KR200479627Y1 - Patch with micro-needles - Google Patents

Abstract

The present invention relates to a micro needle patch for medical or cosmetic purposes. A microneedle patch according to one embodiment of the present invention includes a porous flexible liner including a plurality of perforations; And a microneedle layer including a common base portion to be in contact with the porous flexible liner, and microneedles arranged integrally with the common base portion.

Description

Patch with micro-needles < RTI ID = 0.0 >

The present invention relates to patches for pharmaceutical, medical or cosmetic purposes, and more particularly to micro needle patches.

As a method for effective drug delivery of medicines applied to the human body, a method of injecting medicines in liquid form through subcutaneous injection needles is widely applied. However, the subcutaneous injection needle having a diameter of about several millimeters has a problem of requiring a high degree of skill in order to stimulate a large number of nodules present in the skin to give pain to the patient.

Recently, a transdermal drug delivery method using a microneedle device having a diameter and a height of several tens or several hundreds of micrometers has been actively studied to overcome the disadvantages of the subcutaneous injection needle. The microneedle device forms a number of microchannels at one time through the stratum corneum layer of the skin, which is the main barrier layer of transdermal drug delivery by the microneedles. Through the microchannels, a sufficient amount of drug can reach the epidermis layer or the dermis layer, after which the drug is absorbed through the blood vessels and lymph nodes and enters the circulatory system of the human body.

As another application, the micro needles are also used for cosmetic purposes. For example, after applying the physiologically active substance on the skin or on the micro needle, micro-channels are formed in the skin by the micro-needles and transdermal delivery is performed. As another example, there may be a method in which a physiologically active substance for cosmetics is contained in the micro needles, and the physiologically active substance is supplied into the skin or the circulatory system of the human body at the same time as the micro needles are injected into the skin.

The transdermal delivery method of the active material using the above-described microneedles is useful. However, in order to apply the transdermal delivery method, a patch type micro needle device in which a conventional complicated structure of a micro needle device is simplified is preferable. In this case, a microneedle patch of a structure having a process consistency capable of improving the yield in consideration of the manufacturing process of the micro-needles is required.

Korean Patent Publication No. 2002-0081024 (June 25, 2004) Korean Patent Publication No. 2000-0055654 (Jun. 15, 2001)

The technical problem to be solved by the present invention is to provide a micro needle patch which is easy to use, is susceptible to the moisture of the outside air, and can manufacture micro needles with low mechanical strength in high yield.

According to an aspect of the present invention, there is provided a micro needle patch comprising: a porous flexible liner including a plurality of through portions; And a microneedle layer including a common base portion that is in contact with the porous flexible liner, and microneedles that are integrally arranged in the common base portion.

The microneedles may comprise a biocompatible material. A pharmaceutically, medical or cosmetic effective substance may be dispersed or chemically bonded to the biocompatible material, or the effective material may be coated on the surface of the micro-needles.

In one embodiment, the biocompatible material is selected from the group consisting of chitosan, collagen, gelatin, hyaluronic acid (HA), alginic acid, pectin, carrageenan, chondroitin (sulfate), dextran ), A polylysine, a carboxymethyltin, a fibrin, an agarose, a pullulan, and a cellulose; Polyvinylpyrrolidone (PVP); (PEG), polyvinyl alcohol (PVA), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropylmethyl cellulose (HPMC), sodium carboxymethyl cellulose, polyalcohol, Lactose, lactulose, fructose, turanose, melitose, melitose, dextran, sorbitol, xylitol, palatinite, starch, lactose, starch, A biocompatible material that is at least one of polylactic acid, polyglycolic acid, polyethylene oxide, polyacrylic acid, polyacrylamide, polymethacrylic acid, and poly maleic acid; Derivatives of the foregoing substances; Or mixtures thereof.

The area ratio (through-hole area / closed area) of the plurality of through-holes and the confinement portions between the plurality of through-holes is in a range of 1% to 80%. The plurality of through portions may have a pattern that is circular, elliptical, polygonal or slit, or a combination thereof.

The porous flexible liner may be made of one or more materials selected from the group consisting of polyethylene, polypropylene, polyvinyl chloride, PET, nylon, epoxy, polyimide, polyester, urethane, acrylic, polycarbonate, urea, melanin, chlorinated rubber, polyvinyl alcohol, (PVDF-co-HFP), polyvinylidene fluoride (PVDF), polyacrylonitrile, polymethylmethacrylate, polytetrafluoroethylene polytetrafluoroethylene (PTFE), styrenebutadiene rubber (SBR), or ethylene-propylene-diene copolymer (EPDM). In addition, the porous flexible liner may have optical transparency in the range of 30% to 99%. The thickness of the porous flexible liner may be in the range of 0.01 mm to 1.5 mm.

In one embodiment, the common base portion may be bonded to the porous flexible liner via physical adsorption or adhesion, chemical adsorption or adhesion, or hydrogen bonding.

According to the embodiment of the present invention, by forming an array of micro needles using a biocompatible material, it is possible to prevent side effects due to breaking at the time of skin folding and to act as an effective active ingredient, thereby achieving a medical or cosmetic effect , The material weakness of the water resistance, the chemical resistance and the low strength of the biocompatible material is protected by protecting the micro needles at the time of manufacturing or after manufacture by using porous flexible liners having a plurality of penetrations, It is possible to provide a micro needle patch capable of manufacturing a microneedle patch with high yield and a large area by reinforcing the moisture or mechanical strength of the outside air easily.

1 is a plan view of a porous flexible liner of a micro needle patch according to one embodiment of the present invention.
FIGS. 2A and 2B are a perspective view and a cross-sectional view showing a microneedle patch according to an embodiment of the present invention, and FIG. 2C is a cross-sectional view showing a manufactured microneedle patch according to an embodiment of the present invention.
3A and 3B are a perspective view and a cross-sectional view showing a micro needle patch according to another embodiment of the present invention, respectively.
FIGS. 4A and 4B illustrate a mold for explaining a method of manufacturing a micro needle patch according to an embodiment of the present invention, and a laminate in a manufacturing process.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.

Embodiments of the present invention are provided to more fully illustrate the present invention to those skilled in the art, and the following embodiments may be modified in various ways, It is not limited to the embodiment. Rather, these embodiments are provided so that this disclosure will be more thorough and complete, and will fully convey the concept of the invention to those skilled in the art.

In the following drawings, thickness and size of each layer are exaggerated for convenience and clarity of description, and the same reference numerals denote the same elements in the drawings. As used herein, the term "and / or" includes any and all combinations of any of the listed items.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the inventive concept. As used herein, the singular forms "a," "an," and "the" include singular forms unless the context clearly dictates otherwise. Also, " comprise "and / or" comprising "when used herein should be interpreted as specifying the presence of stated shapes, numbers, steps, operations, elements, elements, and / And does not preclude the presence or addition of one or more other features, integers, operations, elements, elements, and / or groups.

Although the terms first, second, etc. are used herein to describe various elements, components, regions, layers and / or portions, these members, components, regions, layers and / It is obvious that no. These terms are only used to distinguish one member, component, region, layer or section from another region, layer or section. Thus, a first member, component, region, layer or section described below may refer to a second member, component, region, layer or section without departing from the teachings of the present disclosure.

1 is a plan view of a porous flexible liner 10 of a micro needle patch according to one embodiment of the present invention.

Referring to FIG. 1, the porous flexible liner 10 is a planar body having a predetermined thickness, and includes a plurality of through portions 10H penetrating the planar body through the front surface and the back surface. The thickness of the porous flexible liner 10 may have a size within a range of 0.01 mm to 1.5 mm for securing flexibility. The plurality of through portions 10H may be a circular through hole as shown in Fig. 1, but this is merely an example, and the present invention is not limited thereto. For example, the plurality of through portions 10H may have a polygonal shape or an elliptical shape such as a triangular shape or a square shape. In some embodiments, the plurality of perforations 10H may have a straight line in the form of a slit, a meander pattern, or a wave pattern and a linear structure, or a composite pattern in which these patterns intersect each other.

The area ratio or the opening ratio (perforation area / (closed area + perforation area)) of the penetrating parts and the closing parts of the porous flexible liner may be in the range of 1% to 80%. If the opening ratio is less than 1%, it is difficult to discharge water or other solvent vapor generated in the drying process in the process of forming micro needles as described later. If the opening ratio exceeds 80%, the porous flexible liner 10 It is difficult to secure a binding force with the base of the micro-needles to be described later, and it is difficult to secure a sufficient supporting force for the skin of the micro-needles.

In one embodiment, when the plurality of through portions 10H have the shape of a through hole as in Fig. 1, the size 10R of the through hole may be in a range of 0.01 mm to 1 mm. When the plurality of penetrating portions 10H have a slit shape, the width of the slit may be in the range of 0.01 mm to 1 mm. The interval 10D between the plurality of through portions 10H may be in the range of 0.1 mm to 2 mm. By the interval 10D, the closed portion 10S of the porous flexible liner 10 can be defined.

The closure 10S serves as a barrier to chemical or moisture in the subsequent process during the production of chemically and mechanically weak micro-needles and, in actual use of the patch after fabrication, the stiffener, which enhances the mechanical strength of the patch, And functions as a protective layer for protecting the micro needle layer. In some embodiments, the porous flexible liner 10 may be antimicrobially treated or may include antimicrobial agents on the surface of the porous flexible liner 10 to prevent contamination by bacteria of the microneedles and the common base, which will be described later.

The porous flexible liner 10 may be a film or sheet structure formed of a resin-based material. Wherein the resin material is selected from the group consisting of polyethylene, polypropylene, polyvinyl chloride resin, polyethylene terephthalate, nylon, epoxy, polyimide, polyester, urethane, acrylic, polycarbonate, urea, melanin, chlorinated rubber, polyvinyl alcohol, polyvinyl ester , Vinylidene fluoride-hexafluoropropylene copolymer (PVDF-co-HFP), polyvinylidenefluoride (PVDF), polyacrylonitrile, polymethylmethacrylate, Based materials such as polytetrafluoroethylene (PTFE), styrenebutadiene rubber (SBR), or ethylene-propylene-diene copolymer (EPDM), which are only illustrative, But the present invention is not limited thereto, and other curable or plastic resin-based materials may be applied. Preferably, the resin-based material may have optical transparency having transmittance to infrared light or ultraviolet light for the transfer of energy such as thermal energy or ultraviolet light in the manufacturing process of micro needles. The optical transparency is not limited to a transmittance of 99% or more, but it is sufficient that the optical transparency is within a range of 30% to 99%. The transparent resin material may include, for example, epoxy, polyimide, unsaturated polyester, urethane, acrylic, polycarbonate, urea, melanin, chlorinated rubber, polyvinyl alcohol, polyvinyl ester or a mixture thereof.

In one embodiment, the porous flexible liner 10 may be coated with a metal layer as a moisture-proof layer. The metal layer may be, for example, aluminum, gold, silver, copper, titanium or manganese, and these materials may be coated by a wet process in the manner of physical vapor deposition such as sputtering or electroless plating.

2A and 2B are a perspective view and a cross-sectional view respectively showing a microneedle patch 100 according to an embodiment of the present invention, and Fig. 2C is a cross-sectional view showing a manufactured microneedle patch 200 according to an embodiment of the present invention Fig.

2A, the micro needle patch 100 includes a micro needle layer 20 on the porous flexible liner 10 and the porous flexible liner 10 described above. The micro needle layer 20 includes a common base portion 20B and a plurality of micro needles 20N arranged in a common base portion 20B in contact with the porous flexible liner 10.

The common base portion 20B may be bonded onto the porous flexible liner 10 via physical adsorption or adhesion, chemical adsorption or adhesion, or hydrogen bonding, and preferably these bonds may be achieved through a low temperature process . The structure of the integrated common base portion 20B and the micro needles 20N can be obtained through a casting process using the same material as described later. The height of the microneedles 20N may be in a range of 50 mu m to 1,500 mu m as a non-limiting example, and the diameter of the base of the microneedles 20N may be in a range of 10 mu m to 1,000 mu m.

The material for the formation of the micro needle layer 20 may include a biocompatible material capable of minimizing human side effects upon the entry of the micro needles 20N and capable of effective drug delivery. The biocompatible material may be, for example, chitosan, collagen, gelatin, hyaluronic acid (HA), alginic acid, pectin, carrageenan, chondroitin (sulfate), dextran (sulfate) A biologically-derived soluble substance, which is at least one of polyol, polylysine, carboxymethyltin, fibrin, agarose, pullulan, and cellulose; Polyvinylpyrrolidone (PVP); (PEG), polyvinyl alcohol (PVA), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropylmethyl cellulose (HPMC), sodium carboxymethyl cellulose, polyalcohol, Lactose, lactulose, fructose, turanose, melitose, melitose, dextran, sorbitol, xylitol, palatinite, starch, lactose, starch, A biocompatible material that is at least one of polylactic acid, polyglycolic acid, polyethylene oxide, polyacrylic acid, polyacrylamide, polymethacrylic acid, and poly maleic acid; Derivatives of the foregoing substances; Or a mixture thereof. Preferably, the micro needle layer 20 comprises biocompatible materials such as chitosan, collagen, gelatin, hyaluronic acid (HA), alginic acid, pectin, carrageenan , Chondroitin (sulfate), dextran (sulfate), polylysine, carboxymethyltin, fibrin, agarose, pullulan and cellulose. The materials described above are exemplary, and the biocompatible material may be other bio-soluble polymers.

The above-mentioned materials may have pharmaceutical, medical or cosmetic effects on the human body as a whole. However, additional physiologically active substances may be mixed with the above-mentioned materials and dispersed in the micro needles for the purpose of promoting their efficacy, May be coated on the surface of the microneedles formed with < RTI ID = 0.0 > For example, there may be mentioned, without limitation, materials such as proteins, peptides, genes, antibodies, anesthetics, insulin, vaccines, polysaccharides, synthetic organic compounds, synthetic inorganic compounds or whitening, Component, and may be any other active substance that is pharmaceutically, medical or cosmetically acceptable

Although the above-mentioned biocompatible materials are substantially solid, they are capable of being decomposed or melted by moisture in raw beans, and are not easily dried during manufacture or are vulnerable to rapid deterioration of shape and / or components when they are exposed to moisture during actual use Respectively. According to embodiments of the present invention, in order to minimize the drying time during manufacture and to prevent the micro needle layer 20 of biocompatible materials from degrading from moisture after manufacture, A porous flexible liner 10 is provided and through the plurality of perforations 10H of the porous flexible liner 10 the cooling and / or drying through rapid drainage of water, as indicated by arrow A in Figure 2b, And after the manufacturing, the outside air exposure of the common base portion 20B is reduced and eliminated by the confinement portion 10S. The porous flexible liner 10 also enhances the strength of the micro needle layer 20 and improves dimensional stability such as prevention of warping in the molding step during the manufacturing process, There is an advantage of improving the productivity.

The microneedle patch 100A is cut and formed into any size and shape that can be stably attached to the application site, such as under the eyes, on the upper part, arms, shoulders, abdomen, etc., An adhesive layer 30a may be provided so as to be retained. For example, the microneedle patch 100B may be cut to have an appropriate size and shape with the microneedle patch 100A of FIG. 2A as a raw fabric, and then the microneedle patch 100B may be extended to extend beyond the edge of the microneedle patch 100 An attachment pad 30 providing an adhesive layer 30a can be manufactured by attaching to the bottom surface of the porous flexible liner 10. [ The attachment pad 30 and the porous flexible liner 10 may be joined together by an adhesive layer disposed therebetween.

3A and 3B are a perspective view and a cross-sectional view showing a micro needle patch 100C according to another embodiment of the present invention, respectively.

3A and 3B, the microneedle patches 100C are formed on the other surface 10b opposite to the one surface 10u of the porous flexible liner 10 to which the common base portion 20a is interposed. And a base layer 20b containing the same material as the base layer 20b.

In one embodiment, by filling the plurality of through portions 10H of the porous flexible liner 10 with the same material as the micro needle layer 20a, the micro needle layer 20a and the ground layer 20b are integrated And a porous flexible liner 10 may be embedded between the micro needle layer 20a and the ground layer 20b. Although not shown, an attachment pad, which provides an attachment surface extending beyond the edge of the micro needle patch 100C for skin attachment, is provided on the bottom surface of the base layer 20b, as described above with reference to Figure 2C, 20b.

FIGS. 4A and 4B illustrate a mold for explaining a method of manufacturing a micro needle patch according to an embodiment of the present invention, and a laminate in a manufacturing process.

Referring to FIG. 4A, the above-described microneedle patch can be manufactured through a molding process using the mold 1. [ The mold 1 comprises an array of recessed cavities MC for molding the microneedles. The mold 1 may be formed of a metal, a ceramic, a glass, a thermoplastic or a thermosetting resin material, and the present invention is not limited thereto.

4B, a solution obtained by dissolving or dispersing the aforementioned biocompatible material or a biodegradable material or a precursor thereof (referred to as a raw material of a microneedle layer; 20 L), which is a material of the microneedle layer, in a suitable solvent The cavity MC of the mold 1 can be filled to overflow. In another embodiment, the raw material 20L may be filled in the cavity MC of the mold 1 in powder, molten, or gel form.

After the raw material 20L is filled in the cavity MC of the mold 10 to overflow, the porous flexible liner 10 is laminated. In some embodiments, depending on the chemical or physical properties of the raw material 20L, for example, if the raw material 20L is in a powder form, the melting step may be performed by heating before the porous flexible liner 10 is laminated have. In addition, when the porous flexible liner 10 is laminated, a certain pressure may be applied to the porous flexible liner 10. In some embodiments, the raw material 20L may be further applied on the porous flexible liner 10 for the manufacture of the micro needle patch 100C described with reference to Fig. 3A.

After the porous flexible liner 10 is laminated, the microneedle layer 20 is solidified through cooling and / or reduced pressure, freezing, or a heat drying process at a temperature within the range of 50 to 100 ° C. Micro-needles using biodegradable materials are fast enough to have sufficient strength for skin entrapment and, if necessary, to maintain mechanical strength for a period of time for drug delivery and to be degraded. This rapid drying is also important in terms of productivity. According to an embodiment of the present invention, vapor or heat release of the organic solvent, such as water or alcohol, as indicated by arrow A during the drying or cooling process through the plurality of through portions 10H of the porous flexible liner 10 By doing so quickly, robust microneedles can be formed in the cavity. If drying is carried out usually within 0.1 to 2 hours, solid and shaped micro needles are obtained, but if it exceeds 2 hours, the yield may be reduced due to deterioration or alteration of the raw material.

After the sufficient cooling or drying step, separating the porous flexible liner 10 from the mold 1, as indicated by arrow B, causes the micro needle layer 20L, coupled to the porous flexible liner 10, . In the absence of the porous flexible liner 10, the microneedle layer 20L can be cracked or decomposed when the microneedle layer 20L is separated from the mold 1. However, according to the embodiment of the present invention, the porous flexible liner 10 reinforces the micro needle layer 20L to ensure a stable separation process of the micro needle layer 20L from the mold 1, ) Can be formed.

Experimental Example

Table 1 below shows the drying time, yield, and maximum molding area measured in the manufacturing process of the micro needle patch with the porous flexible liner according to the embodiment of the present invention. In Examples 1 and 2, a solution obtained by dissolving hyaluronic acid, a biocompatible material, in a concentration of 30% in distilled water was filled in a mold, a porous flexible liner was laminated thereon, and a drying process was performed at 50 ° C. Thereafter, the dry micro needle layer is separated from the mold to prepare a micro needle patch. In Example 1, the diameter of the circular penetration portion of the porous flexible liner is 10 mu m and the gap is 1 mm. In Embodiment 2, the diameter of the circular penetration portion of the porous flexible liner is 100 mu m, and the gap is 1 mm. The comparative example is a measurement result in the case where a micro needle patch was manufactured in the same manner as in Examples 1 and 2, and a porous flexible liner was not applied. The drying time was the time required until the moisture content became less than 5%, and the yields obtained at this time and the maximum available forming area of the microneedle patch were measured.

Experimental Example Drying time Twist yield
(150 cm ² ) Molding form Example 1 15 min none 100%

Example 2 12 min none 100%

Comparative Example 10 min Very severe 50%

Referring to Table 1, it can be seen that when the porous flexible liner is applied according to Examples 1 and 2 of the present invention, there is no substantial increase in drying time by the penetration portions, And a large area molding process was achieved by achieving a yield of 100% at a production area of 150 cm ² for a micro needle using a bio-derived soluble material susceptible to moisture. The above-mentioned embodiments relate to hyaluronic acid, which is a biologically-derived soluble polymeric material, but, by way of example, other biocompatible materials which are vulnerable to moisture or chemicals exhibit the same behavior and advantages by porous flexible liners.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the inventions. Will be clear to those who have knowledge of.

Claims (12)

A porous flexible liner including a plurality of through portions and a closing portion corresponding to an area other than the plurality of through portions; And
And a micro needle layer comprising a common base portion that is in contact with the plurality of through portions of the porous flexible liner and the closing portion, and microneedles integrally arranged in the common base portion. The method according to claim 1,
Wherein the micro-needles comprise a biocompatible material. 3. The method of claim 2,
A microneedle patch in which a pharmaceutical, medical or cosmetic effective substance is dispersed or chemically bonded in the biocompatible material or the effective material is coated on the surface of the micro-needles. 3. The method of claim 2,
The biocompatible material may be selected from the group consisting of chitosan, collagen, gelatin, hyaluronic acid (HA), alginic acid, pectin, carrageenan, chondroitin (sulfate), dextran (sulfate) polylysine, carboxymethyltin, fibrin, agarose, pullulan, and cellulose; Polyvinylpyrrolidone (PVP); (PEG), polyvinyl alcohol (PVA), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropylmethyl cellulose (HPMC), sodium carboxymethyl cellulose, polyalcohol, Lactose, lactulose, fructose, turanose, melitose, melitose, dextran, sorbitol, xylitol, palatinite, starch, lactose, starch, A biocompatible material that is at least one of polylactic acid, polyglycolic acid, polyethylene oxide, polyacrylic acid, polyacrylamide, polymethacrylic acid, and poly maleic acid; Derivatives of the foregoing substances; Or a mixture thereof. The method according to claim 1,
And the area ratio of the plurality of penetrating portions and the closing portion (through-hole area / closed area) is in a range of 1% to 80%. The method according to claim 1,
Wherein the plurality of penetrations have a pattern of circular, elliptical, polygonal or slit or a combination thereof. The method according to claim 1,
The porous flexible liner may be made of one or more materials selected from the group consisting of polyethylene, polypropylene, polyvinyl chloride, PET, nylon, epoxy, polyimide, polyester, urethane, acrylic, polycarbonate, urea, melanin, chlorinated rubber, polyvinyl alcohol, (PVDF-co-HFP), polyvinylidene fluoride (PVDF), polyacrylonitrile, polymethylmethacrylate, polytetrafluoroethylene a microneedle patch comprising polytetrafluoroethylene (PTFE), styrenebutadiene rubber (SBR), or ethylene-propylene-diene copolymer (EPDM). The method according to claim 1,
Wherein the porous flexible liner has optical clarity in the range of 30% to 99%. The method according to claim 1,
Wherein the thickness of the porous flexible liner is in the range of 0.01 mm to 1.5 mm. The method according to claim 1,
Wherein the common base portion is bonded to the porous flexible liner via physical adsorption, adhesion, chemical adsorption or adhesion, or hydrogen bonding. The method according to claim 1,
Further comprising a ground layer interposed on the other surface opposite to one surface of the porous flexible liner to which the common base portion is interposed and includes the same material as the common base portion. 12. The method of claim 11,
And the plurality of penetration portions of the porous flexible liner are filled with the same material as the micro needle layer, whereby the micro needle layer and the base layer are integrated.

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