CN101662955A - Method of producing purified rebaudioside a compositions using solvent/antisolvent crystallization - Google Patents
Method of producing purified rebaudioside a compositions using solvent/antisolvent crystallization Download PDFInfo
- Publication number
- CN101662955A CN101662955A CN200880008552A CN200880008552A CN101662955A CN 101662955 A CN101662955 A CN 101662955A CN 200880008552 A CN200880008552 A CN 200880008552A CN 200880008552 A CN200880008552 A CN 200880008552A CN 101662955 A CN101662955 A CN 101662955A
- Authority
- CN
- China
- Prior art keywords
- rebandioside
- solvent
- glucosides
- alcohol
- composition
- 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.)
- Granted
Links
Images
Abstract
The invention provides methods of purifying rebaudioside A from a mixture comprising glycosides of the plant Stevia rebaudiana. The methods of the invention are useful for preparing highly pure rebaudioside A compositions from crude Stevia starting compositions that are typically considerably lower in rebaudioside A concentration. The highly pure rebaudioside A compositions are useful as non-caloric sweeteners in edible or chewable compositions such as food, beverages, medicine, candy, chewing gum, and the like.
Description
The cross reference of related application
Sequence number that on January 22nd, 2007 submitted to, that be entitled as use solvent/rebandioside A method for compositions that anti-solvent crystallization preparation is purified that present patent application requires is 60/881798 U.S. Provisional Patent Application, and sequence number that submit to, that be entitled as use solvent/rebandioside A method for compositions that anti-solvent crystallization preparation is purified is the priority of 61/008163 U.S. Provisional Patent Application on December 19th, 2007, and above-mentioned temporary patent application all is contained in herein.
Technical field
The present invention relates to use the method for solvent/anti-solvent crystallization purification rebandioside A from the CE of plant STEVIA REBAUDIANA (Stevia rebaudiana).
Background technology
Species STEVIA REBAUDIANA (Stevia rebaudiana) (" Stevia ") has become the important research and the theme of development work on some naturally occurring sweet taste glucosides that has as empty calory sweetener potentiality of purification STEVIA REBAUDIANA (Stevia).The sweet taste glucosides that can extract from STEVIA REBAUDIANA comprises six kinds of rebandiosides (rebaudiosides) (being that rebandioside A is to F), steviol glycoside (stevioside) (from the main glucosides in the extract of wild type STEVIA REBAUDIANA), dulcitol glucoside (dulcosides) and STEVIA REBAUDIANA element (sterebin).
Rebandioside A is the stevioside of sweet taste, and the 250-450 that is about sucrose sweetness doubly.In glucosides, it is generally acknowledged that rebandioside A becomes the optimal glucosides that is used for the empty calory sweetener because of its distribution of good sugariness (sweetness profile), the approval that is subjected to regulations restrict, consumer's acceptance and minimum aftertaste bitter taste.
Reported the whole bag of tricks of purification rebandioside A from the qualities of stevia extract that contains thick rebandioside A.
Day, disclosure text No.56121454 reported a kind of method of separating steviol glycoside and rebandioside A by crystallization with high-purity with high yield.In the method, the method by routine is extracted the mixture of steviol glycoside and rebandioside A from the leaf of stevia rebaudianum (Stevia rebaudiana Bertoni) and stem.This extract is dissolved in 〉=70% ethanol water in, and with optionally crystallization from this solution of rebandioside A.
Japan Patent 63173531 has been described the method for extracting the sweet taste glucosides from stevioside plant.The first step of this method is the liquid solution of extraction sweet taste glucosides from stevioside plant.The second, with the liquid solution of sweet taste glucosides by nonpolar porous resin, and with the elution of water-miscible organic solvent particular methanol.The 3rd, with the solution concentration after the elution and dry, obtain flour.This step has been separated the mixture of sweet taste glucosides, but does not separate single pure sweet taste glucosides, as rebandioside A.
U.S. Patent Application Publication text No.2006/0083838 people such as () Jackson has reported a kind of the separation and the method for purification rebandioside A from the STEVIA REBAUDIANA raw material that is purchased.This method comprises: (1) ethanol prescription step, alcohol solvent with the preparation selection, (2) first reflow step of use STEVIA REBAUDIANA raw material, and the optional additional reflow step of using the retentate that from the purging compound of backflow mixture or stirring, separates, (3) washing steps optional, one or more stirrings, and (4) ethanol cleans and drying steps.In the embodiment that uses than low quality STEVIA REBAUDIANA raw material, before the agitator treating step, add second reflow step usually, so that the maximization of the purity of rebandioside A final products.In reported method, carry out the ethanol prescription is used for reflow step the stage with preparation desirable reflux solvent.Usually, reflux solvent is to have the ethanol of about 5-15 volume % water and the mixture of water.This method also comprises carries out about 1 hour one or more catabiotic reflow step usually under about 89-90 ℃ temperature.It is said that this method has produced 100% pure water-soluble rebandioside A.
U.S. Patent No. 5962678 people such as () Payzant has been reported the method for extracting the sweet taste glucosides of selecting from stevioside plant.In reported method, from stevioside plant, extract sweet taste glucosides and processing, obtain the composition separately in the rapid method of multistep.The first, handle the liquid, aqueous solution that stevioside plant extracts the sweet taste glucosides that contains mixing.By using a series of ion exchange resin, impure non-sweet taste glucosides is separated from the sweet taste glucosides that mixes, be dried.The mixing sweet taste glucosides of these dryings still contains impurity, and then is dissolved in water-miscible organic solvent such as the absolute methanol, to form solution.Reflux this solution and cooling to precipitate the first sweet taste glucosides composition.This first sweet taste glucosides composition is generally steviol glycoside, can pass through filtered and recycled, and can further purify by being used for the described method of second composition.
By the heating concentrating filtrate, can be further processed to obtain the second sweet taste glucosides composition by the filter liquor of sweet taste glucosides crystallization of first precipitation.When this solution of cooling, the second sweet taste glucosides becomes fractional precipitation, and it can be recovered.The second sweet taste glucosides composition is generally rebandioside A.Can further purify by it is dissolved in water-miscible organic solvent such as the methyl alcohol, this water-miscible organic solvent can randomly contain low amounts of water.With this solution heating, backflow, also final cooling, precipitate the second sweet taste glucosides composition with higher degree.This sediment can reclaim by filtering.Can repeat this purification process, until the final crystalline solid that obtains desired purity.This method has reported that the purity of rebandioside A is more than 90% or more than 95%.
U.S. Patent No. 4361697 people such as () Dobberstein has been reported the method that reclaims the diterpene glucosides from stevioside plant.This method comprises the first solvent extraction plant material of sequentially using intermediate polarity, the plant material that is tending towards disturbing the liquid chromatogram of glucosides to separate with extraction, then with second solvent of high polarity to extract glucosides, and by they being incorporated into the glucosides of chromatography ground separation and Extraction on the liquid-phase chromatographic column, this liquid-phase chromatographic column has by the filler that contain oxygen organic fixedly phase of silicon atom covalent bonding to inorganic carrier.With polarity than first solvent higher but than second solvent lower solvent elution glucosides.
U.S. Patent No. 4892938 (Giovanetto) has been reported a kind of by extracting and purifying and reclaim the method for steviol glycoside from the plant material of stevia rebaudianum drying.By then filtering and centrifugal the processing water under from room temperature to about 65 ℃ temperature down obtains extract stirring.Handle this extract with calcium hydroxide, therefore obtain sediment by filtration or centrifugal mode.Handle this sediment, then handle this sediment with strong-acid ion exchange resin, filter and drying with weak-base ion-exchange resin.
U.S. Patent No. 4082858 (DuBois) has been reported a kind of method that reclaims rebandioside A from the leaf of stevioside plant.By liquid chromatogram, then by water and have the alcohol of 1-3 carbon atom, the initial extraction of particular methanol obtains final purification.Also disclosing water and can be used as initial solvent, is the liquid halogenated alkane with 1-4 carbon atom in their preferred solvent of this step.Preferred second solvent is the alcohol with 1-3 carbon atom, and preferred the 3rd solvent is have 1-4 carbon atom pure and mild randomly than water in a small amount.
U.S. Patent application No.2006/0134292 people such as () Abelyan has reported a kind of method that reclaims the sweet taste glucosides from the stevioside plant raw material.In the presence of pectase, cellulase and AMS, with the leaf of water treatment drying and pulverize.It is reported and use this kind of enzyme to increase the next procedure of recovery rate and promotion purification considerably.Use is handled with calcium hydroxide and ultrafiltration is purified resulting extract.Make penetrant by being filled with bentonitic post, and under vacuum, be condensed into the syrup state.Make that with Ethanol Treatment separation is almost pure rebandioside A from this mixture.Wash by ethanol and to obtain to have highly purified rebandioside A after this crystallization with 88-95%.
U.S. Patent No. 5972120 people such as () Kutowy has been reported and has a kind ofly been extracted, then extracts the method for sweet cpd by filtering to purify from stevia rebaudianum by post.This is extracted under 0-25 ℃ the temperature.Preferably, use the pre-treatment step of micro-filtration to clarify this extract.Purification is by ultrafiltration, then undertaken by nanofiltration.The controlled filter condition is optimized the recovery of sweet cpd.
Other technology comprises being reported in and transfers Ajinomoto Company, the day disclosure text No.56121454 of Inc; 56121455; 52062300 and 56121453, and transfer the possession of to the open text No.1243835 of China of Hailin SteviaRebaudium Sugar those.
Improvement that need be in effective technology and from STEVIA REBAUDIANA (" Stevia ") method of purification rebandioside A.Especially need at room temperature to carry out and need not to heat or the method for cooling step or catabiotic backflow.
Summary of the invention
The invention provides the method for purification rebandioside A from the mixture of the glucosides that contains plant STEVIA REBAUDIANA (" Stevia ").Method of the present invention is used for preparing highly purified rebandioside A composition by thick STEVIA REBAUDIANA initial composition, and the concentration of rebandioside A is quite low usually in this thick STEVIA REBAUDIANA initial composition.Highly purified rebandioside A composition is as the sweetener of the empty calory in edible or the chewing composition, edible or chewing composition such as food, beverage, medicine, candy, chewing gum etc.
Advantageously, in some embodiments, method of the present invention can all need not catabiotic backflow, heating and/or cooling step in room temperature or near carrying out under the room temperature.In addition, method of the present invention does not need chromatographic isolation that highly purified rebandioside A composition is provided.Yet in some embodiments of the present invention, this method can comprise following one or more steps: (i) heating, (ii) cooling separates with purification rebandioside A composition with (iii) chromatographic column, obtains desirable purity level.
In one aspect, method of the present invention may further comprise the steps:
(a) provide the STEVIA REBAUDIANA initial composition that contains following composition: rebandioside A; And in rebandioside B, rebandioside C, rebandioside D, rebandioside E, rebandioside F, steviol glycoside and the dulcitol glucoside one or more;
(b) form glucosides solution in the following solvent by the STEVIA REBAUDIANA initial composition is dissolved in, described solvent comprises: (i) mixture of lower alcohol (for example C1-C3 alcohol) and water, or the (ii) mixture of low-grade carboxylic acid's (for example acetate) and water; And
(c) in the glucosides solution of step (b), add anti-solvent, so that to form from the glucosides solution crystallization of small part rebandioside A with the rebandioside A composition of purification, the rebandioside A composition of this purification has the purity level higher than STEVIA REBAUDIANA initial composition.
In many embodiments, the STEVIA REBAUDIANA initial composition contains the above rebandioside A of 40 weight % of having an appointment.For example, the STEVIA REBAUDIANA initial composition can contain the rebandioside A of the 40-80 weight % that has an appointment or the rebandioside A of about 40-60 weight %.
The STEVIA REBAUDIANA initial composition is dissolved in the solvent compositions of following solvent, described solvent compositions comprises: (i) mixture of lower alcohol (for example C1-C3 alcohol) and water, or the (ii) mixture of low-grade carboxylic acid's (for example acetate) and water; To form glycoside composition.The example of useful lower alcohol comprises methyl alcohol, ethanol and propyl alcohol (normal propyl alcohol and isopropyl alcohol).In some embodiments, solvent compositions comprises the mixture of lower alcohol and water, and wherein lower alcohol partly accounts for about 30-70 weight % of solvent compositions, and water section accounts for about 30-70 weight % of solvent compositions.In the exemplary embodiment, this solvent compositions contains the ethanol of the 50 weight % that have an appointment and the water of 50 weight %.Can also use the solvent compositions of low-grade carboxylic acid's (for example acetate) and water.When as solvent, the low-grade carboxylic acid exists with the amount of about 30-90 weight % usually, and water exists with the amount of about 10-70 weight % usually.Particularly, the low-grade carboxylic acid exists with the amount of about 50-90 weight %, and water exists with the amount of about 10-50 weight %.
Although can use any amount that is lower than solubility limit, usually the STEVIA REBAUDIANA initial composition is dissolved in the solvent compositions, so that the glucosides solution that contains have an appointment 15-50 weight % STEVIA REBAUDIANA initial composition and about 50-85 weight % solvent compositions to be provided.For example, the glucosides solution of example contains have an appointment the STEVIA REBAUDIANA initial composition of 30 weight % dissolving and the solvent compositions of about 70 weight, and this solvent compositions of about 50% is that this solvent compositions of ethanol and about 50% is a water.
After being dissolved in the STEVIA REBAUDIANA initial composition in the solvent compositions, in glucosides solution, add the anti-solvent of effective dose, to cause the crystallization of rebandioside A.Anti-solvent plays in gained solution the effect of the equilbrium solubility that changes rebandioside A, makes the concentration supersaturation (that is, at it more than solubility limit) of rebandioside A.Because rebandioside A is at it more than equilbrium solubility limit, so rebandioside A crystallizes out from this solvent compositions with the form of the rebandioside A crystal of purifying.
During as solvent, anti-solvent generally includes lower alcohol, as C1-C3 alcohol with the mixture of lower alcohol (C1-C3 alcohol) and water.Representational example comprises methyl alcohol, ethanol, propyl alcohol (as normal propyl alcohol and isopropyl alcohol), acetoneand ethyl acetate.Anti-solvent can be the C1-C3 alcohol identical with being used for solvent, perhaps can be different C1-C3 alcohol.For example, this solvent can contain the second alcohol and water, and anti-solvent can contain methyl alcohol.When low-grade carboxylic acid and water during as solvent, useful anti-solvent comprises methyl alcohol, ethanol, propyl alcohol (for example normal propyl alcohol and isopropyl alcohol), acetoneand ethyl acetate.
With respect to the quality of solvent compositions, the quality of anti-solvent is generally about 0.5: 1 to about 9: 1, is more typically about 2: 1 to about 3: 1.
Can the anti-solvent of disposable interpolation (that is, once adding the anti-solvent of whole volumes), perhaps can repeatedly add, the part of required anti-solvent total amount is provided at every turn.Slower interpolation speed or repeatedly add anti-solvent slightly and can provide more highly purified rebandioside A composition than the anti-solvent of disposable interpolation.
After adding anti-solvent, at room temperature stir the composition of gained usually so that rebandioside A produces crystallization.Randomly, this solution can produce crystal by adding crystal seed, and this crystal seed comprises very pure rebandioside A.Usually, crystallization occurs in and adds behind the anti-solvent in about 24 hours.Usually, the purity along with the rebandioside A initial composition increases the crystallization time reduction.For example, if the rebandioside A of initial composition purer (for example 80% rebandioside A), crystallization time can be lower than 1 hour so.In many embodiments, crystallization time is about 1-4 hour.
After the crystallization, can use known technology as filtering or the centrifugal rebandioside A that reclaims purification.After the recovery, can wash the rebandioside A crystal of this purification of further purifying by using lower alcohol such as methyl alcohol or ethanol.
In many embodiments, method of the present invention has produced the rebandioside A composition of purifying, said composition contains the above rebandioside A of 90 weight % of having an appointment, the rebandioside A that for example about 95 weight % are above, more than about 96 weight %, more than about 97 weight %, the rebandioside A that perhaps about 98.5 weight % are above.In many embodiments, method of the present invention has produced the rebandioside A composition of purifying, and said composition contains the following rebandioside B of 2.5 weight % that has an appointment, the rebandioside B that the rebandioside B that for example about 2 weight % are following or about 1 weight % are following.In many embodiments, method of the present invention has produced the rebandioside A composition of purifying, and said composition contains the following rebandioside D of 1 weight % that has an appointment, the rebandioside D that for example about 0.5 weight % is following.The final content of rebandioside A, B and D depends on these amount of substances that are present in the initial feed material usually.
On the other hand, the invention provides the method that washing contains the solid of rebandioside A and rebandioside D, from this solid composite, to remove to small part rebandioside D.This method may further comprise the steps: the solid that contains rebandioside A and rebandioside D (a) is provided; (b) wash this solid from this solid composite, to remove to small part rebandioside D with C1-C3 alcohol.The example of solvent comprises C1-C3 alcohol, as methyl alcohol, ethanol and propyl alcohol.In many embodiments, methyl alcohol is preferred for reducing rebandioside D.
Description of drawings
Fig. 1 is for using methyl alcohol as the anti-solvent rebandioside A X-ray diffraction in crystals figure that crystallization produced from the solvent of ethanol/water.
Fig. 2 is for using the optical microscope image of methyl alcohol as the anti-solvent rebandioside A crystal that crystallization produced from the solvent of ethanol/water.
The specific embodiment
In one aspect, the invention provides the method for compositions that a kind of purification contains rebandioside A.Method of the present invention can be used to prepare highly purified rebandioside A composition, and said composition is suitable as the low calorie sweetener in edible or the chewing composition, as food, beverage, medicine, candy, chewing gum etc.
In one aspect, the invention provides the method for purification rebandioside A from the mixture of glucosides.This method may further comprise the steps:
(a) provide the STEVIA REBAUDIANA initial composition that contains following composition: rebandioside A; And in rebandioside B, rebandioside C, rebandioside D, rebandioside E, rebandioside F, steviol glycoside and the dulcitol glucoside one or more;
(b) by being dissolved in, the glucosides initial composition forms glucosides solution in the solvent that comprises following mixture: (i) mixture of lower alcohol (for example C1-C3 alcohol) and water, or the (ii) mixture of low-grade carboxylic acid's (for example acetate) and water, and
(c) in the glucosides solution of step (b), add anti-solvent, so that to of form crystallization from glucosides solution of small part rebandioside A with the rebandioside A composition of purification.
Step (a):
Method of the present invention is used to purify and contains the initial composition of rebandioside A, to form highly purified rebandioside A composition.Usually, this initial composition is to use known technology to derive from stevioside plant, and for example optional first preliminary treatment (as extracting fat and/or other compound) of this known technology re-uses water or solvent-aqueous solution extracts the diterpene glucosides from the STEVIA REBAUDIANA leaf.Pretreatment operation can comprise clarification and decolouring step (for example using flocculant, adsorbent and/or solvent extraction), and can randomly comprise by the mode of ion-exchange and remove ash content.Subsequently, can handle or make up and finish further purification by selecting absorption, solvent.At last, initial feed can be purified by crystallization and drying.Useful initial composition contains rebandioside A, and also contains in other glucosides one or more, as rebandioside B, rebandioside C, rebandioside D, rebandioside E, rebandioside F, steviol glycoside and dulcitol glucoside.
In many embodiments, initial composition contains the above rebandioside A of 40 weight % of having an appointment, the rebandioside A of for example about 40-95 weight %.Steviol glycoside also is present in the initial composition usually.In some embodiments, the amount of steviol glycoside existence reaches about 40 weight % of initial composition.Other glucosides that may reside in the initial composition comprises, for example rebandioside B, rebandioside C, rebandioside D and rebandioside F.Common initial composition contains the rebandioside B that for example is not higher than about 8 weight %, the rebandioside C that is not higher than about 10 weight %, the rebandioside F that is not higher than about 2 weight % is not higher than the dulcitol glucoside of about 1 weight %, and the rebandioside D that is not higher than about 4 weight %.Rebandioside E also may reside in the initial composition.
Advantageously, method of the present invention can be used for from having very the initial composition of the rebandioside A of the low-purity rebandioside A of purifying.For example, method of the present invention can be used for producing the rebandioside A of purifying from the initial composition with the rebandioside A (rebandioside A of for example about 40-60 weight %) that is lower than about 60 weight %.
Step (b):
In the method for the invention, initial composition is dissolved in the solvent compositions to form solution.Usually, be added into initial composition in the solvent compositions and stir this solvent compositions, so that this initial composition is dissolved in the solvent compositions.This initial composition can be added in the solvent compositions with constant relatively in time speed, perhaps one or many adds discontinuously.Usually, near under the room temperature, for example about 20-25 ℃ is dissolved in initial composition in the solvent compositions.Can also slightly heat this solvent compositions within the scope of the invention, to help to dissolve this initial composition.For example, this solvent compositions can be heated to about 20-70 ℃ temperature, more typically be heated to about 60-70 ℃.
Useful solvent compositions comprises: (i) mixture of lower alcohol (for example C1-C3 alcohol) and water, or the (ii) mixture of low-grade carboxylic acid and water.The example of lower alcohol comprises methyl alcohol, ethanol and propyl alcohol (for example normal propyl alcohol and isopropyl alcohol).Can also use the two or more alcohol and the mixture of water.In many embodiments, based on the gross weight of described solvent compositions, solvent compositions contains the lower alcohol of the 20-80 weight % that has an appointment and the water of about 20-80 weight %.More typically, this solvent compositions contains the lower alcohol of the 30-70 weight % that has an appointment and the water of about 30-70 weight %.In the exemplary embodiment, solvent compositions contains the lower alcohol of the 40-60 weight % that has an appointment and the water of about 40-60 weight %, the water of the lower alcohol of perhaps about 45-55 weight % and about 45-55 weight %.In the exemplary embodiment, initial composition contains the ethanol of the 50 weight % that have an appointment and the water of about 50 weight %.
Low-grade carboxylic acid's example comprises acetate, formic acid and propionic acid, although can also use other low-grade carboxylic acid.When as solvent, the low-grade carboxylic acid exists with the amount of about 30-90 weight % usually, and water exists with the amount of about 10-70 weight % usually.More typically, the low-grade carboxylic acid exists with the amount of about 50-90 weight %, and water exists with the amount of 10-50 weight %.In the exemplary embodiment, solvent compositions is the acetate of 50 weight % and the water of 50 weight %.
Common component of inciting somebody to action before adding the rebandioside A initial composition separately mixes and prepares solvent compositions.Yet, the rebandioside A initial composition can also be dissolved in a kind of composition of solvent compositions, add the second one-tenth then and assign to constitute solvent compositions.
When being dissolved in initial composition in the solvent compositions, resulting glucosides solution contains the solid of dissolving of this initial composition of the 15-50 weight % that has an appointment and the solvent of about 50-85 weight % usually.In some embodiments, glucosides solution contains the have an appointment solid of 30-50 weight % dissolving and the solvent of about 50-70 weight %.
Step (c):
After forming glucosides solution, in this glucosides solution, add the anti-solvent of effective dose to cause the crystallization of rebandioside A.When adding the anti-solvent of effective dose, resulting glucosides solution has surpassed (comprising anti-solvent) solubility limit of rebandioside A, causes that thus rebandioside A crystallizes out from glucosides solution.Because other glucosides that is present in this glucosides solution remains on it below solubility limit, so rebandioside A preferably crystallizes out from this solution.
Useful anti-solvent comprises the material of the solubility limit of effective change rebandioside A in glucosides solution.More particularly, effective anti-solvent not only can be miscible in glucosides solution but also can reduce the solvability of water by the dielectric constant that reduces solution.Usually, anti-solvent be can with the miscible liquid of water and polarity usually less than water.The example of representational anti-solvent comprises that lower alcohol (as C1-C3 alcohol) is as methyl alcohol, ethanol and propyl alcohol (normal propyl alcohol and isopropyl alcohol).Can also use acetoneand ethyl acetate.Anti-solvent can be be present in solvent compositions in identical lower alcohol or can be different lower alcohols.
In the method for the invention, in glucosides solution, add anti-solvent, be present in crystallizing out to the small part rebandioside A in the glycoside composition to cause with effective dose.The amount of needed anti-solvent can depend on Several Factors, comprises amount, crystallization temperature and the solution temperature of other glucosides impurity in the composition of solvent compositions for example, the composition of initiation material, the amount that is present in rebandioside A in the said composition, the solution.Usually, the quality of the anti-solvent that adds with respect to the quality of solvent in the glucosides solution is about 0.5: 1 to about 9: 1.More typically, with respect to the quality of glucosides solution, the quality of anti-solvent is about 2: 1 to about 3: 1.
Can use batch crystallization process or continuous crystallisation process to carry out the crystallization of rebandioside A.In batch process, initial composition, solvent and anti-solvent are all added in the single container that crystallization takes place.After obtaining crystal, can repeat this process.In the continuous crystallisation process, the mixture of charging glucosides is dissolved in the solvent solution.With resulting mixture with in the continuous suction crystallisation vessel of pump.Simultaneously, when mixing, anti-solvent is used in the pump suction crystallisation vessel with the amount that will produce the final anti-solvent strength that needs with solvent and solute mixture.Crystallization occurs in this container, because the continued presence crystal seed, therefore usually than in batch container, having higher speed.Extract product slurry out container with pump continuously with the identical speed of summation that flows into solvent and anti-solvent, therefore kept volume constant in the crystallizer.Filter and centrifugal product slurry, dry then, obtain final products.The solvent that is used for this process can reclaim by distilling.The solute that dissolves when crystallization finishes be can be recovered in, and charging or independent the use are circulated to.
Can be in glucosides solution once add (that is, in interpolation once, adding whole amounts) anti-solvent or can repeatedly add.In some embodiments, anti-solvent is added in glucosides solution with constant in time interpolation speed.The speed of adding anti-solvent in glucosides solution can influence the purity of formed rebandioside A crystal.For example, once add anti-solvent and can cause rebandioside A rapid crystallization from glucosides solution, the purity that causes the rebandioside A crystal is than slowly anti-solvent being added in time or repeatedly to be added into the purity of the formed rebandioside A crystal of glucosides solution on a small quantity low.
Usually, will resist solvent to be added in the glucosides solution, and two kinds of materials all are maintained at about under the room temperature, 20 ± 5 ℃ according to appointment.After adding anti-solvent,, follow the stirring that relaxes to moderate, make rebandioside A from glucosides solution, crystallize out near making resulting glucosides solution left standstill under the room temperature.Usually, add anti-solvent after rebandioside A at about 24 hours intercrystallines.The speed of crystallization is usually along with the reduction of the purity of rebandioside A initiation material and reduce.
In some embodiments, method of the present invention also comprises the step of cooling glucosides solution, to promote rebandioside A crystallization from glucosides solution.Can before add anti-solvent,, perhaps add anti-solvent and cool off glucosides solution afterwards with the anti-solvent while of interpolation.Also can make up and carry out above-mentioned steps.Glucosides solution can be cooled to any temperature that is used to promote the rebandioside A crystallization.In some embodiments, glucosides solution is cooled to about 0 to about-10 ℃ temperature.Cooldown rate can be any speed, but is generally about 1 ℃/minute to about 5 ℃/minute.
In some embodiments, in this solution, add crystal seed to promote crystallization and to improve the purity of the rebandioside A of crystallization.Usually finish by a spot of high-purity rebandioside A of interpolation in solution (for example, the crystal seed based on the about 0.2-10 weight of gross mass % adds) and add crystal seed.
After the crystallization, can use technique known and material by filtering the rebandioside A that removes purification.In some embodiments, use lower alcohol (for example C1-C3 alcohol) to wash the rebandioside A crystal of purification as methyl alcohol, ethanol or propyl alcohol (normal propyl alcohol or isopropyl alcohol) or their mixture.Can remove residual solvent effectively and be dissolved in any glucosides in the solvent with lower alcohol washing.Usually, the rebandioside A composition that has of the glucosides in wet cake liquid part is lower than the amount in the wet cake solid portion.The low that part of glucosides of rebandioside A content has been taken away in washing, in case filtration cakes torrefaction then increased total rebandioside A concentration thus.In addition, unwanted glucosides (for example removing rebandioside B and rebandioside D from the rebandioside A crystal) can be preferably removed in washing.
Method of the present invention can be used to produce the rebandioside A composition of purification.In some embodiments, the rebandioside A composition of purification contains the above rebandioside A of 90 weight of having an appointment.In other embodiment, the rebandioside A composition of purification contains the above rebandioside A of 95 weight % of having an appointment.In other embodiment, the rebandioside A composition of purification contains the above rebandioside A of 97 weight % of having an appointment.In other embodiment, the rebandioside A composition of purification contains above rebandioside A of the 98 weight % that have an appointment or the above rebandioside A of about 99 weight %.In many embodiments, the rebandioside A composition of purification contains have an appointment following rebandioside B of 2.5 weight % or the following rebandioside B of about 2 weight %.In many embodiments, the rebandioside A composition of purification contains following rebandioside D of the 1 weight % that has an appointment or the following rebandioside D of about 0.5 weight %.In many embodiments, the rebandioside A composition of purification contains the following steviol glycoside of 0.1 weight % of having an appointment.
The rebandioside A composition that the present invention purifies can be used as the independent sweetener of food, beverage, medicine, tobacco, medicine and personal-care supplies, perhaps the sweetener (i.e. conduct is sweetener jointly) that mixes with other sweetener in these products.Usually use to surpass a kind of sweetener, distribute and/or physical property to obtain the specific sense of taste.This sweetener comprises conventional sweetener (sucrose, beet sugar, honey, syrup and other " natural " sweetener) and high intensity sweeteners (cyclamate, asccharin, sucralose, aspartame, STEVIA REBAUDIANA and other chemistry is that make and/or natural high intensity sweeteners).
On the other hand, the invention provides use solvent/anti-solvent crystallization and make the method for steviol glycoside crystallization.It can be useful making the steviol glycoside crystallization from the glycoside composition that contains rebandioside A and steviol glycoside, to form the steviol glycoside composition of purifying and the glycoside composition that dissolves also is provided, the glycoside composition of this dissolving is rich in rebandioside A with respect to initial composition.In case concentrated rebandioside A (rebandioside A of for example about 20-50 weight %), this rebandioside A composition that concentrates can be as the initiation material in said process, to form the rebandioside A composition of purifying.
In many embodiments, the method that precipitates steviol glycoside by solvent/anti-solvent crystallization may further comprise the steps:
(a) provide the glycoside composition that contains rebandioside A and steviol glycoside (also having other glucosides usually);
(b) form glucosides solution by glycoside composition being dissolved in the solvent that contains lower alcohol (as C1-C3 alcohol) and water; And
(c) in the glucosides solution of step (b), add anti-solvent,, form glycoside composition thus with respect to the glucosides solution concentration rebandioside A of step (b) so that to the crystallization from glucosides solution of small part steviol glycoside.
In some embodiments, this method further may further comprise the steps:
(d) steviol glycoside of filtering for crystallizing and from the glucosides solution of step (c), reclaim to concentrate the composition of rebandioside A;
(e) be dissolved in the solvent that contains lower alcohol (for example C1-C3 alcohol) and water by the glycoside composition that concentrates and form the second glucosides solution step (d); And
(f) in the sweet taste glucosides solution of step (e), add anti-solvent, so that to of form crystallization from sweet taste glucosides solution of small part rebandioside A with the rebandioside A composition of purification.
Referring now to following unrestriced embodiment the present invention is described.
Embodiment
Raw material
Table 1 has been listed and has been spreaded all over the employed various initial composition of all embodiment.
Table 1
| Raw material | Dulcitol glucoside (%) | Steviol glycoside (%) | Rebandioside A (%) | Rebandioside B (%) | Rebandioside C (%) | Rebandioside F (%) | Rebandioside D (%) |
| ??59RA40 | ??0.6 | ??39.1 | ?44.4 | ?1.0 | ?10.0 | ?1.8 | ?3.1 |
| ??58RA60 | ??0.6 | ??29.7 | ?56.6 | ?1.5 | ?7.6 | ?1.5 | ?2.5 |
| ??26RA80 | ??0.2 | ??9.3 | ?79.2 | ?3.6 | ?3.4 | ?1.0 | ?3.2 |
| ??70RA80 | ??0.1 | ??2.6 | ?86.5 | ?8.1 | ?1.2 | ?1.2 | ?0.4 |
| ??RA20 | ??1.6 | ??74.1 | ?16.0 | ?0.0 | ?7.0 | ?0.7 | ?0.6 |
Embodiment 1
At first, initial composition 70 RA80 (seeing Table 1) are dissolved in the solvent compositions that contains 50 weight % ethanol and 50 weight % water with 30 weight %.Make resulting solution equilibrate overnight at room temperature.After the balance, anti-solvent methanol is added in the sweet taste glycoside composition with the amount shown in the table 2, to cause crystallization.After adding anti-solvent, at room temperature make crystallization proceed to spend the night.After the crystallization, this solution is filtered and the ethanol of resulting filter cake with 2 times of weight (2 weights of) is washed.Analyze to measure glycoside composition by HPLC then with filter cake and supernatant samples drying, and with the filter cake of drying.The gained result reports in table 2.
Embodiment 2
At first, the initiation material shown in the table 3 is dissolved in the solvent compositions that contains 50 weight % ethanol and 50 weight % water with 30 weight %.Make resulting solution equilibrate overnight at room temperature.After the balance, the anti-solvent of 2 volumes is joined in the sweet taste glycoside composition to cause crystallization.After adding anti-solvent, at room temperature make crystallization proceed to spend the night.Observe the anti-solvent of interpolation 2 volumes and in the rebandioside A initiation material of 80% concentration, produce crystallization, but in sweet taste glycoside composition, do not produce crystallization by the preparation of 60% or 40% rebandioside A initial composition.The anti-solvent of additional volumes is added in the glycoside composition that is prepared by 60% and 40% rebandioside A initial composition.The anti-solvent of the ethanol of additional volumes causes in two kinds in three kinds of samples of 60% rebandioside A preparation crystallization takes place.The anti-solvent of the ethanol of additional volumes does not cause in any sample with the preparation of 40% rebandioside A crystallization takes place.The anti-solvent of the methyl alcohol of additional volumes cause in all three kinds of samples of 40% rebandioside A preparation and all three kinds of samples of preparing with 60% rebandioside A in crystallization takes place.After the crystallization, filter this solution and the filter cake that obtains is washed with 2 volume of ethanol.Analyze to measure glycoside composition by HPLC then with filtration cakes torrefaction, and with the filter cake of drying.Resulting result reports in table 3.
Embodiment 3
RA20 (seeing Table 1) is dissolved in the solution of 50% ethanol and 50% water, produces the solution that contains 30 weight %RA20.With this solution with the dilution of the methyl alcohol of 3 times of weight, filter, and with the methanol wash of 2 times of weight.This crystal accounts for 56 weight % of hyle, and is rich in steviol glycoside.Remaining is filter liquor, and is rich in rebandioside A.The purity of resulting crystal and filter liquor is provided in the table 4.
Table 4
| Dulcitol glucoside (%) | Steviol glycoside (%) | Rebandioside A (%) | Rebandioside B (%) | Rebandioside C (%) | Rebandioside F (%) | Other (%) | |
| Crystal | ??0.0％ | ??93.2％ | ?3.9％ | ?0.1％ | ?0.5％ | ?0.0％ | ??2.2％ |
| Filtrate | ??0.0％ | ??29.8％ | ?40.8％ | ?60.0％ | ?21.9％ | ?4.1％ | ??2.8％ |
*Other=summation at peak between rebandioside A and the rebandioside B, it is considered to comprise rebandioside D and stevia rebaudianum disaccharide glucoside
Embodiment 4
The steviol glycoside raw material that will contain the 60 weight % rebandioside As of having an appointment is dissolved in the solvent that contains 65 weight % ethanol and 35 weight % water, contains the solution of 56 weight % steviol glycosides with generation.This solution is heated to about 70 ℃, and at this temperature spot, all glucosides are all dissolved.Add 100% ethanol as anti-solvent, make the ethanol that finally consists of 89.3 weight % of this solvent.When adding ethanol, this solution was slowly cooled to room temperature in about 2 hours.Resulting crystal is filtered from solution, and with 95% the ethanol washing of 2 times of filter cake weight, dry then.Filter cake contains the rebandioside A of 95-97% butt weight.In crystallization process, reclaimed in the solution about 75% rebandioside A.
Embodiment 5
The steviol glycoside raw material that will contain the 80 weight % rebandioside As of having an appointment is dissolved in the solvent that contains 85 weight % ethanol and 15 weight % water, contains the solution of 15 weight % steviol glycosides with generation.This solution is heated to about 70 ℃, and at this temperature spot, all glucosides are all dissolved.Add 100% ethanol as anti-solvent, make the ethanol that finally consists of 89.3 weight % of this solvent.When adding ethanol, this solution was slowly cooled to room temperature in about 2 hours.Resulting crystal is filtered from solution, and with 95% the ethanol washing of 2 times of filter cake weight, dry then.Filter cake contains the rebandioside A of 94-95% butt weight.In crystallization process, reclaimed and surpassed 95% rebandioside A in the solution.
Considering this specification or during from the putting into practice of invention disclosed herein, other embodiment of the present invention is tangible for a person skilled in the art.When reading this specification, the variation of embodiment described herein is tangible to the technical staff in the association area.The inventor expects that the technical staff suitably uses this variation, and plan with the present invention be practiced in this paper the embodiment outside the specific description.Therefore, the present invention includes all changes and equivalent by the theme in the claims that law allowed that are suitable for.All patents that text is quoted, patent document and open text all add herein by reference separately.
Claims (50)
1, the method for purification rebandioside A from the glucosides mixture said method comprising the steps of:
(a) provide the glucosides initial composition, it comprises: rebandioside A; And in rebandioside B, rebandioside C, rebandioside D, rebandioside E, rebandioside F, steviol glycoside and the dulcitol glucoside one or more;
(b) form glucosides solution by described glucosides initial composition being dissolved in the solvent, described solvent comprises: (i) mixture of lower alcohol and water, or the (ii) mixture of low-grade carboxylic acid and water; And
(c) in the glucosides solution of step (b), add anti-solvent, so that to of form crystallization from described glucosides solution of small part rebandioside A with the rebandioside A composition of purification.
2, method according to claim 1, wherein, described method further comprises by add the crystal that contains rebandioside A adds crystal seed with the glucosides solution to step (c) step in described glucosides solution.
3, method according to claim 1, wherein, described method is carried out with the batch crystallization process.
4, method according to claim 1, wherein, described method is carried out with the continuous crystallisation process.
5, method according to claim 1, wherein, described glucosides initial composition contains the above rebandioside A of 40 weight % of having an appointment.
6, method according to claim 1, wherein, described glucosides initial composition contains the rebandioside A of the 40-80 weight % that has an appointment.
7, method according to claim 1, wherein, described glucosides initial composition contains the following rebandioside A of 60 weight % of having an appointment.
8, method according to claim 1, wherein, described glucosides initial composition contains the rebandioside A of the 40-60 weight % that has an appointment.
9, method according to claim 1, wherein, described lower alcohol comprises C1-C3 alcohol.
10, method according to claim 9, wherein, described C1-C3 alcohol is selected from methyl alcohol, ethanol, normal propyl alcohol, isopropyl alcohol or their mixture.
11, method according to claim 9, wherein, described C1-C3 alcohol is ethanol.
12, method according to claim 1, wherein, described solvent contains the C1-C3 alcohol of the 30-70 weight % that has an appointment and the water of about 30-70 weight %.
13, method according to claim 1, wherein, described solvent contains the C1-C3 alcohol of the 40-60 weight % that has an appointment and the water of about 40-60 weight %.
14, method according to claim 1, wherein, described solvent contains the C1-C3 alcohol of the 45-55 weight % that has an appointment and the water of about 45-55 weight %.
15, method according to claim 1, wherein, described anti-solvent comprises C1-C3 alcohol or their mixture.
16, method according to claim 1, wherein, described anti-solvent comprises methyl alcohol, ethanol, isopropyl alcohol, normal propyl alcohol, acetone, ethyl acetate or their mixture.
17, method according to claim 1, wherein, described solvent contains the second alcohol and water; And wherein said anti-solvent contains ethanol.
18, method according to claim 1, wherein, described solvent contains the second alcohol and water; And wherein said anti-solvent contains methyl alcohol.
19, method according to claim 1, wherein, described low-grade carboxylic acid comprises acetate, formic acid, propionic acid or their mixture.
20, method according to claim 1, wherein, the quality of described anti-solvent is about 0.50: 1 to about 9: 1 with respect to the quality of described glucosides solution.
21, method according to claim 1, wherein, the quality of described anti-solvent is about 1: 1 to 3: 1 with respect to the quality of described glucosides solution.
22, method according to claim 1, wherein, described glucosides solution contains the initial composition of the 15-50 weight % that has an appointment; And the solvent of about 50-85 weight %.
23, method according to claim 1, this method also comprise the step by the rebandioside A composition of the described purification of filtered and recycled.
24, method according to claim 1, this method also comprise the step of washing the rebandioside A composition of described purification with C1-C3 alcohol or their mixture.
25, method according to claim 23, wherein, described alcohol is ethanol.
26, method according to claim 23, wherein, described alcohol is methyl alcohol.
27, method according to claim 1, wherein, the rebandioside A composition of described purification contains the above rebandioside A of 90 weight % of having an appointment.
28, method according to claim 1, wherein, the rebandioside A composition of described purification contains the above rebandioside A of 95 weight % of having an appointment.
29, method according to claim 1, wherein, the rebandioside A composition of described purification contains the above rebandioside A of 97 weight % of having an appointment.
30, method according to claim 1, wherein, the rebandioside A composition of described purification contains the above rebandioside A of 98 weight % of having an appointment.
31, method according to claim 1, wherein, the rebandioside A composition of described purification contains the following rebandioside B of 2.5 weight % that has an appointment.
32, method according to claim 1, wherein, the rebandioside A composition of described purification contains the following rebandioside B of 2 weight % that has an appointment.
33, method according to claim 1, wherein, the rebandioside A composition of described purification contains the following rebandioside D of 1 weight % that has an appointment.
34, method according to claim 1, wherein, the rebandioside A composition of described purification contains the following rebandioside D of 0.5 weight % that has an appointment.
35, method according to claim 1 wherein, is added into described anti-solvent in the described glucosides solution in the mode of disposable interpolation.
36, method according to claim 1 wherein, is added into described anti-solvent in the described glucosides solution in the mode of repeatedly adding.
37, method according to claim 1 wherein, is added into described anti-solvent in the described glucosides solution in the mode of continuous interpolation.
38, method according to claim 1, wherein, described glucosides solution and described anti-solvent are about 15-25 ℃ temperature.
39, method according to claim 1, wherein, the step that forms described glucosides solution comprises the temperature that solvent is heated to about 60-70 ℃.
40, method according to claim 1, wherein, described method also comprises the step of cooling off described glucosides solution.
41, according to the described method of claim 40, wherein, the step of cooling off described glucosides solution occurs in: (i) before adding described anti-solvent; (ii) with the described anti-solvent while of interpolation; (iii) after adding described anti-solvent; Perhaps their any combination.
42,, wherein, described glucosides solution is cooled to about 0 ℃ to about-10 ℃ temperature according to the described method of claim 40.
43, according to the described method of claim 40, wherein, the speed of cooling off described glucosides solution is about 1 ℃/minute to about 5 ℃/minute.
44, by using solvent/anti-solvent crystallization to come the selective crystallization steviol glycoside to concentrate the method for the rebandioside A of glycoside composition, this method may further comprise the steps:
(a) provide the glycoside composition that contains rebandioside A and steviol glycoside;
(b) form glucosides solution in the following solvent by glycoside composition is dissolved in, described solvent comprises: (i) mixture of lower alcohol (as C1-C3 alcohol) and water, the perhaps (ii) mixture of low-grade carboxylic acid and water; And
(c) in the glucosides solution of step (b), add anti-solvent,, form the glucosides liquid composite that concentrates rebandioside A thus so that to the crystallization from glucosides solution of small part steviol glycoside.
45, according to the described method of claim 44, this method further may further comprise the steps:
(d) from the glucosides solution of step (c), reclaim the glycoside composition that concentrates.
46, according to the described method of claim 45, this method further may further comprise the steps:
(e) be dissolved in by sweet taste glycoside composition and form glucosides solution in the solvent that comprises the C1-C3 alcohol and water step (d); And
(f) in the glucosides solution of step (e), add anti-solvent, so that to of form crystallization from described glucosides solution of small part rebandioside A with the rebandioside A composition of purification.
47, use solvent/anti-solvent crystallization to come the method for crystallization steviol glycoside, this method may further comprise the steps:
(a) provide the glycoside composition that contains rebandioside A and steviol glycoside;
(b) form glucosides solution in the following solvent by described glycoside composition is dissolved in, described solvent comprises: (i) mixture of lower alcohol (as C1-C3 alcohol) and water, the perhaps (ii) mixture of low-grade carboxylic acid and water; And
(c) in the glucosides solution of step (b), add anti-solvent,, form the steviol glycoside crystal of purifying thus so that to the crystallization from glucosides solution of small part steviol glycoside.
48, the washing contain rebandioside A and rebandioside D solid from described solid composite, to remove to the method for small part rebandioside D, this method may further comprise the steps:
(a) provide the solid that contains rebandioside A and rebandioside D; With
(b) with the described solid of C1-C3 alcohol washing, from described solid composite, to remove to small part rebandioside D.
49, according to the described method of claim 48, wherein, described C1-C3 alcohol is selected from methyl alcohol, ethanol and propyl alcohol.
50, according to the described method of claim 48, wherein, described C1-C3 alcohol is methyl alcohol.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US88179807P | 2007-01-22 | 2007-01-22 | |
| US60/881,798 | 2007-01-22 | ||
| US816307P | 2007-12-19 | 2007-12-19 | |
| US61/008,163 | 2007-12-19 | ||
| PCT/US2008/000700 WO2008091547A2 (en) | 2007-01-22 | 2008-01-18 | Method of producing purified rebaudioside a compositions using solvent/antisolvent crystallization |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101662955A true CN101662955A (en) | 2010-03-03 |
| CN101662955B CN101662955B (en) | 2014-08-06 |
Family
ID=41790580
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200880008552.XA Expired - Fee Related CN101662955B (en) | 2007-01-22 | 2008-01-18 | Method of producing purified rebaudioside a compositions using solvent/antisolvent crystallization |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN101662955B (en) |
| ZA (1) | ZA200905426B (en) |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012073121A3 (en) * | 2010-08-23 | 2012-10-18 | E.P.C. (Beijing) Plant Pharmaceutical Technology Co., Ltd. | Stevia composition with reduced or eliminated aftertaste of stevia |
| CN102775453A (en) * | 2012-06-21 | 2012-11-14 | 黑龙江八一农垦大学 | Method for crystallizing and separating stevioside A3 from stevia total glycoside mixture |
| CN103261211A (en) * | 2010-12-13 | 2013-08-21 | 嘉吉公司 | Glycoside blends |
| CN103492403A (en) * | 2011-03-17 | 2014-01-01 | 伊比西(北京)植物药物技术有限公司 | Rebaudioside b and derivatives |
| CN104159908A (en) * | 2011-12-09 | 2014-11-19 | 苏州景泓生物技术有限公司 | A novel process for the preparation of rebaudioside D and other related naturally occurring sweeteners |
| US9131718B2 (en) | 2009-06-16 | 2015-09-15 | Epc (Beijing) Natural Products Co., Ltd. | Process for rebaudioside D |
| CN106636260A (en) * | 2016-09-12 | 2017-05-10 | 江南大学 | Method for preparing rebaudioside D through variable-temperature catalysis of rebaudioside B by virtue of cutinase |
| CN108558966A (en) * | 2018-01-04 | 2018-09-21 | 常州嘉众新材料科技有限公司 | The production method of Rebaudiodside A D in a kind of enriching stevia sugar |
| US10264811B2 (en) | 2014-05-19 | 2019-04-23 | Epc Natural Products Co., Ltd. | Stevia sweetener with improved solubility |
| US10292412B2 (en) | 2012-02-15 | 2019-05-21 | Kraft Foods Global Brands Llc | High solubility natural sweetener compositions |
| US10357052B2 (en) | 2014-06-16 | 2019-07-23 | Sweet Green Fields USA LLC | Rebaudioside A and stevioside with improved solubilities |
| EP3430145A4 (en) * | 2016-03-14 | 2019-10-23 | PureCircle USA Inc. | Highly soluble steviol glycosides |
| US10485256B2 (en) | 2014-06-20 | 2019-11-26 | Sweet Green Fields International Co., Limited | Stevia sweetener with improved solubility with a cyclodextrin |
| CN113461746A (en) * | 2021-08-11 | 2021-10-01 | 郑然� | Refining method of high-purity stevioside RA |
| CN114437165A (en) * | 2021-12-22 | 2022-05-06 | 厦门医学院 | 96-condition crystallization screening reagent composition suitable for small-molecule natural product and application thereof |
| CN115536709A (en) * | 2022-10-13 | 2022-12-30 | 中国科学院华南植物园 | Efficient crystallization method for preparing rebaudioside A |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5962678A (en) * | 1996-09-13 | 1999-10-05 | Alberta Research Council | Method of extracting selected sweet glycosides from the Stevia rebaudiana plant |
| US20030152500A1 (en) * | 2001-10-17 | 2003-08-14 | Dalziel Sean Mark | Rotor-stator apparatus and process for the formation of particles |
-
2008
- 2008-01-18 CN CN200880008552.XA patent/CN101662955B/en not_active Expired - Fee Related
-
2009
- 2009-08-03 ZA ZA200905426A patent/ZA200905426B/en unknown
Cited By (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9131718B2 (en) | 2009-06-16 | 2015-09-15 | Epc (Beijing) Natural Products Co., Ltd. | Process for rebaudioside D |
| US9635878B2 (en) | 2009-06-16 | 2017-05-02 | Epc (Beijing) Natural Products Co., Ltd. | Process for rebaudioside D |
| US10285425B2 (en) | 2010-08-23 | 2019-05-14 | Epc Natural Products Co. Ltd | Rebaudioside A and stevioside compositions |
| WO2012073121A3 (en) * | 2010-08-23 | 2012-10-18 | E.P.C. (Beijing) Plant Pharmaceutical Technology Co., Ltd. | Stevia composition with reduced or eliminated aftertaste of stevia |
| CN103153093B (en) * | 2010-08-23 | 2015-05-06 | 伊比西(北京)植物药物技术有限公司 | Stevia compositions capable of decreasing or eliminating aftertaste associated with stevia |
| CN104814421A (en) * | 2010-08-23 | 2015-08-05 | 伊比西(北京)植物药物技术有限公司 | Stevia composition with reduced or eliminated aftertaste stevia |
| CN103153093A (en) * | 2010-08-23 | 2013-06-12 | 伊比西(北京)植物药物技术有限公司 | Rebaudioside A and stevioside compositions |
| US11202462B2 (en) | 2010-08-23 | 2021-12-21 | Sweet Green Fields International Co., Limited | Rebaudioside A and stevioside compositions |
| CN104814421B (en) * | 2010-08-23 | 2018-03-30 | 浙江绿世界制药有限公司 | The stevia rebaudianum composition of rear taste with the stevia rebaudianum reduced or eliminated |
| US9578895B2 (en) | 2010-08-23 | 2017-02-28 | Epc (Beijing) Natural Products Co., Ltd. | Rebaudioside A and stevioside compositions |
| CN103261211A (en) * | 2010-12-13 | 2013-08-21 | 嘉吉公司 | Glycoside blends |
| CN107087782B (en) * | 2010-12-13 | 2021-08-31 | 嘉吉公司 | Glycoside blends |
| CN107087782A (en) * | 2010-12-13 | 2017-08-25 | 嘉吉公司 | With sugared blend |
| US9795156B2 (en) | 2011-03-17 | 2017-10-24 | E.P.C (Beijing) Plant Pharmaceutical Technology Co., Ltd | Rebaudioside B and derivatives |
| CN105747183A (en) * | 2011-03-17 | 2016-07-13 | 伊比西(北京)植物药物技术有限公司 | Rebaudioside B and derivatives thereof |
| CN103492403A (en) * | 2011-03-17 | 2014-01-01 | 伊比西(北京)植物药物技术有限公司 | Rebaudioside b and derivatives |
| US11510428B2 (en) | 2011-03-17 | 2022-11-29 | Sweet Green Fields International Co., Limited | Rebaudioside B and derivatives |
| CN103492403B (en) * | 2011-03-17 | 2016-04-06 | 伊比西(北京)植物药物技术有限公司 | Rebaudioside B and derivative thereof |
| CN105747183B (en) * | 2011-03-17 | 2019-11-01 | Sgf国际有限公司 | Rebaudioside B and its derivative |
| CN104159908A (en) * | 2011-12-09 | 2014-11-19 | 苏州景泓生物技术有限公司 | A novel process for the preparation of rebaudioside D and other related naturally occurring sweeteners |
| CN104159908B (en) * | 2011-12-09 | 2016-05-04 | 苏州景泓生物技术有限公司 | A kind of new process of rebaudioside D natural sweetener relevant with other of preparing |
| CN110122841A (en) * | 2012-02-15 | 2019-08-16 | 卡夫食品集团品牌有限责任公司 | Highly dissoluble natural sweetener composition |
| US10292412B2 (en) | 2012-02-15 | 2019-05-21 | Kraft Foods Global Brands Llc | High solubility natural sweetener compositions |
| CN102775453A (en) * | 2012-06-21 | 2012-11-14 | 黑龙江八一农垦大学 | Method for crystallizing and separating stevioside A3 from stevia total glycoside mixture |
| US10264811B2 (en) | 2014-05-19 | 2019-04-23 | Epc Natural Products Co., Ltd. | Stevia sweetener with improved solubility |
| US11206857B2 (en) | 2014-05-19 | 2021-12-28 | Sweet Green Fields International Co., Limited | Stevia sweetener with improved solubility |
| US10561165B2 (en) | 2014-05-19 | 2020-02-18 | Sweet Green Fields International Co., Limited | Stevia sweetener with improved solubility |
| US11241031B2 (en) | 2014-06-16 | 2022-02-08 | Sweet Green Fields Usa, Llc | Rebaudioside A and stevioside with improved solubilities |
| US10357052B2 (en) | 2014-06-16 | 2019-07-23 | Sweet Green Fields USA LLC | Rebaudioside A and stevioside with improved solubilities |
| US10568351B2 (en) | 2014-06-16 | 2020-02-25 | Sweet Green Fields USA LLC | Rebaudioside A and stevioside with improved solubilities |
| US10485256B2 (en) | 2014-06-20 | 2019-11-26 | Sweet Green Fields International Co., Limited | Stevia sweetener with improved solubility with a cyclodextrin |
| EP3430145A4 (en) * | 2016-03-14 | 2019-10-23 | PureCircle USA Inc. | Highly soluble steviol glycosides |
| CN109415736B (en) * | 2016-03-14 | 2022-06-14 | 谱赛科美国股份有限公司 | High-solubility steviol glycoside |
| CN106636260B (en) * | 2016-09-12 | 2019-11-26 | 江南大学 | A method of Lay bud enlightening glycosides D is prepared using cutinase alternating temperature catalysis Lay bud enlightening glycosides B |
| CN106636260A (en) * | 2016-09-12 | 2017-05-10 | 江南大学 | Method for preparing rebaudioside D through variable-temperature catalysis of rebaudioside B by virtue of cutinase |
| CN108558966A (en) * | 2018-01-04 | 2018-09-21 | 常州嘉众新材料科技有限公司 | The production method of Rebaudiodside A D in a kind of enriching stevia sugar |
| CN113461746A (en) * | 2021-08-11 | 2021-10-01 | 郑然� | Refining method of high-purity stevioside RA |
| CN114437165A (en) * | 2021-12-22 | 2022-05-06 | 厦门医学院 | 96-condition crystallization screening reagent composition suitable for small-molecule natural product and application thereof |
| CN115536709A (en) * | 2022-10-13 | 2022-12-30 | 中国科学院华南植物园 | Efficient crystallization method for preparing rebaudioside A |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101662955B (en) | 2014-08-06 |
| ZA200905426B (en) | 2010-04-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101662955B (en) | Method of producing purified rebaudioside a compositions using solvent/antisolvent crystallization | |
| JP5307730B2 (en) | Process for the preparation of a purified rebaudioside A composition using solvent / antisolvent crystallization | |
| CA2788359C (en) | Methods to treat mixtures of glycosides to obtain one or more of these glycosides in more pure form | |
| EP2672839B1 (en) | Method of making an enhanced natural sweetener | |
| AU2020374113A1 (en) | Method for manufacturing revaudioside-D-containing crystallized product, and revaudioside D-containing crystallized product | |
| CN110229201B (en) | Process method for preparing high-purity stevioside RM | |
| CN113461746A (en) | Refining method of high-purity stevioside RA | |
| EP4052772A1 (en) | Method for manufacturing revaudioside-d-containing crystallized product, and revaudioside-d-containing crystallized product | |
| CN110878111A (en) | Preparation method for improving purity and rebaudioside content of inulin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140806 Termination date: 20190118 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |