CN109912403A - A kind of method that Omega-3 prepares large conductance calcium activated potassium channel opener - Google Patents
A kind of method that Omega-3 prepares large conductance calcium activated potassium channel opener Download PDFInfo
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- CN109912403A CN109912403A CN201910314524.0A CN201910314524A CN109912403A CN 109912403 A CN109912403 A CN 109912403A CN 201910314524 A CN201910314524 A CN 201910314524A CN 109912403 A CN109912403 A CN 109912403A
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- 102000016469 Large-Conductance Calcium-Activated Potassium Channels Human genes 0.000 title claims abstract description 18
- 108010092555 Large-Conductance Calcium-Activated Potassium Channels Proteins 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 title claims abstract description 17
- 239000004036 potassium channel stimulating agent Substances 0.000 title claims abstract description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 24
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000012452 mother liquor Substances 0.000 claims abstract description 21
- 239000000126 substance Substances 0.000 claims abstract description 15
- 238000010668 complexation reaction Methods 0.000 claims abstract description 13
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 13
- 238000001704 evaporation Methods 0.000 claims abstract description 13
- 229930195729 fatty acid Natural products 0.000 claims abstract description 13
- 239000000194 fatty acid Substances 0.000 claims abstract description 13
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 13
- 239000011780 sodium chloride Substances 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 238000000926 separation method Methods 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 7
- 238000010494 dissociation reaction Methods 0.000 claims abstract description 7
- 230000005593 dissociations Effects 0.000 claims abstract description 7
- 230000008020 evaporation Effects 0.000 claims abstract description 7
- 238000000746 purification Methods 0.000 claims abstract description 7
- 238000007127 saponification reaction Methods 0.000 claims abstract description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 108
- 239000003208 petroleum Substances 0.000 claims description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
- 239000000243 solution Substances 0.000 claims description 28
- 238000000605 extraction Methods 0.000 claims description 26
- 235000021122 unsaturated fatty acids Nutrition 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 150000004670 unsaturated fatty acids Chemical class 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000012071 phase Substances 0.000 claims description 18
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 12
- 238000012856 packing Methods 0.000 claims description 12
- 239000012266 salt solution Substances 0.000 claims description 12
- 239000013049 sediment Substances 0.000 claims description 12
- -1 unsaturated fatty acid salt Chemical class 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 239000008367 deionised water Substances 0.000 claims description 6
- 229910021641 deionized water Inorganic materials 0.000 claims description 6
- 239000000945 filler Substances 0.000 claims description 6
- 150000002500 ions Chemical class 0.000 claims description 6
- 239000007791 liquid phase Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- XRRQZKOZJFDXON-UHFFFAOYSA-N nitric acid;silver Chemical compound [Ag].O[N+]([O-])=O XRRQZKOZJFDXON-UHFFFAOYSA-N 0.000 claims description 6
- 230000006798 recombination Effects 0.000 claims description 6
- 238000005215 recombination Methods 0.000 claims description 6
- 230000004044 response Effects 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 239000004575 stone Substances 0.000 claims description 6
- 230000002459 sustained effect Effects 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 230000008859 change Effects 0.000 claims description 2
- 239000000344 soap Substances 0.000 claims description 2
- 238000013517 stratification Methods 0.000 claims description 2
- 239000000463 material Substances 0.000 claims 1
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 239000008139 complexing agent Substances 0.000 abstract description 3
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 230000001376 precipitating effect Effects 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 2
- MBMBGCFOFBJSGT-KUBAVDMBSA-N docosahexaenoic acid Natural products CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 47
- 235000020669 docosahexaenoic acid Nutrition 0.000 description 46
- 235000019197 fats Nutrition 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000003643 water by type Substances 0.000 description 4
- 108091006146 Channels Proteins 0.000 description 3
- 102000004310 Ion Channels Human genes 0.000 description 2
- 108090000862 Ion Channels Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000000536 complexating effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 235000021323 fish oil Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229940090949 docosahexaenoic acid Drugs 0.000 description 1
- 150000002066 eicosanoids Chemical class 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
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- Coloring Foods And Improving Nutritive Qualities (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Fats And Perfumes (AREA)
Abstract
The present invention relates to pharmaceutical technology field, the method that specially a kind of Omega-3 prepares large conductance calcium activated potassium channel opener, including following preparation step: step 1: enrichment EPA and DHA；Step 2: saponification；Step 3；Prepare fatty acid mixed；Step 4: silver ion complexation；Step 5: dissociation complex compound；Step 6: evaporation purification；Step 7: mother liquor is prepared.Have the beneficial effect that the present invention using silver ion as complexing agent, using the difference of substance double key number in Omega-3, EPA and DHA separation is realized, and silver ion is recycled as precipitating reagent using sodium chloride, silver ion is avoided to lose, DHA purity after enrichment is up to 85%, and yield is up to 69%, and low energy consumption, it is easy to operate, mild condition, the period is short, high income.
Description
Technical field
The present invention relates to pharmaceutical technology field, specially a kind of Omega-3 prepares large conductance calcium activated potassium channel opener
Method.
Background technique
The big calcium ion activated potassium channel of conductance (channel BK) is distributed widely on vascular smooth muscle cells film, participates in blood vessel
Power is adjusted.EPA and DHA can be metabolized by Cytochrome P450 Cycloxygenase (CYP450), generate eicosanoid and other self
Active material plays biological action.Studies have shown that DHA is that the metabolite generated by CYP450 Cycloxygenase keeps BK logical
Road activation, rather than the direct effect of own.The CYP450 epoxides EDPs of DHA is important BK channel activator,
EDPs can in concentration dependent coronary artery dilator, increase the open probability in the channel BK on vascular smooth muscle cells film.
For example, half effect concentration of 13,14-EDP expansion arteries and increase BK channel open probability is consistent, it is thus regarded that EDPs expands
The mechanism of artery is mainly due to its activation to the channel BK.
DHA, docosahexaenoic acid belong to the important member in Omega-3 unsaturated fatty acid family.Omega-3 is not
Saturated fatty acid is common in deep sea fish oil, seal oil and certain plants, so extracting DHA from Omega-3, is then passed through
CYP450 metabolism, is a kind of reliable approach for preparing large conductance calcium activated potassium channel opener.But DHA content is few in fish oil,
It has to by being enriched with, being concentrated.
Summary of the invention
The purpose of the present invention is to provide a kind of method that Omega-3 prepares large conductance calcium activated potassium channel opener, with
Solve the problems mentioned above in the background art.
To achieve the above object, the invention provides the following technical scheme: a kind of big conductance calcium-activated potassium of Omega-3 preparation is logical
The method of road opener, including following preparation step:
Step 1: enrichment EPA and DHA, by Omega-3 and supercritical CO2It is mixed, is pumped into extraction tower with high pressure constant flow pump
In, supercritical extract is carried out, tower top obtains light component, and the recombination that tower bottom obtains is divided into the enriched substance of EPA and DHA；
Step 2: sodium hydroxide solution is added into the enriched substance of EPA and DHA in saponification, under 60-65 DEG C of water bath with thermostatic control, soap
Change, flow back after 30-90 min, be cooled to room temperature, filters off unsaponifiable matter, obtain unsaturated fatty acid salt solution；
Step 3: preparing fatty acid mixed, and sodium chloride is added into unsaturated fatty acid salt solution, and unsaturated fatty acid is precipitated
Salt after being washed to neutrality with deionized water to unsaturated fatty acid salt, with petroleum ether extraction, obtains the mixing-in fat containing petroleum ether
Acid；
Step 4: the fatty acid mixed containing petroleum ether is transferred in stirred tank by silver ion complexation, opens stirring, mixing speed
Control is 60-120 rpm, and temperature in the kettle control is 40-60 DEG C, and excess nitric acid silver aqueous solution, sustained response 90-120 is added
After min, stratification, liquid separation separates petroleum ether phase, obtains silver ion complexation solution；
Step 5: dissociation complex compound first washs water phase with saturated sodium chloride solution, until spending after no longer there is sediment
Ion water washing recycles sediment, petroleum ether is added in liquid phase, extract, merges petroleum ether phase, obtains the mixing of DHA- petroleum ether
Object；
Step 6: DHA- petroleum ether mixtures are transferred in evaporating column, are evaporated under reduced pressure by evaporation purification, and tower bottom recycles stone
Oily ether, tower top obtain DHA；
Step 7: preparing mother liquor, and product of the DHA after CYP450 is metabolized is dissolved in dehydrated alcohol, mother liquor is prepared into, packing is kept away
Light be stored in -20 DEG C it is spare.
Preferably, in step 1, in the Omega-3, the mass fraction that the mass fraction of EPA is 37%, DHA is 22%.
Preferably, in step 1, filler is corrugated wire gauze packing in the extraction tower, and it is 0.2 mm, silk that silk, which passes through,
Net is 80 mesh, and packed height is 40 mm.
Preferably, in step 1, the column bottom temperature of the extraction tower is 50 DEG C, and tower top temperature is 90 DEG C, and extracting pressure is
12 MPa, charging rate are 1 mL/min.
Preferably, in step 2, the mass fraction of the sodium hydroxide solution is 6%.
Preferably, in step 7, the mother liquid concentration is 100 mmol/L, and the final concentration of dehydrated alcohol is less than in mother liquor
0.2%。
Compared with prior art, the beneficial effects of the present invention are:
1. the present invention realizes EPA and DHA points using the difference of substance double key number in Omega-3 as complexing agent using silver ion
From, and avoid silver ion from losing, the DHA purity after enrichment is up to 85%, yield as precipitating reagent recycling silver ion using sodium chloride
Up to 69%, low energy consumption, easy to operate, and mild condition, the period is short, high income；
2. the present invention is using using CO2EPA in Omega-3 and DHA are purified, are enriched with by the mode of supercritical extract, are reduced
It is subsequent extraction, complexing and etc. solvent usage amount；
3. the final concentration of dehydrated alcohol both can guarantee EDPs normal storage less than 0.2% in mother liquor, has and be avoided that excessive ethyl alcohol
Cell ion channel is impacted.
Specific embodiment
The following is a clear and complete description of the technical scheme in the embodiments of the invention, it is clear that described embodiment
Only a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, the common skill in this field
Art personnel every other embodiment obtained without making creative work belongs to the model that the present invention protects
It encloses.
Embodiment 1
The present invention provides a kind of technical solution: a kind of method that Omega-3 prepares large conductance calcium activated potassium channel opener, including
Following preparation step:
Step 1: enrichment EPA and DHA, by Omega-3 and supercritical CO2It is mixed, is pumped into extraction tower with high pressure constant flow pump
In, supercritical extract is carried out, tower top obtains light component, and the recombination that tower bottom obtains is divided into the enriched substance of EPA and DHA；
Step 2: sodium hydroxide solution is added into the enriched substance of EPA and DHA in saponification, under 60 DEG C of waters bath with thermostatic control, is saponified, returns
It after flowing 30 min, is cooled to room temperature, filters off unsaponifiable matter, obtain unsaturated fatty acid salt solution；
Step 3: preparing fatty acid mixed, and sodium chloride is added into unsaturated fatty acid salt solution, and unsaturated fatty acid is precipitated
Salt after being washed to neutrality with deionized water to unsaturated fatty acid salt, with petroleum ether extraction, obtains the mixing-in fat containing petroleum ether
Acid；
Step 4: the fatty acid mixed containing petroleum ether is transferred in stirred tank by silver ion complexation, opens stirring, mixing speed
Control is 60 rpm, and temperature in the kettle control is 4 DEG C, addition excess nitric acid silver aqueous solution, after 90 min of sustained response, stands and divides
Layer, liquid separation separate petroleum ether phase, obtain silver ion complexation solution；
Step 5: dissociation complex compound first washs water phase with saturated sodium chloride solution, until spending after no longer there is sediment
Ion water washing recycles sediment, petroleum ether is added in liquid phase, extract, merges petroleum ether phase, obtains the mixing of DHA- petroleum ether
Object；
Step 6: DHA- petroleum ether mixtures are transferred in evaporating column, are evaporated under reduced pressure by evaporation purification, and tower bottom recycles stone
Oily ether, tower top obtain DHA；
Step 7: preparing mother liquor, and product of the DHA after CYP450 is metabolized is dissolved in dehydrated alcohol, mother liquor is prepared into, packing is kept away
Light be stored in -20 DEG C it is spare.
Wherein, in Omega-3, the mass fraction that the mass fraction of EPA is 37%, DHA is 22%；Filler is in extraction tower
Corrugated wire gauze packing, it is 0.2 mm that silk, which passes through, and silk screen is 80 mesh, and packed height is 40 mm；The column bottom temperature of extraction tower is
50 DEG C, tower top temperature is 90 DEG C, and extracting pressure is 12 MPa, and charging rate is 1 mL/min；The quality of sodium hydroxide solution point
Number is 6%；Mother liquid concentration is 100 mmol/L, final concentration of the 0.1% of dehydrated alcohol in mother liquor.
Embodiment 2
The present invention provides a kind of technical solution: a kind of method that Omega-3 prepares large conductance calcium activated potassium channel opener, including
Following preparation step:
Step 1: enrichment EPA and DHA, by Omega-3 and supercritical CO2It is mixed, is pumped into extraction tower with high pressure constant flow pump
In, supercritical extract is carried out, tower top obtains light component, and the recombination that tower bottom obtains is divided into the enriched substance of EPA and DHA；
Step 2: sodium hydroxide solution is added into the enriched substance of EPA and DHA in saponification, under 62 DEG C of waters bath with thermostatic control, is saponified, returns
It after flowing 50 min, is cooled to room temperature, filters off unsaponifiable matter, obtain unsaturated fatty acid salt solution；
Step 3: preparing fatty acid mixed, and sodium chloride is added into unsaturated fatty acid salt solution, and unsaturated fatty acid is precipitated
Salt after being washed to neutrality with deionized water to unsaturated fatty acid salt, with petroleum ether extraction, obtains the mixing-in fat containing petroleum ether
Acid；
Step 4: the fatty acid mixed containing petroleum ether is transferred in stirred tank by silver ion complexation, opens stirring, mixing speed
Control is 80 rpm, and temperature in the kettle control is 48 DEG C, addition excess nitric acid silver aqueous solution, after 100 min of sustained response, stands and divides
Layer, liquid separation separate petroleum ether phase, obtain silver ion complexation solution；
Step 5: dissociation complex compound first washs water phase with saturated sodium chloride solution, until spending after no longer there is sediment
Ion water washing recycles sediment, petroleum ether is added in liquid phase, extract, merges petroleum ether phase, obtains the mixing of DHA- petroleum ether
Object；
Step 6: DHA- petroleum ether mixtures are transferred in evaporating column, are evaporated under reduced pressure by evaporation purification, and tower bottom recycles stone
Oily ether, tower top obtain DHA；
Step 7: preparing mother liquor, and product of the DHA after CYP450 is metabolized is dissolved in dehydrated alcohol, mother liquor is prepared into, packing is kept away
Light be stored in -20 DEG C it is spare.
Wherein, in Omega-3, the mass fraction that the mass fraction of EPA is 37%, DHA is 22%；Filler is in extraction tower
Corrugated wire gauze packing, it is 0.2 mm that silk, which passes through, and silk screen is 80 mesh, and packed height is 40 mm；The column bottom temperature of extraction tower is
50 DEG C, tower top temperature is 90 DEG C, and extracting pressure is 12 MPa, and charging rate is 1 mL/min；The quality of sodium hydroxide solution point
Number is 6%；Mother liquid concentration is 100 mmol/L, and it is 0.1% that the final concentration of dehydrated alcohol, which is less than, in mother liquor.
Embodiment 3
The present invention provides a kind of technical solution: a kind of method that Omega-3 prepares large conductance calcium activated potassium channel opener, including
Following preparation step:
Step 1: enrichment EPA and DHA, by Omega-3 and supercritical CO2It is mixed, is pumped into extraction tower with high pressure constant flow pump
In, supercritical extract is carried out, tower top obtains light component, and the recombination that tower bottom obtains is divided into the enriched substance of EPA and DHA；
Step 2: sodium hydroxide solution is added into the enriched substance of EPA and DHA in saponification, under 63 DEG C of waters bath with thermostatic control, is saponified, returns
It after flowing 70 min, is cooled to room temperature, filters off unsaponifiable matter, obtain unsaturated fatty acid salt solution；
Step 3: preparing fatty acid mixed, and sodium chloride is added into unsaturated fatty acid salt solution, and unsaturated fatty acid is precipitated
Salt after being washed to neutrality with deionized water to unsaturated fatty acid salt, with petroleum ether extraction, obtains the mixing-in fat containing petroleum ether
Acid；
Step 4: the fatty acid mixed containing petroleum ether is transferred in stirred tank by silver ion complexation, opens stirring, mixing speed
Control is 100 rpm, and temperature in the kettle control is 54 DEG C, addition excess nitric acid silver aqueous solution, after 110 min of sustained response, is stood
Layering, liquid separation separate petroleum ether phase, obtain silver ion complexation solution；
Step 5: dissociation complex compound first washs water phase with saturated sodium chloride solution, until spending after no longer there is sediment
Ion water washing recycles sediment, petroleum ether is added in liquid phase, extract, merges petroleum ether phase, obtains the mixing of DHA- petroleum ether
Object；
Step 6: DHA- petroleum ether mixtures are transferred in evaporating column, are evaporated under reduced pressure by evaporation purification, and tower bottom recycles stone
Oily ether, tower top obtain DHA；
Step 7: preparing mother liquor, and product of the DHA after CYP450 is metabolized is dissolved in dehydrated alcohol, mother liquor is prepared into, packing is kept away
Light be stored in -20 DEG C it is spare.
Wherein, in Omega-3, the mass fraction that the mass fraction of EPA is 37%, DHA is 22%；Filler is in extraction tower
Corrugated wire gauze packing, it is 0.2 mm that silk, which passes through, and silk screen is 80 mesh, and packed height is 40 mm；The column bottom temperature of extraction tower is
50 DEG C, tower top temperature is 90 DEG C, and extracting pressure is 12 MPa, and charging rate is 1 mL/min；The quality of sodium hydroxide solution point
Number is 6%；Mother liquid concentration is 100 mmol/L, final concentration of the 0.1% of dehydrated alcohol in mother liquor.
Embodiment 4
The present invention provides a kind of technical solution: a kind of method that Omega-3 prepares large conductance calcium activated potassium channel opener, including
Following preparation step:
Step 1: enrichment EPA and DHA, by Omega-3 and supercritical CO2It is mixed, is pumped into extraction tower with high pressure constant flow pump
In, supercritical extract is carried out, tower top obtains light component, and the recombination that tower bottom obtains is divided into the enriched substance of EPA and DHA；
Step 2: sodium hydroxide solution is added into the enriched substance of EPA and DHA in saponification, under 65 DEG C of waters bath with thermostatic control, is saponified, returns
It after flowing 90 min, is cooled to room temperature, filters off unsaponifiable matter, obtain unsaturated fatty acid salt solution；
Step 3: preparing fatty acid mixed, and sodium chloride is added into unsaturated fatty acid salt solution, and unsaturated fatty acid is precipitated
Salt after being washed to neutrality with deionized water to unsaturated fatty acid salt, with petroleum ether extraction, obtains the mixing-in fat containing petroleum ether
Acid；
Step 4: the fatty acid mixed containing petroleum ether is transferred in stirred tank by silver ion complexation, opens stirring, mixing speed
Control is 120 rpm, and temperature in the kettle control is 60 DEG C, addition excess nitric acid silver aqueous solution, after 120 min of sustained response, is stood
Layering, liquid separation separate petroleum ether phase, obtain silver ion complexation solution；
Step 5: dissociation complex compound first washs water phase with saturated sodium chloride solution, until spending after no longer there is sediment
Ion water washing recycles sediment, petroleum ether is added in liquid phase, extract, merges petroleum ether phase, obtains the mixing of DHA- petroleum ether
Object；
Step 6: DHA- petroleum ether mixtures are transferred in evaporating column, are evaporated under reduced pressure by evaporation purification, and tower bottom recycles stone
Oily ether, tower top obtain DHA；
Step 7: preparing mother liquor, and product of the DHA after CYP450 is metabolized is dissolved in dehydrated alcohol, mother liquor is prepared into, packing is kept away
Light be stored in -20 DEG C it is spare.
Wherein, in Omega-3, the mass fraction that the mass fraction of EPA is 37%, DHA is 22%；Filler is in extraction tower
Corrugated wire gauze packing, it is 0.2 mm that silk, which passes through, and silk screen is 80 mesh, and packed height is 40 mm；The column bottom temperature of extraction tower is
50 DEG C, tower top temperature is 90 DEG C, and extracting pressure is 12 MPa, and charging rate is 1 mL/min；The quality of sodium hydroxide solution point
Number is 6%；Mother liquid concentration is 100 mmol/L, final concentration of the 0.1% of dehydrated alcohol in mother liquor.
DHA yield and purity in four groups of embodiments are counted, following table is made:
By product of the above-mentioned available DHA of the invention of four groups of embodiments after CYP450 is metabolized, wherein embodiment
Two obtained DHA yields and purity are highest, and wherein yield is 69%, purity 85%.
The beneficial effects of the present invention are: the present invention uses silver ion as complexing agent, substance double key number in Omega-3 is utilized
Difference, realize EPA and DHA separation, and using sodium chloride as precipitating reagent recycle silver ion, avoid silver ion from losing, enrichment
DHA purity afterwards is up to 85%, and yield is up to 69%, and low energy consumption, and easy to operate, mild condition, the period is short, high income；The present invention uses
Using CO2EPA in Omega-3 and DHA are purified, are enriched with by the mode of supercritical extract, reduce the steps such as subsequent extraction, complexing
Rapid solvent usage amount；The final concentration of dehydrated alcohol both can guarantee EDPs normal storage, be avoided that less than 0.2% in mother liquor
More ethyl alcohol impact cell ion channel.
It although an embodiment of the present invention has been shown and described, for the ordinary skill in the art, can be with
A variety of variations, modification, replacement can be carried out to these embodiments without departing from the principles and spirit of the present invention by understanding
And modification, the scope of the present invention is defined by the appended.
Claims (6)
1. a kind of method that Omega-3 prepares large conductance calcium activated potassium channel opener, it is characterised in that: walked including following preparation
It is rapid:
Step 1: enrichment EPA and DHA, by Omega-3 and supercritical CO2It is mixed, is pumped into extraction tower with high pressure constant flow pump,
Supercritical extract is carried out, tower top obtains light component, and the recombination that tower bottom obtains is divided into the enriched substance of EPA and DHA；
Step 2: sodium hydroxide solution is added into the enriched substance of EPA and DHA in saponification, under 60-65 DEG C of water bath with thermostatic control, soap
Change, flow back after 30-90 min, be cooled to room temperature, filters off unsaponifiable matter, obtain unsaturated fatty acid salt solution；
Step 3: preparing fatty acid mixed, and sodium chloride is added into unsaturated fatty acid salt solution, and unsaturated fatty acid is precipitated
Salt after being washed to neutrality with deionized water to unsaturated fatty acid salt, with petroleum ether extraction, obtains the mixing-in fat containing petroleum ether
Acid；
Step 4: the fatty acid mixed containing petroleum ether is transferred in stirred tank by silver ion complexation, opens stirring, mixing speed
Control is 60-120 rpm, and temperature in the kettle control is 40-60 DEG C, and excess nitric acid silver aqueous solution, sustained response 90-120 is added
After min, stratification, liquid separation separates petroleum ether phase, obtains silver ion complexation solution；
Step 5: dissociation complex compound first washs water phase with saturated sodium chloride solution, until spending after no longer there is sediment
Ion water washing recycles sediment, petroleum ether is added in liquid phase, extract, merges petroleum ether phase, obtains the mixing of DHA- petroleum ether
Object；
Step 6: DHA- petroleum ether mixtures are transferred in evaporating column, are evaporated under reduced pressure by evaporation purification, and tower bottom recycles stone
Oily ether, tower top obtain DHA；
Step 7: preparing mother liquor, and product of the DHA after CYP450 is metabolized is dissolved in dehydrated alcohol, mother liquor is prepared into, packing is kept away
Light be stored in -20 DEG C it is spare.
2. the method that a kind of Omega-3 according to claim 1 prepares large conductance calcium activated potassium channel opener, feature
Be: in step 1, in the Omega-3, the mass fraction that the mass fraction of EPA is 37%, DHA is 22%.
3. the method that a kind of Omega-3 according to claim 1 prepares large conductance calcium activated potassium channel opener, feature
Be: in step 1, filler is corrugated wire gauze packing in the extraction tower, and it is 0.2 mm that silk, which passes through, and silk screen is 80 mesh, is filled out
Material height is 40 mm.
4. the method that a kind of Omega-3 according to claim 1 prepares large conductance calcium activated potassium channel opener, feature
Be: in step 1, the column bottom temperature of the extraction tower is 50 DEG C, and tower top temperature is 90 DEG C, and extracting pressure is 12 MPa, charging
Speed is 1 mL/min.
5. the method that a kind of Omega-3 according to claim 1 prepares large conductance calcium activated potassium channel opener, feature
Be: in step 2, the mass fraction of the sodium hydroxide solution is 6%.
6. the method that a kind of Omega-3 according to claim 1 prepares large conductance calcium activated potassium channel opener, feature
Be: in step 7, the mother liquid concentration is 100 mmol/L, and the final concentration of dehydrated alcohol is less than 0.2% in mother liquor.
Priority Applications (1)
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