CN110917387A - Developable embolism microsphere and preparation method thereof - Google Patents
Developable embolism microsphere and preparation method thereof Download PDFInfo
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- CN110917387A CN110917387A CN201911230003.3A CN201911230003A CN110917387A CN 110917387 A CN110917387 A CN 110917387A CN 201911230003 A CN201911230003 A CN 201911230003A CN 110917387 A CN110917387 A CN 110917387A
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- 239000004005 microsphere Substances 0.000 title claims abstract description 63
- 208000005189 Embolism Diseases 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000004372 Polyvinyl alcohol Substances 0.000 claims abstract description 24
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 24
- 229910052797 bismuth Inorganic materials 0.000 claims abstract description 23
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims abstract description 23
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims abstract description 20
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims abstract description 17
- 229940057995 liquid paraffin Drugs 0.000 claims abstract description 14
- 239000004094 surface-active agent Substances 0.000 claims abstract description 12
- 238000010557 suspension polymerization reaction Methods 0.000 claims abstract description 4
- 238000005516 engineering process Methods 0.000 claims abstract description 3
- 230000010102 embolization Effects 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- 239000011259 mixed solution Substances 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 230000003073 embolic effect Effects 0.000 claims description 3
- 230000020477 pH reduction Effects 0.000 claims description 3
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical group CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 claims description 2
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims 1
- 229910001451 bismuth ion Inorganic materials 0.000 description 7
- 238000003384 imaging method Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 239000002105 nanoparticle Substances 0.000 description 4
- 230000007547 defect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000003760 magnetic stirring Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000005191 phase separation Methods 0.000 description 3
- 229920001661 Chitosan Polymers 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000010923 batch production Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 239000002872 contrast media Substances 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000004626 scanning electron microscopy Methods 0.000 description 2
- 238000005245 sintering Methods 0.000 description 2
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 2
- 229910052721 tungsten Inorganic materials 0.000 description 2
- 239000010937 tungsten Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000002805 bone matrix Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229960004359 iodixanol Drugs 0.000 description 1
- NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 description 1
- 229960001025 iohexol Drugs 0.000 description 1
- NTHXOOBQLCIOLC-UHFFFAOYSA-N iohexol Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NTHXOOBQLCIOLC-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002405 nuclear magnetic resonance imaging agent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000012876 topography Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic materials
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
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Abstract
The invention discloses a developable embolism microsphere and a preparation method thereof, wherein the embolism microsphere is prepared by polyvinyl alcohol, β -tricalcium phosphate, nano bismuth and glutaraldehyde through an inverse suspension polymerization technology, wherein a continuous phase comprises liquid paraffin and a surfactant, and a disperse phase comprises polyvinyl alcohol, β -tricalcium phosphate, nano bismuth and glutaraldehyde, wherein the dosage ratio of the polyvinyl alcohol, β -tricalcium phosphate, the nano bismuth and the glutaraldehyde is 10: 1-2: 0.1-0.8: 0.7-1.25 by weight.
Description
Technical Field
The invention relates to the technical field of medical science of nuclear magnetic resonance contrast agents, in particular to a developable embolism microsphere and a preparation method thereof.
Background
Currently, in interventional embolization surgery, commercially available contrast agents in wide clinical use include iohexol, iodixanol, and the like. The contrast agent is mixed with embolism microsphere and injected into human body, and the microsphere has better imaging ability due to the existence of iodine element. However, when these commercial imaging agents are mixed with the embolic microspheres, two phases may separate, and the imaging result cannot accurately represent the actual position of the embolic microspheres, which brings certain misdiagnosis factors and adverse factors to diagnosis.
However, the prior embolization microsphere with the self-developing function has certain defects and needs to be improved, and the preparation process of the prior embolization microsphere is complex, for example, in CN106890606A, a method for preparing porous β -TCP microspheres with different particle sizes by oil-in-water solid emulsification, which comprises the steps of dispersing an oil phase in a water phase, wherein the oil phase is an internal phase, and the water is a dispersed phase, sintering the mixture to obtain the β -TCP microspheres, wherein the time consumption is long, the operation process is complex, for example, the record of Qingfeng and the like in the 'influence of chitosan crosslinking characteristics on the balling property of the chitosan/β -TCP microspheres' includes the steps of firstly carrying out primary crosslinking by glutaraldehyde, carrying out secondary crosslinking after a series of operations, finally washing by chloroform, extracting by ethanol for 10 hours, and drying to obtain the dried microspheres.
The existing process for preparing β -TCP microspheres is complex in process, sintering or secondary crosslinking is needed in the preparation process, the time consumption is long, the mass production is not convenient to realize, and the existing process needs to be combined with a commercial developer for use and has no self-developing effect.
Disclosure of Invention
The invention aims to provide a developable embolism microsphere. The embolism microsphere improves the accuracy of real-time imaging of interventional embolism treatment by introducing bismuth into the embolism microsphere, reduces misdiagnosis caused by phase separation, and provides a new design scheme for the imageable embolism microsphere. Meanwhile, bismuth ions can be discharged in vivo, and compared with iodine elements, the bismuth ions are safer; meanwhile, the embolism is simple in process, short in preparation time and easy to realize batch production; and the microspheres are added with TCP materials, so that the biocompatibility of the microspheres is improved.
It is another object of the present invention to provide a method for preparing the developable embolization microspheres.
The above object of the present invention is achieved by the following scheme:
a kind of developable embolism microballoon, prepared from polyvinyl alcohol, β -tricalcium phosphate, nanometer bismuth and glutaraldehyde through the reversed phase suspension polymerization technique, wherein the continuous phase is liquid paraffin and surfactant, the disperse phase is polyvinyl alcohol, β -tricalcium phosphate, nanometer bismuth and glutaraldehyde;
the polyvinyl alcohol, β -tricalcium phosphate, nano bismuth and glutaraldehyde are used in a ratio of 10: 1-2: 0.1-0.8: 0.7-1.25 by weight.
β -tricalcium phosphate (TCP) is mainly composed of calcium and phosphorus elements, the components of which are similar to the inorganic components of bone matrix, and the degradation product is alkaline, has good biocompatibility and osteoinductivity, but has the defects of large brittleness and poor toughness, which limits the application of the TCP.
Bismuth, a heavy metal element having a large X-ray attenuation coefficient. In the research of numerous biomedical materials, it provides a good choice for realizing Computed Tomography (CT) imaging. Meanwhile, the preparation method has the advantages of low production cost, capability of forming trivalent bismuth ions in a human body and successful elimination of the trivalent bismuth ions from the human body. In interventional embolization, the realization of real-time imaging of embolization microspheres is helpful for the application of interventional embolization, and is beneficial to clinical tracking observation and diagnosis. According to the invention, bismuth is introduced into the embolism microsphere, so that the accuracy of real-time imaging of interventional embolism treatment is improved, misdiagnosis caused by phase separation is reduced, and a new design scheme is provided for the imageable embolism microsphere. Meanwhile, bismuth ions can be discharged in vivo, and compared with iodine, the bismuth ion-doped bismuth-doped iodine is safer.
The embolism microsphere prepared by polyvinyl alcohol, β -tricalcium phosphate, nano bismuth and glutaraldehyde not only well plays the role of bismuth, but also effectively overcomes the defects of large brittleness and poor toughness of β -tricalcium phosphate.
Preferably, the weight ratio of the polyvinyl alcohol to the liquid paraffin is 1: 1-1.5.
Preferably, the weight ratio of the liquid paraffin to the surfactant is 50: 20: 1.
Preferably, the surfactant is span-80, span-60, tween-80 or the like.
The invention also provides a preparation method of the developable embolism microsphere, which comprises the following steps:
s1, mixing polyvinyl alcohol and β -tricalcium phosphate in water according to a formula, uniformly mixing, adding nano bismuth, and uniformly stirring;
s2, adding hydrochloric acid into the mixed solution in the step S1 for acidification;
s3, continuous phase configuration: uniformly mixing liquid paraffin and a surfactant according to the formula amount;
and S4, uniformly mixing the acidified mixed solution obtained in the step S2 with a glutaraldehyde solution for reaction, and then dropwise adding the mixed solution into a continuous phase to prepare the developable embolism microsphere.
Preferably, in the step S1, after the nano bismuth is added, the stirring speed is 200-700 r/min. .
Preferably, in step S2, the pH of the acidified mixed solution is 3.0 to 6.0.
Preferably, the specific process of step S3 is: and mixing the liquid paraffin and the surfactant, heating to 40-70 ℃, and stirring at the rotating speed of 200-700 r/min.
More preferably, in step S3, the liquid paraffin and the surfactant are heated at a temperature of 55 ℃.
Preferably, in step S4, the reaction time of the acidified mixed solution in S2 and the glutaraldehyde solution is 15S, and then the solution is quickly dropped into the continuous phase for forming and curing.
A developable embolizing microsphere prepared by the above preparation method is also within the scope of the invention.
Compared with the prior art, the invention has the following beneficial effects:
the embolism microsphere improves the accuracy of real-time imaging of interventional embolism treatment by introducing bismuth into the embolism microsphere, reduces misdiagnosis caused by phase separation, and provides a new design scheme for the imageable embolism microsphere. Meanwhile, bismuth ions can be discharged in vivo, and compared with iodine elements, the bismuth ions are safer;
meanwhile, the embolism is simple in process, short in preparation time and easy to realize batch production; and the microspheres are added with TCP materials, so that the biocompatibility of the microspheres is improved.
Drawings
FIG. 1 is a schematic flow chart of the preparation of developable embolizing microspheres of example 1.
FIG. 2 is a cold field Scanning Electron Microscope (SEM) image of the developable embolization microspheres prepared in example 1.
FIG. 3 is a scanning electron micrograph of a Karl Zeiss ZEISS EVO18 tungsten filament of the developable embolization microspheres prepared in example 1.
Detailed Description
The present invention is further described in detail below with reference to specific examples, which are provided for illustration only and are not intended to limit the scope of the present invention. The test methods used in the following examples are all conventional methods unless otherwise specified; the materials, reagents and the like used are, unless otherwise specified, commercially available reagents and materials.
Example 1
A developable embolism microsphere is prepared by polyvinyl alcohol (PVA), β -tricalcium phosphate (TCP), nano bismuth and glutaraldehyde through an inverse suspension polymerization technology, the preparation flow chart is shown in figure 1, and the specific preparation process is as follows:
s1, dissolving 2g of polyvinyl alcohol in 18g of pure water to obtain 20mL of 10% polyvinyl alcohol solution, adding 0.25g of β -tricalcium phosphate into the solution, namely mixing and dispersing according to the proportion of PVA to TCP (8: 1), stirring for 1h, adding 20mg of Bi nanoparticles, and stirring for 400 r/min;
s2, adding 200 mu L of concentrated hydrochloric acid into the polyvinyl alcohol solution containing the TCP/Bi in the step S1 for acidification;
s3, adding span-800.6 g into a beaker containing 30mL of liquid paraffin, placing the beaker in an oil bath at 55 ℃, rotating speed of 400r/min, and magnetically stirring.
S4, adding 80 mu L of 50% glutaraldehyde (the density of the glutaraldehyde is about 1.06g/mL, and the converted mass of 80 mu L is about 0.0848g) into 10mL of the mixed solution (containing 1g of PVA) in the step S2, mixing the two solutions for 15S under magnetic stirring, and quickly dropwise adding the two solutions into liquid paraffin to prepare the developable embolization microsphere.
The results obtained by characterizing the prepared developable embolization microsphere are shown in fig. 2 and 3, wherein fig. 2 is a cold field scanning topography of the microsphere, and fig. 3 is an element analysis result of an EVO electron microscope, and it can be known from fig. 2 and 3 that the microsphere is good in balling property based on the polyvinyl alcohol composite microsphere and the β -tricalcium phosphate is encapsulated in the microsphere.
The microspheres are nitrified and subjected to ICP (plasma atomic emission spectrometer) detection on bismuth, and the Bi element is detected as a test result, wherein the content of the Bi element is 3.78mg/mL, which indicates that the metal bismuth nanoparticles are successfully encapsulated into the microspheres.
Example 2
A developable embolization microsphere was prepared as in example 1, except that: the mass ratio of PVA to TCP in step S1 was 10:2, and the other steps were the same as in example 1.
Example 3
A developable embolization microsphere was prepared as in example 1, except that: the PVA/TCP mass ratio in step S1 was 6:1, span-800.5 g in step S3 was put in an oil bath at 60 ℃ and the other steps were the same as in example 1.
Example 4
A developable embolization microsphere was prepared as in example 1, except that: in step S1, the Bi nanoparticles are 100mg, the temperature of the oil bath is set at 60 ℃ in step S3, the rotating speed is 600r/min, and the magnetic stirring is carried out, wherein the other steps are the same as those of the embodiment 1.
Example 5
A developable embolization microsphere was prepared as in example 1, except that: the amount of Bi nanoparticles in step S1 was 80mg, the temperature of the oil bath in step S3 was set at 50 ℃, the rotational speed was 500r/min, and magnetic stirring was carried out with the amount of glutaraldehyde being 100. mu.L (the equivalent mass of 100. mu.L glutaraldehyde was about 0.106g), and the other steps were the same as in example 1.
The results of the cold field scanning electron microscopy and Karl Zeiss ZEISS EVO18 tungsten filament scanning electron microscopy of the developable embolization microspheres prepared in examples 2 to 5 above were the same as in example 1.
It should be finally noted that the above examples are only intended to illustrate the technical solutions of the present invention, and not to limit the scope of the present invention, and that other variations and modifications based on the above description and thought may be made by those skilled in the art, and that all embodiments need not be exhaustive. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the claims of the present invention.
Claims (10)
1. The developable embolism microsphere is characterized by being prepared by polyvinyl alcohol, β -tricalcium phosphate, nano bismuth and glutaraldehyde through an inverse suspension polymerization technology, wherein a continuous phase comprises liquid paraffin and a surfactant, and a disperse phase comprises polyvinyl alcohol, β -tricalcium phosphate, nano bismuth and glutaraldehyde;
the polyvinyl alcohol, β -tricalcium phosphate, nano bismuth and glutaraldehyde are used in a ratio of 10: 1-2: 0.1-0.8: 0.7-1.25 by weight.
2. The developable embolization microsphere of claim 1, wherein the weight ratio of the polyvinyl alcohol to the liquid paraffin is 1:1 to 1.5.
3. The developable embolization microsphere of claim 1, wherein the weight ratio of the liquid paraffin to the surfactant is 20-50: 1.
4. The developable embolic microsphere of claim 1, wherein the surfactant is span-80, span-60, tween-60, or tween-80.
5. A method of preparing the developable embolization microspheres of any one of claims 1 to 4, comprising the steps of:
s1, mixing polyvinyl alcohol and β -tricalcium phosphate in water according to a formula, uniformly mixing, adding nano bismuth, and uniformly stirring;
s2, adding hydrochloric acid into the mixed solution in the step S1 for acidification;
s3, continuous phase configuration: uniformly mixing liquid paraffin and a surfactant according to the formula amount;
and S4, uniformly mixing the acidified mixed solution obtained in the step S2 with a glutaraldehyde solution for reaction, and then dropwise adding the mixed solution into a continuous phase to prepare the developable embolism microsphere.
6. The preparation method of the developable embolization microsphere according to claim 5, wherein in step S1, after the nano bismuth is added, the stirring speed is 200-700 r/min.
7. The method for preparing developable embolization microspheres according to claim 5, wherein in step S2, the pH of the acidified mixed solution is 3.0-6.0.
8. The method for preparing the developable embolization microsphere of claim 5, wherein the specific process of step S3 is: and mixing the liquid paraffin and the surfactant, heating to 40-70 ℃, and stirring at the rotating speed of 200-700 r/min.
9. The method for preparing the developable embolization microsphere according to claim 5, wherein in step S4, the reaction time of the acidified mixed solution and the glutaraldehyde solution in S2 is 5-60S, and then the solution is quickly dropped into the continuous phase for forming and curing.
10. A developable embolization microsphere prepared by the method of any one of claims 5 to 9.
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| CN104174342A (en) * | 2014-08-14 | 2014-12-03 | 暨南大学 | Beta-tricalcium phosphate/alginic acid composite microsphere and preparation method and application of beta-tricalcium phosphate/alginic acid composite microsphere |
| WO2017201375A1 (en) * | 2016-05-19 | 2017-11-23 | Amrita Vishwa Vidyapeetham | Non-iodinated radiolabeled radiopaque microbeads with mri contrast for radioembolization |
| CN106668879A (en) * | 2017-01-04 | 2017-05-17 | 武汉大学中南医院 | Preparation method of nano simple-substance bismuth diagnosis and treatment agent for CT (computed tomography)/PAT (pericardial adipose tissue) imaging |
| CN107998443A (en) * | 2017-11-09 | 2018-05-08 | 华中科技大学 | A kind of micro- preparation method for encompassing hybrid microspheres |
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