Login| Sign Up| Help| Contact|

Patent Searching and Data


Title:
MANUFACTURING PROCESS OF HIGH DENSITY MICRONEEDLES
Document Type and Number:
WIPO Patent Application WO/2021/066755
Kind Code:
A2
Abstract:
This invention is the process of producing microneedles consisting of UV or visible light exposure through the lens, mask, substrate sheet to the photopolymer; moving the substrate sheet with polymerized microneedles from the photopolymer; and cleaning the microneedles. The process of producing microneedles, according to this invention, can manufacture a large number of microneedles. Controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask, exposure time, and mask thickness will affect the size of the microneedle base and the size of the open-area-shapelike film under the microneedle base, which will affect the density of the number of microneedles per unit area.

Inventors:
MANAKASETTHARN SUPONE (TH)
KHANCHAITIT PAISAN (TH)
RAYANASUKHA YOSSAWAT (TH)
MARIE CHARLTON TESSA (CA)
TANTISANTISOM KITTIPONG (TH)
BOONKOOM THITIKORN (TH)
JIEMSAKUL THANAKORN (TH)
THONGMA SATTRA (TH)
Application Number:
PCT/TH2020/000059
Publication Date:
April 08, 2021
Filing Date:
August 20, 2020
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
NATIONAL SCIENCE AND TECH DEVELOPMENT AGENCY (TH)
International Classes:
A41B13/06
Attorney, Agent or Firm:
RUANGSIN, RATCHADA et al. (TH)
Download PDF:
Claims:
We claim:

1. The manufacturing process of high density microneedles comprising the steps of: the step of providing a container (110) which contains a photopolymer (100); the step of providing a substrate sheet (400) made of transparent or translucent material which is placed in contact with a part of the-photopolymer (100); the step of providing a lens panel (200) containing at least one lens (210) which is a convex lens with a half-spherical shape, placed upside-down above the mask (500); the step of providing a mask (500) consisting of an opaque area and an open area with one or more geometric shapes for ultraviolet (UV) or visible light to pass through which a number of open areas is at least equal to a number of lenses; the step of radiating UV or visible light through the lens panel (200), the mask (500), the substrate sheet (400), respectively, to the photopolymer (100) which will be polymerized on the substrate sheet (400) as a microneedle from UV or visible light focusing via the convex lens and as an open-area-shape-like film from the diffraction and reflection of UV or visible light; the step of moving the substrate sheet (400) with microneedles away from the photopolymer (100)

Characterized in that the step of radiating UV or visible light consisting of the step controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500) to be in the range of 1-5; the step controlling the exposure time of UV or visible light to be in the range of 0.1-10 seconds; and the step controlling the mask (500) thickness as specified.

2. The manufacturing process of high density microneedles of claim 1, wherein the geometric shape is selected from a circle, an ellipse and a polygon.

3. The manufacturing process of high density microneedles of claim 1, wherein the mask (500) thickness is in the range of 100 micrometers to 5 millimeters.

4. The manufacturing process of high density microneedles of claim 1, wherein the lens diameter is 2.4 mm, the step controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500) is controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500) to be equal to 3, the step controlling the exposure time of UV or visible light is controlling the exposure time of UV or visible light to be 0.5 seconds, and the step controlling the mask (500) thickness is controlling the mask (500) thickness to be 2 millimeters.

5. The manufacturing process of high density microneedles of claim 1, wherein the lens diameter is 3 mm, the step controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500) is controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500) to be equal to 1.5, the step controlling the exposure time of UV or visible light is controlling the exposure time of UV or visible light to be 0.5 seconds, and the step controlling the mask (500) thickness is controlling the mask (500) thickness to be 2 millimeters.

6. The manufacturing process of high density microneedles of claim 1, wherein the lens diameter is 3.6 mm, the step controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500) is controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500) to be equal to 3, the step controlling the exposure time of UV or visible light is controlling the exposure time of UV or visible light to be 0.5 seconds, and the step controlling the mask (500) thickness is controlling the mask (500) thickness to be 2 millimeters.

7. The manufacturing process of high density microneedles of claim 1, wherein the substrate sheet (400) is selected from the group consisting of a transparent plastic sheet, translucent plastic sheet, transparent fabric sheet, translucent fabric sheet, transparent non-woven sheet, translucent non-woven sheet, transparent paper, translucent paper, transparent polymer sheet, translucent polymer sheet, transparent glass sheet, translucent glass, transparent quartz sheet, translucent quartz sheet, transparent metal sheet, translucent metal sheet, transparent ceramic sheet, translucent ceramic sheet, transparent membrane sheet, translucent membrane sheet, transparent hybrid material sheet, and translucent hybrid material sheet.

8. The manufacturing process of high density microneedles of claim 1, wherein the photopolymer (100) is selected from the group consisting of ultraviolet (UV) sensitive resin and visible sensitive resin.

9. The manufacturing process of high density microneedies of claim 1, wherein the photopolymer (100) is ultraviolet (UV) sensitive resin.

10. Microneedles produced from the manufacturing process according to anyone of claims 1 to 9, wherein the microneedle (300) height is in the range of 10 micrometers to 10 millimeters.

Description:
MANUFACTURING PROCESS OF HIGH DENSITY MICRONEEDLES FIELD OF THE INVENTION

The present invention relates to the manufacturing of microneedles.

BACKGROUND OF THE INVENTION

Microneedles are increasingly popular in medical and cosmetic applications. Microneedles are penetrated into the skin area that needs restoration thereby reducing the appearance of scars and wrinkles as the skin repairs itself from micro-injuries created by the needles. The penetration depth of microneedles usually does not reach the nerve-containing layer; therefore, there is no painful feeling when microneedles are pricked on the skin. Microneedles can also be used for drug delivery. The drug may be coated on the surface of microneedles or drug may be encapsulated in microneedles. In addition, microneedles can be used as sensors to detect indications under the skin. The density of microneedles may affect the sensor's performance.

There are many preparation methods for manufacturing microneedles. Molding is one method that can produce a large number of microneedles. Japan Patent Application No. JP2008079915 A, “Needle-like body, and manufacturing method thereof’ describes the manufacturing method of a needle-like body or microneedle by focusing light through a mask having an open part with microlens to a positive photoresist coated on a substrate. The exposed positive photoresist will be removed by the photoresist developer to form a microneedle-shaped mold. Resin is cast into this mold to form a microneedle which can then be removed from the mold. Similarly, Japan Patent Application No. JP2008125864 A, “Manufacturing method of needle-like body” describes the process of manufacturing a microneedle by focusing light through a mask having an open part with microlens to a transparent substrate coated with a negative photoresist film. The exposed negative photoresist will be polymerized to form a microneedle which is used as a prototype or a master of the transfer processing molding.

However, both Japanese patent applications have photosensitive films coated on substrates, such as using a spin-coating or other film coatings, which increase the number of steps and loss a photoresist during the manufacturing process. Thai Petty Patent Application No. 1803001510, “Microneedle preparation method” describes the process of producing microneedles by irradiating light through lenses to a photopolymer which hardens to be a microneedle array. Although the said Thai petty patent has reduced the number of process steps and minimized the loss of photopolymer during the manufacturing process when compared to the two Japanese patent applications above, it has not demonstrated the manufacturing of high- density microneedles which may affect the performance and usability of microneedles. It is the origin of this invention that helps to solve such problems.

The manufacturing process for making microneedles by exposing a photopolymer with light through lenses based on Thai Petty Patent Application No. 1803001510 results in a microneedle array in which the microneedle bases connect to each other on the polymerized film resulted from the same polymerized photopolymer. To separate the microneedle bases from each other, a mask with open areas is used and placed between lenses and the photopolymer to polymerize the photopolymer to be individual cone-shaped microneedles. Due to diffraction and reflection or scattering of UV or visible light, the polymerized microneedles have open-area-shape-like films under the microneedle bases which may be much larger than the needle base diameter causing each microneedle to be far from each other.

SUMMARY OF THE INVENTION

One objective of this invention is the development of the manufacturing process for microneedles, which microneedles on a substrate sheet are dense.

The manufacturing process of high density microneedles comprising the step of: providing a container which contains a photopolymer; providing a substrate sheet made of transparent or translucent material which is placed in contact with a part of the photopolymer; providing a lens panel containing at least one convex lens with a half-spherical shape upside- down above a mask; providing a mask consisting of an opaque area and an open area with one or more geometric shapes for ultraviolet (UV) or visible light to pass through in which the number of open areas is at least equal to a number of lenses; radiating UV or visible light through the lens panel, the mask, and the substrate sheet , respectively, to the photopolymer which will be polymerized on the substrate sheet as a microneedle from UV or visible light focusing via the convex lens and as an open-area-shape-like film from the diffraction and reflection of UV or visible light; and finally moving the substrate sheet with microneedles away from the photopolymer. Characterized in that the step radiating UV or visible light consisting of the step controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask to be in the range of 1-5, the exposure time of UV or visible light to be in the range of 0.1-10 seconds, as well as the mask thickness. The thickness of the mask may be in the range of 100 micrometers to 5 millimeters.

In one aspect, the lens diameter is 2.4 mm; the step controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask is controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask to be equal to 3; the step controlling the exposure time of UV or visible light is controlling the exposure time of UV or visible light to be 0.5 seconds; and the step controlling the mask thickness is controlling the mask thickness to be 2 millimeters.

In another aspect, the lens diameter is 3 mm; the step controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask is controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask to be equal to 1.5; the step controlling the exposure time of UV or visible light is controlling the exposure time of UV or visible light to be 0.5 seconds; and the step controlling the mask thickness is controlling the mask thickness to be 2 millimeters.

In another aspect, the lens diameter is 3.6 mm; the step controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask is controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask to be equal to 3; the step controlling the exposure time of UV or visible light is controlling the exposure time of UV or visible light to be 0.5 seconds; and the step controlling the mask thickness is controlling the mask thickness to be 2 millimeters.

In another aspect, the substrate sheet is selected from the group of a transparent plastic sheet, translucent plastic sheet, transparent fabric sheet, translucent fabric sheet, transparent non-woven sheet, translucent non-woven sheet, transparent paper, translucent paper, transparent polymer sheet, translucent polymer sheet, transparent glass sheet, translucent glass, transparent quartz sheet, translucent quartz sheet, transparent metal sheet, translucent metal sheet, transparent ceramic sheet, translucent ceramic sheet, transparent membrane sheet, translucent membrane sheet, transparent hybrid material sheet, and translucent hybrid material sheet.

In another aspect, the photopolymer is UV sensitive resin.

Microneedles produced from the manufacturing process above, wherein the microneedle height is in the range of 10 micrometers to 10 millimeters.

The manufacturing process of a microneedle(s) consists of UV or visible light exposure (220) through the lens panel (200), the mask (500), the substrate sheet (400) to the photopolymer (100), respectively, to polymerize the photopolymer (100) to be a microneedle(s) (300) on the substrate sheet (400); moving the substrate sheet (400) with the microneedle(s) (300) from the photopolymer (100); and cleaning the microneedle(s) (300). This invention aims to find the optimal variable values to produce high density microneedles (300) which reduces the process time, the steps, and the loss of photopolymer (100) in the manufacturing process.

Various purposes, unique characteristics, and other aspects of this invention will be more evident when they are considered together with the attached drawing and the details of the invention in the best form which will be further described.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: The schematic process diagram of producing microneedles according to this invention. FIG. 2: Examples of microneedles: (a) microneedles with the diameter of the open-area-shapelike films which are much larger than the conical base diameter of microneedles and (b) microneedles with the diameter of the open-area-shape-like films which are about the same as the conical base diameter of microneedles.

FIG. 3: The enlarged schematic showing the lens diameter and the open area diameter. DESCRIPTION OF THE PREFERRED EMBODIMENTS

The description of this invention is made by giving an example of the invention and referring to it by a drawing as an example to make it clearer. The same pieces in the drawing are represented by the same reference numbers, without limitation in any way. The scope of the invention will be in accordance with the attached claims.

This invention controls the ratio of lens diameter to the open area on the mask, exposure time, and mask thickness which control diffraction and reflection of UV or visible light and affect the size of the base diameter of microneedles and the diameter of the open-area-shape- like films under the microneedle bases. This invention can control the diameter of the open- area-shape-like films to be about the same as the base diameter of microneedles, resulting in controlling the density of microneedles.

The density of microneedles may affect the performance and usability of microneedles. For example, in drug delivery, it is desirable to be able to flexibly change the specifications such as the density of microneedles according to the amount and type of drug. In sensing applications, increasing the density of the microneedles that serve as the electrodes increases sensing areas, electrical signals, and maybe sensitivity.

The manufacturing process of high density microneedles in accordance with this invention consists of the following steps providing a container (110) which contains a photopolymer (100); providing a substrate sheet (400) made of transparent or translucent material which is placed in contact with a part of the photopolymer (100); providing a lens panel (200) containing at least one lens which is a convex lens with a half-spherical shape, placed upside-down above the mask (500); providing a mask (500) consisting of an opaque area and an open area with one or more geometric shapes for ultraviolet (UV) or visible light to pass through which a number of open areas is at least equal to a number of lenses; radiating UV or visible light through the lens panel, the mask (500), the substrate sheet (400), respectively, to the photopolymer (100) which will be polymerized on the substrate sheet (400) as a microneedle from UV or visible light focusing via the convex lens and as an open-area-shape-like film from the diffraction and reflection of UV or visible light; moving the substrate sheet (400) with microneedles away from the photopolymer (100). Characteristics in that the step radiating UV or visible light consisting of the step controlling the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500) to be in the range of 1-5; controlling the exposure time of UV or visible light to be in the range of 0.1-10 seconds; and controlling the mask (500) thickness as specified.

In another embodiment, wherein the geometric shape is selected from a circle, an ellipse, and a polygon. And the maximum cord length is the diameter of a circle or the longest diameter (major axis) of an ellipse or the maximum side length of a polygon.

In another embodiment, wherein the mask (500) thickness is in the range of 100 micrometers to 5 millimeters. The photopolymer (100) is selected from the group consisting of ultraviolet (UV) sensitive resin and visible sensitive resin and the photopolymer (100) is ultraviolet (UV) sensitive resin.

In another embodiment, the substrate sheet (400) is selected from the group of a transparent plastic sheet, translucent plastic sheet, transparent fabric sheet, translucent fabric sheet, transparent non-woven sheet, translucent non-woven sheet, transparent paper, translucent paper, transparent polymer sheet, translucent polymer sheet, transparent glass sheet, translucent glass, transparent quartz sheet, translucent quartz sheet, transparent metal sheet, translucent metal sheet, transparent ceramic sheet, translucent ceramic sheet, transparent membrane sheet, translucent membrane sheet, transparent hybrid material sheet, and translucent hybrid material sheet.

Microneedles produced from this manufacturing process maintain heights in the range of 10 micrometers to 10 millimeters.

The manufacturing process of high density microneedles in accordance with this invention consists of a photopolymer (100) in a container (110); a substrate sheet (400) which is made of transparent or translucent material; a lens panel (200) made of transparent material which has at least one lens (210) for focusing UV or visible light (220) to the photopolymer (100) ;a mask (500) which has an opaque area and an open area for UV or visible light to pass through; controlling the ratio of lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500); UV or visible light exposure (220) through the lens panel (200), the mask (500), the substrate sheet (400) to the photopolymer (100), respectively, to polymerize the photopolymer (100) to be a microneedle(s) (300) on the substrate (400); moving the substrate sheet (400) with the microneedle(s) (300) from the photopolymer (100); and cleaning the microneedle(s) (300) to remove the remaining photopolymer from the microneedle(s) (300) Examples of the microneedle manufacturing process based on this invention.

The process of producing microneedles according to this invention, as shown in Fig. 1, starts by placing a substrate sheet (400), such as a transparent plastic sheet with a size of 100 micrometers, in contact with a photopolymer (100) such as the visible sensitive resin and an ultraviolet (UV)-sensitive resin which is named NextDent SG, in the container (110). The UV- sensitive resin, NextDent SG, is commercially available on the market and consists of methacrylic oligomers (more than 90% w/w) and phosphine oxides (less than 3% w/w). A mask (500) which has a thickness of 2 millimeters is then placed on the substrate sheet (400). Thereafter, a lens panel (200) which has the convex half-spherical lens (210), such as with the diameter of 2.4, 3, 3.6 millimeters is placed on the mask (500). The mask (500) has the same amount of an open area as the number of lenses (210) on the lens panel (200) for UV or visible light passing each lens (210). The open area on the mask (500) is a circle which has the diameter such as 1/3, 2/3, 3/3 of the lens diameter. After that, UV or visible light (220) is open to the lens panel (200) with an exposure system, such as the UV exposure system, Brand Ushio Model ML-501 D/B, with the UV intensity of about 43.8 mill watts per square centimeter for the set period of time, such as 0.5, 1.0, 1.5 or 2.0 seconds. The substrate sheet (400) with the microneedles (300) which is polymerized from the photopolymer (100) is subsequently removed, cleaned with ethyl alcohol and water, and dried with compressed air. As shown in Figure 2, the microneedle has a conical shape on an open-area-shape-like film. Conical microneedles are formed by the polymerization of the photopolymer (100) according to the focus of UV or visible light (220) of the convex lens to come together at the focal point. The open-area-shape-like film is caused by the polymerization of the photopolymer (100) according to diffraction or reflection of UV or visible light (220) passing through the open area on the mask (500) to the photopolymer (100). If the conical base size of the microneedles is the same, as shown in Fig. 2(a), the conical bases of the two micrometers needles cannot be adjacent (lower density) because the open-area-shape-like film is larger than the conical base of the microneedle. Compared to the microneedles in Fig. 2(b), the conical bases of the two microneedles are closer to each other (higher density) because the conical base size of the microneedles is almost the same as the size of an open-area-shape-like film - in other words, the ratio of the base size of the conical microneedle to the size of the open-area-shape-like film is close to 1.0.

For a 2.4 millimeter-diameter lens, the variables causing the maximum ratio of the base size of the conical microneedles to the size of the open-area-shape-like film which is equal to 0.7 are the exposure time of 0.5 seconds and the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500) is equal to 3. Fig. 3 shows the enlarged schematic of the lens diameter and the maximum cord length of the equivalent circle of the open area. For the 2.4 millimeter-diameter lens, the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area of 3. For a 3 millimeter- diameter lens, the variables causing the maximum ratio of the base size of the conical microneedles to the size of the open-area-shape-like film which is equal to 0.9 are the exposure time of 0.5 seconds and the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500) is equal to 1.5. For a 3.6 millimeter- diameter lens, the variables causing the maximum ratio of the base size of the conical microneedles to the size of the open-area-shape-like film which is equal to 0.8 are the exposure time of 0.5 seconds and the ratio of the lens diameter to the maximum cord length of the equivalent circle of the open area on the mask (500) is equal to 3.

Although this invention has been fully described by using the attached drawing and figures as an example, it is understandable that modifications or various edits by people with general expertise in the arts and related sciences still within the scope and objectives of the invention may be done. The scope of this invention is in accordance with the characteristics of the invention specified in the attached claims including the nature of the invention which is not specified in the specific claims, but it is something that has a useful function and produces results similar to the nature of the invention specified in the claim as well.