) preparation of the hydroxyapatite microcapsule bioabsorbable carrier material modified:
Dried product nano granule 20mg step (1) obtained is placed in test tube, adds 5ml and steams
Distilled water, abundant ultrasonic disperse；Then in test tube, add 100 μ l edible oil, acutely shake 5min, formed
The hydroxyapatite microcapsule bioabsorbable carrier material modified, its pattern is shown in Fig. 7, stands 7, non-water breakthrough oil phase
Lamination, it was demonstrated that edible oil is wrapped in microcapsule bioabsorbable carrier material completely as core.
Embodiment 3 (application): hydroxyapatite microencapsulation material should as the carrier of fluorescent dye calcein
With experiment
Select use 10-5Mol/l calcein normal saline solution is as aqueous phase, and edible oil is oil phase.Calcium is yellowish green
Element (Calcein) is a kind of micromolecular water soluble fluorescein, and stable in properties can apply fluorescence spectrophotometer light easily
Degree method or ultraviolet visible spectrophotometry detection, frequently as the model drug of pharmaceutical carrier.
The edible oil of use 1ml is as oil phase, after adding modification prepared by 20mg embodiment 1 step (1)
Hydroxyapatite nanoparticle, uses ultrasound wave to be well-dispersed in oil phase, is subsequently adding 100 μ l's
10-5Mol/l calcein normal saline solution, acutely shakes, and forms emulsion.With observation by light microscope:
Visible formation is with calcein normal saline solution as core, and the hydroxyapatite nanoparticle after modification is wall material
Microencapsulation material；With fluorescence microscope, it is seen that excite fluorescence, foreign minister's unstressed configuration to excite in microcapsule existing
As, see Fig. 8.
The calcein normal saline solution concentration carried in measuring microcapsule by ultraviolet visible spectrophotometry
Carrying drug ratio, carrying drug ratio=c is calculated with the ratio of calcein normal saline solution initial concentrationMedicine carrying/cInitially=
98.88%.
Having no profit phase lamination after the microencapsulation material of gained is stood 7, microencapsulation material still keeps shape
State is stable；Being transferred in aqueous phase by microencapsulation material, microencapsulation material ruptures, in calcein release to aqueous phase,
Understanding calcein complete tunicle material and be wrapped to form microencapsulation material, microencapsulation material keeps stable in oil phase,
Rupture in microcapsule Release of core material to external environment when microencapsulation material runs into aqueous phase.
Embodiment 4 (application): hydroxyapatite microencapsulation material is as vitamin D2Carrier application experiment
Select to use Xylitol injection as aqueous phase, the 10mg/l vitamin D that will have configured2Edible oil solution
(COFCO, good fortune board non-transgenic near the house squeezing Oleum Helianthi) is oil phase.Vitamin D2It it is steroid
Derivant, is the bioactive substance of a class relation Ca,P metabolism.
Using the Xylitol injection of 5ml as aqueous phase, prepared by addition 20mg embodiment 2 step (1) repaiies
Hydroxyapatite nanoparticle after decorations, uses ultrasound wave that it is fully dispersed, adds the 10mg/l of 100 μ l
Vitamin D2Edible oil solution, acutely shakes, and forms emulsion.With observation by light microscope: visible formation
With vitamin D2Edible oil solution is core, and the hydroxyapatite nanoparticle after modification is the microcapsule of wall material
Material, is shown in Fig. 9, by the vitamin D of carrying in high effective liquid chromatography for measuring microcapsule2Edible oil solution is dense
Degree and vitamin D2The ratio of edible oil initial concentration solution calculates carrying drug ratio, carrying drug ratio=cMedicine carrying/cInitially=
94.08%.
Gained microencapsulation material stands 7, non-water breakthrough oil phase lamination, it was demonstrated that vitamin D2Edible oil soluble
Liquid is wrapped in microcapsule bioabsorbable carrier material completely as core.
Embodiment 5 (prepared by product):
A kind of hydroxyapatite microcapsule bioabsorbable carrier material of modification, preparation process is as follows:
(1) modification of hydroxyapatite nanoparticle:
By 0.500g (4.98 × 10-4Mol), during hydroxyapatite nanoparticle is placed in round-bottomed flask, it is subsequently adding
10mmol dibutylphosphoric acid ester, adds the dispersion of 100ml acetone and forms reaction system, di(2-ethylhexyl)phosphate in reaction system
Butyl ester concentration is 0.10mol/L.Under 57 DEG C of water bath condition, it is stirred at reflux 5 hours；After backflow terminates, take out
Filter separates product, then with acetone with suction method washed product 8 times；By the product nano powder collection after washing,
Put 60 DEG C of vacuum drying oven to be dried 24 hours.
(2) preparation of the hydroxyapatite microcapsule bioabsorbable carrier material modified:
Dried product nano granule 40mg step (1) obtained is placed in test tube, adds 2ml food
With oil, abundant ultrasonic disperse；Then in test tube, add 40 μ l glucose injections, acutely shake 5min.
Forming the hydroxyapatite microcapsule bioabsorbable carrier material modified, its pattern is shown in Figure 11, stands 7, have no
Water oil phase lamination, it was demonstrated that glucose injection is wrapped in microcapsule bioabsorbable carrier material completely as core
In.
Embodiment 6 (prepared by product):
A kind of hydroxyapatite microcapsule bioabsorbable carrier material of modification, preparation process is as follows:
(1) modification of hydroxyapatite nanoparticle:
By 0.500g (4.98 × 10-4Mol), during hydroxyapatite nanoparticle is placed in round-bottomed flask, it is subsequently adding
1mmol dibutylphosphoric acid ester, adds the dispersion of 20ml acetone and forms reaction system, di(2-ethylhexyl)phosphate fourth in reaction system
Ester concentration is 0.05mol/L.Under 57 DEG C of water bath condition, it is stirred at reflux 5 hours；After backflow terminates, sucking filtration
Separate product, then with acetone with suction method washed product 8 times；By the product nano powder collection after washing, put
60 DEG C of vacuum drying oven is dried 24 hours.
(2) preparation of the hydroxyapatite microcapsule bioabsorbable carrier material modified:
Dried product nano granule 10mg step (1) obtained is placed in test tube, adds 1ml food
With oil, abundant ultrasonic disperse；Then in test tube, add 25 μ l Xylitol injections, acutely shake 5min.
Forming the hydroxyapatite microcapsule bioabsorbable carrier material modified, its pattern is shown in Figure 12, stands 7, have no
Water oil phase lamination, it was demonstrated that Xylitol injection is wrapped in microcapsule bioabsorbable carrier material completely as core
In.
Embodiment 7 (application): hydroxyapatite microencapsulation material is applied real as the carrier of bovine serum albumin
Test
Use bovine serum albumin normal saline solution (BSA, molecular weight the is 67000) conduct of 50mg/ml
Aqueous phase, edible oil is oil phase.Bovine serum albumin (BSA) is a kind of biomacromolecule, has in biochemical test
It is widely applied, stable in properties, Bradford method can be applied easily to carry out detection by quantitative, frequently as egg
The model of Bai Zaiti.
The edible oil of use 1ml is as oil phase, after adding modification prepared by 20mg embodiment 1 step (1)
Hydroxyapatite nanoparticle, uses ultrasound wave to be well-dispersed in oil phase, is subsequently adding 100 μ l's
The bovine serum albumin normal saline solution of 50mg/ml, acutely shakes, and forms emulsion.Observe with microscope,
Visible formation is with bovine serum albumin normal saline solution as core, and the hydroxyapatite nanoparticle after modification is
The microencapsulation material of wall material, uses Bradford method to carry in measuring microcapsule by ultraviolet-uisible spectrophotometer
Bovine serum albumin normal saline solution concentration and the ratio of bovine serum albumin normal saline solution initial concentration
Example calculates carrying drug ratio, carrying drug ratio=cMedicine carrying/cInitially=93.23%.
Gained microencapsulation material stands 7, non-water breakthrough oil phase lamination, it was demonstrated that bovine serum albumin physiology salt
Aqueous solution is wrapped in microcapsule bioabsorbable carrier material completely as core.
Claims (5)
1. the hydroxyapatite microcapsule bioabsorbable carrier material modified, the step of its preparation method is as follows:
(1) modification of hydroxyapatite nanoparticle:
Hydroxyapatite nanoparticle is placed in container, then dibutylphosphoric acid ester is added in this container, be subsequently adding acetone dispersion and form reaction system, under the conditions of 57 DEG C, be stirred at reflux 4-6 hour；After backflow terminates, with acetone for solvent by product washes clean；By the product collection after washing, it is dried, obtains the hydroxyapatite nanoparticle after modification；
In described reaction system, the amount of hydroxyapatite material with acetone magnitude relation is: 1mmol:40-200ml；
In described reaction system, dibutylphosphoric acid ester concentration is 0.01-0.10mol/l；
(2) preparation of the hydroxyapatite microcapsule bioabsorbable carrier material modified:
Hydroxyapatite nanoparticle after the modification obtain step (1) is placed in container, adds A phase, fully dispersed, is then added to by B, acutely shakes, to obtain final product；
Described A phase is oil phase or aqueous phase, and described B phase is oil phase or aqueous phase；
When A phase is oil phase, B phase is aqueous phase；When A phase is aqueous phase, B phase is oil phase；
Hydroxyapatite nanoparticle after described modification is 20mg:(1-5 with the ratio of A phase) ml；
Hydroxyapatite nanoparticle after described modification is 20mg:(20-100 with the ratio of B phase) μ l.
The hydroxyapatite microcapsule bioabsorbable carrier material of a kind of modification the most according to claim 1, it is characterised in that: described oil phase is the liquid vegetable oil fat that naturally can be absorbed by organism.
The hydroxyapatite microcapsule bioabsorbable carrier material of a kind of modification the most according to claim 1, it is characterised in that: described aqueous phase is the aqueous solution with biocompatibility.
The hydroxyapatite microcapsule bioabsorbable carrier material of a kind of modification the most according to claim 3, it is characterised in that: described aqueous phase is distilled water, normal saline, Xylitol injection or glucose injection.
5. the hydroxyapatite microcapsule bioabsorbable carrier material of described modification arbitrary in claim 1-4 is applied to the carrying of biomaterial；Described biomaterial is biomacromolecule or drug molecule；
Described biomaterial is carried in the hydroxyapatite microcapsule bioabsorbable carrier material of modification by the way of being directly dissolved in B phase.
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| CN114452908A (en) * | 2022-02-17 | 2022-05-10 | 山东泰山生力源集团股份有限公司 | Preparation method and microscopic examination method of chitosan-embedded calcium alginate microcapsule |
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| CN102504311A (en) * | 2011-10-26 | 2012-06-20 | 河南师范大学 | Method for polylactic acid high polymer material surface modified hydroxyapatite coating |
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