KR20230113931A - Device and method for drug introduction into exosomes - Google Patents

Abstract

The present invention relates to an apparatus and method for loading a drug into exosomes, which can more effectively promote drug loading into exosomes by directly applying energy such as ultrasound or laser to cause temporary damage in exosomes.
An apparatus for loading drugs into exosomes according to the present invention includes an inlet into which a sample liquid containing exosomes and drugs separated from a biological sample is injected, an outlet separated from the inlet, and connecting the inlet and the outlet. A flow pipe comprising a pipe portion to; a flow generating unit generating a flow of the sample liquid so that the sample liquid flows from the inlet to the discharge unit within the flow pipe; and a shear force applier for applying a shear force to the sample solution in the flow pipe so that the drug is loaded into the exosomes.

Description

Device and method for drug introduction into exosomes

The present invention relates to an apparatus and method for loading drugs into exosomes, and more particularly, promotes more effective drug loading into exosomes by directly applying energy such as ultrasound or laser to cause temporary damage in exosomes It relates to a device and method for loading drugs into exosomes that can

Exosomes are nano-sized vesicles that are naturally produced within cells, and contain proteins and genetic information. They transmit various signals, including genetic information, to other cells outside of the cell to help develop, proliferate, differentiate, regulate immunity, and blood vessels. It is involved in the development and progression of various diseases.

In the case of exosomes, which are biological nanovesicles, they can avoid immune reactions, have excellent human body compatibility, and have recently attracted great attention as drug delivery systems through their advantages such as drug loading function, target delivery effect to specific cells, and stability in blood. Accordingly, various technologies for effectively loading drugs into exosomes are being developed.

In this regard, Patent Registration No. 10-2232757 and Patent Registration No. 10-210995 disclose a method for delivering a target substance into extracellular vesicles using extracorporeal shock waves. However, extracorporeal shock waves are mainly used for the purpose of relieving pain by applying shock wave stimulation to a specific part of the body, and because they mainly focus on pressure waves that generate vibration effects, there is a limit to effectively delivering a target substance into the endoplasmic reticulum.

KR 10-2232757 B1 KR 10-210995 B1

Therefore, the present invention has been made to solve the above problems, and by directly applying energy such as ultrasound or laser to cause temporary damage in exosomes, exosomes that can more effectively promote drug loading into exosomes. One object is to provide a drug loading device and method.

Other objects and advantages of the present invention will be described below, and will be learned by way of examples of the present invention. Furthermore, the objects and advantages of the present invention may be realized by means of the instrumentalities and combinations indicated in the claims.

In order to achieve the above object, the device for loading drugs into exosomes according to the present invention includes an inlet portion into which a sample liquid containing exosomes and drugs separated from a biological sample is injected, and a discharge portion spaced apart from the inlet portion. And, a flow pipe including a pipe connecting the inlet and the outlet; a flow generating unit generating a flow of the sample liquid so that the sample liquid flows from the inlet to the discharge unit within the flow pipe; and a shear force applicator for applying a shear force to the sample solution in the flow tube so that the drug is loaded into the exosome, wherein the shear force applier applies a rotational shear force by a mechanical force to the sample solution.

In addition, the method for loading drugs into exosomes according to the present invention includes an inlet portion into which a sample solution containing exosomes and drugs separated from a biological sample is injected, an outlet portion spaced apart from the inlet portion, and the inlet portion and the drug loading method. providing a flow pipe including a pipe portion connecting the discharge portion; generating a flow of the sample liquid by a flow generating unit so that the sample liquid flows from the inlet portion to the discharge portion within the flow pipe; and applying a shear force to the sample solution so that the drug is loaded into the exosome by a shear force application unit, wherein the shear force application unit applies a rotational shear force by a mechanical force to the sample solution. .

The shear force applying part is selected from among a moving part type, a parallel plate type, a cone-and-plate type, and a concentric cylinders type by the pipe part of the flow pipe, can be configured.

The flow-type shear force applying unit includes a plurality of necks of the pipe of the flow pipe, and the plurality of necks are repeatedly formed by reducing or expanding the hydraulic diameter of the pipe of the flow pipe, and the pipe of the flow pipe is formed repeatedly. It may be formed of any one of a circular tube, a rectangular tube, and a polygonal tube.

The parallel plate-type shear force applying unit includes a pair of first and second plate-shaped disks having a plate shape, and an upper surface of any one of the pair of first and second plate-shaped disks increases the shear force. A plurality of fan plate-shaped projections are formed so as to be spaced apart from each other in the circumferential direction and protrude upward, and the plurality of fan plate-shaped projections have a shear rate of 0.1 mm to 500 1/s to 50,000 1/s to form a shear rate in the range of 500 1/s to 50,000 1/s. It can be formed at intervals in the range of 2 mm.

The cone-and-plate type shear force application unit includes a cone-shaped disk having a conical conical surface and a third plate-shaped disk having a plate shape, and the inclination angle of the conical surface of the cone-shaped disk is formed in the range of 3 ° to 15 °. It can be.

On the upper surface of the third plate-shaped disk, a plurality of fan plate-shaped protrusions are formed so as to be spaced apart from each other in the circumferential direction and protrude upward to increase shear force, and the plurality of fan plate-shaped protrusions have a pressure of 500 1/s to 500 1/s. It may be formed at intervals in the range of 0.1 mm to 2 mm to form a shear rate in the range of 50,000 1/s.

The shear force applying unit of the concentric cylinder type includes a circular tube having a c-shaped cross section and a cylindrical disk arranged to have a concentric axis with the circular tube in the circular tube, and the circular tube and the cylindrical disk are directed in different directions It can be configured to rotate.

The cylindrical disk includes a plurality of protrusions spaced apart from each other on the outer circumferential surface to increase shear force, and the plurality of protrusions have a shear rate of 0.1 mm to 2 to form a shear rate in the range of 500 1/s to 50,000 1/s. It can be formed at intervals in the range of mm.

It may further include an external force applying unit for applying an external force using energy to the sample liquid so that the drug is more efficiently loaded into the exosomes in cooperation with the shearing force applying unit.

The external force application unit may be disposed at a front end or a rear end of the shear force application unit.

The external force application unit may be selected from a focused ultrasound application unit, a focused laser application unit, or a combination thereof.

The focused ultrasound applied by the focused ultrasound application unit may have a center frequency in the range of 200 kHz to 10 MHz and an intensity in the range of 2 W/cm 2 to 40 W/cm 2 .

The laser applied by the focusing laser application unit may be a laser having a wavelength (Nd:YAG) in the range of 1060 nm to 1070 nm or a wavelength in the range of 750 nm to 760 nm.

In order to improve the efficiency of the external force applying unit, nanoparticles may be included in the sample solution.

In the device for loading drugs into exosomes according to the present invention, a washing unit connected to the flow pipe and receiving a washing sample solution; a second flow generating unit for discharging the sample liquid through the discharge unit after loading the drug into the exosome, and then allowing the washing sample liquid to pass through the flow tube to wash the inside of the flow tube; and a recovery unit for recovering the washed sample liquid from the washing unit.

In the drug loading method into exosomes according to the present invention, after the sample solution containing the drug-loaded exosomes moves to the discharge unit in the flow pipe, the washing sample solution of the washing unit is discharged by the second flow generating unit. passing through the flow pipe to clean the inside of the flow pipe; and recovering the washing sample solution washed from the washing part to the recovery part.

The biological sample is at least one selected from the group consisting of blood, lymph, cerebrospinal fluid, urine, amniotic fluid, breast milk, saliva, semen, and cell culture fluid, and the drug is from the group consisting of antitumor drugs, chemotherapy drugs, and immunomodulatory drugs. There may be one or more selected.

As described above, according to the device and method for loading drugs into exosomes according to the present invention, a plurality of necks that are repeatedly formed in the flow tube are formed, and a rotational shear force by a mechanical force is applied by the shear force applying unit, thereby effectively exosome There is an effect that can promote drug loading into.

In addition, the present invention has an excellent effect of more efficiently loading the drug into exosomes in cooperation with the shear force applying unit by additionally providing an external force applying unit capable of applying an external force using energy such as ultrasound or laser.

1 is a diagram for explaining a device for loading drugs into exosomes according to a first embodiment of the present invention.
2 to 4 are views showing examples of a shear force applying unit according to the present invention.
5 is a diagram for explaining a device for loading drugs into exosomes according to a second embodiment of the present invention.
6 to 8 are views showing examples of an external force application unit according to the present invention.
9 is a diagram for explaining a device for loading drugs into exosomes according to a third embodiment of the present invention.

Details of other embodiments are included in the detailed description and drawings.

Advantages and features of the present invention, and methods of achieving them, will become clear with reference to the detailed description of the following embodiments taken in conjunction with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below and can be implemented in various different forms, and in the following description, when a part is connected to another part, this is not only the case where it is directly connected It also includes the case where it is connected through another medium in the middle. In addition, parts not related to the present invention in the drawings are omitted to clarify the description of the present invention, and the same reference numerals are attached to similar parts throughout the specification.

Hereinafter, the present invention will be described with reference to the accompanying drawings.

1 is a diagram for explaining a device for loading drugs into exosomes according to a first embodiment of the present invention, FIGS. 2 to 4 are diagrams showing an example of a shear force applying unit according to the present invention, and FIG. 6 to 8 are diagrams showing an example of an external force application unit according to the present invention, and FIG. 9 is a third embodiment of the present invention. It is a drawing for explaining the drug loading device to the exosome according to.

First, referring to FIG. 1 , the device for loading drugs into exosomes according to the first embodiment of the present invention includes a flow tube 100, a flow generator P1, and a shear force application unit M.

In the present invention, the biological sample may be one or more selected from the group consisting of blood, lymph, cerebrospinal fluid, urine, amniotic fluid, breast milk, saliva, semen, and cell culture fluid, but is not limited thereto.

In the case of the exosome 10, it has recently received great attention as a drug delivery system through its advantages such as avoidance of immune response, excellent human body compatibility, drug loading function, target delivery effect to specific cells, and stability in blood. In addition, the drug 20 may be one or more selected from the group consisting of antitumor drugs, chemotherapy drugs and immunomodulatory drugs, but is not limited thereto.

A sample solution containing the exosomes 10 and the drug 20 separated from the biological sample flows through the flow pipe 100 .

The material of the flow pipe 100 may be formed of metal such as silicon or stainless steel, or plastic such as polystyrene, but is not limited thereto.

The flow pipe 100 includes an inlet 102 into which a sample solution containing exosomes 10 and drugs 20 separated from a biological sample is injected, and an outlet 103 spaced apart from the inlet 102. and a pipe part 101 connecting the inlet part 102 and the discharge part 103.

A sample solution including the exosomes 20 loaded with the drug 20 may be collected in the discharge unit 103 through the drug loading process.

The flow generating unit P1 generates a flow of the sample liquid from the inlet 102 to the outlet 103 within the flow pipe 100, and according to the present invention, the exo loaded with the drug 20 The sample solution including moths 10 may be discharged to the discharge unit 103.

The flow generating unit P1 may be a vacuum device that is connected to the discharge unit 103 to provide a constant vacuum negative pressure, and may include, for example, a negative pressure generating device such as a syringe pump.

A shear force may be applied to the sample solution in the flow pipe 100 by the shear force applying unit M so that the drug 20 is loaded into the exosomes 10 .

Preferably, the shear force applying unit (M) may apply a rotational shear force by a mechanical force to the sample liquid.

Here, the rotational shear force refers to the force received by the material between them when two surfaces facing each other in parallel move in opposite directions. Rotation generates very high shear forces that can break the material between them into very small pieces.

In the present invention, by inducing temporary perturbations (eg, temporary opening of the cell membrane, etc.) in the cell membrane of the exosome 10 by the principle of such rotational shear force, the drug into the exosome 10 more effectively ( 20) can facilitate mounting.

As an example, nanoparticles may be included in the sample solution. When nanoparticles are included in the sample solution, the nanoparticles can adsorb negatively charged exosomes by conjugating a positively charged material to the surface, thereby directly or indirectly transferring heat or energy to the sample solution or exosomes. was found to be effective.

The shear force applying unit (M) is a shearing force applying unit (M1) of a moving part type by the pipe part 101 of the flow pipe 100, a shearing force applying unit (M2) of a parallel plate type, a cone-and- Any one of a cone-and-plate type shear force application unit M3 and a concentric cylinders type shear force application unit M3 may be selected and configured.

Referring to FIG. 1 , in the shearing force applying unit M1 of the floating unit type, the tube unit 101 of the flow tube 100 may include a plurality of neck units 104 .

For example, the plurality of neck portions 104 may be repeatedly formed by reducing or expanding the hydraulic diameter of the pipe portion 101 of the flow pipe 100 .

The pipe part 101 of the flow pipe 100 may be formed of any one of a circular pipe, a rectangular pipe, and a polygonal pipe.

Referring to FIG. 2 , the parallel plate type shearing force application unit M2 may include a pair of first and second plate-shaped disks D1 and D2 having a plate shape.

A plurality of upper surfaces of one of the pair of first and second plate-shaped disks D1 and D2 (eg, D1) are spaced apart from each other in the circumferential direction and protrude upward to increase shear force. A fan plate-shaped protrusion D11 of may be formed.

Preferably, the plurality of fan plate-shaped protrusions D11 may be formed at intervals ranging from 0.1 mm to 2 mm to form a shear rate ranging from 500 1/s to 50,000 1/s.

A shear force generating unit S1 is formed between the first and second plate-shaped disks D1 and D2.

Although the first plate-shaped disk D1 is shown as rotating in this embodiment, it is possible to configure the second plate-shaped disk D2 to rotate, and if necessary, the first and second plate-shaped disks D1 and D2 Of course, both may be configured to rotate in different directions.

Referring to FIG. 3 , the cone-and-plate type shear force applying unit M3 may include a cone-shaped disk D3 having a conical conical surface and a third plate-shaped disk D4 having a plate shape. .

Preferably, the inclination angle of the conical surface narrowing from the top to the bottom of the conical disk D3 may be 3° to 15°, preferably 3° to 7° to provide a constant shear rate distribution.

Similar to the first and second plate-shaped disks D1 and D2, on the upper surface of the third plate-shaped disk D4, a plurality of plates disposed to be spaced apart from each other in the circumferential direction and protruding upward to increase shear force. Fan plate-shaped protrusions (not shown) may be formed. At this time, the plurality of fan plate-shaped protrusions may be formed at intervals ranging from 0.1 mm to 2 mm to form a shear rate ranging from 500 1/s to 50,000 1/s.

A shear force generating unit S2 is formed between the cone-shaped disk D3 and the plate-shaped disk D4.

In this embodiment, the cone-shaped disk D3 is shown as rotating, but the plate-shaped disk D4 can be configured to rotate, and if necessary, both disks D3 and D4 can be configured to rotate in different directions. Of course it can.

The distance between the end of the cone-shaped disk D3 and the plate-shaped disk D4 may range from 0.3 mm to 0.5 mm.

Referring to FIG. 4, the concentric cylinder type shearing force application unit (M4) has a circular tube (D6) having a c-shaped cross section, and the circular tube (D6) and the circular tube (D6) in the circular tube (D6) Arranged to have a concentric axis and a cylindrical disk (D5), and the circular tube (D6) and the cylindrical disk (D5) may be configured to rotate in different directions.

A shear force generating unit S3 is formed between the circular tube D6 and the cylindrical disk D5.

Preferably, the cylindrical disk D5 may include a plurality of protrusions D51 protruding at regular intervals around the outer circumferential surface to increase shear force.

The plurality of protrusions D51 may be formed at intervals ranging from 0.1 mm to 2 mm to form a shear rate ranging from 500 1/s to 50,000 1/s.

Referring to FIG. 5, there is shown a device for loading drugs into exosomes according to the second embodiment of the present invention, except that, compared to the first embodiment, it further includes an external force application unit 110 , it can be seen that the rest of the components are the same.

The external force applying unit 110 may apply an external force using energy to the sample solution so that the drug 20 is more efficiently loaded into the exosomes 10 .

In one embodiment, in order to improve the efficiency of the external force application unit 110, nanoparticles may be included in the sample solution. When nanoparticles are included in the sample solution, efficient heat transfer or energy transfer can be achieved with respect to the sample solution or exosomes.

For example, the external force application unit 110 may be selected from a focused ultrasound application unit (U), a focused laser application unit (L), or a combination thereof, which will be described later.

The external force application unit 110 may be disposed in the pipe part 101 at the front or rear end of the shear force application unit M separately from the shear force application unit M.

Preferably, the external force application unit 110 may be configured to cooperate with the shear force application unit M.

Most preferably, the external force application unit 110 may have a configuration that cooperates with the shear force application unit M1 of the flow type by the pipe portion 101 of the flow pipe 100 among the shear force application units M. .

Of course, the external force application unit 110 is any one of a parallel plate type shear force application unit (M2), a cone-and-plate type shear force application unit (M3), or a concentric cylinder type shear force application unit (M3). It may have a configuration that cooperates with.

As an example, a configuration in which the external force applying unit 110 cooperates with the shearing force applying unit M1 of the flow unit type by the pipe unit 101 of the flow pipe 100 is as follows.

Referring to FIG. 6 , a focused ultrasound application unit U is illustrated as the external force application unit 110 .

Ultrasound can be divided into High-intensity Focused Ultrasound (HIFU) and Low-intensity Focused Ultrasound (LIFU) depending on its intensity. While used for direct treatment such as necrosis, low-intensity focused ultrasound is known to obtain medical effects without necrotizing body tissues.

In the present invention, the focused ultrasound applying unit (U) may output low-intensity focused ultrasound.

For example, the focused ultrasound applied by the focused ultrasound application unit U may have a center frequency in the range of 200 kHz to 10 MHz and an intensity in the range of 2 W/cm 2 to 40 W/cm 2 .

Referring to FIG. 7 , a focused laser application unit L is illustrated as the external force application unit 110 .

The laser has characteristics of monochromaticity, linearity, and coherence, so beam focusing is easy and energy transmission is possible efficiently. Based on these characteristics, it is widely used in a wide range of fields.

For example, the laser applied by the focusing laser application unit L may be a laser having a wavelength (Nd:YAG) in the range of 1060 nm to 1070 nm or a wavelength in the range of 750 nm to 760 nm.

Referring to FIG. 8 , a focused ultrasound application unit U and a focused laser application unit L combined as the external force application unit 110 are illustrated.

When the focused ultrasound application unit (U) and the focused laser application unit (L) are provided, both the energy of ultrasound and laser are applied to cause temporary damage in the exosome 10, thereby more effectively exosome 10 It is possible to promote the loading of the drug 20.

9 shows a device for loading drugs into exosomes according to a third embodiment of the present invention. Compared to the first embodiment, the washing unit 120, the flow generation unit P2 and the recovery unit 130 are shown. Except for the fact that it contains more, it can be seen that the rest of the components are the same.

The washing unit 120 is connected to the front end of the flow pipe 100 and contains a washing sample solution. Here, the washing sample solution may be a washing sample solution such as PBS (Phosphate-Buffered Saline).

The recovery unit 130 performs a function of recovering the washed sample liquid from the cleaning unit 120.

At this time, fine valves may be installed in the washing unit 120, the recovery unit 130, and the discharge unit 103 to control the flow. Although not shown in the drawing, a fine valve may be installed at the inlet 102 to control the flow.

The discharge part 103 is provided with a flow generating part (P1), and the recovery part 130 is provided with a flow generating part (P2).

The flow generating unit (P1) allows the sample liquid in the inlet unit 102 to flow through the flow pipe 100, and the sample liquid including the exosome 10 loaded with the drug 20 flows through the discharge unit 103. It can perform a function that moves to .

To this end, in a state where the fine valve V1 of the washing part 120 and the fine valve V2 of the recovery part 130 are turned off and the fine valve V3 of the discharge part 103 is turned on, the flow When negative pressure is provided to the flow pipe 100 through the generator P1, the sample liquid in the inlet 102 flows through the flow pipe 100, and at this time, the shear force applying unit M ) In the neck portion 104, rotational shear force may be applied to the sample liquid passing through the neck portion 104, and thus the drug 10 may be loaded into the exosome 10, and the drug 20 may be loaded The sample liquid containing the exosomes 10 may be collected by moving to the discharge unit 103.

After the sample liquid including the exosome 10 loaded with the drug 20 is collected in the discharge unit 103, the flow generating unit P2 is configured to discharge the washing sample liquid of the washing unit 120 to the flow pipe 100. ) to wash the inside of the flow pipe 100 and to recover the washing sample liquid washed from the cleaning unit 120 to the recovery unit 130.

To this end, in a state where the fine valve V1 of the washing part 120 and the fine valve V2 of the recovery part 130 are turned on and the fine valve V3 of the discharge part 103 is turned off, the flow When negative pressure is applied to the flow pipe 100 through the generation unit P2, the cleaning sample solution in the washing unit 120 flows through the flow pipe 100 to wash the inside of the flow pipe 100, and after washing The washing sample liquid may be recovered to the recovery unit 130 .

Those skilled in the art to which the present invention pertains will understand that the present invention can be embodied in other specific forms without changing its technical spirit or essential features. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention is indicated by the claims to be described later rather than the detailed description above, and all changes or modifications derived from the meaning and scope of the claims and equivalent concepts thereof are included in the scope of the present invention. should be interpreted

100: fluid pipe
101: government department
102: entrance
103: discharge unit
104: neck
M: shear force application unit
P1: flow generating unit
110: external force application unit

Claims (32)

a flow pipe including an inlet into which a sample solution including exosomes and drugs separated from a biological sample is injected, an outlet spaced apart from the inlet, and a pipe connecting the inlet and the outlet;
a flow generating unit generating a flow of the sample liquid so that the sample liquid flows from the inlet to the discharge unit within the flow pipe; and
A shear force application unit for applying a shear force to the sample solution in the flow tube so that the drug is loaded into the exosomes;
The shear force applying unit is a drug loading device to the exosome, characterized in that for applying a rotational shear force by a mechanical force to the sample solution. According to claim 1,
The shear force applying part is selected from among a moving part type, a parallel plate type, a cone-and-plate type, and a concentric cylinders type by the pipe part of the flow pipe, A drug loading device to exosomes, characterized in that the configuration. According to claim 2,
The flow-type shear force applying unit includes a plurality of necks of the pipe of the flow pipe, and the plurality of necks are repeatedly formed by reducing or expanding the hydraulic diameter of the pipe of the flow pipe, and the pipe of the flow pipe is formed repeatedly. A drug loading device into exosomes, characterized in that it is formed of any one of a circular tube, a rectangular tube and a polygonal tube. According to claim 2,
The parallel plate-type shear force applying unit includes a pair of first and second plate-shaped disks having a plate shape, and an upper surface of any one of the pair of first and second plate-shaped disks increases the shear force. A plurality of fan plate-shaped projections are formed so as to be spaced apart from each other in the circumferential direction and protrude upward, and the plurality of fan plate-shaped projections have a shear rate of 0.1 mm to 500 1/s to 50,000 1/s to form a shear rate in the range of 500 1/s to 50,000 1/s. A device for loading drugs into exosomes, characterized in that they are formed at intervals in the range of 2 mm. According to claim 2,
The cone-and-plate type shear force application unit includes a cone-shaped disk having a conical conical surface and a third plate-shaped disk having a plate shape, and the inclination angle of the conical surface of the cone-shaped disk is formed in the range of 3 ° to 15 °. A device for loading drugs into exosomes, characterized in that. According to claim 5,
On the upper surface of the third plate-shaped disk, a plurality of fan plate-shaped protrusions are formed so as to be spaced apart from each other in the circumferential direction and protrude upward to increase shear force, and the plurality of fan plate-shaped protrusions have a pressure of 500 1/s to 500 1/s. A drug loading device into exosomes, characterized in that formed at intervals in the range of 0.1 mm to 2 mm to form a shear rate in the range of 50,000 1 / s. According to claim 2,
The shear force applying unit of the concentric cylinder type includes a circular tube having a c-shaped cross section and a cylindrical disk arranged to have a concentric axis with the circular tube in the circular tube, and the circular tube and the cylindrical disk are directed in different directions A drug loading device to exosomes, characterized in that it is configured to rotate. According to claim 7,
The cylindrical disk includes a plurality of protrusions spaced apart from each other on the outer circumferential surface to increase shear force, and the plurality of protrusions have a shear rate of 0.1 mm to 2 to form a shear rate in the range of 500 1/s to 50,000 1/s. A device for loading drugs into exosomes, characterized in that they are formed at intervals in the mm range. According to claim 1,
Further comprising an external force applying unit for applying an external force using energy to the sample solution so that the drug is more efficiently loaded into the exosome, and the external force applying unit is configured to cooperate with the shear force applying unit To exosomes, characterized in that drug loading device. According to claim 9,
The external force application unit is a drug loading device to exosomes, characterized in that selected from a focused ultrasound application unit, a focused laser application unit, or a combination thereof. According to claim 10,
The focused ultrasound applied by the focused ultrasound application unit has a center frequency in the range of 200 kHz to 10 MHz and can be set to have an intensity in the range of 2 W / cm 2 to 40 W / cm 2 Drug to exosomes, characterized in that mounting device. According to claim 10,
The laser applied by the focused laser application unit is a drug loading device into exosomes, characterized in that the laser having a wavelength (Nd: YAG) in the range of 1060 nm to 1070 nm or a wavelength in the range of 750 nm to 760 nm. According to claim 1,
A drug loading device to exosomes, characterized in that nanoparticles can be included in the sample solution. According to claim 9,
Drug loading device to exosomes, characterized in that nanoparticles can be included in the sample solution in order to improve the efficiency of the external force application unit. According to claim 1,
a washing unit connected to the flow pipe and containing a washing sample solution;
a second flow generating unit for discharging the sample liquid through the discharge unit after loading the drug into the exosome, and then allowing the washing sample liquid to pass through the flow tube to wash the inside of the flow tube; and
The drug loading device into the exosome, characterized in that it further comprises a recovery unit for recovering the washing sample solution washed from the washing unit. According to claim 1,
The biological sample is at least one selected from the group consisting of blood, lymph, cerebrospinal fluid, urine, amniotic fluid, breast milk, saliva, semen, and cell culture fluid,
The drug loading device into exosomes, characterized in that at least one selected from the group consisting of antitumor drugs, chemotherapeutic drugs and immunomodulatory drugs. providing a flow pipe including an inlet into which a sample solution including exosomes and drugs separated from the biological sample is injected, an outlet spaced apart from the inlet, and a pipe connecting the inlet and the outlet;
generating a flow of the sample liquid by a flow generating unit so that the sample liquid flows from the inlet portion to the discharge portion within the flow pipe; and
Applying a shear force to the sample solution so that the drug is loaded into the exosome by a shear force applying unit,
The shear force applying unit applies a rotational shear force by a mechanical force to the sample solution. According to claim 17,
The shear force applying unit is a drug loading method into exosomes, characterized in that any one of a moving part type, a parallel plate type, a cone-and-plate type, and a concentric cylinder type is selected from the pipe part of the flow tube. According to claim 18,
The flow-type shear force applying unit includes a plurality of necks of the pipe of the flow pipe, and the plurality of necks are repeatedly formed by reducing or expanding the hydraulic diameter of the pipe of the flow pipe, and the pipe of the flow pipe is formed repeatedly. A method for loading a drug into an exosome, characterized in that it is formed of any one of a circular tube, a rectangular tube and a polygonal tube. According to claim 18,
The parallel plate-type shear force applying unit includes a pair of first and second plate-shaped disks having a plate shape, and an upper surface of any one of the pair of first and second plate-shaped disks increases the shear force. A plurality of fan plate-shaped projections are formed so as to be spaced apart from each other in the circumferential direction and protrude upward, and the plurality of fan plate-shaped projections have a shear rate of 0.1 mm to 500 1/s to 50,000 1/s to form a shear rate in the range of 500 1/s to 50,000 1/s. A method for loading drugs into exosomes, characterized in that they are formed at intervals in the range of 2 mm. According to claim 18,
The cone-and-plate type shear force application unit includes a cone-shaped disk having a conical conical surface and a third plate-shaped disk having a plate shape, and the inclination angle of the conical surface of the cone-shaped disk is formed in the range of 3 ° to 15 °. A method of loading a drug into exosomes, characterized in that. According to claim 21,
On the upper surface of the third plate-shaped disk, a plurality of fan plate-shaped protrusions are formed so as to be spaced apart from each other in the circumferential direction and protrude upward to increase shear force, and the plurality of fan plate-shaped protrusions have a pressure of 500 1/s to 500 1/s. A method for loading drugs into exosomes, characterized in that formed at intervals in the range of 0.1 mm to 2 mm to form a shear rate in the range of 50,000 1 / s. According to claim 18,
The shear force applying unit of the concentric cylinder type includes a circular tube having a c-shaped cross section and a cylindrical disk arranged to have a concentric axis with the circular tube in the circular tube, and the circular tube and the cylindrical disk are directed in different directions A method for loading a drug into exosomes, characterized in that it is configured to rotate. According to claim 23,
The cylindrical disk includes a plurality of protrusions spaced apart from each other on the outer circumferential surface to increase shear force, and the plurality of protrusions have a shear rate of 0.1 mm to 2 to form a shear rate in the range of 500 1/s to 50,000 1/s. A method for loading drugs into exosomes, characterized in that they are formed at intervals in the mm range. According to claim 17,
Further comprising an external force applying unit for applying an external force using energy to the sample solution so that the drug is more efficiently loaded into the exosome, and the external force applying unit is configured to cooperate with the shear force applying unit To exosomes, characterized in that Drug loading method. According to claim 25,
The external force application unit is a drug loading method into exosomes, characterized in that selected from a focused ultrasound application unit, a focused laser application unit, or a combination thereof. The method of claim 26,
The focused ultrasound applied by the focused ultrasound application unit has a center frequency in the range of 200 kHz to 10 MHz and can be set to have an intensity in the range of 2 W / cm 2 to 40 W / cm 2 Drug to exosomes, characterized in that mounting method. The method of claim 26,
The laser applied by the focused laser application unit is a drug loading method into exosomes, characterized in that the laser having a wavelength (Nd: YAG) in the range of 1060 nm to 1070 nm or a wavelength in the range of 750 nm to 760 nm. According to claim 17,
A drug loading method into exosomes, characterized in that nanoparticles can be included in the sample solution. According to claim 25,
Drug loading method into exosomes, characterized in that nanoparticles can be included in the sample solution in order to improve the efficiency of the external force applying unit. According to claim 17,
after the sample liquid containing the drug-loaded exosomes moves to the discharge unit in the flow tube, allowing the washing sample liquid of the washing unit to pass through the flow tube and wash the inside of the flow tube by a second flow generating unit; and
The method of loading the drug into exosomes, characterized in that it further comprises the step of recovering the washed sample liquid from the washing unit to the recovery unit. According to claim 17,
The biological sample is at least one selected from the group consisting of blood, lymph, cerebrospinal fluid, urine, amniotic fluid, breast milk, saliva, semen, and cell culture fluid,
The drug loading method into exosomes, characterized in that at least one selected from the group consisting of antitumor drugs, chemotherapeutic drugs and immunomodulatory drugs.