CN102199182A - One-step extraction method for disodium 5'-inosinate - Google Patents
One-step extraction method for disodium 5'-inosinate Download PDFInfo
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- CN102199182A CN102199182A CN2011100882959A CN201110088295A CN102199182A CN 102199182 A CN102199182 A CN 102199182A CN 2011100882959 A CN2011100882959 A CN 2011100882959A CN 201110088295 A CN201110088295 A CN 201110088295A CN 102199182 A CN102199182 A CN 102199182A
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- disodium
- inosinate
- acid disodium
- naoh solution
- inosine
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Abstract
The invention relates to a one-step extraction method for disodium 5'-inosinate, which comprises the following steps: carrying out phosphorylation reaction on inosine and triethyl phosphate (TEP), cooling, and carrying out low-temperature salt-free hydrolysis; dropwisely adding a 40wt% NaOH solution at (-10)-5 DEG C after the low-temperature salt-free hydrolysis is finished, regulating the pH value to about 5.0, and ensuring that turbid points emerge in the liquid, thus precipitating emulsible disodium 5'-inosinate microcrystals; continuing dropwisely adding the 40wt% NaOH solution, and growing the crystals when the pH value rises to 8.0-8.5; quickly carrying out vacuum filtration on the crystals; washing disodium 5'-inosinate crystal filter cakes 2-3 times with identical volume of 80-85% (v/v) ethanol of 0-5 DEG C; and drying while depressurizing to obtain a disodium 5'-inosinate product. The one-step extraction method for disodium 5'-inosinate simplifies the process, saves the production cost and improves the product yield.
Description
Technical field
The present invention relates to belong to 5 '-the inosine acid disodium extractive technique, particularly relate to a kind of 5 '-a step extracting method of inosine acid disodium.
Background technology
5 '-inosine acid disodium, another name Sodium Inosinate (hereinafter to be referred as IMP), proterties is colourless crystallization to white, or white crystalline powder.Delicious, the delicate flavour threshold value is 0.025g/100ml, and delicate flavour intensity is lower than sodium guanylate, but the two has obvious synergy, mixes and 0.8% Sodium Glutamate and usefulness with 1:1 when the two, and its delicate flavour exceeds 40～100 times than general monosodium glutamate, and local flavor is better.Water-soluble, stabilized aqueous solution is neutral, easily decomposes in acidic solution, loses to be flavor power.
Chinese patent CN1539846A mention 5 '-preparation technology of disodium 5 '-ribonucleotide in, the phosphinylidyne reaction finishes the back and adopts icy salt solution to be hydrolyzed, the hydrolyzed solution static layering is separated water layer and organic layer, and water layer is regulated pH 〉=13 with 50%NaOH solution under cooling, remove by filter sodium phosphate in 0 ℃ of crystallization, solution is neutralized to pH=8～9 with concentrated hydrochloric acid, and the crude product that obtains IMP is filtered in concentrating under reduced pressure postcooling to 0～5 ℃, the water recrystallization obtains the IMP finished product again.This method contains a large amount of inorganic salt because solution decompression concentrates the cooling suction filtration in the product, purity is not high, needs repeatedly recrystallization to improve concentration.Complex process, yield is low, production cost is high.
Propose 5 among the Chinese patent CN1616475A '-preparation technology of cytidine mono-phosphate in, phosphorus acylation reaction finishes, again after hydrolysis, distillation; water is transferred to pH=3～4 freezing and crystallizings; though product can reach more than 98% through purity behind the secondary crystal, this method complex process, yield is very low.
KR9500259 proposes to adopt strategic point dialysis crystallization guanosine monophosphate, starting soln pH is controlled at 8.4～8.6, improve the solution degree of supersaturation by adding formic acid or ethanol, when nucleus is about to produce, change stream and add form and speed and obtain 5 '-the sodium guanylate crystal.This method crystallisation process is wayward, consumes unnecessary organic solvent, has increased cost and post-processing difficulty.
Mentioned among the Chinese patent CN1861624A a kind of 5 '-crystallization method of nucleosides-sodium phosphate salt, this method the pH value be 5.0～9.0 and mass percent be 5 of 5～30% concentration '-nucleosides-phosphate aqueous solution in, add the solute mass percent and be 110% inorganic sodium and initial 5 '-the dissolved agent of 0.5～10 times of nucleosides-phosphate aqueous solution volume come crystallization separate out 5 '-nucleosides-sodium phosphate salt crystal.This method produces a large amount of inorganic sodiums in the big production of industry, consume the organic solvent as the dissolved agent, has increased cost, does not reach the purpose of energy-conserving and environment-protective.
Summary of the invention
The present invention is for solving above-mentioned the deficiencies in the prior art, provide a kind of easy 5 '-a step extracting method of inosine acid disodium, its operating procedure is simplified, the equipment input reduces, solvent consumption reduces, and has the advantage of energy-conserving and environment-protective.
The technical scheme that technical solution problem of the present invention is taked is: a kind of 5 '-a step extracting method of inosine acid disodium, leaching process is: lower the temperature behind inosine and triethyl phosphate (hereinafter to be referred as TEP) phosphorus acylation reaction, carry out low temperature and do not have salt hydrolysis; After low temperature does not have salt hydrolysis and stops, between-10 ℃～5 ℃, drip the quality percentage composition and be 40% NaOH solution, make pH pull back to about 5.0 and feed liquid cloud point appears, promptly have 5 '-inosine acid disodium emulsus crystallite separates out; Continuation dropping quality percentage composition is 40% NaOH solution, growing the grain when pH rises to 8.0～8.5; Carry out the crystal suction filtration then fast; With 5 '-inosine acid disodium crystallization filter cake with the volumn concentration of equal volume be 80%～85% and temperature be 0 ℃～5 ℃ washing with alcohol 2～3 times; Decompression oven dry, obtain 5 '-the inosine acid disodium product.
In the said extracted process, be 40% NaOH solution when dripping the quality percentage composition, make pH pull back to about 5.0 and feed liquid when cloud point occurring, can add 5 '-the inosine acid disodium parent crystal.
As a kind of preferred, described growing the grain is to keep 30～60 minutes between-5 ℃～0 ℃.
As a kind of preferred, described crystal suction filtration carries out under the not stratified condition of triethyl phosphate keeping, and temperature is controlled at consistent with Tc, promptly-10 ℃～5 ℃.
In the present invention, low temperature does not have salt hydrolysis and has guaranteed once to extract product qualified rate, and Tc is controlled between-10 ℃～5 ℃.Tc influences required crystallization powder crystalline thickness, and it is thin that temperature is lower than-5 ℃ of crystallization gained powders, opposite Tc height, and then the crystallization crystal presents thicker phenomenon.Cloud point appears in feed liquid during the readjustment pH5.0 left and right sides, growing the grain under the cold condition, and the filtrate that the crystal suction filtration obtains is detected pH immediately should be greater than 7.0, between best pH7.0～8.0.
Beneficial effect of the present invention: the present invention is a kind of 5 '-a step extracting method of inosine acid disodium, after hydrolysis finishes, saved the adding of inorganic salt and dissolved agent, simplified technical process, saved production cost, improved product yield.Compared with prior art has following advantage.
1. save NaCl salt and consumption of ethanol, do not used in the crystallisation process and saltout and the dissolved agent, directly controlled pH value step in solution and separate out most of IMP crystallization, reduced process procedure, reached the purpose of saving cost.
2. reduced the number of times of recrystallization, the IMP crystal crystalline form that disposable crystallization is separated out is complete, with volumn concentration is TEP solvent and a spot of inorganic salt that 80%～85% cold ethanol can flush away adheres to, improved the purity of finished product, save the step of recrystallization, further improved crystallization yield.
Embodiment
Embodiment 1:
Carry out phosphorus acylation reaction with the 27.22g inosine, transformation efficiency 96% finishes the back and slowly add the hydrolysis of 450ml frozen water in reaction solution, hydrolysis time 30 min, and temperature finally is-5 ℃.With the quality percentage composition is the neutralization of 40% NaOH solution, when the pH value〉5.0 the time, feed liquid is become turbid, and has crystal to separate out.Continuation dropping quality percentage composition is 40% NaOH solution, stablizes material liquid pH value=8.3, growing the grain 30 min.Fast behind the suction filtration, the filter cake volumn concentration be 85% and temperature be that 0 ℃ cold ethanol cleans three times, consumption 200ml at every turn.Primary crystallization obtains crystalline flour 46.4g after vacuum-drying, crystallization yield 90.3%, HPLC tire 99.4%, moisture 23.2%.
Embodiment 2:
Carry out phosphorus acylation reaction with the 27.22g inosine, reaction finishes to add the 450ml frozen water, hydrolysis 20 min, and temperature finally is 0 ℃.With the quality percentage composition is that 40% NaOH solution is neutralized to pH=8.0, drips the quality percentage composition more on a small quantity and be 40% the solution-stabilized pH value of NaOH, growing the grain 1 hour.Quick suction filtration, filter cake volumn concentration be 80% and temperature be that 5 ℃ cold ethanol cleans three times, consumption 200ml at every turn.Primary crystallization obtains crystalline flour 44.6g after vacuum-drying, crystallization yield 85.6%, HPLC tire 98.0%, moisture 24.5%.
Embodiment 3:
Carry out phosphorus acylation reaction with the 27.22g inosine, reaction finishes to add 450ml frozen water hydrolysis 1 hour, and temperature finally is-5 ℃.With the quality percentage composition is that 40% NaOH solution is when being neutralized to pH=5, add a small amount of crystalline flour (inosine acid disodium crystallization) as nucleus, accelerate separating out of crystalline flour, continuing with the quality percentage composition is that 40% NaOH solution is adjusted to pH=8.2, growing the grain is (≤0 ℃ of temperature control) after 1 hour, quick suction filtration, filter cake volumn concentration be 85% and temperature be that 2 ℃ cold ethanol cleans three times, consumption 200ml at every turn.Primary crystallization obtains crystalline flour 47.5g after vacuum-drying, crystallization yield 90.7%, HPLC tire 97.5%, moisture 22.5%.
Claims (4)
1. one kind 5 '-inosine acid disodium one the step extracting method, it is characterized in that leaching process is: behind inosine and triethyl phosphate phosphorus acylation reaction, lower the temperature, carry out low temperature and do not have salt hydrolysis; After low temperature does not have salt hydrolysis and stops, between-10 ℃～5 ℃, drip the quality percentage composition and be 40% NaOH solution, make pH pull back to about 5.0 and feed liquid cloud point appears, promptly have 5 '-inosine acid disodium emulsus crystallite separates out; Continuation dropping quality percentage composition is 40% NaOH solution, growing the grain when pH rises to 8.0～8.5; Carry out the crystal suction filtration then fast; With 5 '-inosine acid disodium crystallization filter cake with the volumn concentration of equal volume be 80%～85% and temperature be 0 ℃～5 ℃ washing with alcohol 2～3 times; Decompression oven dry, obtain 5 '-the inosine acid disodium product.
2. a step extracting method according to claim 1 is characterized in that, is 40% NaOH solution when dripping the quality percentage composition, makes pH pull back to about 5.0 and feed liquid when cloud point occurring, add 5 '-the inosine acid disodium parent crystal.
3. a step extracting method according to claim 1 is characterized in that described growing the grain is to keep 30～60 minutes between-5 ℃～0 ℃.
4. a step extracting method according to claim 1 is characterized in that, described crystal suction filtration carries out under the not stratified condition of triethyl phosphate keeping, and temperature is controlled at consistent with Tc, promptly-10 ℃～5 ℃.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011100882959A CN102199182A (en) | 2011-04-10 | 2011-04-10 | One-step extraction method for disodium 5'-inosinate |
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| CN2011100882959A CN102199182A (en) | 2011-04-10 | 2011-04-10 | One-step extraction method for disodium 5'-inosinate |
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| CN102199182A true CN102199182A (en) | 2011-09-28 |
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| CN2011100882959A Pending CN102199182A (en) | 2011-04-10 | 2011-04-10 | One-step extraction method for disodium 5'-inosinate |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114302888A (en) * | 2019-10-17 | 2022-04-08 | Cj第一制糖株式会社 | Method for separating disodium 5' -inosinate |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3413282A (en) * | 1965-03-17 | 1968-11-26 | Ajinomoto Kk | Method of preparing 5'-nucleotides |
| US4958017A (en) * | 1987-12-17 | 1990-09-18 | Takeda Chemical Industries, Ltd. | Purification of inosine from guanosine |
| CN1539846A (en) * | 2003-10-29 | 2004-10-27 | 徐昌洪 | Technique for preparing 5'nucleotide bi-sodium |
| CN101109017A (en) * | 2006-07-19 | 2008-01-23 | Cj株式会社 | Method for purifying 5-inosinic acid zymotic fluid by crystallization |
| CN101293907A (en) * | 2008-06-24 | 2008-10-29 | 广东肇庆星湖生物科技股份有限公司 | Technique for preparing 5'-inosine acid disodium |
| CN101665525A (en) * | 2009-09-10 | 2010-03-10 | 广东肇庆星湖生物科技股份有限公司 | Synthetic method of nucleotide |
-
2011
- 2011-04-10 CN CN2011100882959A patent/CN102199182A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3413282A (en) * | 1965-03-17 | 1968-11-26 | Ajinomoto Kk | Method of preparing 5'-nucleotides |
| US4958017A (en) * | 1987-12-17 | 1990-09-18 | Takeda Chemical Industries, Ltd. | Purification of inosine from guanosine |
| CN1539846A (en) * | 2003-10-29 | 2004-10-27 | 徐昌洪 | Technique for preparing 5'nucleotide bi-sodium |
| CN101109017A (en) * | 2006-07-19 | 2008-01-23 | Cj株式会社 | Method for purifying 5-inosinic acid zymotic fluid by crystallization |
| CN101293907A (en) * | 2008-06-24 | 2008-10-29 | 广东肇庆星湖生物科技股份有限公司 | Technique for preparing 5'-inosine acid disodium |
| CN101665525A (en) * | 2009-09-10 | 2010-03-10 | 广东肇庆星湖生物科技股份有限公司 | Synthetic method of nucleotide |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114302888A (en) * | 2019-10-17 | 2022-04-08 | Cj第一制糖株式会社 | Method for separating disodium 5' -inosinate |
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Application publication date: 20110928 |