CN108686259B - Drug-loaded microsphere capable of being developed under X-ray for intravascular embolism and preparation method thereof - Google Patents
Drug-loaded microsphere capable of being developed under X-ray for intravascular embolism and preparation method thereof Download PDFInfo
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- CN108686259B CN108686259B CN201810764430.9A CN201810764430A CN108686259B CN 108686259 B CN108686259 B CN 108686259B CN 201810764430 A CN201810764430 A CN 201810764430A CN 108686259 B CN108686259 B CN 108686259B
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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
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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
Abstract
The invention discloses a drug-loaded microsphere which can be developed under X-ray for intravascular embolization, and is characterized in that the drug-loaded microsphere comprises the following preparation raw materials: 3-35 parts by weight of 5-25% w/v polyvinyl alcohol solution, 1-10 parts by weight of acrylic acid; the drug-loaded microspheres are microspheres obtained by barium precipitation. The invention has the following advantages: provides a simple and economic manufacturing process of the nondegradable X-ray developing drug-loaded microspheres which is beneficial to quantitative production; the prepared microsphere is a non-degradable intravascular embolism microsphere capable of carrying medicine and being developed under X-rays.
Description
Technical Field
The invention relates to the technical field of medical treatment, in particular to a drug-loaded microsphere capable of being developed under X-ray for intravascular embolism and a preparation method thereof.
Background
At present, the endovascular embolization treatment is an important treatment means for benign and malignant tumors, and the embolization materials used clinically at present comprise embolization materials (gelatin sponge particles, polyvinyl alcohol [ PVA ], Embosphere and the like) which can not carry medicines and embolization microspheres (DC-Bead, Gal raw microspheres, Hepasphere microspheres and the like) which can carry medicines. The imaging can not be carried out under X-ray, and only the indirect judgment can be carried out by injecting contrast agent, which is not beneficial to the tracking of the embolism degree and the embolism range after embolism.
Disclosure of Invention
The invention aims to provide a drug-loaded microsphere which can be developed under X-ray for intravascular embolization and a preparation method thereof, and aims to provide a non-degradable drug-loaded intravascular embolization microsphere which can be developed under X-ray.
In order to achieve the above object, a first aspect of the present invention provides a drug-loaded microsphere for intravascular embolization X-ray imaging, wherein the drug-loaded microsphere is prepared from the following raw materials: 3-35 parts by weight of 5-25% w/v polyvinyl alcohol solution, 1-10 parts by weight of acrylic acid; the drug-loaded microspheres are microspheres obtained by barium precipitation.
In one possible implementation mode, the particle size of the drug-loaded microspheres is 2-1000 μm.
In one possible implementation, the drug-loaded microspheres include one or more of the following drugs:
adriamycin, epirubicin, bleomycin, cisplatin, carboplatin, oxaliplatin, lobaplatin, paclitaxel, docetaxel, fluorouracil, mitomycin and irinotecan.
In a second aspect, the invention provides an embolizing agent for intravascular embolization, comprising the drug-loaded microsphere of the first aspect.
The third aspect of the present invention provides a preparation method of the drug-loaded microsphere according to the first aspect, comprising the following steps:
(1a) uniformly mixing 3-35 parts by weight of 5-25% w/v polyvinyl alcohol solution, 1-10 parts by weight of acrylic acid, an initiator and a cross-linking agent to obtain a mixed solution;
(1b) adding 50-90 parts by weight of liquid paraffin and 0.2-1.8 parts by weight of SPAN-80 into a reaction vessel, and mixing;
(2) under the protection of protective gas, dropwise adding the mixed solution obtained in the step (1a) into a reaction container, adding a catalyst after a first preset time, maintaining the temperature at 55-60 ℃ at 600 revolutions per minute after 300 revolutions per minute, and after reacting for a second preset time, ending the reaction to obtain wet microspheres;
(3) and (3) putting the wet microspheres obtained in the step (2) into a solution containing barium ions, carrying out barium precipitation, centrifuging to remove supernatant, and drying to obtain dry microspheres.
In one possible implementation, before the wet microspheres obtained in step (2) are placed in a solution containing barium ions for barium precipitation, the method further comprises washing the wet microspheres with a surfactant to remove liquid paraffin.
In one possible implementation manner, in the step (1b), the mixing is performed at a rotation speed of 300-; the reaction vessel is a three-neck flask.
In a possible implementation, the first preset time is 10 minutes, and the second preset time is 2-6 hours.
In one possible implementation manner, in the step (3), the solution containing barium ions is a 0.1-1mmol/L barium chloride solution or a 0.1-1mmol/L barium nitrate solution; the barium precipitation is carried out at 200-400 rpm, and the reaction is carried out for 2-6 hours at room temperature.
In one possible implementation, the initiator is ammonium persulfate, the crosslinking agent is N, N-methylenebisacrylamide, the catalyst is TEMED, and the protective gas is nitrogen or an inert gas.
The invention has the following advantages: provides a simple and economic manufacturing process of the nondegradable X-ray developing drug-loaded microspheres which is beneficial to quantitative production; the prepared microsphere is a non-degradable intravascular embolism microsphere capable of carrying medicine and being developed under X-rays.
Detailed Description
The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.
Example 1
Preparation of microspheres
In this embodiment, a non-degradable drug-loaded intravascular embolic microsphere that can be developed under X-ray is prepared, and the preparation method comprises the following steps:
15 parts by weight of a 10% w/v polyvinyl alcohol solution, 4 parts by weight of acrylic acid, 1.6 parts by weight of ammonium persulfate (used as an initiator), and 0.4 part by weight of N, N-methylenebisacrylamide (used as a crosslinking agent) were taken, mixed uniformly, and sufficiently impacted to obtain a mixed solution.
Adding 80 parts by weight of liquid paraffin and 0.4 part by weight of SPAN-80 into a three-neck flask container, setting the temperature to be 55-60 ℃ at 300-600 r/m, dropwise adding the obtained mixed solution into a reaction container under the protection of nitrogen after 10 minutes, adding 0.4 part by weight of TEMED (used as a catalyst) after 10 minutes, maintaining the temperature to be 55-60 ℃ at 300-600 r/m, and washing off the liquid paraffin by Tween-80 after reacting for 2-6 hours to obtain the wet microspheres.
The anion of acrylic acid is utilized to react with barium ions on barium chloride to form barium precipitate. Specifically, the washed wet microspheres are placed in 0.1-1mmol/L barium chloride solution, reacted at room temperature for 2-6 hours at 400 rpm, centrifuged to remove supernatant, repeatedly washed with Tween-80 and deionized water, and freeze-dried to obtain dry microspheres.
Cell compatibility test
Using 10% fetal calf serum containing double-antibody DMEM high glucose as culture solution, and culturing at 37 deg.C under 5% CO2The L929 cell line was cultured in an incubator.
Soaking the sterilized particles in a culture solution at a volume ratio of 1: 5, standing at 37 deg.C for 24 hr, collecting the leaching solution as 100% sample, and diluting half of the sample with the culture solution to 50% sample. The positive control adopts industrial polyvinyl chloride standard leaching liquor, and the culture solution is used as the negative control.
After the sample addition, the culture plate was taken out on days 1, 3 and 5, respectively, the leaching solution of the sample was aspirated, 20. mu.L/well MTT solution was added, the culture was continued for 6 hours, then the sample was aspirated, 150. mu.L/well DMSO was added, the shaking was carried out for 10 minutes, the absorbance A was measured at a wavelength of 500nm on an immunomicroplate reader, and the Relative Growth Rate (RGR) was calculated by the following formula.
RGR＝(AExperiment of-ABlank space)/(ANegative control-ABlank space)×100％
The experimental results show that the cell growth rate of the particulate extract is slightly lower than that of the negative control, the cell growth rate of 50% of the extract is slightly higher than that of 100% of the particulate extract, and both are far higher than those of the positive control. Meanwhile, the cells maintain a certain rate of growth from 1 day to 3 days and then to 5 days as time goes by. The relative cell proliferation rate was converted into toxicity classification, and the toxicity classification results of each microparticle experiment group were 0 to 1 class (RGR 75 to 99%). It is demonstrated that the microparticles of this example have good cell compatibility.
Development effect under X-ray
The microparticles prepared in this example and physiological saline were separately loaded into an EP tube and observed under an X-ray radiography system (stereo V type, GE). The results show that the microparticles prepared in this example were visualized under X-ray, whereas the saline was not visualized under X-ray.
Measurement of particle diameter
Random determination sampleAt least 500 particles in the product, and calculating the average diameter (D) by the following formula, wherein DiIs the particle diameter, niFor the number of particles of this size, N is the total number of particles.
The particle size produced in this example is between 2 and 700 μm.
The microspheres prepared by the embodiment can be loaded with various antitumor drugs, including: adriamycin, epirubicin, bleomycin, cisplatin, carboplatin, oxaliplatin, lobaplatin, paclitaxel, docetaxel, fluorouracil, mitomycin, irinotecan and the like.
Example 2
Preparation of microspheres
In this embodiment, a non-degradable drug-loaded intravascular embolic microsphere that can be developed under X-ray is prepared, and the preparation method comprises the following steps:
taking 15 parts by weight of 20% w/v polyvinyl alcohol solution, 4 parts by weight of acrylic acid, 0.8 part by weight of ammonium persulfate (used as an initiator) and 0.1 part by weight of N, N-methylene bisacrylamide (used as a cross-linking agent), uniformly mixing, and fully impacting to obtain a mixed solution.
Adding 80 parts by weight of liquid paraffin and 0.8 part by weight of SPAN-80 into a three-neck flask container, setting the temperature to be 55-60 ℃ at 300-600 r/m, dropwise adding the obtained mixed solution into a reaction container under the protection of nitrogen after 10 minutes, adding 0.4 part by weight of TEMED (used as a catalyst) after 10 minutes, maintaining the temperature to be 55-60 ℃ at 300-600 r/m, and washing off the liquid paraffin by Tween-80 after reacting for 2-6 hours to obtain the wet microspheres.
The anion of acrylic acid is utilized to react with barium ions to form barium precipitates. Specifically, the washed wet microspheres are placed in 0.1-1mmol/L barium nitrate solution, reacted for 2-6 hours at room temperature at 200-400 rpm, centrifuged to remove supernatant, repeatedly washed by Tween-80 and deionized water, and freeze-dried to obtain dry microspheres.
Cell compatibility test
The cell compatibility was measured in the same manner as in example 1, and the result showed that the cell compatibility was good.
Development effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Measurement of particle diameter
The particle size of the microspheres was adjusted in the same manner as in example 1 to obtain a particle size of 5-1000 μm for this example.
The microspheres prepared by the embodiment can be loaded with various antitumor drugs, including: adriamycin, epirubicin, bleomycin, cisplatin, carboplatin, oxaliplatin, lobaplatin, paclitaxel, docetaxel, fluorouracil, mitomycin, irinotecan and the like.
Example 3
Preparation of microspheres
In this embodiment, a non-degradable drug-loaded intravascular embolic microsphere that can be developed under X-ray is prepared, and the preparation method comprises the following steps:
20 parts by weight of a 5% w/v polyvinyl alcohol solution, 6 parts by weight of acrylic acid, 0.6 part by weight of ammonium persulfate (used as an initiator), and 0.2 part by weight of N, N-methylenebisacrylamide (used as a crosslinking agent) were taken, mixed uniformly, and sufficiently impacted to obtain a mixed solution.
Adding 90 weight parts of liquid paraffin and 0.6 weight part of SPAN-80 into a three-neck flask container, setting the temperature to be 55-60 ℃ at 300-600 r/m, dropwise adding the obtained mixed solution into a reaction container under the protection of nitrogen after 10 minutes, adding 0.4 weight part of TEMED (used as a catalyst) after 10 minutes, maintaining the temperature to be 55-60 ℃ at 300-600 r/m, and washing off the liquid paraffin by Tween-80 after reacting for 2-6 hours to obtain the wet microspheres.
The anion of acrylic acid is utilized to react with barium ions to form barium precipitates. Specifically, the washed wet microspheres are placed in 0.1-1mmol/L barium nitrate solution, reacted for 2-6 hours at room temperature at 200-400 rpm, centrifuged to remove supernatant, repeatedly washed by Tween-80 and deionized water, and freeze-dried to obtain dry microspheres.
Cell compatibility test
The cell compatibility was measured in the same manner as in example 1, and the result showed that the cell compatibility was good.
Development effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Measurement of particle diameter
The particle size of the microspheres was adjusted in the same manner as in example 1 to obtain a particle size of 2-900 μm for this example.
The microspheres prepared by the embodiment can be loaded with various antitumor drugs, including: adriamycin, epirubicin, bleomycin, cisplatin, carboplatin, oxaliplatin, lobaplatin, paclitaxel, docetaxel, fluorouracil, mitomycin, irinotecan and the like.
Example 4
Preparation of microspheres
In this embodiment, a non-degradable drug-loaded intravascular embolic microsphere that can be developed under X-ray is prepared, and the preparation method comprises the following steps:
taking 10 parts by weight of 25% w/v polyvinyl alcohol solution, 8 parts by weight of acrylic acid, 0.4 part by weight of ammonium persulfate (used as an initiator) and 0.2 part by weight of N, N-methylene-bisacrylamide (used as a cross-linking agent), uniformly mixing, and fully impacting to obtain a mixed solution.
Adding 50 parts by weight of liquid paraffin and 0.4 part by weight of SPAN-80 into a three-neck flask container, setting the temperature to be 55-60 ℃ at 300-600 r/m, dropwise adding the obtained mixed solution into a reaction container under the protection of nitrogen after 10 minutes, adding 0.2 part by weight of TEMED (used as a catalyst) after 10 minutes, maintaining the temperature to be 55-60 ℃ at 300-600 r/m, and washing off the liquid paraffin by using washing after reacting for 2-6 hours to obtain the wet microspheres.
The anion of acrylic acid is utilized to react with barium ions to form barium precipitates. Specifically, the washed wet microspheres are placed in 0.1-1mmol/L barium chloride solution, reacted at room temperature for 2-6 hours at 400 rpm, centrifuged to remove supernatant, repeatedly washed by washing agent and deionized water, and freeze-dried to obtain dry microspheres.
Cell compatibility test
The cell compatibility was measured in the same manner as in example 1, and the result showed that the cell compatibility was good.
Development effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Measurement of particle diameter
The particle size of the microspheres was adjusted in the same manner as in example 1 to obtain a particle size of 2-500. mu.m.
The microspheres prepared by the embodiment can be loaded with various antitumor drugs, including: adriamycin, epirubicin, bleomycin, cisplatin, carboplatin, oxaliplatin, lobaplatin, paclitaxel, docetaxel, fluorouracil, mitomycin, irinotecan and the like.
Example 5
Preparation of microspheres
In this embodiment, a non-degradable drug-loaded intravascular embolic microsphere that can be developed under X-ray is prepared, and the preparation method comprises the following steps:
taking 25 parts by weight of 15% w/v polyvinyl alcohol solution, 6 parts by weight of acrylic acid, 0.8 part by weight of ammonium persulfate (used as an initiator) and 0.4 part by weight of N, N-methylene-bisacrylamide (used as a cross-linking agent), uniformly mixing, and fully impacting to obtain a mixed solution.
Adding 80 parts by weight of liquid paraffin and 0.4 part by weight of SPAN-80 into a three-neck flask container, setting the temperature to be 55-60 ℃ at 300-600 r/m, dropwise adding the obtained mixed solution into a reaction container under the protection of nitrogen after 10 minutes, adding 0.4 part by weight of TEMED (used as a catalyst) after 10 minutes, maintaining the temperature to be 55-60 ℃ at 300-600 r/m, and washing off the liquid paraffin by using a surfactant after reacting for 2-6 hours to obtain the wet microspheres.
The anion of acrylic acid is utilized to react with barium ions to form barium precipitates. Specifically, the washed wet microspheres are placed in 0.1-1mmol/L barium chloride solution, reacted at room temperature for 2-6 hours at 200-400 rpm, centrifuged to remove supernatant, repeatedly washed with surfactant and deionized water, and freeze-dried to obtain dry microspheres.
Cell compatibility test
The cell compatibility was measured in the same manner as in example 1, and the result showed that the cell compatibility was good.
Development effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Measurement of particle diameter
The particle size of the microspheres was adjusted in the same manner as in example 1 to obtain a particle size of 2-900 μm for this example.
The microspheres prepared by the embodiment can be loaded with various antitumor drugs, including: adriamycin, epirubicin, bleomycin, cisplatin, carboplatin, oxaliplatin, lobaplatin, paclitaxel, docetaxel, fluorouracil, mitomycin, irinotecan and the like.
Example 6
Preparation of microspheres
In this embodiment, a non-degradable drug-loaded intravascular embolic microsphere that can be developed under X-ray is prepared, and the preparation method comprises the following steps:
5 parts by weight of a 20% w/v polyvinyl alcohol solution, 6 parts by weight of acrylic acid, 0.8 part by weight of ammonium persulfate (used as an initiator), and 0.4 part by weight of N, N-methylenebisacrylamide (used as a crosslinking agent) were taken, mixed uniformly, and sufficiently impacted to obtain a mixed solution.
Adding 50 parts by weight of liquid paraffin and 0.2 part by weight of SPAN-80 into a three-neck flask container, setting the temperature to be 55-60 ℃ at 300-600 r/m, dropwise adding the obtained mixed solution into a reaction container under the protection of nitrogen after 10 minutes, adding 0.4 part by weight of TEMED (used as a catalyst) after 10 minutes, maintaining the temperature to be 55-60 ℃ at 300-600 r/m, and washing off the liquid paraffin by using a surfactant after reacting for 2-6 hours to obtain the wet microspheres.
The anion of acrylic acid is utilized to react with barium ions to form barium precipitates. Specifically, the washed wet microspheres are placed in 0.1-1mmol/L barium chloride solution, reacted at room temperature for 2-6 hours at 200-400 rpm, centrifuged to remove supernatant, repeatedly washed with surfactant and deionized water, and freeze-dried to obtain dry microspheres.
Cell compatibility test
The cell compatibility was measured in the same manner as in example 1, and the result showed that the cell compatibility was good.
Development effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Measurement of particle diameter
The particle size of the microspheres was adjusted in the same manner as in example 1 to obtain a particle size of 2-500. mu.m.
Example 7
Preparation of microspheres
In this embodiment, a non-degradable drug-loaded intravascular embolic microsphere that can be developed under X-ray is prepared, and the preparation method comprises the following steps:
30 parts by weight of 15% w/v polyvinyl alcohol solution, 10 parts by weight of acrylic acid, 0.8 part by weight of ammonium persulfate (used as an initiator), and 0.4 part by weight of N, N-methylenebisacrylamide (used as a crosslinking agent) were uniformly mixed and sufficiently impacted to obtain a mixed solution.
Adding 60 weight parts of liquid paraffin and 1.0 weight part of SPAN-80 into a three-neck flask container, setting the temperature to be 55-60 ℃ at 300-600 r/m, dropwise adding the obtained mixed solution into a reaction container under the protection of nitrogen after 10 minutes, adding 0.4 weight part of TEMED (used as a catalyst) after 10 minutes, maintaining the temperature to be 55-60 ℃ at 300-600 r/m, and washing off the liquid paraffin by using washing after reacting for 2-6 hours to obtain the wet microspheres.
The anion of acrylic acid is utilized to react with barium ions to form barium precipitates. Specifically, the washed wet microspheres are placed in 0.1-1mmol/L barium chloride solution, reacted at room temperature for 2-6 hours at 400 rpm, centrifuged to remove supernatant, repeatedly washed by washing agent and deionized water, and freeze-dried to obtain dry microspheres.
Cell compatibility test
The cell compatibility was measured in the same manner as in example 1, and the result showed that the cell compatibility was good.
Development effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Measurement of particle diameter
The particle size of the microspheres obtained in this example was between 300 and 900 μm, according to the same method as in example 1.
Example 8
Preparation of microspheres
In this embodiment, a non-degradable drug-loaded intravascular embolic microsphere that can be developed under X-ray is prepared, and the preparation method comprises the following steps:
taking 35 parts by weight of 15% w/v polyvinyl alcohol solution, 8 parts by weight of acrylic acid, 0.8 part by weight of ammonium persulfate (used as an initiator) and 0.4 part by weight of N, N-methylene-bisacrylamide (used as a cross-linking agent), uniformly mixing, and fully impacting to obtain a mixed solution.
Adding 70 parts by weight of liquid paraffin and 0.4 part by weight of SPAN-80 into a three-neck flask container, setting the temperature to be 55-60 ℃ at 300-.
The anion of acrylic acid is utilized to react with barium ions to form barium precipitates. Specifically, the washed wet microspheres are placed in 0.1-1mmol/L barium chloride solution, reacted at room temperature for 2-6 hours at 400 rpm, centrifuged to remove supernatant, repeatedly washed by washing agent and deionized water, and freeze-dried to obtain dry microspheres.
Cell compatibility test
The cell compatibility was measured in the same manner as in example 1, and the result showed that the cell compatibility was good.
Development effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Measurement of particle diameter
The particle size of the microspheres obtained in this example was between 100 and 500 μm by the same method as in example 1.
Example 9
Preparation of microspheres
In this embodiment, a non-degradable drug-loaded intravascular embolic microsphere that can be developed under X-ray is prepared, and the preparation method comprises the following steps:
3 parts by weight of a 20% w/v polyvinyl alcohol solution, 6 parts by weight of acrylic acid, 0.8 part by weight of ammonium persulfate (used as an initiator), and 0.4 part by weight of N, N-methylenebisacrylamide (used as a crosslinking agent) were taken, mixed uniformly, and sufficiently impacted to obtain a mixed solution.
Adding 80 parts by weight of liquid paraffin and 0.4 part by weight of SPAN-80 into a three-neck flask container, setting the temperature to be 55-60 ℃ at 300-600 r/m, dropwise adding the obtained mixed solution into a reaction container under the protection of nitrogen after 10 minutes, adding 0.4 part by weight of TEMED (used as a catalyst) after 10 minutes, maintaining the temperature to be 55-60 ℃ at 300-600 r/m, and washing off the liquid paraffin by using washing after reacting for 2-6 hours to obtain the wet microspheres.
The anion of acrylic acid is utilized to react with barium ions to form barium precipitates. Specifically, the washed wet microspheres are placed in 0.1-1mmol/L barium chloride solution, reacted at room temperature for 2-6 hours at 400 rpm, centrifuged to remove supernatant, repeatedly washed by washing agent and deionized water, and freeze-dried to obtain dry microspheres.
Cell compatibility test
The cell compatibility was measured in the same manner as in example 1, and the result showed that the cell compatibility was good.
Development effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Measurement of particle diameter
The particle size of the microspheres was adjusted in the same manner as in example 1 to obtain a particle size of 50-300 μm for this example.
Example 10
Preparation of microspheres
In this embodiment, a non-degradable drug-loaded intravascular embolic microsphere that can be developed under X-ray is prepared, and the preparation method comprises the following steps:
taking 10 parts by weight of 25% w/v polyvinyl alcohol solution, 6 parts by weight of acrylic acid, 0.8 part by weight of ammonium persulfate (used as an initiator) and 0.4 part by weight of N, N-methylene-bisacrylamide (used as a cross-linking agent), uniformly mixing, and fully impacting to obtain a mixed solution.
Adding 80 parts by weight of liquid paraffin and 0.4 part by weight of SPAN-80 into a three-neck flask container, setting the temperature to be 55-60 ℃ at 300-600 r/m, dropwise adding the obtained mixed solution into a reaction container under the protection of nitrogen after 10 minutes, adding 0.4 part by weight of TEMED (used as a catalyst) after 10 minutes, maintaining the temperature to be 55-60 ℃ at 300-600 r/m, and washing off the liquid paraffin by using a surfactant after reacting for 2-6 hours to obtain the wet microspheres.
The anion of acrylic acid is utilized to react with barium ions to form barium precipitates. Specifically, the washed wet microspheres are placed in 0.1-1mmol/L barium chloride solution, reacted at room temperature for 2-6 hours at 200-400 rpm, centrifuged to remove supernatant, repeatedly washed with surfactant and deionized water, and freeze-dried to obtain dry microspheres.
Cell compatibility test
The cell compatibility was measured in the same manner as in example 1, and the result showed that the cell compatibility was good.
Development effect under X-ray
The development effect under X-ray was measured in the same manner as in example 1, and the result showed that the development effect was good.
Measurement of particle diameter
The particle size of the microspheres was between 100 and 600 μm according to the same method as in example 1.
Although the invention has been described in detail above with reference to a general description and specific examples, it will be apparent to one skilled in the art that modifications or improvements may be made thereto based on the invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.
Claims (8)
1. The utility model provides a can develop medicine carrying microsphere under being used for embolism X line in blood vessel which characterized in that, the preparation raw materials of medicine carrying microsphere include: 3-35 parts by weight of 5-25% w/v polyvinyl alcohol solution, 1-10 parts by weight of acrylic acid;
the drug-loaded microspheres are microspheres obtained by barium precipitation;
the particle size of the drug-loaded microspheres is 2-1000 μm;
the drug-loaded microspheres comprise one or more of the following drugs:
doxorubicin, epirubicin, bleomycin, cisplatin, carboplatin, oxaliplatin, lobaplatin, paclitaxel, docetaxel, fluorouracil, mitomycin, irinotecan;
the preparation method of the drug-loaded microsphere comprises the following steps:
1a) uniformly mixing 3-35 parts by weight of 5-25% w/v polyvinyl alcohol solution, 1-10 parts by weight of acrylic acid, an initiator and a cross-linking agent to obtain a mixed solution;
(1b) adding 50-90 parts by weight of liquid paraffin and 0.2-1.8 parts by weight of SPAN-80 into a reaction vessel, and mixing;
(2) under the protection of protective gas, dropwise adding the mixed solution obtained in the step (1a) into a reaction container, adding a catalyst after a first preset time, maintaining the temperature at 55-60 ℃ at 600 revolutions per minute after 300 revolutions per minute, and after reacting for a second preset time, ending the reaction to obtain wet microspheres;
(3) and (3) putting the wet microspheres obtained in the step (2) into a solution containing barium ions, carrying out barium precipitation, centrifuging to remove supernatant, and drying to obtain dry microspheres.
2. An embolic agent for intravascular embolization comprising the drug-loaded microsphere of claim 1.
3. The preparation method of the drug-loaded microsphere of claim 1, which comprises the following steps:
(1a) uniformly mixing 3-35 parts by weight of 5-25% w/v polyvinyl alcohol solution, 1-10 parts by weight of acrylic acid, an initiator and a cross-linking agent to obtain a mixed solution;
(1b) adding 50-90 parts by weight of liquid paraffin and 0.2-1.8 parts by weight of SPAN-80 into a reaction vessel, and mixing;
(2) under the protection of protective gas, dropwise adding the mixed solution obtained in the step (1a) into a reaction container, adding a catalyst after a first preset time, maintaining the temperature at 55-60 ℃ at 600 revolutions per minute after 300 revolutions per minute, and after reacting for a second preset time, ending the reaction to obtain wet microspheres;
(3) and (3) putting the wet microspheres obtained in the step (2) into a solution containing barium ions, carrying out barium precipitation, centrifuging to remove supernatant, and drying to obtain dry microspheres.
4. The method according to claim 3, wherein before the wet microspheres obtained in step (2) are placed in a solution containing barium ions for barium precipitation, the method further comprises washing the wet microspheres with a surfactant to remove liquid paraffin.
5. The method as claimed in claim 3, wherein in the step (1b), the mixing is performed at a rotation speed of 300-600 rpm and a temperature of 55-60 ℃ for 10 minutes; the reaction vessel is a three-neck flask.
6. The method according to claim 3, wherein the first predetermined time is 10 minutes and the second predetermined time is 2 to 6 hours.
7. The production method according to claim 3, wherein in the step (3), the solution containing barium ions is a 0.1 to 1mmol/L barium chloride solution or a 0.1 to 1mmol/L barium nitrate solution; the barium precipitation is carried out at 200-400 rpm, and the reaction is carried out for 2-6 hours at room temperature.
8. The method of claim 3, wherein the initiator is ammonium persulfate, the cross-linking agent is N, N-methylenebisacrylamide, the catalyst is TEMED, and the protective gas is nitrogen or an inert gas.
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| CN101125225A (en) * | 2007-08-10 | 2008-02-20 | 苏州迦俐生生物医药科技有限公司 | Microsphere type embolic agent and preparation technology thereof |
| CN101670095B (en) * | 2009-04-13 | 2012-05-23 | 北京大学 | Pharmaceutical composition for treating embolism and preparation method thereof |
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| CN102139128A (en) * | 2011-03-22 | 2011-08-03 | 杭州艾力康医药科技有限公司 | Developable polyvinyl alcohol microballoon/particle embolic agent and preparation process thereof |
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