KR101985301B1 - Microneedle for drug delivery system and method thereof - Google Patents

Abstract

A method for producing a microcapsule in a drug delivery system, comprising the steps of: preparing a first substrate; forming a first pattern on the first substrate, the first pattern including a shape of an upper layer in the longitudinal direction of the microcapsule including a body and a needle bar; Forming a second pattern including a shape of a lower layer in the longitudinal direction of the extremely fine contact on the second substrate; joining the first substrate and the second substrate; And forming the extreme microcapsules by etching the bonded first and second substrates based on the first pattern and the second pattern.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a drug delivery system,

The present invention relates to a method for preparing a drug delivery system, and a method for producing the same.

Intradermal drug delivery is known to be good for different dosing and treatment ranges such as immunity, immunomodulation, gene delivery, dermatology, allergies, irritability and cosmetics. In general, intradermal drug delivery is performed by a skilled medical technician using a hypodermic needle placed at a shallow angle to the skin surface. Attention is paid to achieving the correct penetration depth to ensure successful injection into the skin layer, not subcutaneous. In order for the needle to be inserted into the skin surface at a shallow angle, a slanted needle direction is desired, and a standard rule is that the hypodermic needle is inserted at an acute angle. The use of subcutaneous needles for intradermal drug delivery is known to be painful, as large needles are typically difficult to tolerate nerve endings in the dermal layer.

As an alternative to conventional needle structures, many attempts have been made to develop " ultra-fine " structures using various micromachining techniques and various materials. An initial embodiment of the " extreme approach " approach is disclosed in U.S. Patent No. 3,964,482 to Gustel et al., Which discloses that the drug reaches the epidermis by projecting (projecting) up to 10 microns to penetrate the stratum corneum A drug delivery device for percutaneously administering a drug is disclosed. The device has a plurality of needles projected outwardly from one surface, delivering the drug from the reservoir through the centered hole in one run.

And to provide a method for manufacturing a drug delivery system and a method for manufacturing the drug delivery system that can minimize the suffering of a patient. It is also possible to form a pattern of a shape in the longitudinal direction of the ultrasound including the body and the needle bar on the first substrate and the second substrate to form a microcapsule so that the electrode of the drug delivery system having a sufficient length, And to provide a production method capable of easily producing the same. It is to be understood, however, that the technical scope of the present invention is not limited to the above-described technical problems, and other technical problems may exist.

As a technical means for achieving the above technical object, an embodiment of the present invention is a method for manufacturing a semiconductor device, comprising the steps of preparing a first substrate, forming a shape of an upper layer in the longitudinal direction of the micro- Forming a second pattern including a shape of a lower layer in the longitudinal direction of the extremely fine contact on the second substrate; forming a first pattern on the first substrate, And bonding the second substrate and etching the bonded first and second substrates based on the first pattern and the second pattern to form the extreme micro- Can be provided.

In one embodiment, the first pattern and the second pattern may further include a shape of a dummy needle bar connected to a tip of the needle bar and having a symmetrical structure with the needle bar.

In one embodiment, the step of forming the ultrafine needle by etching the first substrate and the second substrate on the basis of the first pattern and the second pattern may be performed by using an anisotropic And etching the bonded first and second substrates through a wet etching process or an anisotropic dry etching process to form a needle bar having a predetermined angle.

In one embodiment, the step of forming the extremely fine contact by etching the bonded first substrate and the second substrate based on the first pattern and the second pattern includes etching the first substrate to form the extremely fine Forming an upper layer, etching the bonding layer of the first substrate and the second substrate, and etching the second substrate to form the bottom layer of the extremely fine bonding.

In one embodiment, the forming of the first pattern may include forming the first pattern by etching the first substrate using a deep reactive ion etching (DRIE) method.

In an embodiment, the second pattern may further include a shape of a channel through which the drug flows.

In one embodiment, the forming of the second pattern may include forming the second pattern by etching the second substrate using a deep reactive ion etching (DRIE) method.

In one embodiment, the step of bonding the first substrate and the second substrate may include one of direct bonding, anodic bonding, eutectic bonding, and polymer bonding. The first substrate and the second substrate can be bonded to each other.

In one embodiment, the method may further include forming a protective film on the bonded first and second substrates after the step of forming the uppermost layer by etching the first substrate.

In one embodiment, the protective film may be one of a silicon oxide film, a silicon nitride film, and a polymer film.

In one embodiment, the first and second bonded substrates are etched through an anisotropic wet etching process or an anisotropic dry etching process so as to cut the needle bar and the dummy barb to form a needle bar having a predetermined angle The method may further include removing the protective film corresponding to the needle bar and the dummy needle bar.

In one embodiment, after the step of etching the second substrate to form the lower layer, the step of removing the protective film other than the protective film corresponding to the needle bar and the dummy needle bar may be further included.

Another embodiment of the present invention is directed to a method of manufacturing a semiconductor device, comprising: forming a first substrate having a first pattern including a shape of an upper layer in a longitudinal direction of an extremely fine needle including a body and a needle bar and a first substrate bonded to the first substrate, And a second substrate on which a second pattern including the shape of the lower layer is formed.

In an embodiment, the second pattern may further include a shape of a channel through which the drug flows.

In one embodiment, the first substrate and the second substrate are bonded together using one of direct bonding, anodic bonding, eutectic bonding, and polymer bonding. .

In one embodiment, the microcapsule may be formed using MEMS (Micro Electro Mechanical System) technology.

According to any one of the above-mentioned objects of the present invention, it is possible to provide a drug delivery system which can minimize the pain of a patient, and a method for manufacturing the drug delivery system. It is also possible to form a pattern of a shape in the longitudinal direction of the ultrasound including the body and the needle bar on the first substrate and the second substrate to form a microcapsule so that the electrode of the drug delivery system having a sufficient length, And a manufacturing method capable of easily producing the same can be provided.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is an exemplary diagram illustrating a drug delivery system according to an embodiment of the present invention. FIG.
FIG. 2 is a view illustrating an example of a shape of a drug delivery system according to an embodiment of the present invention viewed from the top. FIG.
3 is a cross-sectional view illustrating a drug delivery system according to an embodiment of the present invention.
FIG. 4 is a cross-sectional view illustrating the shape of a cross-section of a drug delivery system according to an embodiment of the present invention, when the tip of the drug is cut in a direction orthogonal to the longitudinal direction.
5 is a view illustrating an exemplary shape of a first substrate on which a first pattern is formed according to an embodiment of the present invention.
6 is a view illustrating an exemplary shape of a second substrate on which a second pattern is formed according to an embodiment of the present invention.
FIGS. 7A and 7B are diagrams for explaining a method of manufacturing a microcapsule in a drug delivery system according to an embodiment of the present invention.
FIG. 8 is a view for explaining a method for manufacturing a microcapsule in a drug delivery system according to another embodiment of the present invention.
FIG. 9 is a flowchart illustrating a method for manufacturing a microcapsule in a drug delivery system according to an embodiment of the present invention.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, which will be readily apparent to those skilled in the art. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In order to clearly illustrate the present invention, parts not related to the description are omitted, and similar parts are denoted by like reference characters throughout the specification.

Throughout the specification, when a part is referred to as being "connected" to another part, it includes not only "directly connected" but also "electrically connected" with another part in between . Also, when an element is referred to as " including " an element, it is to be understood that the element may include other elements as well as other elements, And does not preclude the presence or addition of one or more other features, integers, steps, operations, components, parts, or combinations thereof.

Further, throughout the specification, when a member is positioned "on" or "under" another member, this includes not only the case where a member is in contact with another member but also the case where another member exists between the two members do. Also, when an element is referred to as " comprising ", it means that it can include other elements as well, without departing from the other elements unless specifically stated otherwise.

Hereinafter, a drug delivery system according to an embodiment of the present invention will be described with reference to FIG.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is an exemplary diagram illustrating a drug delivery system according to an embodiment of the present invention. FIG.

Referring to Figure 1, the drug delivery system 10 may be, but is not limited to, an intradermally injectable injector for intradermal drug delivery. For example, the drug delivery system 10 may also be used in a syringe for subcutaneous and intramuscular injection.

The drug delivery system 10 includes a body 100 having a drug-flowing body 110 and an acupuncture needle 100 including a needle bar 120, a space for allowing the drug to be sucked, and a finger flange a barrel 20 in which a finger flange is formed and a packing member inserted in the barrel 20 and provided at an end of the barrel 20 so as to be movable in a sealed state inside the barrel 20, And a plunger 30 in which a pusher for providing an enlarged surface is formed.

Hereinafter, the ultrafiltration according to an embodiment of the present invention will be described with reference to FIG. 2 to FIG.

FIG. 2 is a view illustrating an example of a shape of a drug delivery system according to an embodiment of the present invention viewed from the top. FIG. 3 is a cross-sectional view illustrating a cross-sectional shape of the drug delivery system according to an embodiment of the present invention when the ultrafiltration is cut in the longitudinal direction. 4 is a cross-sectional view illustrating a cross-sectional shape of a drug delivery system according to an embodiment of the present invention when the micro-fine needle is cut in a direction orthogonal to the longitudinal direction.

2 to 4, the polarizer 100 includes a body 110 and a needle 120. The polarizer 100 includes a first pattern including a shape of an upper layer in a longitudinal direction of the polarizer 100, And a second substrate 300 on which a second pattern including a shape of a lower layer in the longitudinal direction of the substrate 200 and the polarizing element 100 is formed. In addition, the second pattern may further include a channel 130 through which the drug flows.

Here, the first substrate 200 and the second substrate 300 may be, for example, a silicon substrate.

The first and second substrates 200 and 300 may be formed by using direct bonding, anodic bonding, or the like, using a micro electro mechanical system (MEMS) ), Eutectic bonding, and polymer bonding.

As described above, by using the MEMS technique to form the microcapsule 100 of the drug delivery system 10, for example, it is possible to minimize the patient's pain during intradermal injection.

It is also possible to form a pattern including the shape of the cross section of the body 110 and the needle bar 120 of the ultrasound probe 100 on the substrate when the pole tip 100 is formed vertically, There is a problem that it is difficult to form the extreme microcapsule 100 so as to have a length enabling the formulation of the intracutaneous or subcutaneous injection when the substrate is etched to form the intricate microcapsule 100. [

Further, there is a problem that the manufacturing process is complicated, thereby increasing the manufacturing cost.

On the contrary, the present invention is characterized in that the polarizing element 100 is formed on the substrate by forming a pattern of a shape in the longitudinal direction of the polarizing element 100, for example, to form a polarizing element 100 having a sufficient length for intracardial drug delivery Can be easily produced.

In addition, the manufacturing process is simpler than that in the case of forming the pole tip 100 in a vertical direction, thereby reducing manufacturing costs.

A detailed description of the first pattern formed on the first substrate 200 and the second pattern formed on the second substrate 300 will be described later.

Hereinafter, a method of manufacturing a microcapsule in a drug delivery system according to an embodiment of the present invention will be described with reference to FIGS. 5 to 8. FIG.

5 is a view illustrating an exemplary shape of a first substrate on which a first pattern is formed according to an embodiment of the present invention. 6 is a view illustrating an exemplary shape of a second substrate on which a second pattern is formed according to an embodiment of the present invention. 7A and 7B are diagrams for explaining a method for manufacturing a microcapsule in a drug delivery system according to an embodiment of the present invention. FIG. 8 is a view for explaining a method for manufacturing a microcapsule in a drug delivery system according to another embodiment of the present invention. FIG. 9 is a flowchart illustrating a method for manufacturing a microcapsule in a drug delivery system according to an embodiment of the present invention. Referring to FIG.

Referring to FIG. 7A, the first substrate 200 is prepared. The shape of the upper layer in the longitudinal direction of the polarizing element 100 including the shape of the body 110 and the shape 212 of the needle wire 120 on the first substrate 200, And a first pattern 210 including a dummy wire shape 213 having a symmetrical structure with the needle wire 120 is formed.

Here, the dummy needle bar is a dummy pattern having a symmetrical structure with the needle bar 120. The dummy needle bar is formed by forming a pattern including the shape in the longitudinal direction of the polarizing element 100 on the substrate and forming an anisotropic etching Thereby forming a sharp tip of the needle bar 120 in forming the needle point 100. [

In order to form the first pattern 210 on the first substrate 200, a photolithography process and an etching process may be performed.

For example, a first photoresist layer (not shown) corresponding to the first pattern 210 is formed on the first substrate 200. Subsequently, the first substrate 200 is etched using the first photoresist layer as a mask.

Here, the etching process may be a dry etching process, for example, a deep reactive ion etching (DRIE) process.

The depth reactive ion etching process can be performed, for example, as follows. Polymer deposition step for 5 seconds, and the polymer etch step of 3 seconds, a silicon etching step between 5 seconds performed sequentially, wherein the silicon etching step may be performed in an atmosphere of SF ₆ gas.

The first photoresist layer is then removed. For example, the first photoresist layer may be removed using an O ₂ plasma process or a mixed solution of sulfuric acid and hydrogen peroxide.

5 illustrates a first substrate 200 having a first pattern 210 formed thereon.

Then, the second substrate 300 is prepared. The shape of the lower layer in the longitudinal direction of the polarizing element 100 including the shape 311 of the body 100 and the shape 312 of the needle wire 120 on the second substrate 300, And a second pattern 310 including a shape 313 of the dummy needle bar having a symmetrical structure with the needle bar 120 and a shape 314 of the channel 130 for flowing the drug is formed.

Here, the dummy needle bar is used as a dummy pattern having a symmetrical structure with the needle bar 120 as described above, so that the tip of the needle bar 120 is sharply formed.

Further, the channel 130 has a width of 100 mu m and can be formed to have a depth of 100 mu m.

In order to form the second pattern 310 on the second substrate 300, a photolithography process and an etching process may be performed.

For example, as described above, a second photoresist layer (not shown) corresponding to the second pattern 310 is formed. Then, the second substrate 300 is etched by a dry etching process, for example, a depth reactive ion etching process, using the second photoresist layer as a mask.

The second photoresist layer may then be removed using an O ₂ plasma process or a mixed solution of sulfuric acid and hydrogen peroxide.

FIG. 6 illustrates a second substrate 300 having a second pattern 310 formed thereon.

As described above, according to the present invention, a pattern of a shape in the longitudinal direction of a polarizing element 100 is formed on a substrate to form a polarizing element 100, for example, a polarizing element 100 having a sufficient length for intracardial drug delivery ) Can be easily produced.

In addition, the manufacturing process is simpler than that in the case of forming the pole tip 100 in a vertical direction, thereby reducing manufacturing costs.

Then, as shown in FIG. 7 (b), the first substrate 200 and the second substrate 300 are bonded.

Here, the first substrate 200 and the second substrate 300 are bonded to each other by using one of direct bonding, anodic bonding, eutectic bonding, and polymer bonding, .

When anodic bonding, eutectic bonding or polymer bonding is used, an adhesive layer is formed between the first substrate 200 and the second substrate 300, and a process of etching the adhesive layer as described below is further performed .

Then, a protective film 400 is formed on the bonded first and second substrates 200 and 300. The protective film 400 functions to prevent the body 110 of the ultrasound probe 100 from being etched during a subsequent wet etching process.

Here, the protective layer 400 may be formed using one of a silicon oxide layer, a silicon nitride layer, and a polymer layer using, for example, physical vapor deposition (PVD) or chemical vapor deposition (CVD) have.

Subsequently, as shown in Fig. 7 (c), the protective film 400 covering the needle bar 120 of the ultrasound probe 100 and the dummy needle bar 140 is removed.

For example, a third photoresist layer corresponding to the needle bar 120 and the dummy needle line 140 of the ultrasound probe 100 is formed, and the first photoresist layer (not shown) 200 and the second substrate 300 are wet-etched. The third photoresist layer is then removed.

7B, the bonded first and second substrates 200 and 300 are etched based on the first pattern 210 and the second pattern 210, (100) is formed. The needle bar 120 and the dummy needle bar 140 are cut during the process of etching the first substrate 200 and the second substrate 300 so that the tip of the needle bar 120 can be sharply formed.

In this regard, the process of etching the first substrate 200 and the second substrate 300 bonded together with reference to FIG. 8 will be described. 8 shows a state in which the channel 130 is not formed, that is, a part of the first substrate 200 and the second substrate 300, which is separated from the center, is cut in the longitudinal direction. Channel 130 is not shown in FIG.

Referring to FIG. 8, a fourth photoresist layer 600 is formed on a part of the needle bar 120 and a part of the dummy wire 140 (FIG. 8A) The adhesive layer 500 of the first substrate 200 and the second substrate 300 and the second substrate 300 are sequentially etched using the first substrate 200 as a mask.

The first substrate 200 may be etched to form an upper layer of the microcapsule 100. The adhesive layer 500 between the first substrate 200 and the second substrate 300 is etched and the second substrate 300 is etched to form a lower layer of the microcapsule 100.

Here, the bonded first and second substrates 200 and 300 are etched through an anisotropic wet etching process or a dry anisotropic dry etching process to form the needle bar 120 having a predetermined angle.

For example, when the first substrate 200 and the second substrate 300 are etched through the anisotropic wet etching process, the first substrate 200 and the second substrate 300 are bonded to each other, Etchants such as KOH, TMAH, EPD, etc. have a high etching rate on the <100> plane. Accordingly, the <111> surface of the <100> surface and the surface of the <111> surface at 54.7 degrees are exposed through the anisotropic wet etching process.

By this anisotropic wet etching process, the needle bar 120 and the dummy needle bar 140 are cut, and thus the sharp needle 120 can be formed. Here, the fourth photoresist layer 600 is etched The width of the pattern of the fourth photoresist layer 600 can be appropriately controlled so that the needle bar 120 and the dummy needle wire 140 can be cut through the process.

Subsequently, the protective film 400 which has not been removed in the above-described process is removed, and as shown in Fig. 7 (f), the extreme microcapsules 100 can be formed by removing portions other than the extreme microcapsules 100. For example, the extreme microcapsule 100 can be completed by cutting the extreme microcapsule 100 through a dicing process.

FIG. 9 is a flowchart illustrating a method for manufacturing a microcapsule in a drug delivery system according to an embodiment of the present invention. The method of manufacturing the microcapsule of the drug delivery system according to the embodiment shown in FIG. 9 includes the method of manufacturing the microcapsule of the drug delivery system described above with reference to FIG. 1 to FIG. Therefore, even if omitted below, the method of manufacturing the drug delivery system according to the embodiment shown in FIG. 9 is also applicable.

Referring to FIG. 9, the first substrate 200 may be prepared in step S900.

The first pattern 210 including the shape of the upper layer in the longitudinal direction of the polarizer 100 including the body 110 and the needle bar 120 may be formed on the first substrate 200 in step S910 .

In step S920, the second substrate 300 may be prepared.

The second pattern 310 including the shape of the lower layer in the longitudinal direction of the polarizing element 100 may be formed on the second substrate 300 in step S930.

In step S940, the first substrate 200 and the second substrate 300 may be bonded.

The extreme microcapsule 100 may be formed by etching the first substrate 200 and the second substrate 300 bonded at step S950 based on the first pattern 210 and the second pattern 310. [

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.

The scope of the present invention is defined by the appended claims rather than the detailed description and all changes or modifications derived from the meaning and scope of the claims and their equivalents are to be construed as being included within the scope of the present invention do.

10: Drug delivery system
20: Barrel
30: plunger
100: Extreme
110: Body
120: Slippery
130: channel
140: Dummy sailboat
200: first substrate
210: first pattern
300: second substrate
310: second pattern
400: Shield
500: adhesive layer
600: fourth photoresist layer

Claims (16)

A method for producing a microcapsule in a drug delivery system,
Preparing a first substrate;
Forming a first pattern on the first substrate, the first pattern including a shape of an upper layer in a longitudinal direction of a deep penetration including a body and a needle bar;
Preparing a second substrate;
Forming a second pattern on the second substrate, the second pattern including a shape of a lower layer in the longitudinal direction of the uncollected pattern;
Bonding the first substrate and the second substrate; And
Forming the extremely fine contact by etching the bonded first and second substrates based on the first pattern and the second pattern,
Lt; / RTI &gt;
Wherein the first pattern and the second pattern are connected to the tip of the needle, further comprising a shape of a dummy needle having a symmetrical structure with the needle.
delete The method according to claim 1,
Wherein the step of forming the extremely fine needle by etching the bonded first and second substrates based on the first pattern and the second pattern comprises:
Etching the bonded first and second substrates through an anisotropic wet etching process or an anisotropic dry etching process so as to cut the needle bar and the dummy needle bar to form a needle bar having a predetermined angle
Wherein the drug delivery system comprises a drug delivery system.
The method according to claim 1,
Wherein the step of forming the extremely fine needle by etching the bonded first and second substrates based on the first pattern and the second pattern comprises:
Etching the first substrate to form an uppermost layer of the microcrystalline substrate;
Etching the bonding layer of the first substrate and the second substrate; And
And etching the second substrate to form a bottom layer
Wherein the drug delivery system comprises a drug delivery system.
The method according to claim 1,
The forming of the first pattern may include:
Wherein the first substrate is etched using a deep reactive ion etching (DRIE) method to form the first pattern.
The method according to claim 1,
Wherein the second pattern further comprises a shape of a channel through which the drug flows.
The method according to claim 1,
The forming of the second pattern may include:
Wherein the second substrate is etched using a deep reactive ion etching (DRIE) method to form the second pattern.
The method according to claim 1,
Wherein the step of bonding the first substrate and the second substrate comprises:
Wherein the first substrate and the second substrate are bonded using one of direct bonding, anodic bonding, eutectic bonding and polymer bonding, A method for manufacturing a microfibre system.
5. The method of claim 4,
After the step of etching the first substrate to form the uppermost layer of the microcrystalline substrate,
Forming a protective film on the bonded first and second substrates
Further comprising the steps of: preparing a drug delivery system;
10. The method of claim 9,
Wherein the protective film is one of a silicon oxide film, a silicon nitride film and a polymer film.
10. The method of claim 9,
Prior to the step of etching the bonded first and second substrates by an anisotropic wet etching process or an anisotropic dry etching process so as to cut the needle bar and the dummy needle bar to form the needle bar having the predetermined angle,
Removing the protective film corresponding to the needle bar and the dummy needle bar
Further comprising the steps of: preparing a drug delivery system;
12. The method of claim 11,
After the step of etching the second substrate to form the bottom layer of extremely fine impurities,
Removing the protective film other than the protective film corresponding to the needle bar and the dummy needle bar
Further comprising the steps of: preparing a drug delivery system;
At the expense of the drug delivery system,
A first substrate on which a first pattern including a shape of an upper layer in a longitudinal direction of a deep penetration including a body and a needle bar is formed; And
And a second pattern formed on the second substrate, the second pattern including a shape of a lower layer in the longitudinal direction of the extremely fine contact,
/ RTI &gt;
Wherein the first substrate and the second substrate are etched based on the first pattern and the second pattern,
Wherein the first pattern and the second pattern are connected to the tip of the needle bar, and further comprising a shape of a dummy needle bar having a symmetrical structure with the needle bar.
14. The method of claim 13,
Wherein the second pattern further comprises a shape of a channel through which the drug flows.
14. The method of claim 13,
Wherein the first substrate and the second substrate are bonded using one of direct bonding, anodic bonding, eutectic bonding, and polymer bonding. Extremely low system performance.
14. The method of claim 13,
Wherein the ultrasound is formed using MEMS (Micro Electro Mechanical System) technology.

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