CN108157908A - It is a kind of to utilize the method for vacuumizing and preparing high heap density I+G mixed crystal - Google Patents
It is a kind of to utilize the method for vacuumizing and preparing high heap density I+G mixed crystal Download PDFInfo
- Publication number
- CN108157908A CN108157908A CN201810132321.5A CN201810132321A CN108157908A CN 108157908 A CN108157908 A CN 108157908A CN 201810132321 A CN201810132321 A CN 201810132321A CN 108157908 A CN108157908 A CN 108157908A
- Authority
- CN
- China
- Prior art keywords
- mixed crystal
- dissolved
- crystal
- heap density
- agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/20—Synthetic spices, flavouring agents or condiments
- A23L27/23—Synthetic spices, flavouring agents or condiments containing nucleotides
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Nutrition Science (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
Abstract
The application is a kind of theoretical using the method combination cocrystallization for preparing high heap density I+G mixed crystal is vacuumized, introducing vacuumizes means, the parameters such as dissolved agent drop rate, stir speed (S.S.), vacuum degree are studied, it is high that a kind of heap density is prepared, granularity is big, product is uniform, the I+G mixed crystal of good fluidity.Technical process is simple, is easy to control, and solves in I+G mixed crystal preparation process, influence factor is excessive, the mixed crystal product of high-quality can be prepared in the technical issues of many factors are difficult to coordinate in constant parameter area, significantly reduce the difficulty of technical process control.The I+G mixed crystal Lens capsule d (50) of preparation are 481~569 μm, and heap density is 0.90~0.96g/ml.When vacuumizing crystallization, dissolved agent is recycled, and the dissolved agent of recycling is added in solution and continues to participate in dissolved, has saved cost.
Description
Technical field
A kind of preparation method of the sapidity nucleotide disodium is claimed in the present invention, belongs to food dressing field, specifically relates to
A kind of and method that the sapidity nucleotide disodium is prepared using crystallization mode.
Background technology
The sapidity nucleotide disodium (Disodium 5 '-ribonucleotide, abbreviation I+G) is 5 '-inosine acid disodium
(Disodium 5 '-inosinate, abbreviation IMP) and 5 '-Sodium guanylate (5 '-guanylate of Disodium
, abbreviation GMP) crystal or mixture,.IMP, GMP are nucleotide derivative, are widely present in the various meat of the Nature
In class and mushroom class, in natural meat delicate flavour and mushroom delicate flavour.The process of production flavour nucleotide mainly has microorganism hair
Ferment method, enzymatic isolation method, enzyme catalysis method and chemical synthesis etc..By IMP and GMP stostes made from above-mentioned several method, through overrich
The operations separation such as contract, crystallize, being filtered, washed and dried can obtain respective crude product.The crystallization process of IMP easily carries out, molten
Crystal can directly be precipitated in liquid crystallization；And that GMP is precipitated in the solution is usually amorphous, to obtain GMP and have to pass through one
The process of crystalline form conversion, process control is more complicated, and crystal product poor morphology, the heap density generally yielded is low, easy coalescence.
Due to the difference of the various crystal shapes of IMP and GMP and powder characteristics, if the solid for simply crystallizing the two zymotic fluid
Powder-product mechanical mixture in proportion, not only mixed process have various operational difficulties, but also obtained mix product
It is difficult to obtain ideal mixed effect.
The process of production flavour nucleotide mainly has microbe fermentation method, enzymatic isolation method, enzyme catalysis method and chemical synthesis
Method etc..By IMP and GMP stostes made from above-mentioned several method, by concentrating, crystallizing, the operations such as being filtered, washed and dried and detach
It can obtain respective crude product.The crystallization process of IMP easily carries out, and crystal can directly be precipitated in solution crystallization；And GMP is in solution
Middle precipitation it is usually amorphous, to obtain the process that GMP has to pass through the conversion of crystalline form, process control is more complicated,
The crystal product poor morphology, the heap density that generally yield is low, easy coalescence.Due to the various crystal shapes of IMP and GMP and powder characteristics
Difference, if the solid powder product for simply crystallizing the two zymotic fluid mechanical mixture in proportion, not only mixed process
There are various operational difficulties, and obtained mix product also is difficult to obtain ideal mixed effect.
Dilution crystallization is the difference using separated object matter and solvent molecule Interaction Force, by solute be dissolved in water or
In other solvents, then other solvent is so that solubility of the solute in former solvent reduces, so as to make solute that crystallization be precipitated.It crosses
Saturation degree is the important factor in order of lolute crystallization, and degree of supersaturation is small, and growth rate is slow, advantageously forms that grain size is big, crystal form is complete
Whole, good dispersion crystal, degree of supersaturation is too big, and crystal growth rate and nucleation rate increase, easily formed it is explosive into
Core easily forms irregular crystal.
The Chinese patent of CN101619086A discloses a kind of flavour nucleotide crystal and preparation method.In preparation process
In, using IMP, GMP crude product as raw material, component ratio 1:1.By dissolving, eluting, dissolved, natural cooling, again dissolved, cold again
But, filtering, vacuum drying step, obtain reported crystal form.The technique is changed by adjusting the parameters such as stirring, solution temperature, pH
It has been apt to product crystal form and quality.But the preparation method cools down fine grain by standing, makes its outburst nucleation, the granularity and shape of crystal
Shape can not regulate and control, and final product heap density is 0 .58-0 .63g/ml, and crystal angle of repose is 38-46 °.The heap of crystal
Density is still relatively low, mobility is poor.
CN105495528A discloses a kind of method for preparing high heap density the sapidity nucleotide disodium mixed crystal, with IMP,
GMP crude products are raw material, and dissolving, the agent of addition dissolved carry out growing the grain, by adding nucleus, and adjust the adding rate of solvent to control
Crystallization process processed, the Lens capsule d (50) being prepared are 200~450 μm, and heap density is 0.76~0.86g/ml, not
Angle till is 20~30 °.However, its heap density is still relatively low, and the crystal structure time is long, low production efficiency.Control of keeping under strict control is needed simultaneously
The adding rate of dissolved agent processed, technique are relatively complicated.
The comprehensive analysis prior art, the method for finding to prepare I+G mixed crystal in the prior art, technical process is complex, mistake
Journey is difficult to control, and the I+G mixed crystal heap density prepared is relatively low, and particle is smaller, and mobility is poor.
Invention content
In view of the deficiencies of the prior art, the application provides a kind of method that can quickly prepare I+G, and technical process is easily controlled
System, process is simple, and the I+G heaps density being prepared is high, and granularity is big, good fluidity.
The present invention is achieved through the following technical solutions.
A kind of method for preparing high heap density the sapidity nucleotide disodium mixed crystal；It is it is characterized in that as follows including step：
1) IMP, GMP crude product are pressed 0.95 ~ 1.05:1 is added to the water, and compound concentration is the aqueous solution of 150 ~ 180g/L, and stirring is molten
Solution adjusts pH to 7.5~8.0；2) solubilization analysis agent to solution is in saturation state, and the I+G for then adding in crude product quality 2 ~ 3% is brilliant
Kind；It at the uniform velocity stirs, while constant-speed material-adding solubilization analysis agent, and vacuumizes crystallization；3) suction filtration, washing and normal temperature and pressure drying are in
Flavor nucleotide disodium mixed crystal product.
When vacuumizing crystallization, dissolved agent is recycled, and the dissolved agent of recycling is then added in solution and carries out dissolved.
Step 2）In, stir speed (S.S.) is 100rpm ~ 125rpm.
Step 2）In, dissolved agent is ethyl alcohol, and dissolved agent at the uniform velocity drop rate is 0.5 ~ 2ml/min.
Step 2）In, vacuum degree control is in 0.07 ~ 0.09MP.
The size distribution d (50) of crystal product is 481~569 μm, and heap density is 0.90~0.96g/ml.
The drop rate of dissolved agent and the crystallization of flavour nucleotide and growing the grain have very big relationship, usually faster to be added dropwise
Rate causes high degree of supersaturation, leads to the generation of a large amount of nucleus, conversely, slower drop rate then have using formed it is larger
Crystal.The size of stir speed (S.S.) has a great impact to the speed of crystallization, the size of crystal, form more, is not stirred after gentle agitation
The supersaturated solution mixed can form wider metastable region, and crystallization induction time is elongated, and the crystal of preparation is larger, and particle
It is more uniform, and during stir speed (S.S.) increase, metastable region narrows, degree of supersaturation increase, easily explosive to be nucleated, and obtains smaller crystalline substance
Body product.Temperature is one of important parameter for influencing Crystallization and growth, and when solution degree of supersaturation is certain, crystallization temperature is low
When, obtained crystal is comparatively fine, and the extraction then obtained when temperature is high is larger, and higher temperature can change crystallization medium and solution
The interfacial tension of phase, diffusion coefficient increase, nucleus generates rate and reduces, but the growth rate of nucleus increases, and can obtain larger
Crystal grain.The addition of crystal seed all has very important influence to the rate and crystal growth of crystallization, adds suitable crystalline substance
Kind can make crystal seed suspend in the solution, and most of solute will be attached to seed crystals, promote nucleus growth, can obtain
Even crystal product.With reference to cocrystallization theory, applicant has carried out above-mentioned technological parameter analysis experiment, it is intended to find a kind of behaviour
Make simple, superior product quality I+G products, however, since the factor influenced on solution degree of supersaturation is too many, any one amount
Variation can all cause larger change, and research, which once entered, stagnates, however, when applicant introduces and vacuumizes means, surprisingly
It was found that dissolved agent adding rate, stir speed (S.S.) can maintained constant, and do not have on the basis of additionally temperature is adjusted,
A kind of I+G products of high-quality are prepared.It vacuumizing in crystallization process, solvent and dissolved agent are evaporated concentration simultaneously, but by
In the instillation for keeping dissolved agent, solution is remained in hypersaturated state, the study found that control vacuum degree control 0.07 ~
In the range of 0.09MP, it is 0.5 ~ 2ml/min to keep solvent drop rate.Solution degree of supersaturation can be maintained to maintain Jie steady
Area, solute are uniformly attached on crystal seed, and product form is uniform.On the other hand, it due to the presence of vacuum state, is formd in nucleus
Certain negative pressure due to the propulsion of pressure, promotes solute closer when being attached on crystal seed, close so as to improve the heap of product
Degree.Crystal product size distribution d (50) prepared by the application is 481~569 μm, and heap density is 0.90~0.96g/ml.
The application has the advantages that relative to the prior art：
1. technical process is simple, it is easy to control, solves in I+G mixed crystal preparation process, influence factor is excessive, and many factors are difficult to
The mixed crystal product of high-quality can be prepared in constant parameter area, significantly reduce work the technical issues of coordination
The difficulty of skill process control.
3. vacuumize crystallization, dissolved agent is recycled, and the dissolved agent of recycling is added in solution and is continued to participate in
Dissolved has saved cost.
3. in I+G mixed crystal preparation process, vacuum crystallization means are introduced, with reference to dissolved agent drop rate, stir speed (S.S.)
The control of technological parameters is waited, the I+G mixed crystal of high-quality has been prepared, Lens capsule d (50) is 481~569 μm, heap
Density is 0.90~0.96g/ml.
Specific embodiment
With reference to embodiment, the invention will be further described.
Embodiment 1：
1) 95gIMP crude products, 100gGMP crude products is taken to be added to the water, compound concentration is the aqueous solution of 180g/L, and stirring and dissolving is adjusted
PH to 7.5；2) solubilization analysis agent to solution is in saturation state, then adds in the I+G crystal seeds of crude product quality 3%；100rpm is at the uniform velocity stirred
It mixes, ethyl alcohol is at the uniform velocity added, and vacuumize by the rate of 2ml/min, maintenance vacuum degree is 0.09MP, is crystallized；3) filter, wash,
It is dry, obtain I+G mixed crystal products；When vacuumizing crystallization, recycle dissolved agent, and by the dissolved agent of recycling be then added in solution into
Row dissolved, after measured, product heap density are 0.93g/ml, and granularity is 532 μm.
Embodiment 2：
1) 105gIMP crude products, 100gGMP crude products is taken to be added to the water, compound concentration is the aqueous solution of 150g/L, and stirring and dissolving is adjusted
Save pH to 7.7；2) solubilization analysis agent to solution is in saturation state, then adds in the I+G crystal seeds of crude product quality 2%；110rpm is at the uniform velocity
Stirring, ethyl alcohol is at the uniform velocity added, and vacuumize by the rate of 2ml/min, and maintenance vacuum degree is 0.08MP, is crystallized；3) it filters, wash
It washs, dry, obtain I+G mixed crystal products.When vacuumizing crystallization, dissolved agent is recycled, and the dissolved agent of recycling is then added to solution
Middle carry out dissolved.After measured, product heap density is 0.95g/ml.Granularity is 569 μm.
Embodiment 3：
1) 100gIMP crude products, 100gGMP crude products is taken to be added to the water, compound concentration is the aqueous solution of 160g/L, and stirring and dissolving is adjusted
Save pH to 7.6；2) solubilization analysis agent to solution is in saturation state, then adds in the I+G crystal seeds of crude product quality 2.5%；115rpm is even
Speed stirring, ethyl alcohol is at the uniform velocity added, and vacuumize by the rate of 1.0ml/min, and maintenance vacuum degree is 0.08MP, is crystallized；3) filter,
Washing, drying, obtain I+G mixed crystal products.When vacuumizing crystallization, dissolved agent is recycled, and the dissolved agent of recycling is then added to molten
Dissolved is carried out in liquid.After measured, product heap density is 0.93g/ml.Granularity is 501 μm.
Embodiment 4：
1) 103gIMP crude products, 100gGMP crude products is taken to be added to the water, compound concentration is the aqueous solution of 170g/L, and stirring and dissolving is adjusted
Save pH to 8.0；2) solubilization analysis agent to solution is in saturation state, then adds in the I+G crystal seeds of crude product quality 2.3%；125rpm is even
Speed stirring, ethyl alcohol is at the uniform velocity added, and vacuumize by the rate of 0.5ml/min, and maintenance vacuum degree is 0.07MP, is crystallized；3) filter,
Washing, drying, obtain I+G mixed crystal products.When vacuumizing crystallization, dissolved agent is recycled, and the dissolved agent of recycling is then added to molten
Dissolved is carried out in liquid.After measured, product heap density is 0.90g/ml.Granularity is 545 μm.
Comparative example 1：
1) 100gIMP crude products, 100gGMP crude products is taken to be added to the water, compound concentration is the aqueous solution of 160g/L, and stirring and dissolving is adjusted
Save pH to 7.6；2) solubilization analysis agent to solution is in saturation state, then adds in the I+G crystal seeds of crude product quality 2.5%；115rpm is even
Speed stirring, ethyl alcohol is at the uniform velocity added, and vacuumize by the rate of 1.0ml/min, and maintenance vacuum degree is 0.12MP, is crystallized；3) filter,
Washing, drying, obtain I+G mixed crystal products.After measured, product heap density is 0.78g/ml.Granularity is 394 μm.
Comparative example 2：
1) 99gIMP crude products, 100gGMP crude products is taken to be added to the water, compound concentration is the aqueous solution of 170g/L, and stirring and dissolving is adjusted
PH to 8.0；2) solubilization analysis agent to solution is in saturation state, then adds in the I+G crystal seeds of crude product quality 2.3%；125rpm is at the uniform velocity
Stirring, ethyl alcohol is at the uniform velocity added by the rate of 1ml/min, is crystallized；3) it filters, wash, is dry, obtaining I+G mixed crystal products.Through surveying
Fixed, product heap density is 0.50g/ml.Granularity is 315 μm.
Above-described embodiment is the preferable embodiment of the application, and contrast test reflects the application technical process and technique
Influence of the adjustment of parameter to the crystal quality of preparation, but presently filed embodiment and be not restricted to the described embodiments,
Parameter is adjusted all within the protection domain of the application in the range that the application gives.
Claims (5)
1. it is a kind of using the method for preparing high heap density I+G mixed crystal is vacuumized, it is characterized in that as follows including step：
1) IMP, GMP crude product are pressed 0.95 ~ 1.05:1 is added to the water, and compound concentration is the aqueous solution of 150 ~ 180g/L, and stirring is molten
Solution adjusts pH to 7.5~8.0；2) solubilization analysis agent to solution is in saturation state, and the I+G for then adding in crude product quality 2 ~ 3% is brilliant
Kind；It at the uniform velocity stirs, while constant-speed material-adding solubilization analysis agent, and vacuumizes crystallization；3) suction filtration, washing and normal temperature and pressure drying are in
Flavor nucleotide disodium mixed crystal product；When vacuumizing crystallization, recycle dissolved agent, and by the dissolved agent of recycling be then added in solution into
Row dissolved.
2. the method as described in claim 1, step 2）In, stir speed (S.S.) is maintained in the range of 100rpm ~ 125rpm.
3. the method as described in claim 1, step 2）In, dissolved agent is ethyl alcohol, and dissolved agent at the uniform velocity drop rate control is 0.5
In the range of ~ 2ml/min.
4. the method as described in claim 1, step 2）In, vacuum degree control is in the range of 0.07 ~ 0.09MP.
5. I+G mixed crystal prepared by any one of claim 1 ~ 4 the method, the size distribution d (50) of crystal is 481~569 μ
M, heap density are 0.90~0.96g/ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810132321.5A CN108157908A (en) | 2018-02-09 | 2018-02-09 | It is a kind of to utilize the method for vacuumizing and preparing high heap density I+G mixed crystal |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810132321.5A CN108157908A (en) | 2018-02-09 | 2018-02-09 | It is a kind of to utilize the method for vacuumizing and preparing high heap density I+G mixed crystal |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108157908A true CN108157908A (en) | 2018-06-15 |
Family
ID=62514006
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810132321.5A Pending CN108157908A (en) | 2018-02-09 | 2018-02-09 | It is a kind of to utilize the method for vacuumizing and preparing high heap density I+G mixed crystal |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108157908A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102718823A (en) * | 2012-06-26 | 2012-10-10 | 华南理工大学 | Process method for elution, crystallization and refining of 5'-flavor nucleotide disodium |
| CN103755723A (en) * | 2014-02-07 | 2014-04-30 | 天津大学 | Method for preparing rifampicin I crystal form |
| CN105495528A (en) * | 2015-11-27 | 2016-04-20 | 天津大学 | Method for preparing high-bulk-density flavor nucleotides disodium mixed crystal |
| CN106008297A (en) * | 2016-06-03 | 2016-10-12 | 宁夏紫光天化蛋氨酸有限责任公司 | Novel methionine crystal form II and preparation method thereof |
| CN106928297A (en) * | 2017-03-10 | 2017-07-07 | 南京工业大学 | A kind of method of oil analysis conversion regulation and control Sodium guanylate crystallization process |
-
2018
- 2018-02-09 CN CN201810132321.5A patent/CN108157908A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102718823A (en) * | 2012-06-26 | 2012-10-10 | 华南理工大学 | Process method for elution, crystallization and refining of 5'-flavor nucleotide disodium |
| CN103755723A (en) * | 2014-02-07 | 2014-04-30 | 天津大学 | Method for preparing rifampicin I crystal form |
| CN105495528A (en) * | 2015-11-27 | 2016-04-20 | 天津大学 | Method for preparing high-bulk-density flavor nucleotides disodium mixed crystal |
| CN106008297A (en) * | 2016-06-03 | 2016-10-12 | 宁夏紫光天化蛋氨酸有限责任公司 | Novel methionine crystal form II and preparation method thereof |
| CN106928297A (en) * | 2017-03-10 | 2017-07-07 | 南京工业大学 | A kind of method of oil analysis conversion regulation and control Sodium guanylate crystallization process |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109608372A (en) | A kind of multistage continuous crystallisation process of corynebacterium methionine crystal | |
| CN102924539A (en) | Method for preparing trehalose crystals | |
| CN105495528B (en) | A method of preparing high heap density the sapidity nucleotide disodium mixed crystal | |
| CN105031963B (en) | A kind of integrated anti-solvent-vacuum evaporation-cooling or the method for crystallising of anti-solvent | |
| CN113620794A (en) | Crystallization method for preparing large-particle-size ethyl vanillin | |
| CN105753728B (en) | A kind of dilution crystallization method of pharmaceutical grade L valines | |
| CN108157908A (en) | It is a kind of to utilize the method for vacuumizing and preparing high heap density I+G mixed crystal | |
| TW201217311A (en) | Process for the production of L-carnitine tartrate | |
| CN107447058A (en) | A kind of preparation method of crystalline maltose | |
| CN108997430A (en) | A kind of crystal of Calcium Dibutyryladenosine Cyclophosph-ate salt | |
| EP1411059B1 (en) | Method for producing mixed crystal of disodium 5'-guanylate and disodium 5'-inosinate | |
| CN110114333A (en) | The improvement of lysine acetylsalicylate salt glycine particle synthesizes | |
| CN108690049A (en) | The method that Amoxicillin is detached from the reaction product that enzyme process prepares Amoxicillin | |
| CN111961102B (en) | 5' -uridine monophosphate crystal and preparation method thereof | |
| CN103937866B (en) | A kind of preparation method of the ampicillin of improvement | |
| CN109400491B (en) | Crystallization preparation method of L-p-hydroxyphenylglycine methyl ester | |
| CN109694337B (en) | Sodium isethionate ellipsoidal crystal and preparation method thereof | |
| CN106928297B (en) | A kind of method of oil analysis conversion regulation Sodium guanylate crystallization process | |
| CN106432021B (en) | A kind of preparation method of Fudosteine crystallization | |
| CN1219788C (en) | Dynamic controlled crystalline method of preparing erythromycin from erythromysin salt | |
| CN110817903A (en) | Controllable synthesis of potassium nitrate crystal by difference of cold shock mode | |
| CN114009734A (en) | Method for producing IMP + GMP through anti-solvent cooling crystallization based on solvent spraying oscillation | |
| CN112552188B (en) | Preparation method of sertraline hydrochloride crystal form I | |
| RU2795523C1 (en) | Method for separating 5'-inosinate disodium | |
| CN115721020B (en) | Preparation method of instant branched-chain amino acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180615 |
|
| RJ01 | Rejection of invention patent application after publication |