CN101575625A - Method for crystallizing D-glucuronic acid gamma-lactone - Google Patents
Method for crystallizing D-glucuronic acid gamma-lactone Download PDFInfo
- Publication number
- CN101575625A CN101575625A CNA2009100230055A CN200910023005A CN101575625A CN 101575625 A CN101575625 A CN 101575625A CN A2009100230055 A CNA2009100230055 A CN A2009100230055A CN 200910023005 A CN200910023005 A CN 200910023005A CN 101575625 A CN101575625 A CN 101575625A
- Authority
- CN
- China
- Prior art keywords
- glucuronic acid
- lactone
- value
- add
- acid gamma
- 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
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
D－葡萄糖醛酸γ－内酯结晶方法，根据氧化淀粉酶解产物性质差异，采用乙醇进行分离提纯的，实现了D－葡萄糖醛酸γ－内酯的常温结晶，母液回用，提高了D－葡萄糖醛酸γ－内酯的产率，实现了D－葡萄糖醛酸γ－内酯的清洁生产。具体方法为：将玉米淀粉，的水和FeSO4混合，用NaOH调节pH值为9～11，加入H2O2反应结束后升温至沸，再调节pH值为6.0～6.5，按加入α－淀粉酶水解，加热杀灭α－淀粉酶，调pH值4.0～4.5，再加入糖化酶过滤，给滤液中加乙醇，收集上层清液浓缩后加乙酸、乙酸酐出现微细晶种，分离晶体，用乙醇重结晶，得各项指标符合国家药典标准的产品，本发明简化了市场工艺，降低了生产成本。D-glucuronic acid γ-lactone crystallization method, according to the difference in properties of oxidized starch enzymatic hydrolysis products, using ethanol for separation and purification, realizes the normal temperature crystallization of D-glucuronic acid γ-lactone, reuses the mother liquor, and improves D -The yield of glucuronic acid γ-lactone realizes the clean production of D-glucuronic acid γ-lactone. The specific method is: mix cornstarch, water and FeSO 4 , use NaOH to adjust the pH value to 9-11, add H 2 O 2 after the reaction is completed, heat up to boiling, then adjust the pH value to 6.0-6.5, and press α- Amylase hydrolysis, heat to kill α-amylase, adjust the pH value to 4.0-4.5, then add glucoamylase to filter, add ethanol to the filtrate, collect the supernatant, concentrate, add acetic acid and acetic anhydride to form fine crystal seeds, separate the crystals, Recrystallize with ethanol to obtain a product whose various indexes meet the standards of the national pharmacopoeia. The invention simplifies the market process and reduces the production cost.
Description
Technical field
The invention belongs to medicine material or health products production field, be specifically related to a kind of D-glucuronic acid gamma lactone crystallization method.
Background technology
D-glucuronic acid gamma lactone has wide practical use in medicine, food, healthcare products industry, present industrial main employing nitric acid oxidation process, the shortcoming of this technology maximum is: seriously polluted, the product needed cryogenic freezing is separated, energy consumption is bigger, does not meet the industry policy of country.There is the glucoside of employing oxidation style to produce Glucuronic acid lactone abroad, oxidizing reaction need be catalyzer with Pt/C, cost is very high, and catalyzer is difficult to obtain, people such as Yuan Hua adopt load oxygenant method that Pt is loaded in the uhligite, reduced production cost to a certain extent, but the not well solution of problems such as product separation difficulty rests on also on the basis of former technology one.
The crystallization of D-glucuronic acid gamma lactone at present adopts vacuum concentration, freezing 6～8 days method to carry out crystallization.This method not only energy consumption is big, and since mixed solution thickness too, the Crystallization Separation difficulty.(publication number: CN1817895) adopt the triple dewatering method, carry out dynamic gradient cooling crystallization with 1～2 ℃/hour speed, the crystallization final temperature is 25 ± 5 ℃ to people such as Wuhan chemical industry Yuan Hua in 2006, crystallization total time≤40 hour.Crystalline mixture obtains D-glucuronic acid gamma lactone after filtration, and this method has improved the crystallization of D-glucuronic acid gamma lactone, has significantly reduced crystallization time and has reduced the crystallization energy consumption.But as secondary band aqua, there is the cost height with butylacetate in this method, and because butylacetate boiling point height, the D-glucuronic acid easily decomposes, the liquid thickness, and the difficult isolating problem of xln still is not well solved.
Summary of the invention
The object of the present invention is to provide a kind of difference to separate purification, turn cold and freeze brilliant be normal temperature crystallization, effective simplification production operation, the D-glucuronic acid gamma lactone crystallization method that reduces production costs according to hydrolyzate character.
For achieving the above object, the technical solution used in the present invention is:
1) at first with the 100g W-Gum, the water of 150～200mL and the FeSO of 0.05～0.1g
4Adding in the there-necked flask that band stirs, is 9～11 with the NaOH adjusting pH value of 0.1mol/L, slowly adds the H of 5～8g while stirring
2O
2, at 45 ℃ of following reaction 4h, be warming up to after reaction finishes seethe with excitement Sumstar 190;
2) the pH value of cooling and adjusting oxidized starch solution is 6.0～6.5, ratio adding vigor in α-Dian Fenmei/g starch of 100～150 μ is the α-Dian Fenmei of 20000 μ/g,, kill α-Dian Fenmei and get liquefier to boiling and maintenance 10min at 85～90 ℃ of following hydrolysis 0.5～2.0h post-heating;
3) liquefier being cooled to 60～65 ℃ and to regulate its pH value be 4.0～4.5, is the saccharifying enzyme of 10000 μ/g in the ratio adding vigor of saccharifying enzyme/g starch of 100～150 μ, at 60～65 ℃ of insulation 12～16h down, and heating go out enzyme and filtered while hot;
4) add ethanol in filtrate and be stirred well to the filtrate muddiness, leave standstill, collect supernatant liquor, triplicate merges supernatant liquor and concentrating under reduced pressure;
5) add 20mL acetate and 10mL diacetyl oxide in the supernatant liquor behind concentrating under reduced pressure, react 1～2h down at 45～55 ℃, leave standstill the fine crystal seed of appearance, occur D-glucuronic acid gamma lactone behind the 12h, isolation of crystalline promptly gets D-glucuronic acid gamma lactone with ethyl alcohol recrystallization.
The present invention is directed to the crystallization processes separation difficulty, the energy consumption height, problems such as the time is long, according to glucuronic acid, glucose, D-glucuronic acid gamma lactone and other disaccharides, polysaccharide properties difference, proposition is extracted glucuronic acid with Ethanol Method behind the Sumstar 190 enzymolysis, behind the recovery ethanol, add acetate, diacetyl oxide lactonizes, carry out crystallization at normal temperature and make Glucuronic acid lactoneization.Biggest advantage of the present invention is: replace freezing or triple dewatering crystallization method with the normal temperature crystallization, overcome the crystal separation problem of difficult, simplified production technique, reduced production cost greatly.
Embodiment
Embodiment 1:1) at first with the 100g W-Gum, the water of 150mL and the FeSO of 0.1g
4Adding in the there-necked flask that band stirs, is 10 with the NaOH adjusting pH value of 0.1mol/L, slowly adds the H of 6g while stirring
2O
2, at 45 ℃ of following reaction 4h, be warming up to after reaction finishes seethe with excitement Sumstar 190; Purpose is to allow excessive H
2O
2Thermal degradation is avoided the further oxidation of aldehyde radical (glucuronic acid, glucose) in the enzymolysis solution, gets carboxyl-content 〉=8%, the Sumstar 190 of carbonyl content≤0.2%;
2) the pH value of regulating oxidized starch solution is 6.2, is the α-Dian Fenmei of 20000 μ/g by the ratio adding vigor of α-Dian Fenmei/g starch of 120 μ,, kills α-Dian Fenmei and gets liquefier to seething with excitement and maintenance 10min at 90 ℃ of following hydrolysis 0.5h post-heating;
3) liquefier being cooled to 62 ℃ and to regulate its pH value be 4.5, is the saccharifying enzyme of 10000 μ/g in the ratio adding vigor of saccharifying enzyme/g starch of 120 μ, at 63 ℃ of insulation 14h down, and heating go out enzyme and filtered while hot;
4) concentrated filtrate (main purpose removal redundant moisture) and add ethanol be stirred well to the filtrate muddiness in filtrate leaves standstill, and collects supernatant liquor, and triplicate merges supernatant liquor and concentrating under reduced pressure (purpose recovery ethanol); The main component of enzymolysis is glucuronic acid, glucose, maltose and polysaccharide, and glucuronic acid is soluble in water, can be dissolved in ethanol, and glucose, maltose and polysaccharide is soluble in water, are slightly soluble in ethanol;
5) add 20mL acetate and 10mL diacetyl oxide in the supernatant liquor behind concentrating under reduced pressure, react 2h down at 45 ℃, leave standstill the fine crystal seed of appearance, occur D-glucuronic acid gamma lactone behind the 12h, isolation of crystalline promptly gets D-glucuronic acid gamma lactone with ethyl alcohol recrystallization.
Embodiment 2:1) at first with the 100g W-Gum, the water of 180mL and the FeSO of 0.08g
4Adding in the there-necked flask that band stirs, is 9 with the NaOH adjusting pH value of 0.1mol/L, slowly adds the H of 8g while stirring
2O
2, at 45 ℃ of following reaction 4h, be warming up to after reaction finishes seethe with excitement Sumstar 190;
2) the pH value of regulating oxidized starch solution is 6.5, is the α-Dian Fenmei of 20000 μ/g by the ratio adding vigor of α-Dian Fenmei/g starch of 140 μ,, kills α-Dian Fenmei and gets liquefier to seething with excitement and maintenance 10min at 86 ℃ of following hydrolysis 1.5h post-heating;
3) liquefier being cooled to 65 ℃ and to regulate its pH value be 4.2, is the saccharifying enzyme of 10000 μ/g in the ratio adding vigor of saccharifying enzyme/g starch of 140 μ, at 60 ℃ of insulation 16h down, and heating go out enzyme and filtered while hot;
4) concentrated filtrate adds ethanol and is stirred well to the filtrate muddiness in filtrate, leaves standstill, and collects supernatant liquor, and triplicate merges supernatant liquor and concentrating under reduced pressure;
5) add 20mL acetate and 10mL diacetyl oxide in the supernatant liquor behind concentrating under reduced pressure, react 1.5h down at 50 ℃, leave standstill the fine crystal seed of appearance, occur D-glucuronic acid gamma lactone behind the 12h, isolation of crystalline promptly gets D-glucuronic acid gamma lactone with ethyl alcohol recrystallization.
Embodiment 3:1) at first with the 100g W-Gum, the water of 160mL and the FeSO of 0.05g
4Adding in the there-necked flask that band stirs, is 11 with the NaOH adjusting pH value of 0.1mol/L, slowly adds the H of 5g while stirring
2O
2, at 45 ℃ of following reaction 4h, be warming up to after reaction finishes seethe with excitement Sumstar 190;
2) the pH value of regulating oxidized starch solution is 6.0, is the α-Dian Fenmei of 20000 μ/g by the ratio adding vigor of α-Dian Fenmei/g starch of 100 μ,, kills α-Dian Fenmei and gets liquefier to seething with excitement and maintenance 10min at 88 ℃ of following hydrolysis 1h post-heating;
3) liquefier being cooled to 61 ℃ and to regulate its pH value be 4.0, is the saccharifying enzyme of 10000 μ/g in the ratio adding vigor of saccharifying enzyme/g starch of 100 μ, at 64 ℃ of insulation 13h down, and heating go out enzyme and filtered while hot;
4) concentrated filtrate and add ethanol be stirred well to the filtrate muddiness in filtrate leaves standstill, and collects supernatant liquor, and triplicate merges supernatant liquor and concentrating under reduced pressure;
5) add 20mL acetate and 10mL diacetyl oxide in the supernatant liquor behind concentrating under reduced pressure, react 1.8h down at 48 ℃, leave standstill the fine crystal seed of appearance, occur D-glucuronic acid gamma lactone behind the 12h, isolation of crystalline promptly gets D-glucuronic acid gamma lactone with ethyl alcohol recrystallization.
Embodiment 4:1) at first with the 100g W-Gum, the water of 200mL and the FeSO of 0.09g
4Adding in the there-necked flask that band stirs, is 9 with the NaOH adjusting pH value of 0.1mol/L, slowly adds the H of 7g while stirring
2O
2, at 45 ℃ of following reaction 4h, be warming up to after reaction finishes seethe with excitement Sumstar 190;
2) the pH value of regulating oxidized starch solution is 6.3, is the α-Dian Fenmei of 20000 μ/g by the ratio adding vigor of α-Dian Fenmei/g starch of 150 μ,, kills α-Dian Fenmei and gets liquefier to seething with excitement and maintenance 10min at 85 ℃ of following hydrolysis 2.0h post-heating;
3) liquefier being cooled to 63 ℃ and to regulate its pH value be 4.3, is the saccharifying enzyme of 10000 μ/g in the ratio adding vigor of saccharifying enzyme/g starch of 150 μ, at 65 ℃ of insulation 12h down, and heating go out enzyme and filtered while hot;
4) concentrated filtrate and add ethanol be stirred well to the filtrate muddiness in filtrate leaves standstill, and collects supernatant liquor, and triplicate merges supernatant liquor and concentrating under reduced pressure;
5) add 20mL acetate and 10mL diacetyl oxide in the supernatant liquor behind concentrating under reduced pressure, react 1.3h down at 52 ℃, leave standstill the fine crystal seed of appearance, occur D-glucuronic acid gamma lactone behind the 12h, isolation of crystalline promptly gets D-glucuronic acid gamma lactone with ethyl alcohol recrystallization.
Embodiment 5:1) at first with the 100g W-Gum, the water of 170mL and the FeSO of 0.07g
4Adding in the there-necked flask that band stirs, is 10 with the NaOH adjusting pH value of 0.1mol/L, slowly adds the H of 8g while stirring
2O
2, at 45 ℃ of following reaction 4h, be warming up to after reaction finishes seethe with excitement Sumstar 190;
2) the pH value of regulating oxidized starch solution is 6.1, is the α-Dian Fenmei of 20000 μ/g by the ratio adding vigor of α-Dian Fenmei/g starch of 130 μ,, kills α-Dian Fenmei and gets liquefier to seething with excitement and maintenance 10min at 87 ℃ of following hydrolysis 1h post-heating;
3) liquefier being cooled to 60 ℃ and to regulate its pH value be 4.4, is the saccharifying enzyme of 10000 μ/g in the ratio adding vigor of saccharifying enzyme/g starch of 130 μ, at 62 ℃ of insulation 15h down, and heating go out enzyme and filtered while hot;
4) concentrated filtrate and add ethanol be stirred well to the filtrate muddiness in filtrate leaves standstill, and collects supernatant liquor, and triplicate merges supernatant liquor and concentrating under reduced pressure;
5) add 20mL acetate and 10mL diacetyl oxide in the supernatant liquor behind concentrating under reduced pressure, react 1h down at 55 ℃, leave standstill the fine crystal seed of appearance, occur D-glucuronic acid gamma lactone behind the 12h, isolation of crystalline promptly gets D-glucuronic acid gamma lactone with ethyl alcohol recrystallization.
Because Sumstar 190 is under the effect of enzyme, α-1.4 glycosidic link is opened, form glucuronic acid, glucose, maltose and polysaccharide (relevant) with the degree of its hydrolysis, because the water-soluble and ethanol of glucuronic acid energy, and glucose, maltose and polysaccharide are soluble in water, be slightly soluble in ethanol, so in the Sumstar 190 enzymolysis solution, add ethanol, it is muddy that saccharification liquid becomes, and glucose, maltose and polysaccharide are separated out, and glucuronic acid is dissolved in the ethanol, reclaim ethanol and just get glucuronic acid, give in the glucuronic acid to add acetate, at H
+Effect under, SN takes place in the glucuronic acid intramolecule
2Substitution reaction, condensation reaction takes place in OH on γ-position and 1-COOH, because this reaction is reversible reaction, the water that reaction generates is impelled diacetyl oxide to form acetate, makes reaction carry out to the positive reaction direction, thereby helps the generation of D-glucuronic acid gamma lactone.After lactonization reaction finished, at normal temperatures, about 2h just had D-glucose gamma lactone crystal seed to form, leave standstill 12h, filter, promptly obtain D-glucuronic acid gamma lactone crystal, mother liquor is used for next Glucuronic acid lactoneization, and the productive rate of D-glucuronic acid gamma lactone can reach 14g/100g starch.D-glucuronic acid gamma lactone ethyl alcohol recrystallization with obtaining can obtain C
6H
8O
6The D-glucuronic acid gamma lactone of content 〉=98.5%.
Method of the present invention can reach the cleaner production of D-glucuronic acid gamma lactone, reagent is not only saved in the especially reuse of mother liquor, reduces cost, and has eliminated the pollution to environment of acetate, diacetyl oxide; Reduced the Tc of D-glucuronic acid gamma lactone greatly, turned cold and freeze the brilliant normal temperature crystallization that is, crystallization when elongated (6～8 days or 55h) is crystallization in short-term (12h).Production technique is simple, has reduced technical requirements; Improved yield rate, the D-glucuronic acid gamma lactone product purity, fusing point, the productive rate that adopt the present invention to produce all reach the state-promulgated pharmacopoeia standard.
Claims (1)
1, D-glucuronic acid gamma lactone crystallization method is characterized in that:
1) at first with the 100g W-Gum, the water of 150～200mL and the FeSO of 0.05～0.1g
4Adding in the there-necked flask that band stirs, is 9～11 with the NaOH adjusting pH value of 0.1mol/L, slowly adds the H of 5～8g while stirring
2O
2, at 45 ℃ of following reaction 4h, be warming up to after reaction finishes seethe with excitement oxidized starch solution;
2) the pH value of cooling and adjusting oxidized starch solution is 6.0～6.5, ratio adding vigor in α-Dian Fenmei/g starch of 100～150 μ is the α-Dian Fenmei of 20000 μ/g,, kill α-Dian Fenmei and get liquefier to boiling and maintenance 10min at 85～90 ℃ of following hydrolysis 0.5～2.0h post-heating;
3) liquefier being cooled to 60～65 ℃ and to regulate its pH value be 4.0～4.5, is the saccharifying enzyme of 10000 μ/g in the ratio adding vigor of saccharifying enzyme/g starch of 100～150 μ, at 60～65 ℃ of insulation 12～16h down, and heating go out enzyme and filtered while hot;
4) concentrated filtrate and add ethanol be stirred well to the filtrate muddiness in filtrate leaves standstill, and collects supernatant liquor, and triplicate merges supernatant liquor and concentrating under reduced pressure;
5) add 20mL acetate and 10mL diacetyl oxide in the supernatant liquor behind concentrating under reduced pressure, react 1～2h down at 45～55 ℃, leave standstill the fine crystal seed of appearance, occur D-glucuronic acid gamma lactone behind the 12h, isolation of crystalline promptly gets D-glucuronic acid gamma lactone with ethyl alcohol recrystallization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2009100230055A CN101575625A (en) | 2009-06-19 | 2009-06-19 | Method for crystallizing D-glucuronic acid gamma-lactone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2009100230055A CN101575625A (en) | 2009-06-19 | 2009-06-19 | Method for crystallizing D-glucuronic acid gamma-lactone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101575625A true CN101575625A (en) | 2009-11-11 |
Family
ID=41270698
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2009100230055A Pending CN101575625A (en) | 2009-06-19 | 2009-06-19 | Method for crystallizing D-glucuronic acid gamma-lactone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101575625A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104119405A (en) * | 2014-07-04 | 2014-10-29 | 陕西科技大学 | Fast vacuum concentration method for glucurolactone |
| CN105198940A (en) * | 2015-10-19 | 2015-12-30 | 陕西科技大学 | Preparation technology of glucuronolactone |
-
2009
- 2009-06-19 CN CNA2009100230055A patent/CN101575625A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104119405A (en) * | 2014-07-04 | 2014-10-29 | 陕西科技大学 | Fast vacuum concentration method for glucurolactone |
| CN105198940A (en) * | 2015-10-19 | 2015-12-30 | 陕西科技大学 | Preparation technology of glucuronolactone |
| CN105198940B (en) * | 2015-10-19 | 2018-07-17 | 陕西科技大学 | A kind of glucurone preparation process |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104356251B (en) | A kind of method with starch for raw material production polydextrose | |
| CN104152512B (en) | Preparation method of isomaltooligosacharide | |
| CN101735999B (en) | Method for improving content of resveratrol by converting giant knotweed materials through immobilized enzyme method | |
| CN104212854A (en) | Method for producing isomalto-oligosaccharide by using high-concentration starch | |
| CN104762346B (en) | Beta cyclodextrin and superhigh maltose syrup coproduction preparation technology | |
| CN101497633A (en) | Method for preparing isosteviol and sophorose at the same time | |
| CN102952108A (en) | Method for preparing quercetin and rhamnose by using flos sophora | |
| CN101089009A (en) | Diosmin producing process | |
| CN109371078B (en) | Preparation process of high-purity maltose | |
| CN103834713B (en) | A kind of extracting method of tigogenin | |
| CN105384714A (en) | Decolorizing and refining process of sodium dehydroacetate | |
| CN111500661A (en) | Method for simultaneously preparing L-rhamnose and isoquercetin | |
| CN109180627B (en) | Semi-synthesis method of diosmetin | |
| CN106631753B (en) | Method for producing gallic acid by using superfine gallnut powder | |
| CN110468169A (en) | A kind of method of corncob production L-arabinose | |
| CN107880081B (en) | Method for synthesizing isoquercitrin | |
| WO2012068832A1 (en) | Method for preparing mogroside iv | |
| CN111187328B (en) | A kind of method for preparing mogrosinol | |
| CN101575625A (en) | Method for crystallizing D-glucuronic acid gamma-lactone | |
| CN101792780B (en) | Separation method of D-glucuronic acid gamma-lactone | |
| CN102605109A (en) | Method for producing xylose by sugarcane leaves | |
| CN101979616A (en) | A kind of method utilizing broken rice to produce erythritol | |
| CN104387357A (en) | Quercetin production technology | |
| US10351888B2 (en) | Highly efficient method for synthesizing difructose anhydride III | |
| CN112111537A (en) | A kind of semi-synthetic method of isoquercetin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20091111 |