CN112972753A - Sustained-release embolism microsphere for treating bronchiectasis hemoptysis caused by chronic inflammation - Google Patents
Sustained-release embolism microsphere for treating bronchiectasis hemoptysis caused by chronic inflammation Download PDFInfo
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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
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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
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
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- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
Abstract
The invention discloses a sustained-release embolism microsphere for treating bronchiectasis hemoptysis caused by chronic inflammation, which has the particle size of 10-1000 mu m, is made of degradable or non-degradable organic material and is loaded with glucocorticoid. The invention can slowly release glucocorticoid while stopping bleeding by embolism, relieve and inhibit local inflammation, treat the change of lung structure caused by bronchitis and effectively avoid the relapse of hemoptysis. The slow release of the glucocorticoid in the invention can greatly improve the drug concentration of the focus part, relatively reduce the concentration of the drug in the circulatory system and reduce the side effect of the drug.
Description
Technical Field
The invention belongs to the technical field of interventional medical treatment, and particularly relates to a sustained-release embolism microsphere for treating bronchiectasis hemoptysis caused by chronic inflammation.
Background
Hemoptysis is a bleeding of the respiratory system, mainly caused by diseases of the trachea, bronchi and lung tissues. Among the most common causes of hemoptysis are infectious lung diseases, a class of which includes tuberculosis (40%), bronchiectasis (30%), necrotizing pneumonia (10%), lung abscesses (5%) and fungal infections (5%). Whereas lung cancer and arteriovenous malformations account for only 10% of all cases.
Bronchiectasis is chronic airway inflammation and irreversible dilation and deformation of the bronchial wall caused by various reasons. The factors such as infection, obstruction and the like cause the airway of a patient with bronchiectasis to have chronic inflammatory reaction, so that the epithelial cells of the bronchial mucosa are damaged, fall-off and necrosis occur, the wall of a single or multiple bronchial tubes of the patient is damaged, and then hemoptysis and even acute hemoptysis occur. The Bronchus Artery Embolization (BAE) has the advantages of minimal invasion, safety, rapid hemostatic effect and the like, and has become a preferred method for clinically treating hemoptysis caused by bronchiectasis.
Disclosure of Invention
The invention aims to provide a sustained-release embolism microsphere for treating bronchiectasis hemoptysis caused by chronic inflammation.
The technical scheme of the invention is as follows:
a sustained release embolism microsphere for treating bronchiectasis hemoptysis caused by chronic inflammation is prepared from degradable or non-degradable organic material loaded with glucocorticoid
The organic material is chitin, Chitosan (Chitosan), carboxymethyl Chitosan, sodium alginate, gelatin, collagen, Hyaluronic Acid (HA), polypeptide, silk fibroin, carboxymethyl starch, starch acetate, Polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA), polylactic acid-polyglycolic acid copolymer (PLGA), polycaprolactone triol, polycaprolactone diol, poly (ethylene glycol) -block-poly (epsilon-caprolactone) methyl ether, polyvinyl alcohol (PVA), polyethylene terephthalate, Polyacrylamide (PAM), polyacrylate, polyhydroxyethyl methacrylate, aromatic polyester, polysiloxane, polyurethane, polyethylene oxide, linear aliphatic polyester, polyamino acid or polyvinylpyrrolidone (PVP).
In a preferred embodiment of the present invention, the glucocorticoid is at least one of clinically useful derivatives including dexamethasone, betamethasone, triamcinolone acetonide and dexamethasone, betamethasone and triamcinolone acetonide.
Further preferably, the glucocorticoid comprises at least one of dexamethasone, betamethasone, triamcinolone acetonide, dexamethasone acetate, dexamethasone sodium phosphate, betamethasone dipropionate and triamcinolone acetonide acetate.
In a preferred embodiment of the invention, the particle size is from 10 to 1000. mu.m.
In a preferred embodiment of the present invention, the organic material is water-soluble, and the preparation method thereof comprises:
(1) preparing the glucocorticoid into an aqueous solution, and mixing the aqueous solution with the organic material to prepare a water phase;
(2) adding a surfactant into the liquid paraffin, and uniformly stirring to prepare an oil phase;
(3) adding the water phase into the oil phase, fully mixing, and carrying out emulsification or crosslinking reaction;
(4) and (4) centrifuging, washing and vacuum freeze-drying the material obtained in the step (3) to obtain the sustained-release embolism microsphere.
Further preferably, the surfactant is at least one of sorbitan monooleate, propylene glycol monolaurate and propylene glycol fatty acid ester.
Still further preferably, the sorbitan monooleate is Span-80 or Arlacel-80, the propylene glycol monolaurate is Atlas G-917 or Atlas G-3851, and the propylene glycol fatty acid ester is Emcol PL-50.
In a preferred embodiment of the present invention, the organic material is insoluble in water and is prepared by a method comprising:
(1) preparing the glucocorticoid into an aqueous solution;
(2) adding the aqueous solution into an organic phase containing the organic material, and performing vortex emulsification to form a water-in-oil emulsion;
(3) adding the water-in-oil emulsion into a water-soluble dispersant, and further emulsifying to form a water-in-oil-in-water emulsion;
(4) and (3) placing the water-in-oil-in-water emulsion in ice bath for ultrasonic treatment, stirring for 10-15h, and then sequentially centrifuging, washing and vacuum freeze-drying to obtain the slow-release embolism microsphere.
The invention has the beneficial effects that:
1. the invention can slowly release glucocorticoid while stopping bleeding by embolism, relieve and inhibit local inflammation, treat the change of lung structure caused by bronchitis and effectively avoid the relapse of hemoptysis.
2. The slow release of the glucocorticoid in the invention can greatly improve the drug concentration of the focus part, relatively reduce the concentration of the drug in the circulatory system and reduce the side effect of the drug.
3. The combination of the medicine and the microspheres in the invention is convenient for doctors to operate and brings convenience to patients.
Drawings
FIG. 1 is a scanning electron microscope image of dexamethasone sodium phosphate gelatin sustained-release embolization microspheres prepared in example 2 of the present invention.
FIG. 2 is a scanning electron microscope image of dexamethasone sodium phosphate polyvinyl alcohol sustained-release embolization microspheres prepared in example 3 of the present invention.
FIG. 3 is a scanning electron microscope image of dexamethasone sodium phosphate polycaprolactone sustained-release embolization microspheres prepared in example 4 of the present invention.
FIG. 4 is a scanning electron microscope image of dexamethasone sodium phosphate PLGA sustained-release embolization microspheres prepared in example 5 of the present invention.
FIG. 5 is a diagram of the results of in vitro drug release experiments of dexamethasone sodium phosphate gelatin sustained-release embolization microspheres prepared in example 2 of the invention.
FIG. 6 is a diagram showing the results of in vitro drug release experiments of dexamethasone sodium phosphate-polyvinyl alcohol sustained release embolization microspheres prepared in example 3 of the present invention.
FIG. 7 is a diagram showing the results of in vitro drug release experiments of dexamethasone sodium phosphate polycaprolactone sustained-release embolization microspheres prepared in example 4 of the present invention.
FIG. 8 is a graph showing the results of in vitro drug release experiments of dexamethasone sodium phosphate PLGA sustained release embolization microspheres prepared in example 5 of the present invention.
Detailed Description
The technical solution of the present invention will be further illustrated and described below with reference to the accompanying drawings by means of specific embodiments.
Example 1
A sustained-release embolism microsphere for treating bronchiectasis hemoptysis caused by chronic inflammation has particle diameter of 10-1000 μm. The material is degradable or non-degradable organic material, which is loaded with glucocorticoid, wherein
The organic material is chitin, Chitosan (Chitosan), carboxymethyl Chitosan, sodium alginate, gelatin, collagen, Hyaluronic Acid (HA), polypeptide, silk fibroin, carboxymethyl starch, starch acetate, Polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA), polylactic acid-polyglycolic acid copolymer (PLGA), polycaprolactone triol, polycaprolactone diol, poly (ethylene glycol) -block-poly (epsilon-caprolactone) methyl ether, polyvinyl alcohol (PVA), polyethylene terephthalate, Polyacrylamide (PAM), polyacrylate, polyhydroxyethyl methacrylate, aromatic polyester, polysiloxane, polyurethane, polyethylene oxide, linear aliphatic polyester, polyamino acid or polyvinylpyrrolidone (PVP).
The glucocorticoid is at least one of dexamethasone, betamethasone, triamcinolone acetonide and derivatives of dexamethasone, betamethasone and triamcinolone acetonide which can be used clinically. Further preferably, the glucocorticoid comprises at least one of dexamethasone, betamethasone, triamcinolone acetonide, dexamethasone acetate, dexamethasone sodium phosphate, betamethasone dipropionate and triamcinolone acetonide acetate.
When the organic material is water-soluble, the preparation method thereof comprises:
(1) preparing the glucocorticoid into an aqueous solution, and mixing the aqueous solution with the organic material to prepare a water phase;
(2) adding a surfactant into the liquid paraffin, and uniformly stirring to prepare an oil phase, wherein the surfactant is at least one of sorbitan monooleate (Span-80/Arlacel-80), propylene glycol monolaurate (Atlas G-917/Atlas G-3851) and propylene glycol fatty acid ester (Emcol PL-50);
(3) adding the water phase into the oil phase, fully mixing, and carrying out emulsification or crosslinking reaction;
(4) and (4) centrifuging, washing and vacuum freeze-drying the material obtained in the step (3) to obtain the sustained-release embolism microsphere.
When the organic material is not soluble in water, the preparation method thereof comprises:
(1) preparing the glucocorticoid into an aqueous solution;
(2) adding the aqueous solution into an organic phase containing the organic material, and performing vortex emulsification to form a water-in-oil emulsion;
(3) adding the water-in-oil emulsion into a water-soluble dispersant, and further emulsifying to form a water-in-oil-in-water emulsion;
(4) and (3) placing the water-in-oil-in-water emulsion in ice bath for ultrasonic treatment, stirring for 10-15h, and then sequentially centrifuging, washing and vacuum freeze-drying to obtain the slow-release embolism microsphere.
Example 2 preparation of dexamethasone sodium phosphate gelatin sustained release embolization microspheres
(1) Preparation of microspheres
Completely dissolving the prepared chitosan solution with the concentration of 20% in a water bath at 50-60 ℃, adding the dexamethasone sodium phosphate solution, and fully and uniformly mixing to prepare a water phase. Adding a proper amount of Span-80 into liquid paraffin as an oil phase, placing the oil phase into a three-necked bottle in a constant-temperature water bath at 50 ℃, slowly and dropwise adding the water phase into the oil phase for emulsification under the condition that the stirring speed is 200-1 r.min < -1 >, and the water-oil ratio is 1: 4-1: 8. When the emulsion drops are made into spheres with proper size through microscopic examination, namely emulsifying to form stable W/O type emulsion, rapidly cooling to below 5 ℃, respectively adding formaldehyde or 50% glutaraldehyde for curing for 1-2h, centrifuging the obtained product at 3000r/min, washing with isopropanol and acetone for 3 times, filtering, and freeze-drying in vacuum to finally obtain the dexamethasone sodium phosphate gelatin sustained-release embolism microsphere shown in figure 1.
(2) Encapsulation efficiency and drug load measurements
Chromatographic conditions are as follows: c18Analytical column 4.6mm × 2.5mm, 5 μm;
mobile phase triethylamine solution-methanol-acetonitrile 55: 40: 5
Wherein the triethylamine solution: adding water into 7.5mL of triethylamine to dilute to 1000mL, and adjusting with phosphoric acid
The pH value is 3.0.
An ultraviolet detector with a detection wavelength of 242nm
In the preparation process of the microspheres, collecting the waste liquid in each step, detecting the content of dexamethasone sodium phosphate in the waste liquid by using a high performance liquid chromatography, and calculating the encapsulation rate and the drug loading rate according to the following formula:
(3) in vitro drug release assay
Weighing a proper amount of the dexamethasone sodium phosphate gelatin sustained-release embolism microsphere, adding PBS (20mmol/L, pH7.4) for wetting, then placing into a 50mL conical flask, adding 30mL of PBS containing 1 per mill of sodium azide, then placing the conical flask into a constant-temperature water bath shaking table, setting the temperature at 37 ℃, and rotating at 80 rpm. Samples were taken at 1, 2, 3, 5, 7, 14, 21, 28d after placement, 5mL each time, supplemented with 5mL PBS. Centrifuging the sample, taking the supernatant to detect the content of dexamethasone sodium phosphate, and calculating the cumulative release according to the following formula:
as a result: the average entrapment rate of the dexamethasone sodium phosphate gelatin sustained-release embolism microsphere prepared by the embodiment reaches 83.61%, and the average drug loading rate is 7.82%; according to the in vitro release law, as can be seen from the cumulative release curve shown in fig. 5, the release rate is faster in week 1, and the release rate gradually slows down from week 2, with the curve also tending to be slightly gentle. The cumulative release of drug from the microspheres exceeded 40% over a 4 week period. Can meet the characteristics of taking intervention embolism as the main part and taking drug therapy as the auxiliary part in the clinical treatment of bronchiectasis hemoptysis.
Example 3 preparation of dexamethasone sodium phosphate polyvinyl alcohol sustained release embolization microspheres
(1) Preparation of microspheres
Under the condition of stirring, adding 2g of surfactant Span-80 into 40mL of liquid paraffin to form a continuous phase oil phase; after stirring uniformly, 10mL of a mixed solution of polyvinyl alcohol and dexamethasone sodium phosphate is added into the continuous oil phase, after full mixing, 1g of Sodium Trimetaphosphate (STMP) is added as a cross-linking agent, and 1mL of NaOH is immediately added as a catalyst. The rotation speed is set to be 400rpm, the temperature is set to be 50 ℃, and the crosslinking reaction time is set to be 16 h. After the crosslinking reaction was completed, the mixture was allowed to stand for 30 min. Adding a small amount of anhydrous ethanol, centrifuging in a centrifuge, taking out supernatant, repeatedly washing precipitate with anhydrous ethanol, isopropanol and pure water, and vacuum freeze drying to obtain dexamethasone sodium phosphate polyvinyl alcohol sustained-release embolism microsphere shown in figure 2.
(2) Encapsulation efficiency and drug load measurements
Chromatographic conditions are as follows: c18Analytical column 4.6mm × 2.5mm, 5 μm;
mobile phase triethylamine solution-methanol-acetonitrile 55: 40: 5
Wherein the triethylamine solution: adding water into 7.5mL of triethylamine to dilute to 1000mL, and adjusting with phosphoric acid
The pH value is 3.0.
An ultraviolet detector with a detection wavelength of 242nm
In the preparation process of the microspheres, collecting the waste liquid in each step, detecting the content of dexamethasone sodium phosphate in the waste liquid by using a high performance liquid chromatography, and calculating the encapsulation rate and the drug loading rate according to the following formula:
(3) in vitro drug release assay
Weighing a proper amount of the dexamethasone sodium phosphate polyvinyl alcohol sustained-release embolism microsphere, adding PBS (20mmol/L, pH7.4) for wetting, then placing into a 50mL conical flask, adding 30mL of PBS containing 1 per mill of sodium azide, then placing the conical flask into a constant-temperature water bath shaking table, setting the temperature at 37 ℃, and rotating at 80 rpm. Samples were taken at 1, 2, 3, 5, 7, 14, 21, 28d after placement, 5mL each time, supplemented with 5mL PBS. Centrifuging the sample, taking the supernatant to detect the content of dexamethasone sodium phosphate, and calculating the cumulative release according to the following formula:
as a result: the average encapsulation rate of the dexamethasone sodium phosphate gelatin sustained-release embolism microsphere prepared by the embodiment reaches 85.2%, and the average drug-loading rate is 8.14%; according to the in vitro release law, as can be seen from the cumulative release curve shown in fig. 6, the release rate is faster in week 1, and the release rate gradually slows down from week 2, with the curve also tending to be slightly gentle. The cumulative release of drug from the microspheres exceeded 40% over a 4 week period. Can meet the characteristics of taking intervention embolism as the main part and taking drug therapy as the auxiliary part in the clinical treatment of bronchiectasis hemoptysis.
Example 4 preparation of dexamethasone sodium phosphate polycaprolactone sustained-release embolism microsphere
(1) Preparation of microspheres
Dissolving polycaprolactone in dichloromethane under a closed condition, adding Span-80, and uniformly mixing to obtain an oil phase; adding dexamethasone sodium phosphate solution as internal water phase into the oil phase, and performing ultrasonic treatment for 3min to form primary emulsion; adding PVA water solution into the primary emulsion, and performing ultrasonic treatment again to form W/O/W type composite emulsion; stirring the obtained composite emulsion for 3 hours at room temperature under an open condition, and volatilizing dichloromethane; washing with distilled water for 2 times, and lyophilizing to obtain dexamethasone sodium phosphate polycaprolactone sustained-release embolism microsphere shown in figure 3.
(2) Encapsulation efficiency and drug load measurements
Chromatographic conditions are as follows: c18Analytical column 4.6mm × 2.5mm, 5 μm;
mobile phase triethylamine solution-methanol-acetonitrile 55: 40: 5
Wherein the triethylamine solution: adding water into 7.5mL of triethylamine to dilute to 1000mL, and adjusting with phosphoric acid
The pH value is 3.0.
An ultraviolet detector with a detection wavelength of 242nm
In the preparation process of the microspheres, collecting the waste liquid in each step, detecting the content of dexamethasone sodium phosphate in the waste liquid by using a high performance liquid chromatography, and calculating the encapsulation rate and the drug loading rate according to the following formula:
(3) in vitro drug release assay
Weighing a proper amount of the dexamethasone sodium phosphate gelatin sustained-release embolism microsphere, adding PBS (20mmol/L, pH7.4) for wetting, then placing into a 50mL conical flask, adding 30mL of PBS containing 1 per mill of sodium azide, then placing the conical flask into a constant-temperature water bath shaking table, setting the temperature at 37 ℃, and rotating at 80 rpm. Samples were taken at 1, 2, 3, 5, 7, 14, 21, 28d after placement, 5mL each time, supplemented with 5mL PBS. Centrifuging the sample, taking the supernatant to detect the content of dexamethasone sodium phosphate, and calculating the cumulative release according to the following formula:
as a result: the average entrapment rate of the dexamethasone sodium phosphate gelatin sustained-release embolism microsphere prepared by the embodiment reaches 76.23%, and the average drug loading rate is 6.84%; according to the in vitro release law, as can be seen from the cumulative release curve shown in fig. 7, the release rate is faster in week 1, and the release rate gradually slows down from week 2, with the curve also tending to be slightly gentle. The cumulative release of drug from the microspheres exceeded 40% over a 4 week period. Can meet the characteristics of taking intervention embolism as the main part and taking drug therapy as the auxiliary part in the clinical treatment of bronchiectasis hemoptysis.
Example 5 preparation of dexamethasone sodium phosphate PLGA sustained Release embolic microspheres
(1) Preparation of microspheres
Under a closed condition, dissolving PLGA in dichloromethane, adding Span-80, and uniformly mixing to obtain an oil phase; adding dexamethasone sodium phosphate solution as internal water phase into the oil phase, and performing ultrasonic treatment for 3min to form primary emulsion; adding PVA water solution into the primary emulsion, and performing ultrasonic treatment again to form W/O/W type composite emulsion; stirring the obtained composite emulsion for 3 hours at room temperature under an open condition, and volatilizing dichloromethane; washing with distilled water for 2 times, and lyophilizing to obtain dexamethasone sodium phosphate PLGA sustained release embolism microsphere shown in figure 4.
(2) Encapsulation efficiency and drug load measurements
Chromatographic conditions are as follows: c18Analytical column 4.6mm × 2.5mm, 5 μm;
mobile phase triethylamine solution-methanol-acetonitrile 55: 40: 5
Wherein the triethylamine solution: adding water into 7.5mL of triethylamine to dilute to 1000mL, and adjusting with phosphoric acid
The pH value is 3.0.
An ultraviolet detector with a detection wavelength of 242nm
In the preparation process of the microspheres, collecting the waste liquid in each step, detecting the content of dexamethasone sodium phosphate in the waste liquid by using a high performance liquid chromatography, and calculating the encapsulation rate and the drug loading rate according to the following formula:
(3) in vitro drug release assay
Weighing a proper amount of the dexamethasone sodium phosphate gelatin sustained-release embolism microsphere, adding PBS (20mmol/L, pH7.4) for wetting, then placing into a 50mL conical flask, adding 30mL of PBS containing 1 per mill of sodium azide, then placing the conical flask into a constant-temperature water bath shaking table, setting the temperature at 37 ℃, and rotating at 80 rpm. Samples were taken at 1, 2, 3, 5, 7, 14, 21, 28d after placement, 5mL each time, supplemented with 5mL PBS. Centrifuging the sample, taking the supernatant to detect the content of dexamethasone sodium phosphate, and calculating the cumulative release according to the following formula:
as a result: the average entrapment rate of the dexamethasone sodium phosphate gelatin sustained-release embolism microsphere prepared by the embodiment reaches 78.22%, and the average drug loading rate is 6.37%; according to the in vitro release law, as can be seen from the cumulative release curve shown in fig. 8, the release rate is faster in week 1, and the release rate gradually slows down from week 2, with the curve also tending to be slightly gentle. The cumulative release of drug from the microspheres exceeded 40% over a 4 week period. Can meet the characteristics of taking intervention embolism as the main part and taking drug therapy as the auxiliary part in the clinical treatment of bronchiectasis hemoptysis.
The above description is only a preferred embodiment of the present invention, and therefore should not be taken as limiting the scope of the invention, which is defined by the appended claims.
Claims (8)
1. A sustained release embolization microsphere for treating bronchiectasis hemoptysis caused by chronic inflammation, which is characterized in that: the material is degradable or non-degradable organic material, which is loaded with glucocorticoid, wherein the organic material is chitin, chitosan, carboxymethyl chitosan, sodium alginate, gelatin, collagen, hyaluronic acid, polypeptide, silk fibroin, carboxymethyl starch, starch acetate, polycaprolactone, polylactic acid, polyglycolic acid, polylactic acid-polyglycolic acid copolymer, polycaprolactone triol, polycaprolactone diol, poly (ethylene glycol) -block-poly (epsilon-caprolactone) methyl ether, polyvinyl alcohol, polyethylene glycol terephthalate, polyacrylamide, polyacrylate, polyhydroxyethyl methacrylate, aromatic polyester, polysiloxane, polyurethane, polyethylene oxide, linear aliphatic polyester, polyamino acid or polyvinylpyrrolidone.
2. The sustained-release embolic microsphere of claim 1, wherein: the glucocorticoid is at least one of dexamethasone, betamethasone, triamcinolone acetonide and derivatives of dexamethasone, betamethasone and triamcinolone acetonide which can be used clinically.
3. The sustained-release embolic microsphere of claim 2, wherein: the glucocorticoid comprises at least one of dexamethasone, betamethasone, triamcinolone acetonide, dexamethasone acetate, dexamethasone sodium phosphate, betamethasone dipropionate and triamcinolone acetonide acetate.
4. The sustained-release embolic microsphere of claim 1, wherein: the grain diameter is 10-1000 μm.
5. A slow release embolic microsphere as claimed in any one of claims 1 to 4, wherein: the organic material is water-soluble, and the preparation method comprises the following steps:
(1) preparing the glucocorticoid into an aqueous solution, and mixing the aqueous solution with the organic material to prepare a water phase;
(2) adding a surfactant into the liquid paraffin, and uniformly stirring to prepare an oil phase;
(3) adding the water phase into the oil phase, fully mixing, and carrying out emulsification or crosslinking reaction;
(4) and (4) centrifuging, washing and vacuum freeze-drying the material obtained in the step (3) to obtain the sustained-release embolism microsphere.
6. The sustained-release embolic microsphere of claim 5, wherein: the surfactant is at least one of sorbitan monooleate, propylene glycol monolaurate and propylene glycol fatty acid ester.
7. The sustained-release embolic microsphere of claim 6, wherein: the sorbitan monooleate is Span-80 or Arlacel-80, the propylene glycol monolaurate is Atlas G-917 or Atlas G-3851, and the propylene glycol fatty acid ester is Emcol PL-50.
8. A slow release embolic microsphere as claimed in any one of claims 1 to 4, wherein: the organic material is insoluble in water and is prepared by a method comprising:
(1) preparing the glucocorticoid into an aqueous solution;
(2) adding the aqueous solution into an organic phase containing the organic material, and performing vortex emulsification to form a water-in-oil emulsion;
(3) adding the water-in-oil emulsion into a water-soluble dispersant, and further emulsifying to form a water-in-oil-in-water emulsion;
(4) and (3) placing the water-in-oil-in-water emulsion in ice bath for ultrasonic treatment, stirring for 10-15h, and then sequentially centrifuging, washing and vacuum freeze-drying to obtain the slow-release embolism microsphere.
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