WO2019053600A1 - Applicateur et appareil d'électroporation - Google Patents

Applicateur et appareil d'électroporation Download PDF

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Publication number
WO2019053600A1
WO2019053600A1 PCT/IB2018/056952 IB2018056952W WO2019053600A1 WO 2019053600 A1 WO2019053600 A1 WO 2019053600A1 IB 2018056952 W IB2018056952 W IB 2018056952W WO 2019053600 A1 WO2019053600 A1 WO 2019053600A1
Authority
WO
WIPO (PCT)
Prior art keywords
applicator
needle
layer
support
electroporation
Prior art date
Application number
PCT/IB2018/056952
Other languages
English (en)
Inventor
Fabrizio Dughiero
Elisabetta SIENI
Luca Biasiolo
Luca Giovanni CAMPANA
Paolo Francesco BARIANI
Original Assignee
Universita' Degli Studi Di Padova
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 Universita' Degli Studi Di Padova filed Critical Universita' Degli Studi Di Padova
Publication of WO2019053600A1 publication Critical patent/WO2019053600A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0412—Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0472—Structure-related aspects
    • A61N1/0476—Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/327—Applying electric currents by contact electrodes alternating or intermittent currents for enhancing the absorption properties of tissue, e.g. by electroporation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0412—Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
    • A61N1/0416—Anode and cathode
    • A61N1/042—Material of the electrode
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0412—Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
    • A61N1/0416—Anode and cathode
    • A61N1/0424—Shape of the electrode

Definitions

  • the present invention relates to an electroporation applicator and an electroporation apparatus which uses such an applicator.
  • the present invention relates to a medical electroporation applicator in electrochemotherapy.
  • electroporation is a technique used in the field of electrochemotherapy (ECT) to facilitate the entry of the antitumor drug into tumor cells and thus enhance the cytotoxic effect limited to the tissues exposed to the electroporation itself.
  • ECT electrochemotherapy
  • ECT is a locoregional therapy for the treatment of superficial tumors, based on the application of electric field pulses (electroporation) in conjunction with the infusion of non-permeating drugs possessing high intrinsic cytotoxicity (such as bleomycin), or little-permeating drugs but with known efficacy (such as cisplatin).
  • Electroporation also known as cellular electropermeabilization
  • Electroporation is a physical process that affects all types of cells, both tumors and not. In concomitance with the injection of an in situ chemotherapy, however, it favors the passage of the injected drug through the cell membranes, thus increasing the cytotoxicity thereof by various orders of magnitude.
  • the electroporation phenomenon can be - reversible temporary permeabilization of the cell membrane with pore formation.
  • the reversibility of the phenomenon allows the cells to return to their original state when there is no longer any pulse applied;
  • irreversible electroporation is nowadays very widespread as a method that facilitates the administration of some types of molecules or genes to cells; the pores that form in the cell membrane can in fact be used as channels to improve the absorption of drugs or the penetration of genes or molecular probes.
  • irreversible electroporation also aroused interest as an independent means of removing a part, usually superficial, of biological tissues (ablation) and could have a role in the treatment of some types of tumors in the future.
  • ECT treatment is based on three elements: the pulse generator, the electrodes and the pulse generator activation protocol.
  • the pulse generator is normally a pulse generator capable of allowing the regulation of the amplitude of the pulses (i.e. the applied voltage V) and of the shape of the pulses (i.e. of their trend as a function of time). In the case of clinical electroporation, rectangular pulses are normally used.
  • pulse a voltage or current signal will be understood, with a non-zero amplitude that occurs for a short period of time.
  • the pulses used in ECT are generally monopolar since it is possible to control their duration and their amplitude independently. Generally they have amplitude that is a function of the tissue to be treated and of the distance between the electrodes (note that in ECT, the electric field is of the order of hundreds of V/ cm or kV/ cm depending on the molecules of the drug that must be able to pass through the cell membrane).
  • the width of the membrane area which is permeabilized can be controlled by controlling the intensity of the applied pulse, the greater the amplitude of the pulse, that is, the greater the intensity of the electric field, E, the more extensive the area through which the diffusion of certain molecules may occur.
  • the duration and the number of pulses mainly affect the number and size of the pores that are formed due to the application of an electric field of an intensity greater than the critical value, i.e. 200-500 V/cm.
  • the critical value i.e. 200-500 V/cm.
  • Known studies have shown that in ECT the pulses must have duration in the order of hundreds of ⁇ and that the number of pulses sufficient to open the pores is equal to eight. However, other studies have tested a greater number of pulses.
  • the plate-type ones intended for external use As far as the electrodes are concerned, there are currently two large families, the plate-type ones intended for external use, and the needle-type ones intended to be used after partial insertion under the skin.
  • the present invention is directed to the electrodes of this second type.
  • these electrodes are associated with a specific applicator which, according to the conventional technology, consists of a rigid handpiece on which the electrodes are positioned according to a regular geometry.
  • the operator holds the handpiece and inserts the needle electrodes through the skin of the zone to be treated, after which the intended protocol is implemented. If the extension of the area to be treated requires it, this may be repeated by gradually moving the handpiece up to cover the entire area provided.
  • each handpiece must have a limited number of needles so that the resistance opposed by the skin during insertion is not excessive.
  • a particularly widespread embodiment provides that each handpiece has seven needles arranged at the vertices and at the center of a regular hexagon.
  • patent U.S. 6208893 has proposed an embodiment in which the applicator comprises a rigid base provided with a matrix of through holes in which the electrodes can be inserted. Electrical contacts made inside the through holes allow the pulses to be fed to the electrodes; it is also provided both that each electrode is supplied separately, and that the electrodes are supplied to groups in parallel.
  • this embodiment solution does not allow treating excessively large areas; the particular conformation of the applicator would make it impossible to use it in areas of the body that are not relatively flat (like the bust), if its dimensions were too large.
  • such an applicator comprises an electrically insulating support and a plurality of needle-shaped conductive electrodes, which can be mounted on the support (therethrough).
  • the support has at least one working face which in use is adapted to be applied to the area to be treated; in fact, it is flexible to be adaptable to the external physical conformation of the subject to be treated.
  • the support is a flexible stratiform body consisting of one or more layers of flexible material and can be provided with the adhesive means associated with the working face to allow in use the adhesion of the working face to a zone to be treated.
  • the adhesive means may consist of a plurality of pieces of double- sided material attached to the second main face of the support on one side and protected by a removable protective film on the other. In this way, at the time of use it is sufficient to remove the protective film to attach the working face to the zone to be treated.
  • the adhesive means may comprise the whole support which may present the entire second main adhesive face protected by a protective film.
  • the support has a plurality of first through holes, and each electrode is slidingly inser table into one of the first through holes. In this way, the electrodes can be fixed in the patient one by one, once the support has been positioned.
  • the applicator comprises a plurality of connecting bodies secured to the support, each at a first through hole and adapted to receive one electrode each. Each connecting body has in turn a second through hole axially aligned with the relative first through hole formed in the support.
  • the conductive electrodes on the other hand, are shaped like a needle and have a working end protruding with respect to the working face, which in use is adapted to be inserted into the subject to be treated.
  • each electrode may be clutched, preferably by friction, in the relative first through hole and/ or in the relative second through hole, respectively.
  • the applicator comprises at least one electrical conductor 9 which has a first end which is electrically connected to the electrode when it is inserted in the support, and a second end which can be connected in use to a pulse generator.
  • Each electrical conductor 9 extends at least partly inside the support and consists of a flexible sheet of conductive material.
  • the first end of each electrical conductor 9 has at least one contact terminal arranged at the first through hole and/ or the second through hole in which the electrode is inserted or insertable; each electrode is then electrically connected to the contact terminal when it is inserted into such a hole.
  • the contact terminal is arranged at least partly at an inner surface of the relative first through hole and/ or second through hole, respectively, so as to constitute at least part of the friction clutch for the relative electrode.
  • the connecting body is almost entirely made of electrically conductive material and is part of the relative electrical conductor 9.
  • the electrode comprises a central part shaped like a needle to which it is rigidly and coaxially secured, and a conductive hollow part (cylindrical in the accompanying figures) provided with an abutment edge, and which can be frictionally clutched on the connecting body.
  • the electrical contact between the electrode and the corresponding electrical conductor 9 is therefore ensured by the friction coupling between the hollow part and the connecting body.
  • the implementation of the support proved to be complicated and difficult to manage, especially for applicators having a high density of electrodes per surface unit (close electrodes).
  • the technical task underlying the present invention is to provide an electroporation applicator which remedies the aforementioned drawbacks.
  • FIG. 1 shows a schematic axonometric view, with some parts removed, of an electroporation applicator made according to the present invention
  • figure 2 shows a top view of the electroporation applicator in figure 1;
  • figure 3 shows the electroporation applicator of figure 2, sectioned along line III-III;
  • figure 4 shows the enlarged detail IV of figure 3
  • figure 5 shows the electroporation applicator of figure 1 in a side view
  • figure 6 shows an exploded view of the electroporation applicator of figure 5;
  • FIG. 7 shows an axonometric view of an electrode of an electroporation applicator according to the present invention, before being mounted on a support;
  • figure 8 shows a side view of the electrode of figure 7;
  • FIG. 9 shows the electrode in figure 8, sectioned along line ⁇ - ⁇ ;
  • figure 10 shows an axonometric view of a first layer of a support which is part of the electroporation applicator of figure 6;
  • figure 11 shows a top view of a second layer of the electroporation applicator support of figure 6;
  • figure 12 shows the second layer of figure 11 in a side view
  • figure 15 shows the enlarged detail XV of figure 14.
  • reference numeral 1 globally indicates an applicator for electroporation according to the present invention.
  • the applicator 1 object of the present invention is disposable, is sterile and is packaged in a protective casing (not shown) designed to preserve the sterility thereof until use.
  • a protective casing (not shown) designed to preserve the sterility thereof until use.
  • that according to the present invention comprises a flexible support 2 operable to cover a portion of a subject to be treated conforming thereto, and a plurality of electrodes 3 each of which comprises a needle 4 consisting of an electrically conductive material.
  • the support 2 conforms to the subject to be treated, it is understood at the macroscopic level; furthermore, from this definition, situations in which the subject's body may vary considerably in narrow spaces (and in particular within distances comparable with the distance between pairs of adjacent electrodes 3), such as in the case of the auricle, may be excluded. If placed on a flat surface as in figure 1, the extension of support 2 is mainly flat with a reduced thickness compared to the other dimensions.
  • adhesive means associated with the working face that is the second main face 6, may be provided, in order to allow in use to attach the support 2 to the subject to be treated.
  • a first main face 5 and a second main face 6 can be identified, arranged on opposite sides.
  • the second main face 6 in use is adapted to be directed towards the subject to be treated and supported against it.
  • the first main face 5, on the other hand, is the one at which, in use, the electrodes 3 can be coupled to the support 2 to be fixed to the patient.
  • the support 2 has a plurality of housing seats 7 distributed on the first main face 5.
  • Each housing seat 7 has a transverse (perpendicular) extension direction with respect to the extension direction of the main face (measured at the housing seat 7 if the support 2 is not arranged in plane).
  • Each electrode 3 can be mounted in one of the housing seats 7 of the support 2 in such a way that a working end 8 of the needle 4 protrudes with respect to the second main face 6 so as to be able to be used in the body of the subject to be treated (the needle 4 must therefore be adequately long).
  • the support 2 further comprises at least one electrical conductor 9 that has a first end 10 which is placed at the housing seat 7 itself and is electrically connectable to an electrode 3 inserted in the housing seat 7, and a second end 11 in use connectable to an electric pulse generator. Since the connection between the second ends 11 and the pulse generator may take place in any known manner (and in particular through a multipolar cable in which each conductor of the cable is connected, preferably by welding, to one or more second ends 11) it has not been illustrated in the accompanying figures nor will it be further described below. Preferably, however, all the second ends 11 are joined at a connecting portion 12 of the support 2 preferably placed along one side thereof (figure 13).
  • the support 2 always comprises at least a first layer 13 which defines the first main face 5 and a second layer 14 coupled to the first layer 13 at a face of the first layer 13 arranged on the opposite side with respect to the first main face 5.
  • the electrical conductors 9 are positioned in the second layer 14.
  • the first layer 13 comprises firstly a sheet 15 of flexible plastic material.
  • the first layer 13 comprises a guiding element 16 which has a first through hole 28 which defines the housing seat 7, and in which the needle 4 of one 10 of the electrodes 3 may be slidably inserted.
  • the first end 10 of each electrical conductor 9 is aligned with the respective housing seat 7 to be in electrical contact with the needle 4 which in use is inserted into such housing 7.
  • Each guiding element 16 is rigid, is made of plastic material, is partially incorporated in the sheet 15 of flexible plastic material and protrudes with respect to the first main face 5.
  • the sheet 15 of flexible plastic material and the guiding elements 16 are produced simultaneously by means of an additive manufacturing process (3D printing). In this way, the guiding elements 16 are integral with the sheet 15.
  • the guiding elements 16 are arranged mutually so that (with the support 2 arranged in plane) each guiding element 16 is placed at the center of a regular hexagon and that the other guiding elements 16 closest to it (which surround it in whole or in part) are arranged at - li the vertices of this regular hexagon.
  • the second layer 14 advantageously comprises at least a base layer 17 of flexible electrically insulating material (a non-limiting example of a suitable material is a polyamide, such as Kapton ®) and a plurality of conductive tracks 18 made of flexible material (a non-limiting example of suitable material is a Copper Clad Laminate, such as Akaflex ® ) fixed to the base layer 17.
  • a suitable material is a polyamide, such as Kapton ®
  • conductive tracks 18 made of flexible material a non-limiting example of suitable material is a Copper Clad Laminate, such as Akaflex ®
  • Each conductive track 18 defines at least one of the aforementioned electrical conductors 9 (note that in the accompanying figures the conductive tracks have been intentionally represented with a simple line, therefore without highlighting the width thereof) with the exception of the respective first ends 10 and respective intermediate portions 19 better described below.
  • the conductive tracks 18 may be obtained in any manner suitable for the purpose. In particular, they may be advantageously obtained by removing material starting from a solid metal sheet fixed to the base layer 17 (for example, the etching technique may be used).
  • the second layer 14 comprises a plurality of base layers 17 of electrically insulating material overlapping each other, in the example of the figures in contact with each other, to each of which respective conductive tracks 18 are fixed, defining each an electrical conductor 9.
  • a first base layer 13 carries the electrical conductors 9 which define first ends 10 relatively far from the connecting portion 12 of the support 2
  • a second base layer 17 carries the electrical conductors 9 which define first ends 10 closer to the connecting portion 12 of the support 2.
  • the conductive tracks 18 may have the same extension direction in the different base layers 17 (at least at the overlapping portion of the various base layers 17). Depending on the design choices, however, it may be provided both that the conductive tracks 18 in the different base layers 17 are offset from each other, and that they are arranged mutually overlapping as in the case illustrated in the accompanying figures (figure 13). In alternative embodiments, the conductive tracks 18 in two or more overlapping base layers 17 may extend along transverse directions.
  • two or more base layers 17 have different lengths in the direction of length of the conductive tracks 18 (as shown in figure 11) and may be overlapped with each other to form an applicator 1 of the desired overall length, based on the extension of the portion of the subject to be treated and/ or the number of electrodes 3 to be applied portion of a subject to be treated.
  • each conductive track 18 has an hexagonal shape with only a small hole in the center (hole which constitutes a second through hole 20 intended for the passage of the needle 4 with mechanical interference as better explained hereafter), the intermediate portion 19 of the second conductive track 18 intended to be overlapped on a first end 10 has an outer shape similar to that of the first end 10, but a substantially larger central hole 21 (substantially even larger than the needle 4 of the electrode 3); in this way a needle 4 which fits into the through hole of the first end 10 of the first conductive track 18 crosses in a central zone of the central hole 21 of the second conductive track 18 without establishing any electrical contact with the latter.
  • first ends 10 of the conductive tracks 18 are advantageously provided that the first end 10 of each electrical conductor 9 is located at the corresponding housing seat 7 (aligned thereto along the extension direction of the housing seat 7) and defining the second through hole 20 aligned with the first through hole 28.
  • This second through hole 20 will have a dimension such as to allow the insertion of each needle 4 only with mechanical interference.
  • the second through hole 20 advantageously has a maximum width smaller than the maximum width of the needle 4 and is delimited by a portion of the respective conductor which is plastically and/ or elastically deformable at the time of manual insertion of the needle 4 in the second through hole 20 itself (in the illustrated embodiment, the possibility of deformation is guaranteed by the choice of making the electrical conductors 9 with conductive paths 18 of reduced thickness).
  • the support 2 further comprises a third layer 22 consisting of an electrically insulating plastic material which defines the second main face 6.
  • the second layer 14 is enclosed between the first layer 13 and the third layer 22.
  • the plastic material of the third layer 22 is also flexible, for example it corresponds to the material used to make the sheet 15.
  • the second layer 14 (and in particular a base layer 17 thereof) defines the second main face 6.
  • each of them comprises a grip 23 of electrically insulating material which incorporates an enlarged portion 24 of the needle 4.
  • the grip 23 is made with additive manufacturing techniques; in the illustrated embodiment, moreover, it consists of two parts 25 irremovably coupled by mechanical engagement so as to clamp the enlarged portion 24 of the needle 4 therebetween.
  • the grip 23 may also be coupled to the guiding elements 16, advantageously by means of a male-female friction coupling to ensure a guided insertion of the needle 4 into the body of the subject to be treated.
  • each grip 23 is provided with one or more stabilising feet 26 which extend radially outwardly with respect to a extension direction of the needle 4 and which are intended to rest on the first main face 5 when the needle 4 is completely inserted into the respective housing seat 7.
  • the stabilising feet 26 are shaped in such a way that stabilising feet 26 of adjacent electrodes 3 can alternate with each other as shown in figure 2.
  • the feet of each grip 23 circumferentially affect only a limited angle about the extension direction of the needle 4 and, radially project, with respect to said extension direction of the needle 4, by a distance greater than half the distance between two adjacent needles 4 (i.e. the distance between each vertex and the center of the regular hexagon in the accompanying figures).
  • each grip 23 comprises four stabilising feet 26 which extend along radial directions emerging from the extension direction uniformly distributed around the needle 4 itself (one every 90° around the extension direction of the needle 4).
  • each electrode 3 may comprise a removable protective cap 27 mounted on the needle 4 to cover the first end 10 thereof before use (figures 7-9). At the time of use the protective cap 27 is removed and disposed of. Alternatively, the protective cap 27 may be reapplied to the needle 4 once the treatment of the subject is completed before disposal of the electrode 3, to ensure the safety of operators in charge of disposing of medical waste.
  • any method may be adopted according to the design choices (in series, parallel, etc.).
  • the connection methods described in the aforementioned patent IT 1419655 to the name of this same applicant are particularly advantageous.
  • an electroporation apparatus which includes one or more applicators made in accordance with the foregoing is obviously also an object of the present invention.
  • the apparatus will further comprise a pulse generator electrically connected or connectable to the second ends 11 of the electrical conductors 9 for applying a potential difference between pairs of electrodes 3 according to the known ECT methods.
  • the operation of the electroporation applicator 1 according to the present invention derives from the structural description reported in the foregoing and provides first of all the positioning (possibly by means of adhesive means) of the support 2 on the zone to be treated) and the subsequent fixing of the needles
  • the coupling with mechanical interference between the needles 4 and the second through holes also determines the conductive coupling of the needles 4 with the relative electrical conductor 9.
  • the present invention therefore achieves important advantages.
  • the electroporation applicator object of the present invention ensures an adequate electrical supply of all the electrodes in a simple and cost- effective manner due to the coupling with interference between the needle and the conductive track.
  • the applicator 1 may be simply produced and/ or modified - by adding one or more layers 17 - to adhere to a portion of the subject to be treated of desired dimensions and, therefore, ensure the possibility of inserting a desired number of electrodes 3 necessary for treatment.
  • an apparatus that provides for the use of multiple applicators 1 - as mentioned above - allows further extending the area of the treatable portion of the subject and/ or increasing a number of electrodes 3 fixed in the portion of the subject to be treated.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Electrotherapy Devices (AREA)

Abstract

L'invention porte sur un appareil d'électroporation et sur un applicateur, l'applicateur comprenant un support souple (2) qui délimite une pluralité de sièges de boîtier (7), et une pluralité d'électrodes (3) comprenant chacune une aiguille conductrice (4) et pouvant être montées dans les sièges de boîtier (7) ; le support (2) comprend au moins une première couche (13) qui comprend une feuille (15) de matière plastique souple et, au niveau de chaque siège de boîtier (7), un élément de guidage rigide (16) en matière plastique et dans lequel l'aiguille (4) de l'une des électrodes (3) peut être insérée à coulissement, une première extrémité (10) d'un conducteur électrique (9) étant alignée avec chaque siège de boîtier (7) de manière à être en contact électrique avec une aiguille (4) insérée dans ledit siège de boîtier (7), les conducteurs électriques (9) s'étendant eux-mêmes dans une deuxième couche (14) du support (2).
PCT/IB2018/056952 2017-09-13 2018-09-12 Applicateur et appareil d'électroporation WO2019053600A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT102017000102644A IT201700102644A1 (it) 2017-09-13 2017-09-13 Applicatore ed apparecchiatura per elettroporazione
IT102017000102644 2017-09-13

Publications (1)

Publication Number Publication Date
WO2019053600A1 true WO2019053600A1 (fr) 2019-03-21

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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999037358A1 (fr) * 1998-01-27 1999-07-29 Genetronics, Inc. Appareil d'electroporation avec modele d'electrode connective
WO2000023143A1 (fr) * 1998-10-22 2000-04-27 Genetronics, Inc. Appareil d'administration de medicaments et de genes par electroporation
WO2003077970A2 (fr) * 2002-03-11 2003-09-25 Altea Therapeutics Corporation Dispositif transdermique a actionneur integre, procedes de fabrication et d'utilisation de celui-ci
CN102755691A (zh) * 2012-06-19 2012-10-31 吉林大学 高灵敏医用微针阵列电极
WO2012172424A1 (fr) * 2011-06-15 2012-12-20 Crontech Pharma Ab Aiguille et dispositif d'injection
WO2013066427A1 (fr) * 2011-06-28 2013-05-10 Inovio Pharmaceuticals, Inc. Dispositif d'électroporation dermique à effraction minimale
WO2013084189A2 (fr) * 2011-12-08 2013-06-13 Pilogics L.P. Appareil et procédé de stimulation de la croissance capillaire et/ou de prévention de la chute des cheveux
EP3006552A1 (fr) * 2013-06-08 2016-04-13 Etta Biotech Co., Ltd Dispositif d'électrode stéréoscopique distribuée haute densité
US20170028184A1 (en) * 2015-07-27 2017-02-02 Catura Corporation Device and method of skin care and treatment via microneedles having inherent anode and cathode properties, with or without cosmetic or pharmacological compositions

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999037358A1 (fr) * 1998-01-27 1999-07-29 Genetronics, Inc. Appareil d'electroporation avec modele d'electrode connective
WO2000023143A1 (fr) * 1998-10-22 2000-04-27 Genetronics, Inc. Appareil d'administration de medicaments et de genes par electroporation
WO2003077970A2 (fr) * 2002-03-11 2003-09-25 Altea Therapeutics Corporation Dispositif transdermique a actionneur integre, procedes de fabrication et d'utilisation de celui-ci
WO2012172424A1 (fr) * 2011-06-15 2012-12-20 Crontech Pharma Ab Aiguille et dispositif d'injection
WO2013066427A1 (fr) * 2011-06-28 2013-05-10 Inovio Pharmaceuticals, Inc. Dispositif d'électroporation dermique à effraction minimale
WO2013084189A2 (fr) * 2011-12-08 2013-06-13 Pilogics L.P. Appareil et procédé de stimulation de la croissance capillaire et/ou de prévention de la chute des cheveux
CN102755691A (zh) * 2012-06-19 2012-10-31 吉林大学 高灵敏医用微针阵列电极
EP3006552A1 (fr) * 2013-06-08 2016-04-13 Etta Biotech Co., Ltd Dispositif d'électrode stéréoscopique distribuée haute densité
US20170028184A1 (en) * 2015-07-27 2017-02-02 Catura Corporation Device and method of skin care and treatment via microneedles having inherent anode and cathode properties, with or without cosmetic or pharmacological compositions

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