Online dilution device for lipid nanoparticle preparation

Abstract

The utility model discloses an on-line dilution device for preparing lipid nanoparticles, which comprises a discharge pipe, one end of the discharge pipe is an open pipe orifice, the other end of the discharge pipe is a sealed end and is connected with a feed pipe, one end of the feed pipe is an open pipe orifice, the other end of the feed pipe is sealed, and the feed pipe extends to penetrate through the end part of the discharge pipe and is provided with an extension section corresponding to the interior of the discharge pipe. A liquid outlet hole is formed in the side wall of the extension section part; the side wall of the discharge pipe corresponding to the sealed end is communicated with a dilution pipe, and the inner side wall of the discharge pipe is provided with a spiral groove. After lipid and mRNA are prepared into coated particles through a lipid nanoparticle (LNP) technology, the coated particles are diluted through a diluent, a coated mRNA solution is guided into a discharging pipe through a feeding pipe, and a port of the feeding pipe is closed, so that liquid is uniformly distributed from the circumferential side of the feeding pipe through a liquid outlet hole and enters the discharging pipe, and the end part of the discharging pipe is communicated with a dilution pipe for injecting the diluent; and the mixing device is used for mixing the diluent and the coated mRNA solution while moving in the discharge pipe, and synchronously diluting the diluent and the coated mRNA solution.

Description

TECHNICAL FIELD

[0001] The utility model belongs to the technical field of biological preparation equipment, in particular to a kind of online dilution device for lipid nanoparticle preparation. BACKGROUND

[0002] In addition to inactivated antigens, a large part of vaccine drugs is mainly mRNA vaccines, which transcribe mRNA in the human body to produce target proteins with immunogenicity, thereby preventing or treating various diseases. The mRNA drug preparation process is roughly as follows: first, Escherichia coli is used as a carrier for culture, then concentrated by hollow fiber column to obtain high-concentration Escherichia coli bacterial solution, then obtained by fermentation, alkaline lysis, filtration clarification and other steps to obtain stock solution, and then purified by chromatography column to obtain plasmid DNA template, and then obtained by enzyme cutting and in vitro transcription to obtain mRNA, and finally wrapped by LNP technology to obtain mRNA vaccine product.

[0003] The preparation of LNP-mRNA is to mix ionizable cationic lipids, phospholipids, cholesterol and PEG lipids with mRNA by microfluidic technology to form stable and efficient delivery nanoparticles. The initial LNP-mRNA needs to be diluted to reduce the ethanol concentration and enhance the particle stability, and then the liquid is changed. However, during the dilution of the diluent to the LNP-mRNA, the stability of the particles is often adversely affected. Therefore, it is urgent to develop an online dilution device that can simultaneously dilute the freshly prepared unstable LNP-mRNA at a stable flow rate to improve the stability of the initial LNP-mRNA and optimize the subsequent process. UTILITY MODEL CONTENT

[0004] The utility model aims at providing a kind of online dilution device for lipid nanoparticle preparation, can with the stable flow rate to the freshly prepared unstable LNP-mRNA is simultaneously diluted, to improve the stability of the initial LNP-mRNA and optimize subsequent process.

[0005] To solve the above technical problems, the utility model is realized by the following technical solutions:

[0006] An online dilution device for lipid nanoparticle preparation includes a discharge pipe, one end of which is an open pipe opening for discharge, and the other end is a sealed end connected with a feed pipe, the feed pipe is coaxially arranged with the discharge pipe, one end of the feed pipe is an open pipe opening for feeding, the other end is sealed, and extends through the end of the discharge pipe and has an extension section corresponding to the inside of the discharge pipe, and the extension section has a liquid outlet hole in the side wall.

[0007] The dilution pipe is communicated with the side wall of the sealing end of the discharge pipe, and is used for injecting dilution liquid.

[0008] Further, the discharge pipe has a flared portion corresponding to the sealing end, and the dilution pipe is communicated with the side wall of the flared portion.

[0009] Further, a heat preservation sleeve is sleeved outside the discharge pipe, so as to form a heat preservation layer between the discharge pipe.

[0010] The utility model has the following beneficial effects: after the lipid and mRNA are coated by the lipid nanoparticle (LNP) technology, the coated mRNA solution is diluted by the dilution liquid, and then is introduced into the discharge pipe through the feeding pipe, and the feeding pipe port is closed, therefore, the liquid is uniformly distributed from the feeding pipe circumferential side through the liquid outlet hole, enters the discharge pipe, and the end of the discharge pipe is communicated with the dilution pipe, which is used for injecting dilution liquid, so that the dilution liquid and the coated mRNA solution are mixed when moving in the discharge pipe, and the dilution is simultaneously carried out. BRIEF DESCRIPTION OF DRAWINGS

[0011] In order to more clearly illustrate the technical scheme of the embodiments of the utility model, the following will briefly introduce the drawings needed to be used for the embodiment description.

[0012] Figure 1 The utility model structural schematic diagram.

[0013] Figure 2 The utility model discharge pipe has the structure schematic diagram of the section.

[0014] In the drawings, the component list represented by each sign is as follows: discharge pipe 1, feeding pipe 2, liquid outlet hole 21, dilution pipe 3, spiral groove 12, flared portion 11, heat preservation sleeve 4, regulating valve 5. DETAILED DESCRIPTION

[0015] The technical scheme in the embodiments of the utility model will be clearly and completely described in combination with the drawings in the embodiments of the utility model, and obviously, the described embodiments are only part of the embodiments of the utility model, not all the embodiments.

[0016] As Figures 1-2As shown: an online dilution device for lipid nanoparticle preparation, comprising a discharge pipe 1 corresponding to the axis of the pipe, one end of the discharge pipe 1 is an open mouth for the discharge port, the other end is a sealed end and is connected with a feed pipe 2, the feed pipe 2 is coaxially arranged with the discharge pipe 1, one end of the feed pipe 2 is an open mouth for the feed port, the other end is sealed and extends through the end of the discharge pipe 1 and has an extension section corresponding to the inside of the discharge pipe 1, the extension section has liquid outlet holes 21 on the side wall.

[0017] The discharge pipe 1 has a dilution pipe 3 connected to the side wall of the corresponding sealed end for injecting dilution liquid, and the inner side wall of the discharge pipe 1 has a spiral groove 12.

[0018] After the lipid and mRNA are coated into particles by the lipid nanoparticle (LNP) technology, the coated mRNA solution is diluted by the dilution liquid, introduced into the discharge pipe through the feed pipe, and the feed pipe port is closed, so that the liquid is uniformly distributed from the circumferential side of the feed pipe through the liquid outlet holes, enters the discharge pipe, and the end of the discharge pipe is connected to the dilution pipe for injecting dilution liquid, so that the dilution liquid and the coated mRNA solution are mixed when moving in the discharge pipe.

[0019] At the same time, after the dilution liquid and the multi-point released coated mRNA solution are mixed, the spiral groove in the discharge pipe provides a guiding effect during the movement of the solution in the discharge pipe, so that the solution flows spirally, and the mixing degree of the dilution liquid and the coated mRNA solution is improved.

[0020] The discharge pipe 1 has a flared portion 11 corresponding to the sealed end, and the dilution pipe 3 is connected to the side wall of the flared portion. The flared portion is integrally connected to the discharge pipe and has a shape similar to a funnel, so that the dilution liquid in the dilution pipe first fills the flared portion, then passes through the spiral groove, improves the stability of the one-way flow of the dilution liquid, and makes the flow rate of the feed pipe corresponding to the extension section of the side wall at each position the same.

[0021] As shown in Figure 1 The discharge pipe 1 is sleeved with a heat preservation sleeve 4 outside for forming a heat preservation layer between the discharge pipe 1. It is used for heat preservation during dilution to prevent temperature change from affecting the stability of the coated mRNA. The dilution pipe 3 is provided with an adjusting valve 5 outside the heat preservation sleeve 4 for controlling the flow rate of the dilution pipe 3. According to the flow rate of the solution in the discharge pipe, the flow rate of the dilution pipe is adjusted to accurately dilute the coated mRNA solution and the dilution liquid in a predetermined ratio per unit volume.

[0022] The embodiments are selected and specifically described in the specification in order to better explain the principles and practical applications of the utility model, so that those skilled in the art can well understand and utilize the utility model.

Claims

1. An online dilution device for lipid nanoparticle preparation, characterized in that: it comprises a discharge pipe (1) with one end being an open nozzle for a discharge port and the other end being a sealed end and connected with a feed pipe (2), the feed pipe (2) is coaxially arranged with the discharge pipe (1), one end of the feed pipe (2) is an open nozzle for a feed port, the other end is sealed and extends through the end of the discharge pipe (1) and has an extension section corresponding to the inside of the discharge pipe (1), the side wall of the extension section has liquid outlet holes (21); the side wall of the sealed end of the discharge pipe (1) is connected with a dilution pipe (3) for injecting dilution liquid, and the inner side wall of the discharge pipe (1) has a spiral groove (12).

2. The online dilution device for the preparation of lipid nanoparticles according to claim 1, characterized in that: The sealed end of the discharge pipe (1) has a flared portion (11), and the dilution pipe (3) is connected to the side wall of the flared portion.

3. The online dilution device for the preparation of lipid nanoparticles according to claim 1, characterized in that: The outside of the discharge pipe (1) is sleeved with a heat preservation sleeve (4) for forming a heat preservation layer between the discharge pipe (1) and the heat preservation sleeve (4).

4. The online dilution device for the preparation of lipid nanoparticles according to claim 3, characterized in that: The dilution pipe (3) is provided with an adjusting valve (5) outside the heat preservation sleeve (4) for controlling the flow rate of the dilution pipe (3).

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