CN214020875U - LNP nucleic acid vaccine preparation instrument - Google Patents
LNP nucleic acid vaccine preparation instrument Download PDFInfo
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- CN214020875U CN214020875U CN202023120219.5U CN202023120219U CN214020875U CN 214020875 U CN214020875 U CN 214020875U CN 202023120219 U CN202023120219 U CN 202023120219U CN 214020875 U CN214020875 U CN 214020875U
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Abstract
The invention relates to an LNP nucleic acid vaccine preparation instrument, which comprises two parallel liquid supply pipelines, wherein the liquid supply pipelines comprise a liquid supply bottle and a micro-fluid pressure pump which are communicated with each other, a liquid inlet and a liquid outlet on the micro-fluid pressure pump are respectively connected with a hose, the two liquid supply pipelines are respectively communicated with one end of a micro-fluid mixing control chip, a Y-shaped micro-channel is arranged in the micro-fluid mixing control chip, the double heads of the Y-shaped micro-channel are respectively communicated with the two liquid supply pipelines, a mixing micro-channel communicated with the single head of the Y-shaped micro-channel is also arranged on the micro-fluid mixing control chip, the mixing micro-channel consists of two sections of wavy micro-channels, the wavy micro-channel comprises four wave crests and four wave troughs, the two wavy micro-channels are communicated with each other through a linear micro-channel, and the inner diameter of the linear micro-channel is smaller than the inner diameter of the wavy micro-channel; the invention provides an LNP nucleic acid vaccine preparation instrument capable of preparing qualified LNP liposome nanoparticles.
Description
Technical Field
The invention relates to the field of pharmacy, in particular to an LNP nucleic acid vaccine preparation instrument.
Background
Lipid Nanoparticles (LNP) are used as a nano-drug carrier, and are particularly suitable for delivery of siRNA, mRNA, pDNA and small molecule drugs. Because of the advantages of high entrapment rate of active ingredients, good stability, small toxic and side effects and the like, the medicine is concerned by more and more medicine research and development and production mechanisms.
With the spread of new coronaviruses, the worldwide demand for mRNA-based nucleic acid vaccines is also increasing. LNP lipid nanoparticle technology is particularly suitable as a drug carrier for such mrnas due to its unique properties. At present, mRNA vaccine prepared by the technology is approved to be on the market abroad, and related products in China are still in clinical tests.
LNP is used as a novel drug carrier, the preparation technology and corresponding equipment thereof are not mature at present at home, and only a few foreign manufacturers can provide corresponding equipment. However, the equipment provided by foreign manufacturers is only suitable for laboratory research and development, and is not mature in Chinese style or production stage.
The existing equipment is generally a batch-type preparation method for preparing LNP lipid nanoparticles, i.e. a single preparation amount is fixed (such as 5ml), and if the subsequent industrialization is carried out, the equipment cannot meet the requirement due to large batch. The process parameters found in the experimental stage cannot be directly used as the process parameters in production, further finding is needed, failure risk factors are large, in addition, the existing equipment is generally not provided with a perfect temperature control unit, the temperature control in the LNP particle preparation process cannot be realized, and unqualified samples can be caused.
In view of the above-mentioned drawbacks, the present inventors have conducted active research and innovation to create an apparatus for preparing LNP nucleic acid vaccine according to industrial value.
Disclosure of Invention
In order to solve the above technical problems, the present invention aims to provide an LNP nucleic acid vaccine preparation apparatus with uniform LNP particle distribution and controllable PI value below 0.1.
The LNP nucleic acid vaccine preparation instrument comprises two parallel liquid supply pipelines, wherein the liquid supply pipelines comprise a liquid supply bottle and a microfluid pressure pump which are communicated, the liquid inlet and the liquid outlet on the microfluid pressure pump are respectively connected with a hose, two liquid supply pipelines are respectively communicated with one end of a microfluid mixing control chip, a Y-shaped micro-channel is arranged in the micro-fluidic mixing control chip, the double ends of the Y-shaped micro-channel are respectively communicated with the two liquid supply pipelines, the micro-fluidic mixing control chip is also provided with a mixing micro-channel communicated with the single head of the Y-shaped micro-channel, the mixed micro-channel is composed of two sections of wave-shaped micro-channels, each wave-shaped micro-channel comprises four wave crests and four wave troughs, the two wave-shaped micro-channels are communicated with each other through a straight line-shaped micro-channel, and the inner diameter of the straight line-shaped micro-channel is smaller than that of the wave-shaped micro-channel.
Furthermore, one end of one section of the wavy micro-channel in the two sections of the wavy micro-channels is communicated with the previous section of the wavy micro-channel, and the other end of one section of the wavy micro-channel in the two sections of the wavy micro-channels is communicated with the linear micro-channel.
Furthermore, two liquid inlet holes are formed in one end of the microfluidic hybrid control chip, and a liquid outlet hole is formed in the other end of the microfluidic hybrid control chip.
Furthermore, a display screen is arranged on the microfluid pressure pump.
By the scheme, the invention at least has the following advantages:
1. one-step preparation of LNP: the LNP has a relatively complex internal structure, the formed particles cannot be further processed by other means or equipment after the particles are formed, otherwise the internal structure of the particles is easily damaged to cause loss of functions, the invention accurately controls the entering speed of two-phase raw materials, and realizes accurate control on the contact area and reaction time of the two phases, so that the LNP lipid nanoparticles are further formed in a preparation instrument, the size of the formed particles is accurately controlled by controlling the contact area and reaction time of the reaction, the particle size of the particles can be effectively controlled within the range of 50-100 nm, and the prepared LNP particles are uniformly distributed because the equipment is continuous preparation equipment, and the PI value can be controlled below 0.1;
2. temperature control: in the process of forming the LNP microparticles, because the change of the temperature in the process of forming the LNP microparticles can cause the change of the characteristics of mRNA or other nucleic acid active ingredients, and the fluctuation of the temperature can cause the nonuniformity of the structure size formed by the microparticles, the precise temperature control needs to be carried out on the preparation unit and the main body configuration, thereby ensuring the uniformity of the temperature in the process of preparing the LNP microparticles and preparing the qualified lipid nanoparticles;
3. is suitable for industrial amplification: the present invention utilizes a continuous preparation for the preparation of LNP microparticles. Namely, the inlet end of the equipment continuously conveys the raw materials, the preparation unit continuously prepares particles through a special structure of the equipment, the outlet end continuously outputs the particles, all process control parameters of the preparation unit can be used as process parameters in production, and the equipment is very comprehensive, so that the equipment is very suitable for industrial amplification and has no amplification risk.
The foregoing description is only an overview of the technical solutions of the present invention, and in order to make the technical solutions of the present invention more clearly understood and to implement them in accordance with the contents of the description, the following detailed description is given with reference to the preferred embodiments of the present invention and the accompanying drawings.
Drawings
FIG. 1 is a sectional view of an LNP nucleic acid vaccine preparation apparatus of the present invention.
1 liquid supply bottle 2 microfluid pressure pump
3 hose 4 micro-fluidic hybrid control chip
5Y-shaped micro-channel 6 wave-shaped micro-channel
7 straight line type micro-channel 8 display screen
Detailed Description
The following detailed description of embodiments of the present invention is provided in connection with the accompanying drawings and examples. The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.
An LNP nucleic acid vaccine preparation apparatus shown in fig. 1, which is a continuous preparation apparatus, the prepared LNP particles are uniformly distributed, and the PI value can be controlled below 0.1, the LNP nucleic acid vaccine preparation apparatus includes two parallel liquid supply pipelines, the liquid supply pipeline includes a liquid supply bottle 1 and a micro-fluid pressure pump 2 which are connected, the liquid inlet and the liquid outlet on the micro-fluid pressure pump 2 are respectively connected with a hose 3, which can prevent the LNP lipid nanoparticles from being broken, the two liquid supply pipelines are respectively connected with one end of a micro-fluid mixing control chip 4, a Y-shaped micro-channel 5 is provided in the micro-fluid mixing control chip 4, the double heads of the Y-shaped micro-channel 5 are respectively connected with the two liquid supply pipelines, so that the two phases respectively flow into the single-head channel of the Y-shaped micro-channel 5 from the double heads of the Y-shaped micro-channel 5 under the precise control of a certain entry speed, contact area and reaction time, the micro-fluidic mixing control chip 4 is further provided with a mixing micro-channel communicated with a single head of the Y-shaped micro-channel 5, the mixing micro-channel is composed of two sections of wave-shaped micro-channels 6, the wave-shaped micro-channels 6 comprise four wave crests and four wave troughs, two phases can be uniformly mixed through the wave-shaped micro-channels 6, the two wave-shaped micro-channels 6 are communicated with each other through a linear micro-channel 7, and the inner diameter of the linear micro-channel 7 is smaller than that of the wave-shaped micro-channels 6.
In this embodiment, in order to uniformly mix two phases in the microfluidic mixing control chip 4, the particle size of the two phases is controlled within a range of 50 to 100nm, one end of one section of the wavy micro-channel 6 in the two sections of wavy micro-channels 6 is communicated with the previous section of the wavy micro-channel 6, and the other end of one section of the wavy micro-channel 6 in the two sections of wavy micro-channels 6 is communicated with the linear micro-channel 7.
In this embodiment, two liquid inlet holes are formed at one end of the microfluidic hybrid control chip 4, and a liquid outlet hole is formed at the other end of the microfluidic hybrid control chip 4.
In this embodiment, the microfluidic pressure pump 2 is provided with a display screen 8.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, it should be noted that, for those skilled in the art, many modifications and variations can be made without departing from the technical principle of the present invention, and these modifications and variations should also be regarded as the protection scope of the present invention.
Claims (4)
1. An LNP nucleic acid vaccine preparation instrument, which is characterized in that: comprises two parallel liquid supply pipelines, wherein the liquid supply pipelines comprise a liquid supply bottle and a microfluid pressure pump which are communicated, the liquid inlet and the liquid outlet on the microfluid pressure pump are respectively connected with a hose, two liquid supply pipelines are respectively communicated with one end of a microfluid mixing control chip, a Y-shaped micro-channel is arranged in the micro-fluidic mixing control chip, the double ends of the Y-shaped micro-channel are respectively communicated with the two liquid supply pipelines, the micro-fluidic mixing control chip is also provided with a mixing micro-channel communicated with the single head of the Y-shaped micro-channel, the mixed micro-channel is composed of two sections of wave-shaped micro-channels, each wave-shaped micro-channel comprises four wave crests and four wave troughs, the two wave-shaped micro-channels are communicated with each other through a straight line-shaped micro-channel, and the inner diameter of the straight line-shaped micro-channel is smaller than that of the wave-shaped micro-channel.
2. The LNP nucleic acid vaccine preparation apparatus of claim 1, wherein: one end of one section of the wavy micro-channel in the two sections of the wavy micro-channel is communicated with the previous section of the wavy micro-channel, and the other end of one section of the wavy micro-channel in the two sections of the wavy micro-channel is communicated with the linear micro-channel.
3. The LNP nucleic acid vaccine preparation apparatus of claim 1, wherein: two liquid inlet holes are formed in one end of the microfluidic hybrid control chip, and a liquid outlet hole is formed in the other end of the microfluidic hybrid control chip.
4. The LNP nucleic acid vaccine preparation apparatus of claim 1, wherein: and a display screen is arranged on the microfluid pressure pump.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202023120219.5U CN214020875U (en) | 2020-12-23 | 2020-12-23 | LNP nucleic acid vaccine preparation instrument |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202023120219.5U CN214020875U (en) | 2020-12-23 | 2020-12-23 | LNP nucleic acid vaccine preparation instrument |
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| CN214020875U true CN214020875U (en) | 2021-08-24 |
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