WO2011148995A1 - 微小突起付きアレイ - Google Patents
微小突起付きアレイ Download PDFInfo
- Publication number
- WO2011148995A1 WO2011148995A1 PCT/JP2011/062026 JP2011062026W WO2011148995A1 WO 2011148995 A1 WO2011148995 A1 WO 2011148995A1 JP 2011062026 W JP2011062026 W JP 2011062026W WO 2011148995 A1 WO2011148995 A1 WO 2011148995A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- array
- skin
- microprojections
- substrate
- microprotrusions
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/158—Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/162—Needle sets, i.e. connections by puncture between reservoir and tube ; Connections between reservoir and tube
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D5/00—Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0038—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a channel at the side surface
Definitions
- One embodiment of the present invention relates to an array with microprojections for administering an active ingredient through the skin.
- an array for improving percutaneous absorption of a drug an array provided with microprotrusions on a substrate (array with microprotrusions) is known.
- the microprojections are intended to puncture the stratum corneum, which is the outermost layer of the skin, and various sizes and shapes have been proposed (see Patent Document 1).
- Patent Document 2 describes coating a drug on the surface of a microprojection, providing a groove or a hollow part for allowing the drug or a biological component to pass through the microprojection, mixing the drug on the microprojection itself, and the like. Yes.
- the reservoir medium contains saccharide, and in particular, it may contain a stabilizing saccharide such as lactose, raffinose, trehalose or sucrose forming glass (amorphous solid substance).
- a stabilizing saccharide such as lactose, raffinose, trehalose or sucrose forming glass (amorphous solid substance).
- the height of the microprojections is set to 10 ⁇ m to 3 mm, and the tip of the microprojections is formed into a flat shape or a rounded shape so that the microprojections penetrate the stratum corneum.
- compounds such as cosmetics, medicines, and plastics that are attached to or contained in the protrusions can be administered without stretching the epidermis.
- an array with microprojections includes a substrate and a tapered microprojection that is provided on the substrate and that narrows from a bottom portion that is connected to the substrate toward a tip portion.
- a tapered microprojection that is provided on the substrate and that narrows from a bottom portion that is connected to the substrate toward a tip portion.
- the portion of the skin that comes into contact with the protuberances extends at the maximum value a / b.
- the value a / b indicates an elongation rate when it is assumed that the skin is completely stretched along the side surface of the microprojection, and can be called a maximum elongation rate of the skin by the microprojection.
- the present inventors have found that if this maximum elongation is suppressed to 7.5 or less, there is no possibility of penetrating the stratum corneum of the skin.
- the stratum corneum is stretched and thinned while suppressing damage to the stratum corneum.
- the active ingredient can be administered to the skin without pain.
- An array with microprotrusions includes a substrate and microprotrusions, and the microprotrusions stretch the skin by 1.01 to 3.0 times. According to such an array with microprotrusions, the elongation rate of the skin can be suppressed to 1.01 to 3.0, so that the stratum corneum is stretched and thinned while suppressing the damage to the stratum corneum.
- the active ingredient can be administered to the skin without pain and with certainty.
- the microprojections may be made of polylactic acid. Since polylactic acid is biodegradable, in this case, the burden on the skin or the like can be reduced even if the microprotrusions remain on the skin. Polylactic acid is also advantageous in terms of antigenicity and unit cost of material.
- the height of the microprojections may be 20 to 400 ⁇ m, and the width of the bottom may be 10 to 200 ⁇ m.
- the density of microprojections may be 100 to 10,000 / cm 2 .
- the tip portion may be flat and the area of the tip portion may be 20 to 600 ⁇ m 2 . In this case, since the pressure received by the skin in contact with the tip of the microprojection is reduced, damage to that portion can be avoided more reliably.
- the tip portion may be rounded, and the radius of curvature of the tip portion may be 2 to 100 ⁇ m. In this case, since the pressure received by the skin in contact with the tip of the microprojection is reduced, damage to that portion can be avoided more reliably.
- the tip may be sharp and the tip angle of the tip projected on an arbitrary reference plane orthogonal to the substrate may be 16 degrees or more.
- the value a / b can be in the range of 1.0 ⁇ (a / b) ⁇ 7.5, the active ingredient can be suppressed while suppressing damage to the stratum corneum even if the fine protrusions are sharp. Can be administered to the skin without pain.
- the microprojections do not have to penetrate the stratum corneum of the skin.
- the distance from the tip to the bottom of the side surface of the microprojection is a, and the length of the second line segment formed by projecting the first line segment indicating the distance onto the substrate.
- B is determined so that the relationship of 1.0 ⁇ (a / b) ⁇ 7.5 is satisfied, and the active ingredient is suppressed while suppressing damage to the stratum corneum of the skin. It can be administered to the skin without pain.
- FIG. 2 is a sectional view taken along line II-II in FIG.
- A is a perspective view of a conical microprojection
- (b) is a cross-sectional view taken along line BB of (a)
- (c) is a perspective view of a quadrangular pyramidal microprojection
- (d ) Is a sectional view taken along line DD of (c).
- 10 is a graph showing the amount of moisture evaporation in Example 3. It is a graph which shows the impedance change in Example 4. It is a figure which shows typically the state from which the skin extended without following a microprotrusion completely.
- FIG. 1 is a perspective view showing an example of an array 1 according to the embodiment.
- 2 is a cross-sectional view taken along line II-II in FIG.
- FIG. 3 is a perspective view and a cross-sectional view of the minute protrusion 3.
- the array 1 includes a substrate 2 and a plurality of minute protrusions 3 arranged in a two-dimensional manner on the substrate 2.
- the substrate 2 is a base for supporting the minute protrusions 3.
- a plurality of through holes 4 are formed in the substrate 2 in a two-dimensional manner.
- the minute projections 3 and the through holes 4 are alternately arranged in the diagonal direction of the substrate 2.
- the area of the substrate 2 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 .
- a plurality of substrates 2 may be connected to form a substrate having a desired size.
- the microprotrusion 3 has a micro structure, and its height (length) h is, for example, 20 to 400 ⁇ m.
- the length of the microprotrusions 3 is set to 20 ⁇ m or more in order to ensure the transdermal administration of the active ingredient, and the reason why the microprotrusions are set to 400 ⁇ m or less is to prevent the microprotrusions from perforating the keratin of the skin. This is for sure prevention.
- the length of the microprotrusions 3 is 300 ⁇ m or less, an amount of the active ingredient that should enter the skin can be efficiently administered.
- the length of the fine protrusion 3 may be 50 to 300 ⁇ m.
- the microprotrusion is a tapered structure that narrows from the bottom connected to the substrate 2 toward the tip, and means a structure having a needle shape or a needle shape in a broad sense.
- the microprotrusions are not limited to needle-shaped ones having a sharp tip, but also include shapes that are not pointed.
- the diameter at the base thereof may be about 5 to 250 ⁇ m, or 10 to 200 ⁇ m.
- a polygonal pyramidal minute protrusion such as a quadrangular pyramid may be used.
- FIG. 3 shows a case where the minute protrusion 3 is a cone or a quadrangular pyramid.
- the microprojection 3 is a cone as shown in FIG. 3 (a)
- the line segment indicating the distance a from the tip portion P to the bottom portion on the side surface thereof is the triangle PQR (tip portion P shown in FIG. 3B).
- It is a hypotenuse PQ in a sectional view including.
- a line segment formed by projecting the oblique side PQ onto the substrate 2 along the direction orthogonal to the substrate 2 is the line segment QM in the triangle PQR.
- the point M is a perpendicular foot from the point P to the base QR.
- the value a / b is an index indicating an elongation rate when it is assumed that the skin in a normal state is stretched completely along the side surface of the microprojection 3, that is, an index indicating how many times the skin is elongated by the microprojection 3. Yes, it can be said that the maximum elongation rate of the skin by the microprotrusions 3 is obtained.
- the maximum elongation rate of the skin is expressed by the above formula ( 1) may be satisfied. This is because if the skin stretch rate is suppressed to that level, damage to the stratum corneum when the array 1 is applied can be avoided more reliably.
- the elongation percentage may be 1.01 to 3.0 or 1.01 to 2.0.
- the tip angle ⁇ (see FIGS. 3C and 3D) of the tip projected onto an arbitrary reference plane orthogonal to the substrate 2 is 16 degrees or more (180 degrees). Less). That is, the minimum value of the tip angle ⁇ of the tip projected onto the arbitrary reference plane may be 16 degrees or more.
- the above formula (1) does not hold only in the example of FIG. 3, but also holds even if the minute protrusion is an arbitrary pyramid or an arbitrary oblique cone. However, if the minute protrusion is a pyramid, the expression (1) is established for an arbitrary side surface, and if it is a cone, the expression (1) is required for an arbitrary bus bar.
- the microprotrusions do not have to be cones.
- the tip may be flat or rounded.
- the area of the flat portion may be 20 to 600 ⁇ m 2 or 50 to 250 ⁇ m 2 .
- the radius of curvature of the tip may be 2 to 100 ⁇ m or 5 to 30 ⁇ m. Even if the microprotrusions have such shapes, the above formula (1) is established.
- microprotrusions 3 do not normally penetrate the stratum corneum of the skin during use, but some microprotrusions 3 may penetrate the stratum corneum as long as there is no inconvenience such as inflammation from the cosmetic viewpoint of the skin. . That is, the epidermis is stretched and thinned by the microprotrusions 3, and the active ingredient penetrates into the easily permeated epidermis. However, a part of the active ingredient may enter the skin from the keratin with a hole.
- the microprojections 3 are typically spaced to provide a density of about 1 to 10 per mm for the rows of needles. In general, adjacent rows are separated from each other by a substantially equal distance with respect to the space of the needles in the row and have a needle density of 100 to 10,000 per cm 2 .
- the density of the fine protrusions 3 may be 200 to 5000, 300 to 2000, or 400 to 850.
- Examples of the material of the substrate 2 or the microprojections 3 include silicon, silicon dioxide, ceramic, metal (stainless steel, titanium, nickel, molybdenum, chromium, cobalt, etc.) and synthetic or natural resin materials.
- biodegradable polymers such as polylactic acid, polyglycolide, polylactic acid-co-polyglycolide, pullulan, caprolactone, polyurethane, polyanhydride, non-degradable polymers such as polycarbonate, polymethacrylate
- non-degradable polymers such as polycarbonate, polymethacrylate
- synthetic or natural resin materials such as acid, ethylene vinyl acetate, polytetrafluoroethylene, and polyoxymethylene.
- it may be a polysaccharide such as hyaluronic acid, sodium hyaluronate, pullulan, dextran, dextrin or chondroitin sulfate, cellulose derivative and the like.
- the material of the microprojections 3 may be a biodegradable resin such as polylactic acid, considering that it has broken on the skin.
- the polylactic acid includes poly-L-lactic acid, poly-lactic acid homopolymer of poly-D-lactic acid, poly-L / D-lactic acid copolymer, and mixtures thereof. Any of these may be used. . Further, the higher the average molecular weight of polylactic acid, the stronger the strength, and those having 40,000 to 100,000 can be used.
- the substrate 2 or the minute protrusions 3 wet etching processing or dry etching processing using a silicon substrate, precision machining using metal or resin (electric discharge processing, laser processing, dicing processing, hot embossing processing, injection molding processing) Etc.), machine cutting and the like.
- the projecting portion and the support portion are integrally molded.
- the method for hollowing the protrusion include a method of performing secondary processing by laser processing or the like after the protrusion is manufactured.
- the coating 5 is obtained by fixing a coating liquid containing a polymer carrier having compatibility with an active ingredient onto a part or the whole surface of the microprojections 3 and / or the substrate 2.
- the polymer carrier include carboxyvinyl polymer, polyethylene oxide, polyvinyl pyrrolidone, polyvinyl alcohol, and cellulose derivatives described later. “Fixed” refers to maintaining a state in which the coating liquid adheres almost uniformly to the object.
- the coating solution is fixed in a dry state by a known drying method such as air drying, vacuum drying, freeze drying, or a combination thereof, but after transdermal administration, the moisture content in equilibrium with the surrounding atmosphere and Since an organic solvent or the like may be retained, it is not always fixed in a dry state.
- the coating agent contains an active ingredient and purified water and / or a coating carrier.
- Coating carriers include polyethylene oxide, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, carboxymethylcellulose, carmellose sodium, dextran, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, chondroitin sulfate, hyaluronic acid, sodium hyaluronate, dextrin Gum arabic, ethanol, isopropanol, methanol, propanol, butanol, dimethyl sulfoxide, N, N-dimethylformamide, polyethylene glycol, benzyl benzoate, sesame oil, soybean oil, lactic acid, benzyl alcohol, polysorbate 80, amphothioglycerin, ethylenediamine N, N-dimethyl Acetamide, thioglycolic acid, and phenoxyethanol.
- the content of the coating carrier in the coating agent may be 0.1 to 70% by weight. Further, it may have a certain degree of viscosity so as not to drip.
- the liquid composition used to coat the substrate 2 and / or the microprojections 3 is a volatile liquid containing a biocompatible carrier, a beneficial active ingredient to be delivered, and possibly any coating aids.
- the volatile liquid can be water, dimethyl sulfoxide, dimethylformamide, ethanol, isopropyl alcohol and mixtures thereof.
- Liquid coating solutions or suspensions can typically have a beneficial bioactive ingredient concentration of 0.1 to 65% by weight, the concentration being 1 to 40% by weight, alternatively 10 to 30% by weight. But you can.
- the coating can be in a fixed state.
- Surfactants can be zwitterionic, zwitterionic, cationic, anionic, or nonionic.
- Tween 20 and Tween 80 other sorbitan derivatives such as sorbitan laurate, and alkoxylated alcohols such as laureth-4.
- it is also effective to add a surfactant to dissolve more active ingredients in the coating carrier.
- the active ingredient used in the present embodiment is not particularly limited, and is an antioxidant, a free radical scavenger, a humectant, a depigmenting agent, a fat regulator, an ultraviolet reflector, a wetting agent, an antibacterial agent, an antiallergic agent, Anti-acne, anti-aging agent, anti-wrinkle agent, bactericidal agent, analgesic agent, anti-cough agent, anti-itch agent, local anesthetic agent, anti-hair loss agent, hair growth aid, hair growth inhibitor, anti-dandruff agent, antihistamine agent, keratin Lysing drugs, anti-inflammatory drugs, soft drinks, therapeutic drugs, anti-infective drugs, anti-inflammatory drugs, antiemetics, anticholinergics, vasoconstrictors, vasodilators, trauma healing aids, peptides, polypeptides, proteins, Body odor prevention agent, antiperspirant, emollient, skin moisturizer, softener, hair conditioner, hair soften
- the active ingredient used in the present embodiment may also include a plant preparation such as an extract or tincture for the treatment of local skin conditions.
- extracts or tinctures include oak bark extract, walnut extract, arnica tincture, witch hazel extract, psyllium extract, pansy extract, thyme or sage extract; St. John's wort Tinctures, extracts of perilla, chamomile flower, or calendula tinctures; for example, oak leaf extract, nettle extract, colesfoot, for the care of heavily tired and damaged skin Extract, tincture tincture, horsetail extract, or aloe extract, extract of Tochinoki and Nagii Kada, extract of Arnica, calendula and capsicum.
- amino acids include amino acids obtained from hydrolysis of various proteins as well as salts, esters, and acyl derivatives thereof.
- amino acid drugs include amphoteric amino acids such as alkylamidoalkylamines, stearyl acetyl glutamate, capryloyl silk amino acids, capryloyl collagen amino acids; capryloyl keratin amino acids; caproyl pea amino acids; cocodimonium hydroxypropyl Amino acid silk; corn gluten amino acid; cysteine; glutamic acid; glycine; hair keratin amino acid; eg aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, half cystine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, cysteic acid , Lysine, histidine, arginine, cysteine, trypto
- peptides, polypeptides, and proteins include long chains having, for example, at least about 10 carbon atoms, and polymers having a high molecular weight, for example, at least 1000, which are amino acids Formed by self-condensation.
- proteins include: collagen; deoxyribonuclease; iodinated corn protein; keratin; milk protein; protease; serum protein; silk; sweet tonsil protein; wheat malt protein; Beta helix; including hair proteins such as intermediate filament protein, high sulfur content protein, very high sulfur content protein, intermediate filament related protein, high tyrosine protein, high glycine tyrosine protein, trichohyalin, and mixtures thereof It is done.
- anti-wrinkle components examples include hyaluronic acid, sodium hyaluronate, retinol (vitamin A), silybin peptides (HTC collagen, palmitoyl penta, peptide 3, argylline), amino acids, hydroxyproline, Examples include tocopheryl retinoic acid, ursolic acid, vitamin C derivative, coenzyme Q10, astaxanthin, fullerene, polyphenols, ⁇ lipoic acid, soybean extract, pullulan, activated isoflavone, saccharide, polysaccharide, glycerin, glycerin derivative and the like.
- the anti-wrinkle component is not limited to these, and mixing is also conceivable.
- vitamins examples include vitamin B complexes; including thiamine, nicotinic acid, biotin, pantothenic acid, choline, riboflavin, vitamin B6, vitamin B12, pyridoxine, inositol, carnitine, for example vitamin A palmitate And vitamins A, C, D, E, K and derivatives thereof; and provitamins such as panthenol (provitamin B5) and panthenol triacetate; and mixtures thereof.
- vitamin B complexes including thiamine, nicotinic acid, biotin, pantothenic acid, choline, riboflavin, vitamin B6, vitamin B12, pyridoxine, inositol, carnitine, for example vitamin A palmitate And vitamins A, C, D, E, K and derivatives thereof; and provitamins such as panthenol (provitamin B5) and panthenol triacetate; and mixtures thereof.
- antibacterial substances examples include bacitracin, erythromycin, neomycin, tetracycline, chlortetracycline, benzethonium chloride, phenol, and mixtures thereof.
- emollients and skin moisturizers examples include mineral oil, lanolin, vegetable oil, isostearyl isostearate, glyceryl laurate, methyl glutes-10, methyl glutes-20, chitosan, and mixtures thereof. Is mentioned.
- hair conditioners that can be used in this embodiment include not only fat-soluble compounds such as cetyl alcohol, stearyl alcohol, hydrogenated polydecene, and mixtures thereof, but also behenamidopropyl PG-dimonium chloride, tricetyl chloride. Quaternary compounds such as ammonium, hydrogenated tallow amidoethyl hydroxyethylmonium methosulphate, and mixtures thereof may be mentioned.
- sunscreen agents examples include butyl methoxydibenzoyl methane, octyl methoxycinnamate, oxybenzone, octocrylene, octyl salicylate, phenylbenzimidazole sulfonic acid, ethyl hydroxypropyl aminobenzoate, menthyl anthranilate. , Aminobenzoic acid, sinoxate, diethanolamine methoxycinnamate, glyceryl aminobenzoate, titanium dioxide, zinc oxide, oxybenzone, paddymate O, red petrolatum, and mixtures thereof.
- a tanning agent that can be used in this embodiment is dihydroxyacetone.
- Examples of skin lightening agents that can be used in this embodiment 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.
- anti-inflammatory analgesics examples include acetaminophen, methyl salicylate, monoglycol salicylate, aspirin, mefenamic acid, flufenamic acid, indomethacin, diclofenac, alclofenac, diclofenac sodium, ibuprofen, ketoprofen, naproxen, Examples include pranoprofen, fenoprofen, sulindac, fenclofenac, clidanac, flurbiprofen, fenthiazac, bufexamac, piroxicam, phenylbutazone, oxyphenbutazone, clofesone, pentazocine, mepyrazole, thiaramide hydrochloride.
- Examples of steroidal anti-inflammatory analgesics that can be used with the patch of this embodiment include hydrocortisone, prednisolone, dexamethasone, triamcinolone acetonide, fluocinolone acetonide, hydrocortisone acetate, prednisolone acetate, methylprednisolone, dexamethasone acetate, betamethasone, Examples include betamethasone valerate, flumethasone, fluorometholone, and beclomethasone dipropionate.
- antihistamines examples include diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine, chlorpheniramine hydrochloride, chlorferramine maleate, istipendyl hydrochloride, triperamine hydrochloride, promesazine hydrochloride, methodiazine hydrochloride, and the like.
- Examples of local anesthetics that can be used with the patch of this embodiment include dibucaine hydrochloride, dibucaine, lidocaine hydrochloride, lidocaine, benzocaine, p-butylaminobenzoic acid 2- (diethylamino) ethyl ester hydrochloride, procaine hydrochloride, tetracaine Tetracaine hydrochloride, chloroprocaine hydrochloride, oxyprocaine hydrochloride, mepivacaine, ***e hydrochloride, piperocaine hydrochloride, dichronin, dichronin hydrochloride and the like.
- bactericides and disinfectants examples include thimerosal, phenol, thymol, benzalkonium chloride, benzethonium chloride, chlorohexidine, popidone iodine, cetylpyridinium chloride, eugenol, and trimethylammonium bromide.
- vasoconstrictors examples include naphazoline nitrate, tetrahydrozoline hydrochloride, oxymetazoline hydrochloride, phenylephrine hydrochloride, tramazoline hydrochloride, and the like.
- hemostatic agents examples include thrombin, phytonadione, protamine sulfate, aminocaproic acid, tranexamic acid, carbazochrome, carbazochrome sodium sulfonate, rutin, hesperidin and the like.
- chemotherapeutic agents examples include sulfamine, sulfathiazole, sulfadiazine, homosulfamine, sulfisoxazal, sulfisomidine, sulfamethizole, nitrofurazone, and the like.
- antibiotics examples include penicillin, methicillin, oxacillin, cephalothin, cephalodine, erythromycin, lincomycin, tetracycline, chlorotetracycline, oxytetracycline, metacycline, chloramphenicol, kanamycin, streptomycin , Gentamicin, bacitracin, cycloserine and the like.
- antiviral agents examples include protease inhibitors, thymazine kinase inhibitors, sugar or glycoprotein synthesis inhibitors, constituent protein synthesis inhibitors, adhesion and adsorption inhibitors, and for example, acyclovir, penciclovir , Nucleoside analogs such as valaciclovir and ganciclovir.
- hair growth or hair growth agents examples include minoxidil, carpronium chloride, pentadecanoic acid glyceride, tocopherol acetate, piroctone olamine, glycyrrhizic acid, isopropylmethylphenol, hinokitiol, assembly extract, ceramide and precursor Body, nicotinamide and chili tincture.
- cosmetic active ingredients examples include D-alpha-tocopherol, DL-alpha-tocopherol, D-alpha-tocopheryl acetate, DL-alpha-tocopheryl acetate, ascorbyl palmitate, vitamin F and vitamin F.
- Glyceride vitamin D, vitamin D2, vitamin D3, retinol, retinol ester, retinyl palmitate, retinyl propionate, beta-carotene, coenzyme Q10, D-pantenol, farnesol, farnesyl acetate; abundant in essential fatty acids Jojoba oil and blackfuzzy oil; 5-n-octanoylsalicylic acid and esters thereof, salicylic acid and esters thereof; alkyl esters of alpha-hydroxy acids such as citric acid, lactic acid, glycolic acid; In ceramides such as ciatinic acid, madeacicic acid, asiaticoside, total extract of cinnamon, beta-glycyrrhetinic acid, alpha-bisabolol, eg 2-oleoylamino-1,3-octadecane; phytantriol, polyunsaturated essential fatty acids Marine phospholipids, ethoxyquin; rosemary extract,
- Vitamin C used in this embodiment promotes collagen (connective tissue) synthesis, lipid (fat) and carbohydrate metabolism, and neurotransmitter synthesis. Vitamin C is also essential for optimal maintenance of the immune system. Vitamin C is toxic to a wide range of cancer cells, particularly melanoma. Tyrosine oxidase, which catalyzes the tyrosine aerobic activity that changes to melanin and other pigments, is also hindered by the presence of vitamin C. Vitamin C has been found to be effective in catalyzing immune responses against many viral and bacterial infections. In addition to the many applications mentioned above, vitamin C is essential for collagen synthesis and trauma treatment. The patch to which this embodiment is applied may include vitamin C, vitamin E, and combinations of other ingredients such as humectants, collagen synthesis promoters, and scrub face wash.
- Skin conditioner ingredients in this embodiment are mineral oil, petrolatum, vegetable oil (such as soybean oil or maleated soybean oil), dimethicone, dimethicone copolyol, cationic monomers and polymers (such as guar hydroxypropyltrimonium chloride and distearyl). Dimethylammonium chloride), as well as mixtures thereof.
- Illustrative humectants are, for example, polyols such as sorbitol, glycerin, propylene glycol, ethylene glycol, polyethylene glycol, polypropylene glycol, 1,3-butanediol, hexylene glycol, isoprene glycol, xylitol, fructose, and mixtures thereof. .
- these active ingredients may be used alone or in combination of two or more kinds, and any active ingredient in the form of an inorganic salt or an organic salt is naturally included as long as it is a pharmaceutically acceptable salt.
- the active ingredient is basically included in the coating carrier, but the active ingredient is not included in the coating carrier and may be supplied later through the through-hole 4 formed in the substrate 2. it can. It is also possible to apply the active ingredient directly to the skin and then apply the array 1 with microprojections to the same part of the skin. In this case, penetration of the active ingredient into the skin can be promoted by the effect of stretching the skin and the effect of ODT (sealed wrap therapy) on the skin.
- an auxiliary device for fixing the array 1 may be used.
- direct administration by hand is better than an array that generates high collision energy, for example, in JP-T-2004-510535.
- the array 1 When the array 1 is in contact with the skin, it is administered with a force of 1.0 to 10 kg, alternatively with a force of 1.0 to 7 kg, or with a force of 1.0 to 4 kg.
- the administration time with that force is not so long, and it is about 120 minutes at the maximum from several seconds.
- the administration time may be within 60 minutes or within 15 minutes. In some cases, there may be an instantaneous administration of less than 1 second. However, it is also possible to continue to administer the active ingredient after fixing to the skin.
- Kbl Japanese white rabbit
- Skin primary irritation was determined by calculating a primary irritation index (PI) and using the following Draize evaluation criteria (Table 2).
- PI primary irritation index
- Table 2 Draize evaluation criteria
- the skin primary irritation index (P.I.I) was 0.0 in each of the arrays having three types of microprojections (70 ⁇ m, 110 ⁇ m, and 150 ⁇ m) and the substrate-only array. Met.
- test paper for measurement Pretest II (urine occult blood test paper, manufactured
- Example 3 Rabbit Skin Moisture Evaporation (TEWL) Measurement ⁇ Operation Method> Three types (h: 70 ⁇ m, 110 ⁇ m, and 150 ⁇ m) of polylactic acid microprojections with different projection lengths and an array consisting only of a substrate were used. For the three types of arrays having microprojections, the shape of the projections was a quadrangular pyramid, and the density of the projections was 841 pieces / cm 2 . In the same manner as in Example 1, the array was pressed and attached to the rabbit skin, and the amount of water transpiration was measured about 2 hours after the application.
- Skin moisture transpiration (TEWL) is an index for measuring the barrier function of the skin, and it is known that when the barrier structure of the stratum corneum is damaged, the amount of moisture transpiration from the damaged site increases.
- the amount of skin moisture transpiration was measured before applying the array and after a few minutes after peeling, and using VapoMeter (Dlefin).
- VapoMeter Vefin
- As a positive control group a 500 ⁇ m-high array with similar microprojections was used, and as a negative control group, an array consisting only of a substrate was used.
- Example 4 Measurement of human isolated skin impedance ⁇ Operation method> Three types (h: 70 ⁇ m, 110 ⁇ m, and 150 ⁇ m) of polylactic acid microprojections with different projection lengths and an array consisting only of a substrate were used. The shape of each protrusion was a quadrangular pyramid, and the density of each protrusion was 841 pieces / cm 2 . Each array was pressed against the human excised skin at a pressure of 3 kg for 5 seconds, and the impedance value of the skin before and after pressing was measured. The skin impedance value is an index indicating the barrier function of the skin like TEWL, and it is known that the impedance value decreases when the skin is damaged.
- the skin impedance value is measured by placing a skin piece (skin thickness of about 500 ⁇ m, 5 cm ⁇ 5 cm) on a stainless steel substrate, impregnating a physiological saline solution on the substrate application site, a circular nonwoven fabric with a diameter of ⁇ 14, a silver electrode with a diameter of ⁇ 12, The stainless steel substrate and the silver electrode were connected to an LCR measuring instrument (3522-50, Hioki Electric Co., Ltd.) (measurement conditions: 1 V, 10 Hz).
- an LCR measuring instrument 3522-50, Hioki Electric Co., Ltd.
- As a positive control group a 500 ⁇ m-high array with similar microprojections was used, and as a negative control group, an array consisting only of a substrate was used.
- FIG. 6 schematically shows a state in which a part of the skin is in contact with the substrate surface 2a between adjacent microprojections 3 and the skin extends without being along the side surfaces of the microprojections 3 by pressing the array with microprojections. ing. Assuming that the skin touches the substrate surface 2a at the midpoint Q ′ between the microprojections 3, the skin having the length b ′ along the line segment Q′M in the normal state has a length along the line segment PQ ′. It will be stretched to a '.
- the skin elongation rate a ′ / b ′ is the value shown in Table 8 below according to the height of the microprotrusions 3. Become.
- the active ingredient for cosmetic purposes can be administered to the skin without pain and surely while suppressing damage to the stratum corneum of the skin. And therefore has industrial applicability.
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Anesthesiology (AREA)
- Dermatology (AREA)
- Medical Informatics (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Vascular Medicine (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Media Introduction/Drainage Providing Device (AREA)
- Length-Measuring Instruments Using Mechanical Means (AREA)
- Toys (AREA)
- Instructional Devices (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
1.0<(a/b)≦7.5 …(1)
<操作手法>
突起の長さが異なる3タイプ(h:70μm、110μm、150μm)のポリ乳酸製微小突起付きアレイと、基板のみから成るアレイとを使用した。微小突起を備える3種類のアレイについて、突起の形状はいずれも四角錐であり、突起の密度はいずれも841本/cm2であった。18週齢の雌性日本白色種ウサギ(Kbl:JW)の毛を剃った背中の部分に被験物質を3kgの力で5秒間皮膚に押し付けた後に2時間貼付(カバー材有り)した(個体数n=6)。そして、投与から2時間後に被験物質を剥離し、剥離後0.5,2,24,48及び72時間目に紅斑・痂皮及び浮腫形成について肉眼的に観察し,Draizeらの評価基準(表1)に基づいて採点した。
<操作手法>
突起の長さが150μmのポリ乳酸製微小突起付きアレイを使用した。このアレイにおいて、突起の形状は四角錐であり、突起の密度は841本/cm2であった。上記実施例1と同様にウサギの皮膚にアレイを押し付け、2時間貼付した後の潜血反応を測定した(個体数n=6)。潜血の判断基準は、アレイ(MN)を除去した直後に生理食塩液20μLを適用部位に滴下し、試験紙を当てた時の呈色反応により判断した。測定用試験紙は、Pretest II(尿潜血試験紙、和光純薬株式会社製)を用いた。陽性対照として、18Gの針を使って皮膚上に擦過傷を負わせ、同様に試験を行った。
<操作手法>
突起の長さが異なる3タイプ(h:70μm、110μm、150μm)のポリ乳酸製微小突起付きアレイと、基板のみから成るアレイとを使用した。微小突起を備える3種類のアレイについて、突起の形状はいずれも四角錐であり、突起の密度はいずれも841本/cm2であった。上記実施例1と同様にウサギの皮膚にアレイを押し付けて貼り付け、貼付後2時間前後における水分蒸散量を測定した。皮膚水分蒸散量(TEWL)は皮膚のバリア機能を測定する際の指標であり、角質層のバリア構造が損傷すると損傷部位からの水分蒸散量が増加することが分かっている。
<操作手法>
突起の長さが異なる3タイプ(h:70μm、110μm、150μm)のポリ乳酸製微小突起付きアレイと、基板のみから成るアレイとを使用した。突起の形状はいずれも四角錐であり、突起の密度はいずれも841本/cm2であった。各アレイをヒト摘出皮膚に3kgの圧で5秒間押し付け、押圧前後の皮膚のインピーダンス値を測定した。皮膚のインピーダンス値は、TEWLと同様に皮膚のバリア機能を示す指標で、皮膚が損傷するとインピーダンス値が低下することが分かっている。
<皮膚が微小突起の側面に完全に沿って伸びた場合>
この場合について図3(c),(d)を用いて説明する。平常状態において線分QMに沿っている長さbの皮膚が線分PQに完全に沿って長さaまで引き伸ばされた場合において、その伸び率は微小突起3の長さに関わらずその先端角度αに依存する。下記の表5~7に示すように、先端角度αが16,18,20度の場合の伸び率は、それぞれ7.19、6.37、5.74であった。
Claims (9)
- 基板と、
前記基板に設けられ、該基板と接続する底部から先端部に向けて細くなるテーパ状の微小突起と、
を備え、
前記微小突起の任意の側面における前記先端部から前記底部までの距離をaとし、該距離を示す第1の線分を前記基板上に投影してなる第2の線分の長さをbとした場合に、1.0<(a/b)≦7.5の関係が成立する、
微小突起付きアレイ。 - 基板と微小突起とを備え、
前記微小突起が皮膚を1.01~3.0倍伸ばす、
微小突起付きアレイ。 - 前記微小突起がポリ乳酸製である、
請求項1に記載の微小突起付きアレイ。 - 前記微小突起の高さが20~400μmであり、前記底部の幅が10~200μmである、
請求項1又は3に記載の微小突起付きアレイ。 - 前記微小突起の密度が100~10000本/cm2である、
請求項1,3及び4のいずれか一項に記載の微小突起付きアレイ。 - 前記先端部が平坦であり、該先端部の面積が20~600μm2である、
請求項1及び3~5のいずれか一項に記載の微小突起付きアレイ。 - 前記先端部が丸みを帯びており、該先端部の曲率半径が2~100μmである、
請求項1及び3~5のいずれか一項に記載の微小突起付きアレイ。 - 前記先端部が尖っており、前記基板と直交する任意の基準面に投影された該先端部の先端角度が16度以上である、
請求項1及び3~5のいずれか一項に記載の微小突起付きアレイ。 - 前記微小突起が皮膚の角質層を貫通しない、
請求項1及び3~8のいずれか一項に記載の微小突起付きアレイ。
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/699,471 US20130084316A1 (en) | 2010-05-28 | 2011-05-25 | Array with fine protrusions |
EP11786694.7A EP2578265B1 (en) | 2010-05-28 | 2011-05-25 | Array with fine protrusions |
ES11786694T ES2728479T3 (es) | 2010-05-28 | 2011-05-25 | Matriz con protuberancias finas |
CN2011800263798A CN102917752A (zh) | 2010-05-28 | 2011-05-25 | 带微小突起的阵列 |
KR1020127033657A KR101759370B1 (ko) | 2010-05-28 | 2011-05-25 | 미소 돌기가 형성된 어레이 |
JP2012517303A JP5797644B2 (ja) | 2010-05-28 | 2011-05-25 | 微小突起付きアレイ |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010122989 | 2010-05-28 | ||
JP2010-122989 | 2010-05-28 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2011148995A1 true WO2011148995A1 (ja) | 2011-12-01 |
Family
ID=45003981
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2011/062026 WO2011148995A1 (ja) | 2010-05-28 | 2011-05-25 | 微小突起付きアレイ |
Country Status (7)
Country | Link |
---|---|
US (1) | US20130084316A1 (ja) |
EP (1) | EP2578265B1 (ja) |
JP (1) | JP5797644B2 (ja) |
KR (1) | KR101759370B1 (ja) |
CN (1) | CN102917752A (ja) |
ES (1) | ES2728479T3 (ja) |
WO (1) | WO2011148995A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017528239A (ja) * | 2014-09-15 | 2017-09-28 | ノヴォクセル リミテッド | 組織の熱的蒸散および熱圧迫のための方法および装置 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5937092B2 (ja) | 2010-10-19 | 2016-06-22 | トラスティーズ オブ タフツ カレッジ | シルクフィブロインベースのマイクロニードルおよびその製造方法 |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001506904A (ja) | 1996-12-20 | 2001-05-29 | アルザ・コーポレーション | 経皮作用剤流量を強化するための組成物と方法 |
JP2004504120A (ja) | 2000-07-21 | 2004-02-12 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | ワクチン |
JP2004510535A (ja) | 2000-10-13 | 2004-04-08 | アルザ・コーポレーシヨン | 微小突起を用いて皮膚を穿孔するための装置および方法 |
JP2006149818A (ja) * | 2004-11-30 | 2006-06-15 | Nitto Denko Corp | 経皮投薬デバイス |
JP2007089792A (ja) | 2005-09-28 | 2007-04-12 | Nano Device & System Research Inc | 経皮投与装置 |
JP2007130417A (ja) | 2005-11-08 | 2007-05-31 | Nano Device & System Research Inc | 経皮投与装置 |
JP2008509723A (ja) * | 2004-08-10 | 2008-04-03 | アラーガン、インコーポレイテッド | 無針微小突起システム |
JP2008522731A (ja) * | 2004-12-10 | 2008-07-03 | スリーエム イノベイティブ プロパティズ カンパニー | 医療用デバイス |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6565532B1 (en) * | 2000-07-12 | 2003-05-20 | The Procter & Gamble Company | Microneedle apparatus used for marking skin and for dispensing semi-permanent subcutaneous makeup |
KR101323980B1 (ko) * | 2002-07-19 | 2013-10-30 | 쓰리엠 이노베이티브 프로퍼티즈 컴파니 | 마이크로 니들 장치, 마이크로 니들 장치를 사용하는 방법 및 마이크로 니들 장치를 송출하는 방법 |
JPWO2008020632A1 (ja) * | 2006-08-18 | 2010-01-07 | 凸版印刷株式会社 | マイクロニードル及びマイクロニードルパッチ |
AU2008209537B2 (en) * | 2007-01-22 | 2013-01-31 | Corium Pharma Solutions, Inc. | Applicators for microneedle arrays |
JP2008284318A (ja) * | 2007-05-15 | 2008-11-27 | Kosumedei Seiyaku Kk | 生体由来物質からなる投薬用微細針 |
KR100938631B1 (ko) | 2008-06-18 | 2010-01-22 | 주식회사 누리엠웰니스 | 솔리드 마이크로구조체의 제조방법 |
EP2383013A4 (en) * | 2008-12-26 | 2012-11-28 | Hisamitsu Pharmaceutical Co | MICRO NEEDLE DEVICE |
-
2011
- 2011-05-25 WO PCT/JP2011/062026 patent/WO2011148995A1/ja active Application Filing
- 2011-05-25 KR KR1020127033657A patent/KR101759370B1/ko active IP Right Grant
- 2011-05-25 ES ES11786694T patent/ES2728479T3/es active Active
- 2011-05-25 EP EP11786694.7A patent/EP2578265B1/en active Active
- 2011-05-25 CN CN2011800263798A patent/CN102917752A/zh active Pending
- 2011-05-25 US US13/699,471 patent/US20130084316A1/en not_active Abandoned
- 2011-05-25 JP JP2012517303A patent/JP5797644B2/ja active Active
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001506904A (ja) | 1996-12-20 | 2001-05-29 | アルザ・コーポレーション | 経皮作用剤流量を強化するための組成物と方法 |
JP2004504120A (ja) | 2000-07-21 | 2004-02-12 | グラクソスミスクライン バイオロジカルズ ソシエテ アノニム | ワクチン |
JP2004510535A (ja) | 2000-10-13 | 2004-04-08 | アルザ・コーポレーシヨン | 微小突起を用いて皮膚を穿孔するための装置および方法 |
JP2008509723A (ja) * | 2004-08-10 | 2008-04-03 | アラーガン、インコーポレイテッド | 無針微小突起システム |
JP2006149818A (ja) * | 2004-11-30 | 2006-06-15 | Nitto Denko Corp | 経皮投薬デバイス |
JP2008522731A (ja) * | 2004-12-10 | 2008-07-03 | スリーエム イノベイティブ プロパティズ カンパニー | 医療用デバイス |
JP2007089792A (ja) | 2005-09-28 | 2007-04-12 | Nano Device & System Research Inc | 経皮投与装置 |
JP2007130417A (ja) | 2005-11-08 | 2007-05-31 | Nano Device & System Research Inc | 経皮投与装置 |
Non-Patent Citations (1)
Title |
---|
See also references of EP2578265A4 |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11083515B2 (en) | 2013-12-18 | 2021-08-10 | Novoxel Ltd. | Methods and devices for thermal tissue vaporization and compression |
US11291498B2 (en) | 2013-12-18 | 2022-04-05 | Novoxel Ltd. | Methods and devices for thermal tissue vaporization and compression |
JP2017528239A (ja) * | 2014-09-15 | 2017-09-28 | ノヴォクセル リミテッド | 組織の熱的蒸散および熱圧迫のための方法および装置 |
Also Published As
Publication number | Publication date |
---|---|
KR20130111243A (ko) | 2013-10-10 |
JP5797644B2 (ja) | 2015-10-21 |
KR101759370B1 (ko) | 2017-07-18 |
ES2728479T3 (es) | 2019-10-24 |
CN102917752A (zh) | 2013-02-06 |
EP2578265A1 (en) | 2013-04-10 |
US20130084316A1 (en) | 2013-04-04 |
JPWO2011148995A1 (ja) | 2013-07-25 |
EP2578265A4 (en) | 2013-12-04 |
EP2578265B1 (en) | 2019-04-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5597254B2 (ja) | 微小突起付きアレイを有するデバイス | |
EP2835147B1 (en) | Puncture device | |
RU2750904C2 (ru) | Массивы микроигл и способы их получения и использования | |
US10953220B2 (en) | Device and method of skin care and treatment via microneedles having inherent anode and cathode properties, with or without cosmetic or pharmacological compositions | |
JP2021529760A (ja) | 活性物質の送達のための三次元マイクロ流体デバイス | |
JP5797644B2 (ja) | 微小突起付きアレイ | |
EP4327803A1 (en) | Microneedle patch | |
JP2024074537A (ja) | マイクロニードル貼付剤 | |
TWI842068B (zh) | 微針貼附劑 | |
US20160361264A1 (en) | Delivery of pharmaceutical active ingredients through the skin and hair follicles into dermis and transdermal delivery |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 201180026379.8 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 11786694 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2012517303 Country of ref document: JP |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 13699471 Country of ref document: US |
|
ENP | Entry into the national phase |
Ref document number: 20127033657 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2011786694 Country of ref document: EP |