CN100548465C - High molecular microcapsule of multiple response and preparation method thereof - Google Patents
High molecular microcapsule of multiple response and preparation method thereof Download PDFInfo
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- CN100548465C CN100548465C CNB2007100399986A CN200710039998A CN100548465C CN 100548465 C CN100548465 C CN 100548465C CN B2007100399986 A CNB2007100399986 A CN B2007100399986A CN 200710039998 A CN200710039998 A CN 200710039998A CN 100548465 C CN100548465 C CN 100548465C
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Abstract
The invention belongs to the high molecular microcapsule and preparation method thereof of the multiple response of bio-medical material technical field.There are single or some little holes in micro-capsule of the present invention inside, normal pressure is saturated in the hole biologically inert gas, there is polymeric membrane to intercept mutually between hole and the hole, inorganic nano-particle combines with macromolecular chain by Van der Waals force, twined parcel by macromolecular chain, and be present in the shell and inner membrance of high score ascus.The present invention also provides the preparation method of the high molecular microcapsule of above-mentioned multiple response.The high molecular microcapsule of the multiple response of preparation method of the present invention and acquisition, but the multi-functional inorganic nano-particle of embedding also can wrap up gas to be used for ultrasonic contrast.High molecular microcapsule diverse in function of the present invention, range of application is also wide.The present invention has broad application prospects in fields such as medical treatment, biochemistry.
Description
Technical field
What the present invention relates to is high molecular microcapsule of high molecular microcapsule of a kind of bio-medical material technical field and preparation method thereof, particularly a kind of multiple response and preparation method thereof.
Background technology
Material is carried out encapsulatedly can realizing many purposes: improve Stability of Substance; Separate immiscible composition; Make material avoid the influence of environment; Parcel fragrance, taste, agricultural chemicals, adhesive, organized enzyme, living cells, medicament, ink and dyestuff etc.; Liquid is changed into solid; Active component is controlled release; Make medicine have target function; Adverse effect that the minimizing noxious material causes environment or the like.Thereby microcapsules technology is noticeable day by day, and growing with each passing day in the Study on Microencapsulation field, spreads to nearly all chemical system.When gas or gas precursor are encapsulated in the microvesicle that is formed by protein, surfactant, liposome, carbohydrate or various natural, synthetic macromolecule, can be used as the medical ultrasonic contrast preparation.It produces the radiography effect by changing organization ultrasonic acoustic characteristic (as backscattering coefficient, the velocity of sound and nonlinear effect etc.), is used for the supply of blood flow situation inspection of interior many vitals (as liver, kidney, uterus, ovary etc.) of human body and cardiovascular system etc.With the macromolecular material is the gas microbubbles of shell, is the material that has future in the acoustic contrast agent development.And inorganic nano-particle has the performance of many excellences, is having a wide range of applications aspect biotechnology, medical diagnosis and the treatment.Such as semiconductor nano,,, can be used on aspects such as biomolecular labeling and detection, bio-separation as fluorescent marker because quantum size effect has special optical effect; Metal, ferrite nano material are because functions such as the thermo-responsive that nanometer size effect caused, superparamagnetism can be applicable to biomedical the detection and the treatment aspect.Therefore, inorganic nano-particle is combined with microcapsules, have more wide application prospect.
Find through literature search prior art, Chinese invention patent publication number CN1669629A, name is called the patent of " method for preparing inorganic-organic hybridization nano microcapsule that with the polymer is nuclear ", proposition is a template with the synthetic organic polymer of emulsion polymerisation, in shell, introduce double bond containing siloxanyl monomers and vinyl monomer copolymerization, and generation hydrolysis-condensation reaction in copolymerization, form the inorganic network of Si-O-Si, it promptly is the hud typed emulsion particle of polymer core-hydridization shell, then, the organic polymer template that remains in the hud typed emulsion particle is removed by solvent-extracted method.Defective is: independent high molecular microcapsule function is more single, and range of application is also narrower; Simultaneously, the micro-capsule that is obtained by this method is difficult to the multi-functional inorganic nano-particle of embedding, also should not wrap up gas to be used for ultrasonic contrast.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, high molecular microcapsule of a kind of multiple response and preparation method thereof is provided.The high molecular microcapsule of the multiple response of preparation method of the present invention and acquisition, but the multi-functional inorganic nano-particle of embedding also can wrap up gas to be used for ultrasonic contrast.High molecular microcapsule diverse in function of the present invention, range of application is also wide.
Multiple response high molecular microcapsule of the present invention is achieved through the following technical solutions, and there are single or some holes high molecular microcapsule inside, in the hole normal pressure saturated biologically inert gas; There is polymeric membrane to intercept mutually between hole and the hole; Inorganic nano-particle combines with macromolecular chain by Van der Waals force, is present in the shell and inner membrance of high molecular microcapsule, twines parcel by macromolecular chain.
Described macromolecule, the mass percentage content of its material are 50%～99%.
Described micro-capsule, its average grain diameter is between 1 μ m～10 μ m, and wall thickness is 200nm～2000nm, and the number of inner cavity is 1～10.
Described inorganic nano-particle, its mass percentage content are 1%～50%.
The polymer matrix of described micro-capsule satisfies oil-soluble and gets final product, for natural or synthetic, can biodegradation etc. and have no special requirements.Can be selected from the lipophile macromolecular material or contain the copolymer of lipophile segment, comprise polyethylene, polypropylene, polyvinyl chloride, polytetrafluoroethylene (PTFE), polymethyl methacrylate, polyethyl methacrylate, polyvinyl acetate, poly (glycidyl methacrylate), polystyrene, Merlon, polyamide polybutylcyanoacrylate, poe, polyaminoacid, aliphatic polyester etc.; Aliphatic polyester can be the binary between polylactide, polycaprolactone, lactone or ternary is random or block copolymer, lactone and polyethers between binary or ternary is random or block copolymer etc.
The described inorganic nano-particle that is wrapped up by macromolecular material is meant the oil-soluble inorganic particulate with specific functions such as magnetic, fluorescence, fuel factors of average grain diameter between 1nm～50nm, be coated with metal or the semiconductor nano particle and the magnetic nano-particle of non-polar group as the surface, specifically comprise Au, Ag, CdS, CdSe, CdTe, InP, InAs, CdSe/CdS, CdSe/ZnS, CdSe/ZnSe, CdTe/ZnS, CdTeSe, Fe
3O
4, γ-Fe
2O
3, Co-Fe
3O
4, Ni-Fe
3O
4In one or more combination.
Saturated biologically inert gas is the fluorine carbon or the fluorine sulphur gas of high density, HMW, low dispersivity and low blood saturation degree in the described inner cavity, comprises one or more the combination in sulfur hexafluoride, octafluoropropane, octafluorobutane, ten fluorine butane, octafluoro pentane, R-4112, octafluoro hexane, the Tetradecafluorohexane.
The characteristics and the principle of multiple response high molecular microcapsule of the present invention are:
For realizing the feature structure of this high molecular microcapsule, utilize the characteristics of W/O/W double emulsion.Inner water droplet is as " predecessor " in hole, and outside water is a suspension media, dissolving dispersed polymer material and inorganic nano-particle in the oil phase liquid film between the inside and outside water.By interface deposition principle, the oil phase liquid film is solidified, thereby the macromolecular material film forming becomes shell again, inorganic nano-particle is twined parcel by macromolecular chain.Inner water droplet is removed in decompression distillation at last, obtains inner cavity, and in the hole the saturated biologically inert gas of normal pressure.Thereby the feature structure and the composition of this hybrid inorganic-organic high molecular microcapsule have been realized.This technology of preparing combines microencapsulation process and hydridization process (hydridization of inorganic nano-particle and macromolecular material) together, and a step is realized inner cavity and hybrid inorganic-organic structure.The hollow rate of high score bulbec and the size of inner cavity and number can be easily by the volume-adjustment of inner water, and the apparent size of micro-capsule can be controlled by the concentration of the protective colloid aqueous solution, the conditions such as power of emulsification mechanical force.
The beneficial effect of multiple response high molecular microcapsule of the present invention:
The present invention combines microcapsules technology, acoustic contrast agent technology of preparing with the function of inorganic nano-particle, a kind of multiple response high molecular microcapsule that has ultrasonic contrast and inorganic nano-particle subfunction concurrently is provided, it has corresponding responsive feedback for outside stimulus such as sound, magnetic, light, heat, can be applicable to many each fields such as medical treatment, medicine, biochemistry.
The preparation method of the high molecular microcapsule of the multiple response that the present invention relates to specifically comprises the steps:
(1) prepare the organic solution that macromolecular material mixes with inorganic nano-particle, wherein the concentration of macromolecular material and inorganic nano-particle is respectively 10mg/mL-200mg/mL and 0.5mg/mL-10mg/mL;
(2) with the above-mentioned mixed solution of 2～20 times of volumes of water injection, stir 1min-5min, make water-in-oil emulsion with 10000rpm-25000rpm;
(3) the preparation mass percent concentration is the protective colloid aqueous solution of 0.5%-5%, and the protective colloid solution with 1～10 times of volume of water-in-oil emulsion injection stirs 5min-10min with 5000rpm-20000rpm, makes the W/O/W double emulsion;
(4) double emulsion is mixed with the water of equal volume, stir 1h-6h with 100rpm-1000rpm;
(5) centrifugal collection micro-capsule is washed 1-2 time, nonpolar lotion and is washed 1-3 time, and negative pressure charges into biologically inert gas after the freeze drying, obtains pulverous multiple response high molecular microcapsule.
Organic solvent described in the step (1) is that boiling point is lower than 100 ℃, and solvent that can not be miscible with water comprises benzene, cyclohexane, ether, carbon tetrachloride, chloroform, carrene, halo ethane etc., but is not limited to above-mentioned several material.
Protective colloid described in the step (3) is natural or artificial synthetic water soluble polymer, comprises gelatin and derivative thereof, polyvinyl alcohol, hydroxyethylcellulose, hydroxypropyl cellulose, glucan, shitosan etc., but is not limited to above-mentioned several material.
Nonpolar lotion described in the step (5) is meant and can dissolves the lipophile inorganic nano-particle that does not wrap into, and do not dissolve the solvent of macromolecular material, as one or more the combination in n-hexane, dodecane, chlorinated dodecane, atoleine, toluene, dimethylbenzene, the parachlorotoluene, but be not limited to above-mentioned several material.
Preparation method's of the present invention characteristics:
The kind of size, the wall thickness that the present invention can be by regulating micro-capsule, the kind of macromolecular material and molecular weight, inorganic nano-particle and consumption etc. change the ultrasonic acoustic characteristic of micro-capsule; Can also make micro-capsule possess magnetic (nuclear-magnetism), light (fluorescence), heat single or multiple functions such as (infrared) by one or more inorganic nano-particle of parcel form.This multiple response high molecular microcapsule has overcome the shortcoming of traditional microcapsular ultrasound contrast agent function singleness; Simultaneously, the utilization of the similar principle that mixes has realized the mutual matched combined of the inorganic nano-particle of difference in functionality the response performance of micro-capsule being regulated and control according to the actual requirements; The potentiality that the inner cavity structure makes that micro-capsule possesses also that catalyst is loaded with, the control of medicine and other materials discharges.
Preparation method's of the present invention beneficial effect:
This method needn't be regulated pH value and heating and cooling tempestuously, does not also need special reaction reagent, and for the emulsion isoreactivity material of enzyme, hemoglobin, photography usefulness, all available this method microencapsulation can not cause any qualitative change in encapsulation process.Multiple response polymeric capsule of the present invention can be used as general medical science contrast preparation, is applicable to the angiographic diagnosis of ultrasonic, X-CT and nuclear-magnetism simultaneously; Or be used for therapeutic treatment magnetic therapy, thermotherapy, medicine and gene target etc.
The specific embodiment
Below embodiments of the invention are elaborated: present embodiment is being to implement under the prerequisite with the technical solution of the present invention, provided detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.
Embodiment 1
Present embodiment 1 is implemented under following implementation condition and specification requirement condition:
(1) with the 0.2g molecular weight is 500,000 PLLA and 200mg Fe
3O
4Magnetic nano-particle is dissolved in the 20mL chloroform; Preparation 30mL 0.5% (mass percent concentration) polyvinyl alcohol water solution is standby down together;
(2) the 10mL distilled water is injected above-mentioned mixed solution, stir 1min with 10000rpm and obtain water-in-oil emulsion;
(3) above-mentioned water-in-oil emulsion is injected the polyvinyl alcohol water solution prepared (volume ratio by water-in-oil emulsion and protective colloid solution is 1: 1-1: 10, down with), with 5000rpm stirring 5min, obtain double emulsion;
(4) the above-mentioned double emulsion of 60ml is mixed with 60mL water, stir 4h with 400rpm;
(5) centrifugal collection micro-capsule, distillation washing 1 time, n-hexane are washed 3 times, and negative pressure charges into sulfur hexafluoride gas after the freeze drying, promptly gets Powdered micro-capsule.
Obtain the ultrasonic high molecular microcapsule with magnetic responsiveness of having of brown powder shape, its average grain diameter is 10 μ m, the about 200nm of wall thickness, the quality percentage composition of macromolecular material is about 50%, the quality percentage composition of inorganic nano-particle is about 50%, in fill sulfur hexafluoride gas.
Embodiment 2
Present embodiment 2 is implemented under following implementation condition and specification requirement condition:
(1) with the 2g molecular weight is 100,000 poly-DL lactic acid and 100mg γ-Fe
2O
3Magnetic nano-particle is dissolved in the 20mL carrene; The polyvinyl alcohol water solution of preparation 200mL 2% is standby;
(2) the 2mL distilled water is injected above-mentioned mixed solution, stir 2min with 15000rpm and obtain water-in-oil emulsion;
(3) above-mentioned water-in-oil emulsion is injected the polyvinyl alcohol water solution of having prepared, stir 4min, obtain double emulsion with 10000rpm;
(4) the above-mentioned double emulsion of 220mL is mixed with 220mL water, stir 6h with 800rpm;
(5) centrifugal collection micro-capsule, distillation washing 2 times, n-hexane are washed 1 time, negative pressure charges into sulfur hexafluoride gas after the freeze drying, both Powdered micro-capsule.
Obtain the ultrasonic high molecular microcapsule with magnetic responsiveness of having of brown powder shape, its average grain diameter is 4 μ m, the about 1000nm of wall thickness, the quality percentage composition of macromolecular material is about 95%, the quality percentage composition of inorganic nano-particle is about 5%, in fill sulfur hexafluoride gas.
Embodiment 3
Present embodiment 3 is implemented under following implementation condition and specification requirement condition:
(1) with the 0.5g molecular weight be 350,000 poly-third hand over glycolide and 150mg CdSe is nanocrystalline is dissolved in the 20mL chloroform; The aqueous gelatin solution of preparation 60mL 1% is standby;
(2) the 8mL distilled water is injected above-mentioned mixed solution, stir 2min with 15000rpm and obtain water-in-oil emulsion;
(3) above-mentioned water-in-oil emulsion is injected the aqueous gelatin solution of having prepared, stir 5min, obtain double emulsion with 10000rpm;
(4) the above-mentioned double emulsion of 90mL is mixed with 90mL water, stir 2h with 800rpm;
(5) centrifugal collection micro-capsule, distillation washing 1 time, n-hexane are washed 2 times, and negative pressure charges into octafluoropropane gas after the freeze drying, promptly gets Powdered micro-capsule.
Obtain the ultrasonic high molecular microcapsule with optical Response of having of pink powder shape, its average grain diameter is 8 μ m, the about 2000nm of wall thickness, the quality percentage composition about 75% of macromolecular material, the quality percentage composition of inorganic nano-particle is about 25%, in fill octafluoropropane gas.
Embodiment 4
Present embodiment 4 is implemented under following implementation condition and specification requirement condition:
(1) with the 1.5g molecular weight is 450,000 polycaprolactone and 200mg CdTe is nanocrystalline is dissolved in the 20mL carrene; The aqueous gelatin solution of preparation 100mL 0.5% is standby;
(2) the 5mL distilled water is injected above-mentioned mixed solution, stir 3min with 25000rpm and obtain water-in-oil emulsion;
(3) above-mentioned water-in-oil emulsion is injected the aqueous gelatin solution of having prepared, stir 7min, obtain double emulsion with 15000rpm;
(4) the above-mentioned double emulsion of 125mL is mixed with 125mL water, stir 3h with 500rpm;
(5) centrifugal collection micro-capsule, distillation washing 2 times, n-hexane are washed 3 times, and negative pressure charges into octafluoropropane gas after the freeze drying, promptly gets Powdered micro-capsule.
Obtain the ultrasonic high molecular microcapsule with optical Response of having of pink powder shape, its average grain diameter is 10 μ m, the about 2000nm of wall thickness, the quality percentage composition about 85% of macromolecular material, the quality percentage composition of inorganic nano-particle is about 15%, in fill octafluoropropane gas.
Embodiment 5
Present embodiment 5 is implemented under following implementation condition and specification requirement condition:
(1) with the 1g molecular weight is 200,000 polypropylene, 50mg Fe
3O
4Magnetic nano-particle and 50mgCdTe are nanocrystalline to be dissolved in the 20mL carrene; The hydroxyethyl cellulose aqueous solution of preparation 125mL 2% is standby;
(2) the 5mL distilled water is injected above-mentioned mixed solution, stir 3min with 15000rpm and obtain water-in-oil emulsion;
(3) above-mentioned water-in-oil emulsion is injected the hydroxyethyl cellulose aqueous solution of having prepared, stir 7min, obtain double emulsion with 10000rpm;
(4) the above-mentioned double emulsion of 150mL is mixed with 150mL water, stir 1h with 1000rpm;
(5) centrifugal collection micro-capsule, distillation washing 1 time, n-hexane are washed 1 time, negative pressure charges into ten fluorine butane gas after the freeze drying, both Powdered micro-capsule.
Obtain coffee-like pulverous high molecular microcapsule with ultrasonic, magnetic and light multiple response, its average grain diameter is 5 μ m, the about 1000nm of wall thickness, the quality percentage composition about 90% of macromolecular material, the quality percentage composition of inorganic nano-particle is about 10%, in fill ten fluorine butane gas.
Embodiment 6
Present embodiment 6 is implemented under following implementation condition and specification requirement condition:
(1) with the 2g molecular weight is 200,000 Merlon, 120mg γ-Fe
2O
3Magnetic nano-particle and 80mgAu nano particle are dissolved in the 20mL dichloroethanes; The hydroxyethyl cellulose aqueous solution of preparation 200mL 3% is standby;
(2) the 10mL distilled water is injected above-mentioned mixed solution, stir 1min with 20000rpm and obtain water-in-oil emulsion;
(3) above-mentioned water-in-oil emulsion is injected the hydroxyethyl cellulose aqueous solution of having prepared, stir 5min, obtain double emulsion with 15000rpm;
(4) the above-mentioned double emulsion of 230mL is mixed with 230mL water, stir 6h with 5000rpm;
(5) centrifugal collection micro-capsule, distillation washing 2 times, n-hexane are washed 2 times, and negative pressure charges into ten fluorine butane gas after the freeze drying, promptly gets Powdered micro-capsule.
Obtain coffee-like pulverous high molecular microcapsule with ultrasonic, magnetic and hot multiple response, its average grain diameter is 3 μ m, the about 500nm of wall thickness, the quality percentage composition about 91% of macromolecular material, the quality percentage composition of inorganic nano-particle is about 9%, in fill ten fluorine butane gas.
Embodiment 7
Present embodiment 7 is implemented under following implementation condition and specification requirement condition:
(1) be that 100,000 polyvinyl chloride and 50mg Ag nano particle are dissolved in the 20mL dichloroethanes with the 2g molecular weight; The hydroxypropyl cellulose aqueous solution of preparation 160mL 3% is standby;
(2) the 2mL distilled water is injected above-mentioned mixed solution, stir 4min with 20000rpm and obtain water-in-oil emulsion;
(3) above-mentioned water-in-oil emulsion is injected the hydroxypropyl cellulose aqueous solution of having prepared, stir 7min, obtain double emulsion with 15000rpm;
(4) the above-mentioned double emulsion of 180mL is mixed with 180mL water, stir 2h with 100rpm;
(5) centrifugal collection micro-capsule, distillation washing 1 time, n-hexane are washed 3 times, and negative pressure charges into R-4112 gas after the freeze drying, promptly gets Powdered micro-capsule.
Obtain the ultrasonic high molecular microcapsule with thermo-responsive of having of pink powder shape, its average grain diameter is 3 μ m, the about 1000nm of wall thickness, the quality percentage composition about 95% of macromolecular material, the quality percentage composition of inorganic nano-particle is about 5%, in fill R-4112 gas.
Embodiment 8
Present embodiment 8 is implemented under following implementation condition and specification requirement condition:
(1) be that 200,000 polyaminoacid and 200mg Au nano particle are dissolved in the 20mL carrene with the 1g molecular weight; The hydroxypropyl cellulose aqueous solution of preparation 80mL 5% is standby;
(2) the 4mL distilled water is injected above-mentioned mixed solution, stir 2min with 25000rpm and obtain water-in-oil emulsion;
(3) above-mentioned water-in-oil emulsion is injected the hydroxypropyl cellulose aqueous solution of having prepared, stir 10min, obtain double emulsion with 20000rpm;
(4) the above-mentioned double emulsion of 100mL is mixed with 100mL water, stir 5h with 1000rpm;
(5) centrifugal collection micro-capsule, distillation washing 2 times, n-hexane are washed 1 time, and negative pressure charges into R-4112 gas after the freeze drying, promptly gets Powdered micro-capsule.
Obtain the ultrasonic high molecular microcapsule with thermo-responsive of having of pink powder shape, its average grain diameter is 1 μ m, the about 200nm of wall thickness, the quality percentage composition about 80% of macromolecular material, the quality percentage composition of inorganic nano-particle is about 20%, in fill R-4112 gas.
Embodiment 9
Present embodiment 9 is implemented under following implementation condition and specification requirement condition:
(1) with the 4g molecular weight is 50,000 nanocrystalline being dissolved in the 20mL dichloroethanes of polymethyl methacrylate, 3mgAu nano particle and 7mgCdSe; The glucan aqueous solution of preparation 200mL 5% is standby;
(2) the 1mL distilled water is injected above-mentioned mixed solution, stir 5min with 25000rpm and obtain water-in-oil emulsion;
(3) above-mentioned water-in-oil emulsion is injected the glucan aqueous solution of having prepared, stir 10min, obtain double emulsion with 20000rpm;
(4) the above-mentioned double emulsion of 220mL is mixed with 220mL water, stir 3h with 200rpm;
(5) centrifugal collection micro-capsule, distillation washing 1 time, n-hexane are washed 2 times, and negative pressure charges into Tetradecafluorohexane gas after the freeze drying, promptly gets Powdered micro-capsule.
Obtain that having of pink powder shape is ultrasonic, the high molecular microcapsule of light and hot multiple response, its average grain diameter is 1 μ m, the about 300nm of wall thickness, the quality percentage composition about 99% of macromolecular material, the quality percentage composition of inorganic nano-particle is about 1%, in fill Tetradecafluorohexane gas.
Embodiment 10
Present embodiment 10 is implemented under following implementation condition and specification requirement condition:
(1) with the 1g molecular weight is 300,000 nanocrystalline being dissolved in the 20mL chloroform of poe, 2mgAg nano particle and 8mgCdTe; The glucan aqueous solution of preparation 200mL 0.5% is standby;
(2) the 5mL distilled water is injected above-mentioned mixed solution, to obtain water-in-oil emulsion behind the 15000rpm stirring 2min;
(3) above-mentioned water-in-oil emulsion is injected the glucan aqueous solution of having prepared, stir 5min, obtain double emulsion with 10000rpm;
(4) the above-mentioned double emulsion of 220mL is mixed with 220mL water, stir 6h with 400rpm;
(5) centrifugal collection micro-capsule, distillation washing 2 times, n-hexane are washed 3 times, and negative pressure charges into Tetradecafluorohexane gas after the freeze drying, promptly gets Powdered micro-capsule.
Obtain that having of pink powder shape is ultrasonic, the high molecular microcapsule of light and hot multiple response, its average grain diameter is 10 μ m, the about 1000nm of wall thickness, the quality percentage composition about 98% of macromolecular material, the quality percentage composition of inorganic nano-particle is about 2%, in fill Tetradecafluorohexane gas.
Claims (9)
1. the high molecular microcapsule of a multiple response is characterized in that, there are single or some holes high molecular microcapsule inside, in the hole normal pressure saturated biologically inert gas; There is the macromolecule inner membrance to intercept mutually between hole and the hole; Inorganic nano-particle combines with macromolecular chain by Van der Waals force, is present in the shell and macromolecule inner membrance of high molecular microcapsule, twines parcel by macromolecular chain;
Described biologically inert gas is the fluorine carbon or the fluorine sulphur gas of high density, HMW, low dispersivity and low blood saturation degree, comprises one or more the combination in sulfur hexafluoride, octafluoropropane, octafluorobutane, ten fluorine butane, octafluoro pentane, R-4112, octafluoro hexane, the Tetradecafluorohexane.
2. the high molecular microcapsule of multiple response according to claim 1 is characterized in that, described micro-capsule, and its average grain diameter is between 1 μ m～10 μ m, and wall thickness is 200nm～2000nm, and the number of inner cavity is 1～10.
3. the high molecular microcapsule of multiple response according to claim 1 is characterized in that, described inorganic nano-particle, and its mass percentage content is 1%～50%.
4. the high molecular microcapsule of multiple response according to claim 1, it is characterized in that, the polymer matrix of described micro-capsule is lipophile macromolecule or the copolymer that contains the lipophile segment, comprises polyethylene, polypropylene, polyvinyl chloride, polytetrafluoroethylene (PTFE), polymethyl methacrylate, polyethyl methacrylate, polyvinyl acetate, poly (glycidyl methacrylate), polystyrene, Merlon, polyamide polybutylcyanoacrylate, poe, polyaminoacid or aliphatic polyester; Its aliphatic polyester comprises the binary between polylactide, polycaprolactone, lactone or ternary is random or block copolymer or lactone and polyethers between binary or ternary is random or block copolymer.
5. according to the high molecular microcapsule of claim 1 or 3 described multiple responses, it is characterized in that, described inorganic nano-particle is meant the oil-soluble inorganic particulate of average grain diameter between 1nm～50nm, comprises Au, Ag, CdS, CdSe, CdTe, InP, InAs, CdSe/CdS, CdSe/ZnS, CdSe/ZnSe, CdTe/ZnS, CdTeSe, Fe
3O
4, γ-Fe
2O
3, Co-Fe
3O
4, Ni-Fe
3O
4In one or more combination.
6. the preparation method of the high molecular microcapsule of a multiple response as claimed in claim 1 is characterized in that, specifically comprises the steps:
(1) prepare the organic solution that macromolecular material mixes with inorganic nano-particle, wherein the concentration of macromolecular material and inorganic nano-particle is respectively 10mg/mL-200mg/mL and 0.5mg/mL-10mg/mL;
(2) with the above-mentioned mixed solution of 2～20 times of volumes of water injection, stir 1min-5min, make water-in-oil emulsion with 10000rpm-25000rpm;
(3) the preparation mass percent concentration is the protective colloid aqueous solution of 0.5%-5%, and the protective colloid solution with 1～10 times of volume of water-in-oil emulsion injection stirs 5min-10min with 5000rpm-20000rpm, makes the W/O/W double emulsion;
(4) double emulsion is mixed with the water of equal volume, stir 1h-6h with 100rpm-1000rpm;
(5) centrifugal collection micro-capsule is washed 1-2 time, nonpolar lotion and is washed 1-3 time, and negative pressure charges into biologically inert gas after the freeze drying, obtains pulverous multiple response high molecular microcapsule;
Described biologically inert gas is the fluorine carbon or the fluorine sulphur gas of high density, HMW, low dispersivity and low blood saturation degree, comprises one or more the combination in sulfur hexafluoride, octafluoropropane, octafluorobutane, ten fluorine butane, octafluoro pentane, R-4112, octafluoro hexane, the Tetradecafluorohexane.
7. the preparation method of the high molecular microcapsule of multiple response according to claim 6 is characterized in that, the organic solvent in the described step (1) is benzene, cyclohexane, ether, carbon tetrachloride, chloroform, carrene or halo ethane.
8. the preparation method of the high molecular microcapsule of multiple response according to claim 6 is characterized in that, the protective colloid described in the step (3) is gelatin or derivatives thereof, polyvinyl alcohol, hydroxyethylcellulose, hydroxypropyl cellulose, glucan or shitosan.
9. the preparation method of the high molecular microcapsule of multiple response according to claim 6, it is characterized in that the nonpolar lotion described in the step (5) is meant one or more the combination in n-hexane, dodecane, chlorinated dodecane, atoleine, toluene, dimethylbenzene, the parachlorotoluene.
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| CN103483832B (en) * | 2013-09-16 | 2015-07-22 | 天津理工大学 | Preparation method for quasi-block copolymer inverse macromolecule micelle |
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| CN104383562A (en) * | 2014-11-03 | 2015-03-04 | 中国科学院化学研究所 | Multimode imaging contrast agent and preparation method and application thereof |
| CN105456229A (en) * | 2015-12-22 | 2016-04-06 | 华南理工大学 | Chitosan ultrasound microbubble for treating strictured lumen tissue in human body and preparation method of chitosan ultrasound microbubble |
| CN108251069B (en) * | 2018-02-12 | 2020-11-20 | 吉林大学 | Method for preparing phase change energy storage microcapsule shell material by using graphite waste polystyrene |
| CN109082120B (en) * | 2018-09-28 | 2021-06-01 | 华南协同创新研究院 | Elastic shell microcapsule phase change material and preparation method and application thereof |
| CN110327856B (en) * | 2019-07-13 | 2021-08-10 | 武汉中科先进技术研究院有限公司 | Preparation method of microcapsule with meteorite crater structure |
| CN111504855A (en) * | 2020-04-14 | 2020-08-07 | 王阳 | Method for preparing multifunctional multi-site tracing nanoparticles |
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