CN105148828B - A kind of doping cerium dioxide nano material is in the application for absorption and slow releasing pharmaceutical molecule - Google Patents
A kind of doping cerium dioxide nano material is in the application for absorption and slow releasing pharmaceutical molecule Download PDFInfo
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Abstract
In the application for absorption and slow releasing pharmaceutical molecule, it is related to the doping cerium dioxide nano material and its synthetic method of a kind of absorption and slow releasing pharmaceutical molecule to a kind of doping cerium dioxide nano material.Nano material the invention aims to solve to be currently used for absorption and slow releasing pharmaceutical molecule is relatively low for the load capacity of medicine, the problem that slow-release time is shorter and current material preparation technology is complicated.Method:First, mixing is weighed, mixed material is obtained;2nd, dissolving mixing, obtains mixed solution;3rd, hot pressure reaction, obtains nanometer powder;4th, drying is washed, the doping cerium dioxide nano material for absorption and slow releasing pharmaceutical molecule is obtained;Advantage:For ibuprofen pharmaceutical molecule there is adsorption rate higher to reach 90.1%~97.3%.
Description
Technical field
The present invention relates to a kind of absorption and the synthetic method of the doping cerium dioxide nano material of slow releasing pharmaceutical molecule.
Background technology
Particle size is less than 10 nanometers, the homogeneous inorganic nanometer functional material of Size Distribution because of its unique physical chemistry
Matter has potential application value in drug loading release, medical diagnosis analysis, biological detection and bio-separation field.Titanium dioxide
Cerium effect with anti-oxidant, good biocompatibility, degraded toxic pollutant as one of important rare earth compound, therefore
It is desirable that cerium dioxide nano biology material of the synthesis with the load of higher drug molecule with slow-release capability, this requires that it has
There is the homogeneous feature of high-specific surface area, small size, Size Distribution.Traditional drug molecule support materials are molecular screen material, its
Preparation technology is complicated, and drug molecule load capacity is not high and discharges not enough thoroughly, and is no longer desirable for absorption and slow releasing pharmaceutical point
Son.The nano material that exploitation has high capacity amount, release time long to drug molecule turns into the important of medical biotechnology development
Task.
The content of the invention
The invention aims to solve to be currently used for the nano material of absorption and slow releasing pharmaceutical molecule for medicine
Load capacity is relatively low, the problem that slow-release time is shorter and current material preparation technology is complicated, and provides a kind of doping cerium dioxide and receive
Rice material is in the application for absorption and slow releasing pharmaceutical molecule.
Doping cerium dioxide nano material for absorption and slow releasing pharmaceutical molecule is the dioxy of rare earth element ion doping
Change cerium nanometer powder, chemical formula is Ce1-xLnxO2-δ, wherein:0.05≤x≤0.15,0.025≤δ≤0.075, Ln is Nd, Sm
Or Gd.The specific surface area for absorption and the doping cerium dioxide nano material of slow releasing pharmaceutical molecule is 105m2/ g~
133m2/g。
For absorption and the synthetic method of the doping cerium dioxide nano material of slow releasing pharmaceutical molecule, particular by following
What step was realized:
First, mixing is weighed:According to chemical formula Ce1-xLnxO2-δIt is (1-x) by the mol ratio of Ce and Ln:X weighs Ce
(NO3)3·6H2O and Ln (NO3)3·6H2O, wherein:0.05≤x≤0.15,0.025≤δ≤0.075, Ln be Nd, Sm or Gd,
Then by Ce (NO3)3·6H2O and Ln (NO3)3·6H2O is ground mixing, obtains mixed material;
2nd, dissolving mixing:Mixed material is dissolved in mixed solvent, and magnetic agitation is mixed, and obtains mixed material molten
Liquid, to stearic acid is added in mixed material solution, adds triethanolamine, and magnetic agitation is mixed, and obtains mixed solution;
3rd, hot pressure reaction:Temperature be 160~200 DEG C and pressure for the sealing condition of 0.5MPa~1.0MPa under to mixed
Closing solution carries out hot pressure reaction, and the hot pressure reaction time is 12h~36h, then naturally cools to room temperature, obtains nanometer powder;
4th, drying is washed:Centrifuge washing is carried out to nanometer powder as detergent using ethanol and deionized water successively, is obtained
Nanometer powder after to washing, so temperature be 60~100 DEG C under the conditions of to washing after nanometer powder carry out heated at constant temperature 12h~
24h, obtains the doping cerium dioxide nano material for absorption and slow releasing pharmaceutical molecule;
Mixed material and stearic mass ratio described in step 2 are (4.1~12.3):1;Described in step 2
The ratio of mixed material quality and triethanolamine is (0.62~1.25) g:1mL.
Advantage of the present invention:
First, the doping cerium dioxide nano material chemical formula for absorption and slow releasing pharmaceutical molecule prepared by the present invention is
Ce1-xLnxO2-δ, wherein Ce ions are+4 valencys, and rare earth ion is+trivalent;Using Ln3+Rare earth ion replaces Ce4+Ion, in order to tie up
The electroneutrality condition in crystal is held, a number of Lacking oxygen can be produced, this can improve nano-material surface and crystals
Lacking oxygen density, the effect of oxygen-containing functional group in reinforcing material surface and drug molecule, and then improve the load of drug molecule
Ability.
2nd, synthetic method of the invention is simple to operate, mild condition, and reaction temperature is only 160~200 DEG C;The use of preparation
In the fluorite structure crystal that the doping cerium dioxide nano material of absorption and slow releasing pharmaceutical molecule is Emission in Cubic, with knot higher
Brilliant degree.Doping cerium dioxide nano material for absorption and slow releasing pharmaceutical molecule receiving for shape of octahedron prepared by the present invention
Rice grain, the average-size of particle is 4.0 nanometers, and Size Distribution is homogeneous;And specific surface area is big, it is easy to absorption and slow releasing pharmaceutical point
Son, can be applied to field of medical biotechnology.
3rd, the present invention prepare for adsorb and slow releasing pharmaceutical molecule doping cerium dioxide nano material specific surface area
It is 105m2/ g~133m2/ g, specific surface area can reach 133m2/ g, the mesoporous average-size constructed between particle is
2.4nm, mesopore volume is 0.21cm3/ g, thus the present invention prepare for adsorb and slow releasing pharmaceutical molecule doping titanium dioxide
Cerium nano material is a kind of stronger adsorption capacity for absorption and the nano material of slow releasing pharmaceutical molecule.
4th, the doping cerium dioxide nano material for absorption and slow releasing pharmaceutical molecule prepared by the present invention is received as absorption
Rice material is used to adsorb brufen, the doping cerium dioxide nanometer material for absorption and slow releasing pharmaceutical molecule prepared by the present invention
Material carries out the load of drug molecule and sustained release is tested, and it is drug target molecule to choose brufen (IBU).1.8 grams of brufens are existed
It is dissolved under conditions of magnetic agitation in 30 milliliters of hexane solvents, is received to doping cerium dioxide obtained in 0.12 gram of addition in this solution
Rice material, magnetic agitation 24 hours in closed glass reagent bottle, then using supercentrifuge under the conditions of 10000 revs/min
Centrifugal dispersion, finally heating obtains loading the nano material of brufen for 24 hours in 60 DEG C, air atmosphere.Thermogravimetric analysis is tested
Show that obtained doping cerium dioxide nano material has adsorption rate higher for ibuprofen pharmaceutical molecule, adsorption rate reaches
90.1%~97.3%.
Brief description of the drawings
Fig. 1 is that the X- for absorption and the doping cerium dioxide nano material of slow releasing pharmaceutical molecule prepared by embodiment 1 is penetrated
Line diffraction spectrogram;
Fig. 2 is the preparation of embodiment 1 for absorption and the low power of the doping cerium dioxide nano material of slow releasing pharmaceutical molecule
Transmission electron microscope image;
Fig. 3 is the preparation of embodiment 1 for absorption and the high power of the doping cerium dioxide nano material of slow releasing pharmaceutical molecule
Transmission electron microscope image;
Fig. 4 is thermal gravimetric analysis curve, and A represents the Ce of load brufen in figure0.95Nd0.05O1.975The thermogravimetric of nano material point
Analysis curve, B represents the CeO of load brufen in figure2The thermal gravimetric analysis curve of nano material;
Fig. 5 is release rate-time plot, and A represents the Ce of load brufen in figure0.95Nd0.05O1.975Nano material is 0
~72h release rates-time plot, B represents the CeO of load brufen in figure2Nano material is bent in 0~72h release rates-time
Line chart.
Specific embodiment
Specific embodiment one:Present embodiment is the doping cerium dioxide nanometer material for absorption and slow releasing pharmaceutical molecule
Expect to be the cerium dioxide nano powder of rare earth element ion doping, chemical formula is Ce1-xLnxO2-δ, wherein:0.05≤x≤0.15,
0.025≤δ≤0.075, Ln is Nd, Sm or Gd.The doping cerium dioxide nanometer material for absorption and slow releasing pharmaceutical molecule
The specific surface area of material is 105m2/ g~133m2/g。
Specific embodiment two:Present embodiment is with the difference of specific embodiment one:It is described for adsorbing and being sustained
The chemical formula of the doping cerium dioxide nano material of drug molecule is Ce0.95Nd0.05O1.975, it is described for absorption and slow releasing pharmaceutical
The specific surface area of the doping cerium dioxide nano material of molecule is 133m2/g.Other are identical with specific embodiment one.
Chemical formula described in present embodiment is Ce0.95Nd0.05O1.975For adsorb and slow releasing pharmaceutical molecule doping
Cerium dioxide nano material reaches 97.3% to the adsorption rate of brufen.
Specific embodiment three:Present embodiment is the doping cerium dioxide nanometer material for absorption and slow releasing pharmaceutical molecule
The synthetic method of material, realizes particular by following steps:
First, mixing is weighed:According to chemical formula Ce1-xLnxO2-δIt is (1-x) by the mol ratio of Ce and Ln:X weighs Ce
(NO3)3·6H2O and Ln (NO3)3·6H2O, wherein:0.05≤x≤0.15,0.025≤δ≤0.075, Ln be Nd, Sm or Gd,
Then by Ce (NO3)3·6H2O and Ln (NO3)3·6H2O is ground mixing, obtains mixed material;
2nd, dissolving mixing:Mixed material is dissolved in mixed solvent, and magnetic agitation is mixed, and obtains mixed material molten
Liquid, to stearic acid is added in mixed material solution, adds triethanolamine, and magnetic agitation is mixed, and obtains mixed solution;
3rd, hot pressure reaction:Temperature be 160~200 DEG C and pressure for the sealing condition of 0.5MPa~1.0MPa under to mixed
Closing solution carries out hot pressure reaction, and the hot pressure reaction time is 12h~36h, then naturally cools to room temperature, obtains nanometer powder;
4th, drying is washed:Centrifuge washing is carried out to nanometer powder as detergent using ethanol and deionized water successively, is obtained
Nanometer powder after to washing, so temperature be 60~100 DEG C under the conditions of to washing after nanometer powder carry out heated at constant temperature 12h~
24h, obtains the doping cerium dioxide nano material for absorption and slow releasing pharmaceutical molecule;
Mixed material and stearic mass ratio described in present embodiment step 2 are (4.1~12.3):1;This reality
The ratio for applying the mixed material quality described in mode step 2 and triethanolamine is (0.62~1.25) g:1mL;
In temperature it is that 160~200 DEG C and pressure are 0.5MPa~1.0MPa (equivalent to reaction in present embodiment step 3
Pressure is 5~10 atmospheric pressure) confined reaction environment is needed, reaction vessel should be with high pressure resistant property, therefore present embodiment conjunction
Glass container should not be used into method, and should be using the container for being resistant to elevated pressures, so present embodiment is from stainless
Steel reactor, and inside is equipped with polytetrafluoroethylkettle kettle lining, its reaction vessel strong alkali-acid resistance, and highest can be heated to 280
DEG C or so.
It is used for the doping cerium dioxide nano material of absorption and slow releasing pharmaceutical molecule described in present embodiment step 4
Specific surface area is 105m2/ g~133m2/g。
Specific embodiment four:Present embodiment is with the difference of specific embodiment three:According to chemistry in step one
Formula Ce0.95Nd0.05O1.975It is 0.95 by the mol ratio of Ce and Ln:0.05 weighs Ce (NO3)3·6H2O and Ln (NO3)3·6H2O。
Other are identical with specific embodiment three.
Specific embodiment five:One of present embodiment and specific embodiment three or four difference is:Institute in step 2
The mixed solvent stated is the mixture of ethanol and deionized water, and ethanol and the volume ratio of deionized water are (1~1.5):1.Its
He is identical with specific embodiment three or four.
Specific embodiment six:One of present embodiment and specific embodiment three to five difference is:Step 4 is centrifuged
Washing concrete operations are as follows:1., using ethanol as detergent, nanometer powder is put into ethanol and is soaked, then using high speed from
Scheming is separated under conditions of 10000 revs/min;2., 1. repeat step operates 3~5 times, obtains nanometer powder after ethanol washing;
3., using deionized water as detergent, nanometer powder is put into deionized water and soaks after ethanol is washed, then using high speed from
Scheming is separated under conditions of 10000 revs/min;4., 3. repeat step operates 3~5 times, nanometer powder after being washed.Other
It is identical with specific embodiment three to five.
Present embodiment purpose is that the nitrate anion of residual in the nanometer powder that will be obtained in step 3 and organic reagent are removed.
Specific embodiment seven:For absorption and the doping cerium dioxide applications to nanostructures of slow releasing pharmaceutical molecule, use
It is used to adsorb brufen as absorption nano material in the doping cerium dioxide nano material of absorption and slow releasing pharmaceutical molecule, to cloth
The adsorption rate of ibuprofen reaches 97.3%.
The described doping cerium dioxide nano material for absorption and slow releasing pharmaceutical molecule is that rare earth element ion adulterates
Cerium dioxide nano powder, chemical formula is Ce1-xLnxO2-δ, wherein:0.05≤x≤0.15,0.025≤δ≤0.075, Ln is
Nd, Sm or Gd.The specific surface area for absorption and the doping cerium dioxide nano material of slow releasing pharmaceutical molecule is 105m2/g
~133m2/g。
Specific embodiment eight:For absorption and the doping cerium dioxide applications to nanostructures of slow releasing pharmaceutical molecule, use
Used as the slow-release material of brufen in the doping cerium dioxide nano material of absorption and slow releasing pharmaceutical molecule.
The described doping cerium dioxide nano material for absorption and slow releasing pharmaceutical molecule is that rare earth element ion adulterates
Cerium dioxide nano powder, chemical formula is Ce1-xLnxO2-δ, wherein:0.05≤x≤0.15,0.025≤δ≤0.075, Ln is
Nd, Sm or Gd.The specific surface area for absorption and the doping cerium dioxide nano material of slow releasing pharmaceutical molecule is 105m2/g
~133m2/g。
Using following verification experimental verifications effect of the present invention
Embodiment 1:For adsorb and slow releasing pharmaceutical molecule doping cerium dioxide nano material synthetic method, specifically
Realized by following steps:
First, mixing is weighed:By 1.1690g Ce (NO3)3·6H2O and 0.0620g Nd (NO3)3·6H2O is put into agate and grinds
Mixing is ground in alms bowl, mixed material is obtained;
2nd, dissolving mixing:The mixed material that step one is obtained is dissolved in 30mL mixed solvents, and magnetic agitation is mixed
It is even, mixed material solution is obtained, to 0.3g stearic acid is added in mixed material solution, 1mL triethanolamines are added, and magnetic force is stirred
Mixing is mixed, mixed solution is obtained;
3rd, hot pressure reaction:Mixed solution is transferred in stainless steel cauldron, described stainless steel cauldron inside is equipped with
Polytetrafluoroethylkettle kettle is served as a contrast, temperature be 180 DEG C and pressure for the sealing condition of 1.0MPa under hot pressure reaction is carried out to mixed solution,
The hot pressure reaction time is 24h, then naturally cools to room temperature, obtains nanometer powder;
4th, drying is washed:1., using ethanol as detergent, nanometer powder is put into ethanol and is soaked, then using at a high speed
Centrifuge is separated under conditions of 10000 revs/min;2., 1. repeat step operates 4 times, obtains nanometer powder after ethanol washing;
3., using deionized water as detergent, nanometer powder is put into deionized water and soaks after ethanol is washed, then using high speed from
Scheming is separated under conditions of 10000 revs/min;4., 3. repeat step operates 4 times, nanometer powder after being washed, 5., in temperature
Spend to carry out heated at constant temperature 24h to nanometer powder after washing under the conditions of 100 DEG C, obtain for adsorbing and slow releasing pharmaceutical molecule is mixed
Miscellaneous cerium dioxide nano material;For adsorbing and the chemical formula of doping cerium dioxide nano material of slow releasing pharmaceutical molecule is
Ce0.95Nd0.05O1.975。
Mixed solvent described in the step 2 of embodiment 1 is mixed by 18mL ethanol and 12mL deionized waters.
Ce (NO described in the step one of embodiment 13)3·6H2The mass fraction of O is 99.99%, institute in the step one of embodiment 1
State Nd (NO3)3·6H2The mass fraction of O is 99.99%.
Stearic mass fraction described in the step 2 of embodiment 1 is 99.0%, triethanolamine in the step 2 of embodiment 1
Mass fraction is 99.0%.
Doping cerium dioxide nano material for absorption and slow releasing pharmaceutical molecule prepared by embodiment 1 is detected,
As shown in figure 1, Fig. 1 be embodiment 1 prepare for adsorb and slow releasing pharmaceutical molecule doping cerium dioxide nano material X-
X ray diffraction spectrogram, the doping cerium dioxide nanometer for absorption and slow releasing pharmaceutical molecule that as shown in Figure 1 prepared by embodiment 1
Material is the fluorite structure compound of Emission in Cubic, and diffraction peak intensity is higher, shows that material has crystallinity higher, and without other
Thing is mutually generated, and is single phase pure material.
Using transmission electronic microscope technology it is prepared by embodiment 1 for adsorb and slow releasing pharmaceutical molecule doping dioxy
Changing cerium nano material carries out morphology observation, and as shown in Figures 2 and 3, Fig. 2 is the transmission electron microscope image for obtaining
Embodiment 1 prepare for adsorb and slow releasing pharmaceutical molecule doping cerium dioxide nano material low power transmission electron microscope
Image, Fig. 3 is the high power transmission for absorption and the doping cerium dioxide nano material of slow releasing pharmaceutical molecule prepared by embodiment 1
Electron microscope image;From Fig. 2 and Fig. 3, embodiment 1 prepare for adsorb and slow releasing pharmaceutical molecule doping titanium dioxide
Cerium nano material is shape of octahedron particle, and particle average size is 4.0 rans.
By the preparation of embodiment 1 knowable to nitrogen adsorption desorption curve test for absorption and the doping of slow releasing pharmaceutical molecule
The specific surface area of cerium dioxide nano material is 133m2/ g, the mesoporous average-size constructed between particle is 2.4nm, mesoporous body
Product is 0.21cm3/g。
Embodiment 2:For adsorb and slow releasing pharmaceutical molecule doping cerium dioxide applications to nanostructures, for adsorb and
The doping cerium dioxide nano material of slow releasing pharmaceutical molecule is used to adsorb brufen as absorption nano material, and concrete operations are such as
Under:1.8g brufens are dissolved in 30mL hexanes under conditions of magnetic agitation, be subsequently adding 0.12g for adsorb and slow releasing medicinal
The doping cerium dioxide nano material of thing molecule, the magnetic agitation 24h in closed glass reagent bottle, then using supercentrifuge
The centrifugation under the conditions of 10000 revs/min, obtains wet-milling powder material, finally dries 24h in temperature 60 C, air atmosphere, obtains
To the Ce of load brufen0.95Nd0.05O1.975Nano material.
The doping cerium dioxide nano material for absorption and slow releasing pharmaceutical molecule described in embodiment 2 is embodiment 1
Prepare.
Embodiment 3:The contrast test of embodiment 2:1.8g brufens are dissolved in 30mL hexanes under conditions of magnetic agitation,
It is subsequently adding 0.12gCeO2Nano material, magnetic agitation 24h, is then existed using supercentrifuge in closed glass reagent bottle
Centrifugation under the conditions of 10000 revs/min, obtains wet-milling powder material, finally dries 24h in temperature 60 C, air atmosphere, obtains
Load the CeO of brufen2Nano material.
Ce to loading brufen0.95Nd0.05O1.975The CeO of nano material and load brufen2Nano material carries out thermogravimetric
Analysis, as shown in figure 4, Fig. 4 is thermal gravimetric analysis curve, A represents the Ce of load brufen in figure0.95Nd0.05O1.975Nano material
Thermal gravimetric analysis curve, in figure B represent load brufen CeO2The thermal gravimetric analysis curve of nano material, it is as shown in Figure 4, real
Apply the absorption for the doping cerium dioxide nano material of absorption and slow releasing pharmaceutical molecule to ibuprofen pharmaceutical molecule of the preparation of example 1
Rate reaches 97.3%, CeO2Nano material is only 37.8% to the adsorption rate of ibuprofen pharmaceutical molecule.
Embodiment 4:For adsorb and slow releasing pharmaceutical molecule doping cerium dioxide applications to nanostructures, for adsorb and
The doping cerium dioxide nano material of slow releasing pharmaceutical molecule is used as the slow-release material of brufen, and detailed process is as follows:1st, match somebody with somebody
Put human body simulation body fluid:By NaCl, NaHCO3、KCl、K2HPO4·3H2O、MgCl2·6H2O、CaCl2And Na2SO4Sequentially add
In 800mL deionized waters, mixed liquor is obtained after mixing, Na in mixed liquor+Concentration be 142.0mmol/L, K+Concentration be
5.0mmol/L, Ca2+Concentration be 2.5mmol/L, Mg2+Concentration be 1.5mmol/L, Cl-Concentration be 147.8mmol/L,
HCO3 -Concentration be 4.2mmol/L, HPO4 2-Concentration be 1.0mmol/L, SO4 2-Concentration be 0.5mmol/L, be by concentration
The trometamol and concentration of 50mmol/L are added in mixed liquor for the HCl solution of 0.1mol/L, and the pH value of mixed liquor is adjusted to
7.4,1000mL finally is settled to using deionized water, obtain human body simulation body fluid;2nd, discharge:By 0.12g load brufens
Ce0.95Nd0.05O1.975Nano material is put into 15mL human body simulation body fluid, and magnetic agitation makes at being 36.5~37.0 DEG C in temperature
Load the Ce of brufen0.95Nd0.05O1.975Brufen is discharged into human body simulation body fluid in nano material, discharges 1h, is contained
There is the human body simulation body fluid of brufen;3rd, detect:It is 10000 revs/min in rotating speed to take the human body simulation body fluid that 1mL contains brufen
Under be centrifuged at a high speed, the supernatant for obtaining, in supernatant add 50mL deionized waters be diluted, obtain liquid to be detected,
The absorbance of liquid to be detected is tested under 220nm wavelength conditions using ultraviolet-visible spectrum, the standard according to brufen solution is inhaled
Receive curve and calculate determination of ibuprofen in the human body simulation body fluid containing brufen.
The Ce of the load brufen described in embodiment 40.95Nd0.05O1.975Nano material is prepared by embodiment 2.
Embodiment 5:The present embodiment is with the difference of embodiment 4:3h is discharged in step 2, the human body containing brufen is obtained
Simulated body fluid.Other are same as Example 4.
Embodiment 6:The present embodiment is with the difference of embodiment 4:5h is discharged in step 2, the human body containing brufen is obtained
Simulated body fluid.Other are same as Example 4.
Embodiment 7:The present embodiment is with the difference of embodiment 4:8h is discharged in step 2, the human body containing brufen is obtained
Simulated body fluid.Other are same as Example 4.
Embodiment 8:The present embodiment is with the difference of embodiment 4:10h is discharged in step 2, the human body containing brufen is obtained
Simulated body fluid.Other are same as Example 4.
Embodiment 9:The present embodiment is with the difference of embodiment 4:12h is discharged in step 2, the human body containing brufen is obtained
Simulated body fluid.Other are same as Example 4.
Embodiment 10:The present embodiment is with the difference of embodiment 4:14h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are same as Example 4.
Embodiment 11:The present embodiment is with the difference of embodiment 4:24h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are same as Example 4.
Embodiment 12:The present embodiment is with the difference of embodiment 4:30h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are same as Example 4.
Embodiment 13:The present embodiment is with the difference of embodiment 4:36h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are same as Example 4.
Embodiment 14:The present embodiment is with the difference of embodiment 4:48h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are same as Example 4.
Embodiment 15:The present embodiment is with the difference of embodiment 4:60h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are same as Example 4.
Embodiment 16:The present embodiment is with the difference of embodiment 4:72h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are same as Example 4.
Embodiment 17:Load the CeO of brufen2Nano material release test, detailed process is as follows:1st, human body simulation is configured
Body fluid:By NaCl, NaHCO3、KCl、K2HPO4·3H2O、MgCl2·6H2O、CaCl2And Na2SO4Sequentially add 800mL deionizations
In water, mixed liquor is obtained after mixing, Na in mixed liquor+Concentration be 142.0mmol/L, K+Concentration be 5.0mmol/L, Ca2+
Concentration be 2.5mmol/L, Mg2+Concentration be 1.5mmol/L, Cl-Concentration be 147.8mmol/L, HCO3 -Concentration be
4.2mmol/L, HPO4 2-Concentration be 1.0mmol/L, SO4 2-Concentration be 0.5mmol/L, by concentration for 50mmol/L slow blood
Acid amide and concentration are added in mixed liquor for the HCl solution of 0.1mol/L, and the pH value of mixed liquor is adjusted into 7.4, finally using go from
Sub- water is settled to 1000mL, obtains human body simulation body fluid;2nd, discharge:0.12g is loaded the CeO of brufen2Nano material is put into
In 15mL human body simulation body fluid, magnetic agitation makes the CeO of load brufen at being 36.5~37.0 DEG C in temperature2In nano material
Brufen is discharged into human body simulation body fluid, discharges 1h, obtains the human body simulation body fluid containing brufen;3rd, detect:1mL is taken to contain
The human body simulation body fluid for having brufen is centrifuged at a high speed under being 10000 revs/min in rotating speed, the supernatant for obtaining, to supernatant
Middle addition 50mL deionized waters are diluted, and obtain liquid to be detected, are surveyed under 220nm wavelength conditions using ultraviolet-visible spectrum
The absorbance of liquid to be detected is tried, the standard absorption curve according to brufen solution calculates the human body simulation body fluid containing brufen
Middle determination of ibuprofen.
The CeO of the load brufen described in embodiment 172Nano material is prepared by embodiment 3.
Embodiment 18:The present embodiment is with the difference of embodiment 17:3h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Embodiment 19:The present embodiment is with the difference of embodiment 17:5h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Embodiment 20:The present embodiment is with the difference of embodiment 17:8h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Embodiment 21:The present embodiment is with the difference of embodiment 17:10h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Embodiment 22:The present embodiment is with the difference of embodiment 17:12h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Embodiment 23:The present embodiment is with the difference of embodiment 17:14h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Embodiment 24:The present embodiment is with the difference of embodiment 17:24h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Embodiment 25:The present embodiment is with the difference of embodiment 17:30h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Embodiment 26:The present embodiment is with the difference of embodiment 17:36h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Embodiment 27:The present embodiment is with the difference of embodiment 17:48h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Embodiment 28:The present embodiment is with the difference of embodiment 17:60h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Embodiment 29:The present embodiment is with the difference of embodiment 17:72h is discharged in step 2, the people containing brufen is obtained
Body simulated body fluid.Other are identical with embodiment 17.
Release rate-time plot is drawn according to the data that embodiment 4 to embodiment 29 is obtained, as shown in figure 5, Fig. 5 is
Release rate-time plot, A represents the Ce of load brufen in figure0.95Nd0.05O1.975Nano material 0~72h release rates-
Time plot, B represents the CeO of load brufen in figure2Nano material in 0~72h release rates-time plot, by Fig. 5
Understand, load the Ce of brufen0.95Nd0.05O1.975Nano material can discharge 92.1% brufen, load cloth Lip river in 36h
Fragrant CeO2Brufen release rate of the nano material in 36h is only 42.6%, embodiment 1 prepare for adsorb and slow releasing medicinal
The doping cerium dioxide nano material of thing molecule has good slow releasing function to brufen.
Claims (1)
1. a kind of doping cerium dioxide nano material is in the application for absorption and slow releasing pharmaceutical molecule, it is characterised in that for inhaling
The synthetic method of attached and slow releasing pharmaceutical molecule doping cerium dioxide nano material is through the following steps that realize:
First, mixing is weighed:By 1.1690g Ce (NO3)3·6H2O and 0.0620g Nd (NO3)3·6H2O is put into agate mortar
Mixing is ground, mixed material is obtained;
2nd, dissolving mixing:The mixed material that step one is obtained is dissolved in 30mL mixed solvents, and magnetic agitation is mixed, and is obtained
To mixed material solution, to 0.3g stearic acid is added in mixed material solution, 1mL triethanolamines are added, and magnetic agitation is mixed
It is even, obtain mixed solution;
3rd, hot pressure reaction:Mixed solution is transferred in stainless steel cauldron, described stainless steel cauldron inside is equipped with poly- four
PVF kettle is served as a contrast, temperature be 180 DEG C and pressure for the sealing condition of 1.0MPa under hot pressure reaction, hot pressing are carried out to mixed solution
Reaction time is 24h, then naturally cools to room temperature, obtains nanometer powder;
4th, drying is washed:1., using ethanol as detergent, nanometer powder is put into ethanol and is soaked, then using high speed centrifugation
Machine is separated under conditions of 10000 revs/min;2., 1. repeat step operates 4 times, obtains nanometer powder after ethanol washing;3., with
Used as detergent, nanometer powder soaks deionized water in being put into deionized water after ethanol is washed, then using supercentrifuge
Separated under conditions of 10000 revs/min;4., 3. repeat step operates 4 times, and 5., in temperature nanometer powder after being washed is
Heated at constant temperature 24h is carried out to nanometer powder after washing under the conditions of 100 DEG C, the doping two for absorption and slow releasing pharmaceutical molecule is obtained
Cerium oxide nano materials;For adsorbing and the chemical formula of doping cerium dioxide nano material of slow releasing pharmaceutical molecule is
Ce0.95Nd0.05O1.975;
Mixed solvent described in step 2 is mixed by 18mL ethanol and 12mL deionized waters;
Ce (NO described in step one3)3·6H2The mass fraction of O is 99.99%, Nd (NO described in step one3)3·6H2O's
Mass fraction is 99.99%;
Stearic mass fraction described in step 2 is 99.0%, and the mass fraction of triethanolamine is 99.0% in step 2;
The specific surface area for absorption and the doping cerium dioxide nano material of slow releasing pharmaceutical molecule that step 4 is obtained is 133m2/
G, the mesoporous average-size constructed between particle is 2.4nm, and mesopore volume is 0.21cm3/g;
The doping cerium dioxide nano material for absorption and slow releasing pharmaceutical molecule that step 4 is obtained is used as absorption nano material
For adsorbing brufen, concrete operations are as follows:1.8g brufens are dissolved in 30mL hexanes under conditions of magnetic agitation, then
Adding 0.12g is used for the doping cerium dioxide nano material of absorption and slow releasing pharmaceutical molecule, the magnetic force in closed glass reagent bottle
Stirring 24h, then using supercentrifuge centrifugation under the conditions of 10000 revs/min, obtains wet-milling powder material, finally in temperature
24h is dried in 60 DEG C of degree, air atmosphere, obtains loading the Ce of brufen0.95Nd0.05O1.975Nano material;It is described for adsorbing
And the doping cerium dioxide nano material of slow releasing pharmaceutical molecule reaches 97.3% to the adsorption rate of ibuprofen pharmaceutical molecule;
Step 4 obtain for adsorb and slow releasing pharmaceutical molecule doping cerium dioxide nano material as brufen sustained release
Materials'use, detailed process is as follows:1st, human body simulation body fluid is configured:By NaCl, NaHCO3、KCl、K2HPO4·3H2O、MgCl2·
6H2O、CaCl2And Na2SO4Sequentially add in 800mL deionized waters, mixed liquor is obtained after mixing, Na in mixed liquor+Concentration be
142.0mmol/L, K+Concentration be 5.0mmol/L, Ca2+Concentration be 2.5mmol/L, Mg2+Concentration be 1.5mmol/L, Cl-
Concentration be 147.8mmol/L, HCO3 -Concentration be 4.2mmol/L, HPO4 2-Concentration be 1.0mmol/L, SO4 2-Concentration be
0.5mmol/L, by concentration for 50mmol/L trometamol and concentration for 0.1mol/L HCl solution add mixed liquor in, will
The pH value of mixed liquor is adjusted to 7.4, is finally settled to 1000mL using deionized water, obtains human body simulation body fluid;2nd, discharge:Will
0.12g loads the Ce of brufen0.95Nd0.05O1.975Nano material is put into 15mL human body simulation body fluid, temperature be 36.5~
Magnetic agitation makes the Ce of load brufen at 37.0 DEG C0.95Nd0.05O1.975Brufen is discharged to human body simulation body in nano material
In liquid, 1h is discharged, obtain the human body simulation body fluid containing brufen;3rd, detect:Take the human body simulation body fluid that 1mL contains brufen
It is centrifuged at a high speed under being 10000 revs/min in rotating speed, the supernatant for obtaining is carried out to 50mL deionized waters are added in supernatant
Dilution, obtains liquid to be detected, tests the absorbance of liquid to be detected under 220nm wavelength conditions using ultraviolet-visible spectrum, according to
The standard absorption curve of brufen solution calculates determination of ibuprofen in the human body simulation body fluid containing brufen;Load brufen
Ce0.95Nd0.05O1.975Nano material discharges 92.1% brufen in 36h.
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