METHOD OF CHROMATOGRAPHIC SEPARATION

Abstract: In a method using a chromatographic separation apparatus consisting of plurality of unit packed beds each having a supply inlet/extraction outlet, wherein the apparatus is effectively divided into four zones; an adsorption zone, a refining zone, a desorption zone, and a concentration zone. A supply and extrac­ tion step is performed in which all of the fluid flowing out of the adsorption zone is extracted through the nonadsorbate fluid extraction outlet, and then a recycle step, in which no fluid is supplied to or extracted from the bed, is performed to move the concentration distributions in the bed to a desired position. As a result, the method requires fewer unit beds, and enables extraction of components of higher purity.

Description: Background of the Invention The present invention relates to a method of chromatographic separation, in which a feedstock fluid and a desorbent fluid are supplied into an adsorbent-packed bed and as the feed-stock fluid moves through the bed, the components in said fluid are separated by interaction with the adsorbent and at least two fluids, one being rich in a component that interacts strongly with the adsorbent and the other being rich in a component that interacts weakly with the adsorbent, are extracted from the bed. Chromatographic separation is one of the separation techniques practiced extensively in industrial applications. While several techniques of chromatographic separation are known, a simulated moving-bed system has been used most extensively in large-scale operations. The apparatus used in a simulated moving-bed system is so adapted that a fluid stream is capable of unidirectional circulation through a bed packed with an adsorbent. The bed is provided with more than one set of supply inlet and extraction outlet, wherein a feed-stock fluid supply inlet, a nonadsorbate fluid extraction outlet, a desorbent fluid supply inlet and an adsorbate fluid extraction outlet are arranged in the order written in the direction of fluid flow. During the separating operation, one set of supply inlet and extraction outlet is always in an active state, and as a predetermined working time lapses, this active set is switched to the next corresponding set which is located immediately downstream. Therefore, when as many switching operations as the sets of supply inlet and extraction outlet in the bed have been effected, the active set of supply inlet and extraction outlet takes a full turn around the bed and returns to its initial position. For the purpose of the following discussion, the zone from a certain supply inlet or extraction outlet to a corresponding supply inlet or extraction outlet that is located immediately downstream is hereinafter referred to as "a unit packed bed". A packed bed can be regarded as a series connection of as many unit packed beds as the sets of supply inlet and extraction outlet employed. The "feedstock fluid supply inlet", "desorbent fluid supply inlet", "nonadsorbate fluid extraction outlet" and "adsorbate fluid extraction outlet" are named based on the function of an apparatus for supplying a fluid into or extracting it from the bed, and in practice, a single apparatus may have the ability to perform some of the four functions of interest. In fact, it is common practice for a single apparatus to serve both as a feedstock fluid inlet and as a desorbent fluid supply inlet, or serve both as a nonadsorbate fluid extraction outlet and as an adsorbate fluid extraction outlet. With respect to a set of supply inlet and extraction outlet that is in an active state, the zone between a feedstock fluid supply inlet and a nonadsorbate fluid extraction outlet is referred to as an adsorption zone, the zone between the nonadsorbate fluid extraction outlet and a desorbent fluid supply inlet as a refining zone, the zone between the desorbent fluid supply inlet and an adsorbate fluid extraction outlet as a desorption zone, and the zone between the adsorbate fluid extraction outlet and the feedstock fluid supply inlet as a concentration zone. Therefore, the packed bed consists of four zones, adsorption, refining, desorption and concentration, and each zone normally contains a plurality of unit packed beds. Each of the components to be separated in the packed bed forms a particular concentration distribution in the direction of feed flow and this concentration distribution, while retaining its shape, will move downstream through successive zones of the bed. A set of supply inlet and extraction outlet is switched to another set in synchronism with the movement of concentration distributions in such a way that a fluid can be supplied to a desired position on a particular concentration distribution while another fluid is extracted from another desired position. In the basic operation of a simulated moving bed, a feedstock fluid and a desorbent fluid are supplied into the bed through certain supply inlets at any point of time whereas a nonadsorbate fluid and an adsorbate fluid are extracted through certain extraction outlets, so taken as a whole, the operation can be regarded as being continuous with respect to the supply and extraction of fluids. The fluid to be extracted is only part of the fluid that reaches a cross section of the bed at which the outlet through which it is extracted is positioned and the greater part of the fluid will move downstream without being extracted. Normally, a fluid 4 ∼ 10 times the volume of the fluid that is supplied into each zone from the outside of the bed or which is extracted from each zone to the outside of the bed will flow into each zone from one located upstream thereof. Therefore, a particular concentration distribution that is formed in the bed is capable of moving downstream without being greatly distorted in spite of fluid extraction from the bed. As described above, a set of supply inlet and extraction outlet is switched to an immediately downstream set in synchronism with the downstream movement of a particular concentration distribution formed in the bed. Although the movement of a concentration distribution is continuous, switching between adjacent sets of supply inlet and extraction outlet is intermittent and this causes a time-dependent change in the composition of a fluid being extracted through one outlet within a unit working time. In order to attain better separation performance, it is preferred that the fluid being extracted should experience the smallest possible change in composition with time. To this end, the duration for which a set of supply inlet and extraction outlet is in active operation must be shortened and this set be frequently switched to successive sets of supply inlet and extraction outlet that are located downstream of the bed. But then, this requires a bed composed of many unit packed beds and the overall equipment becomes complex and costly. In consideration of its cost and the desired separation efficiency, the equipment commercially used typically consists of 6 ∼ 24 unit packed beds. A simulated moving-bed system according to the pre-amble of claim 1 is known from US-A-2 985 589. SUMMARY OF THE INVENTION An object, therefore, of the present invention is to provide a method of chromatographic separation that is capable of attaining a satisfactory separation efficiency with a simpler apparatus such as one composed of four unit packed beds. This object of the present invention can generally be attained by a method which performs separation of respective substances in a feedstock fluid with a chromatographic apparatus including a packed bed that is adapted to allow a fluid to flow cyclically in one direction and which is furnished with at least four sets of feedstock fluid supply inlet, nonadsorbate fluid extraction outlet, desorbent fluid supply inlet and adsorbate fluid extraction outlet, which are disposed in the order written in the direction of fluid flow, and said bed, taken as a whole, being divided into four zones by an active set of supply inlet and extraction outlet during operation, an adsorption zone occupying the space between the feedstock fluid supply inlet and the nonadsorbate fluid extraction outlet, a refining zone occupying the space between the nonadsorbate fluid extraction outlet and the desorbent fluid supply inlet, a desorption zone occupying the space between the desorbent fluid supply inlet and the adsorbate fluid extraction outlet, and a concentration zone occupying the space between the adsorbate fluid extraction outlet and the feedstock fluid supply inlet, and said active set of supply inlet and extraction outlet being switched to another set of supply inlet and extraction outlet located immediately downstream after the lapse of a predetermined working time. The object of the present invention can specifically be attained by performing the following two steps within said predetermined working time: (i) a supply and extraction step in which as part of the fluid flowing out of the desorption zone is allowed to flow into the concentration zone while the fluid flowing out of the concentration zone is allowed to flow into the adsorption zone, a feedstock fluid and a desorbent fluid are supplied into the packed bed through the feedstock fluid supply inlet and the desorbent fluid supply inlet, respectively, and at least part of the fluid flowing out of the adsorption zone is extracted from the packed bed through the nonadsorbate fluid extraction outlet, with part of the fluid flowing out of the desorption zone being extracted from the packed bed through the adsorbate fluid extraction outlet; and (ii) a circulation step in which the fluid in the packed bed is moved downstream without supplying a fluid into the bed or extracting a fluid from the bed. By performing these two steps within the predetermined working time, satisfactory separating performance can be attained in the present invention. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic of an apparatus suitable for use in the practice of the present invention; and Fig. 2 is a diagram showing concentration distributions formed within a packed bed. DETAILED DESCRIPTION OF THE INVENTION Stated more specifically, the method of the present invention is performed with an ordinary simulated moving bed (except that the number of unit packed beds in it may be smaller than in the prior art system) but the difference is in the way of operating such a conventional simulated moving bed. In accordance with the present invention: (i) when a feedstock fluid and a desorbent fluid are supplied into the bed and a nonadsorbate fluid and an adsorbate fluid extracted from the bed simultaneously, a portion of the fluid in the bed that has reached the position of the nonadsorbate fluid extraction outlet and which is greater than in the prior art method, sometimes the entire portion of said fluid, is extracted as a nonadsorbate fluid; and (ii) the fluid is supplied into or extracted from the bed intermittently; in other words, when taken as a whole, the operation of the bed includes a period during which only the fluid in the bed is moved downstream without supplying a fluid into or extracting it from the bed. In these two respects, the method of the present invention differs from both the basic method of operating a simulated moving bed and from any other known methods of operation. As already mentioned, a simulated moving bed consists of four zones and the adsorbate and nonadsorbate components in each zone have concentration distributions as typically shown in Fig. 2. The adsorbate component is present at high concentration in the desorption zone but it is not easy to move this component downstream of the bed because it interacts strongly with the packed adsorbent. On the other hand, the nonadsorbate component is predominant in the refining zone and can be readily moved downstream of the bed because its interaction with the adsorbent is weak. In this way, the ease with which a certain concentration distribution can be moved downstream varies depending upon the zone in which it is formed. The amount or distance the concentration distribution in each zone moves is proportional to the quantity of a fluid flowing through that zone, or the product of its flow rate (volume per time) and time. Therefore, in order to ensure that the concentration distribution in each zone is moved by the same amount, or by the width of a unit packed bed, within the duration of time for which a set of supply inlet and extraction outlet is operated, it is necessary that the quantity of the fluid flowing through each zone be adjusted to an appropriate value. For instance, the flow rate in the refining zone must be set to a value smaller than that in any other zone. In accordance with the present invention, concentration distributions in each zone are moved through two stages. The first stage is where a feedstock fluid and a desorbent fluid are supplied to the bed whereas a nonadsorbate fluid and an adsorbate fluid are extracted from the bed. At this stage, the flow rate of a fluid stream differs from zone to zone as it is subject to the influences of both the rate (volume per time) at which a fluid is supplied to the bed and the rate at which a fluid is extracted from the bed. The second stage is where the fluid is simply allowed to flow downstream of the bed with a fluid being neither supplied into nor extracted from the bed. This stage is solely for the purpose of moving concentration distributions and the flow rate and hence, the quantity, of a fluid in each zone is held constant. In the method of the present invention, an adsorbate fluid and a nonadsorbate fluid are extracted from the bed only at the first stage described above. The amounts by which concentration distributions are moved at this first stage are smaller than the total amount of movement effected when a set of supply inlet and extraction outlet is in an operational state, and therefore, the adsorbate and nonadsorbate fluids being extracted from the bed will experience a smaller time-dependent change in composition. In other words, compared to the prior art simulated moving-bed system in which fluids are extracted from the bed throughout the process of movement of concentration distributions in the bed, thereby causing substantial time-dependent changes in the compositions of extracted fluids, the method of the present invention successfully reduces such time-dependent changes by extracting fluids in only part of the process of movement of concentration distributions. The present invention is described hereinafter in greater detail with reference to the accompanying drawings. Fig. 1 is a schematic of a chromatographic separation apparatus that may be used in the practice of the present invention. Shown by 1 ∼ 4 are unit beds each packed with an adsorbent; 11 is a circulation pump for circulating fluids; 21 is a flow control valve; 31 ∼ 34 are feedstock fluid supply valves; 35 ∼ 38 are desorbent fluid supply valves; 39 ∼ 42 are adsorbate fluid extraction valves; and 43 ∼ 46 are nonadsorbate fluid extraction valves. Fig. 2 is a diagram showing the concentration distributions of the respective components formed within the packed beds when the apparatus shown in Fig. 1 is operated by the method of the present invention. Fig. 2 also shows the positions at which the supply of a feedstock fluid and a desorbent fluid into the bed is started (F and W), as well as the positions at which the extraction of an adsorbate fluid and a nonadsorbate fluid from the bed is started (P and R). Referring to Figs. 1 and 2, a supply and extraction step is first performed with the circulation pump 11 and flow control valve 21 being operated to circulate a predetermined amount of fluid. In this step, the feedstock and the desorbent are supplied through valves 31 and 37, respectively, while at the same time, the adsorbate fluid and the nonadsorbate fluid are extracted through valves 42 and 44, respectively. A fluid flows down the adsorption, refining, desorption and concentration zones at respective rates of R₁, R₂, R₃ and R₄ (volume per unit time), and this supply and extraction step continues for the period ϑ₁. Then, the supply of fluid to the beds and the extraction of fluid from the beds are stopped and a circulation step is performed, in which only the circulation of fluid through beds is effected by means of the circulation pump 11 until the concentration distribution curves are moved to their predetermined positions. A fluid flows down each zone at a rate of R₀ (volume per unit time), and this circulation step continues for the period ϑ₀. The above procedures complete the predetermined operation of valves 31, 37, 42 and 44 (step 1), which are then switched to their corresponding valves located downstream. These are valves 32, 38, 39 and 45 which are brought to an active state for repeating the operation described above (step 2). The apparatus shown in Fig. 1 consists of four unit packed beds, so four valve switching operations will bring the apparatus back to its initial state. The valves which are opened after each switching operation, the switching times and settings of a flowmeter are shown in Table 1 below. Step Description Opened valves Flowmeter setting Switching time 1 Supply/extraction step 31, 37, 42, 44 R₄ ϑ₁ Circulation step R₀ ϑ₀ 2 Supply/extraction step 32, 38, 39, 45 R₃ ϑ₁ Circulation step R₀ ϑ₀ 3 Supply/extraction step 33, 35, 40, 46 R₂ ϑ₁ Circulation step R₀ ϑ₀ 4 Supply/extraction step 34, 36, 41, 43 R₁ ϑ₁ Circulation step R₀ ϑ₀ Let us now consider the case where the apparatus shown in Fig. 1 is run in accordance with the prior art method of operating a simulted moving bed and the working times (i.e. valve switching times) are adjusted to the same values as adopted in the method of the present invention. Let assume that a fluid flows down the adsorption, refining, desorption and concentration zones at respective rates of R₁′, R₂′, R₃′ and R₄′ (volume per unit time). In order to ensure that in both methods, the concentration distributions in each zone are moved within a given working time by the same amount, the flow quantity within that working time must be made equal for each zone, and this requires: R₁′(ϑ₀ + ϑ₁) = R₁ϑ₁ + R₀ϑ₀ (1) R₂′(ϑ₀ + ϑ₁) = R₂ϑ₁ + R₀ϑ₀ (2) R₃′(ϑ₀ + ϑ₁) = R₃ϑ₁ + R₀ϑ₀ (3) R₄′(ϑ₀ + ϑ₁) = R₄ϑ₁ + R₀ϑ₀ (4) In the method of the present invention, the ratio of the amount of movement of concentration distributions in the supply and extraction step to the total amount of movement of concentration distributions in the adsorption zone within a given working time, namely, the ratio γ₁ of the width of the portion of concentration distributions extracted as a nonadsorbate fluid to the width of concentration distributions moved in the adsorption zone is given as follows from eq. (1): Similarly, the ratio γ₂ of the width of the portion of concentration distributions extracted as an adsorbate fluid to the width of concentration distributions moved in the desorption zone is given as follows from eq. (3): The smaller the value of γ, the smaller the change that occurs in the composition of the extracted fluid. Eqs. (5) and (6) show that the value of γ becomes minimum when R₀ϑ₀ is at maximum. As stated earlier in this specification, the quantity of flow in the refining zone is minimum in the usual operation of a simulated moving bed, and eq. (2) shows that when R₂ϑ₁ = 0, the quantity of flow in the refining zone becomes minimum irrespective of the value of R₀ϑ₀. This means that in the supply and extraction step, the quantity of fluid flowing down the refining zone is reduced to zero, or all the quantity of fluid flowing down the adsorption zone is extracted as a nonadsorbate fluid. In this case, the quantity of nonadsorbate fluid extracted is obviously greater than that of the feedstock fluid supplied because the quantity of the adsorbate fluid extracted simultaneously is smaller than that of the desorbent supplied and a fluid of the quantity corresponding to that difference will flow into the adsorption zone via the concentration zone. This also enables the simulated moving bed to be run without violating its basic operating principle that the quantity of flow in the refining zone, R₂ϑ₁ + R₀ϑ₀, must be held smaller than that in the concentration zone, R₄ϑ₁ + R₀ϑ₀. Fig. 2 shows schematically which portion of the concentration distributions in the adsorption and desorption zones will be extracted from the bed. A fluid flows to the right as viewed in the drawing, and the concentration distribution curves are also shifted to the right. In the supply and extraction step of the method of the present invention, the concentration distribution curves are shifted and fluids are extracted from part of the width of the concentration distribution curves in the adsorption and desorption zones. Subsequently, there occurs only a shift in the concentration distribution curves in the circulation step. When the total of the widths by which the concentration distribution curves are shifted in the two steps becomes equal to the width of a unit packed bed, the set of supply inlet and extraction outlet located immediately downstream is activated and the procedures described above will be repeated. The prior art method of chromatographic separation on a simulated moving-bed system does not have a circulation step and fluids are supplied and extracted from the width of concentration curves corresponding to that of a unit packed bed. As a result, γ is always maintained at unity. If the number of beds is small, the concentration at each extracting portion will vary greatly between the starting point of extraction and the end point, thereby making it difficult to produce satisfactory results. Furthermore in the case above-described, the width of each supply portion becomes large and there occurs a corresponding increase in disturbances, leading to low separation efficiency. In accordance with the present invention, the width over which fluids are supplied or extracted can be so adjusted as to ensure high separation efficiency in the presence of a small number of beds. The following examples are provided for the purpose of further illustrating the present invention. EXAMPLE 1 Using an apparatus of the type shown in Fig. 1, a feedstock (a mixture of fructose and glucose in aqueous solution) having the composition shown in Table 2 was separated chromatographically. The absorbent and desorbent used were a Ca-form strongly acidic cation-exchange resin (DIAION®FRK-101 of Mitsubishi Kasei Corp.) and water, respectively. Component Feedstock Fructose fraction Glucose fraction Recovery Fructose 45.1 93.8 3.7 95.5 Glucose 50.3 4.9 89.0 95.6 Oligosaccharide 4.6 1.3 7.3 - wt%-DS 60.2 36.6 25.5 - A bed composed of four series-connected columns packed with a total of 3,140 ml of adsorbent was held at 65°C and cyclic separation was performed under the conditions shown in Table 3 below. Parameter Unit Value R₀ ml/h 1292 R₁ ml/h 1292 R₂ ml/h 0 R₃ ml/h 1209 R₄ ml/h 409 ϑ₁ sec 390 ϑ₀ sec 1022 In order to minimize the width of fluid supply and extraction, R₂ was adjusted to zero and in order to ensure that the pressure loss occurring in the packed bed in the supply and extraction step would be substantially equal to that occurring in the circulation step, R₀ was made equal to R₁. The composition of each fraction after a steady state was reached and the recovery of each component are shown in Table 2. EXAMPLE 2 An aqueous solution of oligosaccharide having the composition shown in Table 4 was subjected to chromatographic separation using the same apparatus as that employed in Example 1 except that a Na-form strongly acidic cation-exchange resin (DIAITON® UBK-530K) was used as an adsorbent. The specific conditions of the experiment are shown in Table 5 below. Component Feedstock DP₂ fraction DP₃+ fraction Recovery DP₁ 1.10 1.20 0.76 - DP₂ 48.30 82.10 4.71 95.8 DP₃+ 50.60 16.70 94.53 81.1 wt%-DS 60.00 15.40 10.1 - Parameter Unit Value R₀ ml/h 1814 R₁ ml/h 1179 R₂ ml/h 0 R₃ ml/h 1814 R₄ ml/h 817 ϑ₁ sec 205 ϑ₀ sec 585 In the experiment of Example 2, R₂ = 0 and R₀ = R₃. The composition of each fraction after a steady state was reached and the recovery of each component are shown in Table 4. COMPARATIVE EXAMPLES 1 AND 2 The same feedstocks as those supplied in Examples 1 and 2 were subjected to chromatographic separation by a prior art 8-bed simulated moving-bed system under the same fluid loads and desorbent ratios as those employed in Examples 1 and 2. The results are shown in Tables 6 and 7. Component Feedstock Fructose fraction Glucose fraction Recovery Fructose 42.4 91.9 4.9 93.8 Glucose 52.3 6.8 87.1 94.4 Oligosaccharide 5.3 1.3 8.0 - wt%-DS 59.9 33.9 26.0 - Component Feedstock DP₂ fraction DP₃+ fraction Recovery DP₁ 1.00 1.00 0.90 - DP₂ 49.30 75.80 5.30 95.9 DP₃+ 49.70 23.20 93.80 71.4 wt%-DS 60.30 18.60 8.40 - In Example 1, the experiment was conducted in order to obtain a pure product of fructose. Comparison between Tables 2 and 6 shows that the method of the present invention achieved an improvement of ca. 2 points in purity and recovery. In Example 2, the experiment was conducted in order to obtain a pure product of DP₃+. Comparison between Tables 4 and 7 shows that the method of the present invention achieved an improvement of ca. 10 points in recovery. As described on the foregoing pages, if the volume of feedstock solution, the value of desorbent ratio and the amount of adsorbent are the same, the chromatographic separation method of the present invention attains results that are comparable to or better than those accomplished by a conventional simulated moving-bed system employing a greater number of beds. Therefore, the method of the present invention permits the use of a simpler apparatus and realizes a significant reduction in initial cost.

Claims: In a method which performs separation of respective substances in a feedstock fluid with a simulated moving bed, a chromatographic apparatus including a packed bed that is adapted to allow a fluid to flow cyclically in one direction and which is furnished with a set of feedstock fluid supply inlet, nonadsorbate fluid extraction outlet, desorbent fluid supply inlet and adsorbate fluid extraction outlet, which are disposed in the order written in the direction of fluid flow, and said bed, taken as a whole, being divided into four zones, an adsorption zone occupying the space between the feedstock fluid supply inlet and the nonadsorbate fluid extraction outlet, a refining zone occupying the space between the nonadsorbate fluid extraction outlet and the desorbent fluid supply inlet, a desorption zone occupying the space between the desorbent fluid supply inlet and the adsorbate fluid extraction outlet, and a concentration zone occupying the space between the adsorbate fluid extraction outlet and the feedstock fluid supply inlet, and said one set of supply inlet and extraction outlet being adapted to be switched to another set of supply inlet and extraction outlet located downstream after the lapse of a predetermined working time, the improvement wherein the following two steps are performed within said predetermined working time: (i) a supply and extraction step in which as part of the fluid flowing out of the desorption zone is allowed to flow into the concentration zone while the fluid flowing out of the concentration zone is allowed to flow into the adsorption zone, a feedstock fluid and a desorbent fluid are supplied into the packed bed through the feedstock fluid supply inlet and the desorbent fluid supply inlet, respectively, and at least part of the fluid flowing out of the adsorption zone is extracted from the packed bed through the nonadsorbate fluid extraction outlet, with part of the fluid flowing out of the desorption zone being extracted from the packed bed through the adsorbate fluid extraction outlet; and (ii) a circulation step in which the fluid in the packed bed is moved downstream without supplying a fluid into or extracting a fluid from the bed. A method according to claim 1 wherein the entire portion of the fluid flowing out of the adsorption zone is extracted through the nonadsorbate fluid extraction outlet in the supply and extraction step. A method according to claim 1 wherein part of the fluid flowing out of the adsorption zone is admitted into the refining zone whereas the remainder is extracted through the nonadsorbate fluid extraction outlet in the supply and extraction step.

Inventors: TAMURA, MASAO C/O RYOKA TECHNO ENGINEERING &, TANIMURA, MASATAKE C/O RYOKA TECHNO ENGINEERING &, TESHIMA, TAKASHI C/O RYOKA TECHNO ENGINEERING &, Tamura, Masao c/o Ryoka Techno Engineering &amp;, Tanimura, Masatake c/o Ryoka Techno Engineering &amp;, Teshima, Takashi c/o Ryoka Techno Engineering &amp;
Applicants: MITSUBISHI KASEI ENGINEERING COMPANY
Application year: 1989
Main classification: B01D15
IPC codes: G01N30, B01D15