CN108686259A - Drug bearing microsphere and preparation method thereof for that can develop under Endovascular Embolization x-ray - Google Patents
Drug bearing microsphere and preparation method thereof for that can develop under Endovascular Embolization x-ray Download PDFInfo
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- CN108686259A CN108686259A CN201810764430.9A CN201810764430A CN108686259A CN 108686259 A CN108686259 A CN 108686259A CN 201810764430 A CN201810764430 A CN 201810764430A CN 108686259 A CN108686259 A CN 108686259A
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- 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
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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
- A61L24/001—Use of materials characterised by their function or physical properties
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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
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
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Abstract
The invention discloses a kind of drug bearing microspheres for that can develop under Endovascular Embolization x-ray, which is characterized in that the raw material for preparing of the drug bearing microsphere includes:The poly-vinyl alcohol solution of the 5-25%w/v of 3-35 parts by weight, 1-10 parts by weight of acrylic acid;The drug bearing microsphere is the microballoon that precipitated barium obtains.The invention has the advantages that:Provide a kind of manufacture craft of simple, economic, conducive to quantization production non-degradable x-ray development drug bearing microsphere;The microballoon being prepared is Endovascular Embolization microballoon can develop under x-ray, nondegradable, medicine-carried.
Description
Technical field
The present invention relates to field of medical technology, and in particular to a kind of load medicine for that can develop under Endovascular Embolization x-ray is micro-
Ball and preparation method thereof.
Background technology
Currently, Endovascular Treatment of External is the important treatment means of innocent and malignant tumour, the embolism material used in current clinic
Material includes embolism materials (absorbable gelatin sponge particle, the polyvinyl alcohol of not medicine-carried;PVA], Embosphere etc.), the bolt of medicine-carried
Fill in microballoon (DC-Bead, gal clever life microballoon, Hepasphere microballoons etc.).It cannot develop under x-ray, be only capable of by injecting comparison
Agent is judged indirectly, is unfavorable for the tracking of embolism degree and range after embolism.
Invention content
The purpose of the present invention is to provide a kind of drug bearing microsphere for that can develop under Endovascular Embolization x-ray and its preparation sides
Method, to provide a kind of Endovascular Embolization microballoon can develop under x-ray, nondegradable, medicine-carried.
To achieve the above object, first aspect present invention provides a kind of load for that can develop under Endovascular Embolization x-ray
The raw material for preparing of medicine microballoon, the drug bearing microsphere includes:Poly-vinyl alcohol solution, the 1-10 weights of the 5-25%w/v of 3-35 parts by weight
Measure part acrylic acid;The drug bearing microsphere is the microballoon that precipitated barium obtains.
In one possible implementation, the grain size of the drug bearing microsphere is 2-1000 μm.
In one possible implementation, the drug bearing microsphere includes one or more in following drug:
Adriamycin, Epi-ADM, bleomycin, cis-platinum, carboplatin, oxaliplatin, lobaplatin, taxol, Docetaxel, fluorine
Uracil, mitomycin, Irinotecan.
Second aspect of the present invention provides a kind of suppository for Endovascular Embolization, including the load medicine described in first aspect
Microballoon.
Third aspect present invention provides the preparation method of drug bearing microsphere as described in relation to the first aspect, includes the following steps:
(1a) takes the poly-vinyl alcohol solution of the 5-25%w/v of 3-35 parts by weight, 1-10 parts by weight of acrylic acid, initiator, friendship
Join agent, is uniformly mixed, obtains mixed liquor;
50-90 part by weight of liquid paraffin and 0.2-1.8 parts by weight SPAN-80, mixing is added in (1b) in the reaction vessel;
(2) under the protection of protective gas, the mixed liquor that step (1a) obtains is added dropwise in reaction vessel, first
After preset time, be added catalyst, maintenance report 300-600 revs/min, temperature be 55-60 DEG C, react the second preset time after,
Reaction was completed, obtains wet microballoon;
(3) wet microballoon that step (2) obtains being placed in the solution containing barium ions, carries out precipitated barium, supernatant is removed in centrifugation,
Dry microballoon is obtained after drying.
In one possible implementation, it is placed in the solution containing barium ions in the wet microballoon for obtaining step (2),
Before carrying out precipitated barium, the method further includes that will use surfactant wash wet microballoon, to remove atoleine.
In one possible implementation, in the step (1b), it is mixed into 300-600 revs/min of rotating speed, temperature is
It 55-60 DEG C, mixes 10 minutes;The reaction vessel is three-necked flask.
In one possible implementation, first preset time is 10 minutes, and the second preset time is that 2-6 is small
When.
In one possible implementation, in the step (3), the solution containing barium ions is 0.1-1mmol/L
Barium chloride solution or 0.1-1mmol/L barium nitrate solution;It is 200-400 revs/min to carry out precipitated barium, and room temperature reaction 2-6 is small
When.
In one possible implementation, the initiator is ammonium persulfate, and the crosslinking agent is N, N- methylene two
Acrylamide, the catalyst are TEMED, and the protective gas is nitrogen or inert gas.
The invention has the advantages that:Provide a kind of simple, economic, conducive to quantization production non-degradable x-ray development
The manufacture craft of drug bearing microsphere;The microballoon being prepared is can developing under x-ray, nondegradable, medicine-carried intravascular
Embolism microball.
Specific implementation mode
The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention..
Embodiment 1
It is prepared by microballoon
It is prepared for that can developing under a kind of x-ray, nondegradable, medicine-carried Endovascular Embolization is micro- in the present embodiment
Ball, preparation method include as follows:
Poly-vinyl alcohol solution, 4 parts by weight of acrylic acid, the 1.6 parts by weight ammonium persulfates of the 10%w/v of 15 parts by weight are taken (to use
Make initiator), 0.4 parts by weight N, N- methylene diacrylamine (be used as crosslinking agent), be uniformly mixed, and fully impact, obtain
Mixed liquor.
80 part by weight of liquid paraffin and 0.4 parts by weight SPAN-80 are added in three-necked flask container, 300- is reported in setting
600 revs/min, temperature be 55-60 DEG C, after ten minutes under nitrogen protection, mixed liquor obtained above is added dropwise to reaction
In container, after ten minutes, 0.4 parts by weight TEMED (being used as catalyst) is added, 300-600 revs/min, temperature 55- are reported in maintenance
It 60 DEG C, after reacting 2-6 hours, washes off atoleine with Tween-80 and obtains wet microballoon.
It is reacted with the barium ions on barium chloride using the anion of acrylic acid, forms precipitated barium.Specifically, by after washing
Wet microballoon is placed in the barium chloride solution of 0.1-1mmol/L, 200-400 revs/min, is reacted at room temperature 2-6 hours, and supernatant is removed in centrifugation,
It is cleaned repeatedly with Tween-80 and deionized water, dry microballoon is obtained after freeze-drying.
Cell compatibility is tested
Using 10% fetal calf serum containing dual anti-DMEM HighGlucose as culture solution, in 37 DEG C, 5%CO2Incubator
Middle culture L929 cell lines.
Sterile particles are soaked in culture solution, the volume ratio of particle and culture solution be 1: 5,37 DEG C stand 24 hours after,
Sample of the leaching liquor as 100% concentration is drawn, its half is diluted to the sample of 50% concentration with culture solution.Positive control is adopted
With industrial polyvinyl chloride standard leaching liquor, using culture solution as negative control.
Culture plate is taken out respectively at the 1st day, the 3rd day, the 5th day after sample-adding, absorbs sample leaching liquor, 20 μ L/ hole MTT are added
Liquid continues culture 6 hours, then absorbs, and adds 150 μ L/ hole DMSO, shakes 10 minutes, with 500nm in immune microplate reader
Absorption value A is measured at wavelength, is calculate by the following formula opposite appreciation rate (Relative growth rate, RGR).
RGR=(AExperiment-ABlank)/(ANegative control-ABlank) × 100%
Experimental result is shown, compared with negative control, the cell growth rate of particle leaching liquid is slightly lower, and 50% leaching liquid is thin
Born of the same parents' growth rate is slightly above 100% particle leaching liquid, both significantly larger than positive control.Meanwhile with time change, from 1 day
By 3 days, then by 5 days, cell kept the growth rate of certain speed.Cell opposite proliferation rate is converted into toxicity grading, each particle
The toxicity grading result of experimental group is 0~1 grade (RGR 75~99%).Illustrate that the particle of the present embodiment has good cell
Compatibility.
Development effect under x-ray
Particle manufactured in the present embodiment and physiological saline are respectively charged into EP pipes, in X-ray shooting system (Steno V
Type, GE) under observed.The results show that particle manufactured in the present embodiment can develop in the case where X is penetrated, and physiological saline under x-ray not
Development.
The measurement of grain size
At least 500 particles in random determination sample, with following formula arithmetic average diameter (D), d in formulaiIt is micro-
Grain diameter, niFor the grain size particle number, N is particulate sum amount.
Grain size manufactured in the present embodiment is between 2-700 μm.
The microballoon that the present embodiment is prepared can load a variety of antitumor drugs, including:Adriamycin, Epi-ADM are won and
Mycin, cis-platinum, carboplatin, oxaliplatin, lobaplatin, taxol, Docetaxel, fluorouracil, mitomycin, Irinotecan etc..
Embodiment 2
It is prepared by microballoon
It is prepared for that can developing under a kind of x-ray, nondegradable, medicine-carried Endovascular Embolization is micro- in the present embodiment
Ball, preparation method include as follows:
Poly-vinyl alcohol solution, 4 parts by weight of acrylic acid, the 0.8 parts by weight ammonium persulfate of the 20%w/v of 15 parts by weight is taken (to use
Make initiator), 0.1 parts by weight N, N- methylene diacrylamine (be used as crosslinking agent), be uniformly mixed, and fully impact, obtain
Mixed liquor.
80 part by weight of liquid paraffin and 0.8 parts by weight SPAN-80 are added in three-necked flask container, 300- is reported in setting
600 revs/min, temperature be 55-60 DEG C, after ten minutes under nitrogen protection, mixed liquor obtained above is added dropwise to reaction
In container, after ten minutes, TEMED (being used as catalyst) is added in 0.4 parts by weight, and 300-600 revs/min, temperature 55- are reported in maintenance
It 60 DEG C, after reacting 2-6 hours, washes off atoleine with Tween-80 and obtains wet microballoon.
It is reacted with barium ions using the anion of acrylic acid, forms precipitated barium.Specifically, the wet microballoon after washing is placed in
In the barium nitrate solution of 0.1-1mmol/L, 200-400 revs/min, react at room temperature 2-6 hours, supernatant is removed in centrifugation, uses Tween-80
And deionized water is cleaned repeatedly, and dry microballoon is obtained after freeze-drying.
Cell compatibility is tested
Cell compatibility is measured according to method similarly to Example 1, as a result shows that cell compatibility is good.
Development effect under x-ray
The development effect under x-ray is measured according to method similarly to Example 1, as a result shows that development effect is good.
The measurement of grain size
According to method microspherulite diameter similarly to Example 1, grain size manufactured in the present embodiment is obtained between 5-1000 μm.
The microballoon that the present embodiment is prepared can load a variety of antitumor drugs, including:Adriamycin, Epi-ADM are won and
Mycin, cis-platinum, carboplatin, oxaliplatin, lobaplatin, taxol, Docetaxel, fluorouracil, mitomycin, Irinotecan etc..
Embodiment 3
It is prepared by microballoon
It is prepared for that can developing under a kind of x-ray, nondegradable, medicine-carried Endovascular Embolization is micro- in the present embodiment
Ball, preparation method include as follows:
Poly-vinyl alcohol solution, 6 parts by weight of acrylic acid, the 0.6 parts by weight ammonium persulfate of the 5%w/v of 20 parts by weight is taken (to be used as
Initiator), 0.2 parts by weight N, N- methylene diacrylamine (be used as crosslinking agent), be uniformly mixed, and fully impact, mixed
Close liquid.
90 part by weight of liquid paraffin and 0.6 parts by weight SPAN-80 are added in three-necked flask container, 300- is reported in setting
600 revs/min, temperature be 55-60 DEG C, after ten minutes under nitrogen protection, mixed liquor obtained above is added dropwise to reaction
In container, after ten minutes, TEMED (being used as catalyst) is added in 0.4 parts by weight, and 300-600 revs/min, temperature 55- are reported in maintenance
It 60 DEG C, after reacting 2-6 hours, washes off atoleine with Tween-80 and obtains wet microballoon.
It is reacted with barium ions using the anion of acrylic acid, forms precipitated barium.Specifically, the wet microballoon after washing is placed in
In the barium nitrate solution of 0.1-1mmol/L, 200-400 revs/min, react at room temperature 2-6 hours, supernatant is removed in centrifugation, uses Tween-80
And deionized water is cleaned repeatedly, and dry microballoon is obtained after freeze-drying.
Cell compatibility is tested
Cell compatibility is measured according to method similarly to Example 1, as a result shows that cell compatibility is good.
Development effect under x-ray
The development effect under x-ray is measured according to method similarly to Example 1, as a result shows that development effect is good.
The measurement of grain size
According to method microspherulite diameter similarly to Example 1, grain size manufactured in the present embodiment is obtained between 2-900 μm.
The microballoon that the present embodiment is prepared can load a variety of antitumor drugs, including:Adriamycin, Epi-ADM are won and
Mycin, cis-platinum, carboplatin, oxaliplatin, lobaplatin, taxol, Docetaxel, fluorouracil, mitomycin, Irinotecan etc..
Embodiment 4
It is prepared by microballoon
It is prepared for that can developing under a kind of x-ray, nondegradable, medicine-carried Endovascular Embolization is micro- in the present embodiment
Ball, preparation method include as follows:
Poly-vinyl alcohol solution, 8 parts by weight of acrylic acid, the 0.4 parts by weight ammonium persulfate of the 25%w/v of 10 parts by weight is taken (to use
Make initiator), 0.2 parts by weight N, N- methylene diacrylamine (be used as crosslinking agent), be uniformly mixed, and fully impact, obtain
Mixed liquor.
50 part by weight of liquid paraffin and 0.4 parts by weight SPAN-80 are added in three-necked flask container, 300- is reported in setting
600 revs/min, temperature be 55-60 DEG C, after ten minutes under nitrogen protection, mixed liquor obtained above is added dropwise to reaction
In container, after ten minutes, TEMED (being used as catalyst) is added in 0.2 parts by weight, and 300-600 revs/min, temperature 55- are reported in maintenance
It 60 DEG C, after reacting 2-6 hours, washes off atoleine with dish detergent and obtains wet microballoon.
It is reacted with barium ions using the anion of acrylic acid, forms precipitated barium.Specifically, the wet microballoon after washing is placed in
In the barium chloride solution of 0.1-1mmol/L, 200-400 revs/min, react at room temperature 2-6 hour, centrifuge and remove supernatant, with dish detergent and
Deionized water is cleaned repeatedly, and dry microballoon is obtained after freeze-drying.
Cell compatibility is tested
Cell compatibility is measured according to method similarly to Example 1, as a result shows that cell compatibility is good.
Development effect under x-ray
The development effect under x-ray is measured according to method similarly to Example 1, as a result shows that development effect is good.
The measurement of grain size
According to method microspherulite diameter similarly to Example 1, grain size manufactured in the present embodiment is obtained between 2-500 μm.
The microballoon that the present embodiment is prepared can load a variety of antitumor drugs, including:Adriamycin, Epi-ADM are won and
Mycin, cis-platinum, carboplatin, oxaliplatin, lobaplatin, taxol, Docetaxel, fluorouracil, mitomycin, Irinotecan etc..
Embodiment 5
It is prepared by microballoon
It is prepared for that can developing under a kind of x-ray, nondegradable, medicine-carried Endovascular Embolization is micro- in the present embodiment
Ball, preparation method include as follows:
Poly-vinyl alcohol solution, 6 parts by weight of acrylic acid, the 0.8 parts by weight ammonium persulfate of the 15%w/v of 25 parts by weight is taken (to use
Make initiator), 0.4 parts by weight N, N- methylene diacrylamine (be used as crosslinking agent), be uniformly mixed, and fully impact, obtain
Mixed liquor.
80 part by weight of liquid paraffin and 0.4 parts by weight SPAN-80 are added in three-necked flask container, 300- is reported in setting
600 revs/min, temperature be 55-60 DEG C, after ten minutes under nitrogen protection, mixed liquor obtained above is added dropwise to reaction
In container, after ten minutes, TEMED (being used as catalyst) is added in 0.4 parts by weight, and 300-600 revs/min, temperature 55- are reported in maintenance
It 60 DEG C, after reacting 2-6 hours, washes off atoleine with surfactant and obtains wet microballoon.
It is reacted with barium ions using the anion of acrylic acid, forms precipitated barium.Specifically, the wet microballoon after washing is placed in
In the barium chloride solution of 0.1-1mmol/L, 200-400 revs/min, react at room temperature 2-6 hours, supernatant is removed in centrifugation, uses surface-active
Agent and deionized water are cleaned repeatedly, and dry microballoon is obtained after freeze-drying.
Cell compatibility is tested
Cell compatibility is measured according to method similarly to Example 1, as a result shows that cell compatibility is good.
Development effect under x-ray
The development effect under x-ray is measured according to method similarly to Example 1, as a result shows that development effect is good.
The measurement of grain size
According to method microspherulite diameter similarly to Example 1, grain size manufactured in the present embodiment is obtained between 2-900 μm.
The microballoon that the present embodiment is prepared can load a variety of antitumor drugs, including:Adriamycin, Epi-ADM are won and
Mycin, cis-platinum, carboplatin, oxaliplatin, lobaplatin, taxol, Docetaxel, fluorouracil, mitomycin, Irinotecan etc..
Embodiment 6
It is prepared by microballoon
It is prepared for that can developing under a kind of x-ray, nondegradable, medicine-carried Endovascular Embolization is micro- in the present embodiment
Ball, preparation method include as follows:
Poly-vinyl alcohol solution, 6 parts by weight of acrylic acid, the 0.8 parts by weight ammonium persulfate of the 20%w/v of 5 parts by weight is taken (to be used as
Initiator), 0.4 parts by weight N, N- methylene diacrylamine (be used as crosslinking agent), be uniformly mixed, and fully impact, mixed
Close liquid.
50 part by weight of liquid paraffin and 0.2 parts by weight SPAN-80 are added in three-necked flask container, 300- is reported in setting
600 revs/min, temperature be 55-60 DEG C, after ten minutes under nitrogen protection, mixed liquor obtained above is added dropwise to reaction
In container, after ten minutes, TEMED (being used as catalyst) is added in 0.4 parts by weight, and 300-600 revs/min, temperature 55- are reported in maintenance
It 60 DEG C, after reacting 2-6 hours, washes off atoleine with surfactant and obtains wet microballoon.
It is reacted with barium ions using the anion of acrylic acid, forms precipitated barium.Specifically, the wet microballoon after washing is placed in
In the barium chloride solution of 0.1-1mmol/L, 200-400 revs/min, react at room temperature 2-6 hours, supernatant is removed in centrifugation, uses surface-active
Agent and deionized water are cleaned repeatedly, and dry microballoon is obtained after freeze-drying.
Cell compatibility is tested
Cell compatibility is measured according to method similarly to Example 1, as a result shows that cell compatibility is good.
Development effect under x-ray
The development effect under x-ray is measured according to method similarly to Example 1, as a result shows that development effect is good.
The measurement of grain size
According to method microspherulite diameter similarly to Example 1, grain size manufactured in the present embodiment is obtained between 2-500 μm.
Embodiment 7
It is prepared by microballoon
It is prepared for that can developing under a kind of x-ray, nondegradable, medicine-carried Endovascular Embolization is micro- in the present embodiment
Ball, preparation method include as follows:
Poly-vinyl alcohol solution, 10 parts by weight of acrylic acid, the 0.8 parts by weight ammonium persulfate of the 15%w/v of 30 parts by weight is taken (to use
Make initiator), 0.4 parts by weight N, N- methylene diacrylamine (be used as crosslinking agent), be uniformly mixed, and fully impact, obtain
Mixed liquor.
60 part by weight of liquid paraffin and 1.0 parts by weight SPAN-80 are added in three-necked flask container, 300- is reported in setting
600 revs/min, temperature be 55-60 DEG C, after ten minutes under nitrogen protection, mixed liquor obtained above is added dropwise to reaction
In container, after ten minutes, TEMED (being used as catalyst) is added in 0.4 parts by weight, and 300-600 revs/min, temperature 55- are reported in maintenance
It 60 DEG C, after reacting 2-6 hours, washes off atoleine with dish detergent and obtains wet microballoon.
It is reacted with barium ions using the anion of acrylic acid, forms precipitated barium.Specifically, the wet microballoon after washing is placed in
In the barium chloride solution of 0.1-1mmol/L, 200-400 revs/min, react at room temperature 2-6 hour, centrifuge and remove supernatant, with dish detergent and
Deionized water is cleaned repeatedly, and dry microballoon is obtained after freeze-drying.
Cell compatibility is tested
Cell compatibility is measured according to method similarly to Example 1, as a result shows that cell compatibility is good.
Development effect under x-ray
The development effect under x-ray is measured according to method similarly to Example 1, as a result shows that development effect is good.
The measurement of grain size
According to method microspherulite diameter similarly to Example 1, obtain grain size manufactured in the present embodiment 300-900 μm it
Between.
Embodiment 8
It is prepared by microballoon
It is prepared for that can developing under a kind of x-ray, nondegradable, medicine-carried Endovascular Embolization is micro- in the present embodiment
Ball, preparation method include as follows:
Poly-vinyl alcohol solution, 8 parts by weight of acrylic acid, the 0.8 parts by weight ammonium persulfate of the 15%w/v of 35 parts by weight is taken (to use
Make initiator), 0.4 parts by weight N, N- methylene diacrylamine (be used as crosslinking agent), be uniformly mixed, and fully impact, obtain
Mixed liquor.
70 part by weight of liquid paraffin and 0.4 parts by weight SPAN-80 are added in three-necked flask container, 300- is reported in setting
600 revs/min, temperature be 55-60 DEG C, after ten minutes under nitrogen protection, mixed liquor obtained above is added dropwise to reaction
In container, after ten minutes, TEMED (being used as catalyst) is added in 0.4 parts by weight, and 300-600 revs/min, temperature 55- are reported in maintenance
It 60 DEG C, after reacting 2-6 hours, washes off atoleine with dish detergent and obtains wet microballoon.
It is reacted with barium ions using the anion of acrylic acid, forms precipitated barium.Specifically, the wet microballoon after washing is placed in
In the barium chloride solution of 0.1-1mmol/L, 200-400 revs/min, react at room temperature 2-6 hour, centrifuge and remove supernatant, with dish detergent and
Deionized water is cleaned repeatedly, and dry microballoon is obtained after freeze-drying.
Cell compatibility is tested
Cell compatibility is measured according to method similarly to Example 1, as a result shows that cell compatibility is good.
Development effect under x-ray
The development effect under x-ray is measured according to method similarly to Example 1, as a result shows that development effect is good.
The measurement of grain size
According to method microspherulite diameter similarly to Example 1, obtain grain size manufactured in the present embodiment 100-500 μm it
Between.
Embodiment 9
It is prepared by microballoon
It is prepared for that can developing under a kind of x-ray, nondegradable, medicine-carried Endovascular Embolization is micro- in the present embodiment
Ball, preparation method include as follows:
Poly-vinyl alcohol solution, 6 parts by weight of acrylic acid, the 0.8 parts by weight ammonium persulfate of the 20%w/v of 3 parts by weight is taken (to be used as
Initiator), 0.4 parts by weight N, N- methylene diacrylamine (be used as crosslinking agent), be uniformly mixed, and fully impact, mixed
Close liquid.
80 part by weight of liquid paraffin and 0.4 parts by weight SPAN-80 are added in three-necked flask container, 300- is reported in setting
600 revs/min, temperature be 55-60 DEG C, after ten minutes under nitrogen protection, mixed liquor obtained above is added dropwise to reaction
In container, after ten minutes, TEMED (being used as catalyst) is added in 0.4 parts by weight, and 300-600 revs/min, temperature 55- are reported in maintenance
It 60 DEG C, after reacting 2-6 hours, washes off atoleine with dish detergent and obtains wet microballoon.
It is reacted with barium ions using the anion of acrylic acid, forms precipitated barium.Specifically, the wet microballoon after washing is placed in
In the barium chloride solution of 0.1-1mmol/L, 200-400 revs/min, react at room temperature 2-6 hour, centrifuge and remove supernatant, with dish detergent and
Deionized water is cleaned repeatedly, and dry microballoon is obtained after freeze-drying.
Cell compatibility is tested
Cell compatibility is measured according to method similarly to Example 1, as a result shows that cell compatibility is good.
Development effect under x-ray
The development effect under x-ray is measured according to method similarly to Example 1, as a result shows that development effect is good.
The measurement of grain size
According to method microspherulite diameter similarly to Example 1, grain size manufactured in the present embodiment is obtained between 50-300 μm.
Embodiment 10
It is prepared by microballoon
It is prepared for that can developing under a kind of x-ray, nondegradable, medicine-carried Endovascular Embolization is micro- in the present embodiment
Ball, preparation method include as follows:
Poly-vinyl alcohol solution, 6 parts by weight of acrylic acid, the 0.8 parts by weight ammonium persulfate of the 25%w/v of 10 parts by weight is taken (to use
Make initiator), 0.4 parts by weight N, N- methylene diacrylamine (be used as crosslinking agent), be uniformly mixed, and fully impact, obtain
Mixed liquor.
80 part by weight of liquid paraffin and 0.4 parts by weight SPAN-80 are added in three-necked flask container, 300- is reported in setting
600 revs/min, temperature be 55-60 DEG C, after ten minutes under nitrogen protection, mixed liquor obtained above is added dropwise to reaction
In container, after ten minutes, TEMED (being used as catalyst) is added in 0.4 parts by weight, and 300-600 revs/min, temperature 55- are reported in maintenance
It 60 DEG C, after reacting 2-6 hours, washes off atoleine with surfactant and obtains wet microballoon.
It is reacted with barium ions using the anion of acrylic acid, forms precipitated barium.Specifically, the wet microballoon after washing is placed in
In the barium chloride solution of 0.1-1mmol/L, 200-400 revs/min, react at room temperature 2-6 hours, supernatant is removed in centrifugation, uses surface-active
Agent and deionized water are cleaned repeatedly, and dry microballoon is obtained after freeze-drying.
Cell compatibility is tested
Cell compatibility is measured according to method similarly to Example 1, as a result shows that cell compatibility is good.
Development effect under x-ray
The development effect under x-ray is measured according to method similarly to Example 1, as a result shows that development effect is good.
The measurement of grain size
According to method microspherulite diameter similarly to Example 1, obtain grain size manufactured in the present embodiment 100-600 μm it
Between.
Although above having used general explanation and specific embodiment, the present invention is described in detail, at this
On the basis of invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.Therefore,
These modifications or improvements without departing from theon the basis of the spirit of the present invention belong to the scope of protection of present invention.
Claims (10)
1. a kind of drug bearing microsphere for that can develop under Endovascular Embolization x-ray, which is characterized in that the preparation of the drug bearing microsphere is former
Material includes:The poly-vinyl alcohol solution of the 5-25%w/v of 3-35 parts by weight, 1-10 parts by weight of acrylic acid;
The drug bearing microsphere is the microballoon that precipitated barium obtains.
2. drug bearing microsphere according to claim 1, which is characterized in that the grain size of the drug bearing microsphere is 2-1000 μm.
3. drug bearing microsphere according to claim 1, which is characterized in that the drug bearing microsphere includes one kind in following drug
Or it is a variety of:
Adriamycin, Epi-ADM, bleomycin, cis-platinum, carboplatin, oxaliplatin, lobaplatin, taxol, Docetaxel, fluorine urine are phonetic
Pyridine, mitomycin, Irinotecan.
4. a kind of suppository for Endovascular Embolization, which is characterized in that it is micro- to carry medicine including claim 1-3 any one of them
Ball.
5. the preparation method of drug bearing microsphere as described in any one of claims 1-3, which is characterized in that include the following steps:
(1a) takes the poly-vinyl alcohol solution of the 5-25%w/v of 3-35 parts by weight, 1-10 parts by weight of acrylic acid, initiator, crosslinking agent,
It is uniformly mixed, obtains mixed liquor;
50-90 part by weight of liquid paraffin and 0.2-1.8 parts by weight SPAN-80, mixing is added in (1b) in the reaction vessel;
(2) under the protection of protective gas, the mixed liquor that step (1a) obtains is added dropwise in reaction vessel, first is default
After time, be added catalyst, maintenance report 300-600 revs/min, temperature be 55-60 DEG C, react the second preset time after, terminate
Reaction, obtains wet microballoon;
(3) wet microballoon that step (2) obtains is placed in the solution containing barium ions, carries out precipitated barium, supernatant is removed in centrifugation, dry
After obtain dry microballoon.
6. preparation method according to claim 5, which is characterized in that the wet microballoon for obtaining step (2) be placed in containing
In the solution of barium ions, before carrying out precipitated barium, the method further includes that will use surfactant wash wet microballoon, to remove
Atoleine.
7. preparation method according to claim 5, which is characterized in that in the step (1b), be mixed into and report 300-
600 revs/min, temperature be 55-60 DEG C, mix 10 minutes;The reaction vessel is three-necked flask.
8. preparation method according to claim 5, which is characterized in that first preset time is 10 minutes, and second is pre-
If the time is 2-6 hours.
9. preparation method according to claim 5, which is characterized in that in the step (3), the solution containing barium ions
For the barium chloride solution of 0.1-1mmol/L or the barium nitrate solution of 0.1-1mmol/L;It is 200-400 revs/min to carry out precipitated barium,
Room temperature reaction 2-6 hours.
10. preparation method according to claim 5, which is characterized in that the initiator is ammonium persulfate, the crosslinking agent
For N, N- methylene diacrylamines, the catalyst is TEMED.The protective gas is nitrogen or inert gas.
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