WO2015147040A1 - Micro-aiguille demeurant dans la couche cornée - Google Patents

Micro-aiguille demeurant dans la couche cornée Download PDF

Info

Publication number
WO2015147040A1
WO2015147040A1 PCT/JP2015/059094 JP2015059094W WO2015147040A1 WO 2015147040 A1 WO2015147040 A1 WO 2015147040A1 JP 2015059094 W JP2015059094 W JP 2015059094W WO 2015147040 A1 WO2015147040 A1 WO 2015147040A1
Authority
WO
WIPO (PCT)
Prior art keywords
microneedle
tip
stratum corneum
skin
staying
Prior art date
Application number
PCT/JP2015/059094
Other languages
English (en)
Japanese (ja)
Inventor
英淑 権
文男 神山
Original Assignee
コスメディ製薬株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by コスメディ製薬株式会社 filed Critical コスメディ製薬株式会社
Publication of WO2015147040A1 publication Critical patent/WO2015147040A1/fr

Links

Images

Classifications

    • 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
    • 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
    • A61M2037/0023—Drug applicators using microneedles
    • 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
    • A61M2037/0046—Solid microneedles

Definitions

  • the present invention relates to a microneedle that remains in the skin stratum corneum even after insertion and a method for fastening the microneedle to the stratum corneum.
  • the skin stratum corneum acts as a barrier for drug permeation, and simply applying the drug to the skin surface does not allow the drug to permeate sufficiently.
  • a microneedle by perforating the stratum corneum using 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 a large number of microneedles integrated on a substrate.
  • microneedles are made by adding an adhesive tape (adhesive film) for attaching the microneedle array to the skin and a cover sheet for maintaining aseptic conditions until use. This is called a patch.
  • a microneedle is created using a substance that dissolves in the body and disappears due to metabolism, such as carbohydrates, and the drug is retained in the microneedle, the inserted microneedle is easily dissolved in the body.
  • the drug can be administered intradermally or subcutaneously (Patent Document 2).
  • a microneedle made of a biosoluble polymer substance such as hyaluronic acid or collagen
  • moisture in the skin diffuses into the microneedle, and the needle portion inserted into the skin swells and then dissolves.
  • hyaluronic acid and collagen diffuse into the skin, and drugs and valuable substances held by the microneedles diffuse into the skin (Patent Documents 3 and 4).
  • microneedle arrays for the administration of drugs and valuable substances as cosmetics, it is required by the Pharmaceutical Affairs Law that the inserted microneedle stays in the stratum corneum of the skin and does not enter further inside. Has been. If it is inserted inside the stratum corneum, it is interpreted as a pharmaceutical product and cannot be manufactured and sold as a cosmetic.
  • the stratum corneum of the skin is hard to some extent, but the inside is not so hard. Therefore, when a thin and long conical needle-like microneedle is inserted, it is known that the microneedle passes through the stratum corneum and enters the back of the skin. This is interpreted as a medicine and cannot be manufactured and sold as a cosmetic. The standards for manufacturing and selling pharmaceuticals are much stricter than cosmetics.
  • the problem to be solved by the present invention is to provide a microneedle that can penetrate the stratum corneum through the skin surface, but the tip stays in the stratum corneum and does not penetrate deeper than the stratum corneum. is there.
  • the present invention comprises a tip and a tip lower part continuous with the tip, and the tip of the tip is sharp enough to penetrate the skin stratum corneum surface, but the tip lower part is more than the tip
  • a microneedle is provided that is thick and stays in the stratum corneum when inserted.
  • the microneedle that stays in the stratum corneum according to the present invention made to solve the above problems is sharp enough that the tip can pierce the surface of the stratum corneum, but the bottom of the tip is thick, and when inserted, it enters the stratum corneum. It is characterized by staying.
  • “lower” refers to the direction from the tip of the microneedle to the substrate, and “lower end” refers to a portion slightly closer to the substrate than the tip of the microneedle.
  • the tip of the microneedle In order for the microneedle to penetrate the stratum corneum surface, the tip of the microneedle must be sharp to some extent. In order to stay in the stratum corneum and prevent deep penetration, it is preferable to make the diameter of the microneedle larger than the vicinity of the tip or make the tip not very sharp.
  • the diameter of the microneedle is increased from the vicinity of the tip, it is not inserted deeply because the momentum of insertion is reduced.
  • the step is caught in the hole created at the beginning of insertion and the microneedle does not penetrate deeper into the skin.
  • a step is not provided, if the cross-sectional area of the microneedle is increased from the tip toward the substrate, resistance to penetration can be obtained and the tip of the microneedle can be retained in the stratum corneum.
  • the tip of the microneedle can penetrate the stratum corneum surface, but in order not to penetrate the stratum corneum and penetrate further into the inside, it is more effective to make the tip slightly dull than to make the tip very sharp. is there.
  • the conventional microneedle includes a microneedle body 12 and a microneedle substrate 13. A microneedle is pressed against the skin surface 14. Since the skin has elasticity, the portion pressed against the microneedle body 12 is recessed, and the microneedle body 12 is in contact with the substrate 13 to prevent the microneedle body 12 from being inserted. Fastening the microneedles to the stratum corneum cannot be achieved simply by shortening the length of the microneedles, but only by selecting an appropriate microneedle shape.
  • the material of the microneedle of the present invention is not limited. It may be a metal, silicon, a resin insoluble in the living body, or a resin insoluble in the living body such as a polysaccharide.
  • the microneedle is a material that is insoluble in the living body, drugs and valuables can be applied to the surface of the microneedle, and the microneedle can be held or allowed to flow by providing a vertical hole or a horizontal hole.
  • the material is soluble in the living body, it can be applied, retained, and flowed in, and can also be contained inside the microneedle.
  • the material of the microneedle is water-soluble so that it quickly dissolves when inserted into the skin and does not penetrate the stratum corneum and enter the skin.
  • microneedles that remain in the stratum corneum of the present invention do not penetrate the stratum corneum and enter the inside, and are legally manufactured and sold as cosmetics. This is because microneedles that pass through the stratum corneum and enter the inside are not recognized as cosmetics.
  • a product with a specific purpose must be designed in accordance with the country's laws regarding that product. It is recognized that the microneedles that remain in the stratum corneum of the present invention are legally manufactured and sold as cosmetics in Japan.
  • FIG. 1 is a schematic diagram showing a state in which a short conventional microneedle is pressed against the skin.
  • FIGS. 2A to 2C are schematic front views showing the microneedles of the embodiments of the present invention.
  • FIG. 3 is a photomicrograph of a skin site to which microneedles are applied. A indicates the stratum corneum, B indicates the living epidermal layer, and C indicates the dermal layer.
  • the design of the shape of the microneedle is basically important in order to keep the microneedle in the stratum corneum when it is inserted.
  • a microneedle 1 shown in FIG. 2A has a microneedle body 2 and a substrate 3. One end of the microneedle body 2 is provided on the substrate 3.
  • the microneedle main body 2 has a front end portion 7 and a lower end of the front end that is continuous with the front end portion and joined to the substrate 3.
  • “Lower” means the substrate 3 side of the microneedle 1.
  • the tip 7 and the tip lower part 8 are continuously connected, and there is no step between them. Moreover, the front-end
  • a step X is provided between the tip lower portion 8 and the tip portion 7.
  • the tip 7 of the tip side closer to the step X has a sharp tip.
  • the relatively thick tip lower part 8 gradually increases in diameter from the step X toward the substrate 3.
  • the outer shape of the tip lower end 8 is a quadratic curve projecting toward the tip 7 side.
  • the tip lower end 8 has the same shape as the tip lower end 8 shown in FIG. 2 (a). But the front-end
  • FIG. The tip 7 has a sharp tip, similar to the tip 7 shown in FIG.
  • microneedle of the present invention is not limited to the specific shape shown in FIGS.
  • the tip is relatively thin so that it is sharp enough to penetrate the skin stratum corneum, and the tip bottom is relatively thicker than the tip. As long as can remain, there is no particular limitation.
  • Both the corner type (Fig. 2 (b)) and the slide type (Fig. 2 (c)) have a sharp tip, a step and a center.
  • the two types differ in that the stepped portion is square or smooth.
  • the sharp tip When the sharp tip is inserted into the skin, it is designed to prevent further insertion at the stepped portion, the tip remains in the stratum corneum, and the center is not inserted. That is, the tip portion is designed to have a length that can stay in the stratum corneum.
  • the shape from the tip to the step not the shape of the center. That is, the base part of the slide type in FIG. 2B may have a widened skirt as shown in FIG. 2C, and the central part of the corner type in FIG. 2C is perpendicular to the substrate as shown in FIG. You may be close to.
  • the cross-sectional shape of the tip portion and the central portion can take various shapes such as a circle, an ellipse, a triangle, and a quadrangle.
  • the step portion passes through a small hole whose tip is opened on the surface of the stratum corneum, and the entire microneedle is inserted. Then, it is thought that the tip passes through the stratum corneum and reaches deeper.
  • the level difference is too large, the phenomenon shown in FIG. 1 occurs due to the elasticity of the skin, and the sharp tip cannot break the stratum corneum surface.
  • the tip is too short or too thin, a sufficient amount of drugs or valuables cannot be delivered into the stratum corneum. This is because drugs and valuables are held at the tip. If the tip is too long, naturally the tip will penetrate the stratum corneum even if the insertion is stopped by a step. This makes it impossible to manufacture and sell it as a cosmetic.
  • the width of the step of the microneedle staying on the horny stratum corneum is preferably 0.01 to 0.1 mm.
  • the width of the step means the difference in radius between the tip and the center of the step when the microneedle has a circular cross section. Even if it is not circular, the width of the corresponding step can be assumed based on the cross-sectional view of the microneedle. If the width of the step is not uniform, an average value may be considered.
  • the length of the tip portion of the square or slide type is 0.01 to 0.1 mm. This is so that as many drugs or valuables as possible can be retained without penetrating from the stratum corneum.
  • the Conide type means a shape like a volcanic mountain as shown in FIG.
  • the tip is slightly flat, gradually getting thicker from the tip, preventing deep penetration.
  • the tip of the Conide type should be slightly flat rather than sharp. This is to counter the momentum of insertion and to keep as many drugs and valuables as possible.
  • the width of the tip is preferably 0.005 to 0.04 mm (25 ⁇ 10 ⁇ 6 to 16 ⁇ 10 ⁇ 4 mm 2 ), assuming a circular shape. Even if it is not circular, it is desirable to have the same area as a circle having this diameter.
  • the tip of the coneide type and the stepped part of the slide type or the corner type are preferably close to a plane, but need not be strictly a plane.
  • a circular microneedle array (diameter 1 cm) having a coneide type microneedle was manufactured using hyaluronic acid (FCH-SU manufactured by Kikkoman Biochemical Co., Ltd.) as a material.
  • FCH-SU hyaluronic acid
  • the height of the microneedles was 200 ⁇ m
  • the tip diameter was 20 ⁇ m
  • the bottom diameter was 300 ⁇ m
  • the spacing between the microneedles was 600 ⁇ m.
  • a circular microneedle patch was prototyped using this microneedle array.
  • a microneedle patch having a 2.5 cm diameter adhesive tape lined on the microneedle array was used for the subsequent experiments.
  • Human skin obtained from IIAM, USA was cut into a circle of 700 ⁇ m in diameter and used as test skin.
  • the microneedle patch was administered to the test skin with a piston type applicator and fixed to the skin with an adhesive tape. Five minutes after administration, the microneedle patch was peeled from the skin, and the microneedle patch administration portion of the test skin was cut. Cut the cut skin. C. It was embedded in T compound and cooled with cold acetone for 10 minutes. The cooled skin was sliced to prepare a frozen section for microscopic observation, which was stained with HE to obtain a skin piece for observation.
  • A indicates the stratum corneum
  • B indicates the living epidermal layer
  • C indicates the dermal layer.
  • the microneedle Even though the height of the microneedle is 200 ⁇ m, it may remain in the stratum corneum because hyaluronic acid has a high hygroscopic property, and when it reaches the stratum corneum, it immediately becomes soft due to moisture from the skin.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Medical Informatics (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Media Introduction/Drainage Providing Device (AREA)

Abstract

Selon les dispositions de la Loi japonaise sur l'industrie pharmaceutique, une micro-aiguille en tant que produit cosmétique ne doit pas percer la couche cornée et pénétrer dans la partie profonde de la peau. La présente invention concerne une micro-aiguille demeurant dans la couche cornée lors de la perforation. La micro-aiguille a une structure telle qu'elle est apte à traverser la surface de la couche cornée de la peau mais à peine apte de perforation en profondeur. À cet effet, une structure appropriée de la micro-aiguille est une structure étagée, par exemple en forme de prismatoïde ou de curseur, pourvue d'une extrémité pointue qui est destinée à perforer seule, ou une structure composite de type volcan pourvue d'une pointe non acérée dans laquelle l'épaisseur augmente progressivement à partir de la pointe.
PCT/JP2015/059094 2014-03-26 2015-03-25 Micro-aiguille demeurant dans la couche cornée WO2015147040A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2014081417 2014-03-26
JP2014-081417 2014-03-26

Publications (1)

Publication Number Publication Date
WO2015147040A1 true WO2015147040A1 (fr) 2015-10-01

Family

ID=54195552

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2015/059094 WO2015147040A1 (fr) 2014-03-26 2015-03-25 Micro-aiguille demeurant dans la couche cornée

Country Status (2)

Country Link
JP (2) JP2015192872A (fr)
WO (1) WO2015147040A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020004666A1 (fr) 2018-06-29 2020-01-02 L'oreal Procédé cosmétique utilisant une feuille de micro-aiguilles
WO2020004428A1 (fr) 2018-06-29 2020-01-02 L'oreal Procédé cosmétique utilisant une feuille à micro-aiguilles
WO2020017441A1 (fr) 2018-07-17 2020-01-23 L'oreal Feuille de micro-aiguilles
CN110769891A (zh) * 2017-08-17 2020-02-07 考司美德制药株式会社 口唇用微针阵列
CN110799238A (zh) * 2017-11-02 2020-02-14 考司美德制药株式会社 齿科用局部麻醉微针阵列
WO2020130157A1 (fr) 2018-12-21 2020-06-25 L'oreal Kit et procédé cosmétique utilisant une feuille à micro-aiguilles
EP3695876A1 (fr) 2019-02-18 2020-08-19 L'oreal Crayon pour insérer des micro-implants à l'intérieur des couches supérieures de la peau
EP3698841A1 (fr) 2019-02-19 2020-08-26 L'oreal Dispositif d'injection
WO2020200407A1 (fr) 2019-03-29 2020-10-08 L'oreal Micro-implants congelés et leur procédé de fabrication
EP3827869A4 (fr) * 2018-08-28 2021-10-27 Nissha Co., Ltd. Feuille d'amélioration de la qualité de la peau
WO2024053625A1 (fr) * 2022-09-08 2024-03-14 コスメディ製薬株式会社 Système d'application locale

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108778012B (zh) * 2016-02-17 2021-05-04 里兰斯坦福初级大学理事会 用于人体冷却和加热的红外透明的多孔聚合物纺织物
KR102366914B1 (ko) * 2019-01-04 2022-02-24 연세대학교 산학협력단 마이크로니들 구조체
KR102316435B1 (ko) * 2019-08-14 2021-10-25 울산대학교 산학협력단 니들 어레이를 이용한 액체류 주입 장치

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003238347A (ja) * 2002-02-18 2003-08-27 Nano Device & System Research Inc 機能性マイクロパイル及びその製造方法
JP2009273872A (ja) * 2008-04-14 2009-11-26 Kosumedei Seiyaku Kk マイクロニードルアレイ

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1086214B1 (fr) * 1998-06-10 2009-11-25 Georgia Tech Research Corporation Dispositifs a microaiguilles et procedes de leur fabrication
US7842008B2 (en) * 2005-11-21 2010-11-30 Becton, Dickinson And Company Intradermal delivery device
CN102039000B (zh) * 2009-10-20 2015-08-26 苏州纳通生物纳米技术有限公司 一种透皮给药试剂盒
JP2013248299A (ja) * 2012-06-01 2013-12-12 Dainippon Printing Co Ltd マイクロニードルデバイス
TWI554289B (zh) * 2012-06-29 2016-10-21 國立成功大學 鑲嵌式經皮藥物釋放貼片及其製造方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003238347A (ja) * 2002-02-18 2003-08-27 Nano Device & System Research Inc 機能性マイクロパイル及びその製造方法
JP2009273872A (ja) * 2008-04-14 2009-11-26 Kosumedei Seiyaku Kk マイクロニードルアレイ

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110769891A (zh) * 2017-08-17 2020-02-07 考司美德制药株式会社 口唇用微针阵列
CN110799238A (zh) * 2017-11-02 2020-02-14 考司美德制药株式会社 齿科用局部麻醉微针阵列
CN115252593A (zh) * 2017-11-02 2022-11-01 考司美德制药株式会社 齿科用局部麻醉微针阵列
WO2020004428A1 (fr) 2018-06-29 2020-01-02 L'oreal Procédé cosmétique utilisant une feuille à micro-aiguilles
WO2020004666A1 (fr) 2018-06-29 2020-01-02 L'oreal Procédé cosmétique utilisant une feuille de micro-aiguilles
WO2020017441A1 (fr) 2018-07-17 2020-01-23 L'oreal Feuille de micro-aiguilles
EP3827869A4 (fr) * 2018-08-28 2021-10-27 Nissha Co., Ltd. Feuille d'amélioration de la qualité de la peau
WO2020130157A1 (fr) 2018-12-21 2020-06-25 L'oreal Kit et procédé cosmétique utilisant une feuille à micro-aiguilles
EP3695876A1 (fr) 2019-02-18 2020-08-19 L'oreal Crayon pour insérer des micro-implants à l'intérieur des couches supérieures de la peau
WO2020169443A1 (fr) 2019-02-18 2020-08-27 L'oreal Stylo pour l'insertion de micro-implants à l'intérieur de couches cutanées supérieures
WO2020169640A1 (fr) 2019-02-19 2020-08-27 L'oreal Dispositif d'injection
EP3698841A1 (fr) 2019-02-19 2020-08-26 L'oreal Dispositif d'injection
WO2020200407A1 (fr) 2019-03-29 2020-10-08 L'oreal Micro-implants congelés et leur procédé de fabrication
WO2024053625A1 (fr) * 2022-09-08 2024-03-14 コスメディ製薬株式会社 Système d'application locale

Also Published As

Publication number Publication date
JP2015192872A (ja) 2015-11-05
JP2021087866A (ja) 2021-06-10

Similar Documents

Publication Publication Date Title
WO2015147040A1 (fr) Micro-aiguille demeurant dans la couche cornée
US10576257B2 (en) Article comprising a microneedle and methods of use
JP6928735B2 (ja) 斜角開口部を有する中空マイクロニードル
EP3021930B1 (fr) Microaiguille creuse avec pointe biseautée
JP5267910B2 (ja) マイクロニードルアレイ
US10099043B2 (en) Hollow microneedle array article
EP1684846B1 (fr) Dispositif d'administration transdermique de substances actives
JP2016511014A5 (fr)
TW201113056A (en) Stamper for micro needle sheet, method for manufacturing the same, and method for manufacturing micro needle sheet utilizing stamper
KR20210025601A (ko) 활성제의 전달을 위한 3차원 미세유체학 장치
JP2010184102A (ja) 経皮投薬装置及びその装置に使用するニードル形成体
EP3247449A1 (fr) Agencement de micro-aiguilles et procédé d'utilisation
EP3723725B1 (fr) Matrice à micro-aiguilles présentant un principe actif sous forme de sels
CN108883262B (zh) 经皮给药装置
NL2011544C2 (en) Micro needle for transporting fluid across or into a biological barrier and method for producing such a micro needle.
JP2016055174A (ja) 穿刺器具
JP6068057B2 (ja) 経皮投薬装置及びその装置に使用される薬液注入針
WO2016039333A1 (fr) Dispositif de piqûre

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15770247

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15770247

Country of ref document: EP

Kind code of ref document: A1