Efficient purification-analysis system for biotechnological medicine and medicine separation detection method thereof

Abstract

The invention discloses an efficient purification-analysis system for a biotechnological medicine and a medicine separation detection method thereof. The efficient purification-analysis system comprises a control system, an analysis-detection unit and a detection interface, wherein the control system comprises a detection device used for online detecting the physical and chemical parameters of a liquid in a liquid pipeline; the detection interface is used for executing a feeding operation; the analysis-detection unit is used for analysing the feeding of the detection interface, and comprises a plurality of independently-arranged analytical type instruments; and the to-be-detected liquid is at least divided into two branches after entering in the system, one branch flows through the detection device, the physical and chemical parameters of the liquid are obtained, the control system identifies the liquid to be a sample or a waste liquid according to judgement rules and on the basis of the physical and chemical parameters of the liquid detected by the detection device, controls the feeding for the liquid identified to be the sample, of the detection interface, and selectively conveys the obtained sample in the analytical type instruments in the analysis-detection unit. Via the instruments, rapid analysis for the components obtained by separation in time can be guaranteed, so as to avoid pollution caused by environment or avoid pollution to environment.

Description

technical field [0001] The invention relates to a separation and detection instrument for biotechnology drugs, in particular to a fast sample purification system after preparation. Background technique [0002] Chromatography is a unit operation often used in modern chemical engineering and biochemical separation processes. For biotechnology drugs with complex components (such as cytokines, plasminogen activators, recombinant plasma factors, growth factors, fusion proteins, receptors, vaccines, and monoclonal antibodies, etc.), it is difficult to separate the active ingredients, the process is complicated, and the time, poor resolution and low efficiency. The products obtained after purification usually need to be detected in time for molecular weight, purity, activity, etc., so as to optimize the purification conditions. Since there is no combined device for preparative liquid chromatography and analytical liquid chromatography (PrepHPLC-HPLC) at this stage, traditional p...

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Problems solved by technology

[0005] 1) Parallel chromatographic instrument, multiple chromatographic columns are connected in parallel on the chromatographic instrument, all chromatographic columns work at the same time, but perform the same operation, as disclosed in Chinese patent CN201161989, this type of system can only improve the processing of chromatographic separation or detection quantity;

[0006] 2) For tandem chromatographic instruments, the chromatographic columns are directly switched through a multi-channel switching valve, that is, components are directly injected from one chromatographic column into another chromatographic column through a multi-channel switching valve. As disclosed in Chinese patent CN10161471, each The chromatographic columns can only be operated in sequence, and only one chromatographic column is working at the same time. This type of system usually only connects two to three preparative chromatographic columns, and the chromatographic modes that can be used are limited;

[0008] U.S. Patent US6485642B (its domestic publication number is CN1327152A) discloses a liquid chromatograph, which can realize the device for analyzing low-concentration samples after concentration, which includes a concentration column and an analysis column, which realizes preparation and elution liquid and introduced into the qualitative analysis instrument, but it only changes the concentration of the sample, the prepared sample solution is still a solution with multiple components, and its analysis can only shorten the analysis time, but not improve The effect of separation during the actual drug preparation

Although it is disclosed that there is an impurity removal column on the diluent pipeline, it only removes impurities in the diluent and cannot be counted as preparative chromatography. There is a huge difference between it and the rapid analysis of preparative chromatographic components.

[0009] Chinese patent CN102369434A provides a liquid chromatograph capable of suppressing sample residue at the injection port. It discloses a sample injection device that can automatically and accurately enter a sample into a chromatographic system. The invention of the device lies in the When sampling, the flow rate of the mobile phase is lower than the flow rate of the analysis conditions, so that the sample is difficult to remain in the gap between the needle and the sealing assembly of the needle, but the sample injection device cannot allow the sample to enter multiple chromatographic devices for further analysis. Detection, the device is an improvement on the sampling method, which helps to obtain more accurate analysis results

However, when it is applied to complex systems, such as when the system contains multiple components, its application is limited because it only detects the value of UV absorption.

[0011] Chinese patent application CN1520330A discloses a device and a sampling method which can realize selective sampling by moving a plurality of chromatographic columns relative to the analyzer through a shift stage. Although the device can realize selective sampling, its Components come from multiple columns, not suitable for preparative columns used for drug separations

[0014] Chinese patent CN201876442 provides a seamless connection device for on-line monitoring of milk antibiotics, which can realize the seamless connection of LC and MS, with good experimental recovery, short operation time and good reproducibility, which belongs to the case of no pretreatment A device for rapid on-line mechanized analysis of antibiotics in milk, but it is also not suitable for the preparation and analysis of drugs containing complex components

[0018] The above-mentioned types of instruments are only improvements to the chromatographic purification steps or analysis, rather than improvements to the subsequent automatic analysis steps, and the technical problems to be solved by the present invention belong to different fields, and they cannot realize the composition obtained by preparative chromatographic purification. Capable of simultaneous chromatographic analysis

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