KR20190028267A - Thermosensitive microneedle patch, and method of preparing the same - Google Patents

Abstract

The present invention relates to a micro-needle patch, a kit including the same, and a micro-needle patch manufacturing method. The micro-needle patch includes: one or more micro-needles; and multiple temperature-sensitive color changing substances with different color change temperatures.

Description

TECHNICAL FIELD [0001] The present invention relates to a temperature sensitive micro needle patch and a method of manufacturing the same,

The present invention is directed to a micro-needle comprising: at least one micro needle; And a plurality of temperature sensitive coloring materials having mutually different discoloration temperatures, a kit including the micro needle patch, and a method of manufacturing the micro needle patch.

A drug delivery system (DDS) is a series of techniques for controlling the delivery of a substance having pharmacological activity to cells, tissues, organs and organs using a variety of physicochemical techniques. The most common drug delivery systems include oral medications, and transdermal drug delivery systems that can be applied locally. In this way, a metal syringe has been used for more than 150 years to inject the liquid drug through the transdermal system. However, the injection of the drug is accompanied by pain and has disadvantages such as needle phobia. In order to improve the drug administration method using such a syringe, a microneedle transdermal microneedle which is much smaller than a syringe has been made and used.

In general, the micro needle is a device for injecting a skin cosmetic substance or drug into the skin tissue or extracting body fluids such as blood from the inside of the skin. Microneedles are able to inject drugs locally and continuously, and minimize pain upon insertion into the skin, and their use in various fields is increasing rapidly in recent years.

[Prior Art Literature]

Korean Patent Publication No. 10-1759354.

The present invention is directed to a micro-needle comprising: at least one micro needle; And a plurality of temperature sensitive coloring materials having different discoloration temperatures, a kit including the microneedle patch, and a method of manufacturing the microneedle patch.

However, the problems to be solved by the present invention are not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.

A first aspect of the present application provides a method of making a microstructure comprising: And a plurality of temperature-sensitive color-changing materials having mutually different discoloration temperatures.

A second aspect of the present invention provides a kit comprising the micro needle patch.

A third aspect of the present disclosure provides a method of making a micro needle pad, comprising: obtaining a micro needle patch in which one or more micro needles are arranged, a temperature responsive discoloration layer comprising a plurality of temperature sensitive coloring materials, and a patch needle; Or obtaining a micro needle patch which is arranged in the sequence of a micro needle sheet on which one or more micro needles are arranged, a patch mattress, and a temperature sensitive color changing layer comprising a plurality of temperature sensitive coloring materials. do.

The microneedle patches according to embodiments of the present invention include a plurality of temperature-sensitive coloring materials that are discolored at different temperatures, thereby exhibiting an effect of discoloring twice or more at different temperatures.

The first temperature sensitive coloring material may be discolored when the micro needle patch according to embodiments of the present invention is attached to the skin, and the second temperature sensitive discoloration material may be discolored when the skin temperature rises above a certain temperature. Accordingly, a micro needle patch according to embodiments of the present disclosure may indicate whether the micro needle patch is well attached to the skin.

The microneedle patches according to the embodiments of the present invention can be used in various fields such as temperature sensitive discoloration, It is possible to indicate whether the temperature of the skin has increased through the discoloration of the substance.

The microneedle patches according to embodiments of the present disclosure can indicate whether the substance is delivered into the skin through the discoloration of the temperature sensitive discoloration material when delivering the material that is better delivered to the skin at a certain temperature range have.

A microneedle patch according to embodiments of the present disclosure can indicate whether the microneedle is effectively delivered to the body when the microneedle additionally includes a substance that recognizes the body temperature.

A microneedle patch according to embodiments of the present disclosure, including a shape memory material, can be adhered to the skin. Since the micro needle patch is closely adhered to the shape of the skin, the micro needle can easily penetrate into the skin, and thus the substance in the micro needle can be transmitted to the body well.

The microneedle patches according to embodiments of the present disclosure may include a photoacceptable coloring material to indicate whether the patch is irradiated with visible light, ultraviolet light, infrared light, or the like. Accordingly, when the micro needle patch is attached to the skin having stain or dullness, the skin can be protected and the stain or the odor can be masked.

1 is a schematic diagram illustrating a microneedle patch according to embodiments of the present disclosure;
FIG. 2 is a schematic diagram of a microneedle patch according to embodiments of the present invention, wherein the temperature responsive color layer comprises a first temperature responsive discoloration layer and a second temperature responsive discoloration layer.
Figure 3 is a schematic diagram of a microneedle patch according to embodiments of the present invention, showing a microneedle patch further comprising a photo sensitive color layer.
4 is a schematic diagram illustrating a micro needle patch according to embodiments of the present invention, further comprising a photo sensitive color-changing layer, wherein the color-change layer comprises a micro-needle including a first temperature-sensitive color-change layer and a second temperature- Patch.
FIGS. 5 and 6 are schematic views illustrating a process of discoloring a first temperature-sensitive discoloration substance and a second temperature-sensitive discoloration substance of a microneedle patch according to embodiments of the present invention.
Figure 7 is a schematic diagram of a micro needle patch in accordance with embodiments of the present invention, wherein the patch mattress comprises a micro needle patch.
8 is an image of a micro needle patch in one embodiment of the present invention.
9A to 9C illustrate discoloration of a micro needle patch including a temperature sensitive discoloration material according to temperature according to an embodiment of the present invention. , (b) when heated to 37 ° C, and (c) after heating to 37 ° C.
10A to 10C illustrate discoloration of a micro needle patch including a temperature sensitive discoloration material according to temperature according to an embodiment of the present invention. , (b) when heated to 37 ° C, and (c) after heating to 37 ° C.
FIGS. 11 (a) to 11 (c) illustrate discoloration of a micro needle patch including a temperature-sensitive color-changing material according to temperature, according to an embodiment of the present invention, , (b) when heated to 37 ° C, and (c) after heating to 37 ° C.
Figures 12 (a) and 12 (b) are images of an embodiment of the present invention, before (a) attaching the microneedle patch to the skin and (b) after attaching it.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily carry out the present invention. It should be understood, however, that the present invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In the drawings, the same reference numbers are used throughout the specification to refer to the same or like parts.

Throughout this specification, when a part is referred to as being "connected" to another part, it is not limited to a case where it is "directly connected" but also includes the case where it is "electrically connected" do.

Throughout this specification, when a member is " on " another member, it includes not only when the member is in contact with the other member, but also when there is another member between the two members.

Throughout this specification, when an element is referred to as " including " an element, it is understood that the element may include other elements as well, without departing from the other elements unless specifically stated otherwise. The terms " about ", " substantially ", etc. used to the extent that they are used throughout the specification are intended to be taken to mean the approximation of the manufacturing and material tolerances inherent in the stated sense, Accurate or absolute numbers are used to help prevent unauthorized exploitation by unauthorized intruders of the referenced disclosure. The word " step (or step) " or " step " used to the extent that it is used throughout the specification does not mean " step for.

Throughout this specification, the term " combination (s) thereof " included in the expression of the machine form means a mixture or combination of one or more elements selected from the group consisting of the constituents described in the expression of the form of a marker, Quot; means at least one selected from the group consisting of the above-mentioned elements.

Throughout this specification, the description of "A and / or B" means "A or B, or A and B". Throughout the present specification, the description of "discoloration" means "a change from colorless to colored, a change from color to colorless, a change from color to another color".

Throughout the present specification, the description of the "shape memory material shape memory temperature" means "the temperature at which the shape memory material is fixed in a deformed state and is not restored to its original state".

Hereinafter, embodiments of the present invention are described in detail, but the present invention is not limited thereto.

A first aspect of the present application provides a method of making a microstructure comprising: And a plurality of temperature-sensitive coloring materials having different discoloration temperatures from each other.

In one embodiment of the present invention, the plurality of temperature-sensitive color materials may include a first temperature-sensitive coloring material and a second temperature-sensitive coloring material.

In one embodiment of the present invention, the first temperature-sensitive coloring material may be discolored at a temperature lower than the skin temperature. Here, the skin may be skin of all animals including human, preferably human skin. The skin temperature may be skin temperature of all animals, preferably human skin temperature. The human skin temperature is about 37 ° C, about 36 ° C to about 38 ° C, about 36.5 ° C to about 38 ° C, about 37 ° C to about 38 ° C, about 37.5 ° C to about 38 ° C, From about 36.5 캜 to about 37.5 캜, from about 37 캜 to about 37.5 캜, from about 36 캜 to about 37 캜, or from about 36.5 캜 to about 37 캜.

In one embodiment of the present invention, the first temperature-sensitive coloring material may be discolored at about 31 ° C to below the skin temperature. Since the micro needle patch according to one embodiment of the present invention can be stored at room temperature, the first temperature-sensitive coloring material may be discolored at a temperature higher than normal temperature and lower than the skin temperature. For example, But it may be, but not limited to, a temperature below about 28 占 폚 to below skin temperature, about 31 占 폚 to below skin temperature, about 34 占 폚 to below skin temperature, or about 37 占 폚 to below skin temperature.

When the micro needle patch according to an embodiment of the present invention is attached to the skin well, the heat of the skin transfers the micro needle patch, and the temperature of the micro needle patch rises to the same or higher temperature than the skin, The first temperature-sensitive coloring material may be discolored. That is, the micro needle patch is a first temperature-sensitive discoloration substance and a second temperature-sensitive discoloration substance which are not discolored before they are attached to the skin, and the discolored first temperature-sensitive discoloration substance and the discolored Can exhibit a second temperature-sensitive coloring material (see step 1 of FIG. 6).

Accordingly, the microneedle patch according to one embodiment of the present invention can indicate whether the microneedle patch is attached to the skin through the degree of discoloration of the first temperature-sensitive coloring material.

In one embodiment of the present invention, the first temperature-sensitive color changing material and the second temperature-sensitive color changing material may include an electron donor and an electron acceptor, and the state of the electron donor and the electron acceptor may vary It may be discolored. In one embodiment of the present invention, depending on the electron donor and the electron acceptor, the color and discoloration temperature of the first temperature-sensitive coloring material and the second temperature-sensitive coloring material may be determined.

In one embodiment of the invention, examples of the electron donor and the electron acceptor are shown in the following Tables 1 and 2, respectively, but are not limited thereto.

Electron donor color 3,6-dimethoxyfluoran yellow 3-Cyclohexylamino-6-chloropoulolane orange color 3-diethylaminobenzofuran Red Rhodamine B lactone Orange - Red Crystal violet lactone blue 3-diethylamino-7-dibenzylaminofluorane green 3-diethylamino-6-aminofluorane black

Electron acceptor Carbon number Discoloration temperature N-octyl alcohol 8 -40 ° C N-decyl alcohol 10 -13 ° C N-lauryl alcohol 12 16 ℃ N-Myristyl alcohol 14 35 ℃ N-cetyl alcohol 16 45 ° C N-stearyl alcohol 18 53 ℃

In one embodiment of the present invention, the first temperature-sensitive coloring material may be discolored at a temperature ranging from 31 ° C to below the skin temperature. For example, the first temperature-sensitive coloring material may be at least one selected from the group consisting of diphenylmethanephthalide and derivatives thereof, Phenyl indolyl phthalide and derivatives thereof, indolyl phthalide and derivatives thereof, diphenyl methane aphthalide and derivatives thereof, phenyl indolizapride and derivatives thereof, fluororan and derivatives thereof, styryl quinoline and derivatives thereof, But are not limited to, materials selected from the group consisting of jarodamine lactones and derivatives thereof, and combinations thereof. In one embodiment of the present invention, the first temperature-sensitive coloring material may further include alcohols, but the present invention is not limited thereto.

In one embodiment of the present invention, the first temperature-sensitive discoloration material may be discolored at a temperature of 31 ° C to below the skin temperature by appropriately selecting the kind and content of the alcohol, but may not be limited thereto.

In one embodiment of the invention, the first temperature-sensitive color-change material may be included in the micro needle patch in the form of a microcapsule of about 1 탆 to about 10 탆 in diameter.

In one embodiment of the invention, the microneedle patch may further include, but is not limited to, an additive.

In one embodiment of the present invention, the first temperature-sensitive coloring material may be included in the microneedle patch in the form of letters, patterns, or pictures as shown in FIG. 6, but is not limited thereto.

In one embodiment of the present invention, the second temperature-sensitive coloring material may be discolored at a normal skin temperature. That is, when the temperature of the skin rises above the normal skin temperature, the second temperature-sensitive coloring material may be discolored (see step 2 of FIG. 6). As a method for raising the temperature of the skin above the normal skin temperature, there may be a method using an external device or a bath, but the method may not be limited thereto. The external device may be a device capable of locally raising the temperature of the skin using light energy including ultraviolet rays, ultraviolet rays, or micro-vibrations, including, but not limited to, a warming device, visible light, near infrared rays, and infrared rays.

In one embodiment of the invention, the second temperature-sensitive coloring material may be discolored at an ordinary skin temperature to 40 ° C, for example, a skin temperature exceeding 40 ° C, a skin temperature exceeding 39.5 ° C, But may be, but not limited to, an over-temperature to 39 ° C, or an over-skin temperature to 38.5 ° C.

In one embodiment of the invention, the second temperature-sensitive color-changing material is selected from, for example, diphenylmethanephthalide and its derivatives, phenylindolylphthalide and its derivatives, indolylphthalide and its derivatives, diphenylmethane A substance selected from the group consisting of azaftalide and derivatives thereof, phenyl indolyazaflate and derivatives thereof, fluororan and derivatives thereof, styrylquinoline and derivatives thereof, diazalodamine lactone and derivatives thereof, and combinations thereof , But may not be limited thereto.

In one embodiment of the present invention, the first temperature-sensitive coloring material may further include alcohols, but the present invention is not limited thereto.

 In one embodiment of the present invention, the first temperature-sensitive coloring material may be selected to suitably select the kind and content of the alcohol, and the first temperature-sensitive coloring material may be discolored at a temperature exceeding the skin temperature to 40 ° C. However, the present invention is not limited thereto.

In one embodiment of the present invention, the second temperature-sensitive coloring material may be discolored at a temperature higher by 3 ° C or more than a temperature at which the first temperature-sensitive coloring material is discolored.

In one embodiment of the present invention, the second temperature-sensitive coloring material may be discolored at a temperature higher by 5 ° C or more than a temperature at which the first temperature-sensitive coloring material is discolored.

In one embodiment of the invention, the second temperature-sensitive color change material may be included in the micro needle patch in the form of a microcapsule of about 1 탆 to about 10 탆 in diameter.

In one embodiment of the present invention, the second temperature-sensitive color changing material may include an electron donor and an electron acceptor, and the state of the electron donor and the electron acceptor may be changed depending on the temperature to be discolored.

In one embodiment of the present invention, the second temperature-sensitive coloring material may be included in the microneedle patch in the form of letters, patterns, pictures, etc. (FIG. 6), but the present invention is not limited thereto.

In one embodiment of the invention, the microneedle patch may further comprise a non-discolored layer. The non-discolored layer may include a non-discolored substance that does not change color even when the temperature changes.

In one embodiment of the present invention, when both of the first temperature-sensitive coloring material and the second temperature-sensitive coloring material of the microneedle patch are discolored and become colorless, the microneedle patch is formed of a non-discoloring material Can be displayed.

In one embodiment of the invention, the non-discolored layer can be located anywhere on the micro needle patch, for example, on top or bottom of the patch mattress, on top or bottom of the temperature responsive discoloration layer, But may be, but not limited to, the top or bottom of the layer.

Typically, the substance to be delivered to the body using the micro needle is transmitted to the body more effectively as the blood circulation in the body becomes more active as the temperature of the skin increases. The microneedle patch according to one embodiment of the present invention, It is possible to indicate whether the temperature of the skin has increased through the discoloration of the discoloration substance. Thus, a micro needle patch according to one embodiment of the present disclosure can indirectly indicate whether the material is well transferred into the body.

Further, when delivering a substance that is better delivered to the skin over a range of specific temperatures, the microneedle patch according to one embodiment of the present invention is capable of delivering the substance through the body, through the discoloration of the second temperature- Can be indirectly displayed.

In one embodiment herein, the microneedle patch may further comprise a shape memory material. In one embodiment of the present invention, the shape memory material may be included at any position that can fix the shape or shape of the microneedle patch. For example, the at least one selected from the micro needle sheet, the patch mattress, the temperature responsive discoloration layer, the photo sensitive discoloration layer, and combinations thereof may further include a shape memory material.

In one embodiment of the invention, as shown in Figure 7, the microneedle patch may additionally include shape memory material along the edges of the patch mattress.

In one embodiment of the present invention, the shape memory temperature of the shape memory material may be a normal skin temperature or more.

In one embodiment of the present application, the micro needle patch is deformed from a first shape (original state) to a second shape (deformed state) when attached to the skin, and the shape memory material deforms the second shape . ≪ / RTI >

The microneedle patches according to embodiments of the present disclosure may further include a shape memory material so that they can adhere well to the skin. Since the micro needle patch is closely adhered to the shape of the skin, the micro needle can easily penetrate into the skin, and thus the substance in the micro needle can be transmitted to the body well.

In one embodiment of the invention, the shape memory material is a biodegradable material such as a poly-L-lactide (PLLA) -polyglycolide caprolactone (PGCL) copolymer, a metal such as a nickel- Elastomers, polymers such as elastomers, and combinations thereof. However, the present invention is not limited thereto.

In one embodiment of the present application, the microneedle patch comprises: a microneedle sheet on which the one or more microneedles are arranged; A patch mattress on which the micro needle sheet is disposed; And a temperature sensitive coloring layer disposed between the micro needle sheet and the patch mattress or below the patch mattress, wherein the temperature sensitive coloring layer includes a plurality of temperature sensitive color materials.

In an embodiment of the present invention, after the patch mattress is removed to adhere the micro needle patch to the skin, the face on which the patch mattress has been removed is contacted with the skin or the like, and the micro needle patch is adhered to and / Lt; / RTI >

In one embodiment of the invention, the microneedles can be prepared from known microneedle forming materials. The material for forming microneedle formation may be formed from a material that is dissolved in the body, metal, polymer, silicon, and combinations thereof, but may not be limited thereto.

The substance to be dissolved in the body is, for example, hyaluronic acid, salt of hyaluronic acid, cellulose, vinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohol, polyvinylpyrrolidone polyvinyl pyrrolidone, saccharide, or a mixture thereof.

Examples of the cellulose include cellulose polymer, microfibrillated cellulose, hydroxypropylmethylcellulose, hydroxyalkylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, ethylhydroxyethylcellulose , Alkylcellulose, carboxymethylcellulose, hydroxypropylmethylcellulose sodium carboxymethylcellulose, or mixtures thereof, but may not be limited thereto.

The sugar may be, for example, xylose, sucrose, maltose, lactose, trehalose, dextran, starch or a mixture thereof However, the present invention is not limited thereto.

In one embodiment of the present invention, the material for forming microneedle may further include, but is not limited to, selected from viscous materials, drugs, and combinations thereof.

In one embodiment, the viscous material is selected from the group consisting of polyvinylpyrrolidone, dextran, gelatin, glycerin, polyethylene glycol, polysorbate, propylene glycol, povidone, carbomer, gum ghatti, Glucosamine, glucosamine, dammer resin, rennetcasein, locust bean gum, psyllium seed gum, xanthan gum, arabinogalactan, arabinogalactan, Gum, alginic acid, gelatin, gellan gum, carrageenan, karaya gum, curdlan, chitosan, chitin, tara gum, tamarind gum, But are not limited to, those selected from the group consisting of tragacanth gum, furcelleran, pectin, pullulan, and combinations thereof.

In one embodiment of the invention, the drug includes physiologically active peptides and derivatives thereof, nucleic acids, oligonucleotides, various antigen proteins, bacteria, and virus fragments. Examples of the physiologically active peptides and derivatives thereof include calcitonin, adrenocorticotropic hormone, parathyroid hormone (PTH), hPTH (1? 34), insulin, exendin, secretin, oxytocin, angiotensin,? -Endorphin, glucagon , Growth hormone, growth hormone releasing hormone, bradykinin, Substance P, dynorphin, thyroid stimulating hormone, prolactin, interferon, thyroid stimulating hormone, vasopressin, somatostatin, gastrin, luteinizing hormone releasing hormone, enkephalin, neurotensin, atrial sodium diuretic peptide, Interleukin, G-CSF, glutathione peroxidase, superoxide dismutase, desmopressin, somatomedin, endothelin and salts thereof. Examples of the antigenic protein include, but are not limited to, those selected from the group consisting of influenza antigens, HBs surface antigens, HBe antigens, and combinations thereof.

In one embodiment of the present invention, the micro needle can further include, but is not limited to, a plasticizer, a surfactant, a preservative, or an anti-inflammatory agent.

In one embodiment of the present invention, referring to FIG. 1, the microneedle patch may include a microneedle sheet on which the one or more microneedles are arranged. The micro needle sheet can be made of the same or different materials as the micro needles. When the micro needle sheet is made of a material different from that of the micro needle, it is preferable to use a material such as hyaluronic acid, hyaluronic acid salt, cellulose, vinyl pyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, But are not limited to, those selected from the group consisting of polyvinyl pyrrolidones, saccharides, and combinations thereof.

In one embodiment of the invention, the microneedle patch may include a patch mattress on which the microneedle sheet is disposed. The patch mattress may be manufactured from a metal, a compound such as silicon and ceramic, a glass such as a polymer, a polyurethane, a graphene, a borosilicate glass, a crystal, and combinations thereof , But may not be limited thereto.

In one embodiment of the present invention, the microneedle patch may include a temperature sensitive coloring layer including the first temperature-sensitive coloring material and the second temperature-sensitive coloring material. The temperature-sensitive color change layer is a layer including a first temperature-sensitive color change material and a second temperature-sensitive color change material, and the entire temperature-sensitive color change layer need not be discolored.

In one embodiment of the invention, the temperature sensitive color change layer may be located anywhere on the micro needle patch if it can exhibit discoloration of the first temperature-sensitive color change material and the second temperature-sensitive color change material. For example, the temperature responsive discoloration layer may be located between, but not limited to, the micro needle sheet and the patch mattress, or below the patch mattress.

In one embodiment of the present invention, the plurality of temperature-sensitive color materials may include a first temperature-sensitive coloring material, a second temperature-sensitive coloring material, and the temperature- And a second temperature-sensitive color changing layer including the second temperature-sensitive color changing material.

2, only one embodiment in which the first temperature-sensitive color-changing layer is located on the second temperature-sensitive coloring layer is shown. However, in another embodiment of the present invention, the first temperature- And may be located below the temperature responsive discoloration layer.

In one embodiment of the invention, the microneedle patch may further comprise a photo sensitive color layer, and the photo sensitive color layer may be located below the patch mattress.

In one embodiment of the present invention, the photochromic discoloration layer may be located above or below the temperature responsive discoloration layer, for example, as shown in FIG. When the photo-sensitive color-changing layer is located above the temperature-sensitive color-change layer, the patch mattress-photo-sensitive color-change layer-temperature-sensitive color-change layer may be positioned in the order from top to bottom. In the case where the photoacceptable coloring layer is located below the temperature sensitive coloring layer, the order of the patch mattress-temperature sensitive coloring layer-photo sensitive coloring layer or the order of the patch temperature sensitive coloring layer-mattress- ≪ / RTI >

In one embodiment of the present invention, since the color of the photoacoustic coloring layer is changed by an external light source, the micro needle patch needs a patch mattress-temperature sensitive coloring layer-photo sensitive coloring layer Order or a patch temperature-sensitive color-change layer-mattress-photo-sensitive color-change layer.

In one embodiment of the invention, the photochromic discoloration layer may comprise a photochromic discoloring material. In one embodiment of the invention, the photochromic discoloring material may be, for example, a material that changes color by visible light, a material that changes color by ultraviolet light, or a material that changes color by infrared rays, have.

In one embodiment of the invention, the microneedles may further comprise a substance that recognizes body temperature. In one embodiment, the body temperature-aware material is a material that changes its physical and / or chemical properties with temperature, for example, reversibly sol-gel transition at a certain temperature or And may be, but not limited to, substances that cause volume phase transitions. Materials that cause reversible sol-gel phase transition or volumetric phase transition at said specific temperature include, for example, Pluronic, PNIPAAm (M. Harmon et al., Macromolecules 36: 1, 2003), hyaluronic acid (HA) (M. Ogiso et al., J. Biomed. Mater. Res. 39: 3, 1998), linear polyethylene glycols (PEG)-polylactic acid / glycol acid copolymers (PLGA) -polyethylene glycol (PEG) (PEG) -Polylactic acid (PLA) -Polyethylene glycol (PEG), star polylactic acid (PLA) -polyethylene glycol (PEG), Star type Poly-ε-caprolactone (PCL) -polyethylene glycol (PEG) (S. Zhao et al., J. Func. Polym. 15: 1, 2002). When the micro-needle further comprises a substance recognizing body temperature, the micro needle patch according to an embodiment of the present invention may indicate whether the components of the micro needle are effectively transferred into the body.

In one embodiment of the present invention, the micro needle patch may further comprise a protective film. 1 to 4, the protective film may be adhered to a region of the patch mattress other than the portion where the micro needle sheet is disposed, and the protective film may be adhered to the micro- It can protect the needle. In addition, the protective film may be included in the outermost portion of the micro needle patch opposite to the direction in which the skin is attached, thereby protecting the micro needle sheet, the temperature sensitive color change layer, or the photo sensitive color layer from external stimuli, .

In one embodiment of the invention, the micro needle sheet, the patch mattress, the temperature responsive discoloration layer, and combinations thereof may be one comprising a shape memory material. In one embodiment of the invention, where the microneedle patch further comprises a photo sensitive color-imparting layer, the micro-needle sheet, patch mattress, temperature responsive discoloration layer, steel discoloration layer, But may include, but is not limited to, a memory material.

In one embodiment of the invention, it is preferred that the length of the micro needle can reach the epidermal layer of the skin. The length of the microneedles may be, for example, from about 10 microns to about 2,000 microns, from about 10 microns to about 1,900 microns, from about 10 microns to about 1,800 microns, from about 10 microns to about 1,700 microns, from about 10 microns to about 1,600 microns From about 10 microns to about 1,100 microns, from about 10 microns to about 1,000 microns, from about 10 microns to about 1,000 microns, from about 10 microns to about 1,000 microns, from about 10 microns to about 1,500 microns, from about 10 microns to about 1,400 microns, from about 10 microns to about 1,300 microns, About 10 microns to about 800 microns, about 10 microns to about 700 microns, about 10 microns to about 600 microns, about 150 microns to about 2,000 microns, about 250 microns to about 2,000 microns, about 350 microns To about 2,000 microns, from about 450 microns to about 2,000 microns, or from about 550 microns to about 2,000 microns.

In one embodiment of the present invention, the cross-sectional shape of the microneedles may be linear and / or curvilinear. The cross section of the microneedles may include, for example, a polygon such as a triangle, a rectangle, a pentagon, a hexagon, an octagon, or a non-polygon such as a circle, an ellipse, a sector, a semicircle, But may not be limited thereto.

A second aspect of the present invention provides a kit comprising the micro needle patch.

The detailed description of the kit including the microneedle patch according to the first aspect of the present invention, which is the same as the first aspect of the present application, has been omitted. However, the description of the first aspect of the present invention, The second aspect of the present invention can be applied equally.

A third aspect of the present application provides a method of making a micro needle patch comprising the steps of sequentially arranging a micro needle sheet on which one or more micro needles are arranged, a temperature responsive coloring layer comprising a plurality of temperature sensitive coloring materials, and a patch mattress; Or a micro needle sheet in which one or more micro needles are arranged, a patch mattress, and a temperature sensitive coloring layer comprising a plurality of temperature sensitive coloring materials are arranged in this order to obtain a micro needle patch. do.

Although the description of the method of manufacturing the microneedle patch according to the third aspect of the present invention has not been described in detail for the first and second aspects of the present application, The contents described in the second aspect can be similarly applied to the third aspect of the present application.

In one embodiment of the invention, a micro needle sheet, in which one or more micro needles are arranged, may be placed on top of the patch mattress. Then, a temperature responsive discoloration layer may be placed between the micro needle sheet and the patch mattress, or below the patch mattress. Here, each of the mattresses or layers may be attached to each other by a known adhesive or a pressure-sensitive adhesive.

In one embodiment of the invention, the patch mattress and / or the temperature responsive color changing layer may comprise a shape memory material.

In one embodiment of the invention, if the microneedle patch further comprises a photo sensitive color-change layer, the photo-sensitive color change layer may be positioned below the patch mattress. For example, a method of making a microneedle patch according to one embodiment of the present invention includes forming a microneedle sheet on which one or more microneedles are arranged, a temperature sensitive coloring layer comprising a plurality of temperature sensitive coloring materials, a patch mattress, To obtain a micro needle patch which is arranged in this order; Obtaining a microneedle patch in which one or more microneedles are arranged, a microneedle sheet arranged in this order, a patch mattress, a photochromic discoloration layer, and a temperature sensitive coloring layer comprising a plurality of temperature-sensitive discoloration materials; Or a microneedle sheet in which one or more micro-needles are arranged, a patch mattress, a temperature sensitive color-changing layer comprising a plurality of temperature-sensitive color-changing materials, and a photo-sensitive discoloration layer.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the following Examples are given for the purpose of helping understanding of the present invention, but the present invention is not limited to the following Examples.

[Example]

Example 1: Preparation of micro needle patches

First, a plurality of micro-needles were attached to a hydrocolloid fabric (Anytape, AT-1477HD), and on top of the above-mentioned hydrocolloid fabric having microneedles containing hyaluronic acid and trehalos as main components, A micro needle patch was produced by printing Chameleon TP-Rose Red 31 (Insilico), which is a temperature-sensitive coloring material whose color changes transparently (Fig. 8). The prepared micro needle patch was placed on a heating plate, and the plate was heated to check the temperature discoloration of the micro needle patch. As shown in FIG. 9, the prepared micro needle patch had red color at 21 ° C, which is room temperature (FIG. 9 (a)), but as the plate was heated at 37 ° C, the red color discolored and gradually disappeared 9 (b)], the red completely disappeared after being completely heated to 37 ° C (FIG. 9 (c)). That is, it was confirmed that the temperature-sensitive color change material Chameleon TP-Rose Red 31 was discolored from red to colorless as the plate was heated to 31 ° C or higher by heating.

Example 2: Preparation of micro needle patches

A plurality of microneedles were attached to the hydrocolloid fabric, and Iriodin® 305 Solar Gold (Merck) was printed as a non-discolored layer on top of the hydrocolloid fabric with the microneedles attached. Thereafter, Chameleon TP-Rose Red 31 (Insilico) whose color changed transparently at 31 캜 was printed as a temperature-sensitive coloring material on the fabric printed with the non-discolored layer to prepare a micro needle patch. The prepared micro needle patch was placed on a heating plate, and the plate was heated to check the temperature discoloration of the micro needle patch. As shown in Fig. 10, the fabricated microneedle patch had an orange type mixed with yellow of Iriodin® 305 Solar Gold and red of Chameleon TP-Rose Red 31 at 21 ° C, which is room temperature (FIG. 10 (a) The red color of the Chameleon TP-Rose Red 31 was discolored and gradually disappeared as the plate was heated to 37 ° C. (FIG. 10 (b)). After completely heated to 37 ° C., the red color completely disappeared and the discolored layer Iriodin® 305 Solar Gold only in yellow color (Fig. 10 (c)).

Example 3: Preparation of micro needle patches

A plurality of microneedles were attached to the hydrocolloid fabric, and Iriodin® 305 Solar Gold (Merck) was printed as a non-discolored layer on top of the hydrocolloid fabric with the microneedles attached. Then, Chameleon TP-Yellow 31 (manufactured by Insilico) whose color changed transparently at 31 ° C as a temperature-sensitive coloring material was printed on the fabric having the non-discolored layer printed thereon to prepare a micro needle patch. The prepared micro needle patch was placed on a heating plate, and the plate was heated to check the temperature discoloration of the micro needle patch. As shown in Fig. 11, the prepared micro needle patch had yellow color due to the Chameleon TP-Yellow 31 and yellow color caused by Iriodin® 305 Solar Gold at 21 ° C (FIG. 11 (a)) at room temperature , And the plate was heated to 37 ° C, and the yellow background of the Chameleon TP-Yellow 31 discolored gradually (Fig. 11 (b)). After the plate was completely heated to 37 ° C, It was confirmed that only the yellow type of the discolored layer Iriodin® 305 Solar Gold was shown (FIG. 11 (c)).

Example 4: Skin adhesion test of micro needle patch

Attachment tests were performed to observe discoloration of the micro needle patches with skin temperature. First, a plurality of micro-needles were attached to a hydrocolloid fabric, and a micro-needle patch was prepared by printing a temperature-sensitive coloring material having a hue change in color near the skin temperature at the top of the hydrocolloid fabric with the micro-needle attached thereto 12 (a)]. After the micro needle patch was attached to the skin, the discoloration degree was observed after about 10 seconds. As shown in FIG. 12 (b), it was confirmed that the micro needle patch was transparently discolored after skin adherence by the temperature-sensitive color change material whose color changed transparently near the skin temperature.

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

The scope of the present invention is defined by the appended claims rather than the detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be interpreted as being included in the scope of the present invention .

1000: Micro needle patch
1100: one or more micro needles
1200: Micro needle sheet
1300: patch mattress
1400: temperature responsive discoloration layer
1410: first temperature-sensitive color change layer
1420: second temperature responsive discoloration layer
1500: Protective film
1600: Photochromic discoloration layer
1910: First temperature-sensitive color change material
1920: the second temperature-sensitive color change material

Claims (23)

One or more micro-needles; And
A plurality of temperature-sensitive color-changing substances having different discoloration temperatures
And a micro needle patch.
The method according to claim 1,
Wherein the plurality of temperature-sensitive color-changing materials comprises a first temperature-sensitive color-changing material and a second temperature-sensitive color-
Micro needle patch.
3. The method of claim 2,
Wherein the first temperature-sensitive coloring material is discolored below the skin temperature.
Micro needle patch.
The method of claim 3,
Wherein the first temperature-sensitive coloring material is discolored at a temperature ranging from < RTI ID = 0.0 > 31 C &
Micro needle patch.
3. The method of claim 2,
Wherein the second temperature-sensitive coloring material is discolored at a temperature above the skin temperature.
Micro needle patch.
6. The method of claim 5,
Wherein the second temperature-sensitive color-changing material is discolored at a temperature exceeding the skin temperature to < RTI ID = 0.0 > 40 C. <
Micro needle patch.
The method according to claim 1,
And the second temperature-sensitive coloring material is discolored at a temperature higher by 3 ° C or more than a temperature at which the first temperature-sensitive coloring material is discolored.
Micro needle patch.
The method according to claim 1,
And the second temperature-sensitive coloring material is discolored at a temperature higher by 5 ° C or more than a temperature at which the first temperature-sensitive coloring material is discolored.
Micro needle patch.
The method according to claim 1,
Further comprising a shape memory material,
Micro needle patch.
10. The method of claim 9,
Wherein the shape memory temperature of the shape memory material is a skin temperature or more,
Micro needle patch.
10. The method of claim 9,
The micro needle patch comprises:
When attached to the skin, is transformed from the first form to the second form,
Wherein the second shape is fixed by the shape memory material contained in the microneedle patch.
Micro needle patch.
The method according to claim 1,
The micro needle patch comprises:
A micro needle sheet on which said one or more micro needles are arranged;
A patch mattress on which the micro needle sheet is disposed; And
And a temperature responsive color change layer positioned between the micro needle sheet and the patch mattress or below the patch mattress,
Wherein the temperature responsive coloring layer comprises the plurality of temperature sensitive coloring materials.
Micro needle patch.
13. The method of claim 12,
Further comprising a photo-sensitive discoloration layer,
Wherein the photo sensitive color layer is located below the patch mattress.
Micro needle patch.
13. The method of claim 12,
Wherein the plurality of temperature-sensitive color materials include a first temperature-sensitive color change material and a second temperature-sensitive color change material,
Wherein the temperature responsive coloring layer comprises a first temperature responsive coloring layer comprising the first temperature sensitive coloring material and a second temperature sensitive coloring layer comprising the second temperature sensitive coloring material.
Micro needle patch.
13. The method of claim 12,
Wherein the patch mattress and / or the temperature responsive coloring layer comprises a shape memory material.
Micro needle patch.
The method according to claim 1,
Wherein the length of the microneedles is from 10 [mu] m to 2,000 [mu] m.
Micro needle patch.
The method according to claim 1,
Wherein the cross-sectional shape of the microneedles is linear and / or curvilinear.
Micro needle patch.
The method according to claim 1,
Wherein the microneedles are formed using a material comprising a microneedle forming material selected from the group consisting of materials soluble in the body, metals, polymers, silicon, and combinations thereof.
Micro needle patch.
19. The method of claim 18,
Wherein the material for forming microneedle further comprises a material selected from the group consisting of a viscous material, a drug, and combinations thereof.
Micro needle patch.
A kit comprising a microneedle patch according to any one of claims 1 to 19.
Disposing a micro needle sheet in which one or more micro needles are arranged, a temperature responsive discoloration layer including a plurality of temperature sensitive coloring materials, and a patch mattress in order to obtain a micro needle patch; or
A microneedle sheet in which one or more micro needles are arranged, a patch mattress, and a temperature sensitive coloring layer containing a plurality of temperature sensitive coloring materials are arranged in order to obtain a micro needle patch
Wherein the micro needle patch comprises a plurality of micro needle patches.
22. The method of claim 21,
Wherein the patch mattress and / or the temperature responsive coloring layer further comprises a shape memory material.
A method of manufacturing a micro needle patch.
22. The method of claim 21,
The microneedle patch further comprises a photo sensitive color layer,
Disposing a micro needle sheet on which the one or more micro needles are arranged, a temperature responsive discoloration layer comprising a plurality of temperature sensitive color materials, a patch mattress, and a photo sensitive color layer in order to obtain a micro needle patch;
Obtaining a micro needle patch by disposing a micro needle sheet in which one or more micro needles are arranged, a patch matrice, a photo sensitive color change layer, and a temperature sensitive color change layer including a plurality of temperature sensitive color change materials in this order; or,
A microneedle sheet on which the one or more microneedles are arranged, a patch matrice, a temperature sensitive coloring layer containing a plurality of temperature-sensitive coloring materials, and a photoacceptable coloring layer are sequentially arranged to obtain a microneedle patch
Wherein the micro needle patch comprises a plurality of micro needle patches.

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