Microneedle patches

Abstract

To provide a microneedle patch that prevents a microneedle array from remaining on skin when peeled from the skin.SOLUTION: A microneedle patch according to an embodiment includes a support, an adhesive layer provided on the principal face of the support, and a microneedle array that is at least partially situated in the adhesive layer. The adhesive layer includes a water-soluble polymer with a total amount of 11-20 mass%, sodium carboxymethyl cellulose of 3.5-7 mass%, and a partially neutralized polyacrylic acid of 2 mass% or more and less than 5 mass%, and a crosslinker of 0.22-1 mass%.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] One aspect of the present disclosure relates to a microneedle patch. [Background technology]

[0002] Patent Document 1 describes a patch with microneedles. This patch is provided with one or more microneedle members inside an adhesive layer that can protrude from the adhesive layer to the adhesive surface side.

[0003] Patent Document 2 describes a patch comprising a support, an adhesive layer containing an active ingredient provided on one side of the support, and a microneedle array having microneedles provided on a substrate. After the microneedles are exposed from within the adhesive layer and pierce the skin, they move away from the skin due to their elasticity. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2007-1938 [Patent Document 2] Japanese Patent Application Laid-Open No. 2015-151380 Summary of the Invention [Problem to be solved by the invention]

[0005] There is a demand for a microneedle patch that does not leave a microneedle array on the skin when removed from the skin. [Means for solving the problem]

[0006] A microneedle patch according to one aspect of the present disclosure comprises a support, an adhesive layer provided on a main surface of the support, and a microneedle array at least partially located within the adhesive layer, wherein the adhesive layer contains a water-soluble polymer in a total amount of 11 to 20% by mass, 3.5 to 7% by mass of sodium carboxymethylcellulose, 2% by mass or more and less than 5% by mass of a partially neutralized polyacrylic acid, and 0.22 to 1% by mass of a crosslinking agent.

[0007] The inventors have discovered that by setting the constituent components of the adhesive layer that covers at least a portion of the microneedles as described above, a microneedle patch that has been applied to the skin can be peeled off without leaving the microneedle array on the skin. [Effects of the Invention]

[0008] According to one aspect of the present disclosure, a microneedle patch can be provided that does not leave a microneedle array on the skin when peeled off from the skin. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 is a perspective view of a microneedle patch according to an embodiment. [Figure 2] FIG. 2 is an enlarged perspective view showing an example of the microneedle array shown in FIG. DETAILED DESCRIPTION OF THE INVENTION

[0010] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. In the description of the drawings, the same or equivalent elements are designated by the same reference numerals, and redundant description will be omitted.

[0011] 1 is a perspective view of a microneedle patch 10 according to an embodiment. The microneedle patch 10 is a preparation used as a cataplasm, tape, or the like. In one example, the microneedle patch 10 comprises a support 12, an adhesive layer 14 formed over substantially the entire main surface of the support 12, a release sheet 16 removably attached to the active surface of the adhesive layer 14, and a microneedle array 20 embedded in the adhesive layer 14. The active surface of the adhesive layer 14 refers to the surface that comes into contact with the user's skin when the microneedle patch 10 is in use.

[0012] The dimensions of the microneedle patch 10 may be set according to the symptoms, age, weight, sex, etc. of the user. For example, the area of ​​the microneedle patch 10 may be 1 to 500 cm. 2 Or 10~400cm 2 It is also acceptable to divide the area into 1cm 2 By increasing the area to 500cm or more, it becomes easier to maintain sufficient skin permeability of the active ingredient. 2 The microneedle patch 10 can be easily handled by the following.

[0013] The support 12 is a sheet-like member. The support 12 may be stretchable. The material of the support 12 may be selected taking into consideration physical properties (thickness, elongation, tensile strength, ease of application, etc.), feel upon application, skin sealability, migration of active ingredients into the support 12, and the like. For example, the material may be a woven fabric, a nonwoven fabric, a resin film, a foam sheet, or paper. An example of a woven fabric is a knitted fabric. When a woven fabric, a nonwoven fabric, or a resin film is used as the support 12, examples of the material include polyolefins such as polyethylene, polypropylene, and polybutylene, polyesters such as polyethylene terephthalate (PET), rayon, polyurethane, and cotton. These materials may be used alone or in combination of two or more. The support 12 may have a single-layer structure or a multi-layer structure. The support 12 may be a sheet-like porous material or a sheet-like foam.

[0014] Examples of knitted fabrics include knitted fabrics made of one or a combination of two or more materials such as polyester, nylon, polypropylene, rayon, etc. For example, knitted fabrics made of polyester polyethylene terephthalate, which has little interaction with the active ingredient, may be used.

[0015] When the backing 12 is a knitted fabric or a nonwoven fabric, if a water-containing pressure-sensitive adhesive composition is spread on the backing 12, the pressure-sensitive adhesive composition may seep out to the back side of the backing through the mesh of the backing 12. In consideration of this point, the basis weight of the knitted fabric or nonwoven fabric is set to 50 to 150 g / m 2 But 75-125g / m 2 By setting the basis weight within this range, the PSA composition tends to be able to be spread without seeping through gaps in the support 12 to the backside of the support 12. In addition, the anchoring properties between the support 12 and the PSA layer 14 can be maintained.

[0016] The stretchability of the support 12 may be such that the 50% modulus (load at 50% elongation) is 0.5 to 10 N / 50 mm in at least one of the longitudinal and transverse directions. Here, the "longitudinal direction" refers to the direction of flow in the process of producing the knitted fabric, and the "transverse direction" refers to the direction perpendicular to the longitudinal direction, i.e., the width direction. The modulus is measured in accordance with JIS L 1018:1999.

[0017] The thickness of the support 12 may be set, for example, in the range of 5 to 1000 μm. The reason for setting the thickness to 5 μm or more is to facilitate handling of the microneedle patch 10. The reason for setting the thickness to 1000 μm or less is to prevent the hardness of the support 12 from affecting the adhesiveness of the microneedle patch 10.

[0018] The adhesive layer 14 is a layer having adhesive properties that allow it to adhere to human skin. In one example, the adhesive layer 14 contains a water-soluble polymer and water. The adhesive layer 14 may further contain an active ingredient (biologically active substance). The phrase "the adhesive layer contains an active ingredient" is a concept that encompasses both an embodiment in which the adhesive layer 14 contains an active ingredient therein and an embodiment in which the active ingredient is attached to the working surface of the adhesive layer 14.

[0019] The water-soluble polymer refers to a polymer having a hydrophilic group. Examples of the hydrophilic group include a hydroxy group, a carboxy group, and an amino group. When the pressure-sensitive adhesive layer 14 contains a water-soluble polymer, the moisture in the microneedle patch 10 can be maintained for a longer period of time.

[0020] The water-soluble polymer may be polyacrylic acid or a neutralized polyacrylic acid (which may be referred to as a "water-soluble acrylic polymer"). When the pressure-sensitive adhesive layer 14 contains polyacrylic acid or a neutralized product thereof, the pressure-sensitive adhesive layer 14 can have excellent adhesive properties.

[0021] The water-soluble acrylic polymer is a polymer obtained by polymerizing an acryloyl group-containing compound having a functional group (hydrophilic group) that exhibits water solubility. The pressure-sensitive adhesive layer 14 exhibits adhesiveness by containing the water-soluble acrylic polymer together with water. The water-soluble acrylic polymer is, for example, a polymer obtained by polymerizing a compound having an acryloyl group, such as polyacrylic acid or its neutralized product, an acrylic acid ester having a hydrophilic group, or an acrylic acid amide having a hydrophilic group. The water-soluble acrylic polymer may be a homopolymer obtained from a compound having one type of acryloyl group, or a copolymer obtained from two or more compounds having acryloyl groups.

[0022] The hydrophilic group may be any of a cationic hydrophilic group, an anionic hydrophilic group, and a nonionic hydrophilic group. An example of a cationic hydrophilic group is a quaternary ammonium group. An example of an anionic hydrophilic group is a carboxy group, a sulfo group, and a phosphate group. An example of a nonionic hydrophilic group is a hydroxy group and an amino group.

[0023] When polyacrylic acid is contained in the adhesive layer 14 as the water-soluble polymer, its content may be adjusted to 0.1 to 5 mass % or 0.5 to 4 mass % based on the total mass of the adhesive layer 14. By making the polyacrylic acid content 0.1 mass % or more, the moldability and shape retention of the adhesive layer 14 tend to be further improved. By making the polyacrylic acid content 5 mass % or less, the adhesive layer 14 tends not to become too hard, and tends to have better adhesion to the skin. Increasing the polyacrylic acid content in the adhesive layer 14 tends to increase the loss tangent.

[0024] The neutralized polyacrylic acid may be a completely neutralized polyacrylic acid, a partially neutralized polyacrylic acid, or a mixture thereof. Examples of the neutralized polyacrylic acid include polyacrylic acid salts, such as sodium salts, potassium salts, calcium salts, and ammonium salts.

[0025] As the neutralized polyacrylic acid, a partially neutralized polyacrylic acid may be used, which increases both the initial adhesion and the adhesion over time. The partially neutralized polyacrylic acid is a composition in which structural units derived from acrylic acid and structural units derived from an acrylate salt are present in any ratio in one polymer chain. As the partially neutralized polyacrylic acid, one in which 20 to 80 mol % of the carboxy groups in one polymer chain are neutralized may be used.

[0026] When the pressure-sensitive adhesive layer 14 contains a neutralized polyacrylic acid as the water-soluble polymer, its content may be adjusted to 1 to 10% by mass, or 2 to 7% by mass, based on the total mass of the pressure-sensitive adhesive layer 14. By adjusting the content of the neutralized polyacrylic acid to 1% by mass or more, the adhesive strength of the neutralized polyacrylic acid can be sufficiently obtained. By adjusting the content of the neutralized polyacrylic acid to 7% by mass or less, the formability and shape retention of the pressure-sensitive adhesive layer 14 can be improved. Increasing the content of the neutralized polyacrylic acid in the pressure-sensitive adhesive layer 14 tends to decrease the loss tangent. When polyacrylic acid and a neutralized polyacrylic acid (preferably a partially neutralized polyacrylic acid) are used in combination as the water-soluble polymer, the suitable contents of each are also as described above.

[0027] In the acrylic ester having a hydrophilic group, the acrylic ester portion may be an alkyl acrylate ester. This alkyl portion may be an alkyl having 1 to 10 carbon atoms or an alkyl having 1 to 8 carbon atoms. In the acrylic ester having a hydrophilic group, the hydrophilic group may be present in this alkyl portion.

[0028] The adhesive layer 14 may contain a component other than a water-soluble acrylic polymer as a water-soluble polymer. For example, the adhesive layer 14 may contain gelatin, polyvinyl alcohol, polyvinylpyrrolidone, sodium alginate, sodium hyaluronate, hydroxypropyl cellulose, sodium carboxymethylcellulose (carmellose sodium), methylcellulose, carrageenan, glucomannan, agar, guar gum, xanthan gum, gellan gum, pectin, or locust bean gum. These may be used alone or in combination of two or more. For example, carmellose sodium, gelatin, or polyvinyl alcohol may be used. These components may be used in combination with a water-soluble acrylic polymer.

[0029] When the pressure-sensitive adhesive layer 14 contains a water-soluble polymer other than a water-soluble acrylic polymer, the content thereof may be adjusted to 0.1 to 30 mass%, 3 to 18 mass%, or 3 to 10 mass%, based on the total mass of the pressure-sensitive adhesive layer 14. If the content of the water-soluble polymer other than a water-soluble acrylic polymer is 3 mass% or more, the cohesive strength of the pressure-sensitive adhesive layer 14 tends to be high. If the content is 10 mass% or less, the active ingredient contained in the pressure-sensitive adhesive layer 14 tends to be dispersed more uniformly. Increasing the content of the water-soluble polymer other than a water-soluble acrylic polymer in the pressure-sensitive adhesive layer 14 tends to decrease the loss tangent.

[0030] The water content of the adhesive layer 14 improves the skin permeability of the active ingredient, allowing the active ingredient to exert its effect more effectively. The water content may be 10 to 90% by mass, 15 to 88% by mass, or 18 to 85% by mass, based on the total mass of the adhesive layer 14.

[0031] The adhesive layer 14 may contain a methyl acrylate-2-ethylhexyl acrylate copolymer resin. In conventional patches, when the weight of the adhesive layer 14 is small, the water content tends to decrease and the adhesive strength tends to decrease. By containing a methyl acrylate-2-ethylhexyl acrylate copolymer resin in the adhesive layer 14, sufficient adhesive strength tends to be maintained even after a long period of time, even when the mass of the adhesive layer 14 is relatively small.

[0032] The adhesive layer 14 may further contain other components such as a solubilizing agent, a crosslinking agent, a moisturizing agent, a cooling agent, a stabilizer, a filler, a preservative, a chelating agent, an inorganic powder, a coloring agent, a flavoring agent, or a pH adjuster.

[0033] The solubilizing agent is used to dissolve the active ingredient. Examples of the solubilizing agent include crotamiton; N-methylpyrrolidone; polyalkylene glycols such as polyethylene glycol (PEG) and polybutylene glycol; fatty acid esters such as isopropyl myristate and diethyl adipate; oxyalkylene fatty acid esters such as polyethylene glycol monostearate; fatty acid esters such as polyoxyalkylene sorbitan fatty acid esters; polyoxyethylene hydrogenated castor oil; and surfactants such as polysorbate 80. These solubilizing agents may be used alone or in combination of two or more. The content of the solubilizing agent may be adjusted to 0.1 to 10% by mass based on the total mass of the adhesive layer 14.

[0034] The crosslinking agent is used to strengthen the pressure-sensitive adhesive layer 14 and provide it with water retention. Examples of crosslinking agents include thermosetting resins such as amino resins, phenolic resins, epoxy resins, alkyd resins, and unsaturated polyesters, isocyanate compounds, blocked isocyanate compounds, organic crosslinking agents, potassium aluminum sulfate (alum), aluminum silicate, magnesium sulfate, and inorganic crosslinking agents such as metals or metal compounds. The content of the crosslinking agent may be 0.01 to 10 mass%, 0.01 to 6.5 mass%, 0.01 to 3 mass%, 0.05 to 2 mass%, or 0.1 to 1 mass%, based on the total mass of the pressure-sensitive adhesive layer 14. Increasing the content of the crosslinking agent in the pressure-sensitive adhesive layer 14 tends to decrease the loss tangent.

[0035] The humectant is used to suppress evaporation of water from the adhesive layer 14 over time. Examples of humectants include polyhydric alcohols such as glycerin, sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, 1,3-propanediol, and 1,4-butanediol, as well as hyaluronic acid, collagen, ceramide, urea, and heparin. These humectants may be used alone or in combination of two or more. The content of the humectant may be adjusted to be 0.1 to 70% by mass, or 3 to 70% by mass, based on the total mass of the adhesive layer 14.

[0036] When the adhesive layer 14 contains a polyhydric alcohol, the adhesive layer 14 becomes softer and tends to further improve the adhesiveness of the microneedle patch 10. When the content of polyhydric alcohol in the adhesive layer 14 is increased, the loss tangent tends to increase.

[0037] When glycerin is contained as the polyhydric alcohol in the adhesive layer 14, the glycerin content may be 5 to 50 mass%, 10 to 40 mass%, or 15 to 35 mass% based on the total mass of the adhesive layer 14. When the glycerin content is 5 mass% or more, the drying of the adhesive layer 14 can be further delayed during use of the microneedle patch 10, making it easier to maintain the adhesive strength of the microneedle patch 10 for a longer period of time. When the glycerin content is 50 mass% or less, glycerin is less likely to separate from the adhesive layer 14, making the surface of the adhesive layer 14 less sticky. Increasing the glycerin content in the adhesive layer 14 tends to increase the loss tangent.

[0038] Examples of the cooling agent include thymol, l-menthol, dl-menthol, l-isopulegol, and peppermint oil. L-menthol may be used as the cooling agent. The content of the cooling agent may be adjusted to 0.5 to 3 mass % based on the total mass of the adhesive layer 14.

[0039] Examples of stabilizers include oxybenzone, dibutylhydroxytoluene (BHT), sodium edetate, UV absorbers (e.g., dibenzoylmethane derivatives), etc. The content of the stabilizer may be adjusted to 0.01 to 3 mass % based on the total mass of the pressure-sensitive adhesive layer 14.

[0040] Examples of fillers include calcium carbonate, magnesium carbonate, silicates (e.g., aluminum silicate, magnesium silicate, etc.), silicic acid, barium sulfate, calcium sulfate, calcium zincate, zinc oxide, titanium oxide, etc. The content of the filler may be 0.01 to 10 mass % or 3 to 9 mass % based on the total mass of the pressure-sensitive adhesive layer 14. Increasing the content of the filler in the pressure-sensitive adhesive layer 14 tends to decrease the loss tangent.

[0041] Examples of preservatives include methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, and butyl parahydroxybenzoate.

[0042] Examples of the chelating agent include ethylenediaminetetraacetate, pyrophosphate, hexametaphosphate, and gluconic acid. The content of the chelating agent may be 0.01 to 1 mass %, 0.05 to 0.5 mass %, or 0.1 to 0.3 mass % based on the total mass of the adhesive layer 14. Increasing the content of the chelating agent in the adhesive layer 14 tends to increase the loss tangent.

[0043] Examples of pH adjusters include organic acids such as acetic acid, lactic acid, oxalic acid, citric acid, and tartaric acid; inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid; and pharmaceutically acceptable salts of these organic acids and inorganic acids. The content of the pH adjuster may be 0.01 to 1 mass%, 0.05 to 0.5 mass%, or 0.1 to 0.3 mass%, based on the total mass of the adhesive layer 14. When a pH adjuster is used in the adhesive layer 14, the loss tangent tends to decrease as the pH of the adhesive layer 14 decreases, and the loss tangent tends to increase as the pH of the adhesive layer 14 increases.

[0044] As the inorganic powder, coloring agent, and flavoring agent, compositions generally used for the microneedle patch 10 can be used.

[0045] The loss tangent (tanδ) of the adhesive layer 14 constituting the microneedle patch 10, i.e., the adhesive layer 14 after the microneedle patch 10 is manufactured and changes in physical properties (e.g., crosslinking reaction) have converged, may be 0.20 to 0.41. The time required for the change in physical properties to converge varies depending on the composition of the adhesive layer 14 and can be confirmed, for example, by the convergence of changes in the loss tangent or gel strength over time. In the present disclosure, the loss tangent (tanδ) is a value obtained by dynamic viscoelasticity measurement. Specifically, the adhesive layer 14 containing a water-soluble polymer and water is peeled from the microneedle patch 10, the peeled adhesive layer 14 is sandwiched between two plates, and the change in stress when a periodic oscillatory strain is applied to one of the plates is measured. The dynamic viscoelasticity measurement is based on JIS K7244-10:2005 (ISO 6721-10:1999). The loss tangent is obtained by the following formula (1): Loss tangent (tanδ) = loss modulus (G”) / storage modulus (G') ... (1)

[0046] Dynamic viscoelasticity measurements are performed, for example, using a rotational rheometer under measurement conditions of an ambient temperature of 25°C and a frequency of 1 Hz. The above-mentioned range of loss tangent, 0.20 to 0.41, is obtained from measurements under these measurement conditions. This loss tangent can be adjusted to a desired value by changing the content of the water-soluble polymer or water.

[0047] In a first example, the adhesive layer contains a total of 11 to 20% by mass of water-soluble polymers, 3.5 to 7% by mass of sodium carboxymethylcellulose, 2% by mass or more and less than 5% by mass of partially neutralized polyacrylic acid, and 0.22 to 1% by mass of a crosslinking agent. The total amount of water-soluble polymers refers to the sum of the mass % of one or more types of water-soluble polymers.

[0048] In a second example, the adhesive layer contains a water-soluble polymer in a total amount of 11.5 to 18.5 mass%, 3.5 to 6 mass% sodium carboxymethylcellulose, 3 to 4.58 mass% partially neutralized polyacrylic acid, and 0.24 to 1 mass% crosslinking agent.

[0049] In a third example, the adhesive layer contains a water-soluble polymer in a total amount of 11 to 20% by mass, sodium carboxymethylcellulose in an amount of 0.5% by mass or more and less than 3.5% by mass, partially neutralized polyacrylic acid in an amount of 1% by mass or more and less than 5% by mass, and a crosslinking agent in an amount of 1 to 9% by mass.

[0050] In a fourth example, the adhesive layer contains a water-soluble polymer in a total amount of 11.5 to 18.5 mass%, sodium carboxymethylcellulose in an amount of 1 mass% or more and less than 3.5 mass%, partially neutralized polyacrylic acid in an amount of 2 to 4.58 mass%, and a crosslinking agent in an amount of 1 to 6.24 mass%.

[0051] In a fifth example, the adhesive layer contains a water-soluble polymer in a total amount of 11 to 20% by mass, sodium carboxymethylcellulose in an amount of 0.5% by mass or more and less than 3.5% by mass, partially neutralized polyacrylic acid in an amount of 5 to 10% by mass, and a crosslinking agent in an amount of 0.18 to 0.7% by mass.

[0052] In a sixth example, the adhesive layer contains a water-soluble polymer in a total amount of 11.5 to 18.5 mass%, sodium carboxymethylcellulose in an amount of 1 mass% or more and less than 3.5 mass%, partially neutralized polyacrylic acid in an amount of 5 to 8 mass%, and a crosslinking agent in an amount of 0.2 to 0.5 mass%.

[0053] In a seventh example, the adhesive layer contains a water-soluble polymer with a total amount of 11 to 20% by mass, 3.5 to 7% by mass of sodium carboxymethylcellulose, 2% by mass or more and less than 5% by mass of partially neutralized polyacrylic acid, 0.22 to 1% by mass of a crosslinking agent, 0.1 to 5% by mass of polyacrylic acid, 1 to 6% by mass of polyvinyl alcohol, and 0.01 to 1% by mass of disodium ethylenediaminetetraacetate, and the ratio of disodium ethylenediaminetetraacetate to the crosslinking agent is 0.04 to 2.

[0054] In an eighth example, the adhesive layer contains a water-soluble polymer with a total amount of 11.5 to 18.5 mass%, 3.5 to 6 mass% sodium carboxymethylcellulose, 3 to 4.58 mass% partially neutralized polyacrylic acid, 0.24 to 1 mass% crosslinking agent, 0.1 to 5 mass% polyacrylic acid, 1 to 6 mass% polyvinyl alcohol, and 0.01 to 1 mass% disodium ethylenediaminetetraacetate, and the ratio of disodium ethylenediaminetetraacetate to the crosslinking agent is 0.04 to 1.67.

[0055] In a ninth example, the adhesive layer contains a water-soluble polymer in a total amount of 11 to 20% by mass, 0.5% by mass or more and less than 3.5% by mass of sodium carboxymethylcellulose, 1% by mass or more and less than 5% by mass of partially neutralized polyacrylic acid, 1 to 9% by mass of a crosslinking agent, 0.1 to 5% by mass of polyacrylic acid, 1 to 6% by mass of polyvinyl alcohol, and 0.01 to 1% by mass of disodium ethylenediaminetetraacetate, and the ratio of disodium ethylenediaminetetraacetate to the crosslinking agent is 0.04 to 2.

[0056] In a tenth example, the adhesive layer contains a water-soluble polymer in a total amount of 11.5 to 18.5 mass%, carboxymethylcellulose sodium in an amount of 1 mass% or more and less than 3.5 mass%, partially neutralized polyacrylic acid in an amount of 2 to 4.58 mass%, a crosslinking agent in an amount of 1 to 6.24 mass%, polyacrylic acid in an amount of 0.1 to 5 mass%, polyvinyl alcohol in an amount of 1 to 6 mass%, and disodium ethylenediaminetetraacetate in an amount of 0.01 to 1 mass%, and the ratio of disodium ethylenediaminetetraacetate to the crosslinking agent is 0.04 to 1.67.

[0057] In an eleventh example, the adhesive layer contains a water-soluble polymer in a total amount of 11 to 20% by mass, 0.5% by mass or more and less than 3.5% by mass of sodium carboxymethylcellulose, 5 to 10% by mass of partially neutralized polyacrylic acid, 0.18 to 0.7% by mass of a crosslinking agent, 0.1 to 5% by mass of polyacrylic acid, 1 to 6% by mass of polyvinyl alcohol, and 0.01 to 1% by mass of disodium ethylenediaminetetraacetate, and the ratio of disodium ethylenediaminetetraacetate to the crosslinking agent is 0.04 to 2.

[0058] In a twelfth example, the adhesive layer contains a water-soluble polymer in a total amount of 11.5 to 18.5 mass%, carboxymethylcellulose sodium in an amount of 1 mass% or more and less than 3.5 mass%, partially neutralized polyacrylic acid in an amount of 5 to 8 mass%, crosslinking agent in an amount of 0.2 to 0.5 mass%, polyacrylic acid in an amount of 0.1 to 5 mass%, polyvinyl alcohol in an amount of 1 to 6 mass%, and disodium ethylenediaminetetraacetate in an amount of 0.01 to 1 mass%, and the ratio of disodium ethylenediaminetetraacetate to the crosslinking agent is 0.04 to 1.67.

[0059] In any of the above first to twelfth examples, by setting the constituent components of the adhesive layer as described above, the loss tangent of the adhesive layer can be set in the range of 0.20 to 0.41, which makes it possible to peel off the microneedle patch that has been applied to the skin without leaving the microneedle array on the skin.

[0060] In this disclosure, the environmental temperature refers to the temperature of the working environment where the measurement or test is performed. In one example, the environmental temperature refers to both the temperature of the working space and the temperature of at least the part of the measuring device that is in contact with the adhesive layer. The working space may be indoors or outdoors, and therefore the temperature of the working space may be room temperature or the ambient temperature.

[0061] Active ingredients include, for example, antioxidants, free radical scavengers, moisturizers, depigmenting agents, fat regulating agents, UV reflectors, humectants, antibacterial agents, anti-allergy agents, anti-acne agents, anti-aging agents, anti-wrinkle agents, disinfectants, analgesics, cough suppressants, anti-itching agents, local anesthetics, hair loss prevention agents, hair growth promoters, hair growth inhibitors, anti-dandruff agents, antihistamines, keratolytic agents, anti-inflammatory agents, soft drinks, therapeutic agents, anti-infectives, anti-inflammatory agents, antiemetics, anticholinergics, vasoconstrictors, vasodilators, wound healing aids, peptides, polypeptides, proteins, body odor inhibitors, antiperspirants, emollients, skin moisturizers, softeners, hair conditioners, and the like. The active ingredient may be selected from the group consisting of conditioners, hair softeners, hair moisturizers, tanning agents, skin lightening agents, antifungal agents, hair removers, topical analgesics, counterirritants, hemorrhoid medications, insecticides, poison ivy treatments, poison sumac treatments, burn treatments, anti-diaper rash medications, heat rash medications, lotions, vitamins, amino acids, amino acid derivatives, herbal extracts, retinoids, flavonoids, sensory markers, skin conditioners, hair lighteners, chelating agents, cell turnover enhancers, colorants, sunscreens, anesthetics, immunostimulants, nourishing agents, moisture absorbents, sebum absorbents, skin beautifying ingredients, and mixtures thereof.

[0062] The active ingredient may include a plant preparation, such as an extract or tincture, for topical treatment of skin conditions. Examples of extracts or tinctures include oak bark extract, walnut extract, arnica tincture, witch hazel extract, plantain lance extract, pansy extract, thyme or sage extract; St. John's wort tincture, red sedge extract, chamomile flower extract, or calendula tincture; for treating severely fatigued and damaged skin, for example, birch leaf extract, nettle extract, colesfoot extract, comfrey tincture, horsetail extract, or aloe extract; horse chestnut and raft extract, arnica, calendula, and capsicum extract.

[0063] As active ingredients, amino acids may include not only their salts, esters or acyl derivatives, but also amino acids obtained by hydrolysis of various proteins.Examples of such amino acid drugs include: amphoteric amino acids such as alkylamidoalkylamine, glutamic acid stearyl acetyl, capryloyl silk amino acid, capryloyl collagen amino acid; capryloyl keratin amino acid; capryloyl pea amino acid; cocodimonium hydroxypropyl silk amino acid; corn gluten amino acid; cysteine; glutamic acid; glycine; hair keratin amino acid; hair amino acid such as aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, half-cysteine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, cysteic acid, lysine, histidine, arginine, cysteine, tryptophan, citrulline; lysine; silk amino acid; wheat amino acid; and mixtures thereof.

[0064] Active ingredients include peptides, polypeptides, and proteins, including polymers with long chains, e.g., at least about 10 carbon atoms, and high molecular weights, e.g., at least 1,000, formed by the self-condensation of amino acids. Examples of such proteins include collagen, deoxyribonuclease, iodized corn protein, keratin, milk protein, protease, serum protein, silk, sweet almond protein, wheat germ protein, wheat protein, wheat protein, alpha and beta helices of keratin protein, and hair proteins, e.g., intermediate filament proteins, high sulfur content proteins, very high sulfur content proteins, intermediate filament-associated proteins, high tyrosine proteins, high glycine-tyrosine proteins, trichohyalin, and mixtures thereof.

[0065] Examples of anti-wrinkle ingredients include hyaluronic acid, sodium hyaluronate, retinol (vitamin A), silybin peptides (HTC collagen, palmitoyl pentaerythritol, peptide 3, argireline), amino acids, hydroxyproline, tocopheryl retinoate, ursolic acid, vitamin C derivatives, coenzyme Q10, astaxanthin, fullerene, polyphenols, alpha-lipoic acid, soybean extract, pullulan, active isoflavones, sugars, polysaccharides, glycerin, glycerin derivatives, etc. The anti-wrinkle ingredient may be a mixture of at least two of these compositions.

[0066] Examples of vitamins include B complex vitamins; vitamins A, C, D, E, K and derivatives thereof, such as vitamin A palmitate, including thiamine, nicotinic acid, biotin, pantothenic acid, choline, riboflavin, vitamin B6, vitamin B12, pyridoxine, inositol, carnitine; and provitamins, such as panthenol (provitamin B5) and panthenol triacetate; and mixtures thereof.

[0067] Examples of antibacterial agents include bacitracin, erythromycin, neomycin, tetracycline, chlortetracycline, benzethonium chloride, phenol, and mixtures thereof.

[0068] Examples of emollients and skin moisturizers include mineral oil, lanolin, vegetable oil, isostearyl isostearate, glyceryl laurate, methyl gluceth-10, methyl gluceth-20, chitosan, and mixtures thereof.

[0069] Examples of hair conditioners include fat-soluble compounds such as cetyl alcohol, stearyl alcohol, hydrogenated polydecene, and mixtures thereof, as well as quaternary compounds such as behenamidopropyl PG-dimonium chloride, tricetylammonium chloride, hydrogenated tallowamidoethyl hydroxyethylmonium methosulfate, and mixtures thereof.

[0070] Examples of sunscreens include butyl methoxydibenzoylmethane, octyl methoxycinnamate, oxybenzone, octocrylene, octyl salicylate, phenylbenzimidazole sulfonic acid, ethyl hydroxypropyl aminobenzoate, menthyl anthranilate, aminobenzoic acid, cinoxate, diethanolamine methoxycinnamate, glycerin aminobenzoate, titanium dioxide, zinc oxide, oxybenzone, padimate O, red petrolatum, and mixtures thereof. An example of a tanning agent is dihydroxyacetone.

[0071] Examples of skin lightening agents include hydroquinone and its derivatives, catechol and its derivatives, ascorbic acid and its derivatives, ellagic acid and its derivatives, kojic acid and its derivatives, tranexamic acid and its derivatives, resorcinol derivatives, placenta extract, arbutin, oil-soluble licorice extract, and mixtures thereof.

[0072] Examples of anti-inflammatory analgesics include acetaminophen, methyl salicylate, monoglycol salicylate, aspirin, mefenamic acid, flufenamic acid, indomethacin, diclofenac, alclofenac, diclofenac sodium, ibuprofen, ketoprofen, naproxen, pranoprofen, fenoprofen, sulindac, fenclofenac, clidanac, flurbiprofen, fentiazac, bufexamac, piroxicam, phenylbutazone, oxyphenbutazone, clofezone, pentazocine, mepirizole, and tiaramide hydrochloride. Examples of steroidal anti-inflammatory analgesics that may be used with the microneedle patch 10 include hydrocortisone, prednisolone, dexamethasone, triamcinolone acetonide, fluocinolone acetonide, hydrocortisone acetate, prednisolone acetate, methylprednisolone, dexamethasone acetate, betamethasone, betamethasone valerate, flumethasone, fluorometholone, and beclomethasone dipropionate.

[0073] Examples of antihistamines include diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine, chlorpheniramine hydrochloride, chlorpheniramine maleate, isothipendyl hydrochloride, tripeleramine hydrochloride, promethazine hydrochloride, and methdilazine hydrochloride. Examples of local anesthetics that can be used with the microneedle patch 10 include dibucaine hydrochloride, dibucaine, lidocaine hydrochloride, benzocaine, p-butylaminobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, procaine hydrochloride, tetracaine, tetracaine hydrochloride, chloroprocaine hydrochloride, oxyprocaine hydrochloride, mepivacaine, cocaine hydrochloride, piperocaine hydrochloride, dyclonine, and dyclonine hydrochloride.

[0074] Examples of disinfectants and antiseptics include thimerosal, phenol, thymol, benzalkonium chloride, benzethonium chloride, chlorhexidine, povidone-iodine, cetylpyridinium chloride, eugenol, and trimethylammonium bromide. Examples of vasoconstrictors that can be used with the microneedle patch 10 include naphazoline nitrate, tetrahydrozoline hydrochloride, oxymetazoline hydrochloride, phenylephrine hydrochloride, and tramazoline hydrochloride. Examples of hemostatic agents that can be used with the microneedle patch 10 include thrombin, phytonadione, protamine sulfate, aminocaproic acid, tranexamic acid, carbazochrome, carbazochrome sodium sulfonate, rutin, and hesperidin.

[0075] Examples of chemotherapeutic agents include sulfamine, sulfathiazole, sulfadiazine, homosulfamine, sulfisoxazol, sulfisomidine, sulfamethizole, and nitrofurazone. Examples of antibiotics that may be used with the microneedle patch 10 include penicillin, methicillin, oxacillin, cephalothin, cephalosporin, erythromycin, lincomycin, tetracycline, chlorotetracycline, oxytetracycline, methacycline, chloramphenicol, kanamycin, streptomycin, gentamicin, bacitracin, and cycloserine.

[0076] Examples of antiviral agents include protease inhibitors, thymazine kinase inhibitors, sugar or glycoprotein synthesis inhibitors, constitutive protein synthesis inhibitors, attachment and adsorption inhibitors, and nucleoside analogues such as acyclovir, penciclovir, valacyclovir, and ganciclovir.

[0077] Examples of hair growth or hair restoration agents include minoxidil, carpronium chloride, pentadecanoic acid glyceride, tocopherol acetate, piroctone olamine, glycyrrhizic acid, isopropylmethylphenol, hinokitiol, Swertia japonica extract, ceramides and precursors, nicotinamide, and capsicum tincture.

[0078] Examples of cosmetic active ingredients include D-alpha-tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, ascorbyl palmitate, vitamin F and vitamin F glycerides, vitamin D, vitamin D2, vitamin D3, retinol, retinol esters, retinyl palmitate, retinyl propionate, beta-carotene, coenzyme Q10, D-panthenol, farnesol, farnesyl acetate; jojoba oil and blackcurrant oil, which are rich in essential fatty acids; 5-n-octanoyl salicylic acid and its esters, salicylic acid and its esters; e.g. alkyl esters of alpha-hydroxy acids such as citric acid, lactic acid, glycolic acid; asiatic acid, madecassic acid, asiaticoside, Centella asiatica total extract, beta-glycyrrhetinic acid, alpha-bisabolol, ceramides such as 2-oleoylamino-1,3-octadecane; phytantriol, a phospholipid of marine origin rich in polyunsaturated essential fatty acids, ethoxyquin; rosemary extract, balm extract, quercetin, extracts of dried microalgae, anti-inflammatory drugs such as steroidal anti-inflammatory drugs, and biochemical stimulants such as hormones or compounds involved in fat and / or protein synthesis.

[0079] Vitamin C promotes collagen (connective tissue) synthesis, lipid (fat) and carbohydrate metabolism, and neurotransmitter synthesis. Vitamin C may also contribute to optimal immune system maintenance. Vitamin C is toxic to a wide range of cancer cells, particularly melanoma. Tyrosine oxidase, which catalyzes the aerobic conversion of tyrosine into melanin and other pigments, is also inhibited by the presence of vitamin C. Vitamin C has been found to be effective in catalyzing immune responses to many viral and bacterial infections. In addition to the many applications mentioned above, vitamin C is essential for collagen synthesis and wound healing. The microneedle patch 10 may contain a combination of vitamin C, vitamin E, and other ingredients, such as moisturizers, collagen synthesis promoters, and facial scrubs.

[0080] Skin conditioner ingredients may include mineral oil, petrolatum, vegetable oils (such as soybean oil or maleated soybean oil), dimethicone, dimethicone copolyol, cationic monomers and polymers (such as guar hydroxypropyltrimonium chloride and distearyl dimethyl ammonium chloride), and mixtures thereof. The humectant may be a polyol, such as sorbitol, glycerin, propylene glycol, ethylene glycol, polyethylene glycol, polypropylene glycol, 1,3-butanediol, hexylene glycol, isoprene glycol, xylitol, fructose, and mixtures thereof.

[0081] The skin-beautifying ingredient may include tea extract (e.g., karatsu tea extract, ureshino tea extract, Shizuoka tea extract, etc.), sake lees extract (e.g., junmai daiginjo sake lees extract, daiginjo sake lees extract, junmai ginjo sake lees extract, ginjo sake lees extract, etc.), citrus extract (e.g., genko extract, sudachi extract, unshu mandarin orange extract, etc.), seaweed extract (e.g., nori extract, etc.), and plant extract (e.g., asparagus extract, etc.), as well as mixtures thereof.

[0082] These active ingredients may be used alone or in combination of two or more. As long as the salt is pharmaceutically acceptable, the active ingredient may be in the form of either an inorganic salt or an organic salt. The active ingredient may be applied directly to the skin, and then the microneedle array 20 (described below) may be applied to the same area of ​​the skin. In this case, the skin stretching effect and the ODT (occlusive dressing therapy) effect on the skin can promote the penetration of the active ingredient into the skin.

[0083] The mass of the adhesive layer 14 is, for example, 500 g / m 2 It can be more than 700g / m 2 The mass of the adhesive layer 14 may be, for example, 2000 g / m 2 It may be less than 1500g / m 2 The mass of the pressure-sensitive adhesive layer 14 may be 700 to 1500 g / m 2In this case, the fit is improved and adhesion can be maintained for a longer period of time. By setting the mass of the adhesive layer 14 as described above, the overall thickness of the microneedle patch 10 can be reduced, and as a result, the microneedle patch 10 can easily conform to the skin and become less likely to peel off.

[0084] The release sheet 16 is a sheet-like member that protects the adhesive layer 14 before the microneedle patch 10 is used.

[0085] The release sheet 16 may have weakened portions 16a formed along its entire length or width. The weakened portions 16a are provided to make it easier to tear the release sheet 16. In the example of FIG. 1, the weakened portions 16a are linear perforations, but the form of the weakened portions 16a is not limited to this. For example, the weakened portions 16a may be thin-walled, half-cut, or may have other shapes. The weakened portions 16a may also have a wave-like or sawtooth shape.

[0086] The release sheet 16 may be a plastic film such as polypropylene (for example, unstretched polypropylene or stretched polypropylene), polyethylene terephthalate, polybutylene terephthalate, polyethylene, polyester, polyurethane, polyvinyl chloride, or polystyrene, or may be a silicone-coated paper obtained by silicone-coating synthetic resin, synthetic paper, or synthetic fiber, or may be a laminated paper obtained by laminating polyethylene or the like onto aluminum foil or kraft paper. The release sheet 16 may be colorless, or may be at least partially colored.

[0087] The microneedle array 20 is an instrument for puncturing or pressing the skin. The example in Fig. 1 shows one microneedle array 20, but multiple microneedle arrays 20 may be embedded in the adhesive layer 14. When multiple microneedle arrays 20 are used, they may have the same shape and dimensions, or at least one of the shape and dimensions may be different from each other.

[0088] In one example, at least a portion of the microneedle array 20 is embedded in the adhesive layer 14 (i.e., at least a portion of the microneedle array 20 is located within the adhesive layer 14). For example, at least a portion of each microneedle 22 may be located within the adhesive layer 14. The entire microneedle array 20 may be embedded in the adhesive layer 14 (i.e., the entirety of each microneedle 22 may be located within the adhesive layer 14).

[0089] 2 is an enlarged perspective view showing an example of the microneedle array 20. In one example, the microneedle array 20 includes a substrate 21 and at least one microneedle 22 provided on the substrate 21.

[0090] Materials for the microneedle array 20 (substrate 21 and microneedles 22) may include, for example, silicon, silicon dioxide, ceramic, metal (stainless steel, titanium, nickel, molybdenum, chromium, cobalt, etc.), synthetic or natural resin materials, etc. Alternatively, biodegradable polymers such as polylactic acid, polyglycolide, polylactic acid-co-polyglycolide, pullulan, caprolactone, polyurethane, and polyanhydride may be used, taking into consideration the antigenicity of the microneedles 22 and the unit cost of the material. Non-degradable polymers such as polyethylene, polypropylene, polyamide, polyethylene terephthalate, cyclic olefin copolymer, polycarbonate, polymethacrylic acid, polymethyl methacrylate, rigid polyvinyl chloride, ethylene vinyl acetate, polytetrafluoroethylene, tetrafluoroethylene-ethylene copolymer, polyoxymethylene, and acrylonitrile-butadiene-styrene copolymer may also be used. Alternatively, polysaccharides such as hyaluronic acid, sodium hyaluronate, pullulan, dextran, dextrin, or chondroitin sulfate, or cellulose derivatives may be used. Considering the possibility that the microneedles 22 may break on the skin, a biodegradable resin may be employed, such as polylactic acid. Polylactic acid includes polylactic acid homopolymers such as poly-L-lactic acid and poly-D-lactic acid, poly-L / D-lactic acid copolymers, and mixtures thereof, and any of these may be used. The greater the average molecular weight of polylactic acid, the stronger its strength; for example, polylactic acid with an average molecular weight of 40,000 to 100,000 may be used. The substrate 21 and the microneedles 22 may be made of the same material or different materials.

[0091] The substrate 21 is a base for supporting the microneedles 22. In the present disclosure, the surface from which the microneedles 22 stand is referred to as the main surface of the substrate 21, and the side opposite to the main surface is referred to as the back surface of the substrate 21. In the example of FIG. 1, the back surface of the substrate 21 is in contact with the main surface of the support 12. The dimensions of the substrate 21 may be determined taking into consideration the dimensions of the adhesive layer 14. In the example of FIG. 1, the area of ​​the substrate 21 is smaller than the area of ​​the adhesive layer 14. In another example, the areas of the substrate 21 and the adhesive layer 14 may be the same. Alternatively, the area of ​​the substrate 21 may be larger than the area of ​​the adhesive layer 14, in which case part of the substrate 21 will be exposed. The area of ​​the substrate 21 is 0.5 cm 2 ~300cm 2 Or 1cm 2 ~100cm 2 Or 1cm 2 ~50cm 2 Alternatively, the area of ​​the substrate 21 may be 0.5 cm 2 ~10cm 2 , 0.5cm 2 ~5cm 2 , 1cm 2 ~5cm 2 , 0.5cm 2 ~3cm 2 , or 1 cm 2 ~3cm 2 A substrate of a desired size may be formed by joining several of these substrates 21. The lower limit of the thickness of substrate 21 may be 5 μm or 20 μm, and the upper limit of the thickness may be 1000 μm or 300 μm.

[0092] The microneedles 22 are minute structures rising from the main surface of the substrate 21. The microneedles 22 have a tapered shape that narrows from the bottom connected to the substrate 21 towards the tip. In this specification, the term "microneedle" is a concept that includes not only needle-shaped structures in the broad sense and structures including a needle shape, but also blunt shapes.

[0093] The lower limit of the density of the microneedles 22 is, for example, 0.05 needles / cm 2 , 1 piece / cm 2 , 100 pieces / cm 2 , 200 pieces / cm2 , 300 pieces / cm 2 , or 400 lines / cm 2 On the other hand, the upper limit of the density is, for example, 10,000 fibers / cm 2 , 5000 pieces / cm 2 , 2000 pieces / cm 2 , or 850 lines / cm 2 The lower limit of density is calculated from the number of needles required to administer 1 mg of active ingredient and the required area. The upper limit of density is determined by taking into account the shape of the needles.

[0094] The lower limit of the length of the microneedle 22 may be 20 μm or 50 μm, and the upper limit may be 1000 μm, 600 μm, or 500 μm. The length of the microneedle 22 is the distance from the base where it connects to the substrate 21 to the tip. The reason for setting the length of the microneedle 22 to 20 μm or more is to ensure transdermal absorption of the active ingredient. Setting the length of the microneedle 22 to 600 μm or less prevents the microneedle 22 from contacting nerves, reducing the possibility of pain and avoiding the possibility of bleeding. A microneedle length of 500 μm or less allows for efficient administration of the desired amount of active ingredient into the skin, and for example, allows for administration of the active ingredient without perforating the basement membrane. In one example, the length of the microneedle 22 is selected so that it does not penetrate the stratum corneum of the skin during normal use, although some of the microneedles 22 may penetrate the stratum corneum. That is, the microneedles 22 stretch and thin the epidermis, allowing the active ingredient to penetrate the more permeable epidermis, but some of the active ingredient may also penetrate into the skin through holes formed in the stratum corneum.

[0095] In the example of FIG. 2, the microneedle 22 has a three-dimensional shape. For example, the microneedle 22 may be a cone or any other pyramid such as a square pyramid. The microneedle 22 does not have to be a cone, and may have a flat or rounded tip, for example. A flat or rounded tip may be obtained by intentional processing or may be obtained without such processing. When the tip is flat, the area of ​​the flat part is 20 to 600 μm 2 may be 50 to 250 μm 2 When the tip is rounded, the radius of curvature of the tip may be 2 to 100 μm, or 5 to 30 μm.

[0096] Methods for manufacturing the microneedle array 20 having three-dimensional microneedles 22 include wet etching or dry etching using a silicon substrate, precision machining using metal or resin (electrical discharge machining, laser machining, dicing, hot embossing, injection molding, etc.), and mechanical cutting. By these processing methods, the substrate 21 and the microneedles 22 are integrally molded. A method for making the microneedles 22 hollow includes a method in which the microneedles 22 are fabricated and then subjected to secondary processing such as laser machining.

[0097] The microneedles 22 may contain an active ingredient, or a coating containing the active ingredient may be formed on the surface of the microneedles 22.

[0098] The microneedles 22 may be planar. For example, the microneedles 22 may be triangular or may have other shapes such as a diamond. The planar microneedles 22 are formed by punching the substrate 21 to form the microneedles 22 and then elevating the microneedles 22 from the substrate 21. Therefore, the substrate 21 and the microneedles 22 have the same thickness. If the substrate 21 is metal, a large number of microneedles 22 can be formed by punching the sheet with a chemical solution, and the microneedles 22 can be raised to form the microneedle array 20. If the substrate 21 is nonmetallic, a large number of microneedles 22 can be formed by punching the substrate 21 with a laser, and the microneedles 22 can be raised in the same manner as in the case of a metal sheet. When etching is used in this manner, voids are formed around each microneedle 22.

[0099] Regardless of whether the microneedle 22 has a three-dimensional or planar shape, the direction in which the tip of the microneedle 22 faces (the tip direction of the microneedle 22) may be perpendicular to the surface of the substrate 21 or may be at an acute angle to that surface (i.e., the inclination angle of the microneedle 22 is greater than 0 degrees and less than 90 degrees).

[0100] Next, an example of a method for producing the microneedle patch 10 will be described. First, an adhesive layer 14 is formed by spreading an adhesive composition on a release sheet 16. Next, the microneedle array 20 is placed on the adhesive layer 14 so that at least a portion of each microneedle 22 is embedded in the adhesive layer 14. Next, the support 12 is placed on the adhesive layer 14 and the microneedle array 20 so that the main surface of the support 12 and the back surface of the substrate 21 are in contact. As a result, the adhesive layer 14 and the microneedles 22 are sandwiched between the support 12 and the release sheet 16.

[0101] The microneedle patch 10 may be stored inside a packaging bag. This storage method can prevent a decrease in the water content of the adhesive layer 14 and reduce the adhesion of dirt and the like to the adhesive layer 14. The microneedle patch 10 may be stored in a packaging bag in a state where it is folded multiple times. In this case, the space required for storing the microneedle patch 10 is saved, and therefore the material used for the packaging bag can be reduced.

[0102] The present disclosure has been described in detail above based on the embodiments. However, the present disclosure is not limited to the above examples. Various modifications are possible within the scope of the present disclosure.

[0103] In the above example, the microneedle patch 10 is generally rectangular, but the microneedle patch may have other shapes. For example, the microneedle patch may have any shape, such as a square, circle, ellipse, crescent, magatama, or other polygon. In the above example, the microneedle array 20 is generally rectangular, but the microneedle array may have other shapes. For example, the microneedle array may have any shape, such as a square, circle, ellipse, crescent, or other polygon. The shape of the microneedle array may be the same as or different from the shape of the microneedle patch.

[0104] [Note] The present disclosure includes the following aspects. (Appendix 1) A support; a pressure-sensitive adhesive layer provided on a main surface of the support; a microneedle array at least a portion of which is located within the adhesive layer; Equipped with the pressure-sensitive adhesive layer comprises a water-soluble polymer in a total amount of 11 to 20% by mass, 3.5 to 7% by mass of sodium carboxymethylcellulose, 2% by mass or more and less than 5% by mass of a partially neutralized polyacrylic acid, and 0.22 to 1% by mass of a crosslinking agent; Microneedle patch. (Appendix 2) A support; a pressure-sensitive adhesive layer provided on a main surface of the support; a microneedle array at least a portion of which is located within the adhesive layer; Equipped with The pressure-sensitive adhesive layer comprises a water-soluble polymer in a total amount of 11 to 20% by mass, 0.5% by mass or more and less than 3.5% by mass of sodium carboxymethylcellulose, 1% by mass or more and less than 5% by mass of a partially neutralized polyacrylic acid, and 1 to 9% by mass of a crosslinking agent. Microneedle patch. (Appendix 3) A support; a pressure-sensitive adhesive layer provided on a main surface of the support; a microneedle array at least a portion of which is located within the adhesive layer; Equipped with the pressure-sensitive adhesive layer comprises a water-soluble polymer in a total amount of 11 to 20% by mass, 0.5% by mass or more and less than 3.5% by mass of sodium carboxymethylcellulose, 5 to 10% by mass of a partially neutralized polyacrylic acid, and 0.18 to 0.7% by mass of a crosslinking agent; Microneedle patch.

[0105] The inventors have discovered that for each of Appendices 1 to 3, by setting the constituent components of the adhesive layer that covers at least a portion of the microneedles as shown in the Appendices, a microneedle patch that has been applied to the skin can be peeled off without leaving the microneedle array on the skin. [Example]

[0106] Examples will be specifically described below, but the present disclosure is not limited thereto.

[0107] Six types of adhesive compositions were prepared according to the compositions (unit: mass %) shown in Table 1 below. Each of the six types of adhesive compositions was used to prepare a microneedle patch by the manufacturing method exemplified above. The microneedle patch had an area of ​​15 cm. 2 The adhesive layer had a mass of 1000 g / m 2The microneedle array had a thickness of 700 μm and an area of ​​1.4 cm 2 On a circular substrate, 640 microneedles with a length of 500 μm were placed per cm. 2 The support was made of a sheet with a basis weight of 100 g / m 2 A PET nonwoven fabric was used. An adhesive layer was formed so that the microneedles were entirely buried. Below, the six types of microneedle patches are distinguished as Examples 1 and 2 and Comparative Examples 1 to 4.

[0108] [Table 1]

[0109] The microneedle patches were stored in packaging at an ambient temperature of 25°C and a relative humidity of 50% for 14 days after production, allowing the crosslinking reaction of each of the six types of microneedle patches to fully converge. The adhesive layer was then peeled off from each microneedle patch, and the dynamic viscoelasticity of the adhesive layer was measured using a rheometer "HAAKE MARS" (manufactured by Thermo Fisher Scientific Co., Ltd.) under the following measurement conditions. The loss tangent (tanδ) was then calculated from the measured storage modulus (G') and loss modulus (G") using the method (1) above.

[0110] [Measurement conditions] Sample part: 20mm diameter flat plate Gap spacing: 1mm Sample size: 0.8-1.2g Ambient temperature: 25°C (This ambient temperature corresponds to both the temperature of the working space and the temperature of the part of the rheometer that comes into contact with the adhesive layer.) Frequency: 1Hz ·Distortion: 1%

[0111] A 90° peel test was performed on each of the five types of microneedle patches excluding Comparative Example 1. Comparative Example 1 had low adhesion of the pressure-sensitive adhesive layer, and the microneedle patch easily fell off from the target, so Comparative Example 1 was excluded from the evaluation. The microneedle patch was attached to a PTFE (polytetrafluoroethylene) plate, and 15 minutes later, a 90° peel test was performed using an autograph at an ambient temperature of 25°C and a peel speed of 50 mm / min. This test was performed three times for each of the five types of microneedle patches excluding Comparative Example 1. A score of "1" was assigned if the microneedle array did not fall off the microneedle patch during the test, and a score of "0" was assigned if the microneedle array fell off, with the average of the three scores being the final score.

[0112] A peeling sensory test was carried out for each of the five types of microneedle patches excluding Comparative Example 1. The microneedle patches were attached to the upper arms of five subjects, and 15 minutes later, the microneedle patches were peeled off from the skin. During this peeling, it was visually confirmed whether the microneedle array had fallen off from the microneedle patch. When the microneedle array did not fall off from the microneedle patch during the test, the score was set to "1", and when it fell off, the score was set to "0", and the average of the scores of the five subjects was obtained as the final score.

[0113] Table 1 above also shows the calculated loss tangent and the results of the two types of tests. The 90° peel test score and peel sensory test score of 1 for Examples 1 and 2 indicate that the microneedle array never fell off the microneedle patch. The 90° peel test score and peel sensory test score of 0 for Comparative Example 2 indicate that the microneedle array fell off in all microneedle patches. The peel sensory test score of 0.4 for Comparative Examples 3 and 4 indicates that the microneedle array fell off the microneedle patch in 3 out of 5 people.

[0114] Using the same method as for the six types of adhesive compositions described above, 38 additional types of adhesive compositions were prepared according to the compositions (unit: mass %) shown in Tables 2 to 6 below, and microneedle patches were fabricated using each adhesive composition. Hereinafter, the 38 types of microneedle patches are distinguished as Examples 3 to 18 and Comparative Examples 5 to 26. For each of the additional 38 types of microneedle patches, the loss tangent of the adhesive layer was calculated, and a 90° peel test and a peel sensory test were performed, as with the six types of microneedle patches described above. However, comparative examples in which a microneedle patch could not be fabricated and comparative examples in which the adhesive layer had low adhesion and the microneedle patch easily peeled off from the target were excluded from the evaluation. Comparative Example 12 received a score of "0" in the 90° peel test, so the peel sensory test was omitted.

[0115] [Table 2]

[0116] [Table 3]

[0117] [Table 4]

[0118] [Table 5]

[0119] [Table 6]

[0120] Tables 2 to 5 differ from Table 1 in that they further include three rows: "Water-soluble polymer," "Crosslinker," and "EDTA / Crosslinker." The "Water-soluble polymer" row indicates the total mass percent of polyacrylic acid, partially neutralized polyacrylic acid, sodium carboxymethylcellulose, and polyvinyl alcohol. That is, the "Water-soluble polymer" row indicates the total amount of water-soluble polymer. The "Crosslinker" row indicates the total mass percent of alum and aluminum silicate. The "EDTA / Crosslinker" row indicates the ratio of disodium ethylenediaminetetraacetate to the crosslinker. Examples 1 and 2 and Comparative Examples 1 to 4 shown in Table 1 are also shown in Tables 2 to 5 as necessary.

[0121] Table 2 relates to the above-mentioned Examples 1 to 12. Table 2 shows that when the total amount of the water-soluble polymer falls outside the range of 11 to 20% by mass, the loss tangent falls outside the range of 0.20 to 0.41, and at least one of the scores in the 90° peel test and the peel sensory test is not "1." In other words, when the total amount of the water-soluble polymer falls outside the specified range, the microneedle array falls off from the microneedle patch during the test or peeling, the microneedle patch could not be produced, or the adhesive strength of the pressure-sensitive adhesive layer is so low that the microneedle patch easily falls off from the target.

[0122] Table 3 relates to the first, second, seventh, and eighth examples. Table 3 shows that when the amount of sodium carboxymethylcellulose is outside the range of 3.5 to 7% by mass, when the amount of partially neutralized polyacrylic acid is outside the range of 2% to less than 5% by mass, or when the amount of crosslinker is outside the range of 0.22 to 1% by mass, the loss tangent falls outside the range of 0.20 to 0.41, and at least one of the scores in the 90° peel test and the peel sensory test is not "1." In other words, when the amount of sodium carboxymethylcellulose, partially neutralized polyacrylic acid, or crosslinker is outside the corresponding specified range, the microneedle array fell off the microneedle patch during testing or peeling, the microneedle patch could not be prepared, or the microneedle patch easily fell off the target due to poor adhesiveness of the pressure-sensitive adhesive layer.

[0123] Table 4 relates to the third, fourth, ninth, and tenth examples. Table 4 shows that when the amount of sodium carboxymethylcellulose is out of the range of 0.5% by mass or more and less than 3.5% by mass, when the amount of partially neutralized polyacrylic acid is out of the range of 1% by mass or more and less than 5% by mass, or when the amount of crosslinker is out of the range of 1 to 9% by mass, the loss tangent falls out of the range of 0.20 to 0.41, and at least one of the 90° peel test score and the peel sensory test score is not "1." In other words, when the amount of sodium carboxymethylcellulose, partially neutralized polyacrylic acid, or crosslinker is out of the corresponding specified range, the microneedle array fell off the microneedle patch during testing or peeling, the microneedle patch could not be prepared, or the microneedle patch easily fell off the target due to poor adhesion of the pressure-sensitive adhesive layer.

[0124] Table 5 relates to Examples 5, 6, 11, and 12 above. Table 5 shows that when the amount of sodium carboxymethylcellulose is out of the range of 0.5% by mass or more and less than 3.5% by mass, when the amount of partially neutralized polyacrylic acid is out of the range of 5 to 10% by mass, or when the amount of crosslinker is out of the range of 0.18 to 0.7% by mass, the loss tangent is out of the range of 0.20 to 0.41, and at least one of the 90° peel test score and the peel sensory test score is not "1." In other words, when the amount of sodium carboxymethylcellulose, partially neutralized polyacrylic acid, or crosslinker is out of the corresponding specified range, the microneedle array fell off the microneedle patch during the test or peeling, the microneedle patch could not be prepared, or the microneedle patch easily fell off the target due to low adhesiveness of the pressure-sensitive adhesive layer.

[0125] Table 6, like Tables 2 to 5, includes three rows: "Water-soluble polymer," "Crosslinker," and "EDTA / Crosslinker." However, the "Crosslinker" row in Table 6 indicates the total mass percent of alum, aluminum silicate, and magnesium aluminometasilicate. Example 15 demonstrates that the loss tangent can be set in the range of 0.20 to 0.41 without using alum. Examples 16 and 17 demonstrate that the loss tangent can be set in the range of 0.20 to 0.41 without using glycerin. Example 18 demonstrates that the loss tangent can be set in the range of 0.20 to 0.41 without using tartaric acid. In all of Examples 15 to 18, the 90° peel test score and peel sensory test score were both "1," corresponding to the loss tangent results. [Explanation of symbols]

[0126] 10...microneedle patch, 12...support, 14...adhesive layer, 16...release sheet, 16a...weakened portion, 20...microneedle array, 21...substrate, 22...microneedle.

Claims

1. A support; a pressure-sensitive adhesive layer provided on a main surface of the support; a microneedle array at least a portion of which is located within the adhesive layer; Equipped with the pressure-sensitive adhesive layer comprises a water-soluble polymer in a total amount of 11 to 20% by mass, 3.5 to 7% by mass of sodium carboxymethylcellulose, 2% by mass or more and less than 5% by mass of a partially neutralized polyacrylic acid, and 0.22 to 1% by mass of a crosslinking agent; the crosslinking agent includes at least one of an amino resin, a phenolic resin, an epoxy resin, an alkyd resin, an unsaturated polyester, an isocyanate compound, a blocked isocyanate compound, alum, aluminum silicate, magnesium sulfate, and magnesium aluminometasilicate; Microneedle patch.

2. A support; a pressure-sensitive adhesive layer provided on a main surface of the support; a microneedle array at least a portion of which is located within the adhesive layer; Equipped with the pressure-sensitive adhesive layer comprises a water-soluble polymer in a total amount of 11 to 20% by mass, 0.5% by mass or more and less than 3.5% by mass of sodium carboxymethylcellulose, 1% by mass or more and less than 5% by mass of a partially neutralized polyacrylic acid, and 1 to 9% by mass of a crosslinking agent; the crosslinking agent includes at least one of an amino resin, a phenolic resin, an epoxy resin, an alkyd resin, an unsaturated polyester, an isocyanate compound, a blocked isocyanate compound, alum, aluminum silicate, magnesium sulfate, and magnesium aluminometasilicate; Microneedle patch.

3. A support; a pressure-sensitive adhesive layer provided on a main surface of the support; a microneedle array at least a portion of which is located within the adhesive layer; Equipped with the pressure-sensitive adhesive layer comprises a water-soluble polymer in a total amount of 11 to 20% by mass, 0.5% by mass or more and less than 3.5% by mass of sodium carboxymethylcellulose, 5 to 10% by mass of a partially neutralized polyacrylic acid, and 0.18 to 0.7% by mass of a crosslinking agent; the crosslinking agent includes at least one of an amino resin, a phenolic resin, an epoxy resin, an alkyd resin, an unsaturated polyester, an isocyanate compound, a blocked isocyanate compound, alum, aluminum silicate, magnesium sulfate, and magnesium aluminometasilicate; Microneedle patch.

Images