Method for producing d-allulose crystals

Abstract

To provide a new method for producing D-allulose crystals that allows for a continuous production process and ensures a high yield.SOLUTION: A process for producing D-allulose crystals comprises: a step of providing a composition rich in D-allulose; a step of concentrating the solution so as to form a stock solution to be crystallized; a step of crystallizing the stock solution so as to form D-allulose crystals and mother liquors; and at least one nanofiltration step, the step taking place in a step prior to the step of concentrating the composition rich in D-allulose.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a new process for producing D-allulose crystals, which allows to operate continuously and obtain high yields.The subject of the present invention is also a new D-allulose crystal.Another subject of the present invention relates to the use of a nanofiltration unit in the process for producing D-allulose crystals to improve its yield and / or the quality of the crystals obtained. [Background technology]

[0002] D-Allulose (or D-psicose) is a rare sugar, whose sweetening power is equivalent to 70% of that of sucrose. In contrast to sucrose, D-allulose does not cause weight gain since it is not metabolized by humans. D-Allulose has a very low calorie content (0.2 kcal per gram) and therefore prevents the increase of body fat. Furthermore, studies have shown that D-allulose is non-cariogenic or even anti-cariogenic. These properties have therefore generated great interest from the food and pharmaceutical industries recently.

[0003] Although it is possible to obtain D-allulose chemically, for example by reacting an aqueous solution of glucose in an acidic medium in the presence of ammonium molybdate catalyst, D-allulose is generally obtained enzymatically, for example by reacting an aqueous solution of D-fructose with D-psicose epimerase, as described in WO 2015 / 032761 A1 in the name of the applicant.In these two cases, the reaction is not complete.For example, the amount of D-fructose converted into D-allulose after epimerization is generally less than 30%.

[0004] Therefore, at the end of the epimerization reaction, in order to increase the concentration of the resulting D-allulose composition, it is necessary to carry out a step of separating D-allulose.To carry out this separation, chromatography of the composition resulting from the epimerization reaction is very commonly carried out, for example by simulated moving bed type continuous chromatography.

[0005] JP 2001-354690 A describes a process for producing D-allulose syrup starting from a mixture of fructose and D-allulose, said process comprising a separation step consisting of a series of sequential chromatographic steps using a specific series of samples of various products of the mixture.A fraction rich in D-allulose (D-allulose concentration can reach 98%) and a reaction product rich in fructose are collected.The recovery yield of the fraction rich in D-allulose is 96%.

[0006] At the end of the above separation steps, liquid compositions rich in D-allulose are obtained. These liquid compositions, generally called syrups, are therefore used for the manufacture of food or pharmaceutical products.

[0007] By way of example, WO 2015 / 094342, also in the name of the applicant, describes the production of solid food products containing D-allulose syrup, which contains 50% to 98% D-allulose and natural proteins. It is mainly in this syrup form that various companies have announced the sale of D-allulose to date.

[0008] D-Allulose is also sold in powder form, however, as explained below, the preparation of said powder can be quite complicated.

[0009] It is possible to produce powders, for example, using spray drying techniques. However, spray-dried powders, the composition of which depends on the raw materials spray-dried, generally contain a large amount of impurities. Moreover, these spray-dried powders are weakly crystalline; they are very hygroscopic, which therefore causes water resistance problems. This also generally produces a more substantial caking phenomenon.

[0010] Due to these difficulties, there are very few literature descriptions of spray drying of D-allulose.As an example, EP 1 860 195 can be mentioned, which describes the spray drying of a mixture of D-allulose and D-allose.Regarding the enantiomer of D-allulose, L-allulose, JP 4 761 424 can be mentioned, which describes the spray drying of cooked mass of D-allulose.

[0011] It is also possible to produce the powder using granulation techniques, as described, for example, in WO 2016 / 012853 in the name of the Applicant.

[0012] Another form of powder relates to crystals obtained by crystallization of a stock solution of D-allulose.

[0013] The process for producing D-allulose crystals is described in the specification of the Chinese Patent Application Publication No. 104447888 A. This document describes, more specifically in the examples, a process including the steps of producing a solution of D-allulose from glucose using a molybdate catalyst, then decolorizing the solution using activated carbon, then filtering to remove the activated carbon, deionizing by electrodialysis, separating by successive chromatography to form a solution of D-allulose with a purity in the range of 70% to 90%, concentrating the solution to obtain a concentrated solution of D-allulose, followed by crystallization from ethanol to obtain a crystalline D-allulose product with a limiting purity of at most 99%. The crystallization yield is not shown in the document.

[0014] Another crystallization process is also described in WO 2011 / 119004 in the name of CJ Cheiljedang, with a crystallization yield of about 50%. This process for producing D-allulose crystals includes the steps of providing a solution of D-allulose, purifying this solution, concentrating the solution of D-allulose to provide a stock solution, and crystallizing this stock solution, where the crystallization step is carried out while maintaining the stock solution in the metastable zone. The purification step described in said document is a chromatographic separation step, which allows D-glucose to be separated from fructose. However, said document acknowledges that the production of a powder in crystalline form is difficult to carry out: First, the crystallization is difficult to control, as shown in paragraph

[36] , which specifies that the crystallization must be carried out carefully, with continuous observation of the crystals, while also measuring the concentration of the supernatant (to regulate the temperature of the crystallizer). However, the document is silent as to why this crystallization is difficult to carry out. Furthermore, the crystals obtained have a size of less than 200 μn (see paragraph

[89] ) and are therefore difficult to separate from the mother liquor from the crystallization during centrifugation due to their small size. The recovered crystals are also difficult to handle during subsequent use.

[0015] WO 2016 / 064087, also in the name of CJ Cheiljedang, also describes in Example 3 a process for the production of D-allulose crystals, in which the raw solution is introduced into the crystallizer at four separate times. Between each introduction, four heating and cooling cycles are performed, thereby resulting in a process lasting more than 80 hours. Compared to the process described in WO 2011 / 119004, the crystallization yield is not improved (it is 52.8%). The obtained crystals have a larger average size (3.0 mm). The crystals obtained, however, show impurities. Moreover, the crystals sold by the company CJ Cheiljedang are needle-like, which results in a totally unsatisfactory flowability. Summary of the Invention [Problem to be solved by the invention]

[0016] From the above, it appears that many problems still remain in the production of D-allulose crystals.

[0017] First, the total yield of D-allulose crystals is too low.The term "total yield of D-allulose crystals" is intended to mean the ratio of the mass of D-allulose crystals obtained to the mass of D-fructose introduced, expressed as dry mass.This low yield of about 15% for D-fructose is essentially related to the yield of epimerization step (less than 30%) and the yield of crystallization step (generally about 50%).

[0018] To improve the yield of the process, it is therefore essential to carry out a "recycling step". The term "recycling step" in the process is intended to mean the reuse, in the preceding step of the procedure, of a fraction of the product obtained during the separation step. In the present application, the term "separation step" is intended to mean any step that allows a composition comprising product A and product B to be separated at least into a first fraction enriched in product A and a second fraction enriched in product B. The fractions may be in any form, for example in solid form, in liquid form or even in the form of a suspension of a solid in a liquid. The separation step may be of any type, for example a chromatography step, in which a liquid composition is separated into at least two liquid fractions, or a crystallization step, in which a liquid component is separated into a solid fraction and a liquid fraction.

[0019] A process in which the fructose-rich fraction is recycled has already been described with the aim of improving the yield of the process for producing D-allulose syrup.In particular, the above-cited JP 2001354690 A describes the recycling of the fructose-rich fraction obtained during the chromatography step to be subjected to an epimerization step.This makes it possible to improve the yield of D-allulose in the form of a liquid composition.

[0020] When attempting to apply the teachings of said documents to processes for the production of D-allulose crystals (such as those described in WO 2011 / 119004), the Applicant was able to realise that they were not easily interchangeable.

[0021] This is because the Applicant was able to notice that when recycling of the fructose-rich fraction is carried out (see FIG. 1), the resulting stock solution becomes increasingly difficult to crystallize, which becomes impossible after a certain time, as will be demonstrated in the experimental part.

[0022] Furthermore, still aiming to improve the overall yield of D-allulose crystals of the process, the Applicant also tried to carry out the recycling of the mother liquors from the crystallization (i.e. the D-allulose-rich solution obtained after separating the crystals obtained during the crystallization step) by mixing them with the D-allulose composition to form a new stock solution after concentration (see Figure 2).It could be noticed that this recycling of the mother liquor causes the same difficulties, which are even faster than in the case of recycling the fructose-rich fraction (see the Examples section).

[0023] In these two cases above, the production of D-allulose crystals was therefore suspended. It must be done.

[0024] Moreover, the applicant has been able to notice that even without recycling, when the teachings described above are transposed into a continuous industrial process for producing D-allulose crystals, "instabilities" are observed. These instabilities result in crystal masses having a somewhat variable appearance during the process. This is particularly troublesome, since crystal masses can be centrifuged and then not at a certain moment without being able to make any prediction of their behavior a priori. If it is desired to reuse them in the process, then the masses obtained must be remelted, which makes the process very impractical and uneconomical.

[0025] Indeed, in order to accelerate the industrial development of D-allulose, which is today mainly sold in syrup form, it is essential to be able to carry out a continuous, stable process for producing D-allulose crystals on an industrial scale in order to be able to supply them at a competitive price.

[0026] After a huge amount of research, the applicant has succeeded in obtaining a production process for D-allulose crystals which can solve the above-mentioned problems.

[0027] Due to the improved process stability, the production of the crystals does not require any systematic control, as shown, for example, in WO 2011 / 119004, which allows the implementation of a continuous process for producing D-allulose crystals.

[0028] Furthermore, the process of the present invention also allows for multiple recycling steps, and the yield of the process can be greatly increased.

[0029] By carrying out a large amount of research, the applicant has been able to find that in the manufacturing process of D-allulose crystals, certain impurities occur during various steps of the raw solution preparation process.To the best of the applicant's knowledge, these impurities have never been reported in the literature.The applicant has been able to identify them by using a specific gas chromatography (GC) technique.Without being bound by any theory, the applicant believes that these impurities are D-allulose dimers that are generated by condensation throughout the process.

[0030] The Applicant has also been able to show that these D-allulose dimers have a very significant anti-crystallization effect, in contrast to other impurities such as glucose or D-fructose.

[0031] Surprisingly, the Applicant has succeeded in eliminating this problem of difficult crystallization of D-allulose by implementing a process for the manufacture of D-allulose crystals in which a specific separation step is carried out, which consists of nanofiltration, making it possible to remove these anti-crystallization impurities.

[0032] This new process represents a major advance in the industrial development of D-allulose crystals, since it makes it possible to achieve a total yield of more than 25%, advantageously more than 50%, or even more than 65% based on the D-fructose introduced, which makes it possible to envisage the production of D-allulose crystals at a competitive price and also the commercial development of such crystals on a large scale.

[0033] Moreover, the applicant has realised that the presence of these impurities is a factor influencing the shape of the crystals, especially when attempting to produce large crystals, especially when their average size exceeds 200 μn.

[0034] During the research, the applicant also succeeded in producing new D-allulose crystals using a unique crystallization process that uses the above-mentioned nanofiltration step in the production process.These crystals, which are another aspect of the present invention, have the particularity of containing a very low mass percentage of D-allulose dimers.The obtained crystals can also have different shapes and improved flow properties.These shapes and flow properties are directly related to the fact that dimers are present in crystals in very small amounts.On the contrary, when it is desired to produce large crystals, the significant presence of D-allulose dimers in the starting solution during crystallization leads to D-allulose crystals that contain a significant amount of these dimers; moreover, the elongation of these crystals is observed to form needle-shaped crystals.In fact, these needle-shaped crystals may show less flow properties than the crystals of the present invention. [Means for solving the problem]

[0035] The present invention therefore provides providing a composition enriched in D-allulose; concentrating said solution to form a stock solution that is to be crystallized; crystallizing the stock solution to form D-allulose crystals and a mother liquor; at least one nanofiltration step, said step being carried out prior to the step of concentrating the D-allulose-enriched composition; The present invention relates to a process for producing D-allulose crystals, comprising:

[0036] As mentioned above, the applicant has been able to systematically notice that in the process of producing D-allulose crystals, certain impurities occur during the process. Said impurities have never been reported in the literature, to the best of the applicant's knowledge. This is explained by the fact that these impurities are not detected on the chromatograms by the high performance liquid chromatography (HPLC) technique traditionally used to measure the purity of D-allulose (see Figures 7 and 8). It is by using gas chromatography technique that the applicant has been able to detect their presence (see Figures 9 and 10).

[0037] The applicant was able to identify these impurities as D-allulose dimers. The applicant was also able to show that these dimers have a very significant anti-crystallization effect, in contrast to other impurities such as glucose or D-fructose. Indeed, since these D-allulose dimers are generated during the process, if the amount of these dimers is too high, their presence can limit the yield of the continuous production process of D-allulose crystals by forming massecuite that cannot be centrifuged, by preventing this crystallization purely and simply. Furthermore, in an industrial, continuous process for producing D-allulose crystals, in which a large number of successive steps are carried out, the amount of these impurities can change over time. This makes the process unstable over time, since massecuite can sometimes be centrifuged and sometimes cannot be centrifuged.

[0038] The applicant can appreciate that it has been successful in identifying these specific impurities and in removing them by carrying out a separation step consisting of at least partially separating these D-allulose dimers by nanofiltration.

[0039] Using the process of the present invention makes the crystallization step very stable, so that it is possible to carry out the process continuously, but also to dramatically increase the overall yield of D-allulose crystals. This is due to the fact that the crystallization step is very stable, so ... This is made possible by the fact that it is possible to provide a stock solution (this is thanks to the nanofiltration process mentioned above).

[0040] The applicant can appreciate that this stock solution has been used to provide new D-allulose crystals, in particular using a specific crystallization process that also limits the in situ formation of said dimer.This results in crystals whose mass percentage of D-allulose dimer is lower than that of the prior art.Another subject of the present invention therefore relates to D-allulose crystals that contain a mass content of D-allulose dimer, as measured by gas chromatography (GC), of less than 0.5%.

[0041] As for the crystals described in WO2011 / 119004 A2, because they have a very fine size, they are difficult to separate from the crystallization mother liquor.The mother liquor contains a large amount of D-allulose dimer, and therefore the dimer content in the crystals recovered after separation is high, which is much higher than the crystals of the present invention.Furthermore, Comparative Example 3 of this application (see Example section) demonstrates that even if the process described in this document is further improved, the applicant cannot obtain the crystals of the present invention.

[0042] As for the crystals described in WO 2016 / 064087, they show impurities, which may be D-allulose dimers, in greater amounts than the crystals of the invention. Without being bound by any theory, the presence of these dimers can be explained by the fact that the D-allulose solution is kept heated before being introduced into the crystallizing dish, i.e. for a period of time that reaches 60 hours. Moreover, this document is completely silent on the method by which the stock solution is prepared, in particular on the conditions of the concentration step. Indeed, as will become clear in the remainder of this description, the selection of the conditions of the crystallization and concentration steps has a substantial influence on the amount of D-allulose dimer formed. Thus, the selection of these conditions makes it possible to limit the amount of dimer formed during the process, thus reducing the D-allulose dimer content in the D-allulose crystals obtained. Since the selection of the conditions of the step of preparing the stock solution has a substantial influence on the amount of D-allulose dimer therein, this document does not describe stock solutions useful for the preparation of the crystals of the invention, nor the crystals themselves.

[0043] EP 1 860 195 describes a tubular type composite crystalline composition of D-allulose and D-allulose in which D-allulose is the minority portion and is not a D-allulose crystal.

[0044] For the crystalline compositions obtained by crystallization from ethanol described in CN 104447888 A, this document is silent on numerous conditions of the process of preparation of the crystalline compositions, especially on the step for concentrating the stock solution. In this respect, it is impossible to reproduce these crystalline composition preparation tests. However, it is useful to note that the crystallization must be carried out specifically in an organic solvent such as ethanol. However, it is known that crystallization in this type of solvent is only used when necessary. In fact, water is generally preferred for obvious cost and environmental reasons. The organic solvent selected (ethanol in the case of D-allulose) has the advantage of facilitating crystallization and allowing crystallization that would be possible from water, although it is more expensive and necessarily difficult to reprocess. This therefore confirms that the stock solution of D-allulose contains a large amount of impurities of the D-allulose dimer type, which can be explained by the fact that no special precautions seem to have been taken for the various steps of preparing the stock solution (especially no conditions are given for the concentration step). Furthermore, from a purification standpoint, crystallization from ethanol may not be more efficient for obtaining pure D-allulose crystals than crystallization from water (if this is possible), since these dimers, which are chemically similar to D-allulose, are also sparingly soluble in ethanol and precipitate as well. Finally, other impurities, also numerous, are found in the crystalline compositions, as evidenced by the low purities obtained in this document.

[0045] Crystalline compositions obtained by crystallization from ethanol are also described in a publication by Takeshita et al. (Mass production of D-psicose from D-fructose by a continuous bioreactor system using immobilized D-tagatose 3-epimerase, Journal of Bioscience and Bioengineering, Vol. 90 No. 4, January 2000, pages 453-455). This publication focuses on the first step of preparing D-allulose, not on the production of D-allulose crystals, and the details are again very few. Since the selection of conditions for the step of preparing the stock solution has a substantial effect on the amount of D-allulose dimer therein, this publication does not describe the stock solution useful for preparing the crystals of this invention, nor the crystals themselves. Furthermore, this document specifies that the crystallization is carried out from ethanol to facilitate the solidification of D-allulose, which demonstrates high amounts of non-crystalline impurities, confirming the impossibility of crystallizing this document's D-allulose stock solution from water.Furthermore, the crystallization in question in this document is in fact merely an uncontrolled "precipitation" by the addition of ethanol, which inevitably results in an impure solid crystalline composition.

[0046] Other crystalline compositions are also described in CN103333935A, but there are no details on their preparation, since the conditions for preparing the stock solution, and any conditions for crystallization (even solvent) are not shown. Moreover, this document does not include preparation tests per se. Since the selection of conditions for the process of preparing the stock solution has a substantial effect on the amount of D-allulose dimer therein, this document does not describe the stock solution useful for preparing the crystals of this invention, nor the crystals themselves. Moreover, the low purity (98%) of the crystalline composition obtained in this document seems to indicate that the crystalline composition is very impure.

[0047] Another subject of the invention also relates to the use of a nanofiltration unit in a production circuit of D-allulose crystals in order to improve the overall yield of D-allulose crystals. [Brief description of the drawings]

[0048] [Figure 1] FIG. 1 diagrammatically depicts a production circuit for D-allulose crystals in which the D-fructose-rich chromatographic raffinate is recycled to be mixed with fructose at the top of the epimerization reaction. [Diagram 2] FIG. 2 illustrates a schematic diagram of a production circuit for D-allulose crystals in which the crystallization mother liquor is recycled to be mixed with the D-fructose / D-allulose composition resulting from the epimerization reaction. [Diagram 3] FIG. 3 is a schematic representation of a production circuit for D-allulose crystals including a nanofiltration unit useful in the process of the present invention. [Figure 4] FIG. 4 depicts an example of an adiabatic crystallizer-evaporator under vacuum, useful in the process variant of the present invention. [Diagram 5] FIG. 5 depicts an example of a vertical crystallizer useful in the process variations of the present invention. [Figure 6] FIG. 6 represents the curve of permeation, ie flux, as a function of volumetric concentration factor in relation to the nanofiltration process. [Figure 7] FIG. 7 represents an HPLC chromatogram of a D-allulose-rich composition sampled in the process of the present invention (see FIG. 3), i.e., before nanofiltration. [Figure 8] FIG. 8 represents the HPLC chromatogram of the permeate sampled in the process of the present invention (see FIG. 3), ie after nanofiltration. [Figure 9] FIG. 9 represents a GC chromatogram of a D-allulose-rich composition sampled in the process of the present invention (see FIG. 3), i.e., before nanofiltration, in the dimer-specific zone. [Figure 10]FIG. 10 represents a GC chromatogram in the dimer-specific zone in the process of the invention (see FIG. 3), ie, of the permeate sampled after nanofiltration. [Figure 11] FIG. 11 shows images obtained by optical microscopy of comparative D-allulose crystals. [Figure 12] FIG. 12 shows an image obtained by optical microscopy of D-allulose crystals according to the present invention. [Figure 13] FIG. 13 represents an image obtained by optical microscopy of D-allulose crystals manufactured and sold by the company CJ CheilJedang Food Ingredients. [Figure 14] FIG. 14 shows the ratio of diameter Feret min / Feret max as a function of volume particle size D4,3 for two types of D-allulose crystals. [Figure 15] FIG. 15 shows the Feret minimum and Feret maximum diameters of the model particles. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0049] The conventional manufacturing process for D-allulose crystals is as follows: concentrating the D-allulose-rich composition to provide a stock solution that is crystallized; crystallizing the stock solution to form D-allulose crystals and a mother liquor; A process for separating the mother liquor from the D-allulose crystals. Includes.

[0050] The process of the present invention has the particularity of including a nanofiltration step.

[0051] This nanofiltration step allows to limit the amount of D-allulose dimer in the raw solution provided in the process of the present invention.This nanofiltration step is carried out in a step before the step of concentrating the composition rich in D-allulose.This step therefore allows to provide a raw solution of D-allulose whose D-allulose dimer content is lower than that obtained without this nanofiltration step and from the same process.

[0052] In the nanofiltration step, which is essential to the process of the present invention, two fractions are formed when the composition of D-allulose is subjected to nanofiltration: Permeate poor in D-allulose dimers; and a retentate, which is also enriched in D-allulose dimers.

[0053] In Figure 3, which represents a production circuit for crystals useful in the process of the invention, stream 6 represents the permeate and stream 12 represents the retentate. For exemplary, but non-limiting reasons, the streams shown in the remainder of the description refer to the production circuit streams of Figure 3.

[0054] The nanofiltration permeate is an intermediate that allows the production of this stock solution.

[0055] The terms "poor in D-allulose dimer" and "enriched in D-allulose dimer" are clearly related to the content of D-allulose oligomers in the nanofiltered composition.The term "D-allulose dimer" is intended to mean a compound that contains D-allulose condensed with at least a second identical or different monosaccharide.These dimers are, for example, dimers of the D-allulose-D-allulose type.

[0056] These dimers can be detected by GC, as demonstrated in the Examples section, but not during HPLC analysis. It follows that the masses of the various constituents, expressed as dry mass, are systematically measured by GC in this application. To measure the amount of each of the chemical species in the composition, the samples generally undergo a treatment step to convert the various chemical species present into their methoxylated trimethylsilyl derivatives. The masses of each of the chemical species are expressed in this application relative to the total dry mass, unless otherwise stated.

[0057] The amounts of glucose, fructose and allulose can be measured in a gas chromatograph equipped with an injector heated to 300°C, equipped with a flame ionization detector (FID) heated to 300°C, and equipped with a 40 meter DB1 capillary column with an inner diameter of 0.18 mm and a film thickness of 0.4 μm, the column temperature is programmed as follows: from 200°C to 260°C at a rate of 3°C / min, then from 260°C to 300°C at 15°C / min, held at 300°C for 5 minutes.

[0058] The term "amount of D-allulose dimer" is intended to mean the difference between the total amount of dimers in a sample measured by GC and the amount of known dimers that are probably present, which are glucose-glucose dimers such as maltose and isomaltose.However, the amount of these glucose-glucose dimers is generally very low or absent.For example, in the stock solution useful for the present invention, the mass of glucose-glucose dimers is generally less than 0.2%, and often less than 0.1%.The same applies to the crystals of the present invention.

[0059] The possible amounts of glucose-glucose dimers under the same conditions as above for glucose, fructose and D-allulose are: by carrying out the hydrolysis of glucose-glucose dimers according to the invention; by measuring the amount of total glucose in the same chromatogram and under the same conditions (said total glucose includes the initial glucose, called free, and the glucose resulting from hydrolysis of glucose-glucose dimers); By subtracting the amount of initial glucose in the sample from this amount of total glucose It can be measured.

[0060] The total amount of dimers, as far as that is concerned, can be measured in a gas chromatograph under the same conditions as those described above, with the difference that the column used is a 30 meter DB1 capillary column with an internal diameter of 0.32 mm and a film thickness of 0.25 μm, and the column temperature is programmed as follows: from 200° C. to 280° C. at a rate of 5° C. / min, then held at 280° C. for 6 minutes, then from 280° C. to 320° C. at 5° C. / min, held at 320° C. for 5 minutes.

[0061] This method is described in more detail in the Examples section.

[0062] To carry out a nanofiltration process useful in the present invention, the composition to be nanofiltered is passed through a nanofiltration membrane, which generally has a dry matter content in the range of 5% to 15%.

[0063] The temperature of the composition to be nanofiltered may range from 10 to 80°C, typically from 15 to 50°C, and often is about 20°C.

[0064] Those skilled in the art will know how to select a membrane useful for this separation. The nanofiltration membrane can have a cutoff threshold of less than 300 Da, preferably in the range of 150-250 Da. Ideally, the membrane will have a MgSO4 rejection rate of at least 98%. It is particularly In particular, it may be a Dairy DK or Duracon NF1 type membrane manufactured by GE®.

[0065] The pressure applied to the membrane can also vary widely and may range from 1 to 50 bar, preferably from 5 to 40 bar and most preferentially from 15 to 35 bar.

[0066] The nanofiltration process can be accomplished by a diafiltration step.

[0067] Preferably, the volumetric concentration factor (VCF) of the nanofiltration is in the range of 2 to 20. This volumetric concentration factor is easily adjusted by one skilled in the art.

[0068] This nanofiltration process can be carried out continuously.

[0069] According to the present invention, the step of providing a composition enriched in D-allulose comprises: providing a composition (stream 1 or 1') comprising D-fructose; an epimerization step to form a composition comprising D-fructose and D-allulose (Stream 2); a chromatography step to obtain a composition enriched in D-allulose (stream 5) and a composition enriched in D-fructose, the raffinate (stream 14); may include.

[0070] Preferably, a nanofiltration step is performed between the step of providing a D-allulose-enriched composition (stream 5) and the step of concentrating to form a stock solution of D-allulose (stream 7). The nanofiltration step of the D-allulose-enriched composition provides a retentate (stream 12) and a permeate (stream 6).

[0071] therefore, providing a composition enriched in D-allulose; nanofiltration of the D-allulose enriched composition to provide a retentate and a permeate; recovering the nanofiltration permeate; concentrating the permeate to provide a stock solution of D-allulose. Preferred variations of the present invention include:

[0072] In the process of the present invention, the nanofiltration step is therefore advantageously carried out on the D-allulose-rich composition obtained from the chromatography step immediately before the concentration step to provide the raw solution.It is in this configuration that the process most effectively limits the amount of D-allulose dimers in the raw solution to be crystallized, thus most substantially increasing the overall yield of D-allulose crystals.

[0073] The term "D-allulose-rich composition" is intended to generally mean a composition having a D-allulose mass content of greater than 80%, advantageously ranging from 80% to 99%, preferentially from 82% to 98%, by dry mass.

[0074] Concerning the permeate obtained, its dry matter content can vary, for example, in the range of 3% to 15%. The permeate can in particular contain D-allulose, D-fructose and glucose, and possibly also other sugars present. The composition of this filtrate can be very different and depends on the composition that is nanofiltered. At the end of this nanofiltration, the recovered permeate can contain, relative to its dry mass, 0% to 1.2%, for example 0.1% to 1.0%, in particular 0.15% to 0.5% D-allulose dimers. The permeate can be further enriched with additional The product may be subjected to one or more steps such as mixing with the product of (a), a separation step, a purification step, an epimerization step or a concentration step.

[0075] As regards the retentate obtained, its dry matter content can also vary widely, for example in the range of 15% to 40%. It can mainly contain D-fructose, D-allulose, glucose and D-allulose dimers. According to one variant, the retentate is recovered and, after an optional concentration step, is optionally mixed with an additional composition of D-allulose to obtain a D-allulose syrup.

[0076] In a preferred variant in which the D-allulose-enriched composition comprising D-allulose dimers is subjected to a nanofiltration process, the resulting permeate (stream 6), referred to as the "preferred permeate", preferably has a dry mass of: 80%-99% D-Allulose; · 0%-20% D-fructose; 0%-10% glucose; 0%~1.2% D-Allulose Dimer Includes.

[0077] As indicated above, this preferred permeate can be directly subjected to a concentration step to obtain the stock solution (stream 7) that is to be crystallized.

[0078] In this application, it is specified that all compositions, except for D-allulose crystals, are generally aqueous compositions.In other words, the solvent of dry constituents comprises water.The solvent of the composition generally consists of water or a mixture of water and alcohol, such as ethanol.Preferentially, the solvent of the composition is water.

[0079] Thus, the stock solution of D-allulose useful in the present invention generally consists of an aqueous solution of D-allulose. The stock solution generally has a dry matter content of at least 75%, for example 80% to 95%, preferentially 81% to 92%, and most preferentially 83% to 89%.

[0080] To achieve this dry matter content, it is necessary to carry out a concentration step. This step can be carried out on the composition rich in D-allulose, the only requirement being that this composition rich in D-allulose has been obtained in a preceding step using a process that includes a nanofiltration step useful in the present invention. This composition rich in D-allulose that is subjected to the concentration step can therefore be the preferred permeate described above, but also the composition rich in D-allulose obtained by chromatography, or a mixture of the permeate and an additional composition rich in D-allulose. Preferentially, the composition rich in D-allulose that is subjected to the concentration step is the preferred permeate.

[0081] Since the formation of D-allulose dimers also occurs during the concentration step, it is preferable to choose conditions that make it possible to limit the formation of these dimers. The concentration step is therefore generally carried out under vacuum, for example at a pressure ranging from 5 to 100 mbar, preferably from 20 to 70 mbar. This vacuum makes it possible to reduce the temperature required for evaporation and to reduce the duration of this concentration step. It can be carried out at a temperature ranging from 30 to 80°C, advantageously from 34 to 70°C, preferentially from 37 to 50°C. This concentration step can be carried out in a single-stage evaporator, a multi-stage evaporator, for example a two-stage evaporator. At the end of the concentration step, a stock solution of D-allulose useful for the invention is obtained.

[0082] This concentration step can be carried out continuously.

[0083] The resulting stock solution, by dry weight, is: 80%-99%, preferably 85%-98% D-allulose; 0% to 20%, preferably 0.5% to 15% D-fructose; 0%-10%, preferably 0%-5% glucose; 0% to 1.5%, e.g. 0.1% to 1.2%, preferentially 0.4% to 1.1% of D-allulose dimer may include.

[0084] The process according to the invention also includes a step of crystallizing said stock solution of D-allulose to form a suspension of D-allulose crystals, the suspension including crystals and mother liquor from the crystallization also formed during this step.

[0085] This crystallization step can be of any type. It can in particular be a crystallization step by cooling or by evaporation. The skilled person will know how to find the operating conditions, in particular those described in WO 2011 / 119004. However, it should be pointed out that the crystallization steps described in these documents are made more difficult to carry out due to the specific preparation of the stock solutions useful for the present invention.

[0086] At the end of the crystallization step, the crystals (stream 10) are separated from the mother liquor (stream 13) using the crystal suspension (stream 9), in particular by a filtration and / or centrifugation step, this separation step being more preferentially carried out batchwise.

[0087] The mother liquors (stream 13) generally have a dry matter content in the range of 70% to 80%. They are, by dry weight: 80%-99%, preferably 82%-95% D-allulose; 0% to 20%, preferably 0.5% to 15% D-fructose; 0%-10%, preferably 0%-5% glucose; 0%-3%, e.g. 0.1%-2.9%, especially 1%-2.5% D-allulose dimer may include.

[0088] The crystals obtained can be subjected to a clarification step with cold water and / or with alcohol, in particular ethanol. These crystals (stream 11) can then be dried by a drying step that can be carried out in any type of suitable dryer. The D-allulose crystals have a water content of less than 5%, preferably less than 1%.

[0089] This crystallization step can be carried out continuously, in particular using a vertical crystallizer, an example of which is shown in FIG.

[0090] According to a most preferred mode, the crystallization process comprises an adiabatic evaporative cooling stage, carried out in an adiabatic crystallizer-evaporator under vacuum to form a mass skid (stream 8), followed by a stage of crystallization by cooling said mass skid to form a suspension of crystals (stream 9). The adiabatic evaporative cooling causes an immediate cooling of the stock solution to be crystallized. Preferably, the crystallizer-evaporator is equipped with a condenser, and the water condensed during this stage is continuously reinjected along the wall at the top of the crystallizer to keep the dry matter content stable. This preferred crystallization process, which comprises two separate stages, combined with a nanofiltration stage in a specific configuration of the process of the invention, makes it possible to continuously obtain the crystals of the invention described below in this description. This means that this preferred crystallization process, especially the evaporative cooling stage, also makes it possible to very significantly limit the in situ formation of D-allulose dimers. This is related to the fact that the raw solution is cooled substantially instantly when it is introduced into the crystallizer-evaporator, without being bound by any theory, and is different from known crystallization processes of D-allulose, which describe natural cooling of the raw solution, or even by a cooling gradient using a heat exchanger, as described in WO 2016 / 064087. The crystals according to the present invention show improved purity and improved properties, even though the first stage of the crystallization process is an immediate evaporative cooling stage, thereby shortening the duration of the crystallization process. In fact, this is contrary to the assumption of those skilled in the art that it is necessary to increase the crystallization time to obtain improved crystals.

[0091] During the evaporative cooling stage, the temperature may be in the range of 30-40°C, preferably in the range of 33-37°C, for example around 35°C. This temperature is easily achieved by the skilled person by determining the appropriate reduced pressure to be applied. The pressure in the crystallizer-evaporator may therefore be in the range of 30-50 mbar. Adiabatic crystallizers are especially suitable for use with forced or indirect forced circulation (IFC) crystallizers. *) DT (for vent tube) or DTB (for vent baffle) pull tubes. Preferably, this evaporative cooling stage is continuous. During this stage, the initiator is continuously produced by spontaneous nucleation phenomena in the evaporative crystallizer due to the supersaturation produced by the quench: thus, strictly speaking, in this case, there is no introduction of initiator at all. In a non-limiting sense, the possibility of carrying out this evaporative cooling stage continuously is described in the Examples section and in FIG. 4, in which a fraction of the crystals formed during the evaporative cooling stage (stream 7d) is mixed with stream 7b to feed the crystallizer-evaporator, thereby making it possible to obtain stream 7c which, at the time of introduction into the crystallizer-evaporator, contains crystals which will be able to grow further during this new pass through the crystallizer-evaporator. According to this example, stream 7b can be obtained from a mixture of stream 7, consisting of the "fines", i.e. the supersaturated syrup of D-allulose recovered in the crystallizer-evaporator, with stream 7a, containing the finest D-allulose crystals of the crystallizer. According to this variant, stream 7 can advantageously be passed through a heat exchanger before mixing, said passage making it possible to substantially immediately reheat stream 7 before immediately mixing it with stream 7a. This then makes it possible to remelt the fines of stream 7a and to cool stream 7 so as to obtain stream 7b free of these fines.

[0092] At the end of this stage, the massecuite of D-allulose crystals (stream 8) is recovered, i.e. a suspension of crystals, generally of small size. The average residence time of the massecuite in this evaporative cooling stage can be between 5 and 15 hours. The volume average size D4,3 of the crystals in suspension in the massecuite is generally in the range of 50 to 200 μm.

[0093] The stage of crystallization by cooling is carried out continuously by cooling the massecuite (stream 8) obtained during the evaporative cooling stage. The duration of this crystallization stage can range from 25 to 50 hours. The temperature at the start of the crystallization generally depends on the temperature of the massecuite introduced and is in particular in the range from 30 to 40 ° C, preferably in the range from 33 to 37 ° C, for example of approximately 35 ° C. This stage is generally carried out with mechanical stirring, preferably during crystallization by cooling the temperature is lowered at a rate in the range of 0.3 to 0.5 ° C per hour. Figure 5 shows an example of a vertical crystallizer with various heat exchangers, on the side, that make it possible to adjust the temperature in the crystallizer. During this operation, the temperature difference between the massecuite and the water of the exchanger preferably does not exceed 5 ° C. The stage of crystallization by cooling can preferably be carried out continuously, especially in vertical crystallizers.

[0094] Thus, a preferred variant of the process of the invention is providing a D-allulose enriched composition (Stream 5); to the D-allulose to provide a retentate (stream 12) and a permeate (stream 6). a step of nanofiltration of the enriched composition; recovering the nanofiltration permeate; concentrating the permeate to provide a stock solution of D-allulose (Stream 7); A crystallization process comprising: i. An adiabatic evaporative cooling step, carried out in an adiabatic crystallizer-evaporator under vacuum to form a masseuse (stream 8); ii. A crystallization step by subsequent cooling of the mass skid to form a suspension of crystals (stream 9). A crystallization process comprising: Includes

[0095] The advantage of this preferred variant of the process of the invention, other than the advantages related to the crystals themselves, is that the crystals obtained can be much more easily separated from the mother liquor from the crystallization and can be more easily dried, which is mainly related to the shape of the crystals obtained.

[0096] To start the crystallization process, D-allulose initiators are generally introduced into the selected crystallizer. These D-allulose initiators consist of small size D-allulose crystals, for example with a size in the range of 10-100 μm. The mass of the initiator can vary widely depending on the type of crystallizer used. It can range from 0.001% to 1%, often 0.01% to 0.7%, generally 0.05% to 0.5%, relative to the mass of D-allulose in the stock solution. These amounts are particularly suitable when a step of crystallization by cooling from a stock solution of D-allulose is carried out. As mentioned above, when an evaporative cooling step is used, it is also possible to generate the initiator in situ.

[0097] Preferably, the crystallization step is carried out less than 1 hour after the concentration step, preferably less than 30 minutes after said step. Most preferentially, the crystallization step is carried out immediately after the concentration step. This makes it possible to further limit the amount of dimer in the stock solution to be crystallized during the crystallization step.

[0098] Once collected after drying, the crystals can also be subjected to an additional sieving step, which allows these crystals to be sieved and the size of the crystals to be increased or decreased by the fraction collected after sieving.For example, this additional step allows to collect the fraction of D-allulose crystals with a smaller volume average size D4,3 that passes through the sieve and also the fraction of D-allulose crystals with a larger volume average size D4,3 that remains on the sieve, with respect to the size of the crystals that are subjected to the sieving step.It is sufficient for the skilled person to select the sieve mesh size in order to modify the crystal population and obtain the desired D4,3 fraction.

[0099] It goes without saying that the process according to the invention can include other steps, such as those appearing in the conventional methods described previously and those described in detail below. The process according to the invention can also include additional purification steps, and also intermediate dilution or concentration steps with the aim of adjusting the dry matter content and thus carrying out the various steps of the process according to the invention under the best conditions. All of these steps can be carried out consecutively.

[0100] The composition of D-fructose (stream 1) provided for carrying out the epimerization step can be a D-fructose syrup, obtainable by dissolving D-fructose crystals in water, or a glucose / D-fructose syrup. Preferentially, this composition comprises a glucose / D-fructose syrup containing at least 90% by dry weight of D-fructose, preferentially at least 94% of D-fructose. In one preferred mode, which will be explained later in this description, a glucose / D-fructose syrup is provided for carrying out the subsequent epimerization step. The D-fructose composition provided for this purpose is a mixture (stream 1') of this D-fructose syrup and at least one recycled fraction which may in whole or in part be a raffinate (stream 14 or 16), which recycled fraction may contain a higher amount of D-allulose.

[0101] The D-fructose composition subjected to the epimerization process is 0%-10% D-Allulose; · 70%-100% D-fructose; 0%-10% glucose; 0%-15% D-Allulose Dimer may include.

[0102] The epimerization step is carried out using the D-fructose composition provided previously, optionally after adjustment of the dry matter content. This step is generally carried out with a dry matter content ranging from 30% to 60%, often from 45% to 55%. An enzyme of the D-psicose epimerase type or a composition comprising this enzyme is introduced into this composition. This enzyme-containing composition may be a lyophilisate of a host microorganism which synthesizes D-psicose epimerase, said microorganism possibly being Bacillus subtilis, in particular one described in WO 2015 / 032761 A1. The pH is adjusted according to the enzyme used, for example in the range of 5.5 to 8.5. The reaction can be carried out by heating at a temperature ranging from 40 to 70° C., often from 45 to 60° C. The reaction can last from 0.1 to 100 hours, for example from 0.2 to 60 hours. This reaction can be carried out, for example, on an enzyme column, which has the advantage of also working continuously with respect to this step. It is also possible to operate several reactors in series in order to operate continuously. To carry out this epimerization step, the teaching of WO 2015 / 032761 A1 may in particular be utilized.

[0103] At the end of the reaction, a composition containing D-fructose and D-allulose is formed, generally with a D-fructose / D-allulose weight ratio ranging from 85 / 15 to 55 / 45, and often with a D-fructose / D-allulose weight ratio ranging from 80 / 20 to 60 / 40. This ratio depends on the epimerization parameters used and quite obviously on the amount of D-allulose and D-fructose in the D-fructose composition provided to the epimerization step; the amount of D-allulose in this composition can be particularly greater in the case of recycling.

[0104] At the end of this epimerization step, if necessary, a filtration step can be carried out in order to recover the cell debris possibly present, especially when a lyophilisate of the host microorganism is used. This step may consist of a microfiltration step. In Figure 3, the microfiltered composition corresponds to stream 3, while the cell debris is recovered in stream 17.

[0105] In the process of the invention, additional purification steps can also be carried out. Before the chromatography step, a step of desalting the composition containing D-fructose and D-allulose (stream 3) is generally carried out, which can be carried out by passing it through one or more cationic ion exchange resins (e.g., cationic resins of the Dowex 88 type), anionic ion exchange resins (e.g., anionic resins of the Dowex 66 type) and cationic-anionic mixtures. In FIG. 3, this composition corresponds to stream 4. The resulting composition containing D-fructose and D-allulose is then desalted, generally to a resistance of 100 kΩ.cm. -1 Prior to this desalting step, it is also possible to carry out a step of decolorizing the composition comprising D-fructose and D-allulose, for example by passing it over a column containing activated carbon.

[0106] The composition comprising D-fructose and D-allulose (stream 4) can then be subjected to a chromatography step to provide at least one composition enriched in D-allulose and one composition enriched in D-fructose. In one preferred mode, which will be described in detail later in this description, the composition comprising D-fructose and D-allulose subjected to the chromatography step is a mixture (stream 4') of the composition resulting from the epimerization step and at least one recycled fraction, which possibly contains a higher amount of D-allulose.

[0107] The composition subjected to the chromatography step has, relative to its dry weight, · 22%-45%, generally 25%-37% D-Allulose; · 45%-75%, typically 46%-70% D-fructose; 0%-10% glucose; 2% to 10% D-Allulose Dimer may include.

[0108] To carry out this chromatography step, it is possible to use any type of continuous chromatography, in particular of the Simulated Moving Bed (SMB) type, the Improved Simulated Moving Bed (ISMB) type, the Divide Improved Simulated Moving Bed (DISMB) type, the Sequential Simulated Moving Bed (SSMB) type or the Nippon Mitsubishi Chromatography Improved (NMCI) type. Water is generally used as eluent. The chromatograph may comprise several columns in succession, for example 4 to 8 columns. The columns contain an ion exchange resin, for example a cationic resin for exchanging with calcium ions. The dry matter content of the composition comprising D-fructose and D-allulose may range from 40% to 70%, generally around 50%. The temperature of the composition during the chromatography generally ranges from 40 to 80°C, preferably from 55 to 65°C. This chromatography lasts for the time necessary to obtain a satisfactory separation and may last for several hours.

[0109] At the end of this process, a D-allulose-rich composition (stream 5) is obtained, which may contain, relative to its dry matter content, at least 80% D-allulose, advantageously at least 90% D-allulose. This D-allulose-rich composition may have a dry matter content ranging from 5% to 15%. At the end of this process, a raffinate (stream 14) is also obtained, which generally contains, relative to its dry matter content, at least 75% D-fructose, often at least 80% D-fructose. This raffinate generally has a dry matter content ranging from approximately 15% to 30%.

[0110] The D-allulose-rich composition obtained at the end of the chromatography (stream 5) therefore has, relative to its dry mass: 80%-98% D-Allulose; · 0%-20% D-fructose; 0%-10% glucose; 1.5% to 5% D-Allulose Dimer may include.

[0111] The raffinate, as far as it is concerned, comprises, relative to its dry mass: 1%-10% D-Allulose; 70%-99% D-fructose; 0%-10% glucose; 5%~20% D-Allulose Dimer may include.

[0112] In contrast to the conventional method, where the total yield of D-allulose crystals is less than 15% based on the D-fructose introduced, the yield of the process of the present invention can be 25% or more.Advantageously, the total yield of D-allulose crystals is 50% or more, for example 60% or more, or even 65% or more.This particularly improved yield is made possible by the fact that the recycling step can be carried out without interrupting the crystallization step.

[0113] Thus, the process of the present invention may include at least one recycling step.

[0114] According to one preferred mode, this recycling step can consist of recycling at least a part of the raffinate (stream 14) resulting from the chromatography step. This raffinate can optionally be concentrated before being mixed. It can advantageously be recycled in whole or in part to be mixed with the above-mentioned D-fructose (stream 1), for example in the form of a D-fructose / glucose syrup, to provide a D-fructose composition (stream 1'). It is this D-fructose composition, which is generally more enriched in D-allulose than the D-fructose syrup, that is then subjected to the epimerization step.

[0115] This recycling step can consist of recycling at least a portion of the mother liquors (stream 13). These mother liquors can advantageously be recycled in whole or in part to be mixed with the composition comprising D-fructose and D-allulose (stream 4). It is this mixture (stream 4') that is then subjected to the chromatography step. These mother liquors can optionally be diluted before being mixed.

[0116] This recycling step can consist of recycling at least a part of the retentate (stream 12). This retentate can advantageously be recycled in whole or in part so as to be mixed with the composition comprising D-fructose and D-allulose (stream 4) and optionally with the recycled mother liquor. It is then this mixture (stream 4') that is subjected to the chromatography step. This retentate can optionally be concentrated before being mixed. In the case where mixing is carried out with the retentate and mother liquor fractions, it may not be necessary to concentrate or dilute these fractions. It should be pointed out that the recycling of the retentate and mother liquor fractions, two fractions with a relatively large amount of D-allulose, makes it possible to increase the concentration of D-allulose (and consequently reduce the amount of D-fructose) of the composition that is subjected to the chromatography step.

[0117] To carry out the optional step of concentrating the recycled fraction, it is possible to use the same equipment and conditions described for the concentration step enabling the production of the raw solution.

[0118] According to one most preferred mode of the invention (FIG. 3 represents a circuit for the manufacture of this preferred process of the invention), the process comprises: a) providing a composition (Stream 1') comprising D-fructose; b) an epimerization step to form a composition (Stream 2) comprising D-fructose and D-allulose; c) a chromatography step to obtain a D-allulose-enriched composition (stream 5) and a raffinate (stream 14) consisting of a D-fructose-enriched composition; d) nanofiltration of the D-allulose-enriched composition to obtain a permeate (stream 6) and a retentate (stream 12); e) concentrating the permeate to form a stock solution (stream 7) that is to be crystallized; f) crystallizing the raw liquor (Stream 9) to form crystals (Stream 10) and mother liquor (Stream 13) wherein said process comprises: recycling at least a portion of the raffinate (stream 14 or 16) so as to be mixed with D-fructose (stream 1) to give the composition of step a) (stream 1′); and / or recycling at least a portion of the retentate (stream 12) resulting from the nanofiltration to be mixed with the composition comprising D-fructose and D-allulose (stream 4) resulting from step b) in order to obtain a composition (stream 4') which is subjected to a chromatography step c); and / or recycling at least a portion of the mother liquor (stream 13) resulting from the crystallization step to be mixed with the composition comprising D-fructose and D-allulose (stream 4) resulting from step b) in order to obtain a composition (stream 4') which is subjected to the chromatography step c). will be implemented.

[0119] The process includes a flushing step, which is a step of flushing at least a part of at least one of the recycled fractions, possibly selected from raffinate, retentate and mother liquor from crystallization.This is because it is absolutely necessary to remove a part of the D-allulose dimer formed during the process from the production circuit in order for the system to remain stable.In general, the more fractions are recycled, the more the amount of D-allulose dimer increases in the circuit.Therefore, one possibility to reduce the amount of D-allulose dimer is to increase the amount flushed.However, this results in a loss of the total yield of D-allulose crystals.The process of the present invention makes it possible to dramatically increase the recycling of the various fractions obtained in the process, while at the same time keeping crystallization possible.

[0120] For example, in the most preferred process variant described above, in which the raffinate, retentate and mother liquor from the crystallization fraction are all recycled, the raffinate recycling step is advantageously a partial recycling, for example 50%-95% of this raffinate is recycled (stream 16) and 5-50% is flashed (stream 15) to provide a D-fructose composition containing D-allulose dimers; in other words, the recycling degree of the D-fructose-rich composition is in the range of 50%-95%. Preferentially, the recycling degree is in the range of 70%-92%. In this case, the other two recyclings are advantageously full recyclings.

[0121] The flashed fraction can then be used to produce a syrup, optionally after steps of concentration and / or mixing with other compositions and / or additives.

[0122] The process according to the invention is particularly advantageous since it can be continuous, since the crystallization step remains stable over time.

[0123] As previously explained, according to a preferred variant of the invention combining a step of nanofiltration with a step of crystallization in an adiabatic crystallizer-evaporator under vacuum, the Applicant has also succeeded in obtaining crystals of improved quality.

[0124] The crystals according to the invention have a mass content of D-allulose dimers of less than 0.50%, preferably less than 0.30%, or even less than 0.20%. These crystals advantageously have a mass content of D-allulose dimers in the range of 0.01% to 0.48%, preferentially in the range of 0.02% to 0.45%, for example in the range of 0.03% to 0.40%, in particular in the range of 0.04% to 0.30%, and especially in the range of 0.05% to 0.20%. The composition may contain a mass content of D-allulose dimer.

[0125] The crystals according to the invention advantageously have a mass content of D-allulose of more than 99.00%, preferably more than 99.50% or even more than 99.70%.

[0126] One advantage of the crystals of the present invention is that they show a small amount of D-allulose dimers.Without being bound by any theory, the applicant explains this by the fact that the useful raw solution for the production of these crystals contains a very small D-allulose dimer content, and by the fact that the crystallization step carried out allows to limit the in-situ formation of these dimers.Therefore, the applicant was able to obtain these crystals using this process by combining a nanofiltration step with a stage of adiabatic evaporation cooling and a stage of crystallization by cooling.

[0127] One disadvantage associated with prior art D-allulose crystals that contain a higher dimer content than those of the present invention is that these crystals are observed to elongate, especially when they are large, so that they have a shape similar to needles.

[0128] Preferentially, the D-allulose crystals of the invention have a volume average size D4,3 greater than 200 μm, advantageously ranging from 210 to 800 μm, preferentially from 220 to 350 μm.

[0129] The crystals of the present invention, which have a lower D-allulose dimer content, have the advantage of having a more "chunky" shape, as demonstrated in Figures 11, 12 and 13.

[0130] This chunkier shape can result in the fact that the D-allulose crystals of the invention have a Feret minimum / Feret maximum ratio greater than 0.60, advantageously ranging from 0.62 to 0.90, for example 0.63 to 0.80, for a given volumetric particle size D4,3 chosen in the range of 200 to 400 μm. Feret diameter is a parameter well known to those skilled in the art. It is estimated from the projected area of ​​the particle using the caliper principle. The Feret minimum diameter consists of the minimum of the dimensions, while the Feret maximum diameter consists of the maximum of the dimensions. Figure 15 represents the Feret minimum and maximum diameter principle for a given particle.

[0131] Preferably, the crystals of the present invention exhibit this Feret minimum / Feret maximum ratio over the entire particle size range of 200 to 400 μm.

[0132] Alternatively, and independently of the content of D-allulose dimers, the subject of the present invention relates to D-allulose crystals having a volume average size D4,3 greater than 200 μm, advantageously ranging from 210 to 800 μm, preferentially from 220 to 350 μm, and for a given volume particle size D4,3 selected from the range extending from 200 to 400 μm, having a Feret minimum / Feret maximum diameter ratio greater than 0.60, advantageously ranging from 0.62 to 0.90, for example from 0.63 to 0.80. Preferably, the crystals of the present invention have this Feret minimum / Feret maximum ratio over the entire particle size range extending from 200 to 400 μm. These crystals of the present invention advantageously contain a mass content of D-allulose dimers of less than 0.50%, preferably less than 0.30%, or even less than 0.20%. These crystals may advantageously contain a mass content of D-allulose dimer in the range of 0.01% to 0.48%, preferentially in the range of 0.02% to 0.45%, for example in the range of 0.03% to 0.40%, in particular in the range of 0.04% to 0.30%, especially in the range of 0.05% to 0.20%. These crystals advantageously have a mass content of D-allulose of 99.00% or more, preferably 99.50% or more, or even 99.70% or more.

[0133] The volume average size D4,3 of the crystals and also the Feret minimum / Feret maximum diameter ratio are measured using a particle size analyzer, in particular a particle size analyzer of the type QICPIC RODOS of the brand SympaTEC, such as the one used in the Examples section. Considering that the crystals are observed randomly in all directions in the particle size analyzer, the values ​​obtained by the particle size analyzer for a population of crystals differ from those obtained by calculation on only one microscopic image of crystals of this population, and the values ​​obtained by particle size analysis are generally higher.

[0134] Preferably, the crystals are not aggregated (or individualized). The fact that the crystals are not aggregated can be verified by simple observation with optical microscopy. As an example, the crystals in Figure 13 are aggregated, unlike those in Figures 11 and 12.

[0135] This different morphology results in improved flowability of the crystals of the invention compared to crystals of the same average size on a macroscopic scale, which in turn allows these crystals to behave better with respect to caking over time.

[0136] Thus, due to their properties, the crystals obtained using the preferred process of the invention are easily flowable. They therefore make it possible to obtain crystals that exhibit a flowability never before achieved. They can therefore be advantageously used, for example, as table sugar.

[0137] The D-allulose crystals of the present invention can be used in the known applications of allulose and generally in sweeteners.Among the applications in which the D-allulose crystals of the present invention can be used, mention may be made of chewing gum in the form of sticks or dragees, suckable sweets and tablets, biscuits, cookies, muffins, cakes, gelatin-based cakes, chewing pastes, especially short-textured chewing pastes, icings and powdered drinks.

[0138] Another subject of the invention also relates to the use of a nanofiltration unit in a production circuit for D-allulose crystals to improve the safety of the process and / or the overall yield of D-allulose crystals, which is particularly advantageous when the raw materials introduced into the circuit contain D-fructose.

[0139] Another subject of the invention also relates to the use of a nanofiltration unit in a production circuit for D-allulose crystals to improve the quality of the crystals obtained.The term "improving the quality of the crystals obtained" is intended in particular to mean reducing the D-allulose dimer content and / or increasing the Feret minimum / Feret maximum diameter ratio of the D-allulose crystals.

[0140] By way of example, other embodiments of the process according to the invention, including a mother liquor recycling step and / or a raffinate recycling step and / or a retentate recycling step, are given below.

[0141] According to a first embodiment, the process comprises: a) providing a composition enriched in D-allulose; b) A concentration step to form a stock solution to be crystallized. Including, at least one recycling step comprises recycling at least a portion of the mother liquor; a nanofiltration process is performed on these recycled mother liquors to form a permeate and a retentate; the permeate is mixed with the D-allulose-enriched composition provided in step a); and This mixture is subjected to a concentration step b) to obtain a stock solution which is subjected to crystallization; At least a portion of the mother liquor and / or the retentate is flashed off It is characterized by:

[0142] According to a second embodiment, the process comprises: a) providing a composition enriched in D-allulose; b) A concentration step to form a stock solution to be crystallized. Including, at least one recycling step comprises recycling at least a portion of the mother liquor; These recycled mother liquors are mixed with the D-allulose-rich composition provided in step a); a nanofiltration process is performed on the mixture to provide a permeate and a retentate; this permeate is subjected to a concentration step b) so as to obtain a stock solution to be crystallized; and At least a portion of the mother liquor is flashed off It is characterized by:

[0143] According to a third embodiment, the process comprises: a) providing a composition comprising D-allulose and D-fructose; b) a chromatography step to provide a D-allulose-enriched composition and a raffinate comprising a D-fructose-enriched composition; c) concentrating the D-allulose-rich composition to form a stock solution that is crystallized. Including, at least one recycling step comprises recycling at least a portion of the mother liquor; a nanofiltration process is performed on these recycled mother liquors to form a permeate and a retentate; the permeate is mixed with the composition provided in step a); this mixture is subjected to a chromatography step b); and At least a portion of the mother liquor is flashed off It is characterized by:

[0144] According to a fourth embodiment, the process comprises: a) providing a composition comprising D-allulose and D-fructose; b) a chromatography step to provide a D-allulose-enriched composition and a D-fructose-enriched composition; c) A concentration step to form a stock solution to be crystallized. Including, at least one recycling step comprises recycling at least a portion of the mother liquor; These recycled mother liquors are mixed with the composition provided in step a); a nanofiltration process is performed on the mixture to provide a permeate and a retentate; this permeate is subjected to a chromatography step b); and At least a portion of the mother liquor is flashed off It is characterized by:

[0145] According to a fifth embodiment, the process comprises: a) providing a composition comprising D-allulose and D-fructose; b) a chromatography step to provide a D-allulose-enriched composition and a D-fructose-enriched composition; c) A concentration step to form a stock solution to be crystallized. Including, at least one recycling step comprises recycling at least a portion of the mother liquor; These recycled mother liquors are mixed with the composition provided in step a); A chromatography step b) is carried out on this mixture; a nanofiltration step is carried out on the D-allulose-enriched composition resulting from this chromatography step b) to obtain a permeate and a retentate; this permeate is subjected to a concentration step c); and At least a portion of the mother liquor is flashed off It is characterized by:

[0146] According to a sixth embodiment, the process comprises: a) providing a composition comprising D-fructose; b) an epimerization step to form a composition comprising D-fructose and D-allulose; c) chromatography of this composition to obtain a D-allulose-enriched composition and a raffinate consisting of a D-fructose-enriched composition; d) concentrating the D-allulose-rich composition to form a stock solution that is crystallized. Including, at least one recycling step comprises recycling the raffinate; a nanofiltration step is performed on the raffinate to provide a permeate and a retentate; the permeate is mixed with the composition comprising D-fructose of step a); an epimerization step b) is carried out on this mixture; and At least a portion of the raffinate is flashed It is characterized by:

[0147] According to a seventh embodiment, the process comprises: a) providing a composition comprising D-fructose; b) an epimerization step to form a composition comprising D-fructose and D-allulose; c) chromatography of this composition to obtain a D-allulose-enriched composition and a raffinate consisting of a D-fructose-enriched composition; d) A concentration step to form a stock solution that is to be crystallized. Including, a recycling step consisting of recycling the raffinate obtained in step c); a first nanofiltration step is performed on the raffinate to provide a first permeate and a first retentate; the first permeate is mixed with the composition comprising D-fructose of step a); the epimerization step b) is carried out on this mixture; the recycling step comprises recycling at least a portion of the mother liquor; a second nanofiltration step is performed on these recycled mother liquors to form a second permeate and a second retentate; the second permeate is mixed with the D-allulose-enriched composition provided in step c); This mixture is subjected to a concentration step d) to obtain a stock solution which is to be crystallized; and At least a portion of the raffinate and / or mother liquor is flashed. It is characterized by:

[0148] According to an eighth embodiment, the process comprises: a) providing a composition comprising D-fructose; b) an epimerization step to form a composition comprising D-fructose and D-allulose; c) chromatography of this composition to obtain a D-allulose-enriched composition and a raffinate consisting of a D-fructose-enriched composition; d) A concentration step to form a stock solution that is to be crystallized. Including, a recycling step consisting of recycling the raffinate obtained in step c); a first nanofiltration step is performed on the raffinate to provide a first permeate and a first retentate; the first permeate is mixed with the composition comprising D-fructose of step a); the epimerization step b) is carried out on this mixture; the recycling step comprises recycling at least a portion of the mother liquor; These recycled mother liquors are mixed with the D-allulose-rich composition provided in step c); a second nanofiltration step is performed on the mixture to provide a second permeate and a second retentate; This second permeate is subjected to a concentration step d) to obtain a stock solution to be crystallized; and At least a portion of the raffinate and / or mother liquor is flashed. It is characterized by:

[0149] According to a ninth embodiment, the process comprises: a) providing a composition comprising D-fructose; b) an epimerization step to form a composition comprising D-fructose and D-allulose; c) a chromatography step to provide a D-allulose-enriched composition and a raffinate comprising a D-fructose-enriched composition; d) concentrating the D-allulose-rich composition to form a stock solution that is crystallized. Including, a recycling step consisting of recycling the raffinate obtained in step c); a first nanofiltration step is performed on the raffinate to provide a first permeate and a first retentate; the first permeate is mixed with the composition comprising D-fructose of step a); the epimerization step b) is carried out on this mixture; the recycling step comprises recycling at least a portion of the mother liquor; a second nanofiltration step is performed on these recycled mother liquors to form a second permeate and a second retentate; the second permeate is mixed with the composition formed in step b); this mixture is subjected to a chromatography step c); and At least a portion of the raffinate and / or mother liquor is flashed. It is characterized by:

[0150] According to a tenth embodiment, the process comprises: a) providing a composition comprising D-fructose; b) an epimerization step to form a composition comprising D-fructose and D-allulose; c) a chromatography step to provide a D-allulose-enriched composition and a raffinate comprising a D-fructose-enriched composition; d) concentrating the D-allulose-rich composition to form a stock solution that is crystallized. Includes a recycling step consisting of recycling the raffinate obtained in step c); a first nanofiltration step is performed on the raffinate to provide a first permeate and a first retentate; the first permeate is mixed with the composition comprising D-fructose of step a); the epimerization step b) is carried out on this mixture; the recycling step comprises recycling at least a portion of the mother liquor; These recycled mother liquors are mixed with the composition formed in step b); a second nanofiltration step is performed on the mixture to provide a second permeate and a second retentate; this second permeate is subjected to a chromatography step c); and At least a portion of the raffinate and / or mother liquor is flashed. It is characterized by:

[0151] According to an eleventh embodiment, the process comprises the steps of: a) providing a composition comprising D-fructose; b) an epimerization step to form a composition comprising D-fructose and D-allulose; c) a chromatography step to provide a D-allulose-enriched composition and a raffinate comprising a D-fructose-enriched composition; d) concentrating the D-allulose-rich composition to form a stock solution that is crystallized. Including, a recycling step consisting of recycling the raffinate obtained in step c); a first nanofiltration step is performed on the raffinate to provide a first permeate and a first retentate; the first permeate is mixed with the composition comprising D-fructose of step a); the epimerization step b) is carried out on this mixture; the recycling step comprises recycling at least a portion of the mother liquor; These recycled mother liquors are mixed with the composition formed in step b); A chromatography step c) is carried out on this mixture; a second nanofiltration step is performed on the D-allulose-enriched composition resulting from this chromatography step b) to form a second permeate and a second retentate; this second permeate is subjected to a concentration step c); and characterised in that at least a portion of the raffinate and / or of the mother liquor is flashed.

[0152] Without being limiting, the present invention will now be described in detail in the following examples for the purpose of illustrating the advantages of the present invention. EXAMPLES

[0153] Analysis method Gas Chromatography The gas chromatograph used is of the Varian 3800 type, - Slit-slitless injectors (with or without partition); - Flame Ionization Detector (FID); - a computer system for processing the signals from the detector; - Auto Sampler (Type 8400) It is equipped with:

[0154] The various amounts are measured by gas chromatography in the form of methoxylated trimethylsilyl derivatives and then quantified by an internal calibration method.

[0155] Measurement of D-allulose, D-fructose and glucose content The response factors applied are 1.25 for D-allulose and D-fructose and 1.23 for glucose. No other monosaccharides were detected.

[0156] Sample preparation Into a for taring dish, weigh out 100-300 mg of the sample to be tested plus 10 ml of internal standard solution consisting of methyl α-D-glucopyranoside at 0.3 mg / ml in pyridine. Remove 0.5 ml from the for taring dish, place in a 2 ml pot and evaporate to dryness under a stream of nitrogen. Add 20 mg of methoxylamine hydrochloride and 1 ml of pyridine. Stopper and leave in Reacti-therm® incubation system at 70°C for 40 minutes. Add 0.5 ml of N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA). Heat at 70°C for 30 minutes.

[0157] Chromatographic conditions Column: DB1 capillary 40 meters, 0.18 mm internal diameter, 0.4 μm film thickness, composed 100% of dimethylpolysiloxane, non-polar (J&W Scientific reference: 121-1043) Column temperature: 100° C. to 260° C. at a rate of 3° C. / min, then program at 15° C. / min to 300° C., hold at 300° C. for 5 min. Injector temperature: 300℃ Detector temperature: 300℃ (range 10 -12 ) Pressure: 40 psi (constant flow rate) Vector gas: Helium Injection mode: Split (Split flow rate: 100ml / min) Injection volume: 1.0μl

[0158] D-Allulose, D-fructose and glucose were detected in that order. The unknown D-Allulose has a retention time of 39.5 to 40 minutes under these conditions.

[0159] Measurement of D-allulose dimer and glucose-glucose dimer content The applied response factors are 1.15 for D-allulose and D-fructose and 1.08 for isomaltose. No other glucose dimers were detected.

[0160] Sample preparation; Into a weighing pan, weigh out 100-300 mg of the sample to be tested plus 10 ml of internal standard solution consisting of phenyl beta-D-glucopyranoside at 0.3 mg / ml in pyridine. Remove 0.5 ml from the weighing dish, place in a 2 ml pot and evaporate to dryness under a stream of nitrogen. Take up with 0.5 ml of a solution of hydroxylamine hydrochloride at 40 g / l in pyridine, stoppered, stirred and left at 70° C. for 40 minutes. Add 0.4 ml of BSTFA and 0.1 ml of N-trimethylsilylimidazole (TMIM). Heat at 70° C. for 30 minutes.

[0161] Chromatographic conditions Column: DB1 capillary 30 meters, 0.32 mm inner diameter, film thickness 0.25 μm (J&W Scientific reference: 123-1032) Column temperature: 200° C. at a rate of 5° C. / min to 280° C. (hold for 6 min), then program at 5° C. / min to 320° C., hold at 320° C. for 5 min. Injector temperature: 300℃ Detector temperature: 300℃ (range 10 -12 ) Pressure: 14psi (constant flow) Vector gas: Helium Injection mode: Split (Split flow rate: 80ml / min) Injection volume: 1.2μl

[0162] Representation of results The contents of the various constituents, expressed in g per 100 g of crude product, are given by the following formula:

number

[0163] If the resulting percentages (expressed herein on a crude material basis) exceed 20% for one of the constituents, the sample is diluted and GC analysis is recommended to obtain a mass below 20%.

[0164] The mass expressed on a crude basis is then expressed on a dry basis by dividing by the dry matter content of the sample tested.

[0165] The masses of D-allulose, D-fructose and glucose are not characteristic peaks. They do not co-elute and are therefore easily measured.

[0166] The maltose and D-allulose dimer peaks may co-elute, however, it should be pointed out that in the crystals of the present invention and described in the examples below, maltose is never present.

[0167] If no characteristic peak of maltose is detected, the surface area Si of the D-allulose dimer is determined by integration of the unknown peak from 10 to 17 min. If a characteristic peak of maltose is detected, which may be the case for the syrup of the invention, the amount of maltose is determined and this amount is subtracted from the total amount of dimer.

[0168] To measure the total amount of glucose-glucose dimer, the following protocol is performed on the samples: Hydrochloric acid hydrolysis Weigh out approximately exactly 50-500 mg of sample into a 15 ml hydrolysis tube with a Teflon screw cap (adjust the amount according to the expected sugar content) and with two graduated pipettes add 2 ml of internal standard solution (galactitol at 5 mg / ml in osmotic water), 3 ml of water and 5 ml of 4N HCl solution. Seal and stopper, vortex for 1 minute, and place the tube in a constant temperature dry bath regulated at 100°C for 1 hour with occasional vortexing. Desalting and concentration After cooling, place the entire hydrolysate in a 50 ml beaker. Add 6-8 g of a 50 / 50 mixture of AG4 X 4 and AG50 W 8 anion resins. Leave to stir magnetically for 5 minutes. Filter on paper. Recover the liquid and repeat the desalting process until a pH close to that of water is obtained. Sample preparation Into a weighing pan, weigh 100-300 mg of sample to be tested + 10 ml of internal standard solution consisting of methyl α-D-glucopyranoside at 0.3 mg / ml in pyridine. Remove 0.5 ml from the weighing pan and place in a 2 ml pot and evaporate to dryness under a stream of nitrogen. Add 20 mg of methoxylamine hydrochloride and 1 ml of pyridine. Stopper and leave in Reacti-therm® at 70°C for 40 minutes. Add 0.5 ml of BSTFA. Heat at 70°C for 30 minutes.

[0169] The total amount of glucose in the solution (including the initial glucose, referred to as "free", and the glucose resulting from hydrolysis, particularly associated with the presence of maltose and isomaltose) is determined by GC analysis of glucose. The amount of maltose and, by the difference between the total amount of dimers attributed to the peaks at 10-17 min, the amount of D-allulose dimers can be easily inferred therefrom.

[0170] Particle size analysis The volume average size of the crystallites D4,3 value and also the ratio of Feret minimum / Feret maximum diameter are measured with a particle size analyzer of the type QICPIC RODOS of the brand SympaTEC, equipped with its powder (dry process) dispersion module, by following the technical manual and specifications of the manufacturer.

[0171] Implementation of a continuous industrial process for producing D-allulose crystals Example 1 Example 1 consists of a method for the continuous production of D-allulose crystals. The process steps used are detailed in Figure 3. The compositions and flow rates of the streams after stabilization of the process are shown in Tables 1a and It is described in 1b.

[0172] Step 1: A 13.1 metric ton mixture of 26% Fructamyl D-fructose syrup (Tereos) (stream 1) containing 95% D-fructose at 50% dry matter content (DM) and 74% stream 16 at 50 DM was delivered to a 12m 3 The entire mixture (Stream 1') is maintained at 55°C. A lyophilisate of the Bacillus subtilis host strain of D-psicose 3-epimerase enzyme detailed in WO 2015 / 032761 is introduced into the reactor at 2.5 x 10 7 The five reactors are used in series to continuously provide a syrup (stream 2) consisting essentially of fructose and allulose at a flow rate of 1.3 t / h. The reaction conditions are as follows: · Temperature: 55℃ pH=7 · Residence time 48h

[0173] At the end of the reaction, the obtained stream 2 contains D-allulose in a concentration approximately equal to 25% and D-fructose in a concentration approximately equal to 75%.

[0174] Step 2: Stream 2 passes through the microfiltration membrane during batch operation. Stream 3, free of cell debris, is obtained together with the microfiltration retentate (stream 17), containing debris resulting from the Bacillus subtilis lyophilisate, which is flushed from the circuit. The microfiltration parameters are: Transmembrane pressure: 0-3 bar · Pore diameter: 0.1μm · Temperature: 50℃ · Average flow: 15 l / h / m 2 · Membrane: Sepro PS35 Volume concentration factor: 33

[0175] [Table 1]

[0176] [Table 2]

[0177] Step 3: Stream 3 is desalted by passing it over a Dowex 88 strong cation resin and then a Dowex 66 weak anion resin at an average flow rate of 2 BV / h. The carboy is maintained at a temperature of 45° C. and the resistivity of stream 4 at the end of the desalting is 100 kΩ.cm at the outlet (stream 4). -1 If this is not the case, the resin is regenerated.

[0178] Step 4: Stream 4 is mixed with stream 12 (nanofiltration retentate) and with stream 13 (crystallization mother liquor) to form stream 4', which is fed to a circuit of continuous simulated moving bed (SMB) chromatography (SCC ARI® equipped with 8 columns). The feed rate is 1673 kg / h at 50% DM.

[0179] The chromatographic parameters are defined as follows: Volume / column: 2m 3 Resin: Dowex Monosphere 99Ca / 320 · Temperature: 60℃ Flow rate Water / flow 4'(volume / volume): 2.4 Load (supply flow rate / resin volume): 0.09h -1

[0180] Two fractions are withdrawn: the SCC raffinate (stream 14) and a fraction rich in D-allulose (stream 5) which is directed to step 5. 7% of stream 14 is flashed to remove the allulose dimers (stream 15), while the remainder (stream 16) is brought to a dry matter content of 50% by evaporator and then directed again to step 1.

[0181] Step 5: Stream 5 is treated in a nanofiltration facility in batch mode with the following parameters: Transmembrane pressure: 30 bar · Temperature: 20℃ · Membrane: GE Duracon NF1 8040C35 Volumetric Concentration Factor (VCF): 16

[0182] The allulose dimers are concentrated in the retentate (stream 12), which is recycled and mixed with stream 4, while the permeate (stream 6) is recovered. Figure 6 shows the details of the permeation of the syrup as a function of VCF.

[0183] Step 6: Stream 6 passes through a two-stage evaporator whose pressure is below 50 mbar. On leaving the first stage, the stream is at a temperature of 38° C. and has a dry matter content of 35%. On leaving the second stage, the stream reaches a temperature of 48° C. and has a dry matter content of 87%. A stock solution of D-allulose (stream 7) is obtained at the end of this process.

[0184] Step 7a: The raw liquid thus formed (stream 7) is heated to 68°C by the exchanger and then immediately passed through a 3m 3 of working volume into an adiabatic crystallizer-evaporator under vacuum.

[0185] The operating principle of the adiabatic crystallizer-evaporator under vacuum used here is described in detail in FIG. 4: Stream 7a consists of a supersaturated D-allulose syrup at 35°C and fine D-allulose particles. It is mixed with stream 7 in a ratio such that the mixture (stream 7b) is just below the solid solubility limit of the mixture (84% dry matter and 46°C). The fine particles are thus remelted. The masseuse is withdrawn from the adiabatic crystallizer-evaporator at a temperature of 35° C. at the same rate as the mixture so as to keep the level constant in the adiabatic crystallizer-evaporator. This recovered masseuse is separated into two streams: stream 7d and stream 8. Stream 7d is entrained in stream 7b to form stream 7c, which contains the stock solution of D-allulose and also the initiator for crystallization. The mixture ratio is formed in such a way that the solubility (85.5% dry matter and 42.7° C.) is again exceeded so that the crystals can continue their growth. Stream 7c is then introduced into an adiabatic crystallizer-evaporator under vacuum to prolong the crystallization and form a masseuse. The water condensed during this stage is continuously reinjected along the wall at the top of the crystallizer.

[0186] The various streams during the evaporative cooling stage in an adiabatic crystallizer-evaporator under vacuum are reported in Table 2.

[0187] [Table 3]

[0188] Step 7b: The extracted mask is 8m 3 The masseuse is injected at the top of a vertical crystallizer having a working volume of 10 ... 1. 34℃ at the entrance, 32℃ at the exit 2. 31℃ at the entrance, 29℃ at the exit 3. 28℃ at the entrance, 26℃ at the exit 4. 25℃ at the entrance, 22℃ at the exit 5. 21℃ at the entrance, 20℃ at the exit

[0189] Step 8: At the bottom of the crystallizer, the crystal suspension (stream 9) is collected and then centrifuged in a Rousselet Robatel SC 100KSA centrifugal dryer. The crystal suspension can be systematically centrifuged, which means that the process is very stable over time. The mother liquor (stream 13) is recycled and mixed with streams 4 and 12. The moist D-allulose crystals are collected (stream 10). A first clarification with water, then a final clarification with about 0.5% m / m ethanol is performed to improve the separation. The clarified crystals contain 3% water.

[0190] Step 9: The wet crystals are passed through a rotary dryer to obtain dry crystals containing 0.4% water. Final cooling in a fluidized bed reduces the temperature of the crystals from 60° C. to 25° C. The final crystals are recovered (stream 11) and then packaged. The overall yield of D-allulose crystals, which is the ratio of the mass of D-allulose crystals obtained to the mass of D-fructose introduced, expressed in dry mass, is 72%.

[0191] Example 2 Example 2 is identical to Example 1 with the difference that no recycling is performed. Stream 7 contains 0.7% D-allulose dimer. The crystal suspension in stream 9 can be centrifuged over time. Although the total crystal yield is only 12%, the process This has the advantage of being stable, in contrast to the comparative process shown below which does not use a nanofiltration step.

[0192] Comparative Example 1 Comparative Example 1 is identical to Example 1 with the following differences: No nanofiltration process is performed; No mother liquor recycling step is performed; Recycling of the raffinate (stream 14) in its entirety to be mixed with the D-fructose syrup stream 1; The crystallization step is carried out as follows: the formed stock solution (stream 7) is mixed with 8 ml of the same solution as that used for the crystallization step 7b of Example 1. 3 The D-allulose is introduced into each crystallizer in turn, with a working volume of 1000 ml. The cooling gradient is 0.33 ° C / h up to 20 ° C. An initiator of D-allulose with a D4,3 approximately equal to 60 μm is introduced into each crystallizer in a mass of 0.1% (this amount is expressed relative to the dry weight of D-allulose introduced into the crystallizer).

[0193] The manufacturing circuit used (i.e. the various steps of the process used) corresponds to FIG.

[0194] Stream 7 contains 1.9% D-allulose dimer. Stream 9 is collected and taken to step 8. Stream 9 is a massecuite that is not necessarily centrifugable. At the end of one week, stream 7 contains 2.2% D-allulose dimer and the massecuite of stream 9 is even systematically impossible to centrifuge (crystals too small in size).

[0195] Comparative Example 2 Comparative Example 2 is identical to Comparative Example 1 with the difference that the mother liquor (stream 13) is recycled in its entirety so as to be mixed with the D-allulose-rich composition (stream 5) resulting from the chromatography step, and the raffinate (stream 14) is not recycled but is flushed from the circuit.

[0196] The manufacturing circuit used corresponds to FIG.

[0197] Stream 7 contains 1.9% D-allulose dimers. Stream 9 is recovered and taken to step 8. This stream 9 is a massecuite that is not necessarily centrifugable. From the moment the mother liquor is recycled, stream 7 contains 2.4% D-allulose dimers and the massecuite of stream 9 is even systematically impossible to centrifuge (crystals too small in size).

[0198] Comparative Example 3 Comparative Example 3 is identical to Comparative Example 1 with the difference that the raffinate is not recycled.

[0199] The manufacturing circuit used corresponds to FIG.

[0200] Stream 7 contains 1.9% D-allulose dimer. Stream 9 is recovered and taken to step 8. This stream 9 is a massecuite that is not necessarily centrifugable. If it is centrifugable, the mother liquor separates from the allulose crystals that can be recovered. However, sometimes stream 9 consists of a large amount of small unseparable crystals, which is synonymous with spontaneous nucleation in a crystallizer. In that case, it is necessary to take this stream out of the circuit. This makes the process industrially unusable.

[0201] A summary of the results obtained for these processes is reported in Table 3. All yields reported are averaged over one week of use.

[0202] The characteristics of the crystals obtained for Examples 1 and 2 and Comparative Example 3, and also of the D-allulose crystals sold by the company CJ Cheiljedang Food Ingredients, are reported in Table 4.

[0203] [Table 4]

[0204] The process of the present invention makes it possible to obtain a crystallization that is stable over time, as demonstrated in the above-exemplified industrial process (Examples 1 and 2). It also makes it possible to perform very sufficient recycling, thus increasing the overall yield of D-allulose crystals (see Example 2). By performing recycling without ensuring the separation of D-allulose dimers using a nanofiltration step, the above exemplary comparative examples 1 and 2 demonstrate that the industrial crystallization process must be stopped because the masseuse cannot be centrifuged systematically (crystals too small in size).

[0205] [Table 5]

[0206] FIG. 14, which shows the ratio of the Feret minimum / Feret maximum diameter as a function of the volumetric particle size D4,3 for the D-allulose crystals of Example 2 and the D-allulose crystals sold by CJ, demonstrates that a clear difference in appearance is observed between the crystals according to the invention and the comparative crystals for the large size populations of 200 μm or more (for example in the range of 200-400 μm). Thus, in this range of 200-400 μm, the Feret minimum / Feret maximum ratio is always less than 0.55 for the comparative crystals, while the crystals according to the invention have a ratio of at least 0.63. This difference is in full agreement with the optical microscope images of FIGS. 11 and 12, which visually demonstrate that the crystals according to the invention have a much chunkier appearance than the comparative crystals. With regard to the CJ crystals in FIG. 13 (optical microscope image), it is noted that they are needle-shaped crystals that are not individualized.

[0207] Comparative Example 3 is not strictly the same as the teaching of WO 2011 / 119004 A2 with regard to the concentration step (especially in that the applicant succeeded in carrying out the concentration step more optimally so as to further reduce the amount of D-allulose dimer formed), but the crystals obtained use the same process as that used to produce the crystals described in Example 6 of WO 2011 / 119004 A2 (especially with regard to the crystallization carried out exclusively by controlled cooling in water). This Comparative Example 3, which produces crystals containing 0.7% D-allulose dimer, therefore fully demonstrates that WO 2011 / 119004 A2 does not allow the crystals of the present invention to be formed.

[0208] Use of the crystals of the present invention in various applications The crystals of Example 2 were used in the preparation of the following products:

[0209] Manufacturing of meal replacement drinks The objective is to create a powdered meal replacement beverage that contains fewer calories. This powdered beverage must be able to exhibit good flowability and form few lumps when it is dispensed.

[0210] [Table 6]

[0211] After being weighed out, the ingredients are vigorously mixed in a dry mixer. The beverage is then easily reconstituted by adding 210 g of water to 30 g of the formulation without the formation of lumps.

[0212] Formulations using the crystals of the present invention have flow behavior completely similar to formulations containing sucrose, while at the same time containing far fewer calories.

[0213] Yellow cake production The objective is to provide a yellow cake having a pleasing texture and appearance whose caloric content is reduced by 25%.

[0214] [Table 7]

[0215] method: 1. Mix flour, salt, Nutriose® and yeast. 2. Cream the butter with sucrose or allulose. 3. Add egg yolks and vanilla to the cream, then add milk to form a creamy mixture. 4. Add the powder mixture to the creamed mixture and mix on a slow setting (1 minute), then mix more vigorously until the formulation is well mixed. 5. Pour 600g of paste into a 9-inch greased circular mold. 6.Bake at 180℃ for 20 minutes.

[0216] This object is achieved: cakes using the crystals of the invention have a very pleasant texture in the mouth (the term "crumb texture" is used) and the cake keeps its shape after baking.

[0217] Chocolate cookie manufacturing The following formulations were prepared:

[0218] [Table 8]

[0219] method: 1. Mix the dry ingredients together. 2. Cream the butter with the sugar or allulose. 3. Add eggs and vanilla to creamed mixture. 4. Add the powder mixture to the creamed mixture and mix on a slow setting (1 minute), then mix more vigorously until the formulation is well mixed. 5. Add chocolate chips and mix. 6. Weigh out 30g portions and bake at 160°C for 8 minutes.

[0220] The allulose-based cookie dough (row 2) spreads less than the sugar-based dough (row 1). However, the dough in row 3 spreads similarly to the dough in row 1.

[0221] During baking, the allulose-based cookies brown faster.

[0222] It should be pointed out that the cookies have a dome shape, the height of the cookies according to the invention is less bulging and said cookies, unlike sugar-based cookies, do not collapse after baking, thereby preserving a better appearance.

[0223] The allulose-based cookies have a good taste, although they are not very sweet. The texture of the cookies according to the invention is soft and moister than sugar-based cookies.

[0224] The water activity (wa) and moisture content (M) of the cookies are measured over time:

[0225] [Table 9]

[0226] Allulose-based cookies show better stability with respect to moisture.

[0227] Oat flake cookie manufacturing

[0228] [Table 10]

[0229] method: 1. Mix flour, Nutriose®, baking soda, yeast and salt. 2. Cream the butter with the sugar or allulose. 3. Add eggs and vanilla to creamed mixture. 4. Add the powder mixture to the creamed mixture and mix on a slow setting (1 minute), then mix more vigorously until the formulation is well mixed. 5. Add oat flakes and mix. 6. Add inclusions and mix. 7. Weigh out 30g portions and bake at 160°C for 10 minutes.

[0230] The cookies obtained using allulose instead of sugar brown slightly better and have a crisper texture after baking.

[0231] Bubble gum manufacturing Bubble gum was produced according to the following recipe:

[0232] [Table 11]

[0233] The bubble gum has a completely pleasing appearance similar to commercial bubble gum.

Claims

1. providing a composition enriched in D-allulose; - concentrating said solution to form a stock solution that is to be crystallized; crystallizing the stock solution to form D-allulose crystals and a mother liquor; at least one nanofiltration step, which is carried out prior to the step of concentrating the D-allulose-enriched composition; A process for producing D-allulose crystals comprising:

2. 2. The process according to claim 1, characterized in that the membrane used for the nanofiltration has a cut-off threshold of less than 300 Da, preferably in the range of 150-250 Da.

3. The resulting stock solution has a dry mass of: - 80% to 99%, preferably 85% to 98% D-allulose; - 0% to 20%, preferably 0.5% to 15% D-fructose; - 0% to 10%, preferably 0% to 5% glucose; 0% to 1.5%, for example 0.1% to 1.2%, preferably 0.4% to 1.1% D-allulose dimer 3. The process according to claim 1 or 2, characterized in that it comprises:

4. 4. The process according to claim 1, wherein the volumetric concentration factor of the nanofiltration is in the range of 5 to 20.

5. The crystallization step comprises: i. an adiabatic evaporative cooling step carried out in an adiabatic crystallizer-evaporator under vacuum to form a masseuse; ii. followed by a crystallization step by cooling said masseuse to form crystals. The process according to any one of claims 1 to 4, characterized in that it comprises

6. 6. A process according to claim 5, characterised in that the temperature during the adiabatic evaporative cooling stage is in the range of 30 to 40°C, preferably in the range of 33 to 37°C, for example around 35°C.

7. A process according to any one of claims 1 to 6, characterized in that it is continuous.

8. A process according to any one of claims 1 to 7, characterised in that it comprises at least one recycling step.

9. The process according to any one of claims 1 to 8, characterized in that it comprises a step of recycling at least a part of the mother liquor.

10. The step of providing the stock solution of D-allulose comprises: providing a composition enriched in D-allulose; nanofiltration of the composition enriched in D-allulose to obtain a retentate and a permeate; - recovering the nanofiltration permeate; concentrating the permeate to provide said stock solution of D-allulose. The process according to any one of claims 1 to 9, characterized in that it comprises

11. 2. The process of claim 1, further comprising recycling at least a portion of the retentate. The process described in 0.

12. Providing the composition enriched in D-allulose comprises: providing a composition comprising D-fructose; epimerizing to form a composition comprising D-fructose and D-allulose; Chromatographic steps to provide a D-allulose-enriched composition and a D-fructose-enriched composition.

12. The process according to claim 10 or 11, characterized in that it comprises

13. 13. The process according to claim 12, characterized in that it comprises a step of recycling at least a portion of the composition enriched in D-fructose.

14. 14. The process according to claim 13, characterized in that the degree of recycling of the composition enriched in D-fructose ranges from 50% to 95%.

15. D-allulose crystals having a mass content of D-allulose dimers, as measured by gas chromatography (GC), of less than 0.50%.

16. D-allulose crystal according to claim 15, characterized in that it contains a mass content of D-allulose dimers in the range of 0.01% to 0.48%, preferentially in the range of 0.02% to 0.45%, for example in the range of 0.03% to 0.40%, in particular in the range of 0.04% to 0.30%.

17. D-allulose crystals according to claim 15 or 16, characterized in that they have a volume average size D4,3 greater than 200 μm, advantageously in the range from 210 to 800 μm, preferentially from 220 to 350 μm.

18. D-allulose crystals according to any one of claims 15 to 17, characterized in that for a given volume particle size D4,3 chosen in the range of 200 to 400 μm, they have a Feret min / Feret max ratio of greater than 0.60, preferably in the range of 0.62 to 0.90, for example 0.63 to 0.

80.

19. D-allulose crystals according to claim 17, characterized in that they have this Feret minimum / Feret maximum ratio over the entire volume particle size D4,3 range of 200 to 400 μm.

20. Use of a nanofiltration unit in a production circuit for D-allulose crystals to improve the overall yield of D-allulose crystals.

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