CN108379666A - A kind of gelatine microsphere/phosphoric acid magnesium-based bone cement slow releasing carrier of medication and preparation method thereof - Google Patents
A kind of gelatine microsphere/phosphoric acid magnesium-based bone cement slow releasing carrier of medication and preparation method thereof Download PDFInfo
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Abstract
The present invention discloses a kind of gelatine microsphere/phosphoric acid magnesium-based bone cement slow releasing carrier of medication and preparation method thereof, first prepares the crosslinked load medicine gelatine microsphere of 1 ethyl (3 dimethylaminopropyl) carbodiimide hydrochloride；Gained is carried medicine gelatine microsphere again to mix uniformly with phosphoric acid magnesium-based bone cement powder, then reconciles and cures with phosphoric acid magnesium-based bone cement liquid phase, obtains the gelatine microsphere/phosphoric acid magnesium-based bone cement slow releasing carrier of medication.1 ethyl (3 dimethylaminopropyl) carbodiimide hydrochloride is as gelatin cross-linker, obtained gelatine microsphere good biocompatibility；Gelatine microsphere can carry a variety of drugs, and the degradation speed of microballoon can be controlled by the concentration of crosslinking agent, and then Drug controlled release speed；The gelatine microsphere/phosphoric acid magnesium-based bone cement pharmaceutical carrier has excellent sustained drug release effect, realizes that drug is up to the sustained release of several months.
Description
Technical field
The present invention relates to biological medicine technical field of material more particularly to a kind of bone with drug therapy effect to fill
The method filled out repair materials and prepare the material.
Background technology
In modern society, the diseases such as the accidents such as aging of population, production, traffic and bone tuberculosis, osteomyelitis, bone tumour cause
Largely need to receive the sufferer of bone tissue defect repair.Traditional bone tissue defect repair is mainly by autologous bone transplanting and of the same race
Allogenic bone transplantation is realized.But all there is different degrees of defect in the two method, the former is a kind of method of " being cured the wound with wound "；The latter
The problems such as transmission and immunological rejection can usually be brought, and the source of the two is limited.And artificial material source is unrestricted,
It has obtained the attention of many researchers and numerous studies has been carried out to it, developed a series of bone renovating materials.However bone defect
Place individually fill up easily causing postoperative complication using bone filler, it is therefore desirable to which the regular period is aided with drug after surgery
Treatment.Clinically common method is progress oral drugs or hypodermic injection drug after operation, however these methods are easy to make
Obtaining drug, drug concentration is unstable in vivo, and utilization ratio of drug is low, and control is bad also to cause toxic side effect to body.If in bone
Upper drug is loaded in repair materials, and makes it in defect point slow release drug, is not only increased the utilization rate of drug, is also reduced
Murder by poisoning to body.
In recent years, have Many researchers to consider drug being loaded into realization repairing bone defect and treatment bone disease in bone cement
Double effects.Taxol is loaded into the calcium phosphate bone cement of injectable and carries out cell experiment by Lopez-Heredia etc., obtains
To carrying, the activity of osteosarcoma cell and metastatic breast cancer cell in medicine group is lower than not carrying medicine group, illustrates that load medicine can in bone cement
To reach certain medication effect (Lopez-Heredia M A et al.An injectable calcium
phosphate cement for the local delivery of paclitaxel to bone[J]
.Biomaterials,2011,32(23):5411–5416.).But this kind of load medicine have it is clearly disadvantageous：By drug and bone water
Mud powder phase or liquid phase, which are directly mixed with, carries medicine bone cement, may will produce mutually between bone cement and drug in hydration process
Detrimental effect；If carrying out load medicine again by cured bone cement, drug can discharge effect that is too fast and being unable to reach sustained release.
Therefore, drug is wrapped up using organic micro-spheres, then being combined in bone cement can be in the phase interaction for avoiding drug with bone cement
With while improve medicament slow release performance, have potential application.Currently, drug bearing microsphere is introduced bone water in spite of research
In mud, but long-term sustained release effect unobvious.The Chinese patent of Publication No. 101564556A disclose a kind of gelatine microsphere and
The composite drug-loaded system of calcium phosphate bone cement, but its drug releasing rate is very fast, release amount of medicine is just more than 90% within 14 days.
Bone defect, the especially bone defect as caused by osteomyelitis, bone tumour, bone tuberculosis etc. by bone disease, it is often necessary to long
Sustained medication up to the several months can be only achieved complete healing, and drug release is then unable to meet demand very much soon.Therefore, exploring one kind can
Carrying medicament, and drug is capable of load Types of Medicine bone renovating material of long-acting slow-release and preparation method thereof and is had far-reaching significance.Except this
Except, as a kind of bone renovating material, system also needs to degradable, and biocompatibility is good.
Invention content
In consideration of it, the object of the present invention is to provide a kind of gelatine microsphere that can be released the drug for a long time/phosphoric acid magnesium-based bone cement medicines
The preparation method of object slow-releasing system.The gelatine microsphere/phosphoric acid magnesium-based bone cement drug controlled release system has good drug
Slow release effect meets bone defect director's phase lasting drug therapy demand.
To achieve the above object, the technical solution adopted by the present invention is as follows：
A kind of preparation method of gelatine microsphere/phosphoric acid magnesium-based bone cement slow releasing carrier of medication, includes the following steps：
(1) 1- ethyls-crosslinked load medicine gelatine microsphere of (3- dimethylaminopropyls) carbodiimide hydrochloride is prepared；
(2) medicine gelatine microsphere will be carried obtained by step (1) to mix uniformly with phosphoric acid magnesium-based bone cement powder, then with phosphoric acid magnesium-based
Bone cement liquid phase, which reconciles, to be cured, and the gelatine microsphere/phosphoric acid magnesium-based bone cement slow releasing carrier of medication is obtained.
Preferably, the load medicine gelatine microsphere preparation method includes：
1) gelatin and drug are dissolved in the deionized water of 40-60 DEG C of temperature and are uniformly mixed, obtaining gelatin mass fraction is
The gelatin of 20%-30% carries drug solns, and drug additive amount is the 1-100% of gelatin quality；
2) using atoleine as oil phase, Span 80 is dispersant, and the two volume ratio is preferably 10:1, it is stirred after the two mixing
Uniformly；
3) gelatin is added dropwise into oil phase at rotating speed 100-600r/min and carries drug solns, ice water is changed after stirring 5-100min
Bath；Continue that 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride solution is added dropwise after stirring 5-60min later；Crosslinking
30-240min, preferably 60-90min；
4) microballoon is taken out, is cleaned with dehydrating agent, air drying, obtains carrying medicine gelatine microsphere.
Preferably, the dosage of crosslinking agent 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride is gelatin dosage
1~25wt%.
Preferably, the dosage of crosslinking agent 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride is gelatin dosage
13wt%.
Preferably, dehydrating agent is following one or more in step 4)：Isopropanol, ethyl alcohol, ether, acetone, petroleum ether.
Preferably, the phosphoric acid magnesium-based bone cement powder phase component is the mixing of magnesia, calcium dihydrogen phosphate, potassium dihydrogen phosphate
Object；Liquid phase component is aqueous citric acid solution.
Preferably, the ratio of phosphoric acid magnesium-based bone cement powder phase and liquid phase is 1.5g/mL-2.5g/mL, it is therefore preferable to 1.6g/
mL-2.2g/mL。
Preferably, the medicine gelatine microsphere and the mass ratio of phosphoric acid magnesium-based bone cement powder phase of carrying is (1~15)：100.
Preferably, the magnesia in the phosphoric acid magnesium-based bone cement powder phase component passes through calcination processing：Calcination temperature is
1600 DEG C, heating rate is 3 DEG C/min, keeps the temperature 1.5h, it is 1-3 μm, preferably 1-2 μm that ball milling, which obtains grain size,.
Preferably, the grain size of the calcium dihydrogen phosphate in the phosphoric acid magnesium-based bone cement powder phase component is 0.5-30 μm；Phosphoric acid
The grain size of potassium dihydrogen is 1-20 μm.
Preferably, in the phosphoric acid magnesium-based bone cement powder phase component, magnesia：Potassium dihydrogen phosphate：The matter of calcium dihydrogen phosphate
Amount is than being 1.5:3:1；In liquid phase component, a concentration of 0.01g/mL-0.05g/mL of citric acid.
Preferably, the contained drug of the gelatin is one or more below：C14H10Cl2NNaO2, paracetamol, sulphur
Sour gentamicin, isoniazid, pyrazinamide, doxorubicin hydrochloride, dexamethasone, Doxycycline Hyclate, quadracycline, Bu Luo
Sweet smell, 5 FU 5 fluorouracil, rifampin, ebutol, clofazimine, vancomycin hydrochloride.
A kind of gelatine microsphere/phosphoric acid magnesium-based bone cement slow releasing carrier of medication, is prepared by the above method.
In preparing gelatine microsphere, the concentration by controlling crosslinking agent can adjust the degradation speed of microballoon, and then control
The rate of release of drug.Again by the load medicine gelatine microsphere and degradable, gluing performance and the good phosphoric acid magnesium-based of biological property
Bone cement carries out compound.In phosphoric acid magnesium-based bone cement energy is chelated with citrate by forming six water magnesium phosphate potassium and free calcium salt
Drug bearing microsphere is tightly wrapped.The release of drug will first pass through the cross-linked network of gelatine microsphere, then be diffused into bone cement
In matrix, released by the micro-nano gap of bone cement, to achieve the purpose that medicament slow release.Gelatin prepared by the present invention
Microballoon/phosphoric acid magnesium-based bone cement slow releasing carrier of medication can carry a variety of drugs, and sustained drug release effect is good.
The present invention beneficial effect be：1, using 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride as bright
Rubber cross linker not only can simply control gelatin degradation speed by controlling crosslinker concentration, while obtained gelatine microsphere life
Object compatibility is good；Both 2, drug is wrapped in gelatine microsphere, the hydration process that drug participates in bone cement can be exempted, reduce
Between issuable adverse effect, greatly keep drug activity；3, gelatine microsphere and phosphoric acid magnesium-based bone cement is compound, medicine
Object need to break through dual media and release, and extend pharmaceutical release time, achieve the effect that medicament slow release is treated, drug release time is up to
2-3 months.4, can also be in-situ pore-formed in bone cement after gelatine microsphere degradation, promote bone tissue in-growth to provide sky for the later stage
Gap, to the potential ability for promoting Bone Defect Repari.
Description of the drawings
Fig. 1 is that the crosslinked gelatine microsphere cytotoxicity of 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride is real
Figure is tested, (mtt assay toxicity test is used, the crosslinked gelatin of 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride will be used
Microballoon is scattered in 200mg/mL concentration in 1640 culture medium, after MTT is added after being co-cultured 1,3 days with mesenchymal stem cell
Continue to be incubated 4h, measures absorbance value to indicate cell viability, absorbance value is bigger, shows that cell viability is better, is not added with microballoon
As a control group)；
Fig. 2 is the scanning electron microscope (SEM) photograph of the load C14H10Cl2NNaO2 gelatine microsphere of 1 gained of embodiment；
Fig. 3 is the scanning electron microscope (SEM) photograph that medicine gelatine microsphere/phosphoric acid magnesium-based bone cement is carried obtained by Examples 1 and 2, and figure a) indicates real
1 composite bone cement pattern of example is applied, figure b) indicates 2 composite bone cement pattern of embodiment；
Fig. 4 is the drug release profiles that 1,2 and 3 gained of embodiment carries medicine gelatine microsphere/phosphoric acid magnesium-based bone cement.
Specific implementation mode
Below by specific implementation, invention is further explained, and however, the present invention is not limited to these examples.With
Unless specific instructions, the reagent of use is the pure chemical reagent of commercially available chemistry to lower embodiment.
Embodiment 1
It weighs 1.5g gelatine microspheres and 0.03g C14H10Cl2NNaO2s is dissolved in 50 DEG C of distilled water, configure uniformly mixed medicine
Object aqueous gelatin solution.Separately take 30mL atoleines and 3mL Spans 80 in round-bottomed flask, in rotating speed 500r/min, temperature 50
10min is stirred at DEG C, then drug gelatin solution is slowly dropped in flask under the rotating speed of 250r/min, stirs 10min
It uses ice-water bath rapidly afterwards, the carbodiimide hydrochloride solution of a concentration of 0.5mol/L of 1mL is added after 15min.Continue stirring crosslinking
It takes out after 60min, is cleaned with isopropanol, drying at room temperature is the gelatine microsphere for obtaining carrying C14H10Cl2NNaO2.Use scanning electron microscopic observation
The pattern of microballoon, as shown in Figure 2.
It with mass ratio is 1.5 that bone cement powder, which is magnesia, potassium dihydrogen phosphate and calcium dihydrogen phosphate,:3:1 be uniformly mixed and
At.Claim 4g bone cement powder, and adds the above-mentioned gelatine microspheres of 0.4g.Then configuration concentration is the citric acid solution of 0.02g/mL,
It takes the citric acid solution of 1.8mL and powder mutually to reconcile 2min, enters to be placed on after mould solidification 37 DEG C, it is solid under the environment under 100% humidity
Change 48h.Cure two days strength of bone cement with the test of omnipotent test machine.By the cured bone cement with 1g:The ratio of 20mL is put
It sets in the PBS buffer solutions of pH=7.4 and releases the drug.
The load medicine gelatine microsphere balling-up effect is good, and grain size is 0-300 μm, such as Fig. 2.Gelatine microsphere/phosphoric acid magnesium-based bone cement
The intensity that drug controlled release system cures two days is 35MPa, cross-section morphology as shown in figure 3,60 days drug releases 53.9% (as schemed
4), drug also sustained release later has good drug release effect.
Embodiment 2
It weighs 1.5g gelatine microspheres and 0.03g C14H10Cl2NNaO2s is dissolved in 50 DEG C of distilled water, configure uniformly mixed medicine
Object aqueous gelatin solution.Separately take 30mL atoleines and 3mL Spans 80 in round-bottomed flask, in rotating speed 500r/min, temperature 50
10min is stirred at DEG C, then drug gelatin solution is slowly dropped in flask under the rotating speed of 350r/min, stirs 10min
It uses ice-water bath rapidly afterwards, the carbodiimide hydrochloride solution of a concentration of 1mol/L of 1mL is added after 15min.Continue stirring crosslinking
It takes out after 60min, is cleaned with isopropanol, drying at room temperature is the gelatine microsphere for obtaining carrying C14H10Cl2NNaO2.Gelatine microsphere and bone water
The compound part of mud is identical as 1 step of embodiment.
The load medicine gelatine microsphere balling-up effect is good, and grain size is 0-250 μm.Gelatin/phosphoric acid magnesium-based bone cement drug controlled-release body
The intensity that system cures two days is 32MPa, 60 days drug releases, 31.9% (such as Fig. 4).
Embodiment 3
It weighs 1.5g gelatine microspheres and 0.03g C14H10Cl2NNaO2s is dissolved in 50 DEG C of distilled water, configure uniformly mixed medicine
Object aqueous gelatin solution.Separately take 30mL atoleines and 3mL Spans 80 in round-bottomed flask, in rotating speed 500r/min, temperature 50
10min is stirred at DEG C, then drug gelatin solution is slowly dropped in flask under the rotating speed of 350r/min, stirs 10min
It uses ice-water bath rapidly afterwards, the carbodiimide hydrochloride solution of a concentration of 0.1mol/L of 1mL is added after 15min.Continue stirring crosslinking
It takes out after 60min, is cleaned with isopropanol, drying at room temperature is the gelatine microsphere for obtaining carrying C14H10Cl2NNaO2.Gelatine microsphere and bone water
The compound part of mud is identical as 1 step of embodiment.
The load medicine gelatine microsphere balling-up effect is good, and grain size is 0-250 μm.Gelatin/phosphoric acid magnesium-based bone cement drug controlled-release body
The intensity that system cures two days is 28MPa, 60 days drug releases, 70% (such as Fig. 4).
Embodiment 4
It weighs 1.5g gelatine microspheres and 1.5g paracetamol is dissolved in 50 DEG C of distilled water, configure uniformly mixed medicine
Object aqueous gelatin solution.Separately take 30mL atoleines and 3mL Spans 80 in round-bottomed flask, in rotating speed 600r/min, temperature 50
10min is stirred at DEG C, then drug gelatin solution is slowly dropped in flask under the rotating speed of 600r/min, stirs 10min
It uses ice-water bath rapidly afterwards, the carbodiimide hydrochloride solution of a concentration of 0.5mol/L of 1mL is added after 15min.Continue stirring crosslinking
It takes out after 120min, is cleaned with isopropanol, drying at room temperature is the gelatine microsphere for obtaining carrying paracetamol.
It with mass ratio is 1.5 that bone cement powder, which is magnesia, potassium dihydrogen phosphate and calcium dihydrogen phosphate,:3:1 be uniformly mixed and
At.Claim 4g bone cement powder, and adds the above-mentioned gelatine microspheres of 0.08g.Then configuration concentration is the citric acid solution of 0.02g/mL,
It takes the citric acid solution of 1.6mL and powder mutually to reconcile 2min, enters to be placed on after mould solidification 37 DEG C, it is solid under the environment under 100% humidity
Change 48h.Cure two days strength of bone cement with the test of omnipotent test machine.By the cured bone cement with 1g:The ratio of 20mL is put
It sets in the PBS buffer solutions of pH=7.4 and releases the drug.
The load medicine gelatine microsphere balling-up effect is general, and grain size is 0-200 μm, and the gelatin/phosphoric acid magnesium-based bone cement drug is slow
To release system to cure two days intensity be 67MPa, 60 days drug releases 50%.
Embodiment 5
It weighs 1.5g gelatine microspheres and 0.75g paracetamol is dissolved in 50 DEG C of distilled water, configure uniformly mixed
Drug aqueous gelatin solution.It separately takes 30mL atoleines and 3mL Spans 80 in round-bottomed flask, is in rotating speed 600r/min, temperature
10min is stirred at 50 DEG C, then drug gelatin solution is slowly dropped in flask under the rotating speed of 450r/min, is stirred
Ice-water bath is used after 10min rapidly, the carbodiimide hydrochloride solution of a concentration of 2mol/L of 1mL is added after 15min.Continue stirring to hand over
It takes out after connection 60min, is cleaned with isopropanol, drying at room temperature is the gelatine microsphere for obtaining carrying paracetamol.
It with mass ratio is 1.5 that bone cement powder, which is magnesia, potassium dihydrogen phosphate and calcium dihydrogen phosphate,:3:1 be uniformly mixed and
At.Claim 4g bone cement powder, and adds the above-mentioned gelatine microspheres of 0.24g.Then configuration concentration is the citric acid solution of 0.02g/mL,
It takes the citric acid solution of 1.8mL and powder mutually to reconcile 2min, enters to be placed on after mould solidification 37 DEG C, it is solid under the environment under 100% humidity
Change 48h.Cure two days strength of bone cement with the test of omnipotent test machine.By the cured bone cement with 1g:The ratio of 20mL is put
It sets in the PBS buffer solutions of pH=7.4 and releases the drug.
The load medicine gelatine microsphere balling-up effect is preferable, and grain size is 0-250 μm, and the gelatin/phosphoric acid magnesium-based bone cement drug is slow
To release system to cure two days intensity be 50MPa, 60 days drug releases 37%.
Embodiment 6
It weighs 1.5g gelatine microspheres and 0.75g to be dissolved in isoniazid in 50 DEG C of distilled water, configures uniformly mixed drug
Aqueous gelatin solution.It separately takes 30mL atoleines and 3mL Spans 80 in round-bottomed flask, is 50 DEG C in rotating speed 500r/min, temperature
Drug gelatin solution, is then slowly dropped in flask under the rotating speed of 600r/min by lower stirring 10min, after stirring 10min
Ice-water bath is used rapidly, and the carbodiimide hydrochloride solution of a concentration of 1mol/L of 1mL is added after 15min.Continue stirring crosslinking 60min
After take out, cleaned with isopropanol, drying at room temperature be obtain carry isoniazid gelatine microsphere.
It with mass ratio is 1.5 that bone cement powder, which is magnesia, potassium dihydrogen phosphate and calcium dihydrogen phosphate,:3:1 be uniformly mixed and
At.Claim 4g bone cement powder, and adds the above-mentioned gelatine microspheres of 0.32g.Then configuration concentration is the citric acid solution of 0.02g/mL,
It takes the citric acid solution of 2mL and powder mutually to reconcile 2min, is placed on 37 DEG C after entering mould solidification, cures under the environment under 100% humidity
48h.Cure two days strength of bone cement with the test of omnipotent test machine.By the cured bone cement with 1g:The ratio of 20mL is placed
To releasing the drug in the PBS buffer solutions of pH=7.4.
The load medicine gelatine microsphere balling-up effect is good, and grain size is 0-150 μm, the gelatin/phosphoric acid magnesium-based bone cement medicament slow release
The intensity that system cures two days is 51MPa, 60 days drug releases 55%.
Embodiment 7
It weighs 1.5g gelatine microspheres and 0.15g pyrazinamides is dissolved in 50 DEG C of distilled water, configure uniformly mixed drug
Aqueous gelatin solution.It separately takes 30mL atoleines and 3mL Spans 80 in round-bottomed flask, is 50 DEG C in rotating speed 500r/min, temperature
Drug gelatin solution, is then slowly dropped in flask under the rotating speed of 100r/min by lower stirring 10min, after stirring 10min
Ice-water bath is used rapidly, and the carbodiimide hydrochloride solution of a concentration of 0.5mol/L of 1mL is added after 15min.Continue stirring crosslinking
It takes out after 240min, is cleaned with isopropanol, drying at room temperature is the gelatine microsphere for obtaining carrying pyrazinamide.
It with mass ratio is 1.5 that bone cement powder, which is magnesia, potassium dihydrogen phosphate and calcium dihydrogen phosphate,:3:1 be uniformly mixed and
At.Claim 4g bone cement powder, and adds the above-mentioned gelatine microspheres of 0.4g.Then configuration concentration is the citric acid solution of 0.02g/mL,
It takes the citric acid solution of 2.2mL and powder mutually to reconcile 2min, enters to be placed on after mould solidification 37 DEG C, it is solid under the environment under 100% humidity
Change 48h.Cure two days strength of bone cement with the test of omnipotent test machine.By the cured bone cement with 1g:The ratio of 20mL is put
It sets in the PBS buffer solutions of pH=7.4 and releases the drug.
The load medicine gelatine microsphere balling-up effect is preferable, and grain size is 0-550 μm, and the gelatin/phosphoric acid magnesium-based bone cement drug is slow
To release system to cure two days intensity be 25MPa, 60 days drug releases 56%.
Embodiment 8
It weighs 1.5g gelatine microspheres and 0.02g C14H10Cl2NNaO2s is dissolved in 50 DEG C of distilled water, configure uniformly mixed medicine
Object aqueous gelatin solution.Separately take 30mL atoleines and 3mL Spans 80 in round-bottomed flask, in rotating speed 500r/min, temperature 50
10min is stirred at DEG C, then drug gelatin solution is slowly dropped in flask under the rotating speed of 300r/min, stirs 10min
It uses ice-water bath rapidly afterwards, the carbodiimide hydrochloride solution of a concentration of 0.5mol/L of 1mL is added after 15min.Continue stirring crosslinking
It takes out after 30min, is cleaned with isopropanol, drying at room temperature is the gelatine microsphere for obtaining carrying pyrazinamide.
It with mass ratio is 1.5 that bone cement powder, which is magnesia, potassium dihydrogen phosphate and calcium dihydrogen phosphate,:3:1 be uniformly mixed and
At.Claim 4g bone cement powder, and adds the above-mentioned gelatine microspheres of 0.8g.Then configuration concentration is the citric acid solution of 0.02g/mL,
It takes the citric acid solution of 2.6mL and powder mutually to reconcile 2min, enters to be placed on after mould solidification 37 DEG C, it is solid under the environment under 100% humidity
Change 48h.Cure two days strength of bone cement with the test of omnipotent test machine.By the cured bone cement with 1g:The ratio of 20mL is put
It sets in the PBS buffer solutions of pH=7.4 and releases the drug.
The load medicine gelatine microsphere balling-up effect is preferable, and grain size is 0-250 μm, and the gelatin/phosphoric acid magnesium-based bone cement drug is slow
To release system to cure two days intensity be 14MPa, 60 days drug releases 90%.
The above is the preferred embodiment of the present invention, cannot limit the right model of the present invention with this certainly
It encloses, it is noted that for those skilled in the art, without departing from the principle of the present invention, may be used also
To make several improvement and variation, these are improved and variation is also considered as protection scope of the present invention.
Claims (10)
1. a kind of preparation method of gelatine microsphere/phosphoric acid magnesium-based bone cement slow releasing carrier of medication, which is characterized in that including walking as follows
Suddenly：
(1) 1- ethyls-crosslinked load medicine gelatine microsphere of (3- dimethylaminopropyls) carbodiimide hydrochloride is prepared；
(2) medicine gelatine microsphere will be carried obtained by step (1) to mix uniformly with phosphoric acid magnesium-based bone cement powder, then with phosphoric acid magnesium-based bone water
Mud liquid phase, which reconciles, to be cured, and the gelatine microsphere/phosphoric acid magnesium-based bone cement slow releasing carrier of medication is obtained.
2. preparation method according to claim 1, which is characterized in that the load medicine gelatine microsphere preparation method includes：
1) gelatin and drug are dissolved in the deionized water of 40-60 DEG C of temperature and are uniformly mixed, it is 20%- to obtain gelatin mass fraction
30% gelatin carries drug solns；
2) using atoleine as oil phase, Span 80 is dispersant, is stirred evenly after the two mixing；
3) gelatin is added dropwise into oil phase at rotating speed 100-600r/min and carries drug solns, ice-water bath is changed after stirring 5-100min；It
After continue that 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride solution is added dropwise after stirring 5-60min；It is crosslinked 30-
240min；
4) microballoon is taken out, is cleaned with dehydrating agent, air drying, obtains carrying medicine gelatine microsphere.
3. preparation method according to claim 1 or 2, which is characterized in that crosslinking agent 1- ethyls-(3- dimethylaminos third
Base) carbodiimide hydrochloride dosage be gelatin dosage 1~25wt%.
4. preparation method according to claim 1 or 2, which is characterized in that crosslinking agent 1- ethyls-(3- dimethylaminos third
Base) carbodiimide hydrochloride dosage be gelatin dosage 13wt%.
5. preparation method according to claim 1, which is characterized in that the phosphoric acid magnesium-based bone cement powder phase component is oxidation
The mixture of magnesium, calcium dihydrogen phosphate, potassium dihydrogen phosphate；Liquid phase component is aqueous citric acid solution.
6. preparation method according to claim 1, which is characterized in that the load medicine gelatine microsphere and phosphoric acid magnesium-based bone cement
The mass ratio of powder phase is (1~15)：100.
7. preparation method according to claim 1, which is characterized in that the oxygen in the phosphoric acid magnesium-based bone cement powder phase component
Change magnesium and passes through calcination processing：Calcination temperature is 1600 DEG C, and heating rate is 3 DEG C/min, keeps the temperature 1.5h, it is 1- that ball milling, which obtains grain size,
3μm。
8. preparation method according to claim 1, which is characterized in that the phosphorus in the phosphoric acid magnesium-based bone cement powder phase component
The grain size of acid dihydride calcium is 0.5-30 μm；The grain size of potassium dihydrogen phosphate is 1-20 μm.
9. preparation method according to claim 1, which is characterized in that in the phosphoric acid magnesium-based bone cement powder phase component, oxygen
Change magnesium：Potassium dihydrogen phosphate：The mass ratio of calcium dihydrogen phosphate is 1.5:3:1；In liquid phase component, a concentration of 0.01g/ of citric acid
mL-0.05g/mL。
10. a kind of gelatine microsphere/phosphoric acid magnesium-based bone cement slow releasing carrier of medication, which is characterized in that by any one of claim 1-9
The method is prepared.
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| CN113713753A (en) * | 2021-09-06 | 2021-11-30 | 昆明理工大学 | Preparation method and application of magnesium oxalate microspheres |
| CN115054724A (en) * | 2022-04-28 | 2022-09-16 | 浙江理工大学 | Hollow embolism microsphere and preparation method, pharmaceutical composition and application thereof |
| CN115054724B (en) * | 2022-04-28 | 2024-01-12 | 浙江理工大学 | Hollow embolism microsphere, preparation method, pharmaceutical composition and application thereof |
| CN115463252A (en) * | 2022-08-31 | 2022-12-13 | 武汉理工大学 | Magnetic bone cement for infectious bone defect treatment and preparation method and application thereof |
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