CN101613524A - Triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material and preparation thereof - Google Patents
Triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material and preparation thereof Download PDFInfo
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Abstract
The invention belongs to the nano meter biomaterial field, be specifically related to a kind of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material and preparation thereof.The microscopic particles of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material of the present invention is a calcium phosphate coated triblock copolymer PEO-PPO-PEO structure; Wherein, in the total mass of nano composite material, the mass percent of triblock copolymer PEO-PPO-PEO is 5%～40%, and the mass percent of calcium phosphate is 60%～95%.Nano composite material of the present invention can be used as pharmaceutical carrier, and poorly water soluble drugs is had higher drug loading and good sustained release performance, has a good application prospect at biomedicine field; Its preparation method has that technology is simple, easy and simple to handle, room temperature preparation, cost is lower and characteristics such as environmental friendliness.
Description
Technical field
The invention belongs to the nano meter biomaterial field, be specifically related to a kind of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material and preparation thereof.
Background technology
Nano composite material is the matrix material that is composited with nanoscale size (1-100nm) at one dimension at least by two or more solid phase.These solid phases can be amorphousness, miocrystalline, crystalloid or have both at the same time, and can be that inorganics, organism or the two have concurrently.Nano composite material can be meant that also dispersed phase size has the matrix material of one dimension less than 100nm, the composition of disperse phase can be a mineral compound, also can be organic compound, mineral compound typically refers to pottery, metal etc., and organic compound typically refers to organic polymer material.When nano material is a disperse phase, when organic polymer is external phase, be exactly polymer based nanocomposites.
Nano composite material is different with conventional mineral filler/polymeric system, be not organic phase and inorganic simple mixing mutually, but two-phase is composited in nano-scale range.Because interfacial area is very big between disperse phase and the external phase, has very strong interaction between the interface, produce the ideal adhesiveproperties, make the interface fuzzy.Organic polymer as disperse phase typically refers to rigid rod-like polymer, comprise lytropic liquid crystals polymkeric substance, TLCP and other upright and outspoken polymer, they are dispersed in the flexible polymer substrate with molecular level, constitute inorganics/organic polymer nano composite material.Organic polymer as external phase can be thermoplastic polymer, thermosetting polymer.Polymer base inorganic nano-composite material not only has character such as the surface effects, quantum size effect of nano material, and rigidity, dimensional stability and the thermostability of inorganics and toughness, processibility and the dielectric properties of polymkeric substance blent into one, thereby produce many special performances.
Calcium phosphate is present in the human body in a large number with amorphous calcium phosphate and two kinds of forms of hydroxyapatite.Calcium phosphate material is widely used in carrier, protein carrier, medicine and the genophore etc. of biomedicine field such as tissue engineering material, orthopaedic materials, cell experiment.Compare other carrier, the composition that calcium phosphate is in the human body to be had, nontoxic, have Bioabsorbable, so calcium phosphate is a kind of good bio-medical material.Another advantage of calcium phosphate is a wetting ability.But calcium phosphate is as drug carrier material, and its loading capacity is often lower, and drug releasing rate is very fast, is unfavorable for treatment.Therefore, be badly in need of the loading capacity that a kind of method improves the calcium phosphate solid support material at present, and slowly discharge medicine wherein.
Amphipathic nature block polymer also is widely used in the research of medicine (especially poorly water soluble drugs) and genophore in recent years.Amphipathic nature block polymer can form nano-micelle in the aqueous solution, micellar nuclear is hydrophobic, and the micellar shell then is hydrophilic.Utilize this micellar characteristic, its hydrophobic core can be as the thesaurus of poorly water soluble drugs; Its hydrophilic shell then can interact with coenocorrelation on every side, and provides protection and stabilization to hydrophobic core simultaneously.This specific character of amphipathic nature block polymer both can guarantee the high loading capacity of poorly water soluble drugs, can guarantee the slow release of poorly water soluble drugs in human circulation again.In addition, this specific character can also make hydrophilic calcium phosphate coated in its hydrophilic shell outside.A kind of amphipathic nature block polymer and triblock copolymer PEO-PPO-PEO (polyoxyethylene-poly-oxypropylene polyoxyethylene) comes to this.
Triblock copolymer PEO-PPO-PEO is meant the parents' triblock copolymer that is made of alternative PEO and PPO block, and this multipolymer has abundant phase behavior in the aqueous solution.Because in the aqueous solution, PEO is a hydrophilic block and PPO is a hydrophobic block.For fear of direct the contacting of hydrophobic block with solvent (water), system forms micella and the various ordered phase that various domain structures comprise different shapes and size with self-assembly.This self-assembly ability has caused experiment and theoretic broad research interest.Yet it is now also few about the relevant report of the application facet of this triblock copolymer PEO-PPO-PEO.
Summary of the invention
The object of the present invention is to provide a kind of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material, the microscopic particles of this triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material is a calcium phosphate coated triblock copolymer PEO-PPO-PEO structure; Wherein, in the total mass of nano composite material, the mass percent of triblock copolymer PEO-PPO-PEO is 5%～40%, and the mass percent of calcium phosphate is 60%～95%.
Preferably, the particle diameter of the microscopic particles of described triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material is 10～100nm; And the microscopic particles of described triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material has vesicular structure.
Preferred, the aperture of described vesicular structure is less than 10nm.
The preparation method of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material of the present invention is: successively solubility calcium salt brine solution and soluble phosphoric acid salt brine solution are joined successively that reaction makes triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material in the triblock copolymer PEO-PPO-PEO aqueous solution.
Preferably, described soluble calcium salt is selected from calcium chloride, nitrocalcite or lime acetate.
Preferably, in the described solubility calcium salt brine solution, the molecular volume concentration of soluble calcium salt is 0.002～0.2mol/L.
Preferably, the volume ratio of the described solubility calcium salt brine solution and the triblock copolymer PEO-PPO-PEO aqueous solution is 1: 4～50.
Preferably, described soluble phosphate is selected from ammonium phosphate, Secondary ammonium phosphate, primary ammonium phosphate, sodium phosphate, Sodium phosphate dibasic or SODIUM PHOSPHATE, MONOBASIC.
Preferably, in the described soluble phosphoric acid salt brine solution, the molecular volume concentration of soluble phosphate is 0.002～0.2mol/L.
Preferably, the volume ratio of the described soluble phosphoric acid salt brine solution and the triblock copolymer PEO-PPO-PEO aqueous solution is 1: 5～60.
The molecular weight of described triblock copolymer PEO-PPO-PEO and block ratio are not limit.
Preferably, described triblock copolymer PEO-PPO-PEO is selected from P123 or F127.
Described P123 is meant that block consists of EO
20-PO
70-EO
20Polyoxyethylene-poly-oxypropylene polyoxyethylene; Described F127 is meant that block consists of EO
106-PO
70-EO
10Polyethylene oxide-poly(propylene oxide)-polyethylene oxide; Wherein EO is an oxyethyl group, and PO is a propoxy-.
Preferably, in the described triblock copolymer PEO-PPO-PEO aqueous solution, the quality volumetric concentration of triblock copolymer PEO-PPO-PEO is 1～10g/L.
Preferably, described reaction also needs reaction product is separated after making triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material, then separated products is washed and drying treatment.
Preferred, the described centrifuging that is separated into is separated.
Preferred, described drying treatment is at air drying under 20～100 ℃ temperature.
Preferably, described triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material can carry out the modification processing through being selected from physics, chemistry or biological method of modifying.
Preferred, described triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material can be through Macrogol 2000 0, acrylamide or amino-acid modified its modifier that makes.
Described concrete operations step through Macrogol 2000 0 modification is: triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material and Macrogol 2000 0 are scattered in make dispersion soln in the water, make triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material modified product through stirring, centrifugation, washing and drying step.Most preferred, in the described dispersion soln, the quality volumetric concentration of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material is 1.25g/L; The quality volumetric concentration of Macrogol 2000 0 is 2.5g/L.
Describedly be: by proportioning solubility calcium salt brine solution and soluble phosphoric acid salt brine solution are successively joined in the triblock copolymer PEO-PPO-PEO aqueous solution successively through acrylic amide modified concrete operations step, and then in above-mentioned solution, add acrylamide, make the modified product of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material through reaction.The mass ratio of described acrylamide and triblock copolymer PEO-PPO-PEO is 0.5～2: 1.
Describedly be: by proportioning solubility calcium salt brine solution and soluble phosphoric acid salt brine solution are successively joined in the triblock copolymer PEO-PPO-PEO aqueous solution successively through amino-acid modified concrete operations step, and then in above-mentioned solution, add amino acid, make the modified product of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material through reaction.The mass ratio of described amino acid and triblock copolymer PEO-PPO-PEO is 0.1～1: 1.
Triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material of the present invention can be used as pharmaceutical carrier, and recording specific surface area through the BET method is 50-200m
2/ g has higher drug loading (loading capacity of Ibuprofen BP/EP is 148 a milligrams/gram) and good sustained release performance to poorly water soluble drugs.Simultaneously, triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material of the present invention and preparation method thereof has the following advantages:
(1) the environmental protection raw material of the friendly type of environment for use can not pollute environment;
(2) preparation method at room temperature carries out, and is swift in response, and has quick synthetic advantage, has improved output efficiency, and has saved the energy;
(3) raw material is cheap and easy to get, and is easy to operate, and preparation technology is simple, do not need cost and complex equipment, is easy to realize suitability for industrialized production;
(4) the PEO-PPO-PEO/ calcium phosphate nanometer composite material particle diameter that makes is little, and specific surface area is bigger, is suitable for using as solid support material.
To sum up, compare with other method of the prior art, the structure of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material of the present invention is the vesicular structure of calcium phosphate coated triblock copolymer PEO-PPO-PEO, can be used as pharmaceutical carrier, poorly water soluble drugs is had higher drug loading and good sustained release performance, have wide purposes at biomedicine field.
Description of drawings
Preparation technology's schema of Fig. 1 triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material of the present invention.
The energy dispersal spectrogram (EDS) of the triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material that makes among Fig. 2 embodiment 1.
The infrared spectrogram of the triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material that makes among Fig. 3 embodiment 1 (FTIR).
The transmission electron microscope photo of the triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material that makes among Fig. 4 embodiment 1.
Fig. 5 has loaded the medicament slow release curve of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material in simulated body fluid of poorly water soluble drugs Ibuprofen BP/EP.
Embodiment
Further describe triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material of the present invention and preparation method thereof below by specific embodiment.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.
Further specify embodiment and effect with detail description embodiment.
Embodiment 1: preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
Compound concentration is the P123 dispersion soln of 2.5g/L, the CaCl of 0.5mol/L respectively
2(the NH of the aqueous solution and 0.5mol/L
4)
3PO
4The aqueous solution.
At room temperature, 0.100 gram P123 is added in 40 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the CaCl of 0.5 mol
2The aqueous solution, and then add (the NH that 0.9 ml concn is 0.5 mol
4)
3PO
4The aqueous solution obtains homodisperse suspension liquid.After reacting completely, use the centrifuging separated product, isolating product washes with water 3 times, and 60 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.Preparation flow figure as shown in fig. 1.
The energy dispersal spectrogram (EDS) of the PEO-PPO-PEO/ calcium phosphate nanometer composite material that makes in the present embodiment as shown in Figure 2, Fig. 2 illustrates the existence of calcium phosphate component in the nano composite material.
The infrared spectrogram (FTIR) of the PEO-PPO-PEO/ calcium phosphate nanometer composite material that makes in the present embodiment as shown in Figure 3, Fig. 3 has illustrated the existence of PEO-PPO-PEO component in the matrix material.
The transmission electron microscope photo of the PEO-PPO-PEO/ calcium phosphate nanometer composite material that makes in the present embodiment as shown in Figure 4, among Fig. 4 as can be seen: the grain diameter of matrix material is less than 100 nanometers, and has vesicular structure, and the aperture is less than 10 nanometers.
Embodiment 2: preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.100 gram P123 is added in 40 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 2.5 ml concns earlier in solution is the Ca (NO of 0.5 mol
3)
2The aqueous solution adds the Na that 1.5 ml concns are 0.5 mol then
3PO
4The aqueous solution obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 60 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Embodiment 3: preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.100 gram F127 is added in 20 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the Ca (CH of 0.5 mol
3COO)
2The aqueous solution, and then add (the NH that 0.9 ml concn is 0.5 mol
4)
2HPO
4The aqueous solution obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 60 ℃ of air dryings obtain the F127-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Embodiment 4: preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.200 gram P123 is added in 20 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the CaCl of 0.5 mol
2The aqueous solution, and then add the Na that 0.9 ml concn is 0.5 mol
2HPO
4The aqueous solution obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 60 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Embodiment 5: preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.100 gram F127 is added in 30 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 2.5 ml concns earlier in solution is the Ca (NO of 0.5 mol
3)
2The aqueous solution, and then add the NaH that 1.5 ml concns are 0.5 mol
2PO
4The aqueous solution obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 60 ℃ of air dryings obtain the F127-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Embodiment 6: preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.200 gram P123 is added in 200 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the CaCl of 0.5 mol
2The aqueous solution, and then add the NH that 0.9 ml concn is 0.002 mol
4H
2PO
4The aqueous solution obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 20 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Embodiment 7: the modified product of preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
Prepare triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material earlier, concrete preparation method is with embodiment 6.Then with 0.025g P123/ calcium phosphate nanometer composite material, 0.05g Macrogol 2000 0 is dispersed in 20 ml waters, stirred 5 hours, use the centrifuging separated product, isolating product washes with water 3 times, 60 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material after Macrogol 2000 0 surface modification.
Embodiment 8: preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.400 gram P123 is added in 200 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the CaCl of 0.002 mol
2The aqueous solution, and then add the NH that 0.9 ml concn is 0.01 mol
4H
2PO
4The aqueous solution obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 80 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Triblock copolymer PEO-PPO-PEO/the calcium phosphate nanometer composite material that makes is carried out modification to be handled, concrete modification procedure is: add the 0.1g arginine in above-mentioned reaction solution, other reaction parameters are constant, obtain the P123-calcium phosphate nanometer composite material after the amino acid surface modification.
Embodiment 9: the modified product of preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.400 gram P123 is added in 200 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the CaCl of 0.002 mol
2The aqueous solution, and then add the NH that 0.9 ml concn is 0.01 mol
4H
2PO
4The aqueous solution and 0.1g arginine obtain homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 80 ℃ of air dryings obtain the modified product of P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Embodiment 10: preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.200 gram P123 is added in 200 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the CaCl of 0.01 mol
2The aqueous solution, and then add the NH that 0.9 ml concn is 0.01 mol
4H
2PO
4The aqueous solution obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 100 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Embodiment 11: the modified product of preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.200 gram P123 is added in 200 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the CaCl of 0.01 mol
2The aqueous solution, and then add the NH that 0.9 ml concn is 0.01 mol
4H
2PO
4The acrylamide of the aqueous solution and 0.2g obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 100 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Embodiment 12: preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.400 gram P123 is added in 200 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the CaCl of 0.002 mol
2The aqueous solution, and then add the NH that 0.9 ml concn is 0.01 mol
4H
2PO
4The aqueous solution obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 80 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Triblock copolymer PEO-PPO-PEO/the calcium phosphate nanometer composite material that makes is carried out modification to be handled, concrete modification procedure is: add the 0.04g arginine in above-mentioned reaction solution, other reaction parameters are constant, obtain the P123-calcium phosphate nanometer composite material after the amino acid surface modification.
Embodiment 13: preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.400 gram P123 is added in 200 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the CaCl of 0.002 mol
2The aqueous solution, and then add the NH that 0.9 ml concn is 0.01 mol
4H
2PO
4The aqueous solution obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 80 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Triblock copolymer PEO-PPO-PEO/the calcium phosphate nanometer composite material that makes is carried out modification to be handled, concrete modification procedure is: add the 0.4g arginine in above-mentioned reaction solution, other reaction parameters are constant, obtain the P123-calcium phosphate nanometer composite material after the amino acid surface modification.
Embodiment 14: the modified product of preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.200 gram P123 is added in 200 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the CaCl of 0.01 mol
2The aqueous solution, and then add the NH that 0.9 ml concn is 0.01 mol
4H
2PO
4The acrylamide of the aqueous solution and 0.1g obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 100 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Embodiment 15: the modified product of preparation triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material
At room temperature, 0.200 gram P123 is added in 200 ml waters, the stirring at room dissolving obtains homodisperse solution.Adding 1.5 ml concns earlier in solution is the CaCl of 0.01 mol
2The aqueous solution, and then add the NH that 0.9 ml concn is 0.01 mol
4H
2PO
4The acrylamide of the aqueous solution and 0.4g obtains homodisperse suspension liquid.After reacting completely, take out product, use the centrifuging separated product, isolating product washes with water 3 times, and 100 ℃ of air dryings obtain the P123-calcium phosphate nanometer composite material.Analysis revealed, product pattern are the porous structure, and particle diameter is less than 100 nanometers.
Embodiment 16: triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material is used for the loading and the slowly-releasing of Ibuprofen BP/EP
Use the triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material that makes among the embodiment 1 to be used for the loading and the slowly-releasing of poorly water soluble drugs Ibuprofen BP/EP, step is as follows:
Load: it is 50ml that the triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material of 1g preparation joins volume, and concentration is in the Ibuprofen BP/EP hexane solution of 40mg/ml, shakes up 24 hours under the air-tight state.Then with the matrix material separation of medicine carrying, dry, compressing tablet (every 0.3 gram).
Slowly-releasing: compressing tablet is immersed 200ml respectively, and the pH value is in 7.4 the simulated body fluid, to shake up at 37 ℃.Take out the 2ml release medium every 2 hours, in former mixed solution, replenish the new simulated body fluid of 2ml simultaneously.The release medium of taking out has been carried out the ultra-violet absorption spectrum test, and the ultra-violet absorption spectrum during to 263 nanometers is analyzed and is drawn.The result as shown in Figure 5, Fig. 5 is the medicament slow release curve of PEO-PPO-PEO/ calcium phosphate nanometer composite material in simulated body fluid that has loaded the poorly water soluble drugs Ibuprofen BP/EP, and as seen from Figure 5: can reach 156 hours the time of releasing of having loaded the matrix material of Ibuprofen BP/EP.
Claims (10)
1, a kind of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material, the microscopic particles of described triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material are calcium phosphate coated triblock copolymer PEO-PPO-PEO structure; Wherein, in the total mass of nano composite material, the mass percent of triblock copolymer PEO-PPO-PEO is 5%～40%, and the mass percent of calcium phosphate is 60%～95%.
2, triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material described in claim 1 is characterized in that, the particle diameter of the microscopic particles of described triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material is 10～100nm; And the microscopic particles of described triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material has vesicular structure.
3, the preparation method of the described triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material of arbitrary claim in the claim 1 or 2 comprises the steps: successively solubility calcium salt brine solution and soluble phosphoric acid salt brine solution successively joined that reaction makes triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material in the triblock copolymer PEO-PPO-PEO aqueous solution.
4, the preparation method of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material described in claim 3, it is characterized in that, described soluble calcium salt is selected from calcium chloride, nitrocalcite or lime acetate, and described soluble phosphate is selected from ammonium phosphate, Secondary ammonium phosphate, primary ammonium phosphate, sodium phosphate, Sodium phosphate dibasic or SODIUM PHOSPHATE, MONOBASIC.
5, as the preparation method of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material as described in arbitrary claim in claim 3 or 4, it is characterized in that, in the described solubility calcium salt brine solution, the molecular volume concentration of soluble calcium salt is 0.002～0.2mol/L; In the described soluble phosphoric acid salt brine solution, the molecular volume concentration of soluble phosphate is 0.002～0.2mol/L.
6, the preparation method of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material described in claim 3, it is characterized in that, in the described triblock copolymer PEO-PPO-PEO aqueous solution, the mass concentration of triblock copolymer PEO-PPO-PEO is 1～10g/L.
7, the preparation method of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material described in claim 3, it is characterized in that, described reaction also needs reaction product is separated after making triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material, and separated products is washed and drying treatment.
8, in the claim 1 or 2 the described triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material of arbitrary claim in the application of biomedicine field.
9, a kind of modifier of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material, by the triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material described in the claim 1 through Macrogol 2000 0, acrylamide or amino-acid modified making.
10, the modifier of triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material described in the claim 9 is in the application of biomedicine field.
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| CN2009100548072A CN101613524B (en) | 2009-07-14 | 2009-07-14 | Triblock copolymer PEO-PPO-PEO/calcium phosphate nanometer composite material and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101787120A (en) * | 2010-03-04 | 2010-07-28 | 中国科学院宁波材料技术与工程研究所 | Triblock polyamino acid and hydrogel thereof |
| CN102102242A (en) * | 2010-12-31 | 2011-06-22 | 中国科学院上海硅酸盐研究所 | Method for preparing polylactic acid-amorphous calcium phosphate nano composite fiber material |
| CN103907159A (en) * | 2011-10-25 | 2014-07-02 | Lg伊诺特有限公司 | Paste composition for printing and touch panel |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1446590A (en) * | 2003-01-21 | 2003-10-08 | 华东理工大学 | New type cement with composite polypeptide/calcium phosphate being as framework |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101787120A (en) * | 2010-03-04 | 2010-07-28 | 中国科学院宁波材料技术与工程研究所 | Triblock polyamino acid and hydrogel thereof |
| CN102102242A (en) * | 2010-12-31 | 2011-06-22 | 中国科学院上海硅酸盐研究所 | Method for preparing polylactic acid-amorphous calcium phosphate nano composite fiber material |
| CN103907159A (en) * | 2011-10-25 | 2014-07-02 | Lg伊诺特有限公司 | Paste composition for printing and touch panel |
| CN103907159B (en) * | 2011-10-25 | 2017-03-29 | Lg伊诺特有限公司 | For the paste composition and touch pad of printing |
| US9818498B2 (en) | 2011-10-25 | 2017-11-14 | Lg Innotek Co., Ltd. | Paste composition for printing and touch panel |
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| CN101613524B (en) | 2011-03-16 |
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