Microneedle and manufacturing method therefor using photolithography

Abstract

The present invention relates to a microneedle and a manufacturing method therefor using photolithography and, more specifically, to a microneedle and a manufacturing method therefor using photolithography, in which the microneedle can be easily manufactured using photolithography.

Description

The fabrication method using microneedles and photolithography

[0001] The present invention relates to a microneedle and a method for fabricating the same using photolithography, and more specifically, to a microneedle and a method for fabricating the same using photolithography that allows for the easy fabrication of a microneedle using photolithography.

[0002] Although numerous drugs and bioactive substances have been developed for the treatment of diseases, there are still areas that need improvement regarding the delivery of drugs and bioactive substances into the body, such as the problem of passing through biological barriers (e.g., skin, oral mucosa, and blood-brain barrier) and the efficiency of drug delivery.

[0003] Although drugs and bioactive substances are generally administered orally in tablet or capsule form, such methods alone cannot effectively deliver them due to reasons such as digestion or absorption in the gastrointestinal tract or elimination through hepatic mechanisms. Furthermore, some drugs cannot effectively diffuse through the intestinal mucosa. Patient compliance is also a concern (e.g., cases requiring medication at specific intervals or critically ill patients unable to take oral medication).

[0004] Another common technique for the delivery of drugs and bioactive substances is the use of conventional needles. While this method is more effective than oral administration, it presents problems such as pain at the injection site, localized skin damage, bleeding, and infection at the injection site.

[0005] To solve the aforementioned problems, various microneedle patches containing microneedles have been developed. These microneedles can be manufactured using a mold method or in various other ways, such as the applicant's DEN (Droplet Extension) method.

[0006] Recently, hollow needles with a hollow center are being developed to increase drug delivery rates using microneedles, and there is an increasing demand for manufacturing methods that can produce these hollow needles more effectively.

[0007] The present invention aims to provide a method for manufacturing hollow needles using microneedles and photolithography, which can effectively produce hollow needles in a shorter time to solve the above-mentioned problems.

[0008] The objective of the present invention as described above can be achieved by a method for producing microneedles using photolithography, characterized by including the step of producing a microneedle base on a first surface of a first mask and the step of producing microneedles on the microneedle base.

[0009] Here, the step of fabricating the microneedle base comprises the step of forming a first photosensitive film of a predetermined thickness on a first surface of the first mask, the step of aligning and placing a second mask on top of the first surface of the first mask, and the step of fabricating the microneedle base on the first surface of the first mask by irradiating radiation from the top of the second mask.

[0010] The first mask comprises a peripheral opaque area through which radiation cannot pass, a central transparent area disposed within the peripheral opaque area through which radiation passes, and a first central opaque area disposed within the central transparent area, through which radiation passes, and the radiation passes through the central transparent area. The second mask may have a peripheral transparent area through which radiation passes and a second central opaque area disposed within the peripheral transparent area through which radiation cannot pass.

[0011] Meanwhile, the central transparent area of ​​the first mask and the second central opaque area of ​​the second mask may have the same shape and size.

[0012] In addition, in the step of aligning and placing a second mask on the upper surface of the first surface of the first mask, the second mask may be aligned and placed spaced apart from the first photosensitive film on the first surface of the first mask.

[0013] Furthermore, in the step of aligning and arranging the first mask and the second mask, the second central opaque area of ​​the second mask and the central transparent area of ​​the first mask may be arranged on concentric circles.

[0014] In addition, in the step of aligning and arranging the first mask and the second mask, the edge of the second central opaque area of ​​the second mask may coincide with the edge of the central transparent area of ​​the first mask.

[0015] Meanwhile, in the step of fabricating the microneedle base by irradiating radiation from the upper part of the second mask, the first photosensitive film that does not overlap with the second central opaque region of the second mask can be photocrosslinked and cured to form the microneedle base.

[0016] In addition, in the step of fabricating the microneedle base by irradiating radiation from the upper part of the second mask, the first photosensitive film that does not overlap with the central transparent region of the first mask can be photocrosslinked and cured to form the microneedle base.

[0017] Meanwhile, the step of fabricating the microneedle may include: a step of forming a second photosensitive film on the first surface of the microneedle base formed on the first surface of the first mask; a step of forming microneedles on the first surface of the microneedle base by irradiating radiation through the second surface of the first mask where the second photosensitive film is not formed; and a step of removing the uncrosslinked photosensitive film.

[0018] Furthermore, the first mask comprises a peripheral opaque area through which radiation cannot pass, a central transparent area disposed within the peripheral opaque area through which radiation passes, and a first central opaque area disposed within the central transparent area, and radiation can pass through the central transparent area between the peripheral opaque area and the first central opaque area.

[0019] Furthermore, the above microneedles may correspond to hollow microneedles with a hollow center.

[0020] Meanwhile, the step of forming a second photosensitive film on the first surface of the microneedle base may involve applying the second photosensitive film to the first surface of the microneedle base, or inverting the first mask vertically and immersing the first mask in a tank containing a photosensitive liquid.

[0021] Meanwhile, the objective of the present invention as described above can be achieved by microneedles produced by the microneedle production method described above.

[0022] According to the present invention having the aforementioned configuration, microneedles can be fabricated in a short time using photolithography.

[0023] Furthermore, according to the present invention, a microneedle base on which microneedles are formed can be manufactured together.

[0024] In addition, according to the present invention, a hollow needle with a hollow center can be effectively produced in a shorter time using photolithography.

[0025] FIGS. 1 and 2 are schematic diagrams illustrating a method for fabricating microneedles according to an embodiment of the present invention.

[0026] Figures 3 and 4 are flowcharts illustrating a method for fabricating microneedles.

[0027] FIG. 5 is a plan view illustrating a first mask and a second mask used in the manufacturing method of the present invention.

[0028] FIG. 6 is a side view illustrating the step of forming a first photosensitive film on the first surface of a first mask,

[0029] FIG. 7 is a side view illustrating a state in which a second mask is aligned and positioned on the upper surface of a first mask.

[0030] FIG. 8 is a side view illustrating a state in which a first photosensitive film placed outside the central transparent region of a first mask is photocrosslinked and cured.

[0031] FIG. 9 is a side view illustrating the step of forming a second photosensitive film on a microneedle base formed on the first surface of a first mask.

[0032] FIG. 10 is a side view illustrating the step of irradiating radiation through the second surface of the first mask,

[0033] FIG. 11 is a side view illustrating a hollow microneedle fabricated by the aforementioned method,

[0034] FIG. 12 is a side view illustrating the step of forming a second photosensitive film on a microneedle base formed on the first surface of a first mask that is inverted vertically.

[0035] FIG. 13 is a side view illustrating the step of irradiating radiation through the second surface of a first mask that is inverted vertically,

[0036] FIG. 14 is a side view illustrating a hollow microneedle with its top and bottom reversed.

[0037] Hereinafter, with reference to the drawings, a method for fabricating microneedles using photolithography according to an embodiment of the present invention will be examined in detail.

[0038] The method for producing microneedles according to the present invention may include the steps of producing a microneedle base (1A, 1B, 1C) (see FIG. 1) on a first surface (101) (see FIG. 6) of a first mask (100) (see FIG. 5) and producing microneedles (500) (see FIG. 11) on the microneedle base (530) (see FIG. 11) (2A, 2B, 2C: 2D, 2E) (see FIG. 1).

[0039] In the present invention, the microneedle base (530) and the microneedle (500) are manufactured together using a photolithography method, thereby reducing the process and time required for manufacturing compared to conventional methods.

[0040] FIGS. 1 and 2 are schematic diagrams illustrating a method for manufacturing microneedles according to an embodiment of the present invention, and FIGS. 3 and 4 are flowcharts illustrating a method for manufacturing microneedles.

[0041] FIGS. 1 and FIGS. 3 illustrate steps (1A, 1B, 1C) for fabricating the microneedle base (530), and FIGS. 2 and FIGS. 4 illustrate steps (2A, 2B, 2C: 2D, 2E) for fabricating microneedles (500) on the microneedle base (530).

[0042] Referring to FIGS. 1 and FIGS. 3, the step of manufacturing the microneedle base (530) may include the step (S310) of forming a first photosensitive film (210) (see FIG. 6) of a predetermined thickness on the first surface (101) of the first mask (100), the step (S330) of aligning and placing a second mask (300) (see FIG. 5) on the upper surface (102) of the first mask (100), and the step (S350) of manufacturing the microneedle base (530) on the first surface (101) of the first mask (100) by irradiating radiation from the upper surface of the second mask (300).

[0043] FIG. 5 is a plan view illustrating the first mask (100) and the second mask (300) used in the manufacturing method of the present invention.

[0044] Referring to FIG. 5, the first mask (100) may include a peripheral opaque area (110) through which radiation cannot pass, a central transparent area (120) through which radiation passes and which is disposed in the peripheral opaque area (110), and a first central opaque area (130) disposed inside the central transparent area (120).

[0045] The above surrounding opaque area (110) and the first central opaque area (130) can be made of a material that cannot transmit radiation.

[0046] On the other hand, the central transparent area (120) can be made of a material through which radiation can pass.

[0047] The central transparent area (120) and the first central opaque area (130) are depicted as circular, but are not limited thereto and can be manufactured in various shapes. For example, the central transparent area (120) and the first central opaque area (130) may be manufactured in a polygonal shape. Below, we will examine the case where the central transparent area (120) and the first central opaque area (130) are formed in a circular shape.

[0048] The central transparent area (120) and the first central opaque area (130) may be arranged on concentric circles. The central transparent area (120) and the first central opaque area (130) may be arranged in multiple numbers in the surrounding opaque area (110), and the specific number is not limited.

[0049] Additionally, the spacing between the adjacent central transparent area (120) and the first central opaque area (130) can be appropriately adjusted.

[0050] Meanwhile, when radiation is irradiated, the radiation may penetrate the central transparent area (120). More precisely, the radiation may penetrate the central transparent area (120) between the surrounding opaque area (110) and the first central opaque area (130).

[0051] Meanwhile, the second mask (300) may have a surrounding transparent area (310) through which radiation passes, and a second central opaque area (320) disposed in the surrounding transparent area (310) through which radiation cannot pass.

[0052] In this case, radiation cannot penetrate the second central opaque region (320) and can penetrate the surrounding transparent region (310) to be irradiated.

[0053] The above second central opaque area (320) may be arranged in multiple numbers in the surrounding transparent area (310), and the specific number is not limited.

[0054] However, the number of the second central opaque area (320) of the second mask (300) may be the same as the number of the central transparent area (120) and the first central opaque area (130) of the first mask (100) described above. This will be examined in detail later.

[0055] Looking at the steps for manufacturing the above microneedle base (530), as shown in FIG. 6, a first photosensitive film (210) of a predetermined thickness can first be formed on the first surface (101) of the first mask (100).

[0056] For example, the first photosensitive film (210) can be applied to the first surface (101) of the first mask (100).

[0057] Here, the first photosensitive film (210) may be composed of a liquid-state photosensitive resin.

[0058] As used herein, “resin” refers to various monomer, oligomer, and / or polymer compositions typically comprising monomers, oligomers, and / or polymers dispersed in a solvent system together with any photoinitiator. Such photosensitive resins are known in the art and include compositions commonly used as negative-tone photoresists in microelectronic manufacturing as well as resins for 3D printing.

[0059] For example, resins include various epoxies, acrylates, polyurethanes, methacrylated oligomers, monomers or polymers, urethane methacrylates, diphenyl (2,4,6-trimethylbenzoyl)phosphine oxide, bisphenol A novolac glycidyl ether (trade name SU-8), etc.

[0060] The viscosity of the composition can be controlled using a solvent such as γ-butyrolactone (γ-Butyrolactone; GBL), propylene glycol methyl ether acetate (PGMEA), isopropyl alcohol (IPA), etc.

[0061] For example, the viscosity of the resin can be adjusted if it is desired to change the tip shape of the microneedle. For instance, low-viscosity liquid resins tend to form a low base angle and a large vertex angle, whereas high-viscosity liquid resins tend to form a large base angle and a small vertex angle. However, almost any photoreactive clear liquid resin can be used, including additive photoinitiators in which a photoinitiator (e.g., phenones such as benzophenones, acetophenones, phosphine oxides, phosphinates, etc.) is added to acrylic and / or methacrylic acid esters. Photoinitiators are commercially available under the brand name Irgacure or include triaryl sulfonium salts (e.g., Cyracure UVI from Union Carbide Corp.). Vegetable photosensitive resins are also commercially available. In some embodiments, a transparent resin is used. In some embodiments, a translucent resin may be used. In some embodiments, the resin may be opaque and may be any number of available colors.

[0062] Meanwhile, the thickness of the first photosensitive film (210) is not limited to a specific value. However, since a part of the first photosensitive film (210) forms the microneedle base (530) described later, it can be formed with a thickness suitable for the microneedle base (530).

[0063] Next, as shown in FIG. 7, a second mask (300) can be aligned and placed on the upper surface (101) of the first mask (100).

[0064] The second mask (300) can be aligned and positioned on the upper part of the first photosensitive film (210) of the first mask (100).

[0065] In this case, the second mask (300) may be placed in contact with the upper surface of the first photosensitive film (210). However, if the second mask (300) is placed in contact with the upper surface of the first photosensitive film (210) in this manner, it may be difficult to separate the second mask (300) from the first photosensitive film (210) later.

[0066] Accordingly, in the case of the present invention, the second mask (300) can be aligned and positioned at a predetermined distance from the first photosensitive film (210) formed on the first surface (101) of the first mask (100).

[0067] Meanwhile, when looking at the first mask (100) and the second mask (300), the central transparent area (120) of the first mask (100) and the second central opaque area (320) of the second mask (300) may have the same shape and size.

[0068] That is, when the first mask (100) and the second mask (300) are aligned and arranged, the edge of the central transparent area (120) of the first mask (100) and the edge of the second central opaque area (320) of the second mask (300) may coincide on a plane.

[0069] In addition, when the central transparent area (120) of the first mask (100) and the second central opaque area (320) of the second mask (300) are formed in a circular shape, the second central opaque area (320) of the second mask (300) and the central transparent area (120) of the first mask (100) may be arranged on concentric circles.

[0070] As described above, the first mask (100) and the second mask (300) are aligned and arranged, and then radiation is irradiated from the upper part of the second mask (300) to produce the microneedle base (530).

[0071] In the state of Fig. 7, if radiation, for example, ultraviolet (UV, ultra violet) is irradiated from the upper part of the second mask (300), the radiation can penetrate the surrounding transparent area (310) of the second mask (300).

[0072] In this case, as illustrated in FIG. 8, the first photosensitive film (210A) placed outside the central transparent region (120) of the first mask (100) can be photocrosslinked and cured. In FIG. 8, for convenience of explanation, the photocrosslinked region of the first photosensitive film (210) is labeled as '210A'. In addition, the crosslinked first photosensitive film (210A) thus forms a microneedle base (530).

[0073] In the present invention, a negative photoresist method may be used. However, although not shown in the drawings, a positive photoresist method may also be used.

[0074] Meanwhile, the first photosensitive film (210), which is not irradiated by radiation due to the second central opaque region (320) of the second mask (300), remains in an uncrosslinked state. That is, the first photosensitive film (210) placed inside the central transparent region (120) of the first mask (100) remains in an uncrosslinked state.

[0075] Next, a microneedle (500) can be fabricated on the microneedle base (530). Referring to FIGS. 2 and FIGS. 4, the step of fabricating a microneedle (500) on the microneedle base (530) may include a step (S410) of forming a second photosensitive film (230) on the first surface of the microneedle base (530) formed on the first surface (101) of the first mask (100), a step (S430) of forming a microneedle (500) on the first surface of the microneedle base (530) by irradiating radiation through the second surface (102) of the first mask (100) (see FIG. 10) where the second photosensitive film (230) is not formed, and a step (S450) of removing the uncrosslinked photosensitive film.

[0076] First, as illustrated in FIG. 9, a second photosensitive film (230) can be formed with a predetermined thickness on the first surface (101) of the first mask (100) or on the first surface of the first photosensitive film (210, 210A). Here, since the cross-linked first photosensitive film (210A) forms the microneedle base (530), it corresponds to the same component but is shown separately for convenience of explanation.

[0077] Meanwhile, the second photosensitive film (230) can be applied (2A in FIG. 2) to the first surface of the microneedle base (530) formed on the first surface of the first mask (100) or to the first surface of the first photosensitive film (210, 210A).

[0078] The second photosensitive film (230) may be the same as the first photosensitive film (210), but is not limited thereto, and the second photosensitive film (230) may be different from the first photosensitive film (210).

[0079] Meanwhile, the thickness (or height) of the second photosensitive film (230) may be determined according to the shape or material of the microneedle (500). For example, when manufacturing a hollow microneedle as described below, the thickness (or height) of the second photosensitive film (230) may be determined so that the upper part of the microneedle (500) is not blocked. The thickness (or height) of the second photosensitive film (230) is not limited to a specific numerical value.

[0080] After forming the second photosensitive film (230), radiation is irradiated. In this case, as shown in FIG. 10, radiation can be irradiated through the second surface (102) of the first mask (100), that is, the second surface (102) where the first photosensitive film (210) and the second photosensitive film (230) are not formed.

[0081] In this case, the radiation can be irradiated by penetrating the central transparent area (120) between the peripheral opaque area (110) and the first central opaque area (130) of the first mask (100).

[0082] The portion of the photoresist exposed to the radiation is cross-linked and / or photopolymerized, causing the liquid resin in that portion to harden and transform into a solid resin structure. When the resin is cross-linked and / or photopolymerized, this transition may be accompanied by a change in the resin's refractive index. This change in refractive index likewise alters the propagation path of the radiation as it penetrates deeper into the photoresist. In particular, the difference in refractive index between the solid-state photoresist and the surrounding liquid-state photoresist creates a barrier to diffraction at the interface, thereby limiting and inducing the direction of radiation propagation. Consequently, the resulting solid-state resin structure has an overall tapered structure, or a structure that converges toward the top, where the base of the cross-linked and / or photopolymerized structure is larger than the top of the structure (i.e., the tip of the structure).

[0083] Accordingly, as shown in FIG. 10, the second photosensitive film (230) can be photocrosslinked and cured by forming a shape that converges from the top.

[0084] In this case, as described above, the thickness (or height) of the second photosensitive film (230) is adjusted so that the cured area of ​​the second photosensitive film (230) does not completely converge.

[0085] In addition, in the above configuration, the radiation is prevented from penetrating the first central opaque region (130) of the first mask (100).

[0086] Accordingly, drying can be performed for a predetermined time in the state of Fig. 10, and then the photosensitive film (230) that has not been crosslinked can be removed by a solvent such as ethanol.

[0087] By doing so, a microneedle (500) as illustrated in FIG. 11 can be produced. The microneedle (500) may be composed of a body part (510) having a hollow part (520) formed in the center and a microneedle base (530) connecting the body part (510). That is, the microneedle (500) may correspond to a hollow microneedle with a hollow center.

[0088] A first opening (522) is formed at the upper part of the body portion (510), and a second opening (524) may be formed at the lower part of the body portion (510). The first opening (522) and the second opening (524) may be connected to each other to form a hollow portion (520) inside the body portion (510).

[0089] Meanwhile, in the step of forming the second photosensitive film (230), the first mask (100) can be inverted vertically and the first mask (100) can be immersed (2D in FIG. 2) in a tank (400) (see FIG. 2) containing a photosensitive liquid. That is, the first mask (100) can be inverted vertically so that the first surface of the first mask (100) faces downward, and then the first mask (100) can be immersed in the tank (400).

[0090] In this case, as illustrated in FIG. 12, the second photosensitive film (230) may be formed on the first surface (101) of the first mask (100) or on the first surface of the first photosensitive film (210, 210A).

[0091] Additionally, the thickness (or height) of the second photosensitive film (230) may be determined by the height of the receiving portion (410) (see FIG. 2) of the tank (400) in which the second photosensitive film (230) is received. In this case, as described above, when producing a hollow microneedle, the height of the receiving portion (410) may be determined so that the upper part of the microneedle (500) is not blocked. The height of such a receiving portion (410) is not limited to a specific numerical value.

[0092] Next, as shown in FIG. 13, radiation can be irradiated through the second surface (102) of the first mask (100), that is, the second surface (102) where the first photosensitive film (210) and the second photosensitive film (230) are not formed. Additionally, drying can be performed for a predetermined time in the state of FIG. 13, and then the photosensitive film (230) that is not crosslinked can be removed by a solvent such as ethanol to produce a hollow microneedle (500) as shown in FIG. 14.

[0093] The description of Figures 13 and 14 is similar to the description of Figures 10 and 11 mentioned above, except for the vertical inversion, so a repetitive description is omitted.

[0094] Although the present invention has been described above with reference to preferred embodiments, those skilled in the art may modify and change the present invention in various ways without departing from the spirit and scope of the invention as described in the claims below. Therefore, if a modified embodiment basically includes the components of the claims of the present invention, it should be considered to be included within the technical scope of the present invention.

[0095] According to the present invention, microneedles can be fabricated in a short time using photolithography.

Claims

1. A step of fabricating a microneedle base on the first surface of the first mask; and A method for producing microneedles using photolithography, characterized by including the step of producing microneedles on the above-mentioned microneedle base.

2. In Paragraph 1, The step of manufacturing the above microneedle base A step of forming a first photosensitive film of a predetermined thickness on the first surface of the first mask, and A step of aligning and placing a second mask on the upper surface of the first mask, The method includes the step of fabricating the microneedle base on the first surface of the first mask by irradiating radiation from the upper part of the second mask, The first mask comprises a peripheral opaque area through which radiation cannot pass, a central transparent area disposed within the peripheral opaque area through which radiation passes, and a first central opaque area disposed within the central transparent area, wherein the radiation passes through the central transparent area. A method for fabricating microneedles using photolithography, characterized in that the second mask comprises a peripheral transparent region through which radiation passes and a second central opaque region disposed in the peripheral transparent region through which radiation cannot pass.

3. In Paragraph 2, A method for producing microneedles using photolithography, characterized in that the central transparent region of the first mask and the second central opaque region of the second mask have the same shape and size.

4. In Paragraph 2, In the step of aligning and placing a second mask on the upper surface of the first face of the first mask, A method for fabricating microneedles using photolithography, characterized by aligning and arranging the second mask spaced apart from the first photosensitive film on the first surface of the first mask.

5. In Paragraph 2, In the step of aligning and arranging the first mask and the second mask, A method for producing microneedles using photolithography, characterized in that the second central opaque region of the second mask and the central transparent region of the first mask are arranged on concentric circles.

6. In Paragraph 2, In the step of aligning and arranging the first mask and the second mask, A method for producing microneedles using photolithography, characterized in that the edge of the second central opaque region of the second mask matches the edge of the central transparent region of the first mask.

7. In Paragraph 2, In the step of fabricating the microneedle base by irradiating radiation from the upper part of the second mask, A method for producing microneedles using photolithography, characterized in that the first photosensitive film, which does not overlap with the second central opaque region of the second mask, is photocrosslinked and cured to form the microneedle base.

8. In Paragraph 2, In the step of fabricating the microneedle base by irradiating radiation from the upper part of the second mask, A method for producing microneedles using photolithography, characterized in that the first photosensitive film, which does not overlap with the central transparent region of the first mask, is photocrosslinked and cured to form the microneedle base.

9. In Paragraph 1, The step of fabricating the above microneedles A step of forming a second photosensitive film on the first surface of the microneedle base formed on the first surface of the first mask; A step of forming microneedles on the first surface of the microneedle base by irradiating radiation through the second surface of the first mask where the second photosensitive film is not formed; and A method for fabricating microneedles using photolithography, characterized by including the step of removing a non-crosslinked photosensitive film.

10. In Paragraph 9, The first mask comprises a peripheral opaque area through which radiation cannot pass, a central transparent area disposed in the peripheral opaque area through which radiation passes, and a first central opaque area disposed inside the central transparent area. A method for fabricating microneedles using photolithography, characterized in that the radiation passes through the central transparent region between the surrounding opaque region and the first central opaque region.

11. In Paragraph 10, A method for producing microneedles using photolithography, characterized in that the above microneedles correspond to hollow microneedles with a hollow central part.

12. In Paragraph 9, The step of forming a second photosensitive film on the first surface of the microneedle base above Applying the second photosensitive film to the first surface of the microneedle base, or A method for producing microneedles using photolithography, characterized by inverting the upper and lower sides of the first mask and immersing the first mask in a tank containing a photosensitive solution.

13. A microneedle produced by a method for producing microneedles according to any one of claims 1 to 12.

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