CN109554231A - A kind of preparation method for the iodized oil that quality is stable - Google Patents
A kind of preparation method for the iodized oil that quality is stable Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11C—FATTY ACIDS FROM FATS, OILS OR WAXES; CANDLES; FATS, OILS OR FATTY ACIDS BY CHEMICAL MODIFICATION OF FATS, OILS, OR FATTY ACIDS OBTAINED THEREFROM
- C11C3/00—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/18—Iodine; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B3/00—Refining fats or fatty oils
- C11B3/001—Refining fats or fatty oils by a combination of two or more of the means hereafter
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- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B3/00—Refining fats or fatty oils
- C11B3/12—Refining fats or fatty oils by distillation
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/0095—Control aspects
- B01J2219/00952—Sensing operations
- B01J2219/00954—Measured properties
- B01J2219/00961—Temperature
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/0095—Control aspects
- B01J2219/00984—Residence time
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Abstract
The invention discloses a kind of preparation methods of iodized oil that quality is stable, comprising the following steps: the first step, the pretreated polyunsaturated vegetable oil that will dewax by degreasing are mixed to form solution with solvent appropriate；Red phosphorus, the crystalline flake of iodine is added in iodate hydrogen generator in second step, and hydroiodic acid is added dropwise, and the iodate hydrogen that reaction generates is imported and is compressed in hydrogen iodide air accumulator；Third step, the polyunsaturated vegetable oil solution that the first step obtains is reacted in micro passage reaction with the iodate hydrogen that second step obtains, micro passage reaction temperature controls -10~60 DEG C, residence time is 10~300s, keep the pressure of reaction system in 0.5bar or less, termination reaction is quenched with water after fully reacting, the oil reservoir separated purifying water washing, vacuum distillation obtain the stable iodized oil of quality.Method of the invention has the characteristics that safety and high production efficiency, at low cost, product are easy to purify, product stability is good, is suitble to efficient large-scale production.
Description
Technical field
The invention belongs to technical field of organic synthesis, specifically, being related to a kind of preparation side of iodized oil that quality is stable
Method.
Background technique
French western doctor Jia Bai of forces has invented iodized oil within 1901, is only applied to disappearing for human skin surface at that time
Poison.1918, property that iodized oil (Lipiodol) has impermeable Ⅹ line is chanced on, so that Lipiodol becomes in the world the
One is used for the Iodine contrast medium of x-ray.
Iodized oil is organoiodine compound of the fatty acid of vegetable oil such as peanut oil, poppy seed oil etc. in conjunction with iodine.China
Pharmacopeia 2015 version two have been recorded iodized oil and iodate fat injection, and iodized oil refers to be prepared by poppy seed oil iodate
, contain iodine (I) 37.0~41.0% (g/g).It is mainly used in iodine deficiency symptom treatment, radiodiagnosis contrast medium (contrast agent) and swells
The adjuvant treatment of tumor.Current iodized oil technique is all that addition reaction directly occurs by vegetable oil and iodate hydrogen, then leads to
It crosses washing process to remove colloid, free-iodine will be converted into conjunction with unstable iodine by aeration process, add weighting sulfurous
Sour sodium removes free-iodine.But existing iodate oil product is in the prevalence of stability problem, due to the combination in iodized oil
Iodine is simultaneously unstable, easily decomposes free iodine out, causes iodized oil product colour to aggravate, amount of iodine is unqualified, can not be used as contrast agent
With the purposes of suppository.
The traditional handicraft of iodized oil preparation at present is intermittent reaction, and reaction speed is slow, the addition reaction time up to 3~
6 days, while there is also troubling security risk and quality problems；Especially iodized oil makes in storage, transport, sale, waiting
During, free-iodine is further increased, and color is also deepened.
Found by technical study, the prior art there are many deficiencies place, be such as difficult to amplify in mass production, amplification then
Need special installation；Gaseous hydrogen iodide generates speed and is difficult to control, and easily causes suck-back, gas-liquid two-phase reaction is not very thorough
Bottom, often will cause the loss of hydrogen iodide gas and the reaction time is longer, be difficult to improve efficiency；Meanwhile the iodine for passing through hydrogen iodide
Changing vegetable oil is in black powder, is difficult to make color reach criterion of acceptability by simply washing.In addition, the stabilization of lipiodine
Property also have some problems, place for a long time it is easy to change, amount of iodine reduce, lead to not using.
Therefore, exploitation one is at low cost, easy to operate, product stability is good, is easily isolated purifying, is suitable for extensive life
The new process route produced is necessary.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of iodized oil that quality is stable, this method has safety and life
Produce high-efficient, at low cost, product be easy to purify, product stability is good, is suitble to the characteristics of efficient large-scale production, even if storing up
Deposit, transport, selling, etc. it is to be used during, free content of iodine will not be significantly raised, and color is also without significant intensification.
To achieve the goals above, The technical solution adopted by the invention is as follows:
The first aspect of the invention provides a kind of preparation method of iodized oil that quality is stable, comprising the following steps:
The first step, the pretreated polyunsaturated vegetable oil that will dewax by degreasing are mixed to form solution with solvent appropriate, no
The mass ratio of saturated vegetable oil and solvent is 1:(0.1~50)；
Polyunsaturated vegetable oil is peanut oil, perilla oil, linseed oil, sand sagebrush seed oil, walnut oil, safflower in the first step
Seed oil, grape seed oil or poppy seed oil；
Solvent appropriate is isopropyl ether, ether, ethyl acetate, methyl acetate in the first step；
Pretreated polyunsaturated vegetable oil is dewaxed the following steps are included: by unsaturated plant by degreasing in the first step
Oil declines 1~5 DEG C of rate of temperature fall Celsius on an hourly basis in low temperature thermostat bath, is cooled to 0~5 DEG C Celsius, continues Celsius 0
~5 DEG C of maintenances 4~for 24 hours, it filters to obtain the pretreated polyunsaturated vegetable oil of degreasing dewaxing；
Red phosphorus, the crystalline flake of iodine is added in iodate hydrogen generator in second step, and hydroiodic acid is added dropwise, the iodate that reaction is generated
Hydrogen is imported and is compressed in hydrogen iodide air accumulator, polyunsaturated vegetable oil, red phosphorus, the crystalline flake of iodine and hydroiodic acid mass ratio be (50
~90): 3:(25~45): 14；
Third step, the iodate hydrogen that the polyunsaturated vegetable oil solution and second step that the first step is obtained obtain is in microchannel
It is reacted in reactor, the mass ratio of control polyunsaturated vegetable oil and iodate hydrogen is (1.2~3.0): 1, micro passage reaction
- 10~60 DEG C Celsius of temperature control, the residence time is 10~300s, keeps the pressure of reaction system in 0.5bar hereinafter, reaction
Termination reaction is quenched with water after completely, the oil reservoir separated purifying water washing, vacuum distillation obtain the stable iodized oil of quality.
Preferably, the mass ratio of polyunsaturated vegetable oil and solvent is 1:(0.2~3 in the first step).
In order to which the vegetable oil iodine number for achieving the purpose that used is high, following high iodine number vegetable oil is selected to do related experiment:
10~40 DEG C Celsius of temperature control in micro passage reaction in the third step.
Reaction time is 30~120s in micro passage reaction in the third step.
Micro passage reaction is high throughput-micro passage reaction in the third step.
Due to the adoption of the above technical scheme, the present invention has the following advantages and beneficial effects:
The preparation method of the stable iodized oil of quality provided by the invention, production security are significantly high with production efficiency；It produces
Product are at low cost, are easy to purify；The characteristics of product stability is good, is suitble to efficient large-scale production.Obtained iodized oil, even if storing up
Deposit, transport, selling, etc. it is to be used during, free content of iodine will not be significantly raised, and color is also without significant intensification.It is logical
Cross experimental studies have found that, will prepare after resulting lipiodine carries out aging process, and unexpectedly obtain stability and significantly mentioned
High iodate oil product.
The preparation method of the stable iodized oil of quality provided by the invention, by testing and detecting discovery, vegetable oil and iodine
The reaction speed for changing hydrogen is faster, and it is easier that the iodized oil crude product of preparation isolates and purifies, and obtained iodized oil fine work color is more shallow, surely
It is qualitative higher, it is not easily decomposed out free-iodine.Show that vegetable oil is rapidly completed with iodate hydrogen addition reaction by analysis,
The pigment of generation is few and is easily removed.
The preparation method of the stable iodized oil of quality provided by the invention, core are to answer by high throughput-microchannel plate
The successive reaction mode of device realizes that addition reaction occurs for vegetable oil and iodate hydrogen, so that large-scale production goes out high-quality doctor
Medicine grade iodized oil；Compared with traditional reaction kettle batch production mode, the reaction time can be even reduced in tens seconds, be had
Reaction speed is fast, with short production cycle, the high distinguishing feature of quality.
Specific embodiment
In order to illustrate more clearly of the present invention, below with reference to preferred embodiment, the present invention is described further.Ability
Field technique personnel should be appreciated that following specifically described content is illustrative and be not restrictive, this should not be limited with this
The protection scope of invention.
Accelerated stability test method in the embodiment of the present invention: by finished product iodized oil be fitted into peace cut open in bottle after, in gas lamp
Upper sealing.It is placed in 40 ± 2 DEG C of insulating box Celsius, after 60 days, project (similarly hereinafter) needed for testing.
In the embodiment of the present invention dissociate iodine detecting method: take this product 1.0g, add chloroform 5ml, shake up, add water 10ml with
Potassium iodide 0.5g after dissolution, adds starch indicator solution 1ml, shaking, and such as aobvious bluish violet of water layer adds 0.1mol/L sodium thiosulfate molten
Liquid 1 drips, and bluish violet should be to disappear.(Chinese Pharmacopoeia 2015 editions " iodized oil ".)
Color detection method in the embodiment of the present invention: taking this product, with No. 10 standard color solutions of yellow (annex IX A first
Method) compare, it must not be deeper.(Chinese Pharmacopoeia 2015 editions " iodized oil ".)
Embodiment 1
The first step, by 440g peanut oil (grain and oil (Qingdao) Co., Ltd, food grade in good.Similarly hereinafter), in low temperature thermostat bath
(it is purchased from Gongyi City Ke Rui Instrument Ltd., model: the auspicious board DFY-50/30 of section.Decline Celsius 1~5 in similarly hereinafter) on an hourly basis
DEG C rate of temperature fall, be cooled to 0~5 DEG C (about 12h) Celsius, continue in 0~5 DEG C of maintenance 12h Celsius, in Bu Shi suction funnel
Middle suction filtration obtains degreasing dewaxing peanut oil 425g, and with 200g isopropyl ether, (Sinopharm Chemical Reagent Co., Ltd., reagent chemistry are pure.
It similarly hereinafter) dissolves spare.
Second step (is purchased from Dezhou City Fu Kai chemical industry Co., Ltd, model: 1000ml in iodate hydrogen generator
Kipp gas generator.In similarly hereinafter), red phosphorus 15g is added and (is purchased from Lianyun Harbour Rui Peng Chemical Co., Ltd., technical grade.Similarly hereinafter), the crystalline flake of iodine
200g (is purchased from Chile ATACAMA MINERIALS CHILE S.C.M, technical grade.Similarly hereinafter), it is molten that hydroiodic acid is continuously slowly added dropwise
Liquid 70g (is purchased from Tai'an Han Wei Group Co., Ltd, technical grade, content 57%.Similarly hereinafter), generated iodate hydrogen is stored
In corrosion-resistant hermetically sealed can, that is, hydrogen iodide air accumulator (liner poly fourfluoroplastics), then by pipeline through mass flowmenter, check valve, peace
It is spare that full valve etc. accesses micro passage reaction.
Third step, in heart-shaped micro passage reaction (the limited public affairs of Suzhou river in Shangdong Province Hao microfluidic technology share that material is special glass
WH-LAB 684 is taken charge of, similarly hereinafter.) in, it operates according to the following steps: (1) passing through peanut oil-isopropyl ethereal solution that the first step obtains
Liquid pump enters micro passage reaction, opens hydrogen iodide valve, enters micro passage reaction through mass flowmenter；(2) reaction process
Middle to use continuous flow micro passage reaction, proportionally 3.09:1 is mixed peanut oil-isopropyl ethereal solution in the reactor with hydrogen iodide
It closes, is reacted by heat exchanger at 30~40 DEG C；(3) by adjusting the flow of liquid pump frequency and hydrogen iodide gas flowmeter, control
The mass ratio of peanut oil processed-isopropyl ethereal solution and hydrogen iodide is 3.09:1, and the residence time 30 seconds, two strands of materials were on reaction module
Reaction；(4) by adjusting the counterbalance valve in reactor outlet, keep the pressure of reaction system in 0.3bar hereinafter, by flue
The pressure gauge of road measures；(5) after micro passage reaction, reaction solution enters in the quantizer equipped with 200ml water to be stirred material
It mixes and termination reaction is quenched, the oil reservoir separated purifying water washing, vacuum distillation removal isopropyl ether obtain iodized oil 623g, amount of iodine
31.5%, yield 98.1% (in terms of iodine), free-iodine is qualified, and color is qualified.
Through 40 DEG C of 60 days accelerated stability tests Celsius, free-iodine is qualified, and color is qualified.
Embodiment 2
440g peanut oil is declined 1~5 DEG C of rate of temperature fall Celsius by the first step on an hourly basis in low temperature thermostat bath, drop
Temperature continues to filter in Bu Shi suction funnel in 0~5 DEG C of maintenance 12h Celsius, it is de- to obtain degreasing to 0~5 DEG C (about 12h) Celsius
Snuff oil generation 425g is dissolved spare with 1200g isopropyl ether.
Second step is added red phosphorus 15g, crystalline flake of iodine 195g, it is molten that hydroiodic acid is continuously slowly added dropwise in iodate hydrogen generator
Generated iodate hydrogen is stored in corrosion-resistant hermetically sealed can by liquid 70g, then by pipeline through mass flowmenter, check valve, peace
It is spare that full valve etc. accesses micro passage reaction.
Third step operates in the heart-shaped micro passage reaction that material is special glass according to the following steps: (1) by the
Peanut oil-isopropyl ethereal solution that one step obtains enters micro passage reaction by liquid pump, hydrogen iodide valve is opened, through mass flow
Meter enters micro passage reaction；(2) continuous flow micro passage reaction, peanut oil-isopropyl ethereal solution and iodine are used in reaction process
Changing hydrogen, proportionally 3.16:1 is mixed in the reactor, is reacted by heat exchanger at 15~25 DEG C；(3) by adjusting liquid pumping frequency
The flow of rate and hydrogen iodide gas flowmeter, the mass ratio for controlling peanut oil-isopropyl ethereal solution and hydrogen iodide is 3.16:1, is stopped
Time 120 seconds, two strands of materials reacted on reaction module；(4) by adjusting the counterbalance valve in reactor outlet, reaction system is kept
The pressure of system is in 0.1bar hereinafter, being measured by the pressure gauge on gas piping；(5) material is after micro passage reaction, reaction
Termination reaction is quenched into stirring in the quantizer equipped with 200ml water in liquid, and the oil reservoir separated purifies water washing, vacuum distillation is gone
Except isopropyl ether, iodized oil 626g is obtained, amount of iodine 30.8%, yield 98.9% (in terms of iodine), free-iodine is qualified, and color is qualified.
Through 40 DEG C of 60 days accelerated stability tests, free-iodine is qualified, and color is qualified.
Embodiment 3
The first step, by 300g poppy seed oil (the land-reclaimable imperial rice biology development corporation, Ltd. in Gansu imperial seal pool, food grade.Similarly hereinafter) exist
Decline 1~5 DEG C of rate of temperature fall Celsius in low temperature thermostat bath on an hourly basis, be cooled to 0~5 DEG C (about 12h) Celsius, continues
0~5 DEG C of maintenance 12h Celsius, filters in Bu Shi suction funnel, obtains degreasing dewaxing poppy seed oil 290g, is mixed with 290g isopropyl ether
It dissolves spare.
Second step is added red phosphorus 15g, crystalline flake of iodine 200g, hydroiodic acid is continuously slowly added dropwise in iodate hydrogen generator
Generated iodate hydrogen is stored in corrosion-resistant hermetically sealed can by 70g, then by pipeline through mass flowmenter, check valve, safety
It is spare that valve etc. accesses micro passage reaction.
Third step operates in the heart-shaped microchannel that material is special glass according to the following steps: (1) first step obtains
Poppy seed oil-isopropyl ethereal solution micro passage reaction is entered by liquid pump, open hydrogen iodide valve, enter through mass flowmenter micro-
Channel reactor；(2) in reaction process using continuous flow micro passage reaction, poppy seed oil-isopropyl ethereal solution and hydrogen iodide according to
Ratio 1.43:1 is mixed in the reactor, is reacted by heat exchanger at 20~30 DEG C；(3) by adjusting liquid pump frequency and iodate
The flow of hydrogen flowmeter body, the mass ratio for controlling poppy seed oil-isopropyl ethereal solution and hydrogen iodide is 1.43:1, residence time 60
Second, two strands of materials react on reaction module；(4) by adjusting the counterbalance valve in reactor outlet, the pressure of reaction system is kept
Power is in 0.5bar hereinafter, being measured by the pressure gauge on gas piping；(5) after micro passage reaction, reaction solution enters material
Termination reaction, the oil reservoir separated purifying water washing, vacuum distillation removal isopropyl is quenched in stirring in quantizer equipped with 200ml water
Ether obtains iodized oil 487g, and amount of iodine 40.5%, yield 98.6% (in terms of iodine), free-iodine is qualified, and color is qualified.
Through 40 DEG C of 60 days accelerated stability tests Celsius, free-iodine is qualified, and color is qualified.
Embodiment 4
300g poppy seed oil is declined 1~5 DEG C of rate of temperature fall on an hourly basis in low temperature thermostat bath, is cooled to by the first step
0~5 DEG C (about 12h) Celsius continues to filter in Bu Shi suction funnel in 0~5 DEG C of maintenance 12h Celsius, obtains degreasing dewaxing small-mouthed jar
Grain oil 290g, it is spare with 145g isopropyl ether mixed dissolution.
Second step is added red phosphorus 15g, crystalline flake of iodine 200g, hydroiodic acid is continuously slowly added dropwise in iodate hydrogen generator
Generated iodate hydrogen is stored in corrosion-resistant hermetically sealed can by 70g, then by pipeline through mass flowmenter, check valve, safety
It is spare that valve etc. accesses micro passage reaction.
Third step operates in the heart-shaped microchannel that material is special glass according to the following steps: (1) first step obtains
Poppy seed oil-isopropyl ethereal solution micro passage reaction is entered by liquid pump, open hydrogen iodide valve, enter through mass flowmenter micro-
Channel reactor；(2) in reaction process using continuous flow micro passage reaction, poppy seed oil-isopropyl ethereal solution and hydrogen iodide according to
Ratio 1:1.43 is mixed in the reactor, is reacted by heat exchanger at 10~20 DEG C；(3) by adjusting liquid pump frequency and iodate
The flow of hydrogen flowmeter body, the mass ratio for controlling poppy seed oil-isopropyl ethereal solution and hydrogen iodide is 1:1.43, residence time 30
Second, two strands of materials react on reaction module；(4) by adjusting the counterbalance valve in reactor outlet, the pressure of reaction system is kept
Power is in 0.5bar hereinafter, being measured by the pressure gauge on gas piping；(5) after micro passage reaction, reaction solution enters material
Termination reaction, the purified washing of the oil reservoir separated, vacuum distillation removing isopropyl is quenched in stirring in quantizer equipped with 200ml water
Ether obtains iodized oil 485g, and amount of iodine 40.9%, yield 99.2% (in terms of iodine), free-iodine is qualified, and color is qualified.
Through 40 DEG C of 60 days accelerated stability tests Celsius, free-iodine is qualified, and color is qualified.
Embodiment 5
300g poppy seed oil is declined 1~5 DEG C of rate of temperature fall on an hourly basis in low temperature thermostat bath, is cooled to by the first step
0~5 DEG C (about 12h) Celsius continues to filter in Bu Shi suction funnel in 0~5 DEG C of maintenance 12h Celsius, obtains degreasing dewaxing small-mouthed jar
Grain oil 290g, it is spare with 1500g isopropyl ether mixed dissolution.
Second step is added red phosphorus 15g, crystalline flake of iodine 195g, hydroiodic acid is continuously slowly added dropwise in iodate hydrogen generator
Generated iodate hydrogen is stored in corrosion-resistant hermetically sealed can by 70g, then by pipeline through mass flowmenter, check valve, safety
It is spare that valve etc. accesses micro passage reaction.
Third step operates in the heart-shaped microchannel that material is special glass according to the following steps: (1) first step obtains
Poppy seed oil-isopropyl ethereal solution micro passage reaction is entered by liquid pump, open hydrogen iodide valve, enter through mass flowmenter micro-
Channel reactor；(2) in reaction process using continuous flow micro passage reaction, poppy seed oil-isopropyl ethereal solution and hydrogen iodide according to
Ratio 9.11:1 is mixed in the reactor, is reacted by heat exchanger at 30~40 DEG C；(3) by adjusting liquid pump frequency and iodate
The flow of hydrogen flowmeter body, the mass ratio for controlling poppy seed oil-isopropyl ethereal solution and hydrogen iodide is 9.11:1, residence time 120
Second, two strands of materials react on reaction module；(4) by adjusting the counterbalance valve in reactor outlet, the pressure of reaction system is kept
Power is in 0.5bar hereinafter, being measured by the pressure gauge on gas piping；(5) after micro passage reaction, reaction solution enters material
Termination reaction, the purified washing of the oil reservoir separated, vacuum distillation removing isopropyl is quenched in stirring in quantizer equipped with 200ml water
Ether obtains iodized oil 470g, and amount of iodine 41.2%, yield 99.3% (in terms of iodine), free-iodine is qualified, and color is qualified.
Through 40 DEG C of 60 days accelerated stability tests Celsius, free-iodine is qualified, and color is qualified.
Comparative example 1 (still reaction)
By 300g poppy seed oil, decline 1~5 DEG C of rate of temperature fall on an hourly basis in low temperature thermostat bath, it is cooled to Celsius 0~
5 DEG C (about 12h), continue to filter in Bu Shi suction funnel in 0~5 DEG C of maintenance 12h Celsius, obtains degreasing dewaxing poppy seed oil
290g is spare.
In iodate hydrogen generator, red phosphorus 15g, crystalline flake of iodine 200g is added, hydroiodic acid 70g is continuously slowly added dropwise, by institute
The iodate hydrogen of generation is slowly passed through under stiring in the poppy seed oil of 290g, about needs fully reacting in 26 hours, and reaction solution is added
Termination reaction is quenched in stirring in the quantizer of 200ml water, and the purified washing of the oil reservoir separated, vacuum distillation moisture obtain iodized oil
498g, amount of iodine 39.5%, yield (in terms of iodine) 98.3%, free-iodine is qualified, and color is qualified.
Through 40 DEG C of 60 days accelerated stability tests, free-iodine is unqualified, and color is unqualified (severe overweight).
Comparative example 2
Method disclosed in CN105062693A:
By 300g perilla oil, (Gongyi City Ke Rui Instrument Ltd., model: the auspicious board DFY- of section are purchased from low temperature thermostat bath
50/30.The rate of temperature fall for declining 1-2 degrees Celsius in similarly hereinafter) on an hourly basis is cooled to -10 degree (about 20 hours) Celsius, continues
It is kept for 24 hours at ± 0.5 degree of -10 degree Celsius.Multiply cold suction filtration in Bu Shi suction funnel, obtains degreasing dewaxing perilla oil 292g.
(it is purchased from Dezhou City Fu Kai chemical industry Co., Ltd, model: 1000ml opens general generation in iodate hydrogen generator
Device.In similarly hereinafter), red phosphorus 15g, crystalline flake of iodine 200g is added, hydroiodic acid 70g is continuously slowly added dropwise, generated iodate hydrogen is existed
It is absorbed under stirring in the degreasing dewaxing perilla oil of 292g, about needs fully reacting in 26 hours, obtain iodized oil 483g.
193g ethyl alcohol (technical grade, granary Xin Tai alcohol Co., Ltd) and 732 type highly acid of 120g are added in iodized oil
Resin cation is heated to 60~70 DEG C, is stirred to react 4h at this temperature, dehydrated alcohol is recovered under reduced pressure, and obtains crude iodine
Change plant ethyl.Unstable iodine is combined in iodized plant ethyl oleate by heating to slough with the method for blowing air again, thus
Iodized plant ethyl oleate 435g is prepared.
Yield (based on average amount of iodine 38%, fatty acid is in terms of linoleic acid) 85.4%, amount of iodine 37.8%, free-iodine are closed
Lattice, color are qualified.
Through 40 DEG C of 60 days accelerated stability tests, free-iodine is unqualified, and color is unqualified (severe overweight).
Comparative example 3
Method disclosed in CN104560406B:
By 300g perilla oil, (Gongyi City Ke Rui Instrument Ltd., model: the auspicious board DFY- of section are purchased from low temperature thermostat bath
50/30) rate of temperature fall for declining 1-2 degrees Celsius on an hourly basis, is cooled to -10 degree (about 20 hours) Celsius, and continuation is being taken the photograph
Family name -10 spends ± 0.5 degree and is kept for 24 hours.Multiply cold suction filtration in Bu Shi suction funnel, obtains degreasing dewaxing perilla oil 292g.
(it is purchased from Dezhou City Fu Kai chemical industry Co., Ltd, model: 1000ml opens general generation in iodate hydrogen generator
Device) in, red phosphorus 15g, crystalline flake of iodine 200g is added, hydroiodic acid 70g is continuously slowly added dropwise, under stiring by generated iodate hydrogen
It is absorbed into the degreasing dewaxing perilla oil of 292g, about needs fully reacting in 26 hours, obtain iodized oil 483g.Yield is (by averagely containing iodine
40% meter of amount) 96.6%, amount of iodine 39.6%, free-iodine is qualified, and color is qualified.
Through 40 DEG C of 60 days accelerated stability tests, free-iodine is unqualified, and color is unqualified (severe overweight).
Comparative example 4
300g poppy seed oil is declined 1~5 DEG C of rate of temperature fall on an hourly basis in low temperature thermostat bath, is cooled to by the first step
0 DEG C (about 12h) Celsius continues to filter in Bu Shi suction funnel in 0~5 DEG C of maintenance 12h Celsius, obtains degreasing dewaxing opium poppy
Oily 290g, it is spare with 145g isopropyl ether mixed dissolution.
Second step is added red phosphorus 15g, crystalline flake of iodine 200g, hydroiodic acid is continuously slowly added dropwise in iodate hydrogen generator
Generated iodate hydrogen is stored in corrosion-resistant hermetically sealed can by 70g.
Third step, the poppy seed oil-that iodate hydrogen caused by second step is absorbed into first step acquisition under stiring are different
In propyl ether solution, fully reacting in about 26 hours, reaction solution is gone out with 200ml water quenching terminates reaction, the purified washing of the oil reservoir separated,
Vacuum distillation removing isopropyl ether, obtains iodized oil 485g, amount of iodine 40.9%, yield 99.2% (in terms of iodine), free-iodine is qualified, color
It is damp qualified.
Through 40 DEG C of 60 days accelerated stability tests, free-iodine is unqualified, and color is unqualified (severe overweight).
The performance of Examples 1 to 5 and comparative example 1~4 is listed in table 1:
1 embodiment of table and its comparative example test data statistics
The embodiment of the present invention 1~5 has the following main features compared with comparative example 1~4:
(1) present invention uses continuous micro passage reaction, and the reaction time foreshortened to a few minutes by traditional more than 20 hours
Even tens seconds, overcome the troubling security risk of traditional still reaction；Production efficiency is greatly improved, production cost
Also it is substantially reduced, has the characteristics that scale is efficient, keeps the safety in production.
(2) product be easy to purify, product stability it is good, advantageously account for its storage, in transportational process color burn matter
Risk is measured, there is the application prospect for meeting current drug high standards to greatest extent.
The above is only presently preferred embodiments of the present invention, is not intended to limit the present invention in any form, though
So the present invention has been disclosed as a preferred embodiment, and however, it is not intended to limit the invention, any technology people for being familiar with this patent
Member without departing from the scope of the present invention, when the technology contents using above-mentioned prompt make it is a little change or be modified to
The equivalent embodiment of equivalent variations, but anything that does not depart from the technical scheme of the invention content, it is right according to the technical essence of the invention
Any simple modification, equivalent change and modification made by above embodiments, in the range of still falling within the present invention program.
Claims (6)
1. a kind of preparation method for the iodized oil that quality is stable, it is characterised in that: the following steps are included:
The first step, the pretreated polyunsaturated vegetable oil that will dewax by degreasing is mixed to form solution with solvent appropriate, unsaturated
The mass ratio of vegetable oil and solvent is 1:(0.1~50)；
Polyunsaturated vegetable oil is peanut oil, perilla oil, linseed oil, sand sagebrush seed oil, walnut oil, kardiseed in the first step
Oil, grape seed oil or poppy seed oil；
Solvent appropriate is isopropyl ether, ether, ethyl acetate, methyl acetate in the first step；
Pretreated polyunsaturated vegetable oil is dewaxed the following steps are included: polyunsaturated vegetable oil is existed by degreasing in the first step
Decline 1~5 DEG C of rate of temperature fall Celsius in low temperature thermostat bath on an hourly basis, be cooled to 0~5 DEG C Celsius, continues Celsius 0~5
DEG C maintain 4~for 24 hours, it filters to obtain degreasing and dewax pretreated polyunsaturated vegetable oil；
Red phosphorus, the crystalline flake of iodine is added in iodate hydrogen generator in second step, and hydroiodic acid is added dropwise, the iodate hydrogen that reaction is generated
Body is imported and is compressed in hydrogen iodide air accumulator, polyunsaturated vegetable oil, red phosphorus, the crystalline flake of iodine and hydroiodic acid mass ratio be (50~
90): 3:(25~45): 14；
Third step answers the iodate hydrogen that the polyunsaturated vegetable oil solution that the first step obtains is obtained with second step in microchannel plate
It is reacted in device, the mass ratio of control polyunsaturated vegetable oil and iodate hydrogen is (1.2~3.0): 1, micro passage reaction temperature
- 10~60 DEG C Celsius are controlled, the residence time is 10~300s, keeps the pressure of reaction system in 0.5bar hereinafter, fully reacting
After termination reaction is quenched with water, the oil reservoir that separates purifying water washing, vacuum distillation obtain the stable iodized oil of quality.
2. the preparation method of the stable iodized oil of quality according to claim 1, it is characterised in that: in the first step not
The mass ratio of saturated vegetable oil and solvent is 1:(0.2~3).
3. the preparation method of the stable iodized oil of quality according to claim 1, it is characterised in that: in the first step not
The iodine number of saturated vegetable oil is as follows:
4. the preparation method of the stable iodized oil of quality according to claim 1, it is characterised in that: micro- in the third step
10~40 DEG C Celsius of temperature control in channel reactor.
5. the preparation method of the stable iodized oil of quality according to claim 1, it is characterised in that: micro- in the third step
Reaction time is 30~120s in channel reactor.
6. the preparation method of the stable iodized oil of quality according to claim 1, it is characterised in that: micro- in the third step
Channel reactor is high throughput-micro passage reaction.
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| CN111234926A (en) * | 2020-03-11 | 2020-06-05 | 上海万巷制药有限公司 | Purification method of vegetable oil for preparing iodized oil |
| CN112300868A (en) * | 2020-11-26 | 2021-02-02 | 兰州大学 | Iodination method of vegetable oil ester |
| CN115612554A (en) * | 2022-11-03 | 2023-01-17 | 陈勇 | Purification method of vegetable oil for preparing iodized oil |
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| CN104560406A (en) * | 2014-12-26 | 2015-04-29 | 上海万代制药有限公司 | Preparation method of iodinated oil with stable quality |
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| CN104560406A (en) * | 2014-12-26 | 2015-04-29 | 上海万代制药有限公司 | Preparation method of iodinated oil with stable quality |
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| 何伟: "微反应器在合成化学中的应用", 《应用化学》 * |
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| CN111234926A (en) * | 2020-03-11 | 2020-06-05 | 上海万巷制药有限公司 | Purification method of vegetable oil for preparing iodized oil |
| CN112300868A (en) * | 2020-11-26 | 2021-02-02 | 兰州大学 | Iodination method of vegetable oil ester |
| CN115612554A (en) * | 2022-11-03 | 2023-01-17 | 陈勇 | Purification method of vegetable oil for preparing iodized oil |
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