JPH10128005A - Method for determining operating condition of pseudo moving bed type separator and pseudo moving bed separator - Google Patents

Abstract

PROBLEM TO BE SOLVED: To enable automatic operation by determining working operating conditions not exceeding upper limit pressure of a pseudo moving bed type separator from the relation between a flow rate of raw material solution and pressure in a single column when the raw material solution is passed through the single column packed with separating packing which is same as those with which columns of the pseudo moving bed type separator is packed. SOLUTION: Through a single column packed with packings which is same as those with which columns of a pseudo moving bed type separator, raw material solution is passed at different flow rates, and pressure of the single column at each flow rate is measured. Each obtained flow rate of the raw material solution and the pressure value in the single column at the flow rate are inputted by an inputting means. From the flow rate value X and the pressure value Y inputted, a linear relational expression, Y=aX+b, is calculated. As an arithmetic means, working operating conditions are determined so that pressure in a zone formed by the column may be within an arbitrary range not exceeding specific system pressure of the pseudo moving bed type separator.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for determining operating conditions of a simulated moving bed type separation apparatus and a simulated moving bed type separation apparatus, and more particularly, to a method for easily determining the operating conditions of a simulated moving bed type separation apparatus. The present invention relates to a method for determining operating conditions that can be performed and a simulated moving bed type separation apparatus that can efficiently and automatically operate under desired conditions by the method for determining operating conditions.

[0002]

2. Description of the Related Art In a conventional chromatographic separation method using a simulated moving bed type separation apparatus, a plurality of columns containing a packing material therein are connected in series, and a front end and a rear end of the columns are connected to a fluid passage (or a fluid passage). A raw material-containing solution containing a raw material that is a mixture of components to be separated, into a packed bed, which is connected endlessly by being connected by a An eluent is introduced, and a liquid containing components separated at the same time and a liquid containing other components are extracted, and the packed bed in the simulated moving bed type separation apparatus has an eluent inlet, an adsorbent, Extraction port for liquids containing substances that are easily absorbed (extract; solution rich in adsorbate or strongly adsorbate), introduction port for solution containing raw materials, and liquids containing substances that are difficult to adsorb (raffinate; The outlets of the fluid are arranged in this order along the flow direction of the liquid, and the inlets and outlets are arranged in the flow direction of the fluid while maintaining their relative positional relationship in the circulation flow path. Are moved intermittently one after another.

[0003] Such a conventional industrial simulated moving bed type separation apparatus is based on a system developed by UOP (Universal Oil Products, Inc.) in 1967, and is now variously improved by various engineering companies. Simulated moving bed separation devices are being developed. As a typical example, a plant example for separating fructose, grape and the like is known. Control of such a system usually involves accurately measuring the flow rate in each pump incorporated in the circulating fluid passage or each zone formed in the circulating fluid passage in the simulated moving bed separation device, and measuring the data of the data. Is generally performed manually by analyzing the data by a computer and presenting flow rate control data to an operator.

[0004] Further, there is also known an apparatus having a system for monitoring by a concentration meter having a low pressure resistance (usually a withstand pressure of 10 kg / cm ² or less) disposed in a circulating fluid passage. However, in these proposed industrial simulated moving bed separators, an ion exchange resin, a synthetic adsorbent, and an inorganic adsorbent (eg, zeolite) are used as fillers, and the particle size of these fillers is 200 μm. As described above, the withstand pressure setting during the operation of the entire system is approximately 10 kg / cm ² or less. Therefore, in these monitoring systems, HPLC level packing material (particle size is 1 to 100 μm)
In the simulated moving bed type separation apparatus using m), there is a relation with the processing flow rate, but the system pressure is generally 50 kg / cm ² or more. It is known that in such a simulated moving bed type separation apparatus, productivity is improved by shortening the cycle time and increasing the flow rate by the pump.

Further, in the current monitoring system and system control method, it is desired to strictly control the flow velocity of the fluid flowing in the circulation flow path.

However, in a simulated moving bed type separation apparatus using a packing material of the HPLC type, in order to efficiently produce a product of stable quality during continuous operation, at present, optimal operating conditions rely on experience and intuition. It is a situation that has to be decided.

However, as an example of a conventional monitoring method in a low pressure simulated moving bed type chromatographic separation, for example, every time the extract or raffinate outlet intermittently moves at regular intervals, it is discharged from the outlet. A method for measuring the concentration of a solute in a solution is known.

However, the concentration of the liquid discharged from the outlet fluctuates greatly before and after the intermittent movement of the outlet, making it difficult to monitor a change in the concentration accurately. In the separation, there is a problem that the state of the separation cannot be accurately monitored by monitoring only the concentration.

Japanese Patent Application Laid-Open No. 4-131104 discloses "In a simulated moving bed type chromatographic separation method, the supply port and the discharge port are intermittently measured by measuring the fluid component concentration of one or both of the fluid discharge ports. A method of controlling a simulated moving bed system, characterized in that a predetermined component purity is adjusted and maintained by shortening or extending the time required for moving the moving bed.

In the control method described in this publication, since the pipes from the supply port and the outlet to the concentration detector are usually long, a time lag actually occurs although the concentration is detected at the supply port or the outlet. And accurate concentration detection is not possible. In addition to the time lag, diffusion or convection of components occurs in the extract or raffinate flowing in the pipe, and there is a problem that accurate concentration detection cannot be performed in this regard.

As described above, in the conventional simulated moving bed type chromatographic separation, it is not possible to accurately grasp the concentration or optical purity that changes with time, and it is not possible to quickly determine the state of the separation. Had. Further, since the state of separation cannot be determined quickly, it is necessary to set the operating conditions such as the time interval for intermittently moving the inlet and the outlet, the flow rate of the circulating fluid, and the temperature to optimal conditions. There is a problem that it is difficult to perform efficient chromatographic separation.

[0012]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a simulated moving bed type separation apparatus which has been separately settled without long-term running-in operation, collecting various data and determining optimum operation conditions. Operating condition determining method for simulated moving bed type separator capable of determining desired optimum operating conditions in simulated moving bed type separator based on data obtained by single column chromatographic analysis, and such operating condition determining method The present invention is to provide a simulated moving bed type separation apparatus capable of automatically performing the separation. Another object of the present invention is to provide a method for determining an operating condition of a simulated moving bed type separation apparatus in which a desired operating condition is easily determined within a range not exceeding an inherent upper limit pressure value of the apparatus, and such a method. An object of the present invention is to provide a simulated moving bed type separation apparatus which can be automatically operated by a simple operation condition determining method.

[0013]

Means of the present invention for solving the above problems are as follows.

(1) A plurality of packed beds accommodating a separating filler are connected endlessly to form a circulating fluid passage in which fluid can be forcedly circulated in one direction. Inside, an eluent inlet for introducing an eluent, an extract outlet for extracting a solution rich in adsorbate or strongly adsorbate, and a raw solution inlet for introducing a raw material solution containing a mixture of components to be separated. A raffinate outlet for extracting a solution rich in non-adsorbate or weakly adsorbate,
It is provided in this order in the flow direction of the fluid, and the respective inlets and outlets are intermittently moved, formed on the packed bed between the eluent inlet and the extract outlet, and concentrated. Desorption zone in which the separated packing material containing the adsorbed component or strongly adsorbate comes into contact with the eluent and the adsorbed component or strongly adsorbed component is expelled from the separating packing material
(IV), a non-adsorbed component or a weakly adsorbed component formed on the packed bed between the extract outlet and the raw material solution inlet and remaining on the separation filler is expelled to adsorb or strongly adsorb A concentration zone (III) where the components are concentrated is formed on a packed bed between the raw material solution inlet and the raffinate outlet, and the raw material solution comes into contact with the separation filler, and the separation filler has an adsorbed component or a strong component. Purification zone where adsorbed components are adsorbed and non-adsorbed or weakly adsorbed components are collected together with the eluent
(II), and the content of the non-adsorbed component or the weakly adsorbed component formed on the packed bed between the raffinate discharge port and the eluent inlet, where the non-adsorbed component or the weakly adsorbed component is adsorbed by the separation filler. Adsorption zone (I) where less eluent is recovered
Is a method for determining operating conditions of a simulated moving bed type separation apparatus formed by a plurality of packed beds, and a single column filled with the same separation filler as the separation filler is provided with a raw material solution containing a plurality of components. Perform chromatographic analysis by injection,
Based on the preparative conditions obtained as a result of the chromatographic analysis, the initial operating conditions of the simulated moving bed type separation device,
The feed amount of the raw material solution, the feed amount of the eluent, the extraction amount from the raffinate extraction port and the extract extraction port, and the step time were determined, and the determined initial operation conditions and the same separation as the separation filler were determined. From the relationship between the flow rate of the raw material solution and the pressure in the single column when passing the raw material solution through the single column filled with the filler,
A method for determining operating conditions of a simulated moving bed type separation device that does not exceed an upper limit pressure of the simulated moving bed type separation device, wherein (2) the simulated moving bed according to (1). In the method for determining the operating conditions of the type separation device, the initial operating conditions are subjected to chromatographic analysis by injecting a raw material solution containing a plurality of components into a single column filled with the same separation filler as the separation filler, Outflow start time (T1s) of a predetermined previous component which first flows out of a single column among the components in the raw material solution, which is data obtained as a result of the chromatographic analysis, and a time at which the amount of distillation of the previous component becomes maximum ( T1), the outflow end time of the predetermined post-component (T2s),
The time (T2) at which the amount of the distillate of the rear component is maximized, between the end time of the outflow of the previous component and the start time of the flow of the rear component, and the time (TV) at which the concentration of the outflow component is the minimum. ,
And (3) a method for determining operating conditions of the simulated moving bed type separation apparatus according to the above (1), which is determined based on the concentration (C) of the raw material solution to be injected into the single column. A plurality of packed beds are connected endlessly to form a circulating fluid flow path in which fluid can be forcedly circulated in one direction, and an eluent inlet for introducing an eluent into the circulating fluid flow path. An extract outlet for extracting a solution rich in adsorbate or strongly adsorbate, a raw solution inlet for introducing a raw solution containing a mixture of components to be separated, and a solution rich in non-adsorbate or weak adsorbate The raffinate outlet is provided in this order in the direction of the flow of the fluid, and the respective inlets and outlets are intermittently moved, so that the filling between the eluent inlet and the extract outlet is provided. A desorption zone (IV), in which a separating packing material formed on a packed bed and containing a concentrated adsorbing component or strongly adsorbate comes into contact with an eluent and an adsorbing component or a strongly adsorbing component is expelled from the separating packing material, an extract Concentration formed on the packed bed between the discharge port and the raw material solution inlet, where non-adsorbed or weakly adsorbed components remaining on the separation filler are expelled and adsorbed or strongly adsorbed components are concentrated. zone
(III), formed on the packed bed between the raw material solution inlet and the raffinate discharge port, the raw material solution comes into contact with the separating filler, and the adsorbing component or the strongly adsorbing component is adsorbed on the separating filler, and A purification zone (II) where adsorbed or weakly adsorbed components are collected together with the eluent, and a packed bed between the raffinate discharge port and the eluent inlet, where non-adsorbed or weakly adsorbed components are packed for separation. A simulated moving bed type separation apparatus in which an adsorption zone (I) for collecting an eluent having a low content of non-adsorbed components or weakly adsorbed components by being adsorbed by the agent is formed by a plurality of packed beds. Chromatographic analysis is performed by injecting a raw material solution containing multiple components into a single column packed with the same packing material for separation as the packing material.As a result of the chromatographic analysis, components in the raw material solution flow out of the single column first Do Flow start time constant before component (T
1s), the time (T1) at which the amount of distillation of the preceding component is maximized,
The time (T2s) at which the outflow of the predetermined rear component is reached, the time (T2) at which the amount of distillation of the rear component is maximized, and the time between the end time of the outflow of the preceding component and the time at which the outflow of the rear component starts. ,
Input means for inputting the time (Tv) at which the concentration of the effluent component becomes minimum and the concentration (C) of the raw material solution to be injected into the single column, and a simulated moving bed based on the chromatographic analysis result input from the input means Calculate the feed amount of the raw material solution, the feed amount of the eluent, the amount of raffinate withdrawal and the amount of withdrawal from the extract withdrawal, and the step time, which are the initial operating conditions of the type separation device, A calculating means for controlling an operating condition that does not exceed an upper limit pressure of the simulated moving bed type separation apparatus from a relationship between a flow rate and a pressure in a single column and the operating initial condition; and an operating operation determined by the calculating means. And a control means for controlling operation according to conditions.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION A method for determining operating conditions of a simulated moving bed separator according to the present invention uses the simulated moving bed separator according to the present invention.

The simulated moving bed type separation apparatus according to the present invention has a circulating fluid flow path capable of forcibly circulating a fluid in one direction by connecting a plurality of packed beds containing a packing material for separation in an endless manner. Have.

The packed bed containing the packing material for separation is usually called a column. The industrial circulating fluid flow path is formed by connecting a plurality of columns accommodating the separation filler in an endless manner via a pipe such as a pipe.

The circulating fluid flow path using the column is provided with a fluid forced circulation means so that the fluid can be forcibly circulated in one direction in the circulating fluid flow path.

The fluid forced circulation means may be of any structure, type, etc. as long as the fluid can be forcibly circulated in one direction. Can be mentioned. Further, even if a pump is not used, a combination of a pressure regulating valve that enables the fluid to circulate by adjusting the pressure balance may be used as the fluid forced circulation means.

In addition, the pipes connecting the columns forming the circulating fluid flow path are provided with an eluent (desorbed liquid or desorbent) along the flow direction of the fluid flowing through the circulating fluid flow path. ), An extract outlet for extracting a solution rich in adsorbate or strongly adsorbate (also referred to as extract), and a raw material containing a mixture of components to be separated. A raw material solution inlet for introducing a solution (also referred to as a feed);
A raffinate outlet for extracting a solution (also referred to as a raffinate) rich in non-adsorbate or weak adsorbate;
They are provided in this order.

In the simulated moving bed type separator according to the present invention, the eluent inlet, extract outlet, raw material solution inlet and raffinate outlet are circulated in this order and without changing their relative positions. It is formed so as to be switched at regular intervals along the flow direction of the fluid. For switching between the inlet and the outlet, switching means such as a rotary valve or an on-off opening / closing valve is employed.

Until the inlet and the outlet are switched, a desorption zone (IV) is formed in the packed bed from the eluent inlet to the extract outlet, and the packed bed from the extract outlet to the raw material solution inlet is formed. A concentration zone (III) is formed, a purification zone (II) is formed in the packed bed from the raw material solution inlet to the raffinate outlet, and an adsorption zone (I) is formed in the packed bed from the raffinate outlet to the eluent inlet. Is formed.

In the desorption zone (IV), the eluent introduced from the eluent inlet flows through the packed bed together with the fluid, and when the eluent comes into contact with the separating packing, it is adsorbed on the separating packing. The adsorbate component (which is an easily adsorbable component and is also referred to as a strongly adsorbed component) is desorbed from the filler, and the adsorbate component or the strongly adsorbed component is extracted from the extract outlet as an extract. . In the desorption zone (IV), the concentration of the adsorbate component in the fluid in the zone immediately after the eluent inlet is substantially close to 0, and the concentration of the adsorbate component in the fluid in this zone along the direction of travel of the fluid. Rises.

In the concentration zone (III), a non-adsorbate component (a component that is difficult to adsorb or a non-adsorbent component in the raw material solution introduced through the raw material solution inlet), and is also referred to as a weakly adsorbed component. ) Is adsorbed to the separation filler, and the adsorbate component is desorbed from the filler. In the concentration zone (III), in the region from the extract outlet to the raw material solution inlet, the non-adsorbate component in the raw material solution is adsorbed on the separation filler, while the adsorbate component is separated from the separation filler. As it is desorbed, the concentration of the adsorbate component in the fluid changes from increasing to decreasing along the traveling direction of the fluid, while the concentration of the non-adsorbate component in the fluid starts to increase.

In the purification zone (II), the adsorbate component in the raw material solution introduced from the raw material solution inlet is adsorbed by the separation filler, and the non-adsorbate component adsorbed by the separation filler is desorbed. You. In this purification zone (II), while adsorbing adsorbate components in the raw material liquid introduced from the raw material solution inlet,
Desorb non-adsorbate components. In this purification zone (II), in the region from the raw material solution inlet to the raffinate outlet, the concentration of the adsorbate component in the fluid approaches substantially 0, and the concentration of the non-adsorbate component increases, A liquid containing a high concentration of non-adsorbate components is extracted from the raffinate extraction port.

In the adsorption zone (I), the non-adsorbate components are completely desorbed, and the separating packing adsorbs the adsorbate components, while only the eluent containing substantially no non-adsorbate components and adsorbate components Is discharged to the recycling line. In the adsorption zone (I), the concentration of the non-adsorbate component in the fluid decreases to substantially zero.

The column contains a separating filler capable of adsorbing the component to be separated. Preferred examples of the separation filler include a filler for liquid chromatogram (LC) such as a normal phase filler and a reversed phase filler, and more preferably a HPLC filler. .

Further, as specific examples of suitable fillers for separation, for example, various known fillers for isomer separation can be used. For example, examples of the filler for separating optical isomers include a filler for optical resolution utilizing an optically active polymer compound and a low molecular compound having optical resolution ability. Examples of the optically active polymer compound include a polysaccharide derivative (eg, an ester or carbamate of cellulose or amylose), a polyacrylate derivative, or a filler in which a polyamide derivative is supported on silica gel, or the polymer itself without using silica gel. And a crosslinked filler obtained by further crosslinking a polymer. Examples of the low molecular weight compound having optical resolution ability include an amino acid or a derivative thereof, a crown ether or a derivative thereof, a cyclodextrin or a derivative thereof, and the like. These low molecular compounds are usually used by being supported on an inorganic carrier such as silica gel, alumina, zirconia, titanium oxide, silicate and diatomaceous earth, and an organic carrier such as polyurethane, polystyrene and polyacrylic acid derivatives.

Commercially available fillers for optical resolution can be used. For example, CH 4 (manufactured by Daicel Chemical Industries, Ltd.) can be used.
IRALCEL OB®, CHIRALCEL OD®,
CROWNPAK CR (+) (registered trademark), CHIRALCEL CA-1 (registered trademark), CHIRALCEL OA (registered trademark), CHIRALCEL OK (registered trademark), CHIRALCEL OJ (registered trademark), CHIRALCEL OC (registered trademark), CHIRALCEL OF ( Registered trademark), CHIRALCEL OG
(Registered trademark), CHIRALPAK WH (registered trademark), CHIRALPAK
WM (R), CHIRALPAK WE (R), CHIRALPA
K OT (+) (registered trademark), CHIRALPAK OP (+) (registered trademark), CHIRALPAK AS (registered trademark), CHIRALPAK AD (registered trademark), CHIRALCEL OJ-R (registered trademark), CHIRALCEL OD-R
(Registered trademark) and the like can be mentioned as a preferable example.

As a filler suitable for dividing an aqueous isomerized saccharide solution containing an oligosaccharide into an aqueous fructose solution rich in fructose and an aqueous glucose solution rich in glucose, alkaline earth metal salts such as calcium, barium and stringium are used. The type of ion exchange resin for strong acidity and the exchangeable cation are ammonium,
Sodium, potassium, calcium, strontium,
A crystalline aluminosilicate such as zeolite Y substituted with barium or the like can be given.

Examples of suitable fillers for separating fatty acids and triglycerides include basic ion exchange resins having a skeleton of a copolymer of styrene and divinylbenzene.・ Weakly basic ion exchange resins such as Amberlite IRA93 manufactured by Haas and Duolite A377 manufactured by Sumitomo Chemical Co., Ltd .; Amberlite IRA manufactured by Rohm and Haas
400, Duolite A16 manufactured by Sumitomo Chemical Co., Ltd.
1 and the like.

In addition, various known fillers which are considered suitable for separating various substances can be used.

The average particle size of the separation filler packed in the column varies depending on the type of the component to be separated, the volume flow rate of the solvent flowing through each unit column, and the like. , Usually 1 to 100 µm, preferably 2 to 5 µm.
0 μm. However, if the pressure loss in the column forming the simulated moving bed is to be suppressed to a small value, 10 to 5
It is desirable to adjust the average particle size of the separation filler to 0 μm. When the average particle size of the separation filler is within the above range, the pressure loss in the simulated moving bed can be reduced, and for example, can be suppressed to 50 kgf / cm ² or less. On the other hand, the larger the average particle size of the separation filler, the lower the theoretical number of adsorption stages. Therefore, considering that a practical theoretical plate number is achieved, the average particle size of the separation filler is usually 15 to 75 μm.

The eluent (sometimes referred to as a desorbent or a desorbent) supplied to the circulating fluid flow path is, for example, alcohols such as methanol, ethanol and isopropanol, pentane, hexane, heptane and the like. Examples thereof include hydrocarbons and various organic solvents, a mixed solution thereof, a mixed solution of a highly polar organic solvent such as methanol and acetonitrile, water and a buffer, and the like.

This eluent can be employed as a normal phase mobile phase or a reverse phase mobile phase. Which eluent is preferable is appropriately determined depending on the type of the component or compound to be separated. In addition, the eluent may contain a basic substance such as diethylamine as an additive, or an acidic compound such as acetic acid. When these additives are contained in the eluate, the separation is improved. be able to. The raw material solution supplied to the circulating fluid flow path is not particularly limited as long as it is a multi-component mixture such as a two-component mixture having a solute that needs to be separated. Examples of various compounds used in the field include thalidomide, a pharmaceutical, EPN, an organic phosphorus-based pesticide, glutamic acid monosodium salt, a chemical seasoning, and menthol, a flavoring agent, and optically active alcohols. And optically active esters.

The solute includes, for example, optical isomers, positional isomers, and a mixture of components necessary and unnecessary from a certain viewpoint.

In the present invention, the solute may be a multi-component mixture of a plurality of components to be separated, for example, a three-component or a four-component.

In the case of a multi-component mixture, in order to separate the required one component using the simulated moving bed type separation apparatus of the present invention, two groups, ie, a group containing the required component and a group not containing the required component are used. The operation of separating into two groups, that is, separating the group containing the required one component into two groups, a small group containing the required one component and another small group, and so on, is performed. The necessary components can be separated by repeating the number of times.

Also, a batch operation using a separation apparatus other than the simulated moving bed type separation apparatus and the simulated moving bed type separation apparatus of the present invention can be used to separate the required one component from the multi-component mixture.

Since the fluid circulates in the circulating fluid flow path in the simulated moving bed type separation apparatus described above, and the column is filled with the separation filler, a predetermined pressure loss occurs. The pressure loss varies depending on the scale of the column, the type and amount of the packing for separation, and the like. In a normal case, for example, 350 to 800 kg / kg in the desorption zone (IV).
cm ² , 20 to 100 kg / cm in the concentration zone (III)
^2. 10-9 in purification zone (II) and adsorption zone (I)
A pressure loss of 0 kg / cm ² occurs, and a pressure loss of about 10 to about 1,000 kg / cm ² occurs in the entire circulating fluid flow path. However, the pressure loss in the entire circulating fluid flow path differs for each simulated moving bed type separation device.

Therefore, it is desired that the simulated moving bed type separator has pressure resistance to withstand such a large pressure loss.

The simulated moving bed type separation apparatus according to the present invention has an input means for inputting data as a single column chromatographic analysis result, and a calculation for calculating an initial operating condition and a maximum operating condition based on the data input by the input means. Means, and control means for controlling each part of the apparatus in accordance with the result of operation by the operation means. Here, the maximum operating conditions refer to conditions under which the maximum pressure not exceeding the maximum pressure loss of the simulated moving bed type separator can operate the simulated moving bed type separator at a flow rate related to the column. It can be said that the maximum operating condition is the most efficient operating condition.

As the input means, a normal keyboard, mouse, or the like is employed. Further, the calculation means has a memory for storing various data and a calculation unit for executing various calculations.

The input means inputs basic data.
This basic data is data irrespective of the raw material solution to be separated, and is specific to the size of the column used in the simulated moving bed type separator, such as the column diameter, length and number used, and the chromatographic analysis. , Ie, the diameter of the single column, the length of the single column, the flow rate of the mobile phase in the single column, the temperature in the single column, the concentration of the raw material solution, the injection amount of the raw material solution, and the like. The input basic data is stored in a memory in the arithmetic means.

When a predetermined component is separated from a predetermined raw material solution, unique data necessary for separating the raw material solution is input by input means.

The unique data input by the input means is
These are fractionation conditions as a result of chromatographic analysis using a single column separate from the simulated moving bed type separation apparatus of the present invention.
This unique data is obtained as follows.

That is, the separation is carried out by a simulated moving bed type separation device using a single column filled with the same packing material as the separation packing material packed in the packed bed used in this simulated moving bed type separation device. The chromatographic analysis of the raw material solution to be performed is performed.

At this time, the conditions of the chromatographic analysis include the amount of the raw material solution to be injected into the single column, the injection interval, the concentration of the raw material solution, the flow rate of the solvent passing through the single column, the temperature, and the separation capacity of the single column. The type and amount of the filler, the length of the single column, the temperature, and the like are set, and these conditions are known. The conditions for the chromatographic analysis are such that the chromatographic analysis can be performed with high efficiency on a single column, and the condition setting is empirically determined for each single column.

The raw material solution is injected into a single column, and the components in the raw material solution are observed to be distilled out. The components in the raw material solution which are distilled out first (sometimes referred to as the former components). ) Is the time until the start of the distillation (distillation start time; T1s), the time until the amount of the previous component distilled out is maximum (T1), the component in the raw material solution, and the last (T2e) until the distillation of the component (which may be referred to as a rear component) is completed, that is, the time until the distillation amount of the rear component becomes substantially zero (T2e). Time (T2), between the time T1 and the time T2, and the time (Tv) until the outflow of the component becomes the minimum.
), The concentration of the raw material solution to be injected into the single column (C), and the volume of one time of the raw material solution to be injected into the single column is (V),
The flow rate (S) of the raw material solution flowing through the single column is specified. Normally, according to a chart shown in FIG. 1 obtained as a result of chromatographic analysis obtained by injecting a raw material solution into a single column, for example, time T1s (unit: minute),
Time T1 (unit: minute), time T2e (unit: minute), time T
2 (unit: minute) and time Tv (unit: minute) are specified.

In the simulated moving bed type separation apparatus of the present invention, the operation for determining the operating conditions based on the above-mentioned unique data (separation conditions) as the result of the single column chromatographic analysis, which is input by the input means. It has control means.

The operation control means calculates the operation initial conditions as follows.

(1) An operation is performed to determine the size difference D between the size of one column used in the simulated moving bed type separation apparatus and the size of a single column used for chromatographic analysis. The operation is
For example, according to the following equation.

D = V1 ÷ V2 where V1 is the internal volume (cm3) of one column.
V2 is the internal volume (cm ³ ) of one single column. When the column used in the simulated moving bed type separation apparatus and the single column have the same length, a size difference may be obtained based on the cross-sectional area of the column and the cross-sectional area of the single column.

(2) The number of injections (B) of the raw material solution per hour is calculated based on the elution time obtained from the results of the separation chromatography on a single column. The calculation is based on, for example, the following equation.

B = 60 ° (T2e−T1s) (3) An operation is performed to find the injection amount A of the raw material per unit time injected into the column in the simulated moving bed type separation apparatus. The calculation is based on the following equation, for example.

A = B × E × D × F (unit: mg / hr / system) where B is the number of times the raw material solution was injected into the single column, and E was the number of raw materials per single time injected into the single column. And F is the number of columns used in the simulated moving bed separator. B can be determined by dividing the length L of the single column by the injection interval (T2s-T1s) of the raw material solution. The amount E of the raw material is determined by the concentration C (pp
m) and the volume V (ml) of the raw material solution per time.

(4) A calculation is performed to determine the injection amount (also referred to as feed supply amount) Sf of the raw material solution injected into the column in the simulated moving bed type separation apparatus per unit time. The calculation is based on the following equation, for example.

Sf = (A ÷ C) ÷ 60 (unit: ml / min) (5) Time T1s determined by single column chromatographic analysis
(Unit: minute), time T1 (unit: minute), time T2e (unit: minute), time T2 (unit: minute), time Tv (unit:
Min) to the set flow rate in the adsorption zone (I), the average flow rate in the purification zone (II) and the concentration zone (III), and the desorption zone (IV)
Is calculated to obtain the set flow velocity.

For example, the set flow rate S1 of the adsorption zone (I)
Is determined by the following equation.

S1 = S × D × T1s ÷ Tv (unit: ml / min) where S is the flow rate of the fluid flowing through the single column,
XD represents the flow rate of the fluid flowing through the column in the simulated moving bed type separation apparatus.

The set flow rate S2 in the purification zone (II) is determined by the following equation.

S 2 = S × D × T 1 ÷ Tv (unit: ml / min) The set flow rate S 3 in the concentration zone (III) is determined by the following equation.

S 3 = S × D × T 2 ÷ Tv (unit: ml / min) The set flow rate S 4 of the desorption zone (IV) is determined by the following equation.

S4 = S × D × T2e ÷ Tv (unit: ml / min) (6) Each flow rate obtained in the above (5), the injection amount of the raw material solution obtained in the above (4), and a correction coefficient From the above, the feed amount of the raw material solution, the feed amount of the eluent, the draw amount from the raffinate outlet and the extract outlet, and the step time, which are the initial operation conditions, are calculated.

The relationship between the flow rate in each zone, the feed amount Sf of the raw material solution, which is the initial operation condition, the feed amount Sd of the eluate, the extract amount Srf from the raffinate outlet, and the extract amount Sex from the extract outlet is shown in FIG. FIG.

First, the purification zone (II) and the concentration zone (III)
The average Sav of the flow velocity is obtained. The arithmetic expression is as follows.

Sav = (S 2 + S 3) ÷ 2 (unit: ml / min) The flow rate S (II) in the purification zone (II) is obtained by the following equation.

S (II) = Sav + Sf (unit: ml / min) The flow rate S (III) in the concentration zone (III) is obtained by the following equation.

S (III) = Sav−Sf (unit: ml / min) The flow rate S (I) in the adsorption zone (I) is obtained by the following equation. S (I) = S1 × K (unit: ml / min) where K is a correction coefficient, which is determined according to the scale of the simulated moving bed type separation apparatus. Is determined.

The flow velocity S (IV) in the desorption zone (IV) is obtained by the following equation. S (IV) = S4 × k (unit: ml / min) where k is a correction coefficient, which is determined according to the scale of the simulated moving bed type separation apparatus. Is determined.

The extraction amount Sex from the extract outlet is obtained by the following equation.

Sex = S (IV) -S (III) (unit: ml / min) The extraction amount Srf from the raffinate extraction port is obtained by the following equation.

Srf = S (II) -S (I) (unit: ml / min) The flow rate of the fluid circulating from the adsorption zone (I) to the desorption zone (IV) is kept at the adsorption zone (I) flow rate .

The supply amount Sd of the eluent is obtained by the following equation.

Sd = S (IV) −S (I) (unit: ml / min) The step time Tstp is obtained by the following equation.

Tstp = Tv × S × D ÷ [(S (II) + S (III)) / 2]
(Unit: minute) On the other hand, the raw material solution is passed at different flow rates through a single column filled with the same packing material as that packed in the column of the simulated moving bed type separation apparatus, and the pressure in the single column at each flow rate is increased. Measure it. Each flow rate of the obtained raw material solution and the pressure value in the single column at that flow rate are input by the input means.

The calculating means calculates a linear relational expression (Y = aX + b) from the input flow velocity value X and pressure value Y, and stores this in a memory. However, in the linear relational expression, a and b
Is a coefficient.

The calculating means calculates the operating condition that does not exceed the system pressure in the following manner. These operating conditions are operating conditions determined such that the pressure in the zone formed by the column does not exceed the inherent system pressure of the simulated moving bed separator.
For example, when it is necessary to perform the separation within a short time, the maximum flow rate of the liquid flowing through each zone is determined so that the pressure in the zone becomes the maximum pressure value not exceeding the system pressure. The feed amount of the raw material solution, the feed amount of the eluent, the draw amount from the raffinate outlet and the extract outlet, and the step time for realizing a maximum flow rate are determined as the operation conditions. The condition including the maximum flow rate can be referred to as the maximum operation condition.

Further, an increase in the pressure in the zone causes various disadvantages, such as deterioration of the device, and is a safe operation.
And when operating at a flow rate faster than the flow rate that is the initial operation conditions, such a flow rate is determined, the feed amount of the raw material solution, the feed amount of the eluent, the raffinate extraction port and the The amount of extraction from the extract extraction port and the step time are determined as operating conditions for execution. Since a safe and efficient flow rate is determined, the operating conditions including this flow rate can be said to be safe operating conditions.

(7) From the initial operation conditions calculated in (6), the expected pressure value of each zone is calculated based on the linear relational expression. At this time, since the pressure in the zone determined by the linear relation is a value for one single column, the expected pressure value is multiplied by the number of columns forming each zone in the simulated moving bed type separation apparatus. ,
Next, the pressure values of the respective zones obtained by the multiplication are summed to obtain an expected system pressure value. The calculating means determines the flow velocity in each zone so that the predicted system pressure value matches the upper limit pressure value unique to the simulated moving bed type separation device and any value within an allowable range.

For example, when a pressure value equal to or less than the system-specific upper limit pressure value is input by the input means, the calculation unit determines the actual operating conditions including the flow rate in each zone corresponding to the input pressure value. decide.

When the operating conditions are determined by the calculating means, the control means controls the pump for supplying the raw material solution so that the flow rate in each zone conforms to the operating conditions.
A control signal for controlling the operation of the pump for supplying the desorbent, the circulation pump for flowing the fluid in the circulation fluid channel, the raffinate extraction pump, and the extract extraction pump is output to each pump to control them.

(Concrete Example) As shown in FIG. 2, a simulated moving bed type separation apparatus 1 which is an embodiment of the present invention has first to eighth columns 2a to 2h. Each column has a fluid passage 3a.
The second column and the first column 2h.
a is connected by a fluid passage 3b. A check valve 4 is provided in the fluid passage 3a connecting each column to the next column.
(Also referred to as check valves) are provided. The check valve 4 has a function of conducting fluid from one column to the next column, but preventing the reverse flow.

In the fluid passage 3a connecting each column to the adjacent column, a branch fluid passage 3c connected to the third rotary valve 5 is provided between the check valve 4 and the next column.
Are combined. In other words, the third rotary valve 5 has a fluid passage 3c from the fluid passage 3a connecting the first column 2a and the second column 2b, and a second column 2b.
A branch fluid passage 3c from the fluid passage 3a connecting the first column to the third column 2c;
and eight branch fluid passages 3c branching from a. The third rotary valve 5 selects one of the eight branch fluid passages 3c, extracts the fluid from the selected fluid passage 3a, and closes the other branch fluid passage 3c. Become.

A circulation pump 6 is connected to the discharge side of the third rotary valve 5. The discharge side of the circulation pump 6 is connected to the fourth rotary valve 7 via the fluid passage 3d.
The circulation pump 6 is an example of a fluid forced circulation means for forcibly circulating a fluid in a circulation fluid flow path in the simulated moving bed type separation device of the present invention.

The fourth rotary valve 7 is supplied with the fluid from the circulation pump 6 and the desorbed liquid from the desorbed liquid introduction pump 11 having a variable suction and discharge amount. The discharge side of the fourth rotary valve 7 is It is divided into eight fluid passages 3e, and each fluid passage 3e is connected between the check valve 4 and the next column of the fluid passage connecting each column to the next column. This fourth rotary valve 7
This is one of the switching means for switching the eluent inlet (the same meaning as the desorbent inlet) in the simulated moving bed type separation apparatus of the present invention.

Reference numeral 8 denotes a first rotary valve. A raw material solution is supplied to the first rotary valve 8 via a raw material introduction pump 12 having a variable suction and discharge amount. Has eight fluid passages 3
and each of the fluid passages 3f is connected between the check valve 4 and the next column of the fluid passage connecting each column to the next column. The first rotary valve 8 is one of the switching means for switching the raw material solution inlet in the simulated moving bed type separation apparatus of the present invention.

A branch fluid passage 3g connected to the second rotary valve 9 is connected between the check valve 4 and the next column in the fluid passage 3a connecting this column to the next column. ing. According to the second rotary valve 9, eight branch fluid passages 3g branched from each of the fluid passages 3a connecting each column to the next column are connected, and one of the branch fluid passages 3g is connected to the other. It is opened, and the other branch fluid passage 3g is closed. And
The second rotary valve 9 discharges a fluid (raffinate) by a raffinate extraction pump 13 having a variable suction and discharge amount. The second rotary valve 9 is one of switching means for switching the raffinate extraction port in the simulated moving bed type separation apparatus of the present invention.

A branch fluid passage 3h connected to the fifth rotary valve 10 is further connected between the check valve 4 and the next column in the fluid passage 3a connecting this column to the next column. ing. This fifth rotary valve 1
From 0, eight branched fluid passages 3g branched from each of the fluid passages 3a connecting each column to the next column.
Are connected, and one of the branch fluid passages 3h is opened, and the other branch fluid passage 3h is closed. The fifth rotary valve 10 discharges an extract by an extract extraction pump 14 having a variable suction and discharge amount. The fifth rotary valve 10 is one of the switching means for switching the extract outlet in the simulated moving bed type separation apparatus of the present invention.

In the simulated moving bed type separation apparatus 1 shown in FIG.
For example, first to fifth rotary valves 5, 7, 8,
9 and 10 are set to the following states.

That is, among the eight fluid passages 3e in the fourth rotary valve 7, the liquid passage 3b connecting the eighth column 2h and the first column 2a is opened, and the other liquid passages 3a are opened. So that it is closed
One fluid passage 3e is selected, and as for the fifth rotary valve 10, only the branch fluid passage 3h branched from the fluid passage 3a connecting the first column 2a and the second column 2b is opened, and the other is opened. The branch fluid passage 3h is selected so that the branch fluid passage 3h is in a closed state, and the first rotary valve 8 includes a third column 2c and a fourth column 2c.
d to a fluid passage 3a communicating with the fluid passage 3d.
Only the fluid path 3f is selected so that only the open state is opened, and the other fluid path 3f is closed. The second rotary valve 9 is connected to the fluid path 3a connecting the seventh column 2g and the eighth column 2h. The branch fluid passage 3g is selected such that only the branch fluid passage 3g branching from the opening is in the open state, and the other branch fluid passage 3g is in the closed state, and the third rotary valve 5 is checked against the eighth column 2h. Only the fluid passage 3c between the valve 4 and the other fluid passage 3c is opened.
The fluid passage 3c is selected so as to be closed.

Each of the columns 2a to 2h contains a filler capable of adsorbing a component to be separated.

In the simulated moving bed type separation apparatus shown in FIG. 2, the first to fifth rotary valves 5, 7, 8, 9, 10
Is in the open state and the closed state described above, the fluid passage 3b communicating the eighth column 2h and the first column 2a
When the desorbed liquid is supplied through the fourth rotary valve 7,
The check valve 4 has a backflow preventing function, and the fluid discharged from the eighth column 2h receives the third fluid through the fluid passage 3c.
The fluid led out to the rotary valve 5 is led into the first column 2a via the third rotary valve 5, the circulation pump 6, the fourth rotary valve 7, the fluid passage 3e, and the fluid passage 3b.

In the simulated moving bed type separation apparatus shown in FIG. 2, in the purification step, for example, a purification zone (II) is formed by the fourth column 2d to the seventh column 2g. Upon contact, the filler readily adsorbs to the filler (which is also an adsorbent or strongly adsorbed component) and other components which are difficult to adsorb (which are also nonadsorbed or weakly adsorbed components). The raffinate is collected together with the desorbed solution, and the second step is performed as a concentration step.
Concentration zone (III) by column 2b to third column 2c
Is formed, and in this concentration zone, the filler adsorbing the strongly adsorbed component comes into contact with a part of the extract, the weakly adsorbed component remaining on the filler is expelled, the strongly adsorbed component is concentrated, and the desorption step is performed. As a result, a desorption zone (IV) is formed by the first column 2a, the filler containing the strongly adsorbed component concentrated in this desorption zone is brought into contact with the desorbing liquid, the strongly adsorbed component is expelled from the filler, and the desorption zone is removed. The extract is discharged from the extract outlet as an extract component along with the liquid separation, and as the desorbed liquid recovery step, an adsorption zone is formed by the eighth column 2h, and the packing material that has substantially adsorbed only the desorbed liquid is raffinate. And a part of the desorbed liquid contained in the filler is recovered as a desorbed liquid recovery part.

The first to fifth rotary valves 5, 7,
The operations of 8, 9, and 10 are controlled by control means.

In this simulated moving bed type separation apparatus, the first to fifth rotary valves 5, 7, 8,
By the operations of Steps 9 and 10, the introduction position of the desorbed liquid, the introduction position of the raw material solution, and each withdrawal position are moved by one column in the flow direction of the solvent.

Therefore, in the second stage, the second column 2
b forms a desorption zone, the third column 2c and the fourth column 2d form a concentration zone, the fifth column 2e to 82h form a purification zone, and the first column 2a forms an adsorption zone. By performing such operations sequentially, each process shifts by one column.
Separation of a mixture of similar compounds is achieved continuously and efficiently.

In this simulated moving bed type separation apparatus 1,
As shown in FIG. 3, a keyboard 15 as an input means is provided.
And operation means 16 and control means 17. The calculation means 16 has a memory 18 and a calculation unit 19.

The memory 18 temporarily stores data input from the keyboard 15 and, if necessary, an arithmetic unit 19
And stores the calculation result calculated by the calculation unit 19.

The operation unit 19 reads out the data stored in the memory 18 and performs a predetermined operation, and outputs the operation result to the control unit 17.

The control means 17 controls the switching operation of the first to fifth rotary valves 5, 7, 8, 9, and 10, the circulation pump 6, the desorbed liquid introduction pump 11, and the raw material introduction pump 1.
2. It outputs a control signal for controlling the driving operation of the raffinate extraction pump 13 and the extract extraction pump 14.

Next, a specific operation using the simulated moving bed type separator will be described.

(A) The specifications of the simulated moving bed type separation apparatus are as follows.

[0104] Circulation pump, desorbed liquid introduction pump, raw material introduction pump, raffinate extraction pump, extract extraction pump ...・ ・ ・ ・ ・ ・ ・ Pump for 1050 HPLC manufactured by JASCO Corporation Number of columns (n) ・ ・ ・ 8 Column dimensions ・ ・ ・ ・ ・ ・ Length: 25cm, Diameter: 1.0cm, Column type ・··· CHIRALCEL OD Eluent type ···· n-hexane / isopropyl alcohol = 90/10 (B) The conditions for chromatographic analysis using a single column are as follows.

Column type: CHIRALCEL OD Column dimensions: length: 25 cm, diameter: 1.0 cm, type of raw material solution: t-stilbene oxide-containing solution (solvent is eluted) Same as liquid) Concentration of raw material solution (C) · 30 mg / ml Kind of eluent ··· n-hexane / isopropyl alcohol = 90/10 Eluent flow rate (S) · · 4.8 ml / min Single column The amount of the raw material solution to be injected once (V) 0.05 ml Temperature 40 ° C (C) The chromatographic analysis results obtained by the above chromatographic analysis are as follows.

T2e = 10.910 min. T2 = 8.958 min. TV = 8.182 min. T1 = 6.412 min. T1s = 5.455 min. (D) The arithmetic unit 17 sends the (A),
Input the data shown in (B) and (C) and execute the following arithmetic processing.

1. A calculation is performed to determine the size difference D between the size of one column used in the simulated moving bed type separation apparatus and the size of a single column used for chromatographic analysis. The calculation is based on the following equation, for example.

D = V1 ÷ V2 = 19.63．19.63 = 1 (times) 2. Calculation of the number of sample injections per hour (B) from the elution time obtained from the separation chromatography on a single column is as follows: I do.

B = 60 ° (T2e−T1s) = 60 ° (1
0.910-5.455) = 11.0 (times / hour) 3. A calculation is performed to find the injection amount A of the raw material per unit time injected into the column in the simulated moving bed separator.
The calculation is based on the following equation, for example.

A = B × E × D × F = 11.0 × 5.0 ×
0.05 × 1 × 8 = 22 (unit: mg / hr / system) 4. Injection amount (also referred to as feed supply amount) Sf of the raw material solution injected into the column in the simulated moving bed type separation apparatus per unit time. Is calculated. The calculation is based on the following equation, for example.

Sf = (A ÷ C) ÷ 60 = (22 ÷ 5) ÷
60 = 0.073 (unit; ml / min) 5. Calculation for calculating the set flow rate in the adsorption zone (I), the average flow rate in the purification zone (II) and the concentration zone (III), and the set flow rate in the desorption zone (IV) I do.

S1 = S × D × T1s ÷ Tv = 4.8 × 1 ×
5.455 / 8.182 = 3.200 (unit: ml /
Min) Set flow rate S2 in purification zone (II) is determined by the following equation.

S2 = S × D × T1 ÷ Tv = 4.8 × 1 ×
6.412 / 8.182 = 3.762 (unit: ml /
Min) The set flow rate S3 of the concentration zone (III) is obtained by the following equation.

S3 = S × D × T2 ÷ Tv = 4.8 × 1 ×
8.958 / 8.182 = 5.255 (unit: ml /
Min) The set flow velocity S4 of the desorption zone (IV) is obtained by the following equation.

S4 = S × D × T2e ÷ Tv = 4.8 × 1 ×
10.91 / 8.182 = 6.400 (unit: ml /
Minutes) 6. Calculate the feed amount of the raw material solution, the feed amount of the eluent, the extraction amount from the raffinate extraction port and the extract extraction port, and the step time.

First, the purification zone (II) and the concentration zone (III)
And the average of the flow rates. The arithmetic expression is as follows.

Sav = (S2 + S3) ÷ 2 = (3.762)
+5.255) ÷ 2 = 4.509 (unit: ml / min) The flow rate S (II) in the purification zone (II) is obtained by the following equation.

S (II) = Sav + Sf = 4.509 + 0.0
73 = 4.582 (unit: ml / min) The flow rate S (III) in the concentration zone (III) is obtained by the following equation.

S (III) = Sav-Sf = 4.509 + 0.
073 = 4.436 (unit: ml /) The flow velocity S (I) in the adsorption zone (I) is obtained by the following equation. S (I) = S1 * K = 3.200 * 0.5 = 1.600
(Unit: ml / min) The flow velocity S (IV) in the desorption zone (IV) is obtained by the following equation. S (IV) = S4 × k = 6.400 × 1.2 = 7.680
(Unit: ml / min) The extraction amount Sex from the extract outlet is obtained by the following equation.

Sex = S (IV) -S (III) = 7.68-4.
436 = 3.244 (unit: ml /) The extraction amount Srf from the raffinate extraction port is obtained by the following equation.

Srf = S (II) -S (I) = 4.582-1.
(600 = 2.982 units: ml / min) The flow rate of the fluid circulating from the adsorption zone (I) to the desorption zone (IV) is kept at the adsorption zone (I) flow rate.

The supply amount Sd of the eluent is obtained by the following equation.

Sd = S (IV) -S (I) = 7.680-1.
600 = 6.08 (unit: ml / min) The switching time of the first to fifth rotary valves 5, 7, 8, 9, and 10, ie, the step time, is determined as follows.

Tstp = Tv × S × D ÷ [(S (II) + S (I
II)) / 2] = 8.182 × 4.8 × 1 ÷ 4.509 =
8.71 (unit: minute) (E) Further, the solvent used in the raw material solution is passed through a single column to examine the relationship between the flow rate of the solvent and the pressure in the single column. First, the solvent used is passed through the single column at various flow rates, and the pressure in the single column at that time is measured. Then, the flow rates and the pressures are input by input means. The input flow velocity data and pressure data are temporarily stored in a memory, and then the pressure Y (unit: ml /
cm ² ) is correlated as a linear function of the flow rate X (unit: ml / min).

The arithmetic section calculates the pressure in the column from the flow rates of the respective zones obtained in the above (D) based on the linear function, multiplies the pressure value by a number equal to the number of columns in the zone, and The sum of the pressures of the respective zones in consideration of the number is obtained to obtain an expected system pressure.

The calculating section further compares the calculated expected system pressure with the system upper limit pressure in the simulated moving bed type separator, and sets the maximum setting of each zone so that the expected system pressure does not exceed the system upper limit pressure. Flow velocity Smax (I)
Smax (IV) is determined.

When the calculation section determines the maximum set flow velocity of each zone, it outputs the data to the control means. The control means 17 controls the first to fifth rotary valves 5, 7, and so that the maximum set flow rate of each zone becomes a determined value.
It outputs control signals for controlling the switching operations of 8, 9, and 10, the driving operations of the circulation pump 6, the desorbed liquid introduction pump 11, the raw material introduction pump 12, the raffinate extraction pump 13, and the extract extraction pump 14.

As a result, in this specific example, when a solution containing t-stilbene oxide is used as the raw material solution, the step time is 5.73 minutes.

While the calculated maximum set flow rate Smax (I) of the adsorption zone (I) is 2.43 ml / min,
The measured maximum set flow rate Smax (I) of (I) is 2.28 ml.
/ Min.

While the calculated maximum set flow rate Smax (II) in the purification zone (II) is 6.96 ml / min, the measured maximum set flow rate Smax (II) in the purification zone (II) is 5.96 ml / min. 6
It was 3 ml / min.

The calculated maximum set flow rate Smax (III) in the concentration zone (III) is 6.74 ml / min, whereas the measured maximum set flow rate Smax (III) in the concentration zone (III) is 5.75 ml / min. Whereas the calculated maximum set flow rate Smax (IV) of the desorption zone (IV) which was 33 ml / min was 11.67 ml / min, the actually measured maximum set flow rate Sma of the desorption zone (IV) was
x (IV) was 10.50 ml / min.

As described above, in this specific example, when the simulated moving bed type separation apparatus is operated in accordance with the operating conditions calculated from the results of the chromatographic analysis using a single column, the operating conditions close to the calculated results are immediately realized. And efficient operation can be performed.

[0133]

According to the present invention, the simulated moving bed type separation device is operated for a long period of time to collect various data and determine the desired operating conditions without deciding the desired operating conditions.
A method for determining operating conditions of a simulated moving bed type separator capable of determining desired operating conditions of a simulated moving bed type separator based on data obtained by a separately determined single column chromatographic analysis, and such operating condition determination It is possible to provide a simulated moving bed type separation apparatus capable of automatically performing the method.

[Brief description of the drawings]

FIG. 1 is an explanatory diagram showing data that can be read from a chart obtained as a result of a chromatographic analysis using a single column.

FIG. 2 is an explanatory view showing a simulated moving bed type separation apparatus according to one embodiment of the present invention.

FIG. 3 is an explanatory diagram showing input means, calculation means, and control means in the simulated moving bed type separation apparatus according to one embodiment of the present invention.

FIG. 4 is a schematic diagram showing the relationship among the flow rate in each zone, the feed amount Sf of the raw material solution, the feed amount Sd of the eluent, the raffinate extraction port Srf, and the extraction amount Sex from the extract extraction port, which are initial operation conditions. FIG.

[Explanation of symbols]

1 ... Pseudo moving floor device with built-in rotary valve, 2
a to 2h: Unit packed bed, 3a, 3b, 3c, 3d,
3e, 3f: fluid passage, 3g, 3h: branch fluid passage, 4: check valve, 5: third rotary valve, 6: circulation pump, 7: fourth rotary Valve, 8: first rotary valve, 9: second rotary valve, 10: fifth rotary valve, 11
... Desorption liquid introduction pump, 12 ... Raw material introduction pump,
13 ... raffinate extraction pump, 14 ... extract extraction pump, 15 ... input means, 1
6 arithmetic means, 17 control means, 18 memory, 19 arithmetic unit.

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[Procedure amendment]

[Submission date] November 13, 1996

[Procedure amendment 1]

[Document name to be amended] Drawing

[Correction target item name] Fig. 1

[Correction method] Change

[Correction contents]

FIG.

[Procedure amendment 2]

[Document name to be amended] Drawing

[Correction target item name] Figure 3

[Correction method] Change

[Correction contents]

FIG. 3

[Procedure amendment 3]

[Document name to be amended] Drawing

[Correction target item name] Fig. 4

[Correction method] Change

[Correction contents]

FIG. 4

Claims (3)

[Claims] 1. A plurality of packed beds accommodating a separating filler are connected endlessly to form a circulating fluid passage in which a fluid can be forcedly circulated in one direction. An eluent inlet for introducing an eluent, an extract outlet for extracting a solution rich in adsorbate or strongly adsorbate, a raw material solution inlet for introducing a raw material solution containing a mixture of components to be separated, A raffinate outlet for extracting a solution rich in non-adsorbate or weak adsorbate is provided in this order in the direction of fluid flow, and the respective inlet and outlet are intermittently moved. Formed on the packed bed between the extract extract outlet and the concentrated adsorbing component or strongly adsorbing material, the adsorbing component or the strongly adsorbing component comes into contact with the eluent, and the adsorbing component or the strongly adsorbing component is separated. Et al desorption zone to be expelled (I
V), a non-adsorbed component or a weakly adsorbed component formed on the packed bed between the extract outlet and the raw material solution inlet and remaining on the separating filler is expelled to remove the adsorbed or strongly adsorbed component Zone (III) where the raw material solution comes into contact with the separation filler, and is adsorbed or strongly adsorbed on the separation filler. The purification zone (I) where the components are adsorbed and the non-adsorbed or weakly adsorbed components are
I), and a non-adsorbed component or a weakly adsorbed component formed on the packed bed between the raffinate discharge port and the eluent inlet, and the content of the non-adsorbed component or the weakly adsorbed component is adsorbed by the separation packing material. The adsorption zone (I) where a small amount of eluent is collected,
A method for determining operating conditions of a simulated moving bed type separation device formed by a plurality of packed beds, wherein a raw material solution containing a plurality of components is injected into a single column filled with the same packing material for separation as the packing material for separation. By performing the chromatographic analysis by the above, based on the preparative conditions obtained as a result of the chromatographic analysis, it is the initial operation conditions of the simulated moving bed type separation device,
The feed amount of the raw material solution, the feed amount of the eluent, the withdrawal amount from the raffinate outlet and the extract outlet, and the step time are determined.The determined initial operation conditions and the same separation From the relationship between the flow rate of the raw material solution and the pressure in the single column when the raw material solution is passed through the single column filled with the filler, the operating conditions that do not exceed the upper limit pressure of the simulated moving bed type separation device are determined. A method for determining operating conditions of a simulated moving bed separator. 2. The method for determining operating conditions of a simulated moving bed type separation apparatus according to claim 1, wherein the initial operation conditions are such that a single column filled with the same separation filler as the separation filler has a plurality of columns. The chromatographic analysis is performed by injecting the raw material solution containing the component, and the flow start time (T1) of the predetermined preceding component, which is the data obtained as a result of the chromatographic analysis, which flows out of the raw material solution from the single column first.
s), the time (T1) at which the amount of distillation of the preceding component is maximum,
The time (T2s) at which the outflow of the predetermined rear component is reached, the time (T2) at which the amount of distillation of the rear component is maximized, and the time between the end time of the outflow of the preceding component and the time at which the outflow of the rear component starts. ,
2. The method for determining operating conditions of a simulated moving bed type separation apparatus according to claim 1, wherein the operation condition is determined based on the time (TV) at which the concentration of the effluent component becomes minimum and the concentration (C) of the raw material solution injected into the single column. . 3. A plurality of packed beds containing a separating filler are endlessly connected to each other to form a circulating fluid passage in which fluid can be forcedly circulated in one direction. An eluent inlet for introducing an eluent, an extract outlet for extracting a solution rich in adsorbate or strongly adsorbate, a raw material solution inlet for introducing a raw material solution containing a mixture of components to be separated, A raffinate outlet for extracting a solution rich in non-adsorbate or weak adsorbate is provided in this order in the direction of fluid flow, and the respective inlet and outlet are intermittently moved. Formed on the packed bed between the extract extract outlet and the concentrated adsorbing component or strongly adsorbing material, the adsorbing component or the strongly adsorbing component comes into contact with the eluent, and the adsorbing component or the strongly adsorbing component is separated. Et al desorption zone to be expelled (I
V), a non-adsorbed component or a weakly adsorbed component formed on the packed bed between the extract outlet and the raw material solution inlet and remaining on the separating filler is expelled to remove the adsorbed or strongly adsorbed component Zone (III) where the raw material solution comes into contact with the separation filler, and is adsorbed or strongly adsorbed on the separation filler. The purification zone (I) where the components are adsorbed and the non-adsorbed or weakly adsorbed components are
I), and a non-adsorbed component or a weakly adsorbed component formed on the packed bed between the raffinate discharge port and the eluent inlet, and the content of the non-adsorbed component or the weakly adsorbed component is adsorbed by the separation packing material. The adsorption zone (I) where a small amount of eluent is collected,
In a simulated moving bed type separation apparatus formed by a plurality of packed beds, chromatographic analysis is performed by injecting a raw material solution containing a plurality of components into a single column packed with the same packing material for separation as the packing material for separation. As a result of the chromatographic analysis, outflow start time (T1s) of a predetermined preceding component which first flows out of a single column among components in the raw material solution, time (T1) at which the amount of the preceding component distilled out becomes maximum, The ending time (T2s) of the predetermined post-component, and the time (T
2) The time (TV) between the end time of the outflow of the preceding component and the start time of the outflow of the subsequent component, at which the concentration of the outflow component becomes the minimum, and the concentration (C) of the raw material solution to be injected into the single column. ), And the flow rate of the raw material solution flowing into the single column and the pressure in the single column, which are initial operation conditions of the simulated moving bed type separation apparatus based on the chromatographic analysis result input from the input means. Computing means for determining an operating condition that does not exceed the upper limit pressure of the simulated moving bed type separation device from the relationship between the operating condition and the initial operating condition; and control for controlling the operation according to the operating condition determined by the computing means. Means for simulating a moving bed type separator.