CN106596761B - The Triangles Optimization method of object in complicated object is separated with Simulated Moving Bed Chromatography - Google Patents
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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Abstract
This patent discloses a kind of Triangles Optimization methods that object in complicated object is separated with Simulated Moving Bed Chromatography, belong to technical field of chromatography.This method determines the interfering component of the object in SMB separation system first, and assign interfering component concentration, then single-column ideal chromatography model is established, the object of SMB separative unit and the adsorption isotherm of interfering component are obtained by inverse method, closer to chromatographic process dynamic characteristic, and thus to obtain the apparant adsorption coefficient of fast component A, slow component B, the II band and the opposite flow rate ratio m of III band of SMB are controlledαIn the delta-shaped region that the apparant adsorption coefficient of fast component A, slow component B are formed, the operating parameter of non-linear SMB separation target components and interfering component can be optimized.
Description
Technical field
The present invention relates to technical field of chromatography more particularly to a kind of objects in the complicated object of Simulated Moving Bed Chromatography separation
Triangles Optimization method.
Background technique
Simulation moving bed (SMB) chromatographic technique has the characteristics that continuous, automatic, efficient, becomes petrochemical industry, fine chemistry industry
With the high-end isolation technics in fields such as pharmacy (especially chiral drug resolution and biological product separates).In general, the operation of SMB
Variable include: switching cycle, sample introduction liquid composition with concentration, mobile phase circular flow, mobile phase inlet flow rate, extract liquor flow,
Sample introduction flow quantity and remaining flow quantity；It includes: product purity, the rate of recovery, yield, mobile phase consumption that SMB, which investigates performance indicator,
With stationary phase usage amount.For the maximization for realizing production efficiency, the operating condition parameter optimization to SMB separation process is very must
It wants.
Triangulation method can obtain initial design parameter because of Simple visual, be the foundation [Lee for selecting SMB separation condition
J W, Wankat P C.J.Chromatography A, 2010,1217:3418-3426].Triangulation method is according to ideal linearity
The retention time method of situation, for second-component system, separation condition is with dimensionless flow-rate ratio (mobile phase and stationary phase velocity ratio)
mαIt indicates, the form of statement are as follows: GA≤mI；GB< mII≤GA；GB≤mIII≤GA；mIV≤GB, the Representative Region α band, GA, GBFor slow component
The adsorption coefficient of A and fast component B, in mII-mIII100% hamiltoian cycle region of plane coordinates formation [Mazzotti M,
Storti G, Morbidelli M.J.Chromatogrphy.A, 1997,769:3-24].Triangle side is used in practical operation
Method must be modified.Jensen [Jensen T B, Reijns T G P, Billiet H A H, et
Al.J.Chromatography A, 2000,873 (2): 149-162] influence of the resistance to mass tranfer to separable section has been investigated,
Mazzotti etc. [Mazzotti M, Storti G., Morbidelli M.AICHE J., 1994,40:1825-1842] is used
[Gentilini A, Migliorini C, the Mazzotti M, et such as Langmuir adsorption isotherm, Gentilini
Al.J.Chromatography A, 1998,805:37-44] separable section is carried out with Bi-Langmuir adsorption isotherm
Correction separates section and reduces [Lin Ping Chang Simulated Moving Bed Chromatography technology Chemical Industry Press, Beijing: 2008] after correction.
When separating complex mixture, mass tranfer coefficient, diffusion coefficient and adsorption isotherm are all difficult to Accurate Determining, encounter unknown component
When, these parameters are unable to get, and also can not just be obtained by the delta-shaped region of separation component, and optimization process at this time is established big
On the experiment basis of amount.
Summary of the invention
The deficiency of optimisation technique, provides when the purpose of the present invention is for the progress complex mixture separation of existing SMB chromatography
A kind of Triangles Optimization method separating object in complicated object with Simulated Moving Bed Chromatography.
The specific technical solution of the present invention is as follows:
A kind of Triangles Optimization method separating object in complicated object with Simulated Moving Bed Chromatography, comprising the following steps:
1, prepare the sample introduction liquid of complex mixture, complex mixture contains 3 kinds or more components, measurement wherein object it is dense
Degree；
2, the chromatography single-column used by Simulated Moving Bed Chromatography determines solid used in Simulated Moving Bed Chromatography separation system
The fixed mutually interfering component with object in mobile phase, and assign the concentration of interfering component；
3, inverse method determines the object of chromatography single-column and the adsorption isotherm parameter of interfering component:
1. acquiring the reality of chromatography single-column used in the Simulation moving bed of 2~5 objects and its interfering component with sample introduction liquid
Elution curve data；
2. the adsorption isotherm of selection one-component describes the absorption behavior of object and interfering component respectively；
3. selection Chromatography Models describe the chromatographic behavior of object and interfering component respectively；
4. solving the single column chromatographic model of object and interfering component with calculus of finite differences, object and interfering component are respectively obtained
The calculating elution curve of single-column；
5. the adsorption isotherm parameter of object and the initial value of single column chromatographic model calculating parameter are set, by adjusting suction
Attached thermoisopleth parameter and calculating parameter solve single column chromatographic model repeatedly and obtain calculating elution curve, flow out the calculating of object
Curve and practical elution curve have the good goodness of fit, thereby determine that the adsorption isotherm parameter and single column chromatographic model of object
Calculating parameter, in the same way determine interfering component adsorption isotherm parameter and single column chromatographic model calculating parameter；
Wherein, single-column model calculating parameter includes time step τ and spatial mesh size h；
4, according to adsorption isotherm qi=f (Ci) obtain apparant adsorption coefficient, apparant adsorption coefficient G 'iIt is defined asG′A
For the biggish component of the adsorption capacity in both object and interfering component, that is, slow component A apparant adsorption coefficient, G 'BFor target
The lesser component of adsorption capacity, that is, fast component B apparant adsorption coefficient in both object and interfering component；The phase of each zone of SMB
Flow rate ratio mαIt indicates,In formula, V is stationary phase volume, QαFor the volume flow rate of mobile phase, ε is hole
Gap rate, the Representative Region α band, α=I, II, III, IV ...；Select the operating condition of SMB separation are as follows: control the II band and III of SMB
The opposite flow rate ratio m of bandαFast component A, slow component B apparant adsorption coefficient between, i.e. G 'B≤mII≤G′A, G 'B≤mIII≤G
′A, in mII-mIIIPlane coordinates forms the delta-shaped region that can separate target components and interfering component；Operation conditions optimization ginseng
Number, makes mαIt falls in delta-shaped region；The parameter includes input concentration, SMB respectively band flow velocity, sample injection time, switching time；
Wherein, the node for having sample introduction liquid stream to enter is F node, is II band before F node, is III band after F node；
5, SMB separation is carried out with the operating condition of optimization.
A kind of Triangles Optimization method separating object in complicated object with Simulated Moving Bed Chromatography, the interference
Component structure is unknown, when concentration can not measure, it is assumed that interfering component concentration.
A kind of Triangles Optimization method separating object in complicated object with Simulated Moving Bed Chromatography, the single-column
Chromatography Models are ideal chromatography model
A kind of Triangles Optimization method separating object in complicated object with Simulated Moving Bed Chromatography, the ideal
The difference solution procedure of Chromatography Models is as follows:
qi=f (Ci) (2)
Formula (1) is ideal chromatography model, and formula (2) is adsorption isotherm, and wherein i represents component i, and i=1 is object, i=
2 be interfering component, ci, qiRespectively component is in the concentration of mobile phase and stationary phase, and u is the flow velocity of mobile phase, and F is compared to F=
(1- ε)/ε, ε is porosity；T represents the time, and x represents position:
Formula (1) is write as
(3) in formula,
It again will be in formula (3)Item backward difference,Item forward difference, establishes explicit difference scheme:In formula, τ is time step, and h is spatial mesh size (plate height), and j indicates current tower
Plate, j=1,2 ..., L/h, n represent the time, n=k τ, k=1,2, and 3 ..., explicit difference scheme stability condition:
Or it will be in formula (3)Xiang HeItem all backward differences, establish implicit difference scheme:
Above two difference scheme boundary condition:CI, FFor in feeding liquid component i it is dense
Degree, tpFor feed time；
By obtaining component i single-column elution curve to above-mentioned explicit difference scheme or implicit difference scheme iterative solution
Ci(L, t)-t, L is column length.
A kind of Triangles Optimization method separating object in complicated object with Simulated Moving Bed Chromatography, the complexity
The sample introduction liquid of mixture is prepared by the proportion of the mobile phase of SMB system.
A kind of Triangles Optimization method separating object in complicated object with Simulated Moving Bed Chromatography, described adopts
The practical elution curve data for collecting chromatography single-column used are to acquire object and its interfering component under single-column linear conditions respectively
The stream of the chromatography single-column of object and its interfering component under the elution curve data of chromatography single-column, and acquisition single-column overload condition
Curve data out.
A kind of Triangles Optimization method separating object in complicated object with Simulated Moving Bed Chromatography, described makes
The method that the calculating elution curve of object has the good goodness of fit with practical elution curve is to utilize Chromatography Models computer chromatography
Elution curve, and be compared with the curve of practical measurement, the two error sum of squares is calculated as follows:In formula,It is measured value of experiment,It is model meter
Calculation value；Optimal value of the parameter is chosen using optimal method, keeps objective function Fun minimum, as calculating elution curve and reality flows
Curve has the good goodness of fit out；
A kind of Triangles Optimization method separating object in complicated object with Simulated Moving Bed Chromatography, when described
SMB is the four band SMB continuously recycled, sets mI> G 'ATo elute slow component A, m is setIV< G 'BTo prevent fast component from entering I
Band.
This triangle optimization method is using the purification index of object as constraint condition, using production efficiency or yield as target letter
Number；It is the mixed liquor of complex material, at least 3 components by isolated mixed liquor, it is assumed that mixed liquor contains only target components 1 and interference
Component 2, when the chromatography single-column used by Simulated Moving Bed Chromatography separates, 2 elution curve of interfering component and target components 1 flow out
Curve is adjacent, and interfering component 2 is the impurity that severe jamming target components 1 are isolated in all impurity；
Object is as slow component, then: object purityObject yieldObject is as fast component, then: Formula
In,AndThe concentration of target components 1 and interfering component 2 respectively in extract liquor,AndRespectively target in raffinate
The concentration of component 1 and interfering component 2, QE/F/RFor each mouth flow velocity.
The beneficial effects of the present invention are:
1, triangle optimization method of the invention is steady with SMB using the wavelet characteristic velocity of chromatography mass-conservation equation as foundation
Based on state mechanism, optimization method is provided for the separation of non-linear binary.
2, the adsorption isotherm of the object and interfering component that SMB separative unit is determined by inverse method of the invention, more connects
Advancing coloud nearside composes dynamic characteristic of the course, and apparant adsorption coefficient is more acurrate to provide optimization region.
3, abbreviation SMB optimization process
The present invention is by the system of complex mixture SMB chromatographic isolation, only to object and interfering component single group
Sub-argument thinks Chromatography Models model solution and determines the adsorption isotherm parameter of object and interfering component, the suction of chromatographic separation process
The parameter and ideal chromatography mould for the one-component adsorption isotherm that attached, desorption, mass transfer, diffusion, competition are solved by inverse method
The parameter of type algorithm embodies, with simplest but most important formal layout it is the most complicated and also be insurmountable
Modeling problem.In existing complicated chromatographic, even if all components it is known that mass tranfer coefficient, diffusion coefficient, competitive relation
It can not accurately determine, also you can't get accurate optimization regions.
4, complex mixture SMB chromatographic isolation is instructed to practice
When the interfering component structure of object in complex mixture sample introduction liquid is unknown, when concentration can not measure, the present invention
It is assumed that interfering component concentration, obtains the adsorption isotherm assumed and the ideal chromatography model for establishing hypothesis from there through inverse method, it can
With the chromatographic behavior of rough predicted interference component.For unknown impuritie, although being measured without corresponding standard substance by experiment
Unknown impuritie elution curve can not be indicated with concentration and time, only be indicated with response signal and time, but the elution curve energy
Reflect the separation situation with each component, after assigning unknown impuritie hypothesis concentration, chromatographic peak peak base width and peak height position
It is still accurate, it still can reflect the separation degree with other components, can model and describe its chromatographic behavior roughly, thus to obtain
Interfering component adsorption isotherm the absorption behavior of its chromatographic separation process can also be described roughly.
Specifically, it when using optimization method of the invention with Lai Baodi A glycosides in SMB separation STEVIA REBAUDIANA, selects by item
The experimental point in delta-shaped region that part adsorption coefficient determines is tested, and according to target component 1 and interfering component 2 consider, separation
The result is that: the yield of Lai Baodi A glycosides is about 90%, and purity is about 96%, considers that separating resulting is: Lai Baodi A glycosides by full constituent
Yield be about 90%, purity is about 63%.
5, method of the invention it is time saving, it is laborsaving, save raw material and mobile phase.
Detailed description of the invention
Fig. 1 is sample introduction liquid HPLC spectrogram in embodiment；
Fig. 2 is practical elution curve (solid line) and simulation elution curve (dotted line) of chromatography single-column in embodiment；
Wherein, (a) chromatography single-column condition 1, (b) chromatography single-column condition 2, (c) chromatography single-column condition 3；
Fig. 3 be in embodiment SMB operating condition 1 in the position in Triangles Optimization section；
Fig. 4 be in embodiment SMB operating condition 2 in the position in Triangles Optimization section；
Fig. 5 be in embodiment SMB operating condition 3 in the position in Triangles Optimization section；
Fig. 6 is the HPLC spectrogram of the extract liquor E of SMB operating condition 1 in embodiment；
Fig. 7 is the HPLC spectrogram of the raffinate R of SMB operating condition 1 in embodiment；
Fig. 8 be in embodiment SMB operating condition 4 in the position in Triangles Optimization section；
Fig. 9 is the HPLC spectrogram of the extract liquor E of SMB operating condition 4 in embodiment；
Figure 10 is the HPLC spectrogram of the raffinate R of SMB operating condition 4 in embodiment；
Wherein, the preceding impurity in Fig. 1, Fig. 2, Fig. 6, Fig. 7, Fig. 9 and Figure 10 is interfering component, ST be stevioside (and
A kind of sugar).
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description.
Embodiment
A kind of Triangles Optimization method separating rebaudioside A (RA) from STEVIA REBAUDIANA extract liquor with SMB chromatography.
SMB chromatographic used: operating mode: 1-1-2, I band are independent；4 root chromatogram columns, chromatographic column specification are D × L=
10mm×100mm；Stationary phase: C18,40~60 μm；Mobile phase: alcohol-water, proportion 1: 1；Chromatographic isolation temperature: room temperature.
HPLC testing conditions: analytical column: 4.6mm × 250mm (C18,5 μm, Agilent, U.S.A.), mobile phase: chromatography
The phosphate sodium dihydrogen buffer solution of acetonitrile and pH=2.6 proportion are 32/68 (v/v), flow velocity 1.0ml/min, measure wavelength 213nm,
30 DEG C of measuring temperature.
Optimization method the following steps are included:
(1) be formulated into sample liquid by the proportion of the mobile phase ethyl alcohol of SMB chromatography and water, with HPLC measurement sample introduction liquid in RA it is dense
Spend C1, F, HPLC spectrogram (Fig. 1) display RA purity 42.4%；
(2) by the elution curve of chromatography single-column used in SMB, determine sample introduction liquid in the SMB chromatographic with object
RA adjacent interfering component, the ratio K of interfering component detection signal and target analyte detection signal in the sample introduction liquid measured with HPLC
Again with target concentration C1, FProduct, assign the concentration of interfering component, the interfering component concentration be assume concentration, C2, F=
KC1, F, here, K=0.5；
(3) inverse method determines the adsorption isotherm parameter of object and interfering component:
1. measuring the practical elution curve of chromatography single-column
Chromatographic condition 1 (under linear conditions):
The concentration C of RA in sample introduction liquid1, F=20mg/ml
Flow velocity Q:2ml/min
Sample injection time: 0.5min
Offline HPLC detection obtains the solid line that practical elution curve under linear conditions is shown in Fig. 2 (a)；
Chromatographic condition 2 (under overload condition):
The concentration C of RA in sample introduction liquid1, F=20mg/ml
Flow velocity Q:2ml/min
Sample injection time: 2min
Offline HPLC detection, obtains the solid line that the practical elution curve under overload condition is shown in Fig. 2 (b)；
Chromatographic condition 3 (under overload condition):
The concentration C of RA in sample introduction liquid1, F=20mg/ml
Flow velocity Q:2ml/min
Sample injection time: 3min
Offline HPLC detection, obtains the solid line that the practical elution curve under overload condition is shown in Fig. 2 (c)；
2. selecting Langmuir adsorption isothermThe absorption row of RA and preceding interfering component are described
For；
3. describing the chromatographic behavior of RA and interfering component respectively with ideal chromatography model equation (1)；
4. ideal chromatography model is expressed as with display calculus of finite differences:In formula, i=1
For RA, i=2 is preceding interfering component, and τ is time step, and h is spatial mesh size, and j indicates that current column plate, n represent time, n=k
τ, k=1,2,3...,Boundary condition:CI, FFor component i in feeding liquid
Concentration, tpFor feed time；It is iteratively solved with difference scheme of the VB software programming to ideal chromatography model, obtains component i stream
Curve C outi(L, t)-t；
5. determining the adsorption isotherm parameter G of RA1、b1With the calculating parameter τ of Chromatography Models1、h1；The absorption of interfering component
Thermoisopleth parameter G2、b2With the calculating parameter τ of Chromatography Models2、h2；
According to the lower practical elution curve (Fig. 2 (a)) and formula t obtained of linear chromatography condition 1Ri=t0(1+FGi), formula
In, tRiFor retention time, t0For the dead time, F is compared to acquisition adsorption coefficient Gi, the absorption parameter G of RA1=4.45, it is preceding dry
Disturb component G2=0.4；
The practical elution curve (Fig. 2 (b) and Fig. 2 (c)) obtained according to the nonlinear condition 2,3 overloaded in sample volume, is surveyed
Determine adsorption coefficient bi, and determine h and τ；
Initial value is assigned for parameter first, is carried out using Chromatography Models computer chromatography elution curve, and with the curve of practical measurement
Compare, the two error sum of squares be calculated as follows:In formula,
It is measured value of experiment,It is model calculation value；Optimal value of the parameter is chosen using optimal method, makes objective function Fun
It is minimum；Thus the b of Tanshinone I I A is acquired1=0.025, preceding interfering component b2=0, h1=h2=0.05, τ1=τ2=0.5, it obtains
Obtain the RA and preceding interfering component elution curve C under chromatographic condition 1~3i(L, t)-t, is shown in the dotted line of Fig. 2 (a), (b) and (c)；Reason
Think that Chromatography Models analog result and experiment achieve preferably identical property；
(4) according to adsorption isothermAnd q2=f (C2)=0.4C2Obtain apparent absorption system
NumberWith G '2=0.4；Select the operating condition of SMB separation are as follows: II band and the opposite flow rate ratio m of III bandα
Fall in byWithIn mII-mIIIPlane coordinates is formed
Delta-shaped region in, it may be assumed that the selection of operating condition parameter meets:With
The following three groups of operating condition parameters of optimization, mαIt falls in delta-shaped region, sees A point, B in Fig. 3-Fig. 5 respectively
Point and C point.
SMB operating condition 1:P flow rate pump: 0.828ml/min
D flow rate pump: 0.828ml/min
F flow rate pump: 0.1ml/min
Switching time: 17min
The concentration C of RA in sample introduction liquidL, F=10mg/ml；
SMB operating condition 2:P flow rate pump: 0.7ml/min
D flow rate pump: 0.7ml/min
F flow rate pump: 0.1ml/min
Switching time: 19.5min
The concentration C of RA in sample introduction liquid1, F=10mg/ml；
SMB operating condition 3:P flow rate pump: 0.6ml/min
D flow rate pump: 0.6ml/min
F flow rate pump: 0.2ml/min
Switching time: 19.5min
The concentration C of RA in sample introduction liquid1, F=10mg/ml；
(5) SMB separation is carried out with the operating condition of optimization.
The separating resulting of SMB operating condition 1 is: the yield of product RA is 90.31%, considers that purity is by two components
98.10%, consider that purity is 63.39% by whole components；The HPLC chromatogram of extract liquor E and raffinate R are shown in Fig. 6 and Fig. 7.
The separating resulting of SMB operating condition 2 is: the yield of product RA is 91.12%, considers that purity is by two components
96.25%, consider that purity is 62.80% by whole components.
The separating resulting of SMB operating condition 3 is: the yield of product RA is 91.82%, considers that purity is by two components
98.30%, consider that purity is 64.90% by whole components.
However work as mαWhen not falling in delta-shaped region, such as SMB operating condition 4: when P flow rate pump: 0.7ml/min, D pump
Flow velocity: 0.7ml/min, F flow rate pump: 0.2ml/min, switching time: 19.5min, the concentration of RA in sample introduction liquid: 10.4mg/ml,
Operating point D is located at except triangle, sees Fig. 8, although being located at the triangle △ Wab of ideal scene (by 0.4 < mIII< 4.45,
0.4 < mII< 4.45 forms delta-shaped region) within, (HPLC chromatogram of extract liquor E and raffinate R are shown in figure to SMB separating resulting
9 and 10) show: RA cannot be separated very well with preceding interfering component；
In above-mentioned SMB operating condition 1-4,
Claims (4)
1. a kind of Triangles Optimization method for separating object in complicated object with Simulated Moving Bed Chromatography, which is characterized in that including
Following steps:
(1) the sample introduction liquid of complex mixture is prepared, complex mixture contains 3 kinds or more components, and measures the dense of wherein object
Degree；
(2) the chromatography single-column used by Simulated Moving Bed Chromatography determines the stationary phase used in Simulated Moving Bed Chromatography separation system
With the interfering component of object in mobile phase, and the concentration of interfering component is assigned；
(3) inverse method determines the object of chromatography single-column and the adsorption isotherm parameter of interfering component:
1. acquiring the practical outflow of chromatography single-column used in the Simulation moving bed of 2~5 objects and its interfering component with sample introduction liquid
Curve data；The practical elution curve data of chromatography single-column used in the acquisition are to acquire mesh under single-column linear conditions respectively
It marks object under the elution curve data of the chromatography single-column of object and its interfering component, and acquisition single-column nonlinear condition and its does
Disturb the elution curve data of the chromatography single-column of component；
2. the adsorption isotherm of selection one-component describes the absorption behavior of object and interfering component respectively；
3. selection Chromatography Models describe the chromatographic behavior of object and interfering component respectively；The Chromatography Models are ideal chromatography mould
Type；
4. solving the single column chromatographic model of object and interfering component with calculus of finite differences, object and interfering component single-column are respectively obtained
Calculating elution curve；
The difference solution procedure of the ideal chromatography model is as follows:
qi=f (Ci) (2)
Formula (1) is ideal chromatography model, and formula (2) is adsorption isotherm, and wherein i represents component i, and i=1 is object, and i=2 is
Interfering component, ci,qiRespectively component is in the concentration of mobile phase and stationary phase, and u is the flow velocity of mobile phase, and F is compared to F=(1-
ε)/ε, ε are porosity；T represents the time, and x represents position；
In turn, formula (1) is write as
In formula,
It again will be in formula (3)Item backward difference,Item forward difference, establishes explicit difference scheme:In formula, τ is time step, and h is spatial mesh size (plate height), and j indicates current tower
Plate, j=1,2, Λ, L/h, n represent the time, n=k τ, k=1,2,3..., explicit difference scheme stability condition:
Or it will be in formula (3)Xiang HeItem all backward differences, establish implicit difference scheme:
Above two difference scheme boundary condition:Ci,FFor the concentration of component i in feeding liquid, tp
For feed time；
By obtaining component i single-column elution curve C to above-mentioned explicit difference scheme or implicit difference scheme iterative solutioni(L,
T)-t, L are column length；
5. the adsorption isotherm parameter of object and the initial value of single column chromatographic model calculating parameter are set, by adjusting absorption etc.
Warm line parameter and calculating parameter solve single column chromatographic model and obtain calculating elution curve, make the calculating elution curve and reality of object
Border elution curve matches, and thereby determines that the adsorption isotherm parameter and single column chromatographic model calculating parameter of object；With same
Mode determine the adsorption isotherm parameter and single column chromatographic model calculating parameter of interfering component；
(4) according to adsorption isotherm qi=f (Ci) obtain apparant adsorption coefficient, apparant adsorption coefficient G 'iIt is defined asG′AFor
The biggish component of adsorption capacity, that is, slow component A apparant adsorption coefficient in both object and interfering component, G 'BFor object
With the lesser component of adsorption capacity, that is, fast component B apparant adsorption coefficient in both interfering components；The each zone of SMB it is opposite
Flow rate ratio mαIt indicates,In formula, V is stationary phase volume, QαFor the volume flow rate of mobile phase, ε is hole
Rate, the Representative Region α band, α=I, II, III, IV, K；Select the operating condition of SMB separation are as follows: control the II band and III band phase of SMB
Flow rate ratio mαFast component A, slow component B apparant adsorption coefficient between, i.e. G 'B≤mII≤G′A, G 'B≤mIII≤G′A,
mII–mIIIPlane coordinates forms the delta-shaped region that can separate target components and interfering component；
Operation conditions optimization parameter, makes mαIt falls in delta-shaped region；The parameter include input concentration, SMB respectively band flow velocity,
Sample injection time, switching time；
(5) SMB separation is carried out with the operating condition of optimization.
2. a kind of Triangles Optimization side for separating object in complicated object with Simulated Moving Bed Chromatography according to claim 1
Method, which is characterized in that the interfering component structure is unknown, and when concentration can not measure, the concentration for assigning interfering component is
It is assumed that interfering component concentration.
3. a kind of Triangles Optimization side for separating object in complicated object with Simulated Moving Bed Chromatography according to claim 1
Method, which is characterized in that the sample introduction liquid of the complex mixture is prepared by the proportion of the mobile phase of SMB system.
4. a kind of Triangles Optimization side for separating object in complicated object with Simulated Moving Bed Chromatography according to claim 1
Method, which is characterized in that when the SMB is the four band SMB continuously recycled, set mI> G 'ATo elute slow component A, setting
mIV< G 'BTo prevent fast component from entering I band.
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