A method for improving the stability of iodized vegetable oil fatty acid ethyl ester
By adding iodine adsorbent such as sodium sulfite to ethylene gas for stirring and dissolving, the problem of insufficient stability of ethyl esters of fatty acids of iodized vegetable oils is solved, and a high stability and low cost process solution is achieved, satisfying the quality of diagnostic contrast drugs standard.
Patent Information
- Application Number
- CN202210503713.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-05-10
- Publication Date
- 2024-12-31
- Estimated Expiration
- 2042-05-10
AI Technical Summary
The ethyl esters of iodized vegetable oil fatty acid prepared in the prior art have stability problems, and the combination of iodine is unstable, which leads to easy decomposition after long-term placement and cannot meet the quality standards of diagnostic contrast drugs.
Iodine adsorbent such as sodium sulfite is added in the presence of ethylene gas, stirred and dissolved with an ether solvent, washed with liquid and water, filtered and concentrated to obtain a stable finished product of ethyl iodized vegetable oil fatty acid.
The stability of the ethyl iodized vegetable oil fatty acid is significantly improved. After 12 months of accelerated stability test, the appearance has not changed significantly, the iodine content remains stable, the process is simple, the cost is low, and the operation is high.
Smart Images
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Abstract
Description
Technical Field
[0001] The invention relates to the technical field of contrast agents, and in particular to a method for improving the stability of iodized vegetable oil fatty acid ethyl ester. Background Art
[0002] Iodized oil is the organic iodine compound that the fatty acid of vegetable oil such as royal rice oil etc. is combined with iodine, and it is super liquid iodized oil (Lipiodol Ultra Fluide) after forming ethyl ester through transesterification, is also referred to as ethiodized oil (Ethiodized oil). Clinically, ethiodized oil can be used as diagnostic imaging, interventional therapy etc., because its viscosity is low, the characteristic of good fluidity, therefore more has clinical advantage with respect to common iodized oil.At present, the main method of preparing iodized vegetable oil fatty acid ester in production is described as follows: under the condition that water exists, alkali metal iodide (such as sodium iodide) and alkyl silyl halide (such as trimethylchlorosilane) react and generate hydroiodic acid, then carry out iodine addition with the unsaturated fatty acid or fatty acid ester of vegetable oil and obtain iodized vegetable oil fatty acid ester. However, due to the complexity of the preparation process of iodized vegetable oil fatty acid esters and the composition of vegetable oil fatty acid esters, the iodized vegetable oil fatty acid esters obtained in the prior art generally have stability problems. The bound iodine therein is not stable and is easily decomposed to release iodine after being left for a long time, causing the color of ethiodized oil to become darker and the iodine content to be unqualified, thus making it unusable.
[0003] CN101245007A reports the preparation method of stable iodized vegetable oil fatty acid ethyl ester, and the method for improving the stability of iodized vegetable oil fatty acid ethyl ester disclosed in the patent is: air is introduced within a certain temperature range to remove unstable iodine, and sodium metabisulfite solution is used for absorption, and then washed with distilled water, and finally dried within a certain pressure and temperature range to obtain the finished product; CN107287029B discloses a method for improving product stability by aging treatment, that is, the refined iodized vegetable oil fatty acid ethyl ester is heated and stirred for a certain time, and then purified. Through process research, it is found that the above methods have complicated operation procedures, and the stability of the iodized vegetable oil fatty acid ethyl ester obtained is still difficult to meet the quality standard of the ethyl iodized oil medicine for diagnosing contrast.
[0004] Therefore, it is necessary to develop a low-cost, simple-to-operate process to improve product stability. Summary of the invention
[0005] In order to solve the problems existing in the prior art, the present invention provides a method for improving the stability of iodized vegetable oil fatty acid ethyl ester, characterized in that it comprises the following steps:
[0006] 1) adding iodine adsorbent to crude ethiodized oil in the presence of ethylene gas and stirring at a certain temperature;
[0007] 2) After the stirring is completed, an ether solvent is added to dissolve it, and after separation, it is washed with water, and then a separation operation is performed to obtain an organic phase;
[0008] 3) filtering the organic phase, collecting the filtrate and concentrating it to obtain a stable iodized vegetable oil fatty acid ethyl ester finished product.
[0009] Preferably, the water in step (2) is drinking water.
[0010] The mass ratio of the crude ethiodized oil to the iodine adsorbent is 1:(0.8-1.3), preferably, the mass ratio of the crude ethiodized oil to the iodine adsorbent is 1:(0.9-1.1), and most preferably, the mass ratio of the crude ethiodized oil to the iodine adsorbent is 1:1.
[0011] The iodine adsorbent is selected from sulfites. Preferably, the iodine adsorbent is selected from one of sodium sulfite, sodium bisulfite and sodium pyrosulfite. Most preferably, the iodine adsorbent is sodium sulfite.
[0012] The iodine adsorbent should be an aqueous solution with a mass concentration of 8-12%. Preferably, the mass concentration of the iodine adsorbent is 10%.
[0013] In step (1), the stirring temperature is controlled at 70-90°C, more preferably 80°C.
[0014] In step (1), the stirring time is controlled to be 3-10 hours, more preferably 4-5 hours.
[0015] In step (2), the ether solvent is selected from one of diethyl ether, isopropyl ether and petroleum ether, preferably isopropyl ether.
[0016] In step (2), the mass volume ratio of the crude ethiodized oil to the ether solvent is 1:(2.0-2.5), preferably 1:(2.1-2.3).
[0017] In step (2), the mass volume ratio of the crude ethiodized oil to water is 1:(1.6-1.9), preferably 1:(1.8-1.9).
[0018] In step (3), the concentration temperature is controlled at 45-60°C, preferably, at 49-50°C.
[0019] The technical solution of the present invention has the following beneficial effects:
[0020] The invention provides a method for improving the stability of iodized vegetable oil fatty acid ethyl ester. Compared with the prior art, the technical solution of the invention has simpler process, low cost, short time consumption and high industrial operability. In addition, the technical solution of the invention uses ethylene to remove unstable iodine, thereby significantly improving the stability of iodized vegetable oil fatty acid ethyl ester. After an accelerated stability test for 12 months, the appearance has no obvious change and is amber, and the iodine content remains stable compared with that before the acceleration. DETAILED DESCRIPTION
[0021] In order to better understand the technical solution of the present invention, the technical solution of the present invention is further described below in conjunction with specific embodiments. The embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.
[0022] Example 1: Refining of crude iodized vegetable oil fatty acid ethyl ester
[0023] Put the crude product of ethiodized poppy oil (55 kg) into a 500L glass-lined kettle, introduce ethylene gas at 80°C, add 10% sodium sulfite aqueous solution (55 kg) and stir for 4 hours, then add isopropyl ether (120 kg) to dissolve, separate the liquids, wash with drinking water (100 kg), separate the liquids. Obtain the organic phase, filter it to a clean area, concentrate the filtrate at 50°C, and obtain about 50 kg of the finished product of ethiodized poppy oil.
[0024] Example 2: Refining of crude iodized vegetable oil fatty acid ethyl ester
[0025] Put the crude product of ethiodized poppy oil (55 kg) into a 500L glass-lined kettle, introduce ethylene gas at 80°C, add 10% sodium thiosulfate aqueous solution (55 kg) and stir for 4 hours, then add isopropyl ether (120 kg) to dissolve, separate the liquids, wash with drinking water (100 kg), separate the liquids. Obtain the organic phase, filter it to a clean area, concentrate the filtrate at 50°C, and obtain about 50 kg of the finished product of ethiodized poppy oil.
[0026] Example 3: Refining of crude iodized vegetable oil fatty acid ethyl ester
[0027] Put the crude product of ethiodized poppy oil (35g) into a 500mL reaction bottle, introduce ethylene gas at 80°C, add 10% sodium sulfite aqueous solution (35g) and stir for 4h, then add petroleum ether (77g) to dissolve, separate the liquids, wash with drinking water (66.5g), separate the liquids. Obtain the organic phase, filter to the clean area, concentrate the filtrate at 50°C, and obtain about 31.8g of the finished product of ethiodized poppy oil.
[0028] Example 4: Refining of crude iodized vegetable oil fatty acid ethyl ester
[0029] Put crude poppy ethiodized oil (35 g) into a 500 mL reaction bottle, add 10% sodium sulfite aqueous solution (35 g) and stir for 4 hours at 80°C, then add isopropyl ether (77 g) to dissolve, separate the liquids, wash with drinking water (66.5 g), separate the liquids. Obtain the organic phase, filter to a clean area, concentrate the filtrate at 50°C, and obtain about 31.5 g of finished poppy ethiodized oil.
[0030] Example 5: Determination of iodine content and accelerated stability test of poppy ethiodized oil
[0031] 1) Determination of iodine content
[0032] The samples prepared in Examples 1-4 were titrated to determine the iodine content. The samples of each example were repeated three times. The specific operation was as follows:
[0033] Weigh 0.6g of sample accurately into a 200ml beaker, add 40ml of potassium hydroxide ethanol solution, evaporate into lumps on a water bath, dissolve the residue completely with 150-200ml hot water, cool to room temperature, add 5ml of glacial acetic acid, and titrate to the end point with silver nitrate titration solution (0.1mol / L) by potentiometric titration. Each 1ml of silver nitrate titration solution (0.1mol / L) is equivalent to 12.69mg of iodine.
[0034] Calculation formula:
[0035]
[0036] Where: V is the volume of silver nitrate titration solution consumed, mL;
[0037] C is the concentration of silver nitrate titration solution, mol / L;
[0038] W is the sample weight of the test sample, g (calculated based on the anhydrous substance).
[0039] 2) Accelerated stability test
[0040] The samples prepared in Examples 1-4 were subjected to a 12-month accelerated test, with three replicates of each sample, and the color, iodine content, moisture content, and absorbance of the samples were examined. The results are shown in the following table:
[0041]
[0042]
[0043] Note: Under normal standards, the color should be amber, the iodine content should be 37%-39% (g / g), the moisture content should be ≤0.06%, 420nm and λ 460nm The absorbance at is ≤0.6.
Claims
1. A method for improving the stability of iodized vegetable oil fatty acid ethyl ester, characterized in that It includes the following steps: 1) adding iodine adsorbent to crude ethiodized oil in the presence of ethylene gas and stirring at a certain temperature; 2) After the stirring is completed, an ether solvent is added to dissolve it, and after separation, it is washed with water, and then a separation operation is performed to obtain an organic phase; 3) filtering the organic phase, collecting the filtrate and concentrating it to obtain a stable iodized vegetable oil fatty acid ethyl ester finished product; In the step (1), the mass ratio of the crude ethiodized oil to the iodine adsorbent is 1:(0.8-1.3); The iodine adsorbent is selected from one of sodium sulfite, sodium bisulfite and sodium pyrosulfite; The iodine adsorbent should be an aqueous solution with a mass concentration of 8-12%; In the step (1), the stirring temperature is controlled at 70-90° C.; and the stirring time is controlled at 3-10 hours.
2. The method according to claim 1, wherein the mass ratio of the crude ethiodized oil to the iodine adsorbent in the step (1) is 1:(0.9-1.1).
3. The method according to claim 2, wherein the mass ratio of the crude ethiodized oil to the iodine adsorbent in step (1) is 1:
1.
4. The method according to claim 1, wherein the mass concentration of the iodine adsorbent is 10%.
5. The method according to claim 1, wherein the stirring temperature in step (1) is controlled at 80°C.
6. The method of claim 1, wherein the stirring time is 4-5 hours.
7. The method according to claim 1, wherein the ether solvent in step (2) is selected from one of diethyl ether, isopropyl ether and petroleum ether.
8. The method according to claim 7, wherein the ether solvent in step (2) is isopropyl ether.
9. The method according to claim 1, wherein the water in step (2) is drinking water; and the concentration temperature in step (3) is controlled at 45-60°C.
10. The method according to claim 9, wherein the concentration temperature in step (3) is controlled at 49-50°C.