[go: up one dir, main page]

WO1995012357A1 - Dispositif et procede permettant d'acceder a la peau des mammiferes sous la couche cornee - Google Patents

Dispositif et procede permettant d'acceder a la peau des mammiferes sous la couche cornee Download PDF

Info

Publication number
WO1995012357A1
WO1995012357A1 PCT/CA1993/000472 CA9300472W WO9512357A1 WO 1995012357 A1 WO1995012357 A1 WO 1995012357A1 CA 9300472 W CA9300472 W CA 9300472W WO 9512357 A1 WO9512357 A1 WO 9512357A1
Authority
WO
WIPO (PCT)
Prior art keywords
frame
skin
adhesive film
rigid frame
reel
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/CA1993/000472
Other languages
English (en)
Inventor
Douglas Gary Murray
John Dennis Zuccolin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Medipro Sciences Ltd
Original Assignee
Medipro Sciences Ltd
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 Medipro Sciences Ltd filed Critical Medipro Sciences Ltd
Priority to PCT/CA1993/000472 priority Critical patent/WO1995012357A1/fr
Priority to AU54145/94A priority patent/AU5414594A/en
Publication of WO1995012357A1 publication Critical patent/WO1995012357A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/54—Chiropodists' instruments, e.g. pedicure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/32—Surgical cutting instruments
    • A61B17/322—Skin grafting apparatus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/32—Surgical cutting instruments
    • A61B2017/320004—Surgical cutting instruments abrasive

Definitions

  • This invention relates to apparatus for effecting the partial or complete removal of the stratum corneum thickness at a defined area of a mammalian patient's skin surface and to a process for using such apparatus to prepare the skin for the transdermal delivery of drugs.
  • Transdermal drug delivery is delivery of a therapeutic agent through the skin of a patient, for distribution of therapeutic agent within the body by the circulation of the blood.
  • the therapeutic agent can be for general or localized treatment purposes.
  • the drug diffuses into the capillaries or tiny blood vessels in the skin, and thence to the circulating blood. Additionally, after having diffused into the skin, the drug may enter into the lymphatic system and thence to the circulating blood.
  • Transdermal drug delivery is to be contrasted with topical drug delivery, which is generally considered to be delivery to a topical wound, lesion, area affected by a skin dis ⁇ order, etc., of a medicament for the purposes of combatting infection, accelerating wound healing, relieving pain, managing skin disorders etc., by treatment of the localized are .
  • Mammalian skin comprises a number of layers.
  • the lowermost layer is the dermis, which consists of a fibrous layer of collagen and other material .
  • the epidermis Overlying the dermis is the epidermis, which consists of a series of layers of living epidermal cells in various stages of maturity. The degree of maturity increases with the distance of the layer from the dermis.
  • the epidermal layer which is most remote from the dermis and forms the outermost layer of skin is called the stratum corneum. It is comprised of a keratinized layer of dead, flattened epidermal cells.
  • the stratum corneum is the principal barrier to ingress of foreign materials into the body.
  • the stratum corneum is continuously shed by the body, and continuously reformed with keratinized epidermal cells from the layers below.
  • transdermal drug delivery has, for the most part, been confined to the delivery of relatively low molecular weight and relatively non-polar therapeutic agents, and accordingly, has not been useful in practice with a large number of effective therapeutic agents.
  • the stratum corneum has in the past been regarded as a reservoir into which the transdermally administered drug deposits, for subsequent diffusion into the body (see Bronaugh and Maibach “Percutaneous Absorption", Marcel Dekker, Inc., New York) .
  • Various means are currently known to increase the permeability of the stratum corneum. These include the use of skin penetration enhancers, e.g. AZONE (trademark) (1- dodecylhexahydro-2H-azepin-2-one) ; ion ophoresis, in which an electrical field is used to create a weak current across the stratum corneum to accelerate the penetration of ionic drugs; sonophoresis, in which ultrasound assists the pass ⁇ age of the drugs across the skin interfaces; and electro- poration, in which ej-ectrical currents create temporary pathways through the skin.
  • skin penetration enhancers e.g. AZONE (trademark) (1- dodecylhexahydro-2H-azepin-2-one)
  • ion ophoresis in which an electrical field is used to create a weak current across the stratum corneum to accelerate the penetration of ionic drugs
  • sonophoresis in which ultrasound assists the pass ⁇ age of the drugs across the skin interfaces
  • U.S. Patent No. 4,883,668 Ohta. issued November 28, 1989 discloses an article comprising a support and a substance capable of removing stratum ccrneum uniformly distributed on the support in small discontinuous areas, for use in removing a portion of the stratum corneum prior to transdermal drug administration.
  • the removing substance is suitably a pressure sensitive adhesive.
  • the drug is subsequently applied for transdermal delivery through the treated area of skin, by putting a plaster on the skin or by iontophoresis.
  • any compromising of the stratum corneum prior to application of transdermal drug delivery devices thereto should be done in a careful, controlled manner. Excessive or sudden, harsh removal of stratum corneum can cause pain to the patient.
  • a proper treatment to remove, in whole or in part, the stratum corneum calls for the initial selection of a skin area, followed by the successive application to that area of a removal device such as an adhesive film, so that each such application removes a small thickness portion of the stratum corneum.
  • the device should be applied repeatedly and reproducibly to the same, preselected area of skin surface, until it has been determined that the appropriate amount of stratum corneum has been removed in this manner.
  • Any procedure involving successive application and removal of adhesive sheets to prepare an area of skin for a drug delivery device be as reproducible as possible, in both delimiting the area of skin from which a portion of stratum corneum is removed in each stripping step and in the depth of stratum corneum removed after a given number of such steps.
  • the present invention provides, according to one aspect thereof, an apparatus for removing in a controlled fashion, at least a portion of the stratum corneum from mammalian skin in a predetermined location, without causing undue pain or irritation to the patient, prior to transdermal drug delivery through the predetermined area.
  • an apparatus for removing in a controlled fashion, at least a portion of the stratum corneum from mammalian skin in a predetermined location, without causing undue pain or irritation to the patient, prior to transdermal drug delivery through the predetermined area Compactness and ease and reproducibility of operation of the device make it suitable for use by the patient himself, where the presence of a clinician is not otherwise necessary.
  • the device includes a first rigid frame with a bottom plate having a central aperture through which the area to be treated is exposed when the device is placed again ⁇ the skin in use.
  • a second rigid frame movably mounted with respect to the first carries a reel of outwardly adhesive film which extends over an applicator having an applying surface, and a take-up device for the film after passage over the applying surface.
  • the adhesive film surface along the applying surface comes into contact with the exposed predetermined skin location below the aperture in the bottom plate, and a portion of the stratum corneum adheres thereto and is removed when the second rigid frame is retracted.
  • this is a ratchet- and-pawl or other suitable mechanism operable positively to turn the reel or take-up device, when the second frame is again extended, a suitable amount to apply fresh tape to the applying surface.
  • the take-up device is a roller journalled in the second said frame. This can be driven to pull the adhesive film off the storage reel and over the applying surface, e.g. by use of a ratchet and pawl mechanismoperated when the two frames are moved relative to one another. Alternatively, it can driven by a motor preset to operate to advance the predetermined length of adhesive film on each manual actuation of the motor.
  • the roller constituting the take-up device can be provided with a plurality of rectangular peripheral edge faces, of similar size, so that the roller as axially viewed exhibits polygonal symmetry.
  • Each said rectangular face constitutes an applying surface, and they are brought successively into registry with the aperture in the bottom plate as the roller is rotated.
  • the take-up roller is separate from the applicator, and is journalled onto the second frame at a position downstream therefrom.
  • the applicator can be in the form of a plunger attached for movement with the second frame, with the lowermost surface thereof being generally rectangular and constituting the applying surface of the device.
  • FIGURE 1 is a schematic view from one side of apparatus according to a first preferred embodiment of e present invention, with the operating mechanism in the rest (retracted) position;
  • FIGURE 2 is a like view of the apparatus of FIG 1, but with the operating mechanism in an intermediate (partially extended) position;
  • FIGURE 3 is a like view of the apparatus of FIG 1 and FIG. 2, but with the operating mechanism in its fully extended (skin contacting) position;
  • FIGURE 4 is a partial cross-sectional view of the apparatus of FIG.l seen at right angles to the view of FIG. 1;
  • FIGURE 5 is a diagrammatic cross sectional view of a second preferred embodiment of the present invention, with the frames in the relatively extended position,-
  • FIGURE 6 is a similar view of the embodiment shown in Fig. 5, with the frames in the retracted position;
  • FIGURE 7 is a view similar to Fig. 6, of a third preferred embodiment according to the invention.
  • FIGS 1 to 4 of the accompanying drawings illustrate apparatus according to a first embodiment of the present invention, including a first rigid frame 10, having a bottom plate 12 with a central rectangular aperture 14.
  • the device is positioned against the skin of a patient so that the selected area from which stratum corneum is to be removed is exposed to the interior of the device through aperture 14.
  • a second rigid frame 16 is slidably movable with respect to frame 10 in the vertical direction only, i.e. in the direction towards and away from the patient's skin.
  • Frame 16 carries the adhesive film changing mechanism, which in the preferred embodiment here illustrated comprises a cylindrical reel 18 and a parallel roller 20 having a regular polygonal symmetry about its axis of rotation, so that it presents a plurality of equiangularly disposed rectangular faces.
  • a supply of outwardly adhesive film 22 goes around reel 18 and roller 20 and extends between them.
  • sliding reel and roller support frame 16 is at its downwardmost (fully extended) position, one horizontally-oriented, tape-covered face 20b of roller 20 is in position to contact the skin of the patient through aperture 14.
  • FIG. 1 to 3 shows the operation of the apparatus from the fully retracted (rest) position to the fully extended (skin contact) position of the adhesive film application mechanism.
  • Reel 18 and roller 20 turn respectively about spindles 19 and 21 each fixed at corresponding ends thereof to sliding support frame 16.
  • a downward stroke of the sliding frame is effected by pushing down on handle 24 symmetrically positioned on and affixed to the top of frame 16.
  • Reel 18 and roller 20 are retained on their spindles and kept from lateral movement, by means of a vertical channel member 25 which is fixed to frame 10 and fits within groove 19a of spindle 19a and groove 21a of spindle 21.
  • Suitable means are included to positively turn reel 18 and unwind adhesive film from roller 20, or to turn roller 20 and wind film onto it from reel 18, over the course of a downstroke of handle 24 by just that angle subended by one rectangular face (20a, 20b, etc.) of the skin-contacting roller, i.e. 360°/n where n is the number of such faces. ith each successive extension stroke of handle 24, a fresh adhesive surface is presented through aperture 14 to contact the desired skin contact area.
  • any of a number of alternative means might be used for advancing and retracting the sliding frame between its fully retracted and fully extended positions while maintaining bottom plate 12 in contact with the skin and aperture 14 positioned over the area from which removal of stratum corneum is desired.
  • alternative equivalent means will be apparent for stepwise rotation of roller 20 or reel 18 to carry out the changing of the film surface from one extension-retraction stripping operation to the next. It is preferred, however, that the tape winding should occur on the downstroke and not on the upstroke, because as roller 20 is being retracted from the skin, the skin surface exposed through aperture 14 is pulled up a short distance. Any rotation of the roller at that stage could irreproducibly affect the interaction between the adhesive and the stratum corneum. It is readily seen from Figures 1 to 3 that the ratchet-and-pawl mechanism is configured to achieve its desired feature.
  • rotation of the type advance mechanism commence at or very near the beginning of the downstroke and finish shortly before skin contact with the newly positioned adhesive surface.
  • each contact face 20a, 20b, etc. be slightly convexly curved, to minimize the pulling- up of skin as a layer of stratum corneum is removed with retraction of roller 20 on the upstroke of handle 26, and thereby further reduce the inconsistency in the amount of stratum corneum removed in a given number of stripping steps. Irreproducibility may be further reduced by providing the perimeter of aperture 14 with a downwardly projecting, preferably serrated, integral ridge formation 14a which reduces the extent to which skin can be pulled up through aperture 10 in the retraction step of operation of the apparatus.
  • Adhesion of adhesive film 22 to the reel and roller for smooth operation as they turn may readily be ensured by fabricating the film as an outwardly adhesive tape having a double-sided adhesive tape against the non- adhesive backing of the skin contacting adhesive film and winding the exposed side of the double-sided adhesive tape about reel 18 or roller 20, whichever functions to take up the advancing adhesive film. It is convenient to provide the reel, roller and tape together as a cassette unit adapted for fitting into the hand-held apparatus. Examples of suitable commercially available skin-coating adhesives and specialty tapes include those sold under the trademarks CO-TRANS (3M Co) , MED 116 and MED 118 (Avery Specialty Tape Division) , TT 5024-00 and the like from Semex Medical, etc.
  • Figs 5 and 6 of the accompanying drawings show another preferred embodiment of the present invention.
  • Lower frame 42 has a bottom plate 44 with an aperture 46 therein, to define the predetermined area of the patient's skin 48 from which the device is to remove a part of the stratum corneum.
  • the upper frame 40 has a lowermost sleeve 50, slidable within lower frame 42, and spring loaded by means of compression spring 52 so that the upper frame 40 is biased towards the fully retracted relative position illustrated in Fig. 6.
  • the upper frame 40 carries within it a cassette 54 having a rotatably mounted reel of adhesive tape 56, guide rollers 58, 60 around which tape from the reel 56 passes, and a take-up roller 62 to receive the adhesive tape after use.
  • a plunger 64 protrudes downwardly from the upper frame 40, and has a lowermost rectangular surface 66 over which the adhesive tape slidably passes, from guide roller 58 to guide roller 60. Plunger 64 moves up and down with upper frame 40 relative to lower frame 42, to bring adhesive tape-bearing lowermost surface 66 into and out of contact with the preselected area of the patient's skin defined by the aperture 46.
  • An electric motor 68 mounted on the upper frame 40 is actuated as the plunger 64 is retracted with upper frame 40 relative to lower frame 42, to drive take-up roller a predetermined amount on each such retraction, so that a fresh length of adhesive tape overlies surface 66 ready for the next application to the patient's skin, i.e. next extension to the position shown in Fig. 5.
  • a light source 70 directed to shine a beam of light at an angle anto the length of adhesive tape 72 last applied to the skin by the lowermost surface 66 of the plunger 64.
  • a light detector 74 is positioned to receive light reflected from adhesive film portion 72, for visual inspection thereof to determine the nature of the stratum corneum portion adhering thereto, and thereby to determine the thickness of stratum corneum removed from the skin area by the operations of the device to that point.
  • Figure 7 of the accompa -.ng drawings show another but essentially similar preferred embodiment of the invention.
  • the device includes a handle 76 for gripping by the operator's hand, and equipped with a trigger which actuates the aforementioned electric motor to drive both the frames relative to one another and the take-up roller 62 within the cassette 54 to advance a predetermined length of adhesive tape across the bottom surface 66.
  • a light source 78 is provided to beam a light onto the skin surface through lowermost aperture 46 when the plunger 64 is in the retracted position, and a light detector 80 is positioned to receive light reflected therefrc ...
  • the progress of stratum corneum removal from the predetermined skin surface area is monitored by direct observation of the treated skin area instead of the removed skin layers.
  • a clinician or the patient holds the apparatus in a fixed location against the skin and repeatedly plunges the upper framework, manually or by use of the motor as described, and allows it to retract, causing a portion of stratum corneum to be removed on each retraction.
  • a transdermal drug delivery device be applied over the treated area.
  • drugs may be transdermally delivered including those of low to high molecular weight, high polarity, ionically charged compounds etc., which were previously unsuitable for such administration because they could not penetrate the skin in therapeutic levels. These include proteinaceous and polysaccharide substances.
  • the devices of the invention have been described for use in connection with transdermal drug delivery, it will be appreciated that they are useful in other systems where the presence of the stratum corneum acts as a barrier.
  • defects in the epidermis or dermis of a patient's skin can be treated with a therapeutic agent which penetrates the outer layers but does not need to enter the general circulation. Examples include skin carcinomas, which may be located in the dermis or epidermis.
  • the devices may be used in cosmetic applications, where skin blemishes (freckles, etc) originating in the lower skin layers, but visible through the stratum corneum to the skin surface are to be removed. In such uses, not only is the stratum corneum totally removed by successive adhesive film layers, but also layers of epidermis and possibly portions of dermis are removed, until the blemish is also removed.
  • Another alternative use for the device of the present invention is in removal of portions of stratum corneum and retention for analysis, e.g. for presence of illegal substances in a mammalian body.
  • a description of suitable analysis techniques is to be found in International Patent Application PCT/US90/06657 Hill, published May 30, 1991.
  • materials can be removed from the body through the port created by removal of the stratum corneum therewith. This can be done by applying over the location of the port an adherent collection patch to collect material diffusing therethrough. Material so collected, i.e. body fluid, can then be analyzed for the presence of foreign substances.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Surgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Media Introduction/Drainage Providing Device (AREA)

Abstract

La présente invention concerne un appareil éliminant une quantité substantielle de couche cornée d'une zone définie de la surface de peau d'un patient préalablement à l'application d'un appareil d'administration de médicaments par voie transdermique sur la zone ainsi définie. L'appareil comporte un premier cadre rigide (10) dont la plaque inférieure comporte une ouverture centrale au travers de laquelle la zone à traiter se trouve exposée lorsque l'appareil est posé contre la peau. Un second cadre (16) monté sur glissières dans le premier cadre comporte un rouleau (18) de pellicule adhésive, la face adhésive est tournée vers l'extérieur, et une surface applicatrice mobile sur laquelle la pellicule adhésive défile par intermittence. En enfonçant et relevant de façon répétée un certain nombre de fois le cadre à glissière, il est possible d'enlever complètement la couche cornée de la zone sélectionnée et d'appliquer ensuite à cet endroit un appareil d'administration de médicaments par voie transdermique.
PCT/CA1993/000472 1993-11-02 1993-11-02 Dispositif et procede permettant d'acceder a la peau des mammiferes sous la couche cornee Ceased WO1995012357A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/CA1993/000472 WO1995012357A1 (fr) 1993-11-02 1993-11-02 Dispositif et procede permettant d'acceder a la peau des mammiferes sous la couche cornee
AU54145/94A AU5414594A (en) 1993-11-02 1993-11-02 Method and apparatus for accessing mammalian skin locations below the stratum corneum

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CA1993/000472 WO1995012357A1 (fr) 1993-11-02 1993-11-02 Dispositif et procede permettant d'acceder a la peau des mammiferes sous la couche cornee

Publications (1)

Publication Number Publication Date
WO1995012357A1 true WO1995012357A1 (fr) 1995-05-11

Family

ID=4172989

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA1993/000472 Ceased WO1995012357A1 (fr) 1993-11-02 1993-11-02 Dispositif et procede permettant d'acceder a la peau des mammiferes sous la couche cornee

Country Status (2)

Country Link
AU (1) AU5414594A (fr)
WO (1) WO1995012357A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002002180A3 (fr) * 2000-06-29 2002-05-02 Becton Dickinson Co Procede et appareil utile pour effectuer un prelevement ou pour administrer une substance a un patient par voie transdermique
WO2004019777A3 (fr) * 2002-08-29 2004-05-21 Becton Dickinson Co Administration d'une substance par l'intermediaire d'une surface micro-abrasive rotative
WO2014136013A1 (fr) 2013-03-04 2014-09-12 Koninklijke Philips N.V. Dispositif de microdermabrasion
WO2014141229A1 (fr) * 2013-03-14 2014-09-18 Syneron Medical Ltd. Appareil de traitement de la peau
WO2018116986A1 (fr) * 2016-12-20 2018-06-28 久光製薬株式会社 Applicateur
WO2019107091A1 (fr) * 2017-11-30 2019-06-06 久光製薬株式会社 Applicateur, cartouche et kit d'application

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2819717A (en) * 1956-08-03 1958-01-14 Heinz W Kugler Surgical skin-treating device
WO1992011879A1 (fr) * 1991-01-09 1992-07-23 Principal Ab Perfusion percutanee de liquides
US5190558A (en) * 1989-11-08 1993-03-02 Nec Corporation Method of eliminating stratum corneum from the skin and an instrument to be used therefor

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2819717A (en) * 1956-08-03 1958-01-14 Heinz W Kugler Surgical skin-treating device
US5190558A (en) * 1989-11-08 1993-03-02 Nec Corporation Method of eliminating stratum corneum from the skin and an instrument to be used therefor
WO1992011879A1 (fr) * 1991-01-09 1992-07-23 Principal Ab Perfusion percutanee de liquides

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002002180A3 (fr) * 2000-06-29 2002-05-02 Becton Dickinson Co Procede et appareil utile pour effectuer un prelevement ou pour administrer une substance a un patient par voie transdermique
US6589202B1 (en) 2000-06-29 2003-07-08 Becton Dickinson And Company Method and apparatus for transdermally sampling or administering a substance to a patient
US8075826B2 (en) 2002-08-29 2011-12-13 Becton, Dickinson And Company Microprotrusion arrays and methods for using same to deliver substances into tissue
US7166086B2 (en) 2002-08-29 2007-01-23 Becton, Dickinson And Company Substance delivery via a rotating microabrading surface
US7316671B2 (en) 2002-08-29 2008-01-08 Becton, Dickinson And Company Microprotrusion arrays and methods for using same to deliver substances into tissue
US7422567B2 (en) 2002-08-29 2008-09-09 Becton, Dickinson And Company Microabrader with controlled abrasion features
WO2004019777A3 (fr) * 2002-08-29 2004-05-21 Becton Dickinson Co Administration d'une substance par l'intermediaire d'une surface micro-abrasive rotative
WO2014136013A1 (fr) 2013-03-04 2014-09-12 Koninklijke Philips N.V. Dispositif de microdermabrasion
CN105120779A (zh) * 2013-03-04 2015-12-02 皇家飞利浦有限公司 微晶研磨装置
US9649131B2 (en) 2013-03-04 2017-05-16 Koninklijke Philips N.V. Microdermabrasion device
WO2014141229A1 (fr) * 2013-03-14 2014-09-18 Syneron Medical Ltd. Appareil de traitement de la peau
WO2018116986A1 (fr) * 2016-12-20 2018-06-28 久光製薬株式会社 Applicateur
JPWO2018116986A1 (ja) * 2016-12-20 2019-10-24 久光製薬株式会社 アプリケータ
WO2019107091A1 (fr) * 2017-11-30 2019-06-06 久光製薬株式会社 Applicateur, cartouche et kit d'application
JPWO2019107091A1 (ja) * 2017-11-30 2020-11-26 久光製薬株式会社 アプリケータ、カートリッジ、およびアプリケーション・キット

Also Published As

Publication number Publication date
AU5414594A (en) 1995-05-23

Similar Documents

Publication Publication Date Title
US7087035B2 (en) Device and method for enhancing skin piercing by microprotrusions
US6589202B1 (en) Method and apparatus for transdermally sampling or administering a substance to a patient
EP0515566B1 (fr) Administration amelioree par ultrasons de matieres a travers la peau
US5231975A (en) Ultrasound-enhanced delivery of materials into and through the skin
US6018678A (en) Transdermal protein delivery or measurement using low-frequency sonophoresis
CA2253549C (fr) Dispositif d'amelioration d'apport ou d'echantillonnage d'agents transdermiques
EP0117027A1 (fr) Dispositif d'administration d'un médicament
US20040064087A1 (en) Microabrader with controlled abrasion features
DE3714140C2 (fr)
CA2316534A1 (fr) Methode et dispositif pour abraser la peau
US20100119586A1 (en) Patch for Cutaneous Application
WO1995012357A1 (fr) Dispositif et procede permettant d'acceder a la peau des mammiferes sous la couche cornee
US6572580B2 (en) Set depth nail notcher with patch system and method for treating nail fungus
EP1858496B1 (fr) Systeme therapeutique transdermique destine a l'administration d'analgesiques
Ouriemchi et al. Processes of drug transfer with three different polymeric systems with transdermal drug delivery
US6868286B1 (en) Device for a transdermal and phonophoretic combination therapy and the use thereof in a method for medical application
CA2196746A1 (fr) Amelioration par ultrasons de la liberation des matieres dans et a travers la peau
US20060130266A1 (en) Dermal drug delivery system
Surber et al. Drug concentration in the skin
CN120617797A (zh) 一种用于微针贴片施药的自动机械施药结构及其施药方法
Hodade et al. Approach on Transdermal Drug Delivery System
JPS61200910A (ja) 医療用絆創膏包帯
CA2515834A1 (fr) Systeme d'administration dermique de medicament

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AT AU BB BG BR BY CA CH CZ DE DK ES FI GB HU JP KP KR KZ LK LU MG MN MW NL NO NZ PL PT RO RU SD SE SK UA VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WA Withdrawal of international application
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

NENP Non-entry into the national phase

Ref country code: CA