EP-4736997-A1 - APPARATUS AND METHOD FOR MANUFACTURING COMPOSITE

EP4736997A1EP 4736997 A1EP4736997 A1EP 4736997A1EP-4736997-A1

Abstract

The present disclosure provides an apparatus and a method for manufacturing a composite. In one aspect, the present disclosure provides a method for manufacturing a formulation comprising a first component and a second component. This method includes: a step for preparing a series of flow paths in which a first flow path through which a first fluid flows at a first flow velocity and a second flow path through which a second fluid flows at a second flow velocity are combined at a merging portion to form a third flow path through which a third fluid flows at a third flow velocity; a step in which the first component is injected into the first flow path at a first time; and a step in which the second component is injected into the second flow path at a second time. The first time and the second time are set so that the first component and the second component reach the merging portion at a time when the components are mixed.

Inventors

MATSUZAKI, TAKASHI
FUJIKI, Daichi

Assignees

The University of Osaka
Shionogi Pharma Co., Ltd.

Dates

Publication Date: 20260506
Application Date: 20240628

Claims (20)

A method for producing a formulation comprising: a first component; and a second component, the method comprising: preparing a series of flow channels comprising a first flow channel through which a first fluid flows at a first flow velocity, a second flow channel through which a second fluid flows at a second flow velocity, and a third flow channel through which a third fluid flows at a third flow velocity, the third flow channel being formed by combining the first flow channel and the second flow channel at a combination portion; injecting a sample comprising the first component into the first flow channel at a first time; and injecting a sample comprising the second component into the second flow channel at a second time, the first time and the second time being set so that the first component and the second component reach the combination portion at a time when the first component and the second component are mixed.
The method according to claim 1, wherein the first component is injected into a middle of the first flow channel and the second component is injected into a middle of the second flow channel.
The method according to claim 1 or 2, wherein a third time is set based on the first time and the second time.
The method according to any one of claims 1 to 3, wherein the first flow velocity or the second flow velocity exceeds about 2.4 mL/min.
The method according to any one of claims 1 to 4, wherein the series of flow channels comprises a fourth flow channel through which a sample comprising a third component flows; the method further comprises injecting the third component into the fourth flow channel at the third time; and the first time, the second time, and the third time are set so that the first component, the second component, and the third component reach the combination portion at a time when the first component, the second component, and the third component are mixed.
The method according to claim 5, wherein the third flow channel and the fourth flow channel are combined at an additional combination portion downstream of the combination portion.
The method according to claim 5 or 6, wherein the first flow channel, the second flow channel, and the fourth flow channel are combined at the combination portion.
The method according to any one of claims 1 to 7, further comprising detecting a combination state of the first component and the second component downstream of the combination portion.
The method according to claim 8, wherein the combination state to be detected is a state selected from the group consisting of a concentration of at least one of the first component and the second component, a particle diameter of particles in a flow, and a state of a chemical bond between the first component and the second component.
The method according to any one of claims 1 to 9, wherein the first flow channel is in a liquid-feeding state in the injection of the sample comprising the first component into the first flow channel and the second flow channel is in a liquid-feeding state in the injection of the sample comprising the second component into the second flow channel.
The method according to any one of claims 1 to 10, wherein, in the injection of the sample comprising the first component into the first flow channel and in the injection of the sample comprising the second component into the second flow channel, retention times taken for the sample comprising the first component and the sample comprising the second component to be introduced into sample injection portions and then injected into the flow channels are independently within 1 minute.
The method according to any one of claims 1 to 11, wherein times taken for the first component and the second component to be injected and reach the combination portion are independently within 2 seconds.
The method according to any one of claims 1 to 12, wherein 1000 µg or less of the first component is injected in the injection of the first component into the first flow channel and 1000 ug or less of the second component is injected in the injection of the second component into the second flow channel.
The method according to any one of claims 1 to 13, wherein a fourth fluid flowing through a fifth flow channel is combined with the third fluid at the additional combination portion to form a sixth flow channel through which a fifth fluid flows.
The method according to any one of claims 1 to 14, wherein the combination portion comprises a T-mixer, a microflow channel device, or a static mixer.
The method according to any one of claims 1 to 15, wherein the third flow channel comprises a mixer.
The method according to claim 16, wherein the mixer on the third flow channel is a static mixer.
The method according to any one of claims 1 to 17, wherein each of the first flow channel and the second flow channel comprises a plurality of branched flow channels, and the combination portion comprises a plurality of branched flow combination portions at which the branched flow channels from the first flow channel and the branched flow channels from the second flow channel are combined.
The method according to claim 18, wherein the first flow channel and/or the second flow channel is branched to form the branched flow channel.
The method according to claim 18 or 19, wherein the branched flow channels downstream of the branched flow combination portion combine with each other in the third flow channel.

Description

[Technical Field] The present disclosure relates to an apparatus and a method for producing a composite. More particularly, the present disclosure relates to a technique for producing a composite by mixing fluids flowing from at least two flow channels. [Background Art] An "in-line liposome production technology" in which liposomes or lipid nanoparticles (LNPs) are continuously formed in a closed tube has been attracting attention as a technology for producing sterile liposomes, and a technology for adjusting a concentration of the thus-formed liposomes in an in-line manner has been developed (see Patent Literature 1). However, various parameters such as a flow velocity need to be adjusted in order to obtain suitable lipid particles for a factor such as a particle size, and parameters set for preparation of a small amount of a sample at a laboratory level often differ from those suitable for mass production for product supply. Therefore, in the past, conditions of manufacture for product supply had to be separately adjusted with many materials consumed. [Citation List] [Patent Literature] [PTL 1] PCT International Publication No. WO 2016/024510 [Summary of Invention] [Solution to Problem] As a result of extensive studies to find a method for reflecting conditions for preparation of a small amount of a lipid particle sample into conditions of manufacture for product supply in order to reduce a need for additional studies to determine the conditions of manufacture for product supply, the present inventors have completed an apparatus and a method of the present disclosure. Therefore, the present invention provides an apparatus and a method for producing drug-loaded lipid particles by mixing fluids flowing from at least two flow channels. Therefore, the present disclosure provides the following items. (Item 1) A method for producing a formulation including: a first component; anda second component, the method including: preparing a series of flow channels including a first flow channel through which a first fluid flows at a first flow velocity, a second flow channel through which a second fluid flows at a second flow velocity, and a third flow channel through which a third fluid flows at a third flow velocity, the third flow channel being formed by combining the first flow channel and the second flow channel at a combination portion;injecting a sample including the first component into the first flow channel at a first time; andinjecting a sample including the second component into the second flow channel at a second time,the first time and the second time being set so that the first component and the second component reach the combination portion at a time when the first component and the second component are mixed. (Item 2) The method according to any of the above items, in which the first component is injected into a middle of the first flow channel and the second component is injected into a middle of the second flow channel. (Item 3) The method according to any of the above items, in which a third time is set based on the first time and the second time. (Item 4) The method according to any of the above items, in which the first flow velocity or the second flow velocity exceeds about 2.4 mL/min. (Item 5) The method according to any of the above items, in which the series of flow channels includes a fourth flow channel through which a sample including a third component flows; the method further includes injecting the third component into the fourth flow channel at the third time; andthe first time, the second time, and the third time are set so that the first component, the second component, and the third component reach the combination portion at a time when the first component, the second component, and the third component are mixed. (Item 6) The method according to any of the above items, in which the third flow channel and the fourth flow channel are combined at an additional combination portion downstream of the combination portion. (Item 7) The method according to any of the above items, in which the first flow channel, the second flow channel, and the fourth flow channel are combined at the combination portion. (Item 8) The method according to any of the above items, further including detecting a combination state of the first component and the second component downstream of the combination portion. (Item 9) The method according to any of the above items, in which the combination state to be detected is a state selected from the group consisting of a concentration of at least one of the first component and the second component, a particle diameter of particles in a flow, and a state of a chemical bond between the first component and the second component. (Item 10) The method according to any of the above items, in which the first flow channel is in a liquid-feeding state in the injection of the sample including the first component into the first flow channel and the second flow channel is in a liquid-