CO2 supercritical continuous liquid chromatography system for intelligent totally-closed operation

Abstract

The invention discloses an intelligent fully-closed operation CO2 supercritical continuous liquid chromatography system which comprises the following steps: S1, selecting pure CO2 in a supercritical state or CO2 which contains an entrainer and is in a supercritical state as a mobile phase according to the property of a sample; s2, setting a purification process route according to a spectrogram under the basic conditions of walking a single column and reading the spectrogram, correcting software parameters in a man-machine conversation mode, and then starting a program; s3, when the post-column liquid enters the corresponding first-stage tank body, a precise pressure regulating valve between the first-stage tank and the second-stage tank is automatically adjusted according to the pressure set by a program, so that the supercritical solution containing sample components enters the second-stage tank, meanwhile, clean liquid appears in the first-stage tank, and the clean liquid is discharged into the clean liquid first-stage tank. A closed operation process method is applied, an LED strong penetrating UV detector is adopted, intelligent control is achieved, and automatic operation, continuous sample injection and automatic sample injection time and sample injection port selection can be achieved. Due to the two-stage pressure release design, automatic control can be achieved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to an intelligent, fully enclosed CO2 supercritical continuous liquid chromatography system. Background Technology

[0002] This technology is applied to the separation and purification of active pharmaceutical ingredients (APIs) in the pharmaceutical industry. Using supercritical CO2 for extraction is an advanced technique. Replacing organic solvents with supercritical CO2 can significantly reduce pollution and lower costs. However, current technology is relatively new and still in the exploratory stage. Especially when applying this technology to high-performance liquid chromatography (HPLC), it involves integrating two cutting-edge technologies. Currently, the following drawbacks remain: The level of automation is low, and the operator is on-site throughout the entire process.

[0003] Without an online monitoring unit, the timing of the appearance of the target object, pre-impurities, and post-impurities is inferred from previous experimental results.

[0004] Open-loop operation, the instantaneous heat absorption when supercritical CO2 releases pressure causes water vapor near the outlet to freeze, creating chaos in the workplace and potentially affecting the quality of the target product.

[0005] 4. The first-level pressure relief tank is manually operated, has low precision, and poses a risk of minor injury. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides an intelligent, fully enclosed CO2 supercritical continuous liquid chromatography system, which solves the problems of insufficient quality and minor injury risks associated with using supercritical CO2 to replace organic solvents.

[0007] To achieve the above objectives, the present invention provides the following technical solution: an intelligent, fully enclosed CO2 supercritical continuous liquid chromatography system, comprising the following steps: S1: Select pure supercritical CO2 or supercritical CO2 containing entrainer as the mobile phase according to the properties of the sample. S2: Run a single column, observe the basic situation of the spectrum, set the purification process route according to the spectrum, correct the software parameters through human-computer interaction, and then start the program. S3: When the post-column liquid enters the corresponding primary tank, the precision pressure regulating valve between the primary and secondary tanks automatically adjusts according to the pressure set in the program, so that the supercritical solution containing the sample components enters the secondary tank. At the same time, the purified liquid appears in the primary tank and is discharged into the purified liquid primary tank. Meanwhile, the precision pressure regulating valve of the secondary tank automatically adjusts according to the pressure set in the program, the sample components are separated, and the CO2 gas-liquid mixture is drawn into the gas-liquid compression pump, restored to the supercritical state, and enters the purified liquid primary tank. S4: After completing the injection of the previous column, the sample pump automatically injects the sample according to the real-time status detected by the UV detector, and enters another single-column working mode. S5: Adjust the flow rate of the mobile phase in a single column so that the injection spacing between several columns is close to 0, thus achieving the continuous injection working mode.

[0008] Preferably, the single column operates as follows: the mobile phase pump operates, the mobile phase passes through the chromatographic column, the UV detector automatically records the data, after baseline equilibration, the mobile phase pump pauses, the sample pump injects the sample, after injection, the mobile phase pump operates again, and the UV detector monitors in real time. In the mobile phase purification zone, the purification tank valve opens, the pre-impurity peak appears, after the pre-impurity tank valve opens, the purification tank valve closes, the main peak in the product zone appears to a set height, after the product tank valve opens, the pre-impurity tank valve closes, the main peak falls back to the set height, after the post-impurity tank valve opens, the product tank valve closes, the post-impurity peak completes its course, the purification tank valve opens, and then the post-impurity tank valve closes.

[0009] This invention provides an intelligent, fully enclosed CO2 supercritical continuous liquid chromatography system with the following advantages: It utilizes a closed-loop process, employs a high-penetration LED UV detector, enables online monitoring and intelligent control, achieving automated operation, continuous sample injection, and automatic selection of injection time and port. The two-stage pressure release design further enhances automatic control. Once the operator sets the program parameters, no manual operation is required, saving manpower. Attached Figure Description

[0010] Figure 1 This is a schematic diagram of the system of the present invention. Detailed Implementation

[0011] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0012] Please see Figure 1 This invention provides a technical solution: an intelligent, fully enclosed CO2 supercritical continuous liquid chromatography system, comprising the following steps: S1: Select pure supercritical CO2 or supercritical CO2 containing an entrainer as the mobile phase according to the properties of the sample; the sample needs to be dissolved in the mobile phase here. S2: Run a single column, observe the basic situation of the spectrum, set the purification process route according to the spectrum, correct the software parameters through human-computer interaction, and then start the program. S3: When the post-column liquid enters the corresponding primary tank, the precision pressure regulating valve between the primary and secondary tanks automatically adjusts according to the pressure set in the program, so that the supercritical solution containing the sample components enters the secondary tank. At the same time, the purified liquid appears in the primary tank and is discharged into the purified liquid primary tank. Meanwhile, the precision pressure regulating valve of the secondary tank automatically adjusts according to the pressure set in the program, the sample components are separated, and the CO2 gas-liquid mixture is drawn into the gas-liquid compression pump, restored to the supercritical state, and enters the purified liquid primary tank. S4: After completing the injection of the previous column, the sample pump automatically injects the sample according to the real-time status detected by the UV detector, and enters another single-column working mode. S5: Adjust the flow rate of the mobile phase in a single column so that the injection spacing between several columns is close to 0, thus achieving the continuous injection working mode.

[0013] Furthermore, the single-column operation is as follows: the mobile phase pump operates, the mobile phase passes through the chromatographic column, the UV detector automatically records the data, after baseline equilibration, the mobile phase pump pauses, the sample pump injects the sample, after injection, the mobile phase pump operates again, and the UV detector monitors in real time. In the mobile phase purification zone, the purification tank valve opens, the pre-impurity peak appears, after the pre-impurity tank valve opens, the purification tank valve closes, the main peak in the product zone appears to the set height, after the product tank valve opens, the pre-impurity tank valve closes, the main peak falls back to the set height, after the post-impurity tank valve opens, the product tank valve closes, the post-impurity peak completes its course, the purification tank valve opens, and then the post-impurity tank valve closes.

[0014] Those skilled in the art can perform the steps in this case sequentially. The specific order of operations should refer to the following working principle. The detailed technical means are well-known in the field. The following mainly introduces the working principle and process.

[0015] Example: In use, first select pure supercritical CO2 or supercritical CO2 containing entrainer as the mobile phase according to the properties of the sample; then observe the basic situation of the spectrum, set the purification process route according to the spectrum, correct the software parameters through human-computer interaction, and then start the program; after completing the injection of the previous column, the sample pump automatically injects the sample according to the real-time status detected by the UV detector, and enters the working mode of another single column; finally, adjust the flow rate of the mobile phase of the single column so that the injection interval between several single columns is close to 0, thus realizing the continuous injection working mode.

[0016] It should be noted that, in this document, relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, the phrase "comprising an element defined as..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0017] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A fully enclosed CO2 supercritical continuous liquid chromatography system, characterized in that, Includes the following steps: S1: Select pure supercritical CO2 or supercritical CO2 containing entrainer as the mobile phase according to the properties of the sample. S2: Run a single column, observe the basic situation of the spectrum, set the purification process route according to the spectrum, correct the software parameters through human-computer interaction, and then start the program. S3: When the post-column liquid enters the corresponding primary tank, the precision pressure regulating valve between the primary and secondary tanks automatically adjusts according to the pressure set in the program, so that the supercritical solution containing the sample components enters the secondary tank. At the same time, the purified liquid appears in the primary tank and is discharged into the purified liquid primary tank. Meanwhile, the precision pressure regulating valve of the secondary tank automatically adjusts according to the pressure set in the program, the sample components are separated, and the CO2 gas-liquid mixture is drawn into the gas-liquid compression pump, restored to the supercritical state, and enters the purified liquid primary tank. S4: After completing the injection of the previous column, the sample pump automatically injects the sample according to the real-time status detected by the UV detector, and enters another single-column working mode. S5: Adjust the flow rate of the mobile phase in a single column so that the injection spacing between several columns is close to 0, thus achieving the continuous injection working mode.

2. The intelligent, fully enclosed CO2 supercritical continuous liquid chromatography system according to claim 1, characterized in that, The single-column operation is as follows: the mobile phase pump operates, the mobile phase passes through the chromatographic column, and the UV detector automatically records the data. After baseline equilibration, the mobile phase pump pauses, and the sample pump injects the sample. After injection, the mobile phase pump operates again, and the UV detector monitors in real time. In the mobile phase purification zone, the purification tank valve opens, and the initial impurity peak appears. After the initial impurity tank valve opens, the purification tank valve closes, and the main peak in the product zone appears at the set height. After the product tank valve opens, the initial impurity tank valve closes, and the main peak falls back to the set height. After the subsequent impurity tank valve opens, the product tank valve closes, the subsequent impurity peak completes its passage, the purification tank valve opens, and then the subsequent impurity tank valve closes.

Images