CN111298189A - Iodized oil suppository easy to inject and preparation method thereof - Google Patents
Iodized oil suppository easy to inject and preparation method thereof Download PDFInfo
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- CN111298189A CN111298189A CN201811507698.0A CN201811507698A CN111298189A CN 111298189 A CN111298189 A CN 111298189A CN 201811507698 A CN201811507698 A CN 201811507698A CN 111298189 A CN111298189 A CN 111298189A
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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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic materials
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- 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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- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Abstract
The invention relates to an iodized oil embolic agent which is easy to inject and has high drug-loading rate and a preparation method thereof. The suppository is provided for solving the problems of difficult injection and medicine loading in the process of iodized oil embolism in clinical application, is a mixture consisting of iodized oil, oil for injection, emulsifier and antitumor drug, and has the functions of embolism, development and chemotherapy. The embolic agent greatly reduces the viscosity of iodized oil by introducing the injection oil with lower viscosity and the emulsifier, is beneficial to injecting, and the particle size of emulsion drops obtained after emulsification can be controlled by adjusting the proportion of the emulsifier and has more stable structure. The suppository can be used for solubilizing oil-soluble antitumor drugs by using oil for injection and an emulsifier, can also be used for solubilizing water-soluble antitumor drugs by forming a W/O emulsion, and is simple and easy to prepare.
Description
Technical Field
The invention relates to an iodized oil embolic agent with easy push injection and high drug-loading rate and a preparation method thereof, belonging to the field of medical diagnosis and interventional therapy.
Background
Malignant tumor is the second leading cause of death in human, seriously threatening human health, wherein the first five cancers dying from malignant tumor are: gastric cancer, liver cancer, lung cancer, esophageal cancer and colorectal cancer. The main methods for treating malignant tumors at present include surgical treatment, radiotherapy, chemotherapy, and interventional therapy. Transcatheter arterial embolization (TCAE) has proven to be a non-surgical, effective method for treating solid tumors by selectively injecting embolization material through a catheter into the supply vessel of a diseased organ, occluding the corresponding vessel, and interrupting the blood supply. Currently available intervening materials are: particulate embolic materials, such as gelatin, albumin, microspheres, and the like; liquid embolic materials such as absolute ethyl alcohol, iodized oil, etc.; large embolic materials such as coils, removable balloons, and the like. The present clinically applied arterial blood vessel embolism of malignant tumor is mainly made of biodegradable material, such as iodized oil, gelatin, etc.
Iodized oil is an organic iodine injection with viscosity, is also called as positive embolic agent because it can be developed under X-ray, and is commonly used as hepatic artery embolic agent in the interventional therapy of clinical liver cancer. On the other hand, the iodized oil has high affinity to malignant tumor tissues and targeting property, and clinically utilizes the characteristics, the iodized oil and an anticancer drug such as 5-fluorouracil are mixed to prepare emulsion for interventional therapy of diseases such as late-stage tumors, the iodized oil blocks blood supply of cancer cells by using viscosity, and the 5-fluorouracil diffuses to the tumor cells and kills the tumor cells. However, this emulsification method has the disadvantage that the chemotherapeutic agent is not dissolved or sufficient, resulting in a reduced efficacy. Meanwhile, the iodine oil is too viscous, so that the iodine oil is not easy to inject in the operation process.
Disclosure of Invention
The invention aims to provide an embolic agent with easy injection and high drug-loading rate and a preparation method thereof, aiming at the problems of difficult injection and difficult drug loading of iodized oil in the clinical application process. The suppository is a mixture of iodized oil, injectable oil, emulsifier and antitumor agent, and has embolization, development and chemotherapy effects. Wherein the iodized oil has developing function, the oil for injection and the emulsifier play roles in solubilizing the chemotherapeutic drugs and reducing the viscosity, and the embolic agent also has slow release function.
The invention is realized by the following technical scheme:
the invention provides an iodized oil suppository which is easy to inject and has high drug-loading rate.
The iodized oil is a commercially available iodized oil injection for CT radiography, and contains 200 iodine and 1000mg/ml iodine.
The oil for injection is grease which conforms to the specification of injection in pharmacopoeia and comprises one or the combination of the following materials: ethyl oleate, medium-chain (C6-10) fatty glyceride, isopropyl myristate, soybean oil, sesame oil, tea oil, olive oil, castor oil, peanut oil, cottonseed oil, etc.
The emulsifier comprises a surfactant and a co-surfactant.
The surfactant comprises one or a combination of the following materials: soybean lecithin, egg yolk lecithin, cephalin, poloxamer 188, Brij 35, Myrj51, Myrj53, Cremophor RH40, Cremophor EL, Tween 80, Tween 85 and the like.
The cosurfactant comprises one or a combination of the following materials: ethanol, 1, 2-propylene glycol, glycerol, polyethylene glycol 400, ethylene glycol monoethyl ether, and the like.
The anti-tumor drug is a water-soluble anti-tumor drug or an oil-soluble anti-tumor drug.
The water-soluble anti-tumor medicine comprises one of the following medicines or the combination of the following medicines: doxorubicin hydrochloride, gemcitabine, cisplatin, 5-fluorouracil, cytarabine, carboplatin, mitomycin, captoposide, pingyangmycin and the like.
The oil-soluble anti-tumor medicine comprises one or the combination of the following medicines: adriamycin, carmustine, camptothecin, paclitaxel, vincristine, elemene, docetaxel, fotemustine, etc.
The embolic agent comprises the following components in percentage by mass: 30-50% of iodized oil, 0-39% of oil for injection, 0-49% of emulsifier, 5-19% of water for injection and 0.1-10% of water-soluble antitumor drug.
The embolic agent comprises the following components in percentage by mass: 30-60% of iodized oil, 0-49% of oil for injection, 0-49% of emulsifier and 0.1-10% of oil-soluble antitumor drug.
The preparation method of the embolic agent comprises the following steps:
for water-soluble antitumor drugs:
(1) dissolving water soluble antitumor agent in appropriate amount of injectable water to obtain water phase.
(2) Mixing iodized oil, oil for injection and emulsifier according to a certain proportion, and stirring in a stirrer at the rotation speed of 500 plus 5000rpm/min for 20-60 min to obtain oil phase.
(3) And (3) adding the water phase in the step (1) into the oil phase in the step (2) (the volume ratio is 1:5-20), stirring the mixture in a stirrer at the rotation speed of 500-5000rpm/min for 20-60 min at the temperature of 20-50 ℃, and obtaining the required embolic agent.
For oil-soluble antitumor drugs:
(1) adding the medicine into a certain amount of oil for injection, stirring with a stirrer at a rotation speed of 100-1000 rpm/min for 20-120 min.
(2) And (3) mixing the oil solution obtained in the step (1), iodized oil and an emulsifier according to a certain proportion, and stirring the mixture in a stirrer at the rotation speed of 500-5000rpm/min for 20-60 min at the temperature of 20-50 ℃ to obtain the required embolic agent.
When the in vitro dilution multiple of the embolic agent is 5 to 100 times, emulsion drops with the grain diameter of 0.1 to 900 mu m are formed.
The invention has the beneficial effects that:
(1) the invention solves the problem of difficult drug loading of iodized oil, can obviously increase the solubility of oil-soluble antitumor drugs by introducing oil for injection and an emulsifier, and increases the drug loading of water-soluble antitumor drugs in a W/O emulsion form. Meanwhile, the suppository prepared by the invention has a slow release effect.
(2) The invention greatly reduces the viscosity of the iodized oil by introducing the injection oil with lower viscosity and the emulsifier, is beneficial to injecting, and has stable structure because the particle size of emulsion drops obtained after emulsification is controlled by adjusting the proportion of the emulsifier.
Drawings
FIG. 1 is a graph showing the particle size distribution of the antitumor agent-containing embolic agent of example 1 after being diluted 5 times
FIG. 2 is a CT image of the embolization agent containing an antitumor agent according to example 1 after the embolization
FIG. 3 is a graph showing the particle size distribution of the embolization agent containing an antitumor agent of example 2 after 5-fold dilution
FIG. 4 is a CT image of the embolization agent containing an anti-tumor agent of example 2 after the embolization.
Detailed Description
Example 1: preparation of suppository containing antineoplastic agent
(1) Adding paclitaxel 20 mg into 1, 2-propylene glycol 150mg, heating to 40 deg.C, and magnetically stirring for 20 min.
(2) 500 mg of iodized oil and Cremophor RH 40330 mg are taken and filled in a small bottle, and the small bottle is placed on a magnetic stirrer to be stirred, wherein the stirring speed is 1200 rpm/min, and the stirring time is 40 min.
(3) And (3) mixing the liquids obtained in the steps (1) and (2), and then placing the mixture on a magnetic stirrer for stirring, wherein the stirring speed is 1000rpm/min, the stirring time is 45 min, and the temperature is maintained at 40 ℃. Finally obtaining a light yellow uniform solution which is the required embolic agent. Diluting the suppository with water for injection 5-10 times before operation to obtain emulsion drop with particle diameter of 5-110 μm (shown in figure 1), which is easy for injection. The development effect is obvious when the patient with liver cancer is subjected to transcatheter arterial embolization (as shown in figure 2).
Example 2: preparation of suppository containing antineoplastic agent
(1) Adding carmustine 30 mg into medium-chain fatty glyceride 150mg, and stirring with a magnetic stirrer at 600 rpm/min for 50 min at 45 deg.C.
(2) 400 mg of iodized oil, 40300 mg of Cremophor RH and 120 mg of PEG 400120 mg are taken and added into a small bottle, and the small bottle is placed on a magnetic stirrer to be stirred, wherein the rotating speed is 1000rpm/min, and the stirring time is 45 min.
(3) And (3) mixing the liquids in the steps (1) and (2), and stirring on a magnetic stirrer at the rotating speed of 800rpm/min for 60 min to obtain a light yellow uniform liquid, namely the required embolic agent. Diluting the suppository with water for injection 5-10 times before operation to obtain emulsion drop with particle diameter of 50-400 μm (as shown in figure 3), which is easy for injection. The development effect is obvious when the patient with liver cancer is subjected to transcatheter arterial embolization (as shown in figure 4).
Example 3: preparation of suppository containing antineoplastic agent
(1) And (3) filling 450 mg of ethyl oleate and 30 mg of docetaxel into a small bottle, preheating to 45 ℃, placing the small bottle on a magnetic stirrer, and stirring at the rotation speed of 500 rpm/min for 30 min to fully dissolve the docetaxel in the ethyl oleate.
(2) Adding 520 mg of iodized oil into the ethyl oleate, and stirring on a magnetic stirrer at the rotation speed of 800rpm/min for 45 min to obtain a slightly yellowish uniform oil solution. The oil solution is the required embolic agent, and the viscosity of the mixed solution is obviously reduced compared with that of iodized oil due to the lower viscosity of the ethyl oleate. The embolic agent is manually emulsified to form small drops with the particle size of 100-.
Example 4: preparation of suppository containing antineoplastic agent
(1) 30 mg of 5-fluorouracil was dissolved in 150mg of water for injection as an aqueous phase.
(2) Putting 350 mg of iodized oil, 250 mg of ethyl oleate, 50mg of Cremophor RH 401and 70mg of 1, 2-propylene glycol into a small bottle, and magnetically stirring at 35 ℃ at the rotating speed of 800rpm/min for 1h to finally obtain uniform liquid serving as an oil phase.
(3) Slowly adding the water phase into the oil phase, and stirring on a magnetic stirrer at 1000rpm/min for 45 min at 25 deg.C. Finally, the W/O emulsion with uniform distribution is obtained, namely the obtained embolic agent. Diluting the mixed solution with water for injection 5-10 times before operation to obtain W/O/W emulsion drop with particle diameter of 5-50 μm. After operation, 5-fluorouracil crosses the oil layer and is slowly released into blood, thereby realizing the purpose of slow release.
Example 5: preparation of suppository containing antineoplastic agent
(1) Doxorubicin hydrochloride 30 mg was dissolved in 150mg water for injection as an aqueous phase.
(2) Putting 450 mg of iodized oil, 150mg of medium-chain fatty glyceride, 80170 mg of Tween and 50mg of glycerol into a small bottle, and magnetically stirring at 35 ℃ at the rotating speed of 1000rpm/min for 1h to finally obtain uniform liquid serving as an oil phase.
(3) Slowly adding the water phase into the oil phase, and stirring on a magnetic stirrer at 1000rpm/min for 45 min at 25 deg.C. Finally, the W/O emulsion with uniform distribution is obtained, namely the obtained embolic agent. Diluting the mixed solution with water for injection 5-10 times before operation to obtain W/O/W emulsion droplet with particle diameter of 20-100 μm. After operation, the doxorubicin hydrochloride crosses an oil layer and is slowly released into blood, so that the purpose of slow release is realized.
Example 6: preparation of suppository containing antineoplastic agent
(1) Cisplatin (50 mg) was dissolved in 150mg of water for injection as an aqueous phase.
(2) And (3) putting 500 mg of iodized oil, 120 mg of Cremophor EL, 120 mg of Cremophor RH 40100 mg and PEG 40080 mg into a small bottle, and magnetically stirring at 35 ℃ at the rotating speed of 1000rpm/min for 1h to finally obtain uniform liquid serving as an oil phase.
(3) Slowly adding the water phase into the oil phase, and stirring on a magnetic stirrer at 1000rpm/min for 45 min at 25 deg.C. Finally, the W/O emulsion with uniform distribution is obtained, namely the obtained embolic agent. Diluting the mixed solution with water for injection 5-10 times before operation to obtain W/O/W emulsion drop with particle diameter of 0.5-20 μm. After operation, cisplatin crosses an oil layer and is slowly released into blood, so that the aim of slow release is fulfilled.
Example 7: preparation of suppository containing antineoplastic agent
(1) Adding 30 mg of elemene into 150mg of soybean oil, and stirring on a magnetic stirrer at the rotation speed of 600 rpm/min for 50 min at the temperature of 45 ℃.
(2) 450 mg of iodized oil, 80300 mg of Tween and 70mg of glycerol are taken and added into a small bottle, and the small bottle is placed on a magnetic stirrer to be stirred, wherein the rotating speed is 1200 rpm/min, and the stirring time is 35 min.
(3) And (3) mixing the liquids in the steps (1) and (2), and stirring on a magnetic stirrer at the rotating speed of 800rpm/min for 60 min to obtain a light yellow uniform liquid, namely the required embolic agent. The suppository is diluted 5-10 times with water for injection before operation to obtain emulsion drop with particle size of 80-500 μm, which is easy to be injected. The development effect is obvious when the transcatheter arterial embolization is carried out on the liver cancer patient.
Example 8: preparation of suppository containing antineoplastic agent
(1) Adding vincristine 15 mg into castor oil 55 mg and ethyl oleate 80 mg, stirring with a magnetic stirrer at 600 rpm/min for 55 min at 45 deg.C.
(2) 350 mg of iodized oil, 35100 mg of Brij, 53200 mg of Myrj and 400200 mg of PEG are taken and added into a small bottle, and the small bottle is placed on a magnetic stirrer to be stirred at the rotating speed of 1000rpm/min for 45 min.
(3) And (3) mixing the liquids in the steps (1) and (2), and stirring on a magnetic stirrer at the rotating speed of 800rpm/min for 60 min to obtain a light yellow uniform liquid, namely the required embolic agent. The suppository is diluted 5-10 times with water for injection before operation to obtain emulsion drop with particle size of 200-.
Example 9: preparation of suppository containing antineoplastic agent
(1) Adding adriamycin 80 mg into medium-chain fatty glyceride 100 mg and ethyl oleate 200 mg, and stirring with a magnetic stirrer at 600 rpm/min for 55 min at 45 deg.C.
(2) Adding 300 mg of iodized oil, 18850 mg of poloxamer, 80200 mg of Tween and 70mg of PEG 40070 mg into a small bottle, and stirring on a magnetic stirrer at the rotation speed of 1000rpm/min for 45 min.
(3) And (3) mixing the liquids in the steps (1) and (2), and stirring on a magnetic stirrer at the rotating speed of 1000rpm/min for 40 min to obtain a light yellow uniform liquid, namely the required embolic agent. Diluting the suppository with water for injection 5-10 times before operation to obtain emulsion drop with particle diameter of 0.5-20 μm.
Example 10: preparation of suppository containing antineoplastic agent
(1) Adding 50mg of fotemustine into 250 mg of medium-chain fatty glyceride, and stirring on a magnetic stirrer at the rotation speed of 800rpm/min for 55 min at the temperature of 35 ℃.
(2) Adding iodized oil 400 mg, soybean lecithin 30 mg, poloxamer 18850 mg, Tween 85200 mg and PEG 40020 mg into a small bottle, and stirring with a magnetic stirrer at 1000rpm/min for 45 min.
(3) And (3) mixing the liquids in the steps (1) and (2), and stirring on a magnetic stirrer at the rotating speed of 1000rpm/min for 40 min to obtain a light yellow uniform liquid, namely the required embolic agent. Diluting the suppository with water for injection 5-10 times before operation to obtain emulsion droplet with particle diameter of 2-200 μm.
Example 11: preparation of suppository containing antineoplastic agent
(1) 5-Fluorouracil (50 mg) was dissolved in 150mg of water for injection as an aqueous phase.
(2) 450 mg of iodized oil, 200 mg of ethyl oleate, 80100 mg of Tween and 20 mg of ethanol are taken and put into a small bottle, and magnetic stirring is carried out at the temperature of 45 ℃, the rotating speed is 1000rpm/min, the stirring time is 1h, and finally uniform liquid is obtained and is used as an oil phase.
(3) Slowly adding the water phase into the oil phase, and stirring on a magnetic stirrer at 1000rpm/min for 45 min at 25 deg.C. Finally, the W/O emulsion with uniform distribution is obtained, namely the obtained embolic agent. Diluting the mixed solution with water for injection 5-10 times before operation to obtain W/O/W emulsion droplet with particle diameter of 50-600 μm. After operation, cisplatin crosses an oil layer and is slowly released into blood, so that the aim of slow release is fulfilled.
Claims (13)
1. An iodized oil suppository easy to inject and high in drug loading is characterized by comprising iodized oil, oil for injection, an emulsifier and an anti-tumor drug.
2. The embolic agent according to claim 1, wherein the iodized oil is commercially available iodized oil injection for CT contrast, containing 200 iodine and 1000mg/ml iodine.
3. The embolic agent according to claim 1, wherein said injectable oil is a fat according to the prescription of injectable in pharmacopoeia, comprising one or a combination of the following materials: ethyl oleate, medium-chain (C6-10) fatty glyceride, isopropyl myristate, soybean oil, sesame oil, tea oil, olive oil, castor oil, peanut oil, cottonseed oil, etc.
4. An embolic agent according to claim 1, characterized in that said emulsifier comprises a surfactant and a co-surfactant.
5. The embolic agent according to claim 4, characterized in that said surfactant comprises one or a combination of the following materials: soybean lecithin, egg yolk lecithin, cephalin, poloxamer 188, Brij 35, Myrj51, Myrj53, Cremophor RH40, Cremophor EL, Tween 80, Tween 85 and the like.
6. The embolic agent according to claim 4, characterized in that said co-surfactant comprises one or a combination of the following materials: ethanol, 1, 2-propylene glycol, glycerol, polyethylene glycol 400, ethylene glycol monoethyl ether, and the like.
7. The embolic agent according to claim 1, wherein said anti-tumor drug is a water-soluble anti-tumor drug or an oil-soluble anti-tumor drug.
8. The embolic agent according to claim 7, wherein said water-soluble antineoplastic agent comprises one or a combination of the following drugs: doxorubicin hydrochloride, gemcitabine, cisplatin, 5-fluorouracil, cytarabine, carboplatin, mitomycin, captoposide, pingyangmycin and the like.
9. The embolic agent according to claim 7, wherein said oil-soluble antineoplastic agent comprises one or a combination of the following drugs: adriamycin, carmustine, camptothecin, paclitaxel, vincristine, elemene, docetaxel, fotemustine, etc.
10. The embolic agent according to claim 1, wherein the mass fractions of the components in the embolic agent are respectively: 30-50% of iodized oil, 0-39% of oil for injection, 0-49% of emulsifier, 5-19% of water for injection and 0.1-10% of water-soluble antitumor drug.
11. The embolic agent according to claim 1, wherein the mass fractions of the components in the embolic agent are respectively: 30-60% of iodized oil, 0-49% of oil for injection, 0-49% of emulsifier and 0.1-10% of oil-soluble antitumor drug.
12. The method for preparing the embolic agent according to claim 1, wherein the method for preparing the embolic agent comprises the steps of ① dissolving the water-soluble antineoplastic agent in a proper amount of water for injection to serve as a water phase, mixing the iodized oil, the oil for injection and an emulsifier according to a certain proportion, stirring the mixture in a stirrer at a rotation speed of 5000rpm/min and a stirring time of 20-60 min to serve as an oil phase, adding the water phase obtained in the step 1 into the oil phase obtained in the step 2 (volume ratio of 1:5-20), stirring the mixture in the stirrer at a rotation speed of 500-5000rpm/min and a stirring time of 20-60 min and a temperature of 20-50 ℃ to obtain the needed embolic agent, ② adding the drug into a certain amount of oil for injection to stir the oil solution in the stirrer at a rotation speed of 100-1000 rpm/min and a stirring time of 20-120 min to obtain the needed embolic agent, and mixing the oil solution in the step 1 with the iodized oil and the emulsifier according to a certain proportion, stirring the mixture in the stirrer at a rotation speed of 500-500 rpm and a stirring time of 20-60 ℃ to obtain the needed embolic agent.
13. The embolic agent of claim 1, wherein said embolic agent forms emulsion droplets having a particle size of 0.1-900 μm when diluted 5-100 times in vitro.
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Cited By (2)
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| CN110302434A (en) * | 2019-07-14 | 2019-10-08 | 大连医科大学 | A kind of Lipiodol embolizatim agent and preparation method thereof for being easy to inject |
| CN114099764A (en) * | 2021-11-29 | 2022-03-01 | 广东粤港澳大湾区国家纳米科技创新研究院 | Preparation method of W/O/W type temperature-sensitive embolic agent |
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