CN107586609A - A kind of fish oil and its purification process of the EPA-E containing high concentration - Google Patents
A kind of fish oil and its purification process of the EPA-E containing high concentration Download PDFInfo
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- CN107586609A CN107586609A CN201711021946.6A CN201711021946A CN107586609A CN 107586609 A CN107586609 A CN 107586609A CN 201711021946 A CN201711021946 A CN 201711021946A CN 107586609 A CN107586609 A CN 107586609A
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Abstract
The invention provides a kind of fish oil and its purification process of the EPA-E containing high concentration, it is related to EPA-E preparation field.The purification process includes：According to the content of each aliphatic acid in fish oil, the crystalline temperature temperature range of each aliphatic acid is obtained；Dynamic fusion crystallisation is used again, is cooled in the crystalline temperature temperature range of each aliphatic acid with 1~3 DEG C/h of rate of temperature fall, impurity fat acid crystal contained in fish oil is removed after separating out.By setting suitable rate of temperature fall in crystalline temperature temperature range, constantly crystallization separates out the impurity aliphatic acid that this method makes easily to crystallize in fish oil, while the EPA-E in fish oil mother liquor is constantly concentrated, and separative efficiency is high.The content of EPA-E is high in this fish oil, and bioactivity is good, and medical usage is extensive.
Description
Technical field
The present invention relates to EPA-E preparation field, in particular to it is a kind of containing high concentration 20
The fish oil and its purification process of carbon 5 alkene acid ethyl ester.
Background technology
Eicosapentaenoic acid (EPA) is that a kind of human body can not belong to ω -3 types long-chain more not from the essential fatty acid of GCMS computer
Saturated fatty acid, mostly come from fish oil.There is regulation endocrine, raising immunologic function, vasodilator, reduction serum courage to consolidate for it
Alcohol and low-density blood lipoprotein are horizontal, reduce the effect such as platelet aggregation, anti-inflammatory, anticancer.The EPA of high-purity can be used for preventing and treating dynamic
The diseases such as pulse atherosclerosis, coronary heart disease, hypertension, inflammatory conditions, tumour, senile dementia, there is development in medical pharmaceutical field pole
Prospect.Because the physiological function of various aliphatic acid is not fully identical, some impurity can also be harmful, thus develops high-purity
The EPA monomers of degree are significant.
At present, the fish oil isolation and purification method of prior art report mainly has：Molecularly distilled, rectification method, low temperature crystallization
Method, urea adduct method, Lipids Enzymatic, supercritical fluid extraction, silver resin chromatography and silver nitrate legitimate network etc..Wherein, divide
The generally obtained product of the sub- way of distillation, the crystallizing process under low temperature, urea adduct method, Lipids Enzymatic, supercritical fluid extraction is 20
The mixture of carbon 5 alkene acid ethyl ester (EPA-EE) and docosahexaenoic acid ethyl (DHA-EE), the purity of EPA-EE monomers are difficult
Reach more than 80%.And silver resin chromatography, silver nitrate legitimate network also have the risk for polluting and bringing into impurity.
The content of the invention
The first object of the present invention is to provide a kind of purifying of the fish oil of the EPA-E containing high concentration
Method, the impurity aliphatic acid that this method makes easily to crystallize in fish oil is by setting suitable gradient temperature, and constantly crystallization separates out, together
When the EPA-E in fish oil mother liquor is constantly concentrated, separative efficiency is high.
The second object of the present invention is to provide a kind of eicosapentaenoic acid containing high concentration prepared by the above method
The fish oil of ethyl ester, the content of EPA-E is high in this fish oil, widely used.
In order to realize the above-mentioned purpose of the present invention, spy uses following technical scheme：
A kind of purification process of the fish oil of the EPA-E containing high concentration, it includes：
According to the content of each aliphatic acid in fish oil, the crystalline temperature temperature range of each aliphatic acid is obtained；
Dynamic fusion crystallisation is used again, with 1~3 DEG C/h in the crystalline temperature temperature range of each aliphatic acid
Rate of temperature fall is cooled, and impurity fat acid crystal contained in fish oil is removed after separating out.
A kind of fish oil of the EPA-E containing high concentration as obtained by above-mentioned purification process.
Compared with prior art, beneficial effects of the present invention for example including：
The purification process of the fish oil of this EPA-E containing high concentration provided by the invention, pass through dynamic
The mode that fusion-crystallization and program cooling are combined, the impurity aliphatic acid for making easily to crystallize in fish oil pass through in crystalline temperature temperature range
Interior to set suitable rate of temperature fall, constantly crystallization separates out, while makes the EPA-E in fish oil mother liquor constantly dense
Contracting, EPA-E is avoided to be separated out with other impurities aliphatic acid in the form of eutectic, separative efficiency is high, product yield
Greatly.The content of EPA-E is increased dramatically (from 20~50wt% in raw material in resulting fish oil product
It is promoted to 60~90wt%), while be also avoided that aliphatic acid aoxidizes at high temperature in fish oil, generate trans-fatty acid, reducing life
The bad phenomenons such as thing activity occur.
Brief description of the drawings
In order to illustrate more clearly about the embodiment of the present invention or technical scheme of the prior art, below will be to embodiment or existing
There is the required accompanying drawing used in technology description to be briefly described.
Fig. 1 is that ethyl linolenate crystalline temperature changes and changed with its mass fraction in the raw material fish oil that empirically data are drawn
Tendency chart (abscissa be determination sample number, ordinate mass fraction)；
Fig. 2 is the structural representation of the dynamic crystallization device provided in embodiment；
Fig. 3 is analysis of the DSC differential scanning calorimeters to Chilean anchovies oil raw material components melting crystalline point in embodiment 1
Spectrogram；
Fig. 4 is the gas-chromatography spectrogram of the EPA-EE containing high concentration obtained in embodiment 1 fish oil.
Label：110- crystallizers；111- refrigerant receiving spaces；112- heat-insulation layers；113- refrigerant imports；114- refrigerants go out
Mouthful；115- charging apertures；116- discharging openings；117- overhead gages；118- lower baffle plates；119- crystallizers；120- Recycling Mother Solution tanks；130-
Collecting tank；140- circulating pumps；150- refrigeration firing equipments.
Embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the present invention.It is unreceipted specific in embodiment
Condition person, the condition suggested according to normal condition or manufacturer are carried out.Agents useful for same or the unreceipted production firm person of instrument, it is
The conventional products that can be obtained by commercially available purchase.
Inventor, which studies, to be found, oxidation reaction easily occurs when the aliphatic acid in fish oil is more than 60 DEG C, more than 130 DEG C
Shi Rongyi decomposes reaction, meanwhile, EPA-E (EPA-EE) can also form trans EPA- at relatively high temperatures
EE.For inventor in molecular distillation it was found that, when the temperature of setting reaches 140 DEG C, the peroxide value of fish oil sample is obvious
Improve, coking phenomenon occur.And a variety of trans-fatty acids (such as trans EPA-EE) and Peroxidation Product, health can be produced
Harm.Therefore, the size of peroxide value, the content without trans-fatty acid are to the product of the fish oil containing EPA-E
Matter is most important.
In order to prevent the reactions such as oxidation occurs during isolating and purifying for aliphatic acid in fish oil, decomposes, trans fats are generated
Acid and reduction bioactivity, inventor propose following technical proposal：
Present embodiment provide a kind of purification process of the fish oil of the EPA-E containing high concentration it include：
Step S1:According to the content of each aliphatic acid in fish oil, the crystalline temperature temperature range of each aliphatic acid is obtained；
Fish oil is a kind of complicated molten mixture being made up of a variety of aliphatic acid, wherein most fatty acid components are in temperature
The phenomenon of eutectic congruent melting can be all produced during change so that the component content of crystal and mother liquor after stationary crystallization is roughly the same,
Crystallization time is grown, and separating effect unobvious.
Therefore, if wanting to avoid the EPA-E during isolating and purifying that eutectic occurs with other impurities aliphatic acid
The phenomenon of congruent melting, it is necessary to according to the content of each fatty acid component in fish oil raw material, to obtain the crystalline temperature temperature of each aliphatic acid
Scope.
But because there is the congruent melting of complexity and eutectic phenomena between each fatty acid component in fish oil so that wherein single fat
Fat acid fusing point and crystalline temperature change with the change of each component content, such as in fish oil raw material ethyl linolenate crystalline temperature
Temperature gradually reduces with the reduction of its molar fraction, as shown in figure 1, when the mass fraction of the ethyl linolenate in mother liquor is
When 2.1%, its crystallization temperature is -60 DEG C or so；And when the mass fraction of the ethyl linolenate in mother liquor is down to 1.45%, its
Crystallization temperature is -75 DEG C or so.Therefore, it is to be difficult to measure the sour crystalline temperature temperature of certain single fat in practice operates
Concrete numerical value.
And simultaneously, the content of each fatty acid component in the fish oil raw material of separate sources and the fish oil raw material of same source
Difference, the searching tool for also resulting in the crystalline temperature of each fatty acid component acquire a certain degree of difficulty.By testing it has been found that in fish oil
Data in the crystalline temperature and documents and materials of each component have very big discrepancy.
Therefore, in order to overcome the problem of searching impurity aliphatic acid crystalline temperature, inventor is carried out using thermal analysis system to sample
Analysis, for example with differential scanning calorimetry, to estimate the crystallization point range of each component in fish oil sample, and is subsequently being divided with this
As the reference for setting gradient temperature from during.
Step S2:Dynamic fusion crystallisation is used again, with 1~3 DEG C/h in the crystalline temperature temperature range of each aliphatic acid
Rate of temperature fall cooled, contained impurity fat acid crystal is removed after separating out, obtain two containing high concentration
The fish oil of ten carbon 5 alkene acid ethyl esters.
Dynamic fusion crystallization be a kind of new isolation technics, it be according to the difference of freezing point between material to be separated,
Liquid material is set to reach partially crystallizable by gradually reducing the temperature of liquid material come what is realized during flowing, crystallization is analysed
The solid phase gone out has the chemical composition different from remaining mother liquor, so as to reach the purpose of separating-purifying.Dynamic fusion crystallized
The motive force of journey is the degree of supersaturation or degree of supercooling of certain component in fused solution in flow regime, and crystallization process is flowing shape
For the temperature of fused solution in state during being gradually reduced, certain component is in hypersaturated state in fused solution, starts to be nucleated,
And it is crystal gradually to increase.
According to the crystalline temperature temperature range of each aliphatic acid obtained in step sl, targetedly to utilize in crystalline temperature temperature
The separation of each impurity aliphatic acid and mother liquor is realized in the cooling of degree scope.Mainly there is contained impurity aliphatic acid in fish oil：Peanut four
Olefin(e) acid ethyl ester, ethyl linolenate and ethyl oleate, there are some other a small amount of aliphatic acid, the knot of these impurity aliphatic acid in addition
Fisheye temperature is different and is far above target product EPA-EE.Inventor it is experimentally confirmed that EPA-EE below -120 DEG C of temperature,
It is not in crystalline polamer.Thus, this step S2 by other impurity aliphatic acid in raw material mother liquor by crystallization by way of
Removed from mother liquor, you can obtain the tail washings of the EPA-EE containing high concentration.Meanwhile it also can obtain different crystalline temperature temperature models
The crystallization of certain fatty acid mono in enclosing, such as ethyl arachidonate, ethyl linolenate and ethyl oleate, pass through simple essence
System can obtain the byproduct of high quality.
Further, dynamic fusion crystallisation includes：Fish oil is cycled through into crystallisation vessel, in crystalline temperature temperature range
Crystallisation vessel is cooled.
Wherein, fish oil is cycled through into crystallisation vessel, referred to：Fish oil is passed through from one end of crystallisation vessel, fish oil is flowing
In being crystallized in crystallisation vessel in dynamic process, the first crystal and the first tail washings are obtained, then the first tail washings is passed through crystallization again
In container, above-mentioned circulation is constantly carried out, until each impurity aliphatic acid crystallizes precipitation in its crystalline temperature temperature range in fish oil, is obtained
Untill the EPA-EE of high concentration tail washings.More preferable, crystallisation vessel is vertical falling-film crystallizer.
Further, the rate of temperature fall of cooling is 1~3 DEG C/h, i.e. crystalline temperature of the crystallisation vessel in each impurity aliphatic acid
Cooled in temperature range with the speed for reducing by 1~3 DEG C per hour, make the impurity fat at the temperature in crystalline temperature temperature
Acid crystal separates out.Rate of temperature fall is 1~3 DEG C/h, is either 2.5~2.5 DEG C/h or is 1.7~2.3 DEG C/h,
It is either 1.8~2.2 DEG C/h or is 1.9~2.1 DEG C/h, or for 2 DEG C/h.
Further, the flow velocity that fish oil cycles through crystallisation vessel is 100~200L/h, or is 120~180L/h, or
Person is 130~170L/h, is either 140~160L/h or is 145~155L/h, or is 150L/h.Fish oil cycles through
The flow velocity of crystallisation vessel is unsuitable excessive or too small, and flow velocity is excessive, and crystallization is insufficient；And flow velocity is too small, crystallization is of long duration, separation effect
Rate is low.
Further, the impurity aliphatic acid in fish oil includes ethyl arachidonate, and the content of ethyl arachidonate is 2
~4wt%, the crystalline temperature temperature range of ethyl arachidonate is -25~-70 DEG C.That is, when ethyl arachidonate in fish oil
Content when being 2~4wt%, the crystalline temperature temperature range of ethyl arachidonate monomer is -25~-70 DEG C, is implementing dynamic
During fusion-crystallization, you can the temperature of crystallisation vessel is first down to -25 DEG C from room temperature, then with 1 between -25 DEG C~-70 DEG C
~3 DEG C/h of rate of temperature fall is cooled, and separates out ethyl arachidonate crystallization.It is more preferable, in dynamic fusion knot
During crystalline substance, the component of the circulating mother liquor monitored in real time, until can't detect ethyl arachidonate in circulating mother liquor, then say
Precipitation is complete from mother liquor for bright ethyl arachidonate.Generally, ethyl arachidonate is in its crystalline temperature temperature range
Interior meeting rapid crystallization separates out, and whole Crystallization Process is no more than 1h.
Or when the content of ethyl arachidonate is 2~3wt%, the crystalline temperature temperature range of ethyl arachidonate
For for -30~-70 DEG C.
Or when the content of ethyl arachidonate is 3~4wt%, the crystalline temperature temperature range of ethyl arachidonate
For -25~-60 DEG C.
Further, the impurity aliphatic acid in fish oil includes ethyl linolenate, the content of ethyl linolenate for 0.5~
5wt%, the crystalline temperature temperature range of ethyl linolenate is -50~-85 DEG C.
Or when the content of ethyl linolenate is 0.5~2.5wt%, the crystalline temperature temperature range of ethyl linolenate is -55
~-85 DEG C；
Or when the content of ethyl linolenate is 2.5~5wt%, the crystalline temperature temperature range of ethyl linolenate is -50
~-80 DEG C；
Further, the impurity aliphatic acid in fish oil includes ethyl oleate, and the content of ethyl oleate is 1~25wt%, oil
The crystalline temperature temperature range of acetoacetic ester is -65~-100 DEG C.
Or the content of ethyl oleate is 1~10wt%, the crystalline temperature temperature range of ethyl oleate is -70~-100 DEG C.
Or the content of ethyl oleate is 10~25wt%, the crystalline temperature temperature range of ethyl oleate is -65~-90 DEG C.
Present embodiment also provides a kind of circulation dynamic crystallization device, as shown in Fig. 2 it includes：Crystallizer 110, mother liquor
Circulating tank 120 and circulating pump 140, wherein, overhead gage 117 and lower baffle plate 118 are provided with crystallizer 110, overhead gage 117 is with
The inwall of baffle plate 118 and crystallizer 110 surrounds refrigerant receiving space 111, is set up in parallel between overhead gage 117 and lower baffle plate 118
There are more crystallizers 119, the upper end open of crystallizer 119 is connected with the charging aperture 115 of crystallizer 110, under crystallizer 119
End opening is connected with the discharging opening 116 of crystallizer 110, and crystallizer 110 is connected with Recycling Mother Solution tank 120 by pipeline, is following
In the presence of ring pump 140, material circulates between crystallizer 119 and Recycling Mother Solution tank 120.
The circulation dynamic crystallization device also includes refrigeration firing equipment 150, freezes in firing equipment 150 and crystallizer 110
Refrigerant receiving space 111 connected by pipeline, refrigerant is freezed after (or heating) in the firing equipment 150 that freezes from crystallization
After the refrigerant import 113 of the bottom of device 110 enters cooling space, after (or heating) is cooled down to crystallizer 119, then from positioned at
The refrigerant exit 114 of the upper end of crystallizer 110 is flowed out in refrigeration firing equipment 150, is circulated successively, wherein, refrigerant uses temperature
It is -125~50 DEG C to spend scope.
In addition, the periphery wall of crystallizer 110 is additionally provided with heat-insulation layer 112；The discharging opening 116 and collecting tank of crystallizer 110
130 pipelines connect.
During operation, suitable parameter is set on refrigeration firing equipment 150 first, is up to the refrigerant conveying of design temperature
Into refrigerant receiving space 111, make the outer wall of refrigerant fractional crystallisation pipe 119, by carrying out hot friendship between refrigerant and crystallizer 119
Change, control the temperature change in crystallizer 119.Fish oil crude material is put into Recycling Mother Solution tank 120 again, it is dilute with suitable solvent
Certain proportion is released, is filled with nitrogen protection.Material is sent into the charging aperture 115 at the top of crystallizer 110 by circulating pump 140, leads to
Cross the liquid distribution trough that the top of crystallizer 110 is set uniformly to be distributed, along the inwall of crystallizer 119 in crystallizer 110 with liquid
Membranaceous form flowing, the component for reaching crystalline temperature crystallize in crystallizer 119, are attached on the inwall of crystallizer 119, do not crystallize
Component flowed into the form of falling liquid film in bottom Recycling Mother Solution tank 120, the circulation repeated.By circulation and to crystallizer temperature
Degree, the crystal that impurity aliphatic acid (auxiliary product) is formed constantly are enriched with crystallizer 119, and in Recycling Mother Solution tank 120
In non-crystal, the content of target product (i.e. EPA-EE) is concentrated.After the completion of crystallization, rising gradually heating makes crystallizer 119
The crystal of the byproducts such as interior oleic acid, leukotrienes, arachidonic acid is respectively melted, and is flowed into collecting tank 130, is obtained high value
Byproduct.
Further, in addition to：Tail washings of the fish oil as obtained by dynamic fusion crystallisation is subjected to liquid chromatogram separation.
On the basis of carrying out initial concentration to fish oil crude product in dynamic fusion crystallization technique, further using liquid phase color
Compose technique and carry out separating-purifying, the EPA-EE contents in fish oil can be risen to more than 96~99% level, wherein EPA-EE
The product yield that content is 96% is up to 80%.The oxidation number of product is below 3meq/kg, and anisidine value is below 6meq/kg,
Meanwhile DHA-EE contents are less than 0.3% (if there is)；Trans EPA-EE contents are less than 0.5% (if there is).This high-quality
EPA-EE products, there is higher bioactivity, high-quality raw material can be provided for pharmaceuticals industry.
Inventor has found that the various fillers of liquid-phase chromatographic column have very big for the separating effect of fish oil fatty acid in an experiment
Difference, even if the filler of phase same material, due to the difference of the parameters such as particle diameter aperture, the retention time of each component appearance also has difference
It is different.Consideration of the present invention based on separating effect and the unit interval output value etc., finally employs C18 reverse chromatograms fillers, grain
Footpath is 10 μm, and aperture isIt is seated on DAC-50*250mm dynamic axial compression columns.And utilize methanol, ethanol, second
Nitrile, water equal solvent, which mutually match, is made specific mobile phase, and flow velocity, applied sample amount, sample time all by verifying repeatedly so that production
The purity and yield of product are all considerable, and technology stability is high, and the output value tool in the unit interval has great advantage.
In addition, a kind of above-mentioned EPA-EE containing high concentration fish oil is also provided in present embodiment is preparing treatment painstaking effort
Application in the medicine of pipe relevant disease.
Cardiovascular related diseases include：Acute myocardial ischemia, acute myocardial infarction AMI, angina pectoris, arrhythmia cordis, human atrial fiber
Property vibration, arteriosclerosis, atrial fibrillation, cardiac insufficiency, chronic heart failure, chronic stable angina pectoris, congestive cardiac decline
Exhaust, coronary artery disease, coronary heart disease, DVT, diabetes, diabetic neuropathy, heart diastolic insufficiency, water
Swollen, essential hypertension, pulmonary embolism, fatty liver, homozygous familial hypercholesteremia (HoFH), homozygous family's sitosterol blood
Ischemic in disease, hypercholesterolemia, hyperlipidemia, hypertension, hypertriglyceridemia, unstable angina and myocardial infarction
Type complication, low blood pressure, metabolic syndrome, mixed dyslipidemia, platelet aggregation, pulmonary hypertension, recurrent blood move
The unstable Ventricular Tachycardia of mechanics (VT), the ventricular arrhythmia of recurrent, recurrent ventricular fibrillation (VF), disruptiveness are moved
Arteries and veins knurl, apoplexy, supraventricular tachycardia, symptomatic atrial fibrillation/flutter, tachycardia, type II diabetes, VTE, the heart
Room arrhythmia cordis.
The feature and performance of the present invention are described in further detail with reference to embodiments：
Embodiment 1
The present embodiment provides a kind of fish oil of the EPA-E containing high concentration, and it is with Chilean anchovies oil
Isolated and purified what is obtained for raw material, wherein, after measured, the weight/mass percentage composition difference of each aliphatic acid in Chilean anchovies oil
For：
EPA-E is 40.66%, ethyl arachidonate 3.99%, ethyl linolenate 4.45%, oleic acid
Ethyl ester 20.43%.
The purification process of the fish oil includes：
Using DSC differential scanning calorimetries Chile anchovies oil sample, as a result as shown in figure 3, scheming to obtain according to DSC
The crystalline temperature temperature range of each aliphatic acid in Chilean anchovies oil, it is respectively：
Ethyl arachidonate be -32 to -50 DEG C, ethyl linolenate be -55 to -75 DEG C, ethyl oleate for -70 DEG C arrive -
85℃。
Crystallizing process：After Chilean anchovies oil raw material moderately dilution, fish oil mother liquor is obtained, fish oil mother liquor is passed through
In crystallizer, in the presence of circulating pump, make fish oil mother liquor with 130L/h flow velocity in crystallizer and outside crystallizer
Circulated between mother liquor collecting tank, while crystallizer is cooled, cooling process is：
First stage crystallizes：First by crystallizer from being reduced to -32 DEG C at room temperature, then make crystallizer with 2 DEG C/h of cooling
Rate reduction completes first stage crystallization to -50 DEG C, crystallizes the ethyl arachidonate in mother liquor and separates out, remaining tail
Liquid is circulated；
Second stage crystallizes：Crystallizer is reduced to -55 DEG C from -50 DEG C, then makes crystallizer with 2 DEG C/h of cooling speed
Rate is reduced to -75 DEG C, completes second stage crystallization, crystallizes the ethyl linolenate in mother liquor and separates out, remaining tail washings is carried out
(in this stage, when the temperature of crystallizer is between -70~-75 DEG C, part ethyl linolenate and ethyl oleate are with altogether for circulation
Brilliant form separates out simultaneously)；
Phase III crystallizes：Crystallizer is reduced to -85 DEG C with 2 DEG C/h of rate of temperature fall from -75 DEG C of continuation, completed
Phase III crystallizes, and crystallizes the ethyl oleate in mother liquor and separates out, obtains tail washings.
Detection is invented, and the content of EPA-E is 83% in tail washings；After tail washings is concentrated, produce containing highly concentrated
The fish oil of the EPA-E of degree；By this fish oil after liquid chromatography technology is refined, you can obtain eicosapentaenoic acid
Product of the ethyl ester purity up to 97%, the gas chromatogram of the product are as shown in Figure 4.
Embodiment 2
The present embodiment provides a kind of fish oil of the EPA-E containing high concentration, and it is using anchovy oil as raw material
Isolated and purified what is obtained, wherein, after measured, the weight/mass percentage composition of each aliphatic acid is respectively in anchovy oil：
EPA-E is 60.2%, ethyl arachidonate 3.2%, ethyl linolenate 0.75%, oleic acid second
Ester 3%.
The purification process of the fish oil includes：
Using DSC differential scanning calorimetry anchovy oil samples, schemed to obtain the knot of each aliphatic acid in anchovy oil according to DSC
Fisheye temperature range, it is respectively：
Ethyl arachidonate be -45 to -65 DEG C, ethyl linolenate be -65 to -80 DEG C, ethyl oleate for -79 DEG C arrive -
95℃。
Crystallizing process：After anchovy oil raw material moderately dilution, fish oil mother liquor is obtained, fish oil mother liquor is passed through crystallizer
In, in the presence of circulating pump, fish oil mother liquor is received with 200L/h flow velocity in crystallizer and the mother liquor outside crystallizer
Circulated between collection tank, while crystallizer is cooled, cooling process is：
First stage crystallizes：First by crystallizer from being reduced to -45 DEG C at room temperature, then make crystallizer with 3 DEG C/h of cooling
Rate reduction completes first stage crystallization to -65 DEG C, crystallizes the ethyl arachidonate in mother liquor and separates out, remaining tail
Liquid is circulated；
Second stage crystallizes：Crystallizer is reduced to -80 DEG C with 1 DEG C/h of rate of temperature fall from -65 DEG C, completes second
Stage crystallization, crystallize the ethyl linolenate in mother liquor and separate out, remaining tail washings, which is circulated, (in this stage, works as crystallization
The temperature of device be -79~-80 DEG C between when, part ethyl linolenate and ethyl oleate are separated out simultaneously in the form of eutectic)；
Phase III crystallizes：Crystallizer is continued from -80 DEG C to be reduced to -95 DEG C with 1.5 DEG C/h of rate of temperature fall, it is complete
Crystallized into the phase III, crystallize the ethyl oleate in mother liquor and separate out, obtain tail washings.
Detection is invented, and the content of EPA-E is 81% in tail washings；After tail washings is concentrated, produce containing highly concentrated
The fish oil of the EPA-E of degree；By this fish oil after liquid chromatography technology is refined, you can obtain eicosapentaenoic acid
Product of the ethyl ester purity up to 98%.
Although illustrate and describing the present invention with specific embodiment, but will be appreciated that without departing substantially from the present invention's
Many other change and modification can be made in the case of spirit and scope.It is, therefore, intended that in the following claims
Including belonging to all such changes and modifications in the scope of the invention.
Claims (10)
1. a kind of purification process of the fish oil of the EPA-E containing high concentration, it is characterised in that it includes：
According to the content of each aliphatic acid in fish oil, the crystalline temperature temperature range of each aliphatic acid is obtained；
Dynamic fusion crystallisation is used again, with 1~3 DEG C/h of cooling in the crystalline temperature temperature range of each aliphatic acid
Speed is cooled, and impurity fat acid crystal contained in the fish oil is removed after separating out.
2. the purification process of fish oil according to claim 1, it is characterised in that the dynamic fusion crystallisation includes：Will
Fish oil cycles through crystallisation vessel, and the crystallisation vessel is cooled in the crystalline temperature temperature range.
3. the purification process of fish oil according to claim 1 or 2, it is characterised in that the rate of temperature fall of the cooling is 1.5
~2.5 DEG C/h.
4. the purification process of fish oil according to claim 2, it is characterised in that the fish oil, which cycles through the crystallization, to be held
The flow velocity of device is 100~200L/h.
5. the purification process of fish oil according to claim 1 or 2, it is characterised in that obtain the crystallization of each aliphatic acid
The method of point temperature range includes thermal analysis system.
6. the purification process of fish oil according to claim 1 or 2, it is characterised in that also include：The fish oil is passed through into institute
State the tail washings obtained by dynamic fusion crystallisation and carry out liquid chromatogram separation.
7. the purification process of fish oil according to claim 1 or 2, it is characterised in that the impurity aliphatic acid in the fish oil
Including ethyl arachidonate, the content of the ethyl arachidonate is 2~4wt%, the knot of the ethyl arachidonate
Fisheye temperature range is -25~-70 DEG C.
8. the purification process of fish oil according to claim 1 or 2, it is characterised in that the impurity aliphatic acid in the fish oil
Including ethyl linolenate, the content of the ethyl linolenate is 0.5~5wt%, the crystalline temperature temperature of the ethyl linolenate
It is -50~-85 DEG C to spend scope.
9. the purification process of fish oil according to claim 1 or 2, it is characterised in that the impurity aliphatic acid in the fish oil
Including ethyl oleate, the content of the ethyl oleate is 1~25wt%, the crystalline temperature temperature range of the ethyl oleate
For -65~-100 DEG C.
A kind of 10. eicosapentaenoic acid containing high concentration obtained by purification process as described in any one of claim 1~9
The fish oil of ethyl ester.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011119677A1 (en) * | 2010-03-24 | 2011-09-29 | LiveFuels, Inc. | Systems and methods for producing eicosapentaenoic acid and docosahexaenoic acid from algae |
| CN105218367A (en) * | 2014-06-09 | 2016-01-06 | 四川国为制药有限公司 | A kind of High Purity Ethyl Eicosapentaenoate enriched material |
| CN106117050A (en) * | 2016-06-24 | 2016-11-16 | 四川欣美加生物医药有限公司 | Improve the method for the purity of EPA-E in fish oil |
| CN107164084A (en) * | 2017-05-15 | 2017-09-15 | 乌鲁木齐上善元生物科技有限公司 | A kind of production method of the vegetable oil rich in high content unrighted acid |
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2017
- 2017-10-27 CN CN201711021946.6A patent/CN107586609B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011119677A1 (en) * | 2010-03-24 | 2011-09-29 | LiveFuels, Inc. | Systems and methods for producing eicosapentaenoic acid and docosahexaenoic acid from algae |
| CN105218367A (en) * | 2014-06-09 | 2016-01-06 | 四川国为制药有限公司 | A kind of High Purity Ethyl Eicosapentaenoate enriched material |
| CN106117050A (en) * | 2016-06-24 | 2016-11-16 | 四川欣美加生物医药有限公司 | Improve the method for the purity of EPA-E in fish oil |
| CN107164084A (en) * | 2017-05-15 | 2017-09-15 | 乌鲁木齐上善元生物科技有限公司 | A kind of production method of the vegetable oil rich in high content unrighted acid |
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