Full-closed sterile connection type mRNA-LNP preparation automatic packaging system

Abstract

The invention relates to the technical field of biological medicine preparations, and discloses a full-closed sterile connection type mRNA-LNP preparation automatic packaging system which comprises a sterile operation cabin and an automatic conveying module, the automatic conveying module is used for conveying raw materials or semi-finished products of mRNA-LNP preparations to a packaging station in the sterile operation cabin according to a preset path, and the packaging station is used for packaging the raw materials or semi-finished products of the mRNA-LNP preparations. The packaging module is installed on a packaging station in the sterile operation cabin, the quality detection module is arranged in the sterile operation cabin, the control system module is electrically connected with the automatic conveying module, the packaging module and the quality detection module through a data bus, and through cooperative work of the automatic conveying module, the packaging module and the quality detection module, the quality detection module is connected with the packaging module. Automatic packaging of the mRNA-LNP preparation is achieved, the automatic conveying module can accurately convey different types of raw materials or semi-finished products to a packaging station according to a preset path, the pollution risk caused by manual operation is reduced, and the production efficiency and the product quality are improved.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical preparations, and particularly to a fully enclosed aseptic connection type mRNA-LNP preparation automatic encapsulation system. Background Art

[0002] With the rapid development of mRNA technology, mRNA preparations are increasingly widely used in the fields of vaccines, gene therapy, etc. mRNA-LNP (lipid nanoparticles) is a nanoscale carrier system for delivering messenger ribonucleic acid (mRNA), and the encapsulation quality of its preparations directly affects the stability and efficacy of the products. However, the existing mRNA-LNP preparation encapsulation technologies have the following defects:

[0003] 1. Traditional encapsulation systems mostly adopt open or semi-open operations, and it is impossible to completely avoid the contamination of external microorganisms. Especially during multi-step operations, the aseptic environment is easily damaged. Existing encapsulation systems often require manual intervention, such as manually transferring raw materials or semi-finished products, manually detecting quality, etc. This not only reduces production efficiency but also increases the risk of human contamination.

[0004] 2. It is difficult to ensure the encapsulation accuracy of mRNA-LNP preparations. Especially during the injection and encapsulation processes, situations such as inaccurate dosage or incomplete encapsulation are likely to occur, affecting product quality. Moreover, quality detection means mostly focus on the finished product detection stage and cannot be monitored and adjusted in real time during the encapsulation process, resulting in a relatively high defective product rate.

[0005] Therefore, it is necessary to provide a fully enclosed aseptic connection type mRNA-LNP preparation automatic encapsulation system to solve the above problems. Summary of the Invention

[0006] The purpose of the present invention is to provide a technical solution to solve the problems in the above-mentioned background art through technical means such as fully enclosed aseptic operation, automatic conveying and encapsulation, and real-time quality monitoring.

[0007] To achieve the above purpose, the present invention adopts the following technical solutions:

[0008] A fully enclosed aseptic connection type mRNA-LNP preparation automatic encapsulation system, including a sterile operation chamber for providing a fully enclosed aseptic operation environment;

[0009] An automatic conveying module, which is used to convey the raw materials or semi-finished products of mRNA-LNP preparations to the encapsulation station in the sterile operation chamber according to a preset path;

[0010] Encapsulation module, which is installed at the encapsulation station in the aseptic operation chamber and performs encapsulation operations on the raw materials or semi-finished products of the mRNA-LNP preparation sent by the automated conveying module. The encapsulation module includes a sterile connection component and an encapsulation unit. The sterile connection component is installed above the interior of the aseptic operation chamber, and the encapsulation unit is installed at the encapsulation station in the aseptic operation chamber. The encapsulation unit and the sterile connection component perform injection encapsulation operations on the raw materials or semi-finished products of the mRNA-LNP preparation;

[0011] Quality inspection module, which is used to perform quality inspection on the encapsulated preparation. The quality inspection module is set in the aseptic operation chamber and is located behind the encapsulation module;

[0012] Control system module, which is used to control the operation of each module and monitor the parameters of the entire encapsulation process. The control system module is electrically connected to the automated conveying module, the encapsulation module, and the quality inspection module through a data bus.

[0013] Preferably, the aseptic operation chamber includes a laminar flow device, which is installed on the inner top surface of the aseptic operation chamber. The inner wall of the aseptic operation chamber is provided with a self-cleaning coating, and the aseptic operation chamber is also equipped with a pressure monitoring unit

[0014] Preferably, the automated conveying module includes a multi-track conveying system, a positioning sensor, and a speed controller. Each track of the multi-track conveying system corresponds to different types of raw materials or semi-finished products of the mRNA-LNP preparation. The positioning sensor for detecting the position of the raw materials or semi-finished products is installed on one side of the encapsulation module. The speed controller is used to adjust the conveying speed to ensure that the raw materials or semi-finished products of the mRNA-LNP preparation on each track accurately reach the encapsulation station of the aseptic operation chamber.

[0015] Preferably, the sterile connection component includes a sterile docking head and a sealing mechanism. The encapsulation unit includes a high-precision injection pump and a multi-chamber encapsulation mold. The high-precision injection pump is aseptically docked with the multi-chamber encapsulation mold through the sterile docking head and the sealing mechanism to accurately inject the mRNA-LNP preparation into the multi-chamber encapsulation mold and perform encapsulation processing.

[0016] Preferably, the quality inspection module includes an appearance inspection unit, a sealing inspection unit, and a content inspection unit. The appearance inspection unit checks the appearance of the mRNA-LNP preparation through a high-resolution camera. The sealing inspection unit detects the sealing performance of the encapsulation container through pressure changes. The content inspection unit uses fluorescence spectroscopy analysis technology to detect the mRNA content in the preparation.

[0017] Preferably, the control system module includes a data processing unit, a processing unit, and an execution unit. The data processing unit collects parameters during the encapsulation process. The processing unit receives the collected data sent by the data processing unit for analysis and processing. The execution unit controls the operation of the system according to the control instructions sent by the processing unit.

[0018] Preferably, it further includes a waste liquid treatment module. The waste liquid treatment module includes a filtration unit, an adsorption unit, and an inactivation unit. The filtration unit is used to remove particulate matter in the waste liquid. The adsorption unit is used to adsorb organic matter in the waste liquid. The inactivation unit is used to inactivate bioactive substances in the waste liquid. The filtration unit, adsorption unit, and inactivation unit are sequentially connected by pipelines. The waste liquid is discharged after passing through the filtration unit, adsorption unit, and inactivation unit in sequence.

[0019] Preferably, the multi-chamber encapsulation mold is provided with a plurality of encapsulation chambers to simultaneously complete the encapsulation operations of multiple mRNA-LNP preparations.

[0020] Preferably, the quality detection module can timely feedback the detection results to the control system module. The control system module adjusts the operation parameters of the encapsulation module according to the feedback results to form a closed-loop control.

[0021] The technical effects and advantages of the present invention: The fully enclosed aseptic connection type mRNA-LNP preparation automatic encapsulation system proposed by the present invention has the following advantages compared with the prior art:

[0022] 1. By setting up a fully enclosed aseptic operation cabin equipped with a laminar flow device, a self-cleaning coating, and a pressure monitoring unit, the present invention provides a highly aseptic environment for the encapsulation of mRNA-LNP preparations. The laminar air flow generated by the laminar flow device can effectively remove particulate matter and microorganisms in the air, ensuring that the air cleanliness reaches ISO Class 5. The self-cleaning coating removes surface contaminants through photocatalysis or electrostatic adsorption to prevent the accumulation of contaminants. The pressure monitoring unit monitors the pressure in the cabin in real time and automatically adjusts the air flow parameters of the laminar flow device to maintain the stability of the aseptic environment. This fully enclosed aseptic operation environment significantly reduces the risk of external microbial contamination, ensures the sterility of mRNA-LNP preparations during the production process, and improves the product quality and safety.

[0023] 2. Through the collaborative work of the automated conveying module, encapsulation module, and quality inspection module, the present invention realizes the automated encapsulation of mRNA-LNP preparations. The automated conveying module can accurately convey different types of raw materials or semi-finished products to the encapsulation station according to a preset path, reducing the risk of contamination caused by manual operations. The aseptic connection component and encapsulation unit in the encapsulation module can precisely complete the injection and encapsulation operations, ensuring the accuracy of the preparation dosage. The quality inspection module can provide real-time feedback of the inspection results after encapsulation, and the control system module adjusts the encapsulation parameters according to the results to form a closed-loop control, promptly discovering and correcting problems in the production process, improving production efficiency and product quality. This automated encapsulation system not only improves production efficiency but also significantly reduces the risk of human contamination, ensuring the encapsulation accuracy and quality stability of mRNA-LNP preparations. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 It is a system block diagram of the fully enclosed aseptic connection type mRNA-LNP preparation automated encapsulation system of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0025] Now, the subject matter described herein will be discussed with reference to exemplary embodiments. It should be understood that discussing these embodiments is only to enable those skilled in the art to better understand and thus implement the subject matter described herein. Without departing from the scope of protection of the content of this specification, changes can be made to the functions and arrangements of the elements discussed. Each example can omit, substitute, or add various processes or components as needed. Additionally, the features described in some examples can also be combined in other examples.

[0026] The invention provides as Figure 1 shown, a fully enclosed aseptic connection type mRNA-LNP preparation automated encapsulation system, including a sterile operation chamber for providing a fully enclosed sterile operation environment. The sterile operation chamber includes a laminar flow device installed on the inner top surface of the sterile operation chamber. The inner wall of the sterile operation chamber is provided with a self-cleaning coating, and the sterile operation chamber is also equipped with a pressure monitoring unit;

[0027] The laminar flow device generates laminar air flow in the vertical or horizontal direction, ensuring that the air cleanliness in the cabin reaches ISO Class 5. The laminar flow device is connected to the pressure monitoring unit through a data cable and automatically adjusts the air flow parameters according to the pressure change. The self-cleaning coating removes surface contaminants through photocatalysis or electrostatic adsorption to ensure the cleanliness of the cabin inner wall. The pressure monitoring unit monitors the cabin pressure in real time to ensure the stability of the aseptic environment and transmits the pressure data to the control system module. The laminar flow device filters the air through a high-efficiency filter to form a laminar air flow, blowing the particulate matter and microorganisms in the air towards the ground or a specific air outlet, thereby maintaining a high cleanliness in the cabin. The pressure monitoring unit can detect whether the cabin pressure is within the set range. If the pressure changes, it indicates that there may be air leakage or other problems. At this time, the laminar flow device will automatically adjust the air flow parameters to maintain the aseptic environment. The self-cleaning coating decomposes organic contaminants through photocatalytic reactions or adsorbs particulate matter on the coating surface through electrostatic adsorption to prevent the accumulation of contaminants, providing a sterile and clean operating environment for the encapsulation of mRNA-LNP preparations, ensuring that the preparations are not contaminated by external microorganisms and particulate matter during the production process, and guaranteeing the product quality and safety.

[0028] The automated conveying module is used to convey the raw materials or semi-finished products of mRNA-LNP preparations to the encapsulation station in the aseptic operation cabin according to a preset path. The automated conveying module includes a multi-track conveying system, a positioning sensor, and a speed controller. Each track of the multi-track conveying system corresponds to a different type of raw material or semi-finished product of mRNA-LNP preparations. The positioning sensor for detecting the position of the raw material or semi-finished product is installed on one side of the encapsulation module. The positioning sensor is used to detect the position of the raw material or semi-finished product and transmit the position information to the control system module. The speed controller adjusts the conveying speed according to the instructions of the control system module to ensure that the raw materials or semi-finished products of mRNA-LNP preparations on each track accurately reach the encapsulation station of the aseptic operation cabin. The multi-track conveying system is similar to multiple independent conveyor belts, and each conveyor belt is responsible for transporting a specific type of raw material or semi-finished product. The positioning sensor can be a photoelectric sensor or other types of sensors, used to detect whether the raw material or semi-finished product reaches the designated position. The speed controller controls the running speed of the conveying track by adjusting the motor speed or other driving methods;

[0029] It realizes the automated conveying of raw materials or semi-finished products, improves production efficiency, reduces the pollution risk brought by manual operations, ensures that the raw materials can accurately and timely reach the encapsulation station, and guarantees the continuity and stability of production. The automated conveying module conveys the raw materials to the encapsulation station in an aseptic environment, ensuring that the raw materials are not contaminated during the conveying process.

[0030] The encapsulation module is installed on the encapsulation station in the aseptic operation chamber to perform encapsulation operations on the raw materials or semi-finished products of the mRNA-LNP preparation sent by the automated conveying module. The encapsulation module includes an aseptic connection component and an encapsulation unit. The aseptic connection component is installed above the interior of the aseptic operation chamber, and the encapsulation unit is installed on the encapsulation station in the aseptic operation chamber. The encapsulation unit and the aseptic connection component perform injection encapsulation operations on the raw materials or semi-finished products of the mRNA-LNP preparation. The aseptic connection component includes an aseptic docking head and a sealing mechanism. The encapsulation unit includes a high-precision injection pump and a multi-chamber encapsulation mold. The high-precision injection pump is aseptically docked with the multi-chamber encapsulation mold through the aseptic docking head and the sealing mechanism to accurately inject the mRNA-LNP preparation into the multi-chamber encapsulation mold and perform encapsulation processing;

[0031] It should be noted that the multi-chamber encapsulation mold is provided with multiple encapsulation chambers to simultaneously complete the encapsulation operations of multiple mRNA-LNP preparations. The aseptic docking head and the sealing mechanism can connect the preparation container with the encapsulation unit without destroying the aseptic environment, preventing external microorganisms from entering. The high-precision injection pump can accurately control the injection dose to ensure the accurate preparation dose in each encapsulation chamber. The multi-chamber encapsulation mold allows simultaneous encapsulation of multiple preparations, improving production efficiency.

[0032] The quality inspection module is used to perform quality inspection on the encapsulated preparation. The quality inspection module is set in the aseptic operation chamber and is located behind the encapsulation module. The quality inspection module includes an appearance inspection unit, a sealing inspection unit, and a content inspection unit. The appearance inspection unit checks the appearance of the mRNA-LNP preparation through a high-resolution camera, and the inspection result is transmitted to the control system module.

[0033] The sealing inspection unit detects the sealing performance of the encapsulation container through pressure changes. The content inspection unit uses fluorescence spectroscopy analysis technology to detect the mRNA content in the preparation. After the encapsulation module completes the encapsulation operation, the quality inspection module can timely feedback the inspection result to the control system module. The control system module adjusts the operating parameters of the encapsulation module according to the feedback result. The quality inspection module performs multi-dimensional inspection on the preparation, and the inspection result is feedback to the control system module. The control system module adjusts the encapsulation parameters according to the result to form a closed-loop control;

[0034] The high-resolution camera can capture the appearance details of the preparation, such as whether there are cracks, foreign objects, etc. The sealing performance is detected by filling a certain pressure of gas into the encapsulation container and then monitoring the pressure change. If the pressure drops, it indicates poor sealing performance. Fluorescence spectroscopy analysis technology can quickly and accurately detect the mRNA content in the preparation to ensure that it meets the quality standards. Performing multi-dimensional quality inspection on the encapsulated preparation ensures that the product quality meets the standards, timely discovers and corrects problems in the production process, and improves production efficiency and product quality.

[0035] The control system module is used to control the operation of each module and monitor the parameters of the entire encapsulation process. The control system module is electrically connected to the automated conveying module, the encapsulation module, and the quality inspection module through a data bus. The control system module includes a data processing unit, a processing unit, and an execution unit. The data processing unit collects parameters during the encapsulation process, such as temperature, humidity, pressure, injection dose, etc. The processing unit receives the collected data sent by the data processing unit for analysis and processing to determine whether it meets the preset standards. The execution unit controls the operation of the system according to the control instructions sent by the processing unit, such as adjusting the conveying speed, injection dose, pausing production, etc., to uniformly control and manage the operation of the entire encapsulation system, ensure the coordinated work of each module, and monitor and adjust the parameters in the production process in real time to ensure the smooth progress of production and the stability of product quality.

[0036] Furthermore, in order to prevent the waste liquid generated during production from affecting the environment, the system is also equipped with a waste liquid treatment module. The waste liquid treatment module includes a filtration unit, an adsorption unit, and an inactivation unit. The filtration unit usually contains filter membranes or filters with different pore sizes to remove particulate matter in the waste liquid. The adsorption unit is used to adsorb organic substances in the waste liquid. The adsorption material in the adsorption unit has a large number of micropores and a large surface area, which can adsorb organic molecule. The inactivation unit is used to inactivate the bioactive substances in the waste liquid. The inactivation unit selects a suitable inactivation method according to the characteristics of the waste liquid and the type of bioactive substances to ensure that the waste liquid discharge meets the environmental protection standards. The filtration unit, the adsorption unit, and the inactivation unit are connected in sequence through pipelines. The waste liquid is discharged after passing through the filtration unit, the adsorption unit, and the inactivation unit in sequence to treat the waste liquid generated during the encapsulation process, remove the pollutants and bioactive substances in it, prevent environmental pollution, and at the same time avoid the pollution of the aseptic operation cabin by the microorganisms in the waste liquid.

[0037] The above describes the embodiments of the present invention, but the present invention is not limited to the above specific embodiments. The above specific embodiments are merely illustrative and not restrictive. Under the inspiration of the present invention, those of ordinary skill in the art can also make many forms, all of which fall within the protection scope of the present invention.

Claims

1. An automated encapsulation system for a fully enclosed sterile connection type mRNA-LNP preparation, characterized in that, It includes a sterile operation chamber for providing a fully enclosed sterile operation environment; An automated conveying module, which is used to convey the raw materials or semi-finished products of the mRNA-LNP preparation to the encapsulation station in the sterile operation chamber along a preset path; An encapsulation module, which is installed at the encapsulation station in the sterile operation chamber and performs encapsulation operations on the raw materials or semi-finished products of the mRNA-LNP preparation fed by the automated conveying module. The encapsulation module includes a sterile connection component and an encapsulation unit. The sterile connection component is installed above the interior of the sterile operation chamber, and the encapsulation unit is installed at the encapsulation station in the sterile operation chamber. The encapsulation unit and the sterile connection component perform injection encapsulation operations on the raw materials or semi-finished products of the mRNA-LNP preparation; A quality inspection module for inspecting the quality of the encapsulated preparation. The quality inspection module is arranged in the sterile operation chamber and is located behind the encapsulation module; A control system module for controlling the operation of each module and monitoring the parameters of the entire encapsulation process. The control system module is electrically connected to the automated conveying module, the encapsulation module, and the quality inspection module through a data bus respectively.

2. The fully enclosed sterile connection type mRNA-LNP preparation automatic encapsulation system according to claim 1, wherein The sterile operation chamber includes a laminar flow device, which is installed on the inner top surface of the sterile operation chamber. The inner wall of the sterile operation chamber is provided with a self-cleaning coating, and the sterile operation chamber is also equipped with a pressure monitoring unit.

3. The fully enclosed sterile connection type mRNA-LNP preparation automatic encapsulation system according to claim 1, wherein, The automated conveying module includes a multi-track conveying system, a positioning sensor, and a speed controller. Each track of the multi-track conveying system corresponds to a different type of raw material or semi-finished product of the mRNA-LNP preparation. The positioning sensor for detecting the position of the raw material or semi-finished product is installed on one side of the encapsulation module. The speed controller is used to adjust the conveying speed to ensure that the raw materials or semi-finished products of the mRNA-LNP preparation on each track accurately reach the encapsulation station of the sterile operation chamber.

4. The fully enclosed sterile connection type mRNA-LNP preparation automatic encapsulation system according to claim 1, characterized in that The sterile connection component includes a sterile docking head and a sealing mechanism. The encapsulation unit includes a high-precision injection pump and a multi-chamber encapsulation mold. The high-precision injection pump is aseptically docked with the multi-chamber encapsulation mold through the sterile docking head and the sealing mechanism to accurately inject the mRNA-LNP preparation into the multi-chamber encapsulation mold and perform encapsulation processing.

5. The fully enclosed sterile connection type mRNA-LNP preparation automatic encapsulation system according to claim 1, characterized in that, The quality inspection module includes an appearance inspection unit, a sealing inspection unit, and a content inspection unit. The appearance inspection unit checks the appearance of the mRNA-LNP preparation through a high-resolution camera. The sealing inspection unit detects the sealing performance of the encapsulation container through pressure changes. The content inspection unit uses fluorescence spectroscopy analysis technology to detect the mRNA content in the preparation.

6. The fully enclosed sterile connection type mRNA-LNP preparation automatic encapsulation system according to claim 1, characterized in that, The control system module includes a data processing unit, a processing unit, and an execution unit. The data processing unit collects the parameters in the encapsulation process. The processing unit receives the collected data sent by the data processing unit for analysis and processing. The execution unit controls the operation of the system according to the control instructions sent by the processing unit.

7. The fully enclosed sterile connection type mRNA-LNP preparation automatic encapsulation system according to claim 1, wherein, It also includes a waste liquid treatment module, and the waste liquid treatment module includes a filtration unit, an adsorption unit and an inactivation unit. The filtration unit is used to remove particulate matter in the waste liquid, the adsorption unit is used to adsorb organic matter in the waste liquid, and the inactivation unit is used to inactivate bioactive substances in the waste liquid. The filtration unit, the adsorption unit and the inactivation unit are sequentially connected by pipelines, and the waste liquid is discharged after passing through the filtration unit, the adsorption unit and the inactivation unit in sequence.

8. The fully enclosed sterile connection type mRNA-LNP preparation automatic encapsulation system according to claim 4, characterized in that, A plurality of encapsulation chambers are provided in the multi-chamber encapsulation mold to simultaneously complete the encapsulation operations of a plurality of mRNA-LNP preparations.

9. The fully enclosed sterile connection type mRNA-LNP preparation automatic encapsulation system according to claim 1, wherein The quality detection module can feedback the detection results to the control system module in real time, and the control system module adjusts the operation parameters of the encapsulation module according to the feedback results to form a closed-loop control.

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