WO2012144718A1

WO2012144718A1 - Tiered microneedle device

Info

Publication number: WO2012144718A1
Application number: PCT/KR2011/009586
Authority: WO
Inventors: Boo Joon Sul; Man Hee Han
Original assignee: Miti Systems Inc.
Priority date: 2011-04-21
Filing date: 2011-12-13
Publication date: 2012-10-26
Also published as: KR20120119250A

Abstract

Disclosed therein is a microneedle device, which includes a needle part adapted to penetrate the skin when the device is applied to the skin and a board part connected to the base of the needle part to support the needle part, wherein the needle part includes a tiered face formed in a direction of a peaked portion of the needle part in such a way as to directly push medicine into the skin when microneedles are applied to the skin, on which the active ingredients are applied.

Description

TIERED MICRONEEDLE DEVICE

The present invention relates to a microneedle device which can make the skin effectively absorb active ingredients, such as skin care ingredients or medicine, or transfer the active ingredients into the body through the skin, and more particularly, to a microneedle device of a distinctive structure that increases a transfer efficiency of active ingredients after applying to the skin.

Methods of applying active ingredients, such as skin care ingredients or medicine, to the skin or putting a pack or a patch, which contains the active ingredients, on the skin to deliver the active ingredients into the body have several advantages in that they can deliver the active ingredients continuously, do not cause pain, and are easy to use. However, the methods have a problem in that an absorption rate of active ingredients in the body is very low because the stratum corneum of a thickness ranging from 10㎛ to 60㎛, which is the outermost layer of the skin, prevents that foreign materials pass through the body. Particularly, in case of active ingredients with great hydrophile property or molecular weight, the absorption rate of the active ingredients in the body gets still lower.

Accordingly, in order to effectively deliver active ingredients into the body, methods of using an injection to inject them into the body with a needle have been used. However, conventional needles having a diameter in millimeters and a length in centimeters stimulate a plurality of pain spots on the skin, and hence, cause pains to subjects. Moreover, the injections have a problem in that general persons cannot easily use the injections at home because being generally applied only in hospitals or skincare clinics.

In order to solve the problem, microneedles having a diameter ranging from tens of ㎛ to hundreds of ㎛ and a length ranging from tens of ㎛ to thousands of ㎛ have been developed. Because the microneedles form fine holes in the stratum corneum of the skin, they can make even active ingredients with hydrophile property or great molecular weight be easily absorbed into the skin or deliver into the body through the skin, and increase the skin absorption rate or transfer rate of ingredients, which are absorbed into the body just by applying to the skin. Furthermore, short microneedles do not cause pain because not perforating to the dermis where nerves are distributed, and long microneedles can considerably reduce pains of the subjects because being small in number of pain spots stimulated as being smaller in diameter and shorter in length than the conventional needles even though perforating to the dermis.

Various methods to make the active ingredients be absorbed into the skin or deliver them into the body through the skin using microneedles have been made, and also, various structures of microneedles appropriate to such methods have been developed. FIGS. 1 to 5 illustrate conceptual views of delivering methods for active ingredients using conventional microneedle devices.

FIG. 1 illustrates a conceptual view of a delivering method of active ingredient in a way of forming fine holes in the stratum corneum of the skin using a microneedle device as disclosed in International Patent Laid-open No. WO02/47555. Such a method has a merit in that it is easy to manufacture, sterilize, and distribute the microneedle device because the microneedle device and active ingredients are separately provided, but has a demerit in that active ingredients are delivered slowly because they are delivered just by diffusion.

FIG. 2 illustrates a conceptual view of a delivering method of active ingredients in a way of previously putting active ingredients on the skin and puncturing the skin with a microneedle device to form fine holes in the stratum corneum of the skin, as disclosed in U.S. Patent No. 5487726. Such a method similar to the method of FIG. 1 has a merit in that it is easy to manufacture, sterilize and distribute the microneedle device, but also has a demerit in that active ingredients are delivered slowly because they are delivered by diffusion. However, compared with the method of FIG. 1, the method of FIG. 2 can deliver active ingredients more rapidly and effectively because a small amount of active ingredients is directly injected into the skin by the microneedles.

FIG. 3 illustrates a conceptual view of another delivering method of active ingredients in a way of coating active ingredients on the surface of microneedles and applying the microneedles as disclosed in U.S. Patent No. 6603998. In order to increase the efficiency of the microneedle devices, the microneedle device may include reservoirs for active ingredients formed on the surface of microneedles as disclosed in U.S. Patent Laid-open No. 2007/0078414. In the meantime, as disclosed in U.S. Patent No. 6132755 and U.S. Patent Laid-open No. 2005/0251088, in the case of microneedles made of a material dissolvable in the skin, active ingredients may be contained in the dissolvable microneedles. Such methods can deliver active ingredients of a relatively fixed amount and are convenient in use, but have a problem in that the quantity of active ingredients to be provided is limited and they require more attention in sterilization and distribution because the microneedles and active ingredients are provided in a package.

As disclosed in U.S. Patent No. 3964482 and Korean Patent No. 682534, FIG. 4 illustrates a conceptual view of another delivering method of active ingredients in a way that active ingredients located at the rear of a microneedle device is delivered into the skin through delivery channels formed in the microneedle device when the microneedle device having the active ingredients at the rear thereof is applied to the skin. The delivery channels generally extend from the rear portion to the front portion of the microneedle device, but may be formed in the front portion as disclosed in U.S. Patent No. 6881203. Such a method has advantages in that a large quantity of active ingredients can be contained in the microneedle device and the active ingredients can be delivered continuously, but has several problems in that it is difficult to manufacture the microneedle device and in that avtive ingredients are delivered slowly.

A microneedle device having a structure to solve the above-mentioned problems and increase the amount of active ingredients directly injected into the skin by microneedles has been developed. As an example, U.S. Patent Laid-open No. 2006/0051404 (See FIG. 5) discloses a microneedle device having a cup-shaped structure to directly inject active ingredients into the skin. The microneedle device has fine cavities of a reverse cup shape that are formed in needle parts and their exits face the front ends of the needles. Accordingly, the microneedle device has several problems in that it is difficult to contain active ingredients in the cavities because positive pressure is applied to the cavities when the microneedles are inserted into the skin. Moreover, it is difficult to obtain good effects because negative pressure is applied to the cavities and the active ingredients injected into the skin escapes from the skin together with the microneedles when the microneedles are separated from the skin. Additionally, the microneedle device has further problems in that the microneedles can be manufactured only by a silicon etching process because it is difficult to form the cup-shaped cavities by a polymer molding that is inexpensive in manufacturing costs and uses biocompatible materials. The silicon etching process is difficult to be commercialized due to a problem of biosafety and high manufacturing costs.

Meanwhile, U.S. Patent Laid-open No. 2003/0181936 discloses a microneedle device having a structure similar to the structure of the microneedle device of FIG. 5, but the microneedle device disclosed in U.S. Patent Laid-open No. 2003/0181936 is unsuitable for the delivering method of FIG. 5 because being proposed for a use purpose to adjust a penetration length of microneedles.

Accordingly, the present invention has been made in an effort to solve the above-mentioned problems occurring in the prior arts, and it is an object of the present invention to provide a microneedle device having a structure that can increase a delivery efficiency of active ingredients while the active ingredients are delivered into the body when microneedles are applied to the skin after putting them on the skin.

To achieve the above objects, the present invention provides a microneedle device, which includes a needle part adapted to penetrate the skin when the device is applied to the skin and a board part connected to the base of the needle part to support the needle part, wherein the needle part includes a tiered face formed in a direction of a peaked portion of the needle part in such a way as to directly push active ingredients into the skin when microneedles are applied to the skin, on which the active ingredients are applied.

The microneedle device may adopt a structure that one needle is formed on one board or a structure that at least two needle parts are connected in lengthwise and/or breadthwise arrays by board parts so that plurality of microneedles are formed on one board.

As described above, the microneedle device according to the present invention can make the skin absorb active ingredients more effectively or effectively transfer the active ingredients into the body through the skin due to the tiered microneedles.

Furthermore, the microneedle device according to the present invention can easily deliver even ingredients of hydrophile property or ingredients with large molecular weight through the skin because it can directly deliver active ingredients utilizing a tiered face to push the medicine and deliver the active ingredients through fine holes formed in the stratum corneum by the microneedles.

Moreover, the tiered microneedle device according to the present invention is convenient in manufacturing due to its simple structure.

In addition, the tiered microneedle device according to the present invention can be mass-produced in a good competitive price because being molded using biocompatible polymer materials.

FIGS. 1 to 4 are conceptual views showing structures and applications of typical microneedle devices according to prior arts.

FIG. 5 is a conceptual view showing a structure and application of a microneedle device having a cup-shaped structure to directly inject medicine into the skin according to a prior art.

FIG. 6 is a view of a tiered microneedle device according to the present invention.

FIG. 7 is a view of a tiered microneedle device according to another preferred embodiment of the present invention.

FIG. 8 is a conceptual view showing a structure and an application of the microneedle device according to the present invention.

Reference will be now made in detail to the preferred embodiments of the present invention with reference to the attached drawings. It should be understood that the example embodiments of the present device are provided to easily describe the technical idea and scope of the present invention, but there is no intent to limit the present invention to the particular forms disclosed, and hence, they do not represent all technical ideas and scopes of the present invention. Accordingly, it should be understood that the example embodiments of the invention are to cover all modifications, equivalents, and alternatives falling within the scope of the invention.

In the present invention, the terms, width of a needle part and thickness of a needle part mean a distance between the outermost points in a horizontal cross section of the needle part that may have various shapes and a distance between outer points that are perpendicular to the above distance, respectively. In the case that the needle part has a zone to keep a width of a fixed value and a thickness of a fixed value, the values become the width and the thickness of the needle part, but in the case that the needle part is tapered without the zone to keep a width of a fixed value and a thickness of a fixed value, the width and the thickness at a half height point of the needle part become the width and the thickness of the needle part. For instance, if the needle part is formed in a conical shape, a width and a thickness are defined as the diameter of the cross section at a half height point of the needle part.

As illustrated in FIGS. 6 and 7, the present invention relates to a microneedle device having a tiered face formed in a direction of a peak. FIG. 6(a) illustrates a microneedle device including a board part and a needle part having a tiered face, and FIGS. 6(b) and 6(c) and 7 illustrate only the needle part for better understanding.

The microneedle device according to the present invention, as illustrated in FIG. 2 or 5, adopts the method that microneedles are applied to the skin to inject active ingredients into the skin after the active ingredients are put on the skin (See FIG. 8).

"Microneedle device 1" itself is well-known in the prior art, and in the present invention, the needle part 10 is a part that penetrates the skin when the device is applied to the skin, and the board part 20 is a part that is not inserted into the skin but supports the needle part and serves to connect needle parts in the case that there are a plurality of needle parts (including arrays).

The needle part 10 generally protrudes from one side of the board part in a perpendicular direction and includes a peaked portion formed in a three-dimensional sharp tip shape to thereby easily penetrate the skin. The needle part may be formed in one of a cone, an elliptical cone, a polypyramid, and other shapes, and hence, the present invention does not limit the shape of the needle part.

The microneedle device according to the present invention includes active ingredients pushing face (tiered face) formed to directly push active ingredients into the skin when the microneedles are applied to the skin.

That is, because the microneedle device 1 according to the present invention includes the tiered face 13 formed in the direction of the peaked portion 12, the tiered face serves to prevent a active ingredients, which are previously coated on the skin, from being pushed out laterally and to help the active ingredients to be pushed into the skin when the microneedle device is applied to the skin.

Because the protruding portions of the microneedles are generally inserted into the skin at the right angles, in order to prevent the active ingredients previously coated on the skin from being pushed out laterally and to help the medicine to be pushed into the skin, it is preferable that the tiered face is located at right angles or at an acute angle to the protruding direction of the needle part. That is, in consideration of an effective delivery of the active ingredients into the skin and easiness in the manufacturing process, it is preferable that the tiered face (medicine pushing face) is formed in such a way as to be at right angles or at an acute angle to a standard axis of the protruding direction of the needle part (See FIG. 6).

Moreover, the tiered face 13 may be formed in a plane, but in order to inject the active ingredients into the skin in a state where the active ingredients are surrounded by the tiered face when the microneedle device is applied to the skin, it is preferable that the tiered face is formed in a concave shape when it is viewed from the base 11 of the needle part. Because that the tiered face is formed in the concave shape when it is viewed from the base of the needle part means that it is formed in a convex shape when it is viewed from the skin, the active ingredients are injected into the skin in the state where the active ingredients are surrounded in the convex space, and hence, the active ingredients can be effectively delivered into the skin. As examples of such a microneedle, as shown in FIG. 7, there are microneedles having a crescent-shaped or multi-stepped portion whose central portion is more furrowed toward the board part than edge portions.

It is preferable that a height (H1) of the needle part 10 is within a range of 0.1mm to 1mm because the needle part may penetrate some part of the stratum corneum 31 or penetrate into the dermis 32 according to use purposes. Meanwhile, a height (H2; depth that active ingredients 33 will be delivered) ranging from the base 11 of the needle part 10 to the tiered face 13 may be varied according to kinds (properties) of active ingredients to be injected and properties of the skin of a subject. Accordingly, it is preferable that a ratio (H2/H1) of the height (H2) ranging from the base 11 of the needle part 10 to the tiered face 13 to the height (H1) of the needle part 10 is within a range of 0.1 to 0.9.

Furthermore, it is preferable that a thickness (T1) of the needle part is within a range of 0.05mm to 0.4mm according to materials because the microneedle device 1 must have strength to resist strength of the skin and penetrate the skin.

In the meantime, it is preferable that a ratio (T2/T1) of a thickness (T2) of the tiered face 13 (active ingredients pushing face) to the thickness (T1) of the needle part 10 is within a range of 1/5 to 3/5 because the three-dimensional tip portion must be thick enough to have sufficient strength and the tiered face 13 must be thick enough to deliver as much active ingredients into the skin as possible.

Additionally, a ratio (H3/T2) of a distance (H3) ranging from the tiered face 13 to the peaked portion 12 of the needle part 10 to the thickness (T2) of the tiered face 13 is 1 to 10, and preferably, 1 to 6. If the ratio (H3/T2) of the distance (H3) ranging from the active ingredients pushing face to the peaked portion 12 of the needle part 10 to the thickness (T2) of the tiered face 13 is less than 1, the active ingredients pushing face does not serve to push the active ingredients but serves to limit a penetration depth of the microneedle device 1. Moreover, if the ratio (H3/T2) is more than 10, a active ingredients injection effect may be deteriorated because the needle part 10 penetrates the skin too thin.

FIG. 8 conceptually illustrates a process that the microneedle device 1 having the tiered structure 13 is applied to the skin. As shown in the drawing, when the microneedle device 1 is applied to the skin after active ingredients are previously put on the skin, the active ingredients 33coated on the skin is pushed into the skin by the tiered face 13 of the microneedle device 1.

Ultimately, the microneedle device according to the present invention must be effectively applied to the skin. In order to maximize the effect of the tiered face 13 of the microneedle device 1, it is preferable that the microneedle device is applied to the skin several times after the active ingredients are put on the skin. For the purpose mentioned above, the microneedle device may consist of a singular needle part, but it is more preferable that the microneedle device consists of a plurality of the needle parts arranged lengthwise and breadthwise on a board.

For instance, the microneedle device according to the present invention may be utilized in forms of a roller type microneedle device disclosed in International Patent Laid-open No. WO02/47555, a stamp type microneedle device disclosed in U.S. Patent No. 5487726, and a cover type microneedle device disclosed in Korean Patent Application No. 2009-4589. Moreover, the microneedle device according to the present invention may be utilized to a patch type microneedle device. In the patch type microneedle device, if it is not in a perfect contact with the skin due to high flexibility of the board part, because the microneedles are inserted into the skin just when the patch type microneedle device is pressed to the skin and go out from the skin by restoring force of the board part when pressure is removed, it is possible to pat the microneedle device to the skin several times after the patch type microneedle device is applied to the skin, and hence, the microneedle device having the tiered face according to the present invention can be utilized to the patch type microneedle device.

Furthermore, according to the present invention, the microneedle device and a liquid material containing active ingredients can be manufactured and used in one set.

Because the microneedle device can be mass-produced using biocompatible materials through the mold fabricating process and the polymer molding process disclosed in Korean Patent Nos. 682534 and 1004014, manufacturing methods of the same will be omitted.

Claims

A microneedle device, comprising a needle part adapted to penetrate the skin when the device is applied to the skin and a board part connected to the base of the needle part to support the needle part,

wherein the needle part includes a tiered face formed on the needle part in a direction of a peaked portion of the needle part.
A microneedle device according to Claim 1, wherein at least two needle parts are connected in lengthwise and/or breadthwise arrays by board parts so that plurality of microneedles are formed on one board.
The microneedle device according to claim 1 or 2, wherein the tiered face is located at right angles or at an acute angle to a direction of a protruding portion of the needle part.
The microneedle device according to claim 1 or 2, wherein the tiered face is formed in a plane, or formed in a concave shape when it is viewed from the base of the needle part.
The microneedle device according to claim 1 or 2, wherein a height (H1) of the needle part is within a range of 0.1mm to 1mm, and a ratio (H2/H1) of the height (H2) ranging from the base of the needle part to the tiered face to the height (H1) of the needle part is within a range of 0.1 to 0.9.
The microneedle device according to claim 1 or 2, wherein a thickness (T1) of the needle part is within a range of 0.05mm to 0.4mm, and a ratio (T2/T1) of a thickness (T2) of the tiered face to the thickness (T1) of the needle part is within a range of 1/5 to 3/5.
The microneedle device according to claim 1 or 2, wherein a ratio (H3/T2) of a distance (H3) ranging from the tiered face to the peaked portion of the needle part to the thickness (T2) of the tiered face is 1 to 10.
A set of microneedle device according to claim 1 or 2 and a liquid material containing active ingredients.