JP7798754B2 - Microneedle patches - Google Patents

Description

One aspect of the present disclosure relates to a microneedle patch.

Patent Document 1 describes a patch with microneedles. This patch has one or more microneedle members inside the adhesive layer that can protrude from the adhesive layer toward the adhesive surface.

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.

Japanese Patent Application Laid-Open No. 2007-1938 JP 2015-151380 A

There is a need for a microneedle patch that does not leave the microneedle array on the skin when removed.

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.

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.

One aspect of the present disclosure provides a microneedle patch that does not leave a microneedle array on the skin when removed from the skin.

FIG. 1 is a perspective view of a microneedle patch according to an embodiment. FIG. 2 is an enlarged perspective view showing an example of the microneedle array shown in FIG. 1.

Embodiments of the present disclosure will be described in detail below with reference to the accompanying drawings. In the description of the drawings, identical or equivalent elements will be designated by the same reference numerals, and duplicate explanations will be omitted.

Figure 1 is a perspective view of a microneedle patch 10 according to an embodiment. The microneedle patch 10 is a preparation used as a poultice, 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 within 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.

The dimensions of the microneedle patch 10 may be set according to the user's symptoms, age, weight, gender, etc. For example, the area of the microneedle patch 10 may be 1 to 500 ^cm2 , or 10 to 400 ^cm2 . By making the area 1 ^cm2 or more, it becomes easier to maintain sufficient skin permeability of the active ingredient. By making the area 500 ^cm2 or less, it becomes easier to handle the microneedle patch 10.

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 seal, and migration of the active ingredient into the support 12. For example, the material may be woven fabric, nonwoven fabric, resin film, foam sheet, or paper. An example of a woven fabric is knitted fabric. When a woven fabric, nonwoven fabric, or 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.

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

When the backing 12 is a knitted fabric or a nonwoven fabric, spreading a water-containing PSA composition on the backing 12 may cause the PSA composition to seep through the mesh of the backing 12 to the backside of the backing. Taking this into consideration, the basis weight of the knitted fabric or nonwoven fabric may be 50 to 150 g/ ^m2 , or 75 to 125 g/ ^m2 . By setting the basis weight within this range, the PSA composition tends to be able to be spread without seeping through the gaps in the backing 12 to the backside of the backing 12. In addition, anchoring properties between the backing 12 and the PSA layer 14 can be maintained.

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, "longitudinal direction" refers to the direction of flow in the knitted fabric manufacturing process, and "transverse direction" refers to the direction perpendicular to the longitudinal direction, i.e., the width direction. The modulus measurement method is based on JIS L 1018:1999.

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 make the microneedle patch 10 easier to handle. 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.

The adhesive layer 14 is a layer with 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" encompasses both an embodiment in which the adhesive layer 14 contains an active ingredient, and an embodiment in which the active ingredient is attached to the working surface of the adhesive layer 14.

A water-soluble polymer refers to a polymer having a hydrophilic group. Examples of hydrophilic groups include a hydroxy group, a carboxy group, and an amino group. By including a water-soluble polymer in the adhesive layer 14, moisture in the microneedle patch 10 can be retained for a longer period of time.

The water-soluble polymer may be polyacrylic acid or a neutralized polyacrylic acid (sometimes referred to as a "water-soluble acrylic polymer"). By including polyacrylic acid or its neutralized product in the adhesive layer 14, it is possible to provide an adhesive layer 14 with excellent adhesive properties.

A water-soluble acrylic polymer is a polymer obtained by polymerizing an acryloyl group-containing compound that has a functional group (hydrophilic group) that exhibits water solubility. The pressure-sensitive adhesive layer 14 exhibits adhesiveness by containing a water-soluble acrylic polymer along with water. Examples of water-soluble acrylic polymers include polymers obtained by polymerizing a compound that has an acryloyl group, such as polyacrylic acid or its neutralized product, an acrylic acid ester that has a hydrophilic group, or an acrylic acid amide that has a hydrophilic group. The water-soluble acrylic polymer may be a homopolymer obtained from a compound that has one type of acryloyl group, or a copolymer obtained from two or more compounds that have acryloyl groups.

The hydrophilic group may be a cationic hydrophilic group, an anionic hydrophilic group, or a nonionic hydrophilic group. An example of a cationic hydrophilic group is a quaternary ammonium group. Examples of anionic hydrophilic groups include a carboxy group, a sulfo group, and a phosphate group. Examples of nonionic hydrophilic groups include a hydroxy group and an amino group.

When polyacrylic acid is included in the adhesive layer 14 as the water-soluble polymer, its content may be adjusted to 0.1 to 5% by mass, or 0.5 to 4% by mass, based on the total mass of the adhesive layer 14. Increasing the polyacrylic acid content to 0.1% by mass or more tends to further improve the moldability and shape retention of the adhesive layer 14. Increasing the polyacrylic acid content to 5% by mass or less tends to prevent the adhesive layer 14 from becoming too hard, and to improve adhesion to the skin. Increasing the polyacrylic acid content in the adhesive layer 14 tends to increase the loss tangent.

The neutralized polyacrylic acid may be a fully 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.

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

When a neutralized polyacrylic acid is included in the adhesive layer 14 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 adhesive layer 14. By setting the content of the neutralized polyacrylic acid to 1% by mass or more, sufficient adhesive strength of the neutralized polyacrylic acid can be obtained. By setting the content of the neutralized polyacrylic acid to 7% by mass or less, the formability and shape retention of the adhesive layer 14 are improved. Increasing the content of the neutralized polyacrylic acid in the 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 preferred contents of each are also as described above.

In acrylic esters 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 acrylic esters having a hydrophilic group, the hydrophilic group may be present in this alkyl portion.

The adhesive layer 14 may contain components other than water-soluble acrylic polymers as water-soluble polymers. 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 water-soluble acrylic polymers.

When the 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% by mass, 3 to 18% by mass, or 3 to 10% by mass, based on the total mass of the adhesive layer 14. If the content of the water-soluble polymer other than a water-soluble acrylic polymer is 3% by mass or more, the cohesive strength of the adhesive layer 14 tends to be high. If the content is 10% by mass or less, the active ingredient contained in the adhesive layer 14 tends to be more uniformly dispersed. Increasing the content of the water-soluble polymer other than a water-soluble acrylic polymer in the adhesive layer 14 tends to decrease the loss tangent.

By including water in the adhesive layer 14, the skin permeability of the active ingredient is improved, allowing the active ingredient to exert its effects 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.

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 including 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.

The adhesive layer 14 may further contain other ingredients 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.

Solubilizers are used to dissolve the active ingredient. Examples of solubilizers 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 solubilizers may be used alone or in combination of two or more. The content of the solubilizer may be adjusted to be 0.1 to 10% by mass based on the total mass of the adhesive layer 14.

A crosslinking agent is used to strengthen the adhesive layer 14 and provide 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% by mass, 0.01 to 6.5% by mass, 0.01 to 3% by mass, 0.05 to 2% by mass, or 0.1 to 1% by mass, based on the total mass of the adhesive layer 14. Increasing the content of the crosslinking agent in the adhesive layer 14 tends to decrease the loss tangent.

Humectants are used to prevent water from evaporating 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.

When the adhesive layer 14 contains a polyhydric alcohol, the adhesive layer 14 becomes softer, which tends to further improve the adhesion of the microneedle patch 10. Increasing the polyhydric alcohol content of the adhesive layer 14 tends to increase the loss tangent.

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

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

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

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, and titanium oxide. The filler content may be 0.01 to 10% by mass, or 3 to 9% by mass, based on the total mass of the adhesive layer 14. Increasing the filler content in the adhesive layer 14 tends to decrease the loss tangent.

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

Examples of chelating agents 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.

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 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.

The inorganic powder, coloring agent, and flavoring agent may be any of the compositions commonly used for microneedle patches 10.

The loss tangent (tan δ) of the adhesive layer 14 constituting the microneedle patch 10, i.e., the adhesive layer 14 after the microneedle patch 10 is manufactured and a change in physical properties (e.g., a crosslinking reaction) has 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 the change in loss tangent or gel strength over time. In the present disclosure, the loss tangent (tan δ) 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. 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 (tan δ) = loss modulus (G″) / storage modulus (G′) (1)

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 numerical range of loss tangent, 0.20 to 0.41, is obtained from measurements under these measurement conditions. This loss tangent can be adjusted to the desired value by changing the content of water-soluble polymer or water.

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 crosslinker. The total amount of water-soluble polymers refers to the sum of the mass percentages of one or more types of water-soluble polymers.

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

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

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

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

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

In a seventh example, 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 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.

In an eighth example, the adhesive layer contains a water-soluble polymer in a total amount of 11.5 to 18.5% by mass, 3.5 to 6% by mass of sodium carboxymethylcellulose, 3 to 4.58% by mass of partially neutralized polyacrylic acid, 0.24 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 1.67.

In a ninth example, the adhesive layer contains a water-soluble polymer in a total amount of 11 to 20% by mass, 0.5% to less than 3.5% by mass of sodium carboxymethylcellulose, 1% to 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.

In a tenth example, the adhesive layer contains a water-soluble polymer in a total amount of 11.5 to 18.5% by mass, 1% by mass or more and less than 3.5% by mass of sodium carboxymethylcellulose, 2 to 4.58% by mass of partially neutralized polyacrylic acid, 1 to 6.24% 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 1.67.

In an eleventh example, the adhesive layer contains a water-soluble polymer in a total amount of 11 to 20% by mass, 0.5% to 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.

In a twelfth example, the adhesive layer contains a water-soluble polymer in a total amount of 11.5 to 18.5% by mass, 1% by mass or more and less than 3.5% by mass of sodium carboxymethylcellulose, 5 to 8% by mass of partially neutralized polyacrylic acid, 0.2 to 0.5% 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 1.67.

In any of the above examples 1 to 12, 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. As a result, it becomes possible to peel off a microneedle patch that has been applied to the skin without leaving the microneedle array on the skin.

In this disclosure, environmental temperature refers to the temperature of the working environment in which a measurement or test is performed. In one example, environmental temperature refers to both the temperature of the working space and the temperature of at least the portion 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.

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, The active ingredient may be selected from the group consisting of conditioners, hair softeners, hair moisturizers, tanning agents, skin whitening 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.

Active ingredients may include botanical preparations such as extracts or tinctures for topical skin treatment. 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 onion extract, chamomile flower extract, or calendula tincture; and for the treatment of severely fatigued and damaged skin, such as birch leaf extract, nettle extract, colesfoot extract, comfrey tincture, horsetail extract, or aloe extract; horse chestnut and raft extract, arnica, calendula, and capsicum extract.

As active ingredients, amino acids may include amino acids obtained by hydrolysis of various proteins, as well as their salts, esters, or acyl derivatives. Examples of such amino acid chemicals include amphoteric amino acids such as alkylamidoalkylamines, stearylacetyl glutamate, capryloyl silk amino acids, and capryloyl collagen amino acids; capryloyl keratin amino acids; capryloyl pea amino acids; cocodimonium hydroxypropyl silk amino acids; corn gluten amino acids; cysteine; glutamic acid; glycine; hair keratin amino acids; hair amino acids such as aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, half-cystine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, cysteic acid, lysine, histidine, arginine, cysteine, tryptophan, and citrulline; lysine; silk amino acids; wheat amino acids; and mixtures thereof.

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; 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.

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, and glycerin derivatives. The anti-wrinkle ingredient may also be a mixture of at least two of these compositions.

Examples of vitamins include B complex vitamins; vitamins A, C, D, E, K and their derivatives, 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.

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

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.

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.

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, glyceryl aminobenzoate, titanium dioxide, zinc oxide, oxybenzone, padimate O, red petrolatum, and mixtures thereof. An example of a tanning agent is dihydroxyacetone.

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.

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 can 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.

Examples of antihistamines include diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine, chlorpheniramine hydrochloride, chlorphenamine 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, 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.

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 may be used with the microneedle patch 10 include naphazoline nitrate, tetrahydrozoline hydrochloride, oxymetazoline hydrochloride, phenylephrine hydrochloride, and tramazoline hydrochloride. Examples of hemostatic agents that may be used with the microneedle patch 10 include thrombin, phytonadione, protamine sulfate, aminocaproic acid, tranexamic acid, carbazochrome, carbazochrome sodium sulfonate, rutin, and hesperidin.

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.

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 analogs such as acyclovir, penciclovir, valacyclovir, and ganciclovir.

Examples of hair growth or hair restoration medications 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.

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. Examples include alkyl esters of alpha-hydroxy acids such as citric acid, lactic acid, and glycolic acid; asiatic acid, madecassic acid, asiaticoside, Centella asiatica total extract, beta-glycyrrhetinic acid, alpha-bisabolol, and ceramides such as 2-oleoylamino-1,3-octadecane; phytantriol, a marine phospholipid found in abundance in polyunsaturated essential fatty acids, ethoxyquin; rosemary extract, balm extract, quercetin, dried microalgae extract, anti-inflammatory drugs such as steroidal anti-inflammatory drugs, and biochemical stimulants such as hormones or compounds involved in fat and/or protein synthesis.

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 to 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.

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.

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

These active ingredients may be used alone or in combination of two or more types. 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 penetration of the active ingredient into the skin.

The mass of the adhesive layer 14 may be, for example, 500 g/ ^m2 or more, or 700 g/ ^m2 or more. The mass of the adhesive layer 14 may be, for example, 2000 g/ ^m2 or less, or 1500 g/ ^m2 or less. The mass of the adhesive layer 14 may be 700 to 1500 g/ ^m2 , in which 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.

The release sheet 16 is a sheet-like member that protects the adhesive layer 14 before use of the microneedle patch 10.

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 shown in Figure 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 have other shapes. The weakened portions 16a may also have a wave-like or sawtooth shape.

The release sheet 16 may be a plastic film such as polypropylene (e.g., unstretched polypropylene or stretched polypropylene), polyethylene terephthalate, polybutylene terephthalate, polyethylene, polyester, polyurethane, polyvinyl chloride, or polystyrene; or it may be a silicone-coated paper obtained by silicone-coating synthetic resin, synthetic paper, or synthetic fiber; or it 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 at least partially colored.

The microneedle array 20 is an instrument for puncturing or pressing the skin. The example in Figure 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 differ from each other.

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).

Figure 2 is an enlarged perspective view showing an example of a 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.

The microneedle array 20 (substrate 21 and microneedles 22) may be made of materials such as silicon, silicon dioxide, ceramic, metals (stainless steel, titanium, nickel, molybdenum, chromium, cobalt, etc.), and synthetic or natural resin materials. Alternatively, biodegradable polymers such as polylactic acid, polyglycolide, polylactic acid-co-polyglycolide, pullulan, caprolactone, polyurethane, and polyanhydrides 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 copolymers, polycarbonate, polymethacrylic acid, polymethyl methacrylate, rigid polyvinyl chloride, ethylene vinyl acetate, polytetrafluoroethylene, tetrafluoroethylene-ethylene copolymers, polyoxymethylene, and acrylonitrile-butadiene-styrene copolymers 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 higher 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.

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 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 contacts 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 a portion of the substrate 21 will be exposed. The area of the substrate 21 may be 0.5 cm ² to 300 cm ² , 1 cm ² to 100 cm ² , or 1 cm ² to 50 cm ² . Alternatively, the area of the substrate 21 may be 0.5 ^cm to 10 ^cm , 0.5 ^cm to 5 ^cm , ^{1 cm} to 5 ^cm , 0.5 ^cm to 3 ^cm , or 1 ^cm to 3 ^cm . A substrate of the desired size may be formed by joining several of these substrates 21. The lower limit of the thickness of the substrate 21 may be 5 μm or 20 μm, and the upper limit of the thickness may be 1000 μm or 300 μm.

The microneedles 22 are tiny structures that rise from the main surface of the substrate 21. The microneedles 22 have a tapered shape that narrows from the base where they connect to the substrate 21 to the tip. In this specification, the term "microneedle" is used to refer not only to needle-shaped structures and structures that include a needle shape in the broad sense, but also to structures with blunt tips.

The lower limit of the density of the microneedles 22 may be, for example, 0.05 needles/cm ² , 1 needle/cm ² , 100 needles/cm ² , 200 needles/cm ² , 300 needles/cm ² , or 400 needles/cm ² . On the other hand, the upper limit of the density may be, for example, 10,000 needles/cm ² , 5,000 needles/cm ² , 2,000 needles/cm ² , or 850 needles/cm ² . The lower limit of the density is a value calculated from the number of needles capable of administering 1 mg of active ingredient and the required area. The upper limit of the density is a limit value taking into consideration the shape of the needles.

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 making the length of the microneedle 22 20 μm or more is to ensure transdermal absorption of the active ingredient. By making the length of the microneedle 22 600 μm or less, the microneedle 22 can avoid contact with nerves, reducing the possibility of pain and avoiding the possibility of bleeding. A microneedle length of 500 μm or less can efficiently administer the amount of active ingredient to be delivered intradermally, and can also administer the active ingredient without perforating the basement membrane, for example. 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 microneedles 22 may penetrate the stratum corneum. In other words, the microneedles 22 stretch and thin the epidermis, making it easier for the active ingredient to penetrate the epidermis, but some of the active ingredient may also penetrate into the skin through holes formed in the stratum corneum.

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; for example, the tip may be flat or rounded. A flat or rounded tip may be obtained by intentional processing, or may be obtained without such processing. If the tip is flat, the area of the flat portion may be 20 to 600 ^μm2 , or 50 to 250 ^μm2 . If the tip is rounded, the radius of curvature of the tip may be 2 to 100 μm, or 5 to 30 μm.

Methods for manufacturing a microneedle array 20 having three-dimensional microneedles 22 include wet etching or dry etching using a silicon substrate, precision machining using metal or resin (such as electrical discharge machining, laser machining, dicing, hot embossing, and injection molding), and mechanical cutting. These methods allow the substrate 21 and microneedles 22 to be molded into a single unit. One method for making the microneedles 22 hollow is to fabricate the microneedles 22 and then perform secondary processing such as laser machining.

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.

The microneedles 22 may be planar. For example, the microneedles 22 may be triangular or may have other shapes such as a diamond. Planar microneedles 22 are formed by punching the substrate 21 to form the microneedles 22, and then raising 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 a microneedle array 20. If the substrate 21 is non-metallic, 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 way as in the case of a metal sheet. When etching is used in this way, voids are created around each microneedle 22.

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).

Next, an example of a method for manufacturing 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 microneedle array 20 so that the main surface of the support 12 contacts the back surface of the substrate 21. As a result, the adhesive layer 14 and microneedles 22 are sandwiched between the support 12 and the release sheet 16.

The microneedle patch 10 may be stored inside a packaging bag. This storage method prevents a decrease in the water content of the adhesive layer 14 and reduces the adhesion of dirt and other particles to the adhesive layer 14. The microneedle patch 10 may be stored in the packaging bag in a folded state multiple times. In this case, the space required to store the microneedle patch 10 is saved, and therefore less material is required for the packaging bag.

The above provides a detailed description of the embodiments of the present disclosure. However, the present disclosure is not limited to the above examples. Various modifications are possible without departing from the spirit and scope of the present disclosure.

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

[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.

The inventors have discovered that, for each of Supplementary Notes 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 respective Supplementary Notes, it is possible to peel off a microneedle patch that has been applied to the skin without leaving the microneedle array on the skin.

Specific examples are described below, but the present disclosure is not limited to them.

Six types of adhesive compositions were prepared according to the compositions (unit: mass %) shown in Table 1 below. Microneedle patches were produced using each of the six types of adhesive compositions by the manufacturing method exemplified above. The microneedle patches were roughly rectangular with an area of 15 ^cm2 . The adhesive layer had a mass of 1000 g/ ^m2 . For the microneedle array, microneedles with a length of 500 μm were arranged at a density of 640/ ^cm2 on a circular substrate with a thickness of 700 μm and an area of 1.4 ^cm2 . A PET nonwoven fabric with a basis weight of 100 g/ ^m2 was used as the support. The adhesive layer was formed so that the microneedles were entirely embedded. Hereinafter, the six types of microneedle patches are distinguished as Examples 1 and 2 and Comparative Examples 1 to 4.

The microneedle patches were stored in their 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 HAAKE MARS rheometer (manufactured by Thermo Fisher Scientific Inc.) 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.

[Measurement conditions]
・Sample part: Flat plate with a diameter of 20 mm ・Gap distance: 1 mm
・Sample amount: 0.8 to 1.2 g
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: 1 Hz
・Distortion: 1%

A 90° peel test was conducted on each of the five types of microneedle patches, excluding Comparative Example 1. Comparative Example 1 had low adhesiveness of the pressure-sensitive adhesive layer, and the microneedle patch easily fell off from the target, so it was excluded from the evaluation. The microneedle patch was attached to a PTFE (polytetrafluoroethylene) plate, and 15 minutes later, a 90° peel test was conducted using an autograph at an ambient temperature of 25°C and a peel rate of 50 mm/min. This test was conducted 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 it fell off, with the average of the three scores being used to obtain the final score.

A peeling sensory test was conducted on 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 the microneedle patch. If the microneedle array did not fall off the microneedle patch during the test, a score of "1" was assigned, and if it did fall off, a score of "0" was assigned. The average of the scores of the five subjects was obtained as the final score.

Table 1 above also shows the calculated loss tangent and the results of the two types of tests. A 90° peel test score and peel sensory test score of 1 for Examples 1 and 2 indicates that the microneedle array never fell off the microneedle patch. A 90° peel test score and peel sensory test score of 0 for Comparative Example 2 indicates that the microneedle array fell off in all microneedle patches. A 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.

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 of these adhesive compositions. Hereinafter, the 38 types of microneedle patches are distinguished as Examples 3 to 18 and Comparative Examples 5 to 26. For each of the 38 additional microneedle patches, the loss tangent of the adhesive layer was calculated, and a 90° peel test and a peel sensory test were conducted, 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.

Tables 2 to 5 differ from Table 1 in that they include three additional rows: "Water-soluble polymer," "Crosslinker," and "EDTA/Crosslinker." The "Water-soluble polymer" row indicates the sum of the mass percentages of polyacrylic acid, partially neutralized polyacrylic acid, sodium carboxymethyl cellulose, and polyvinyl alcohol. That is, the "Water-soluble polymer" row indicates the total amount of water-soluble polymer. The "Crosslinker" row indicates the sum of the mass percentages 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.

Table 2 relates to Examples 1 to 12 above. Table 2 shows that when the total amount of 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 90° peel test score and the peel sensory test score is no longer "1." In other words, when the total amount of water-soluble polymer falls outside the specified range, the microneedle array either falls off the microneedle patch during the test or peeling, the microneedle patch could not be produced, or the microneedle patch easily falls off the target due to the low adhesiveness of the pressure-sensitive adhesive layer.

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 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 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 the low adhesiveness of the pressure-sensitive adhesive layer.

Table 4 relates to the third, fourth, ninth, and tenth examples. Table 4 shows that when the amount of sodium carboxymethylcellulose is outside 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 outside the range of 1% by mass or more and less than 5% by mass, or when the amount of crosslinker is outside the range of 1 to 9% by mass, the loss tangent falls outside 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 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 the low adhesiveness of the pressure-sensitive adhesive layer.

Table 5 relates to Examples 5, 6, 11, and 12 above. Table 5 shows that when the amount of sodium carboxymethylcellulose is outside 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 outside the range of 5 to 10% by mass, or when the amount of crosslinker is outside the range of 0.18 to 0.7% by mass, the loss tangent falls outside 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 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 the low adhesiveness of the pressure-sensitive adhesive layer.

Like Tables 2 to 5, Table 6 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 the peel sensory test score were both "1," corresponding to the loss tangent results.

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

Claims (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, 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. 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. 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.