WO2022239028A1

WO2022239028A1 - A method and system for purifying d-allulose, fructose, and/or glucose

Info

Publication number: WO2022239028A1
Application number: PCT/IN2022/050453
Authority: WO
Inventors: Rahul Raju KANUMURU; Muthuvaduganathan NAGASUNDRAM; Binay Kumar Giri
Original assignee: Petiva Pvt Ltd
Current assignee: Petiva Pvt Ltd
Priority date: 2021-05-08
Filing date: 2022-05-08
Publication date: 2022-11-17
Anticipated expiration: 2023-11-08
Also published as: EP4352070A4; EP4352070A1

Abstract

The present disclosure relates to a system and method for separating and/or purifying D-allulose from a ternary mixture.

Description

Title A METHOD AND SYSTEM FOR PURIFYING D-ALLULOSE, FRUCTOSE,

AND/OR GLUCOSE

RELATED APPLICATION

This application claims the benefit of Indian provisional patent application number 202141007150 filed on May 08, 2021.

TECHNICAL FIELD

The present subject matter disclosed herein, in general, relates to a process and system for purifying allulose from a mixture obtained in the production of allulose from a sugar source such as sucrose by heterogeneous or homogeneous catalysis which includes chemical and/or enzymatic catalysis.

BACKGROUND

D-allulose (known as D-psicose), a rare sugar and C-3 epimer of fructose, is an ideal sugar substitute and has sweetness similar to dextrose or 70 % to sucrose. Allulose is when metabolized by a human body, does not raise blood sugar or insulin levels, and provides minimal calories. A caloric value of allulose is 0.2 kcal per gram and prevents the formation of body fat. Further, it has been reported that allulose is non-cariogenic. Thus, allulose is of great interest in the nutraceutical applications.

Although, allulose attracts the attention for its properties, however its utilization is restricted due to its scarce availability in nature and difficulty in current production methods and systems.

Allulose can be produced by chemical or enzymatic processes. The processes for preparing allulose from a sugar source, preferably from fructose, according to the prior art are not satisfactory in every aspect and there is a need for improvements, and there is presently no industrially applicable method for producing D-allulose.

Conventionally, a simulated moving bed chromatography (SMB) is used for producing allulose from sucrose in a continuous process. It is known that the conventional four zone SMB can successfully separate binary mixtures but cannot separate a multicomponent mixture in three different fractions which constitutes a major drawback. As a result, two SMB systems are required for the separation of ternary mixtures. Further, the conventional process is very complicated with several recycle loops. Furthermore, additional three SMB systems are required (i) for separation of glucose and fructose (ii) for separation of fructose and allulose and (iii) for the separation of glucose from fructose in the purge line, thereby increasing complexity and capital cost. There is considerable amount of loss in the process as purge streams have to be considered for the SMB’s to prevent residual impurity build up due to continuous recycling and the recycling streams increase the capacity of the SMBs. Thus, synchronization of the plant is very difficult because of the recycle and purge streams. Further, an evaporation load is very high because an extract and raffinate fractions from the SMBs are diluted. This would increase steam requirement considerably resulting in higher operational cost. Moreover, additional unit operations like ion exchange and decolorization are required to feed the material to the SMBs

Hence, there need exists for a system and method to seek to mitigate one or more above shortcomings. Consequently, those skilled in the art will appreciate the present disclosure that provides many advantages and overcomes all the above and other limitations.

SUMMARY OF THE DISCLOSURE

The present disclosure relates to a method and a system for purifying D-allulose from a sugar mixture (ternary mixture).

In an aspect, the present disclosure relates to a system for purifying allulose from a ternary mixture, the system comprises: a continuous simulated moving bed (SMB) apparatus having at least eight columns positioned adjacent to each other and fluidly connected in series forming a closed loop configuration, wherein each column of the eight columns is defined with a feed port, a first eluent port, a second eluent port, a first extract port, a second extract port and a first raffinate port and a second raffinate port; a feed tank containing a ternary sugar mixture fluidly connected to the each of the eight columns, wherein the feed tank being configured to continuously feed the ternary sugar mixture into at least one of the eight columns through the feed port in the at least one of the eight columns, and wherein the ternary sugar mixture comprises allulose, one or more isomers of allulose, and optionally, one or more additional sugars; at least one eluent tank containing eluent fluidly connected to the each of the eight, wherein at least one eluent tank being configured to continuously feed the eluent into at least one of the columns of the eight columns through the first eluent port and the second eluent port in the at least of column of the eight columns; a raffinate tank fluidly connected to the each of the eight columns, wherein the raffinate tank being configured to continuously withdraw a second raffinate from at least one of the eight columns through the second raffinate port, wherein the first raffinate port in fluid communication with each column of the eight columns is configured to continuously withdraw and circulate a first raffinate into each column via a raffinate inlet port; a first extract tank and a second extract tank fluidly connected to the each of the eight columns, wherein the first extract tank and the second extract tank being configured to continuously withdraw a first extract and a second extract, respectively from at least one of the eight columns by the first extract port and the second extract port, wherein the second extract comprises purified allulose, wherein feeding of the ternary sugar mixture, the first eluent and the second eluent into the each of the eight columns, and withdrawal of the first extract, second extract, and the second raffinate and circulation of the first raffinate from the eight columns, are incremented in series towards adjacent columns, at a predetermined time intervals.

In a further aspect, the present disclosure relates to a method for purifying allulose from a mixture in a continuous simulated moving bed (SMB) apparatus comprising at least eight columns connected in series with a closed loop configuration and containing a resin; said process comprises: a) providing a feed mixture comprising the allulose, one or more of its isomers, and one or more sugars other than the allulose or its isomer; b) simultaneously, i) feeding a feed mixture from a feed tank into a column; ii) feeding a first eluent from an eluent tank into a column, wherein the column is separated by two columns from the column of step i); iii) feeding a second eluent into a column, wherein the column is separated by six columns from the column of step i); iv) withdrawing from the column of step i) a first raffinate; v) feeding the first raffinate of step iv) into a column, wherein the column is separated by four columns from the column of step i); vi) withdrawing a first extract from the column which is separated by two columns from the column of step i); wherein the first extract comprises one or more isomers of allulose; vii) withdrawing a second extract from the column which is separated by six columns from the column of step i); wherein the second extract comprises allulose in pure form; and viii) withdrawing a second raffinate from the column which is separated by four columns from the column of step i); wherein the second raffinate comprises one or more sugars other than the allulose and its isomer; and c) switching periodically the feed stream, first raffinate, second raffinate, first eluent, second eluent, first extract and second extract forward one column position at a time in the direction of the flow.

In yet another aspect, the present disclosure relates to a process for producing pure D-allulose from a sugar source, the process comprises:

(i) mixing the sugar source with water or with an aqueous liquid and adjusting the concentration of dissolved sugar (such as sucrose) thereby providing a first solution of sugar source;

(ii) converting sugar source to glucose and fructose thereby providing a second solution comprising glucose and fructose;

(iii) converting product(s) of the first solution, fructose, to a corresponding second sugar product(s), allulose;

(iv) separating sugar products of the second solution by an integrated simulated moving bed (SMB) chromatography thereby providing fraction 1 (rich in glucose), fraction 2 (rich in fructose) and fraction 3 (rich in allulose);

(v) producing liquid allulose or solid allulose from the fraction 3; (vi) converting glucose present in fraction 1 to fructose thereby providing a third solution comprising glucose and fructose;

(vii) returning the fraction 2 (rich in fructose) and the third solution to step (ii); and (viii) reiterating steps (ii) to (vii).

The foregoing summary is illustrative only and is not intended to be in any way limiting. In addition to the illustrative aspects, and features described above, further aspects, embodiments, and features will become apparent by reference to the drawings and the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

The novel features and characteristics of the disclosure are explained herein. The embodiments of the disclosure itself, however, as well as a preferred mode of use, further objectives and advantages thereof, will best be understood by reference to the following detailed description of an illustrative embodiment when read in conjunction with the accompanying drawings. One or more embodiments are now described, by way of example only, regarding the accompanying drawing in which:

Figure 1 illustrates a system for purifying allulose of the present disclosure;

Figure 2 schematically illustrates a process for producing allulose according to an embodiment of the present disclosure; Figure 3 illustrates elution profile second extract (allulose fraction) in accordance with an example of the present disclosure;

Figure 4 illustrates elution profile of first extract 1 (fructose fraction) in accordance with an example of the present disclosure; and

Figure 5 illustrates elution profile of raffinate (glucose fraction) in accordance with an example of the present disclosure.

The figures depict embodiments of the disclosure for purposes of illustration only. One skilled in the art will readily recognize from the following description that alternative embodiments of the structure and mechanism illustrated herein may be employed without departing from the principles of the disclosure described herein.

DETAILED DESCRIPTION

The foregoing has broadly outlined the features and technical advantages of the present disclosure in order that the detailed description of the disclosure that follows may be better understood. Additional features and advantages of the disclosure will be described hereinafter. It should be appreciated by those skilled in the art that the conception and specific embodiment disclosed may be readily utilized as a basis for modifying or designing other assemblies for carrying out the same purposes of the present disclosure. The novel features which are believed to be characteristic of the disclosure, both as to its organization and method of operation, together with further objects and advantages will be better understood from the following description when considered in connection with the accompanying figures. It is to be expressly understood, however, that each of the figures is provided for the purpose of illustration and description only and is not intended as a definition of the limits of the present disclosure.

Before the present invention is described in greater detail, it is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

Certain ranges are presented herein with numerical values being preceded by the term "about." The term "about" is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described.

The terms “comprise”, “comprises”, “comprising”, or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a setup, device or method that comprises a list of components or steps does not include only those components or steps but may include other components or steps not expressly listed or inherent to such setup or device or method. In other words, one or more elements in a system or apparatus proceeded by “comprises... a” does not, without more constraints, preclude the existence of other elements or additional elements in the system or apparatus.

The present disclosure relates to a method and a system for purifying D-allulose from a ternary mixture. In an embodiment, the present disclosure relates to a method and a system for purifying D-allulose from a mixture obtained in the production of D-allulose from a sugar source such as sucrose. The process for producing D-allulose from sugar source comprises the steps of: (i) mixing the sugar source with water or with an aqueous liquid and adjusting the concentration of dissolved sugar, preferably sucrose thereby providing a first solution of sugar source;(ii) converting sucrose to glucose and fructose, under heterogeneous or homogeneous catalysis which includes chemical and/or enzymatic catalysis thereby providing a second solution comprising glucose and fructose; and(iii) converting fructose of the second solution to D-allulose under enzymatic catalysis thereby providing a mixture comprising glucose, fructose and allulose. The detailed procedure for the conversion of sucrose to glucose, and fructose to allulose is well known in the art.

The system generally identified by reference numeral 100. The system 100 is more particularly, but not exclusively used for separating sugars and to obtain about 80% to about 98% allulose from a ternary mixture. It is believed that those skilled in the art will readily recognize that as the description proceeds, such systemlOO may be utilized also for obtaining allulose continuously from a mixture comprising the allulose, one or more isomers of allulose, and one or more additional sugars. The systemlOO comprises of a feed tank 10, at least one eluent tank 20, and a simulated moving bed chromatographic (SMB) apparatus 30.

As illustrated in figure 1, the system 100 comprises a feed tank 10 configured to store the ternary mixture [interchangeably referred as “mixture”]. The ternary sugar mixture comprises allulose, one or more isomers of allulose, and one or more additional sugars. The feed tank 10 is in fluid communication with each of eight columns of the simulated moving bed chromatographic (SMB) apparatus 30. The feed tank 10 is configured to continuously feed the mixture into at least eight columns of the SMB apparatus 30. In an embodiment, the mixture is supplied to each of the eight columns via at least one pump 11. Further, the feed tank 10 is in fluid flow communication with an auxiliary pre -heater 12. The auxiliary pre-heater 12 is disposed between the feed tank 10 and the at least eight columns. The auxiliary pre-heater 12 is used for heating the mixture to a desired temperature prior to supplying the mixture into the SMB apparatus 30. In an embodiment, the desired temperature of the mixture may be heated to about 50-70 °C.

The system 100 further comprises at least one eluent tank 20 to store eluent. In an aspect of the present disclosure, the eluent any eluent suitable in the process or system can be used. In an aspect of the present disclosure, the eluent may be water and or any other eluent that meets the requirement. The eluent tank 20 is in fluidly connected to each of the eight columns of with the SMB apparatus 30. The eluent tank 20 is configured to continuously feed the eluent into at least one of the eight columns of the SMB apparatus 30. The eluent is supplied at least one of the eight columns via at least one first pump 21 and at least one second pump 22 as shown in Figure 1. In an embodiment, the eluent tank 20 is in fluid flow communication with a first pre-heater 23 via at least one first pump 21. The first preheater 23 is configured to heat the eluent at a first predetermined temperature before the eluent is supplied to at least one of the eight columns of the SMB apparatus 30. Further, the eluent tank 20 is in fluid flow communication with a second pre-heater 24 via at least one second pump 22. The second preheater 24 is configured to heat the eluent at a second predetermined temperature before this eluent is supplied to at least one of the eight columns of the SMB apparatus 30. In an embodiment, the first and second predetermined temperature of the eluent may be heated of about 50-70 °C using the first preheater and the second preheater, respectively. In certain embodiments, due to high flow rate of diluents/eleuents, desired process temperature may not be achieved if a single pre-heater is used. So, in some instances, multiple preheaters may be required to attain desired process temperature.

The system 100 comprises a raffinate tank 60 fluidly connected with each of the eight columns of the SMB apparatus 30. The raffinate tank 60 is configured to continuously withdraw the raffinate from at least one of the eight columns via a second raffinate port lj to 8j of the SMB apparatus 30. The second raffinate is withdrawn from at least one of the eight columns via at least one pump 61 as shown in Figure 1. In an aspect of the present disclosure, the second raffinate comprises one or more isomers of allulose. In an embodiment, the second raffinate comprises glucose which is about 70-100%pure. Further, a first raffinate port lk to 8k is in fluid communication with each column of the eight columns. The first raffinate port lk to 8k is configured to continuously withdraw and circulate a first raffinate into each of the eight columns via a raffinate inlet port If to 8f.

The system 100 includes a first extract tank 40 and a second extract tank 50 fluidly connected to each of the eight columns of the SMB apparatus 30. The first extract tank 40 is configured to continuously withdraw a first extract from at least one of the eight columns via a first extract port lh to 8h. The first extract is withdrawn from at least one of the eight columns via at least one pump 41 as shown in Figure 1. In an aspect of the present disclosure, the first extract comprises fructose which is about 80-100% pure. Similarly, the second extract tank 50 is configured to continuously withdraw a second extract from at least one of the eight columns via a second extract port li to 8i. The second extract is withdrawn from at least one of the eight columns via at least one pump 51. In an aspect of the present disclosure, the second extract comprises allulose which is about 90-100 % pure.

The system 100 comprises the continuous simulated moving bed (SMB) apparatus 30. The SMB apparatus 30 includes at least eight columns positioned adjacent to each other and are fluidly connected in series forming a closed loop configuration. Referring to Figure 1, the columns include a first column Cl, a second column C2, a third column C3, a fourth column C4, a fifth column C5, a sixth column C6, a seventh column C7 and an eighth column C8. The columns Cl to C8 are connected to each other in series and further the eighth column C8 is connected to first column Cl to form the closed loop configuration. Further, each of the columnsCl to C8 contains a resin. The SMB apparatus 30 employs a chromatographic separation system to obtain the D-allulose. Each of the column Cl to C8 of the SMB apparatus 30 is configured vertically. The columns Cl to C8 may have hollow elongated structure to enclose the resin bed and securely support other components required to perform chromatographic separation to obtain a required product. In certain embodiments, the resin is any suitable resin which may be known to a skilled person and commercially available can be used. In some instances, the resin is cation exchange resin. The resin bed provided in each column Cl to C8 is configured to react with the mixture when supplied by the feed tank 10.

Each of the eight columns Cl to C 8 is surrounded by a jacket lg. The jacket aids in maintaining a required temperature within the each of the eight columns Cl to C8. The jacket lg encloses the column Cl to C8.

Further, each of the eight column Cl to C8 is defined with a first end la, 2a, 3a, 4a, 5a, 6a, 7a and 8a and a second end lb, 2b, 3b, 4b, 5b, 6b, 7b and 8b. The first end la to 8a of each column comprises a feed port lc, 2c, 3c, 4c, 5c, 6c, 7c. 8c, a first eluent port Id, 2d, 3d, 4d, 5d, 6d, 7d, 8d and a second eluent port le, 2e, 3e, 4e, 5e, 6e, 7e and 8e. The feed port la to 8a of each column Cl to C8 is in fluid flow communication with the feed tank 10 for supplying the mixture from the feed tank 10 via the auxiliary preheater 12 at the desired temperature. Further, the first eluent port lb to 8b of each column Cl to C 8 is in fluid flow communication with the eluent tank 20 via the first pre-heater 23 to receive eluent at the first predetermined temperature. Furthermore, the second eluent port lc to 8c is in fluid communication with the eluent tank 20 via the second preheater to receive eluent at the second predetermined temperature. Each column of the eight columns Cl to C8 comprises at least one inlet valve manifolds fluidly connected to the each of the feed port lc to 8c, the first eluent port Id to 8d, the second eluent port le to 8e, and the raffinate inlet If to 8f for selectively receiving the ternary sugar mixture, the first eluent, the second eluent and the first raffinate from the feed tank 10, the eluent tank 20, and the first raffinate from the first raffinate port lk to 8k, respectively.

Each column of the eight columns Cl to C8 further comprises a first extract port lh to 8h, a second extract port li to 8i, and the second raffinate port lj to 8j disposed at the second end lb to 8b of each columnCl to C8 to continuously obtain the first extract, the second extract, and the second raffinate, respectively. In an embodiment, the first extract port lh to 8h is in fluid flow communication with at least one first extract tank 40 via at least one pump 41, such that the first extract tank 40 receives the first extract. In an embodiment, the second extract port li to 8i is in fluid flow communication with at least one second extract tank 50 to via at least one pump 51, such that the second extract tank 50 receives the first extract. The first extract comprises fructose which is about 80-100% pure, the second extract comprises allulose which is about 90-100% pure. Further, the second raffinate comprises glucose which is about 70-100% pure. The second raffinate port lj to 8j is in fluid flow communication with at least one raffinate tank 60 to via at least one pump 61, such that the raffinate tank receives the second raffinate from the columns Cl to C8. The second raffinate comprises glucose. The column Cl to C8 also includes a first raffinate port lk to 8k that is in fluid flow communication with each column Cl to C8. The first raffinate port lk to 8k dispenses and circulates predetermined quantity of first raffinate to each column Cl to C8 via the raffinate inlet If to 8f disposed at the first end la to 8a of each column Cl to C8. Further, the first raffinate port lk to 8k of each column Cl to C8 dispenses and circulates the first raffinate to each column Cl to C8 via at least one recycle pump 70. In an embodiment, each column of the eight columns Cl to C8 comprises at least one outlet valve manifolds fluidly connected to each of the first raffinate port lk to 8k, second raffinate port lj to 8j, the first extract port lh to 8h and the second extract port li to 8i for selectively withdrawing and control or regulate supply or withdrawal of the first raffinate, second raffinate, the first extract and the second extract into the raffinate tank and extract tank, respectively.

These inlet valve manifolds, and the outlet valve manifolds being located in immediate vicinity of each column to control or regulate the supply of at least one of the mixtures, first eluent, second eluent, first raffinate, second raffinate from the feed port, the first eluent port, the second eluent port, the raffinate inlet port, the first extract port, the second extract port, the first raffinate port and the second raffinate port. In an embodiment the control valves may be manually operated or actuator-controlled e.g., programmable logic controller (PLC).

In an embodiment, the first pre heater 23, the second pre heater 24 and the auxiliary pre heater 12 comprises at least one temperature sensor 80 to detect the temperature of the first eluent, the second eluent and the mixture that is supplied to the at least one of the eight columns of the SMB apparatus 30.

In another embodiment, the system 100 includes an auxiliary tank 85 to store and circulate a fluid, at a fourth predetermined temperature, into jackets lg to 8gsurroundingthe columns Cl to C8. The circulation of the fluid at the fourth pre determined temperature into the jacket lg to 8g aids in maintaining the temperature within the column Cl to C8. The fluid may be water, or any suitable fluid known in the art. Further, the fourth pre-determined temperature of the fluid is about 50-60 °C.

Further, the system 100 comprises at least one refractive index detector 86 coupled to each column Cl to C8 to detect and monitor properties of the eluent and the mixture within each column Cl to C 8. In an embodiment, the properties of the eluent and the mixture may include, temperatures, concentrations, viscosity, flow rate, quantity, time period and the like.

The system 100 includes controller communicatively coupled to at least one pump (11, 41, 51, 61), the at least one first and second pump (21, 22), the recycle pump 70, at the least one temperature sensor 85. The controller actuates the at least one pump 11, 41, 51, 61 to supply the mixture, the first and second eluent first raffinate and the fluid into each column Cl to C8 from the feed tanks, eluent tank and the pumps are actuated to collect first extract, second extract and the second raffinate into first extract tank, second extract tank and raffinate tank, respectively. The controller is coupled to the at least one temperature sensor and the refractive index detector 86 to detect temperature and the properties of the feed and the eluent supplied to each column Cl to C8. Further, the controller is in connected with at least one display unit (not shown in Figures) for displaying the detected parameters such as temperature, properties etc of the feed and the eluent.

In an embodiment, the feeding of the ternary sugar mixture and the first and the second eluent and the first raffinate into the eight columns Cl to C8, and withdrawal of the first and second extract and the first and second raffinate from the eight columns Cl to C8, are incremented in series towards adjacent columns, at a predetermined time intervals. Further, the present disclosure provides a method of purifying the allulose from a mixture. More specifically, the method is used for separating sugars in order to obtain about 80% to about 98% of allulose from the mixture. In an embodiment, the mixture is a ternary mixture. In an embodiment, the mixture comprises allulose, one or more isomers of allulose, and one or more additional sugars.

The method for purifying allulose from the mixture comprises the steps of initially providing the mixture comprising the allulose, one or more of its isomers, and one or more further sugars. Simultaneously, the mixture is continuously introduced through a feed inlet into a simulated moving bed chromatographic (SMB) apparatus 30 comprising at least eight columns Cl to C8inter-connected in series with a closed loop configuration and containing a stationary phase. Further, a first eluent of a first pre-determined temperature is continuously fed into the SMB apparatus 30 through a first eluent inlet. Simultaneously, a second eluent of a second pre-determined temperature is continuously feed into the SMB apparatus 30 through a second eluent inlet. Subsequently, a first extract is continuously withdrawn through a first outlet. Simultaneously, a first raffinate is continuously withdrawn through a fourth outlet. The obtained first raffinate is introduced continuously to the SMB apparatus through a raffinate inlet. Consecutively, a second extract is continuously withdrawn from the SMB apparatus through a second outlet. Further, a second raffinate is continuously withdrawn from the SMB apparatus through a third outlet such that the first extract comprises glucose and the second extract comprises the purified allulose which is at least about 95% pure. In certain embodiments, thepresent disclosure provides a method for purifying allulose from a mixture in a continuous simulated moving bed (SMB) apparatus comprising at least eight columns connected in series with a closed loop configuration and containing a resin. The process comprises the steps of: a) providing a feed mixture comprising the allulose, one or more of its isomers, and one or more sugars other than the allulose or its isomer; b) simultaneously, i) introducing a feed mixture from a feed tank into a column through a feed inlet; ii) introducing a first eluent from an eluent tank into a column, wherein the column is separated by two columns from the column of step i); iii) introducing a second eluent into a column, wherein the column is separated by six columns from the column of step i); iv) withdrawing from the column of step i) a first raffinate; v) introducing the first raffinate of step iv) into a column, wherein the column is separated by four columns from the column of step i); vi) withdrawing a first extract from the column which is separated by two columns from the column of step i); wherein the first extract comprises one or more isomers of allulose; vii) withdrawing a second extract from the column which is separated by six columns from the column of step i); and viii) withdrawing a second raffinate from the column which is separated by four columns from the column of step i); wherein the second raffinate comprises one or more sugars other than the allulose or its isomer.

In the method, the inlet connections to which the feed is fed and the outlet connections from which the outlet streams are withdrawn may be periodically moved from their respective columns to adjacent columns. Thus, the method may comprise switching periodically the feed stream, first raffinate, second raffinate, first eluent, second eluent, first extract and second extract forward one column position at a time in the direction of the flow. The switching time and liquid phase flow rates in each column are chosen properly to achieve a ternary separation. In certain embodiments, the switching time is about 50-160 minutes, or about 50-150 minutes. In certain embodiments, the switching time is about 80-90 minutes. In further embodiments, the switching time is about 80-85 or about 85-90 minutes. In certain embodiments, the average feed flow rate is about 50-80 ml/min. In further embodiments, the average feed flow rate is about 65-75 ml/min or about 70-75 ml/min. In certain embodiments, average flow rate of first eluent (diluent-1) is about 100-300 ml/min, about 150-250 ml/min, about 150-200 ml/min, or about 150-190 ml/min. In certain embodiments, average flow rate of first eluent (diluent- 1) is about 100-300 ml/min, about 150-250 ml/min, about 150-200 ml/min, or about 150- 190 ml/min. In some instances, average flow rate of first eluent (diluent-1) is about 156- 184 ml/min. In certain embodiments, average flow rate of second eluent (diluent-2) is about 50-200 ml/min, about 50-150 ml/min, about 60-150 ml/min, or about 70-150 ml/min. In some instances, the average flow rate of second eluent (diluent-2) is about 87- 102 ml/min. In certain embodiments, average raffinate flow rate is about 100-300 ml/min, about 100-200 ml/min, or about 100-150 ml/min. In some instances, average raffinate flow rate is about 120-140 ml/min. In certain embodiments, average flow rate of first extract is about 50-300 ml/min, about 50-250 ml/min, about 50-200 ml/min, about 50-150 ml/min, about 60-150 ml/min, about 70-150 ml/min, or about 80-150 ml/min. In certain embodiments, average flow rate of second extract is about 50-300 ml/min, about 50-250 ml/min, about 50-200 ml/min, about 50-150 ml/min, about 60-150 ml/min, about 70-150 ml/min, or about 80-150 ml/min.

In certain embodiments, the feed stream has a flow rate from about 15 cm/hr to about 30 cm/hr, the diluent has a flow rate of from about 80 cm/hr to about 110 cm/hr, the first extract flow rate is from about 30 cm/hr to about 50 cm/hr, the second extract has a flow rate from about 30 cm/hr to about 50 cm/hr, the second raffinate flow rate is from about 20 cm/hr to about 40 cm/hr.

In certain embodiments of the method, the feed mixture (feed stream), and eluent are supplied from a suitable tank(s). In certain embodiments, the feed stream, the first eluent, and/or the second eluent is/are heated at a temperature of about 50-70 °C prior to introducing into the SMB apparatus. In further embodiments, the diluent is water. In some instance, both the first eluent and the second eluent are water.

In certain embodiments, the process comprises one or more of the following cycles:

Cycle -1: introducing feed into column 1; introducing first diluent into column 3; introducing second diluent into column 7; withdrawing second extract(D-allulose) from column 7 ; withdrawing first raffinate from column 1 ; introducing the first raffinate into column 5; withdrawing a first extract(fmctose)from column 3; and withdrawing raffinate (glucose) column 5; Cycle -2: introducing feed into column 2; introducing first diluent into column 4; introducing second diluent into column 8; withdrawing second extract (D-allulose) from column 8; withdrawing first raffinate from column 2; introducing the first raffinate into column 6; withdrawing a first extract (fructose) from column 4; and withdrawing raffinate (glucose)column 6;

Cycle -3: introducing feed into column 3; introducing first diluent into column 5; introducing second diluent into column 1; withdrawing second extract (D-allulose) from column 1; withdrawing first raffinate from column 3; introducing the first raffinate into column 7; withdrawing a first extract (fructose) from column 5; and withdrawing raffinate(glucose) column 7;

Cycle -4: introducing feed into column 4; introducing first diluent into column 6; introducing second diluent into column 2; withdrawing second extract(D-allulose) from column 2; withdrawing first raffinate from column 4; introducing the first raffinate into column 8; withdrawing a first extract (fructose) from column 6; and withdrawing raffinate (glucose) column 8;

Cycle -5: introducing feed into column 5; introducing first diluent into column 7; introducing second diluent into column 3; withdrawing second extract (D-allulose) from column 3; withdrawing first raffinate from column 5; introducing the first raffinate into column 1; withdrawing a first extract (fructose) from column 7; and withdrawing a raffinate (glucose) column 1;

Cycle -6: introducing feed into column 6; introducing first diluent into column 8; introducing second diluent into column 4; withdrawing second extract (D-allulose) from column 4; withdrawing first raffinate from column 6; introducing the first raffinate into column 2; withdrawing a first extract (fructose) from column 8; and withdrawing a raffinate (glucose) column 2;

Cycle -7: introducing feed into column 7; introducing first diluent into column 1; introducing second diluent into column 5; withdrawing second extract (D-allulose) from column 5; withdrawing first raffinate from column 7; introducing the first raffinate into column 3; withdrawing a first extract (fructose) from column 1; and withdrawing a raffinate (glucose) column 3; and Cycle -8: introducing feed into column 8; introducing first diluent into column 2; introducing second diluent into column 6; withdrawing second extract (D-allulose) from column 6; withdrawing first raffinate from column 8; introducing the first raffinate into column 4; withdrawing a first extract (fructose) from column 2; and withdrawing a raffinate (glucose) column 4. In certain embodiments, at least a part of raffinate is recycled into the SMB apparatus. In certain embodiments, the feed stream comprises allulose, fructose and glucose. In certain embodiments of the method, after a certain time, the method reaches a cyclic steady state (CSS).The CSS is particularly reached after a certain number of cycles as depicted above, but the system state is still varying over the time because of the periodic movement of the inlet and outlet ports along the columns.After the CSS is reached, the first extract, the second extract, the first raffinate and the second raffinate are collected continuously. The first extract, the second extract, the second raffinate are collected in a first extract tank, second extract tank, and a raffinate tank, respectively. In certain embodiments of the method, at least a part of raffinate is recycled into the SMB apparatus.

In certain embodiments, the method is carried out at a temperature of about 50-70 °C. In some instances, temperature of each column in the SMB is maintained by recirculating hot water into a jacket surrounding each column.

In certain embodiments, the resin in each column is selected from a group comprising PCR642 Ca-H- from Purolite company, UBK 555 from Mitsubishi company etc.

In certain embodiments of the method, the feed stream comprises allulose, fructose and glucose. In some instances, the second extract comprises allulose which is about 90-99% pure, the first extract comprises fructose which is about 80-100% pure, and the second raffinate comprises glucose which is about 70-100% pure.

During this entire process, the flow between the columns is maintained by the recycle pump. After a certain point of predetermined time, the mixture, extract, eluent and raffinate are moved ahead by one column by appropriate switching of flows, this simulates the counter current movement of a resin bed. This process of column switching is continued in a cyclic fashion and helps to efficiently separate the sugar streams utilizing a much smaller amount of resin. In an embodiment, design and dimensions of components of the system 100 such as the feed tank 10, eluent tank 20, columns Cl to C8, raffinate tank, first and second extract tank, preheaters etc., can be altered based on the requirements/application.

In certain embodiments, the present disclosure provides a process for producing pure D-allulose from sugar source using a single SMB. The process is simple, cost effective, reduces recycle and reduces process loss. The process is less complex than those of prior art, in particular with a reduced number of SMBs, particularly with a single SMB. The SMB is operated with conditions (in particular flow of feed and flow of solvent) that make it possible to obtain a highly pure allulose, In certain embodiments, the present disclosure provides a process for producing pure D-allulose from sugar source. The process comprises:

(i) mixing the sugar source with water or with an aqueous liquid and adjusting the concentration of dissolved sugar (such as sucrose) thereby providing a first solution of sugar source; (ii) converting sugar source to glucose and fructose thereby providing a second solution comprising glucose and fructose;

(iv) separating sugar products of the second solution by an integrated simulated moving bed (SMB) chromatographythereby providing fraction 1 (rich in glucose), fraction 2 (rich in fructose) and fraction 3 (rich in allulose);

(v) producing liquid allulose or solid allulose from the fraction 3;

(vi) converting glucose present in fraction lto fructose thereby providing a third solution comprising glucose and fructose; (vii) returning the fraction 2 (rich in fructose) and the third solution to step (ii); and

(viii) reiterating steps (ii) to (vii).

The above process is schematically illustrated in Figure 2. In certain embodiments, according to step (i), water is added to sugar source such that the final concentration of sugar source, preferably sucrose, is about 30% w/v to 60% w/v. In certain embodiments, the final concentration of sugar source is about 35% w/v or 40% w/v or 45% w/v or 50% w/v or 55% w/v or 60% w/v. In certain embodiments, sugar source is ‘sucrose source’ and denotes any medium, solid, or liquid containing sucrose in different concentrations, in particular from about 1 to about 100% of sucrose.

The conversion of the sugar source to glucose and fructose can be done using conventional methods. In certain embodiments, the sugar source is converted to glucose and fructose under heterogeneous or homogeneous catalysis which includes chemical and/or enzymatic catalysis. In some instances, the conversion of the sugar source to glucose and fructose according to step (ii) is performed using a strong cation exchange resin. Suitable resins for a given conversion are known to a skilled person and commercially available. Examples of resins include, but are not limited to, PK216H (Mitsubishi chemicals), C124SH (Purolite; Indion) and 225H (Ion exchange).

Any suitable enzyme can be used in the process of step (iii). In certain embodiments, the conversion according to step (iii) is performed under enzymatic catalysis by immobilized D-tagatose 3-epimerase. The conversion of fructose to allulose is carried out at a temperature of about 50-55 °C, at a pH of about 8-9 and with a residence time of about 10-15 min. The enzyme may be freely dissolved or immobilized on a solid carrier. In certain embodiments, the enzyme may be present in dissolved state and may be retained in the reactor by membranes. In yet other embodiments, the enzyme may be immobilized on a solid support. In certain embodiments, the enzyme may be present in microorganisms that in turn are retained in the reactor by membranes. In certain embodiments, the enzyme may be present in microorganisms that in turn are immobilized on a solid support. Examples of solid support materials include, but are not limited to, resins, plastics and glass. The enzyme may also be encapsulated by the solid support material, e.g., in form of alginate beads.

Thereafter, the sugar products present in the second solution are separated by chromatography integrated in an 8-zone simulated moving bed (SMB) to provide fraction 1 (rich in glucose), fraction 2 (rich in fructose) and fraction 3 (rich in allulose). The SMB is operated with conditions (in particular flow of feed and flow of solvent) that make it possible to obtain a highly pure allulose. Typical arrangement of the simulated moving bed (SMB) chromatographic separation system is shown in figurel.The SMB process is carried out as described above.

In certain embodiments, the fraction 3 comprises about 80% to about 100% allulose. In further embodiments, the fraction 3 comprises about 95% to about 100% allulose. In yet other embodiments, the fraction 3 comprises about 98% allulose.

In certain embodiments, the fraction 3 (rich in allulose) may be concentrated to provide a concentrated allulose. The concentrated allulose may be purified further to get a pure allulose as syrup or solid. The pure solid allulose can generally be obtained by precipitation, preferably by crystallization. Any suitable crystallization method known in the art can be employed.

In certain embodiments, the fraction 3 (rich in allulose) is passed through a mixed bed resin and then subjected to concentration followed by crystallization to yield greater than about 99% pure allulose. In certain embodiments, the mixed bed comprises strong base anion exchange resin and weak acidic cation exchange resin. Any suitable strong base anion exchange resin and weak acidic cation exchange resin can be used in the process. In certain embodiments, the strong base anion exchange resin is SAF11AL-C1 (Mitsubishi chemicals) or C150SH (Purolite), and the weak acidic cation exchange resin WK40L (Mitsubishi chemicals) or A133S (Purolite).

The process depicted above is performed continuously and the purity of the allulose obtained is about 80% to about 100%. In further embodiments, the purity is about 95% to about 100%.

The present invention is further described with reference to the following examples, which are only illustrative in nature and should not be construed to limit the scope of the present disclosure in any manner. Experimental information

Set up details:

Resin used for experiment : PCR642Ca++

Number of columns : 8

Column height :150 cm Column diameter :160 mm

Volume of each Column : 301

Total Resin volume : 2401

In a typical experiment, the process of the present examples comprises one or more of the following cycles:

Cycle -1: introducing feed into column 1; introducing first diluent into column 3; introducing second diluent into column 7; withdrawing second extract (D-allulose) from column 7; withdrawing first raffinate from column 1; introducing the first raffinate into column 5; withdrawing a first extract(fructose)from column 3; and withdrawing raffinate (glucose) column 5;

Cycle -2: introducing feed into column 2; introducing first diluent into column 4; introducing second diluent into column 8; withdrawing second extract (D-allulose) from column 8; withdrawing first raffinate from column 2; introducing the first raffinate into column 6; withdrawing a first extract (fructose) from column 4; and withdrawing raffinate (glucose)column 6;

Cycle -5: introducing feed into column 5; introducing first diluent into column 7; introducing second diluent into column 3; withdrawing second extract (D-allulose) from column 3; withdrawing first raffinate from column 5; introducing the first raffinate into column 1; withdrawing a first extract (fructose) from column 7; and withdrawing a raffinate (glucose) column 1; Cycle -6: introducing feed into column 6; introducing first diluent into column 8; introducing second diluent into column 4; withdrawing second extract (D-allulose) from column 4; withdrawing first raffinate from column 6; introducing the first raffinate into column 2; withdrawing a first extract (fructose) from column 8; and withdrawing a raffinate (glucose) column 2;

Cycle -7: introducing feed into column 7; introducing first diluent into column 1; introducing second diluent into column 5; withdrawing second extract (D-allulose) from column 5; withdrawing first raffinate from column 7; introducing the first raffinate into column 3; withdrawing a first extract (fructose) from column 1; and withdrawing a raffinate (glucose) column 3; and

Cycle -8: introducing feed into column 8; introducing first diluent into column 2; introducing second diluent into column 6; withdrawing second extract (D-allulose) from column 6; withdrawing first raffinate from column 8; introducing the first raffinate into column 4; withdrawing a first extract (fructose) from column 2; and withdrawing a raffinate (glucose) column 4.

In the process, the inlet connections to which the feed is fed and the outlet connections from which the outlet streams were withdrawn periodically moved from their respective columns to adjacent columns. Thus, the method included switching periodically the feed stream, first raffinate, second raffinate, first eluent, second eluent, first extract and second extract forward one column position at a time in the direction of the flow. The switching time is 50-160 minutes.

EXAMPLE: 1 (SEPARATION OF ALLULOSE-FRUCTOSE-GLUCOSE

MIXTURE)

Feed composition:

Fructose Concentration : 22.5%

Allulose concentration : 8.0 %

Glucose Concentration : 18 %

Process conditions:

Process temperature : 60 °C Average feed flow rate : 70 ml/min

Average diluents- 1 flow rate : 156 ml/min Average diluents-2 flow rate : 102 ml/min Average raffinate flow rate : 123.5 ml/min Average extract- 1 flow rate : 98.0 ml/min

Average Extract-2 flow rate : 109.5 ml/min

Experimental results:

EXAMPLE: 2 (SEPARATION OF ALLULOSE-FRUCTOSE-GLUCOSE

MIXTURE)

Feed composition: Fructose Concentration : 32.75%

Allulose concentration : 12.75 % Glucose Concentration : 11.75% Process conditions: Process temperature : 60 °C

Average feed flow rate : 72 ml/min Average diluents- 1 flow rate : 184 ml/min Average diluents-2 flow rate : 87 ml/min Average raffinate flow rate : 134 ml/min Average extract- 1 flow rate : 99 ml/min

Average Extract-2 flow rate : 116 ml/min

Experimental results:

The sugar elusion profile of the three different streams is shown in figures 3-5. As shown in figure 3, allulose fraction (second extract) was started with higher value and then the value was gradually decreased and finally ended with zero. Fructose fraction (first extract) was started with higher value then the value was gradually decreased and finally ended with zero (Figure 4). Glucose fraction (raffinate) was started with lower value then the values were gradually increased during process (Figure 5).

Advantages of the present disclosure are illustrated herein:

The present disclosure relates to a method and a system that is simple, easy to operate and affordable.

The method and system according to the present disclosure is easy and inexpensive to manufacture.

List of Reference numerals

Claims

THE CLAIM:

1. A system for purifying allulose from a ternary mixture, the system comprises: a continuous simulated moving bed (SMB) apparatus having at least eight columns positioned adjacent to each other and fluidly connected in series forming a closed loop configuration, wherein each column of the eight columns is defined with a feed port, a first eluent port, a second eluent port, a first extract port, a second extract port and a first raffinate port and a second raffinate port; a feed tank containing a ternary sugar mixture fluidly connected to the each of the eight columns, wherein the feed tank being configured to continuously feed the ternary sugar mixture into at least one of the eight columns through the feed port in the at least one of the eight columns, and wherein the ternary sugar mixture comprises allulose, one or more isomers of allulose, and optionally, one or more additional sugars; at least one eluent tank containing eluent fluidly connected to the each of the eight, wherein at least one eluent tank being configured to continuously feed the eluent into at least one of the columns of the eight columns through the first eluent port and the second eluent port in the at least of column of the eight columns; a raffinate tank fluidly connected to the each of the eight columns, wherein the raffinate tank being configured to continuously withdraw a second raffinate from at least one of the eight columns through the second raffinate port, wherein the first raffinate port in fluid communication with each column of the eight columns is configured to continuously withdraw and circulate a first raffinate into each column via a raffinate inlet port; a first extract tank and a second extract tank fluidly connected to the each of the eight columns, wherein the first extract tank and the second extract tank being configured to continuously withdraw a first extract and a second extract, respectively from at least one of the eight columns by the first extract port and the second extract port, wherein the second extract comprises purified allulose, wherein feeding of the ternary sugar mixture, the first eluent and the second eluent into the each of the eight columns, and withdrawal of the first extract, second extract, and the second raffinate and circulation of the first raffinate from the eight columns, are incremented in series towards adjacent columns, at a predetermined time intervals. The system as claimed in claim 1, wherein the SMB apparatus comprising eight columns arranged and fluidly connected in series forming a closed loop configuration, and each column is operated in a sequence comprising: a) feeding the ternary sugar mixture into a first column fluidly connected to the feed tank; b) feeding the first eluent into a third column fluidly connected to the eluent tank; c) feeding the second eluent into a seventh column fluidly connected to the eluent tank; d) withdrawing the first raffinate at the first column fluidly connected to the raffinate tank; e) feeding the first raffinate into a fifth column fluidly connected to the raffinate inlet port; and f) withdrawing the first extract at the third column fluidly connected to the first extract tank; g) withdrawing the second extract at the seventh column fluidly connected to the second extract tank; h) withdrawing the second raffinate at the fifth column fluidly connected to the raffinate tank wherein, after the predetermined time interval, the eight columns receiving the ternary sugar mixture, the first eluent, the second eluent into the eight columns from which the first raffinate, the second raffinate, the first and the second extract are withdrawn, are incremented in series towards adjacent columns. The system as claimed in claim 1, wherein each column of the eight column comprises at least one inlet valve manifolds fluidly connected to the each of the feed port, the first eluent port, the first eluent port and the raffinate inlet port for selectively receiving the ternary sugar mixture, the first eluent, and the second eluent and the first raffinate from the feed tank, the eluent tank and the first raffinate port, respectively

4. The system as claimed in claim 1, wherein each column of the eight columns comprises at least one outlet valve manifolds fluidly connected to each of the first raffinate port, second raffinate port, the first extract port and the second extract port for selectively withdrawing first raffinate, second raffinate, the first extract and the second extract into the raffinate tank, first and second extract tank, respectively.

5. The system as claimed in claim 1, comprises a first preheater to heat the first eluent to a first predetermined temperature and a second preheater to heat the second eluent to a second predetermined temperature, wherein the first eluent inlet and the second eluent are preheated before feeding into each of the eight columns.

6. The system as claimed in claim 1, comprises a third preheater fluidly connected to the feed tank, wherein the third preheater heats the feed at a third pre-determined temperature, before feeding into the each of the eight columns

The system as claimed in claim 1, comprises a plurality of pumps to supply the ternary sugar mixture, the first eluent, the second eluent from the feed tank and the eluent tank to the eight columns, and to extract first and second raffinate, and the first and second extract from the eight columns.

7. The system as claimed in claim 1, wherein each of the eight column comprises a resin bed and a jacket surrounding the eight columns, and wherein the resin bed enables reaction and separation of the ternary sugar mixture.

8. The system as claimed in claim 8, comprises an auxiliary tank storing a fluid, and fluidly connected to the each of the eight columns, wherein the auxiliary tank being configured to supply the fluid into the jackets surrounding each of the eight columns at a fourth predetermined temperature.

9. The system as claimed in claim 1 to 10, comprises a controller communicatively connected to a plurality of pumps and the inlet/outlet valve manifold for controlling and monitoring flow through the each of the eight columns

10. The system as claimed in claim 1, comprises at least one refractive index detector coupled to each column of the at least eight columns to detect and monitor properties of the first and second eluent within each column. A method for purifying allulose from a mixture in a continuous simulated moving bed (SMB) apparatus comprising at least eight columns connected in series with a closed loop configuration; said process comprises: a) providing a feed mixture comprising the allulose, one or more of its isomers, and one or more sugars other than the allulose or its isomer; b) simultaneously, i) feeding a feed mixture from a feed tank into a column; ii) feeding a first eluent from an eluent tank into a column, wherein the column is separated by two columns from the column of step i); iii) feeding a second eluent into a column, wherein the column is separated by six columns from the column of step i); iv) collecting from the column of step i) a first raffinate; v) feeding the first raffinate of step iv) into a column, wherein the column is separated by four columns from the column of step i); vi) withdrawing a first extract from the column which is separated by two columns from the column of step i); wherein the first extract comprises one or more isomers of allulose; vii) withdrawing a second extract from the column which is separated by six columns from the column of step i); wherein the second extract comprises allulose in pure form; and viii) withdrawing a second raffinate from the column which is separated by four columns from the column of step i); wherein the second raffinate comprises one or more sugars other than the allulose and its isomer; and c) switching periodically the feed stream, first raffinate, second raffinate, first eluent, second eluent, first extract and second extract forward one column position at a time in the direction of the flow.

12. The method as claimed in claim 11, wherein after a certain time, the process reaches cyclic steady state, and after the cyclic steady state is reached, the first extract, the second extract, the first raffinate and the second raffinate are collected continuously.

13. The methodas claimed in claim 11, wherein the feed stream, the first eluent, and/or the second eluent is/are heated at a temperature of about 50-70 °C prior to introducing into the SMB apparatus.

14. The method as claimed in any of the claims 11-13, wherein the process is carried out at a temperature of about 50-70 °C.

15. The method as claimed claim 14, wherein temperature of each column in the SMB is maintained by recirculating hot water into a jacket surrounding each column.

16. The method as claimed in claim 11, wherein both the first eluent and the second eluent are water.

17. The method as claimed in claim 11, wherein at least a part of raffinate is recycled into the SMB apparatus.

18. The method as claimed in claim 11, wherein the feed stream comprises allulose, fructose and glucose.

19. The method as claimed in claim 11, wherein the second extract comprises allulose which is about 90-100% pure, the first extract comprises fructose which is about 80-100% pure, and the second raffinate comprises glucose which is about 70- 100% pure. 0. A process for producing pure D-allulose from a sugar source, the process comprises:

(v) producing liquid allulose or solid allulose from the fraction 3;

(vi) converting glucose present in fraction 1 to fructose thereby providing a third solution comprising glucose and fructose;

(vii) returning the fraction 2 (rich in fructose) and the third solution to step (ii); and

(viii) reiterating steps (ii) to (vii).