WO2020100854A1 - Réseau de micro-aiguilles enduites de manière hydrofuge - Google Patents

Réseau de micro-aiguilles enduites de manière hydrofuge Download PDF

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WO2020100854A1
WO2020100854A1 PCT/JP2019/044242 JP2019044242W WO2020100854A1 WO 2020100854 A1 WO2020100854 A1 WO 2020100854A1 JP 2019044242 W JP2019044242 W JP 2019044242W WO 2020100854 A1 WO2020100854 A1 WO 2020100854A1
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Prior art keywords
microneedle
drug
water
repellent
microneedle array
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PCT/JP2019/044242
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English (en)
Japanese (ja)
Inventor
英淑 権
裕史 山下
文男 神山
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コスメディ製薬株式会社
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Publication of WO2020100854A1 publication Critical patent/WO2020100854A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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

Definitions

  • the present invention relates to a technique for surely and easily applying a drug to a microneedle when the drug is quantitatively applied to the microneedle.
  • Non-patent Document 1 a painless transdermal administration method using a microneedle array has attracted attention.
  • the stratum corneum of the skin acts as a barrier for drug permeation, and simply applying the drug to the skin surface does not necessarily have sufficient permeability.
  • a microneedle by piercing the stratum corneum with a fine needle, that is, a microneedle, the drug permeation efficiency can be significantly improved as compared with the coating method.
  • a microneedle array is formed by accumulating a large number of these microneedles on a substrate.
  • a microneedle patch is a product that is easy to use by adding an adhesive sheet for attaching the microneedle array to the skin or a release sheet for protecting the adhesive surface to the microneedle array to make it a product that is easy to use.
  • microneedles were used as the material for the microneedles, but since then, various polymer materials have received attention from the viewpoint of processability.
  • microneedles are made using a substance such as sugar that disappears by metabolism in the body, even if the needle breaks and remains in the skin, it does not cause an accident.
  • the material of the microneedle is a sugar
  • the drug is included in the sugar to make a microneedle
  • the inserted microneedle is dissolved in the body, so that the drug can be easily injected into the skin or subcutaneously. It can be administered (Patent Document 1).
  • a microneedle made of a biosoluble polymer substance such as hyaluronic acid or collagen
  • moisture in the skin diffuses into the needle portion
  • the needle portion inserted into the skin swells, and then dissolves.
  • the anti-wrinkle effect is expressed by the diffusion of hyaluronic acid or collagen in the skin due to the dissolution of the needle portion, or the drug or valuable substance previously dissolved in the needle portion is released into the skin (Patent Documents 2 and 3).
  • microneedle array is prepared by incorporating such an expensive and valuable drug into a material, the drug is contained not only in the microneedle part but also in the substrate part.
  • this microneedle array is inserted into the skin, the drug contained in the microneedle part is taken into the body and diffused, but the drug present in the substrate part is discarded without being used, and the utilization efficiency of expensive drug is low. Will result.
  • Patent Documents 4--7 A method of coating the surface of a microneedle with a drug using a drug solution
  • Patent Document 8 A method of collecting the drug at the tip of the microneedle by granulating the drug and centrifuging it while the microneedle is soft
  • the method of coating the drug on the surface of the microneedle or the method of attaching the drug to the tip of the microneedle from the drug solution requires the heating of the drug, or the drug adhered with difficulty will peel off when the microneedle is inserted. was there.
  • Patent Document 9 a method has been proposed in which a drug is dissolved in a solvent of a microneedle material to integrate the attached drug and the microneedle body to prevent the drug from peeling off
  • Patent Documents 4-7 and 9 The method of immersing the tip of the microneedle in the drug solution to attach the drug to the tip of the microneedle is simple and easy to put into practical use.
  • Patent Document 10 There is also known a manufacturing method in which the side surface of the needle-shaped body is made uneven so as to increase the drug holding amount at the tip of the microneedle.
  • Patent Document 11 A fine needle-shaped protrusion having multiple steps and a manufacturing method thereof are also known (Patent Document 11).
  • a microneedle made of a hydrophilic material When a microneedle made of a hydrophilic material is simply immersed in an aqueous drug solution, the aqueous drug solution moves up the needle due to capillary action, reaches the substrate from the bottom of the needle, and distributes the drug widely, so the drug is quantified at the tip of the microneedle. It becomes impossible to load it.
  • Hundreds of microneedles are densely forested in a single microneedle array with a gap of 20 ⁇ m to 1,000 ⁇ m, and the drug aqueous solution rises extremely easily due to the capillary phenomenon. Therefore, it has been extremely difficult to immerse the microneedle array in the drug aqueous solution to a certain depth to hold the drug quantitatively, though many attempts have been made so far.
  • Patent Document 5 In order to prevent the capillarity, a method of applying a drug by masking other than the tip of the microneedle has been proposed (Patent Document 5). A method has also been proposed in which a large number of holes are filled with a drug and a microneedle is inserted into the holes to improve the quantitativeness of the amount of drug attached (Patent Document 7). However, implementation of these methods is very complicated.
  • the base of the microneedle array is a hydrophilic substance selected from the group consisting of metal, silica, glass, polylactic acid, polyglycolic acid, nylon, hyaluronic acid, hydroxypropylcellulose, and polyvinylpyrrolidone.
  • Microneedle array of description [3] The base of the microneedle array is selected from the group consisting of nylon, polycarbonate, polylactic acid, poly (lactic acid-glycolic acid) copolymer, polyglycolic acid, polyethylene terephthalate, cyclic olefin polymer and mixtures thereof.
  • the base of the microneedle array is a bioinsoluble polymer selected from the group consisting of hyaluronic acid, dextran, polyvinylpyrrolidone, sodium chondroitin sulfate, hydroxypropylcellulose, polyvinyl alcohol, and a mixture thereof.
  • the water-repellent coating contains a water-repellent substance having a saturated fluoroalkyl group, an alkylsilyl group, or a long-chain alkyl group having 20 or more carbon atoms, according to any one of [1] to [4].
  • Microneedle array. [6] A step of molding a microneedle array using a mold, A microneedle with a drug coating layer at the tip, including the step of water-repellently coating the formed microneedle microneedle array and the step of immersing the tip of the water-repellent coated microneedle in a drug aqueous solution to hold the drug.
  • Array manufacturing method
  • the drug solution By coating the microneedles with a water-repellent coating, the drug solution will not rise due to capillary action and stable drug application will be possible. This makes it possible to retain the drug quantitatively.
  • a microneedle coated with a drug after being water-repellent coated has the following two remarkable effects as compared with a microneedle coated with a drug on a microneedle without a water-repellent coating.
  • the physical properties of the drug-containing microneedle can be greatly improved by a simple manufacturing process of coating the microneedle with a water-repellent coating.
  • FIG. 1 is an example of a microneedle having a step.
  • FIG. 2 shows a microneedle without water repellent treatment. The coating solution rises to the substrate portion due to the capillary phenomenon, and most of the center of the microneedle portion is red.
  • FIG. 3 shows a water repellent microneedle. The coating solution remains on the tip.
  • FIG. 4 is an enlarged view of the water repellent microneedle (FIG. 3). It can be seen that the red dye is applied to the tip.
  • the microneedle forming the microneedle array has a needle length of 100 ⁇ m or more and 2,000 ⁇ m or less, preferably 200 to 1,000 ⁇ m, in order to ensure percutaneous absorption of a drug.
  • the size of the apex of the tip of the needle is expressed as a diameter, it is 80 ⁇ m or less, and preferably 30 ⁇ m or less, in order to facilitate the insertion into the skin and reduce the drug residue on the skin.
  • the individual microneedles include a cylindrical or conical shape with a circular bottom, an elliptic cylinder or elliptical cone with an elliptical bottom, a triangular prism or triangular pyramid with a triangular bottom, and a quadrangular prism or quadrangular pyramid with a quadrangular bottom.
  • the size of the bottom surface represents the major axis as the diameter, and the minor axis is shorter than the major axis as long as the ellipse can be formed.
  • one side may be represented as a representative and a diagonal line may be represented as a representative.
  • the microneedles having these shapes may have steps.
  • the step means that the cross-sectional area of the microneedle is discontinuously reduced from the point where the microneedle is present toward the tip direction, and the cross section has a stepped shape as shown in FIG.
  • FIG. 1 is a three-stage needle having two steps.
  • the shape of the microneedle having a step will be described with reference to FIG.
  • the length of the tip portion 1 is 50 to 500 ⁇ m and the rest is the intermediate portion 3 and the bottom portion 4.
  • the size of the edge 2 of the step between the tip portion and the middle portion and between the middle portion and the bottom portion is larger than 10 ⁇ m and smaller than 100 ⁇ m. It is more preferably 14 to 50 ⁇ m.
  • Reference numeral 5 indicates a substrate of the microneedle array.
  • edge 2 of the step is a surface (a surface parallel to the substrate) orthogonal to the axis of the microneedle within the range of working accuracy.
  • the size of the edge 2 of the step means the difference in radius between the tip and the bottom of the step. The tip and bottom differ depending on the shape of the microneedle.
  • the microneedle of the present invention has a conical shape.
  • the total length (needle length) of the microneedle is preferably about 70 to 1000 ⁇ m.
  • the length of the tip portion 1 is preferably 50 to 500 ⁇ m and the rest is the bottom portion (two-stage needle), or in the three-stage needle, the rest is the intermediate portion and the bottom portion.
  • the size of the edge 2 of the step between the tip portion and the middle portion and between the middle portion and the bottom portion is preferably larger than 10 ⁇ m and smaller than 100 ⁇ m. It is more preferably 14 to 50 ⁇ m.
  • microneedle here is a case of a microneedle made of a hydrophilic substance.
  • hydrophilic substance are metal, silica, glass, polylactic acid, polyglycolic acid, nylon, hyaluronic acid, hydroxypropylcellulose, polyvinylpyrrolidone, and the like.
  • the base of the microneedle array of the present invention may be a bio-insoluble polymer.
  • the bio-insoluble polymer means a polymer having a property of not being completely dissolved for at least 15 minutes after being molded into microneedles and piercing the skin.
  • a polymer that is easily injection-molded or press-molded is preferable, and nylon, polycarbonate, polylactic acid, poly (lactic acid-glycolic acid) copolymer, polyglycolic acid, polyethylene terephthalate, COP (cyclic olefin polymer) is preferable.
  • the base of the microneedle array of the present invention is hyaluronic acid, dextran, polyvinylpyrrolidone, sodium chondroitin sulfate, hydroxy, as long as it has a property of not being completely dissolved for at least 15 minutes after being molded into microneedles and piercing the skin. It may be a polymer selected from the group consisting of propyl cellulose, polyvinyl alcohol, and a mixture thereof.
  • a water repellent material is used to specifically perform the water repellent coating.
  • Representative water-repellent substances are those having the following functional groups. These are (1) saturated fluoroalkyl group, (2) alkylsilyl group, and (3) long-chain alkyl group having 10 or more carbon atoms. Examples of the water-repellent substance (1) include fluororesins. Examples of the water repellent substance (2) include silicone oil. Examples of the water-repellent substance (3) include liquid paraffin.
  • the water repellent coated microneedle array makes the entire surface of the microneedle hydrophobic.
  • the affinity between the drug and the needle is made as small as possible by making the drug application part hydrophobic.
  • the drug used in the present invention is generally a hydrophilic substance, and its affinity with the microneedles is reduced so that the drug can be promptly released from the needle after dermal administration.
  • drugs include all compounds that act on the skin or penetrate the skin to produce some beneficial action.
  • examples of the drug suitable for the purpose of the present invention include, for example, physiologically active peptides and their derivatives, nucleic acids, oligonucleotides, various antigenic proteins, bacteria, virus fragments and the like.
  • examples of the physiologically active peptides and derivatives thereof include calcitonin, adrenocorticotropic hormone, parathyroid hormone (PTH), hPTH (1 ⁇ 34), insulin, exendin, secretin, oxytocin, angiotensin, ⁇ -endorphin, glucagon.
  • the antigen protein include influenza antigen, HBs surface antigen, HBe antigen and the like.
  • the drug may be cosmetics.
  • the microneedle array of the present invention has a drug coating layer on a water-repellent coated microneedle.
  • the drug application layer is located at the tip of the microneedle, and when the tip of the microneedle is directed upward, the lower end of the drug application layer is 200 ⁇ m or more from the root of the needle. If the lower end of the drug application layer is 200 ⁇ m or more from the root of the needle, the upper end may be any height depending on the amount of drug applied. Preferably, the upper end is the tip of the microneedle, but it does not necessarily have to be applied up to the tip.
  • the length of the drug coating layer is typically 100 ⁇ m or more and 800 ⁇ m or less, and preferably 150 ⁇ m or more and 600 ⁇ m or less.
  • the lower end and the upper end of the drug coating layer are values obtained by measuring the lower end and the upper end of the drug-coated microneedle in the vertical direction from the substrate of the microneedle array.
  • the length of the drug coating layer is represented by the difference between the lower end and the upper end of the microneedle coated with the drug.
  • the drug coating layer has a different thickness depending on the drug coating liquid and the number of times of coating.
  • the thickness of the coating layer can be represented by the diameter near the center of the drug coating layer.
  • the diameter near the center of the drug application layer is larger than the diameter of the microneedles before drug application.
  • the thickness of the coating layer in the vicinity of the center varies depending on the purpose and the required amount of drug to be coated, but is preferably 10 to 100 ⁇ m.
  • the base material When applying the drug to the microneedle tip by immersing the tip of the water-repellent coated microneedle in the drug solution, the base material is dissolved in the drug solution, and the drug together with the base material is dried after application and drying. It is desirable to be held by a microneedle. It is necessary that the base material is a substance that does not impair the stability of the drug. For example, it is possible to use high molecular weight substances such as hyaluronic acid, dextrin, dextran, chondroitin sulfate Na, hydroxypropyl cellulose, ethyl cellulose, and carboxymethyl cellulose Na salt.
  • high molecular weight substances such as hyaluronic acid, dextrin, dextran, chondroitin sulfate Na, hydroxypropyl cellulose, ethyl cellulose, and carboxymethyl cellulose Na salt.
  • Examples thereof include saccharides, proteins such as collagen, water-soluble synthetic polymers such as polyvinylpyrrolidone and polyvinyl alcohol, low molecular weight saccharides such as glucose, sucrose, maltose, trehalose, and mixtures thereof.
  • An aqueous solution of the drug to which the base material and the water-soluble salt are added is suitable.
  • the water-soluble salt is preferably a water-soluble salt such as sodium chloride or zinc chloride.
  • a mixture of a water-soluble polymer and a low-molecular-weight saccharide is selected as a coexisting substance of the aqueous drug solution in which the microneedle is dipped, but the dissolution time of the drug in the skin is still long, and therefore the number of microneedle drugs after administration is small. It is necessary to attach the microneedle to the skin for 24 hours or 24 hours, which is not convenient for the patient.
  • the base material to which a water-soluble salt is added in addition to the water-soluble polymer and / or low-molecular-weight sugar can significantly shorten the dissolution time of the drug in the skin, thus shortening the administration time and significantly improving the convenience for the patient. I can.
  • the concentration of the base material in the aqueous drug solution is preferably 2% by mass to 60% by mass.
  • concentration is lower than 2% by mass, the viscosity of the aqueous solution of the drug is small and the amount of coating adhered upon immersion is small.
  • concentration of the drug aqueous solution is too high, and the drug application is not stable.
  • the ratio of high molecular weight to low molecular weight saccharide in the base material can be changed depending on the properties of the drug.
  • the base material may be all low-molecular sugars.
  • Antioxidants, surfactants and the like may be added to the drug aqueous solution, if necessary.
  • glycerin, ethylene glycol and a low molecular weight polymer thereof may be added to further enhance the dissolution of the drug in the skin.
  • the mechanical strength of the coating material is weakened, so caution is required.
  • the microneedle array can be mass-produced using a mold (mold).
  • the microneedle made of a water-soluble polymer may be obtained by pouring an aqueous solution of the material into a mold, drying it, and then taking it out (Japanese Patent Application Laid-Open No. 2009-273872 [0031]-[0033]).
  • the microneedle made of an injection moldable polymer may be manufactured by injection molding the material using a mold (Japanese Patent Laid-Open No. 2003-238347 [0017], [0018]).
  • stainless steel, heat resistant steel, superalloy, or the like can be used for the injection molding die.
  • a typical mold has notches corresponding to 100-900 microneedles per square cm to create the shape of microneedles.
  • a fine processing means such as a grinder can be used to make the cut portion.
  • a known method may be used. For example, a thin needle plate of metal (titanium or stainless steel) is die-cut with a laser, and then the needle is raised 90 degrees to form a microneedle.
  • thermoplastic resin for example, polyglycolic acid, polylactic acid, or a copolymer thereof can be used alone or as a mixture.
  • a composition containing an inorganic filler, another thermoplastic resin, or the like can be used as long as the object of the present invention is not impaired.
  • a composition (compound) in which 100 parts by mass of polyglycolic acid is mixed with 0 to 20 parts by mass of an inorganic filler and 0 to 30 parts by mass of another thermoplastic resin is used.
  • the inorganic filler include silica, titanium oxide, calcium carbonate, calcium silicate, and the like. These may be used alone or in combination of two or more.
  • other thermoplastic resins include homopolymers and copolymers of ⁇ -caprolactone, TPX, and the like. These thermoplastic resins may be used alone or in combination of two or more.
  • the other thermoplastic resin is usually used in a proportion of 0 to 30 parts by mass with respect to 100 parts by mass of polyglycolic acid.
  • the microneedles of the microneedle array formed in the above step are immersed in a solution of the water repellent substance in a solvent and air-dried.
  • the solvent include ethanol, methanol, acetone and the like.
  • the tip of the water-repellent coated microneedle in the above step is immersed in an aqueous drug solution to retain the drug.
  • the retention of the drug in the microneedle array is performed by immersing the tip of the microneedle in a drug aqueous solution and holding the drug at the tip of the microneedle.
  • the drug aqueous solution may contain a solvent other than water in order to dissolve the drug.
  • the drug may be completely dissolved or may be dispersed in a solvent.
  • Immersing time and number of times can be set according to the affinity between the base of the microneedle and the drug solution, and apply so that the diameter near the center of the drug application part will be the desired value. After coating, it is dried until the solvent evaporates. The drying may be natural drying or forced drying by blowing dry air, nitrogen gas, or the like.
  • the drug solution reservoir is filled with the drug solution and the microneedle array is immersed from above to allow the drug to adhere to the needle.
  • the device needs to be capable of controlling the immersion depth with an accuracy of about 20 microns in order to precisely define the immersion depth of the microneedle array.
  • microneedle array including a drug coating layer on the tip can be manufactured.
  • the present invention is not limited to the examples. Although all the examples of the present invention use the conical microneedles, the present invention can be similarly applied to non-conical microneedles such as a quadrangular pyramid and a triangular pyramid.
  • the stepped microneedle using the injection moldable material of the present example is made into a mold having a cavity for molding a microneedle array by using an alloy tool steel, and the mold is used in a FANUC injection molding machine. Was set, and injection molding was performed at an injection temperature of 250 ° C.
  • the stepped microneedles are all used, but it goes without saying that the same effect can be expected even with the stepless microneedles.
  • a microneedle array made of polyglycolic acid and equipped with stepped microneedles was manufactured by injection molding.
  • the injection temperature was 250 ° C. using polyglycolic acid (Kuredax, Kureha Co., Ltd.) as a raw material.
  • the structure of the stepped microneedle is shown in FIG. In the figure, 1 is a tip portion, 2 is a step edge, 3 is a bottom portion, and 4 is a substrate.
  • the tip length was 300 ⁇ m
  • the bottom length was 300 ⁇ m
  • the edge size of the step was 30 ⁇ m
  • the needle gap was 400 ⁇ m.
  • the water repellent treatment was performed as follows.
  • the microneedle was immersed in a solution of silicone oil (MED-460 manufactured by NuSil Technology, Inc.) diluted with ethanol to 50% and air dried.
  • a portion of the microneedle array (diameter: 1 cm) from the tip of the tip of the microneedle to 150 ⁇ m was dipped in an aqueous solution of the base material and the red dye (substance for evaluation) for 0.1 seconds.
  • the microneedle was raised and dried in the air for 30 seconds, and the second immersion was performed.
  • a dipping operation was performed 5 times in total to obtain a sample.
  • the base material in the aqueous solution was 9.0% by mass of carboxymethyl cellulose (Ashland, 7LP EP).
  • Example 2 The same dipping aqueous solution as in Example 1 was used to immerse the portion from the tip of the microneedle to 100 ⁇ m, and the number of operations was once.
  • the water repellent treatment prior to this operation was performed using a fluorine-based coating agent (Fusso Techno Coat, manufactured by Wilson Co., Ltd.).
  • microneedles without water repellent treatment were used. This operation was 100 ⁇ m immersion from the tip portion, and the immersion aqueous solution did not rise even if untreated.
  • Water-repellent treated microneedles and untreated microneedles were administered to the abdomen of a shaved rat (Wistar / ST male rat 8 weeks old), and 20 minutes later, it was taken out.
  • the red dye was extracted from the microneedle after administration with water, and the red dye remaining on the microneedle was evaluated from the absorbance value at a wavelength of 507 nm.

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Abstract

L'invention résout le problème selon lequel, lorsque la pointe d'une micro-aiguille est immergée dans une solution aqueuse de médicament pour revêtir la pointe de la micro-aiguille par le médicament, la solution aqueuse de médicament s'élève en raison d'une action capillaire et la charge quantitative de médicament est extrêmement difficile.　L'invention concerne une micro-aiguille revêtue de manière hydrofuge et un réseau de micro-aiguilles comprenant une couche de revêtement de médicament au niveau de la partie pointe des micro-aiguilles. L'invention concerne également un procédé de production du réseau de micro-aiguilles contenant la couche de revêtement de médicament au niveau des parties pointes, comprenant : une étape d'utilisation d'un modèle pour former le réseau de micro-aiguilles ; une étape de revêtement des micro-aiguilles du réseau de micro-aiguilles formé par un hydrofuge ; et une étape d'immersion des pointes des micro-aiguilles revêtues de manière hydrofuge dans une solution aqueuse de médicament de façon à contenir le médicament.
PCT/JP2019/044242 2018-11-13 2019-11-12 Réseau de micro-aiguilles enduites de manière hydrofuge WO2020100854A1 (fr)

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JP2018-212688 2018-11-13
JP2018212688A JP7306666B2 (ja) 2018-11-13 2018-11-13 撥水コーティングマイクロニードルアレイ

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WO2020100854A1 true WO2020100854A1 (fr) 2020-05-22

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WO2024005192A1 (fr) * 2022-06-30 2024-01-04 コスメディ製薬株式会社 Électrode pour capteurs de glucose

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WO2015190098A1 (fr) * 2014-06-13 2015-12-17 凸版印刷株式会社 Procédé de fabrication de corps en forme d'aiguille et corps en forme d'aiguille
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