Process and device for separation with variable-length

A process for separating at least one component of a mixture in a set of closed-loop chromatographic columns is described, whereby the loop comprises at least one feedstock injection point, a raffinate draw-off point, an eluant injection point, and an extract draw-off point, in which a determination is made between an injection point and a draw-off point or vice-versa a chromatographic zone, and at the end of a given period of time, all of the injection and draw-off points are shifted by one column or column section in a given direction that is defined relative to that of the flow of a main fluid that circulates through the loop. During the period, the shifting of different injection and draw-off points of a column or column section is done at different times in such a way that the lengths of the zones that are defined by said different points are variable. The process is useful for the seperation particularly of stereoisumers for pharmaceuticals.

SUMMARY OF THE INVENTION 
The invention relates to a process and a device for separating at least one 
component of a mixture by contact between liquid and solid phases in 
variable-length chromatographic zones. 
It applies to chiral separations and in particular to the separation of 
stereoisomers that are used especially in the field of pharmaceutics. 
There are different chromatographic processes that can be used for the 
production of chemical components on a large scale. 
The publication by R. M. NICOUD and M. BAILLY (Choice and Optimization of 
Operating Mode in Industrial Chromatography, Proceeding of the 9th 
International Symposium on Preparative and Industrial Chromatography, PREP 
92, April 1992, Nancy, pp. 205-220) illustrates this technological 
background. 
These processes can be classified according to several criteria: the 
process can be either discontinuous or continuous, the composition of the 
eluent can be isocratic, or a composition gradient can be carried out. 
One of these possibilities is the true standard moving-bed 4-zone 
countercurrent process where in a moving-bed system, with a view to 
producing a continuous countercurrent effect, solids circulate 
continuously in a closed loop past the fixed feedstock and eluant 
introduction points alternately, with draw-off points for a raffinate and 
an extract. 
Since this process is perfectly well known and described, only the 
characteristics that are required to understand the nature of this 
invention are summarized below. For the operating mode in a True Moving 
Bed, countercurrent contact between the liquid and solid phases is made in 
the column, which can be divided into four different zones. 
Zone 1: Everything that is located between the eluant injection lines and 
the extract draw-off lines 
Zone 2: Everything that is located between the extract draw-off lines and 
the feedstock injection lines 
Zone 3: Everything that is located between the feedstock injection lines 
and the raffinate draw-off lines 
Zone 4: Everything that is located between the raffinate draw-off lines and 
the eluant injection lines. 
Because of the inlet/outlet flow rates, the liquid flow rate varies 
according to the zone, whereby Q.sub.I, Q.sub.II, Q.sub.III, and Q.sub.IV 
are the respective flow rates in zones I, II, III, and IV. 
In 1961, the UOP Company patented a process that makes it possible to 
simulate the movement of the solid by an elegant connection between the 
columns that are interconnected in a closed loop (U.S. Pat. Nos. 
2,985,589; 3,291,726 and 3,268,605. This process, called a Simulated 
Moving Bed (LMS), then makes it possible to produce the True Moving Bed in 
practice in a simple way. Said process is characterized in that the 
feedstock and eluant introduction points are periodically advanced 
downstream (in the direction of circulation of the main fluid), while the 
draw-off points for a raffinate and an extract are advanced simultaneously 
and according to the same increment (at least one column, for example). 
All of the inlet and output lines are therefore moved simultaneously with 
each period .DELTA.T and cycle time, at the end of which time they find 
their initial position is equal to Nc.times..DELTA.T, whereby Nc is the 
total number of columns. 
This process has been extensively described particularly by CHARTON and 
NICOUD (Complete Design of a Simulated Moving Bed, Journal of 
Chromatography 1995, 702, 97-102). 
Only the minimum information that is necessary for good comprehension of 
this invention will be recapped below. 
The inlet/outlet positions are moved simultaneously at fixed intervals. It 
is advised that the position of the line be marked by line (n), which 
indicates that at a given moment a given inlet/outlet line is connected to 
the inlet of column n. For example, in a 12-column system, feedstock (9) 
means that the feedstock line is connected to the inlet of column 9, 
whereas raffinate (11) means that the raffinate line is connected to the 
inlet of column 11. 
By using this definition, a system can be represented by: 
El(3)/Ext(6)/Feedstock(9)/Raff(11). For this configuration, the number of 
columns in zones 1, II, III, and IV are respectively: 3/3/2/4. The 
configuration of the system is then completely defined by: 
Inlet/Outlet No. of Columns 
At time 0: El(3)/Ext(6)/Feedstock(9)/Raff(11) 3/3/2/4 
After a given time (the PERIOD), all of the inlet/outlet positions are 
moved simultaneously by one column, and the system is described as 
follows: 
At time .DELTA.T: El(4)/Ext(7)/Feedstock(10)/Raff(12) 3/3/2/4 
After a new period, all of the positions will again be moved simultaneously 
by one column, and the system will then be described as follows: 
At time 2.times..DELTA.T: El(5)/Ext(8)/Feedstock(11)/Raff(1) 3/3/2/4 
At time 2.times..DELTA.T, the position of the raffinate has been moved from 
position 12 to position 1. Notice that position 1 can be written as 
position 13 modulo 12. ([13].sub.12). 
This presentation can be generalized to simulated moving beds that comprise 
a number of columns Nc. For a simulated moving bed that consists of Nc 
columns, it is obvious that no position can exceed Nc. For the sake of 
simplicity, we will simply increase all of the positions by one unit with 
each movement, and we will define all of the modulo Nc positions (for 
example, [8].sub.Nc =3 if Nc=5). 
If, at a given moment, the configuration of the simulated moving bed is El 
(e)/Ext(x)/Feedstock(f)/Raff(r), simple reasoning makes it possible to 
find the number of columns that are contained in each zone: 
Zone 1: Nb1=[x-e].sub.Nc ; Zone 2: Nb2=[f-x].sub.Nc 
Zone 3: Nb3=[r-f].sub.Nc ; Zone 4: Nb4=[e-r].sub.Nc 
It is possible to verify simply that: Nb1+Nb2+Nb3+Nb4=Nc and the system is 
completely defined by Table 1. 
TABLE 1 
______________________________________ 
No. of Columns in 
Inlet/Outlet Each Zone 
______________________________________ 
At time 0: 
El(e)/Ext(x)/Feed(f)/Raff(r) 
Nb1/Nb2/Nb3/Nb4 
At time .DELTA.T: El([e + 1].sub.Nc)/Ext([x + 1].sub.Nc)/ Nb1/Nb2/Nb3/Nb 
4 
Feed([f + 1].sub.Nc)/Raff([r + 1].sub.Nc) 
At time n .times. .DELTA.T: El([e + n].sub.Nc)/Ext([x + n].sub.Nc)/ 
Nb1/Nb2/Nb3/Nb4 
Feed([f + n].sub.Nc)/Raff([r + n].sub.Nc) 
______________________________________ 
The injection and draw-off points are shifted by one column after a period 
.DELTA.T and by Nc columns after Nc periods. The number of columns in each 
zone remains unchanged. The injection and draw-off points therefore regain 
their initial positions after cycle time Nc.times..DELTA.T. 
The main characteristics of the simulated moving bed systems (providing a 
practical implementation of the true moving bed) are defined by: 
1. Zones that are defined by the positions of the inlet/outlet lines, 
2. A set number of columns per zone, 
3. Zones of fixed length, 
4. Synchronized movement of all of the inlet/outlet lines. 
Characteristics 2, 3, and 4 are due to the fact that the simulated moving 
bed simulates the behavior of the true moving bed. 
According to French Patent 2,721,528, it is possible to correct the 
composition disturbances of the extract and the raffinate that are caused 
by the dead volume of the recycling pump that is located between the last 
and first beds of the adsorption column, by increasing by a suitable value 
the period of connection of a fluid injection flow or draw-off in the 
system each time that this flow passes from one position that is 
immediately in front to a position that is immediately behind the dead 
volume, and then by reducing said connection period when this flow moves 
from the position that is immediately behind the dead volume to the next 
position. Once per cycle, however, all of the inlets and outlets are 
shifted simultaneously. This technique makes it possible to compensate for 
the technological imperfections in a simple way in order to make it 
operate in a way that is close to that of an ideal simulated moving bed. 
In the processes for separation in a simulated moving bed that use a small 
number of columns, it most often seems that the products that are 
recovered in the extract and in the raffinate exhibit different purities, 
excellent for one of the two but inadequate for the other. In some types 
of separation, when the adsorbent volume that is used is small, the levels 
of purity of the extract and the raffinate can even turn out to be 
inadequate, as can be seen in the examples. 
One of the objects of the invention is to eliminate these drawbacks. 
Another object is therefore to increase the purity of the product that is 
drawn off as an extract and as a raffinate. 
Another object is to minimize the costs of the separation. 
It was thus noted that by not simultaneously moving the positions of the 
inlets and the outlets of fluid during the period and during the cycle 
time, it was possible to obtain improved results. 
More specifically, the invention relates to a separation process that is 
called VARICOL, at least one component of a mixture that contains it, in a 
device that has a set of chromatographic columns or chromatographic column 
sections that contain an adsorbent and are arranged in series and in a 
closed loop, whereby the loop comprises at least one feedstock injection 
point, a raffinate draw-off point, an eluant injection point, and an 
extract draw-off point, in which a chromatographic zone is determined by 
an injection point and a draw-off point or vice-versa, and at the end of a 
given period of time, all of the injection and draw-off points are shifted 
by one column or column section in a given direction that is defined 
relative to that of the flow of a main fluid that circulates through the 
loop, whereby the process is characterized in that during said period, the 
shifting of different injection and draw-off points of a column or column 
section is carried out at different times such that the lengths of the 
zones that are defined by said different points are variable. 
The period is defined as the smallest time interval .DELTA.T at the end of 
which each of the inlets and outlets has been shifted by one column or 
column section, whereby the shifting has not taken place simultaneously 
for all of the inlets and outlets. It should be noted that at the end of a 
cycle time Nc.times..DELTA.T, the system has regained its initial 
position. 
The term adsorbent is used in its most general sense. It can be an 
adsorbent such as a molecular sieve, a zeolitic sieve, for example, that 
is used in the adsorption processes, or an adsorbent such as an 
ion-exchange resin. It may also be a stationary phase on a silica base, an 
inverse-phase adsorbent, and a chiral phase. 
In a more detailed manner, it is possible to produce at least once the 
succession of following stages: 
At moment t1 during said period .DELTA.T, in a given direction, the 
position of the injection point or draw-off point is shifted relative to 
at least one zone by a column or column section, in such a way as to 
increase the length of said zone and to reduce the length of the zone that 
is adjacent to said zone, then at a moment t2 during said period, the 
position of an injection or draw-off point that is relative to at least 
one other zone is shifted in the same direction by a column or column 
section, in such a way as to increase the length of said other zone and to 
reduce the length of the zone that is adjacent to said other zone, and the 
operation is repeated if necessary such that after said time period 
.DELTA.T, the same column configuration as the initial configuration is 
regained with a shifting of all of the positions of the injection points 
and draw-off points of a column or a column section. 
According to a first implementation that is illustrated by Table 2, it is 
possible to continually vary the lengths of zones of a column, whereby the 
increase of one zone is compensated for by the reduction of the next zone. 
TABLE 2 
______________________________________ 
No. of Columns in 
Inlet/Outlet Each Zone 
______________________________________ 
At time 0 
El(e)/Ext(x)/Feed(f)/Raff(r) 
Nb1/Nb2/Nb3/Nb4 
At time dT1 El([e + 1].sub.Nc ]/Ext(x)/Feed(f)/ Nb1 - 1/Nb2/Nb3/ 
Raff(r) Nb4 + 1 
At time dT2 El([e + 1].sub.Nc)/Ext(x)/Feed(f)/ Nb1 - 1/Nb2 - 1/Nb3/ 
Raff([r + 1].sub.Nc) Nb4 
At time dT3 El([e + 1].sub.Nc)/Ext(x)/ Nb1 - 1/Nb2 + 2/Nb3/ 
Feed([f + 1]).sub.Nc)/Raff([r + 1].sub.Nc) Nb4 
At time .DELTA.T El([e + 1].sub.Nc)/Ext([x + 1].sub.Nc)/ Nb1/Nb2/Nb3/Nb4 
Feed([f + 1].sub.Nc)/Raff([r + 1].sub.Nc) 
At time .DELTA.T + El([e + 2].sub.Nc)/Ext([x + 1].sub.Nc)/ Nb1 - 
1/Nb2/Nb3/ 
dT1: Feed([f + 1].sub.Nc)/Raff([r + 1].sub.Nc) Nb4 + 1 
At time .DELTA.T + El([e + 2].sub.Nc)/Ext([x + 1].sub.Nc)/ Nb1 - 
1/Nb2/Nb3 + 1/ 
dT2: Feed([f + 1].sub.Nc)/Raff([r + 2].sub.Nc) Nb4 
At time .DELTA.T + El([e + 2].sub.Nc)/Ext([x + 1].sub.Nc)/ Nb1 - 1/Nb2 
+ 1/Nb3/ 
dT3: Feed([f + 2].sub.Nc)/Raff([r + 2].sub.Nc) Nb4 
At time 2 .times. .DELTA.T El([e + 2].sub.Nc)/Ext([x + 2].sub.Nc)/ 
Nb1/Nb2/Nb3/Nb4 
Feed([f + 2].sub.Nc)/Raff([r + 2].sub.Nc) 
______________________________________ 
According to a second implementation that is illustrated by Table 3, the 
increase in length of a zone can be compensated for by a reduction of the 
opposite zone. 
TABLE 3 
______________________________________ 
No. of Columns in 
Inlet/Outlet Each Zone 
______________________________________ 
At time 0 
El(e)/Ext(x)/Feed(f)/Raff(r) 
Nb1/Nb2/Nb3/Nb4 
At time dT1 El([e + 1].sub.Nc ]/Ext(x)/Feed(f)/ Nb1 - 1/Nb2/Nb3 + 1/ 
Raff([r + 1].sub.Nc) Nb4 
At time .DELTA.T El([e + 1].sub.Nc)/Ext([x + 1].sub.Nc)/ Nb1/Nb2/Nb3/Nb4 
Feed([f + 1].sub.Nc)/Raff([r + 1].sub.Nc) 
At time .DELTA.T + El([e + 2].sub.Nc)/Ext([x + 1/ Nb1 - 1/Nb2/Nb3 + 1/ 
dT1: Feed(f + 1/Raff([r + 2].sub.Nc) Nb4 
At time 2 .times. .DELTA.T El([e + 2].sub.Nc)/ 
Ext([x + 2].sub.Nc)/ Nb1/Nb2/Nb3/Nb4 
Feed([f + 2].sub.Nc)/Raff([r + 2].sub.Nc) 
______________________________________ 
Several other embodiments are possible, whereby some of them are shown in 
the examples. 
According to a characteristic of the process, it is possible during the 
period to perform all of the shiftings of the injection or draw-off 
positions with an approximately constant time phase shift and 
advantageously with a time phase shift that is at least equal to a 
quarter-period. 
According to a variant, it is possible to carry out during the period the 
shifting of the positions of the injection or draw-off points with a 
non-constant time phase shift. 
According to another characteristic, the flow rate of fluid that circulates 
in a given zone is generally kept approximately constant. 
It is advantageous to carry out the shiftings of the positions of the 
injection and draw-off points in the same direction as that of the flow in 
the columns or column section. 
According to another advantageous characteristic of the process, at least 
one flow rate of fluid that circulates in an injection or draw-off line 
can be monitored by the pressure in the device. Preferably, it is the flow 
rate of the raffinate and/or the extract, whereby the other fluids are 
then under flow rate control. 
It is advantageously possible to use a liquid as an eluant, but it is also 
possible to operate with a supercritical fluid or with a subcritical 
fluid. 
The range of pressures in which the separations of products are carried out 
can be between 0.1 and 50 MPa and preferably between 0.5 and 30 MPa. The 
temperature in the columns is generally between 0.degree. C. and 
100.degree. C. It was observed that the process according to the invention 
provided excellent results when the number of columns or column sections 
was less than 8. For values of greater than 8, it is very advantageous to 
optimize the process by studying the influence of the number and the 
lengths of the columns in each zone that is combined at the moment of 
shifting during the period of the cycle. 
The invention also relates to the device particularly for the 
implementation of the process. 
More specifically, said device comprises a number of chromatographic 
columns or a chromatographic column section that contains an adsorbent, 
arranged in series and in a closed loop, whereby said loop comprises at 
least one pump for recirculating a fluid, a number of fluid injection 
lines in each column or column section that are connected to at least one 
injection pump and a number of fluid draw-off lines of each column or 
column section that are connected to at least one draw-off pump, at least 
one valve on each line, whereby said loop defines at least three 
chromatographic zones, whereby each of them is determined by a fluid 
injection point and a fluid draw-off point, whereby the device is 
characterized in that it comprises means for controlling the variation in 
time of the lengths of the zones that are connected to said valve and that 
are suitable for shifting by a column or column section the positions of 
the injection and draw-off points in an intermittent manner. 
The valves that are used are advantageously all-or-none valves. 
The process according to the invention (VARICOL) is better explained in the 
examples below, but its differences compared to the process of the 
simulated moving bed will be noted immediately: 
1. The zone lengths are not constant 
2. The number of columns per zone is not constant over the period 
3. The inlet/outlet lines are not moved simultaneously. 
Although oscillation introduces a disturbance in the system, it seems, 
surprisingly enough, that the performance levels of the VARICOL process 
are often better than those of the simulated mobile bed system (see 
Examples). 
As explained, implementation of the process according to the VARICOL 
invention is cyclic, so that after a given cycle time Nc.times..DELTA.T, 
the system regains its initial configuration. During this cycle, the 
number of columns in each zone has been varied, and for teaching purposes, 
it may be useful to define a mean number of columns per zone: 
&lt;Nb1&gt;=mean number of columns contained in zone 1 during a cycle 
&lt;Nb2&gt;=mean number of columns contained in zone 2 during a cycle 
&lt;Nb3&gt;=mean number of columns contained in zone 3 during a cycle 
&lt;Nb4&gt;=mean number of columns contained in zone 4 during a cycle 
Just as a simulated moving bed system can be presented by: 
LMS Nb1/Nb2/Nb3/Nb4 
we can represent a VARICOL periodic process by: 
VARICOL (Nb1)/(Nb2)/(Nb3)/(Nb4) 
Whereas the number of columns per zone has a real meaning for the LMS 
systems, however, the mean numbers which are not integers and which have 
no technical meaning are used simply for convenience for the VARICOL 
process.

EXAMPLES 
Example 1 
This VARICOL process has been used to achieve the separation of 
stereoisomers of phytol (3,7,1,15-tetramethyl-2-hexadecen-1-ol, C.sub.20 
H.sub.40 O). The synthetic phytol is a mixture of cis and trans isomers, 
whereby the latter is used in perfumery. 
The separation between the isomers of phytol is accomplished on silica 
(Lichroprep Si 60, 25-40 micrometers of Merck KGaA, Darmstadt) with an 
eluant that consists of heptane-ethyl acetate (75/25 v/v) at 27.degree. C. 
For the sake of simplicity, a solution that contains 50% of cis isomer and 
50% of trans isomer is prepared. According to measurements that are made 
on the laboratory scale, the adsorption isotherms were determined and 
adjusted suitably on an equation model of the modified Langmuir type: 
##EQU1## 
whereby n is the concentration of space i that is adsorbed on the solid, 
.lambda..sub.1, .lambda..sub.2, K.sub.1, K.sub.2, K.sub.1 and K.sub.2 are 
adjustable parameters, whereby C.sub.1 and C.sub.2 are the concentrations 
of radicals i and j in the mobile phase. 
With: 
##EQU2## 
Knowledge of the adsorption isotherms is not absolutely necessary to carry 
out the VARICOL process, but it helps to find the operating parameters 
that are suitable for obtaining suitable purities. The techniques that are 
used rely on numerical simulation methods that are described in, for 
example, "Fundamentals of Preparative and Non Linear Chromatography, G. 
Guiochon, S. Golsbran Shirazi and A. M. Katti, Academie Press, 1994." 
The shiftings of the injection point or of the fluid draw-off point are 
done in time t, which is a fraction of the period .DELTA.T. 
1. 5-Column VARICOL System 
Experience has shown that for a feedstock concentration of 6.4 g/l, a 
suitable set of flow rates in a system that comprises 5 columns of a 2.6 
cm-diameter and 16 cm length corresponds to 
______________________________________ 
Q.sub.eluant = 
24.98 ml/min Q.sub.feedstock = 
22.08 ml/min 
Q.sub.extract = 25.42 ml/min Q.sub.recycling = 106.84 ml/min 
______________________________________ 
For this set of flow rates, the optimum movement period of the inlet/outlet 
positions is: .DELTA.T =1.6 min for the simulated mobile bed system (LMS). 
The concentrations and purities of the extract and of the raffinate that 
are obtained by the various processes are given in Table 4. An overall 
purity is defined by the mean value of the purities of the extract and the 
raffinate. 
TABLE 4 
__________________________________________________________________________ 
Extract Raffinate 
cis 
trans 
purity 
cis 
trans 
purity 
Overall 
Configuration (g/l) (g/l) % (g/l) (g/l) % purity 
__________________________________________________________________________ 
VARICOL 
1.25 
1.25 
1.25 
1.25 
0.170 
2.690 
94.1 
3.060 
0.120 
96.2 
95.2 
t = 0 
2111 
t = .DELTA.T/4 1112 
t = .DELTA.T/2 1121 
t = 3.DELTA.T/4 1211 
LMS 1112 0.180 
2.560 
93.4 
3.050 
0.260 
92.1 
92.8 
LMS 1121 0.280 2.670 90.5 2.940 0.120 96.1 93.3 
LMS 1211 0.180 2.500 93.3 3.050 0.260 92.1 92.7 
LMS 2111 0.280 2.640 90.4 2.940 0.170 94.5 92.5 
VARICOL 
1.2 
1.2 
1.4 
1.2 
0.185 
2.694 
93.6 
3.050 
0.108 
96.6 
95.1 
t = 0 
1112 
t = .DELTA.T/5 1121 
t = 3.DELTA.T/2 1211 
t = 4.DELTA.T/5 2111 
__________________________________________________________________________ 
TABLE 4 
______________________________________ 
[Key to Table 4:] 
Extrait = Extract 
purete = purity 
Raffinat = raffinate 
purete = globale = overall purity 
______________________________________ 
All of the possible configurations of the simulated moving bed (for a 
5-column system) are present in Table 4. The best mean purity (93.3%) is 
obtained by the configuration 1/1/2/1. 
The 4-zone VARICOL process with a 1.25 column makes it possible to obtain a 
mean purity of 95.2%, which is therefore about 2% greater than the best 
result that is obtained with the LMS process. Let us emphasize that this 
ability of the VARICOL process to obtain higher purities with columns and 
flow rates that are similar to those of the LMS is extremely interesting. 
The second implementation of the VARICOL process makes it possible to 
illustrate an operation for which the time phase shift from line to line 
is not identical and which also shows good results. 
2. 8-Column Systems 
To keep the length of the column and the amount of stationary phase 
constant in the system, the length of each of the columns was reduced to 
10 cm. The same flow rates as those in the 5-column system were used by 
adjusting the period to .DELTA.T=1 min. 
The concentrations and purities that are obtained in the flow of the 
extract and raffinate for the various processes are presented in Table 5. 
An overall purity is defined as the mean value of the purities of the 
extract and the raffinate. 
TABLE 5 
__________________________________________________________________________ 
Extract Raffinate 
cis 
trans 
purity 
cis 
trans 
purity 
Overall 
Configuration (g/l) (g/l) % (g/l) (g/l) % purity 
__________________________________________________________________________ 
VARICOL 
1.5 
2.5 
1.5 
2.5 
0.80 
2.680 
97.1 3.170 
0.130 
96.1 
96.6 
1 t = 0 
1313 
t = .DELTA.T/2 2222 
VARICOL 
2.5 
2.5 
1.5 
1.5 
0.130 
2.720 
95.4 3.110 
0.090 
97.2 
96.3 
2 t = 0 
2312 
t = .DELTA.T/2 3221 
VARICOL 
1.5 
1.5 
2.5 
2.5 
0.180 
2.770 
93.9 3.060 
0.030 
99.0 
96.5 
3 t =0 1223 
t = .DELTA.T/2 2132 
LMS 2222 0.110 
2.720 
96.100 
3.240 
0.070 
97.8 
97.0 
__________________________________________________________________________ 
TABLE 5 
______________________________________ 
[Key to Table 5:] 
Extrait = Extract 
purete = purity 
Raffinat = raffinate 
purete = globale = overall purity 
______________________________________ 
In this case, the purities of LMS are already high (about 97%), and it was 
not possible to improve on these results with the VARICOL process. The way 
to obtain higher purities would be to increase the column lengths and/or 
to increase the number of columns within the framework of the process 
according to the invention and/or to change the flow rates that are used. 
Example 2 
The separation between fructose and glucose was studied in a Dowex 99 
monosphere (350 micrometers) in the form of calcium that uses water 
(65.degree. C.) as an eluant. Under these conditions, the adsorption 
isotherms are nearly linear, and the retention factors of the two sugars 
are provided by: 
##EQU3## 
1. 5-Column Systems 
Experience has shown that for a feedstock concentration of 50 g/l of each 
radical, a suitable set of flow rates for a system that consists of 
columns with a 2.6 cm diameter and 160 cm length is: 
##EQU4## 
For this set of flow rates, the optimum displacement period of the position 
of inlets/outputs is: .DELTA.T=6.4 minutes for the simulated moving bed 
(LMS). 
TABLE 6 
__________________________________________________________________________ 
Extract Raffinate 
Glucose 
Frucrose 
Purity 
Glucose 
Frucrose 
Purity 
Overall 
Configuration (g/l) (g/l) % (g/l) (g/l) % purity 
__________________________________________________________________________ 
VARICOL 
1.25 
1.25 
1.25 
1.25 
2.710 
39.380 
93.6 
41.890 
2.450 
94.5 
94.1 
t = 0 
1112 
t = .DELTA.T/4 1121 
t = .DELTA.T/2 1211 
t = 3.DELTA.T/4 2111 
LMS 1112 2.860 
37.010 
92.8 
41.820 
4.870 
89.6 
92.2 
LMS 1121 4.500 39.190 89.7 40.040 2.500 94.1 91.9 
LMS 1211 2.540 37.010 89.7 42.130 4.870 89.6 89.7 
LMS 2111 4.500 38.660 89.7 40.040 3.090 92.8 91.3 
__________________________________________________________________________ 
[Key to Table 6:] 
Extrait=extract 
purete=purity 
Raffinat=raffinate 
purete globale=overall purity 
The improvement that is obtained thanks to the 4-zone VARICOL process with 
a 1.25 column (Table 6) is also very significant here. The overall purity 
is nearly 3% greater than that obtained in the case of a standard LMS. 
2. Systems with 6, 7, and 8 Columns 
Other experiments were carried out and are presented in Tables 7, 8, and 9. 
The total column lengths and the flow rates were kept constant in the two 
types of tests for the same system. For each case, the period and the 
lengths of the columns were adjusted. 
6-Column System: L=1.33 m, .DELTA.T=5.32 min 
TABLE 7 
__________________________________________________________________________ 
Extract Raffinate Overall 
Glucose 
Frucrose 
Purity 
Glucose 
Frucrose 
Purity 
purity 
Configuration (g/l) (g/l) % (g/l) (g/l) % % 
__________________________________________________________________________ 
VARICOL 
1.5 
1.5 
1.5 
1.5 
2.11 
39.94 
95.0 
42.50 
1.88 95.8 
95.4 
t = 0 
1212 
t = .DELTA.T/2 2121 
LMS 1122 3.29 
38.73 
92.2 
41.35 
3.00 93.2 
92.7 
LMS 1212 1.02 36.37 97.3 43.79 5.56 88.7 93.0 
LMS 2112 3.29 38.19 92.1 41.35 3.59 92.0 92.0 
LMS 1221 2.97 38.73 92.9 41.67 3.00 93.3 93.1 
LMS 2121 5.05 40.78 89.0 39.44 0.78 98.1 93.5 
LMS 2211 2.97 38.19 92.8 41.67 3.59 92.1 92.4 
__________________________________________________________________________ 
[Key to Table 7:] 
Extrait=extract 
Purete=purity 
Raffinat=raffinate 
purete globale=overall purity 
7-Column System: L=1.14 m, .DELTA.T=4.56 min 
TABLE 8 
__________________________________________________________________________ 
Extract Raffinate Overall 
Glucose 
Frucrose 
Purity 
Glucose 
Frucrose 
Purity 
purity 
Configuration (g/l) (g/l) % (g/l) (g/l) % % 
__________________________________________________________________________ 
VARICOL 
1.75 
1.75 
1.75 
1.75 
1.81 
40.24 
95.7 
42.83 
1.54 96.5 
96.1 
t = 0 
1222 
t = .DELTA.T/4 2122 
t = .DELTA.T/2 2212 
t = 3.DELTA.T/4 2221 
LMS 1222 1.3 38.30 
96.7 
43.49 
3.47 92.6 
94.7 
LMS 2122 3.68 40.52 91.7 40.93 1.07 97.5 94.6 
LMS 2212 1.3 37.76 96.7 43.49 4.07 91.4 94.1 
LMS 2221 3.36 40.52 92.3 41.25 1.07 97.5 94.9 
__________________________________________________________________________ 
[Key to Table 8:] 
Extrait=extract 
Purete=purity 
Raffinat=raffinate 
purete globale=overall purity 
TABLE 9 
__________________________________________________________________________ 
Extract Raffinate Overall 
Glucose 
Frucrose 
Purity 
Glucose 
Frucrose 
Purity 
purity 
Type Configuration (g/l) (g/l) % (g/l) (g/l) % % 
__________________________________________________________________________ 
LMS 2222 1.62 
40.20 
96.1 
43.15 
1.41 96.8 
96.5 
VARICOL 
1.75 
1.75 
2.25 
2.25 
1.79 
40.27 
95.7 
42.93 
1.44 96.8 
96.2 
t = 0 
2132 
t = .DELTA.T/4 2222 
t = 3.DELTA.T/4 1223 
VARICOL 
1.75 
2.25 
1.75 
2.25 
1.26 
39.73 
96.9 
43.49 
1.99 95.6 
96.3 
a t= 0 
2222 
a t = 3.DELTA.T/4 1313 
VARICOL 
1.75 
2.25 
2.25 
1.75 
1.67 
40.33 
96.0 
42.69 
1.42 96.8 
96.4 
t = 0 
1322 
t = .DELTA.T/4 2222 
t = 3.DELTA.T/4 2231 
VARICOL 
2.25 
1.75 
2.25 
1.75 
2.17 
40.72 
94.9 
42.46 
1.00 97.7 
96.3 
t = 0 
2222 
t = 3.DELTA.T/4 3131 
VARICOL 
2.25 
1.75 
1.75 
2.25 
1.74 
40.09 
95.8 
42.94 
1.55 96.5 
96.2 
t = 0 
2213 
t = .DELTA.T/4 2222 
t = 3.DELTA.T/4 3122 
VARICOL 
2.25 
2.25 
1.75 
1.75 
1.7 40.24 
95.9 
42.91 
1.52 96.6 
96.3 
t = 0 
3221 
t = .DELTA.T/4 2222 
t = 3.DELTA.T/4 2312 
__________________________________________________________________________ 
8-Column System, L=1 m, .DELTA.T=4 min 
An analysis of the results that are presented in Tables 6, 7, 8, and 9 
leads to the following conclusions: 
A 5-column VARICOL system is more efficient than all of the possible LMS 5 
columns 
A 6-column VARICOL system is more efficient than all of the possible LMS 6 
columns, 
A 7-column VARICOL system is more efficient than all of the possible LMS 7 
columns, 
A 5-column VARICOL system makes it possible to attain purities that are 
equivalent to that which is obtained with an LMS with 6 columns. The 
VARICOL process therefore does not allow a significant reduction in cost, 
The VARICOL process is more advantageous for a system whose number of 
columns is less than 8.