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WO2000010640A1 - Procede et dispositif d'administration topique de substances - Google Patents

Procede et dispositif d'administration topique de substances Download PDF

Info

Publication number
WO2000010640A1
WO2000010640A1 PCT/IL1998/000395 IL9800395W WO0010640A1 WO 2000010640 A1 WO2000010640 A1 WO 2000010640A1 IL 9800395 W IL9800395 W IL 9800395W WO 0010640 A1 WO0010640 A1 WO 0010640A1
Authority
WO
WIPO (PCT)
Prior art keywords
electrode
electric field
emitter electrode
useful substance
body surface
Prior art date
Application number
PCT/IL1998/000395
Other languages
English (en)
Inventor
Mark Litvak
Miriam Valchikhin
Original Assignee
Gal-Ion Blaze 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 Gal-Ion Blaze Ltd. filed Critical Gal-Ion Blaze Ltd.
Priority to AU88201/98A priority Critical patent/AU8820198A/en
Priority to PCT/IL1998/000395 priority patent/WO2000010640A1/fr
Publication of WO2000010640A1 publication Critical patent/WO2000010640A1/fr

Links

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
    • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
    • A61N1/0432—Anode and cathode
    • A61N1/044—Shape 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
    • A61N1/0428—Specially adapted for iontophoresis, e.g. AC, DC or including drug reservoirs
    • A61N1/0448—Drug reservoir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/44—Applying ionised fluids

Definitions

  • the present invention concerns a method and device for the administration of a useful substance into and across a body surface such as the skin, the eyes, the inner ear, the nose or the respiratory tract, by use of a strong electric field.
  • a useful substance used herein denotes quite generally any substance for medical or cosmetic treatment of humans and non human animals.
  • a second electrode of opposite polarity referred to sometimes as return electrode, is applied to the skin in the proximity of the first electrode, whereby the rate of ionic migration is enhanced.
  • U.S. 5,037,380 discloses an iontophoretic electrode which includes a pouch for holding a solution of an ionic medicament. With such an electrode, the ionic medicament migrates directly from the electrode's pouch across the skin and the need of first spreading the medicament on the skin is obviated. For the rest the mechanism is the same as in all other iontophoretic methods.
  • the object of the present invention to provide an improved method for the administration of useful substances into and across a body surface, free of the shortcomings of iontophoresis.
  • the invention is based on a novel concept whereby the desired useful substance is accelerated to the body surface from a distance under the influence of a strong electric field of the order of 1000-15,000 volts.
  • a strong electric field is capable of imparting an electric charge to an a priori non-ionic substance and accelerate an ion towards the body surface, and also of accelerating towards the body surface an a priori ionized substance.
  • an electric field driven emitter electrode a member holding said useful substance and designed for the emission thereof, to be referred to hereinafter as "an electric field driven emitter electrode"
  • an electric field driven emitter electrode is placed at a desired distance from a target portion of the subject's body surface, e.g. the skin, and subjected to the influence of an electric field within the range of 1000 to 15,000 volts either by directly connecting the electric field driven emitter electrode to an electric power source or by placing said emitter electrode in an electric field established between the electric power source and the subject's body surface.
  • Ionized molecular particles of the useful substance are emitted from the emitter electrode and accelerated onto the subject's body surface.
  • the applied voltage must be strong enough for causing ionization of the useful substance.
  • the applied voltage may possibly be lower than in the case of an a priori electrically neutral substance of similar molecular weight.
  • a beam of charged molecular particles is accelerated across the electric field from the electric field driven emitter electrode on to the body surface and depending on the desired effect, the strength of the electric field is so selected that the particles arrive at the body surface at a velocity suitable for either partial or complete penetration of the body surface.
  • the object of the topical administration will be intradermal penetration, i.e. penetration into the skin and not across it.
  • the strength of the electric field and with it the velocity of the particles will have to be increased accordingly.
  • the factors that have to be taken into consideration for a given treatment in accordance with the present invention include the nature of the useful substance to be administered, i.e. whether it is a priori ionic or non-ionic, its molecular weight and the desired degree of penetration.
  • the useful substance may be used in raw or composite form and be present in the electric field driven emitter electrode in any desired solid or liquid aggregate form, e.g. in comminuted solid form, in form of a paste or gel, in form of a liquid, an aqueous or non-aqueous solution, dispersion or colloid.
  • a method of topical administration of a useful substance to a subject for medical or cosmetic purposes comprising placing at a distance from a target portion of the subject's body surface an electric field driven emitter electrode having a reservoir holding said useful substance, and putting the electric field driven emitter electrode under the influence of an electric field having an intensity within the range of from 1000 to 15,000 volts, whereby ionized molecular particles are emitted from said electric field driven emitter electrode to bombard said target portion of the subject's body surface to produce a desired medical or cosmetic effect.
  • the electric field driven emitter electrode may be connected directly to an electric power source so that the field lines of the electric field extend from the emitter to the body surface or, alternatively, may be unconnected to the power source and be placed in an electric field formed between the electric power source and the subject's body surface.
  • the electric field driven emitter electrode is the only electrode of the system while in accordance with another embodiment, a second electrode is placed on the subject's body surface.
  • the useful substance for use in the performance of the method according to the invention may be pure or compounded and be in any desired solid or liquid aggregate form, e.g. in comminuted solid form, in form of a paste or gel, in form of a liquid, such as an aqueous or non-aqueous solution, a dispersion or a colloid.
  • the subject's body surface or a second electrode placed thereon will be either the positive or negative pole of the said electric field.
  • the strength of the electric field is selected in accordance with the nature of the useful substance, its molecular weight and the desired depth of penetration, and may be determined by means of simple experimentation.
  • the invention further provides for use in the topical administration of a useful substance to a subject for medical and cosmetic purposes, an electrical field driven emitter electrode for bombarding a target portion of the subject's body surface with ionized molecular particles, comprising reservoir means for holding said useful substance, emitter means for the emission of ionized molecular particles of said useful substance, and optionally electrical terminal means for connection to an electric power source.
  • the invention further provides an assembly for bombarding a target portion of a subject's body surface with ionized molecular particles of a useful substance for medical and cosmetic purposes, comprising an electric field driven emitter electrode of the kind specified, spacer means having an open ended passageway for said ionized molecular particles, and an electric power source capable of creating an electric field of 1,000-15,000 volt.
  • the electric field driven emitter electrode is the only electrode of the system, the function of a second electrode being fulfilled by the subject's body surface.
  • the assembly comprises a second electrode and an electric field is formed between the electric field driven emitter electrode and said second electrode, or alternatively between said electric power source and said second electrode, with the electric field driven emitter electrode being placed within the electric field.
  • said second electrode may be located within said spacer means in such a way as to leave a free passageway for the ionized molecular particles, whereby said particles can proceed beyond said second electrode.
  • the second electrode in such an embodiment may be annular or in form of a plate or membrane with a suitably located hole or a plurality of holes.
  • the said reservoir means for holding a useful substance together with said emitter means may be in form of disposable cartridges.
  • the body surface treated in accordance with the present invention is the skin with the administration of the useful substance being either intradermal or transdermal and serving for cosmetic or medical purposes.
  • the substance to be applied in accordance with the invention is placed directly into the reservoir, either in pure or composite form.
  • the reservoir contains an absorbent material, such as for example cotton, which is soaked with the substance for administration.
  • the invention is fundamentally distinguished from conventional, electrically driven transdermal drug administration methods such as iontophoresis.
  • iontophoresis an a priori ionized substance is applied to the skin, a low voltage electric current flows across the skin and the useful substance passes therethrough by electrophoretic migration
  • a target portion of a body surface such as the skin, is bombarded from a distance with ad hoc or a priori ionized molecules of the desired useful substance by the action of a strong electric field of the order of 1,000 to 15,000 volts, and penetration of said substance into the surface and, if desired, across it results from the mechanical impact of the molecules bombarding the target portion of the subject's body surface.
  • the invention provides a high degree of versatility in that it broadens significantly the range of useful substances that may be administered in this way, and in that it enables for the first time to adjust the depth of penetration of the useful substance. Such adjustment was not possible in accordance with the prior art which invariably involves transdermal migration. Accordingly, the present invention opens a new area of surface treatment of a subject, both for cosmetic and medical purposes.
  • Fig. 1 shows one embodiment of an assembly according to the invention in the disassembled state, in cross-sectional and bottom view;
  • Fig. 2 shows a cross-sectional view of the same embodiment of Fig. 1 in the assembled state
  • Fig. 3 shows a cross-sectional and bottom view of another embodiment of an assembly with an emitter electrode according to the invention
  • Fig. 4 shows a cross-sectional and bottom view of a first component of an emitter electrode according to the invention
  • Fig. 5 shows in cross-section an assembled emitter electrode embodying the component of Fig. 4;
  • Fig. 6 shows schematically the emission pattern in an assembly of Fig. 5;
  • Fig. 7 is a diagram showing the rate of ionization as a function of the applied voltage.
  • Fig. 8 is a diagram showing the depth of penetration as a function of time.
  • Figs. 1 and 2 show one embodiment of an assembly according to the invention serving for bombarding a selected portion of a subject's body surface, e.g. of the skin, with electrically charged molecular particles.
  • the assembly is shown in the disassembled state and in Fig. 2 in the assembled state.
  • the assembly comprises an electric field driven emitter electrode 1 having a handle 2 and a head portion 3 all made of electrically insulating material.
  • Head portion 3 comprises a reservoir chamber 4 covered by a lid 5 having a central hole 6 serving for the passage of a high voltage wire 7 and for charging the useful material.
  • the electrically powered emitter electrode 1 further comprises a matrix portion 8 also made of insulating material and holding four capillary emitter tubes 9.
  • the assembly further comprises a spacer device 13 comprising a matrix 14 of insulating material and four tubular members 15 each capable of accommodating one of the capillary emitter tubes 9 in the manner shown in Fig. 2, which tubular members also serve as spacers.
  • each tubular member 15 accommodates one associated capillary emitter tube 9 and electrode 10 is connected by means of wire 7 to the negative pole of an electric power supply 17.
  • electric power supply 17 is connected by means of a wire 18 to an external second electrode 19 covered by an insulator layer 20, which second electrode 19 is in operation placed on the skin.
  • the emitter electrode 1 is the negative one and electrode 19 the positive one.
  • reservoir chamber 4 and each of the capillary tubes 9 are filled via the central hole 6 with a useful substance 21 to be employed for the desired treatment, the openings of the tubular members 15 of spacer device 13 being placed on a subject's skin portion to be bombarded.
  • the second electrode 19 is also placed on the skin, off the portion to be bombarded and with the insulator plate 20 down on the skin.
  • a switch not shown
  • the negative emitter electrode 1 and the second, positive electrode 19 become electrically charged resulting in the formation of an electric field.
  • the voltage will be relatively high, say about 6,000 to 8,000 volts which brings about ionization of the useful substance inside the capillary emitter tubes 9.
  • the negatively ionized molecular particles of the useful substance are accelerated across the electric field established between the emitter electrode 1 and the skin, and they progress inside the tubular members 15 so as to impinge at high speed on to the skin.
  • the embodiment of the assembly according to the invention shown in Fig. 3 also embodies a capillary emitter tube.
  • the electric field driven emitter electrode 31 comprises an electrode 32 having a base plate 33 and a cover plate 34 forming between them a reservoir chamber 35 merging into a capillary tube 36 accommodated within a larger tube 37.
  • Within chamber 35 is located an annular electrode plate 38 with integral high voltage wire 39.
  • the electric field driven emitter electrode 32 is attached to a tubular spacer device 40 fitted with two sets of radial braces 41 and 42 and accommodating the tube 37. At its end the spacer device 40 comprises four feet 43.
  • the desired useful substance is charged into reservoir chamber 35 and capillary tube 36, and the assembly is placed by means of feet 43 on a body surface portion, e.g. the skin, selected for bombardment by ionized molecular particles emitted by the capillary tube 36, and electrode 32 is connected to a high voltage electric power supply (not shown).
  • an electric field driven emitter electrode comprises as a first component emitter electrode assembly 52 having a tubular portion 53 holding a filler of absorbent material soaked with the desired useful substance to be emitted. There are further provided four emitter rods 44 which in operation emit the ionized useful substance from their tree tips.
  • the electrode assembly 52 further comprises a funnel shaped spacer portion 45 holding a second, annular electrode 46. If desired, the emitter electrode assembly 52 may be in form of a disposable cartridge.
  • the second component of the emitter electrode according to Figs. 4 and 5 is a tubular handle member 47 fitted with radial braces 48 and holding an electric conductor rod 49.
  • the tubular member 47 comprises an integral inner annular rib 50 which serves for engagement between tubular portion 53 of the first component 52 and the handle member 47 of the second component.
  • the emitter electrode assembly 52 is connected via conductor rod 49 to one pole of a high electric voltage power supply (not shown) and the second, annular electrode 46 to the other poles.
  • a high electric voltage power supply not shown
  • the second, annular electrode 46 to the other poles.
  • ions arrive from an emitter rod 44 onto the skin 51 across a tubular electrode 46 is shown schematically in Fig. 6 and as shown, some of the ions penetrate the skin 51 while others bounce away.
  • the useful substance particle arrives at the skin still in the charged form, but shortly after their arrival the ions lose their charge and revert to the neutral molecular state.
  • a desired body surface portion may be bombarded with a large variety of substances such as, for example, 1. Aloe extract 21. Resorcin
  • Nicotinic acid 33 Sodium phosphate
  • the substances in the above list are those which are filled into the reservoir of the emitter electrode. Some of the substances in the list such as sodium bromide, sodium hydrocarbonate, potassium iodide, potassium chloride and others are salts which are, a priori in ionized form. In case of such substances and assuming that the polarity of the electrode is negative, only the anionic moiety is emitted and is upon arrival at the skin, converted into the electrically neutral molecular form.
  • the applied voltage and the intensity of the resulting electric field may be significantly weaker than in the case of neutral substances where energy has first to be invested in ionization.
  • Example 1 The invention is further described in the following non-limiting examples.
  • Example 1 The invention is further described in the following non-limiting examples.
  • An electric field driven emitter electrode of the kind shown in Figs. 4 and 5 was used.
  • the absorbent material filler 43 was soaked with a 5% alcoholic iodine solution (I 2 ) and in the second experiment, cypress essential oil (EO) was used.
  • the emitter was connected to the positive terminal of a power supply, the open end was placed at a constant distance from a target, and the ion flux between the emitter electrode and the target surface was measured by means of a multimeter.
  • the quantity of ions was calculated in approximation on the assumption that each ionic particle carries one elementary negative electric charge, i.e. the charge of one electron.
  • Each substance was tested at three different distances of 1 cm, 2 cm and 3 cm, and at three constant voltages of 2 kV, 4 kV and 6 kV.
  • the quantities of the ions also depend on the nature of the substance and it can be seen from Fig. 7 that all being equal, the iodine solution produced more ions than the etheric oil which is accountable by the difference in the molecular weights and sizes of the tested molecules - the molecules of the etheric oil being significantly larger and heavier than those ofI 2 .
  • the penetration of iodine from a 5% alcoholic I 2 solution into an artificial membrane of 6% gelatin gel with 1.5% starch was examined at constant voltage of 2 kV and at the constant distance of 1 cm between the free end of the emitter rod and the artificial membrane.
  • the time for bombardment was 5, 10 and 20 min. and in each case the depth of penetration of I 2 into the membrane was examined by the detection of the color produced due to the iodine-starch reaction.
  • the depth of penetration was tested by means of a molecular microscope having an x 40 resolution and the results are plotted in Fig. 8. As shown, the depth of penetration of iodine into the gel increased with time.
  • the group of participants was composed of 9 women and 1 man. Their ages varied from 18 to 30 years old as follows:
  • the treatment was carried out with an apparatus of the kind shown in Figs. 4 and 5 herein using a physiological solution containing 0.1% w/w of lavender oil and 0.1% w/w eucalyptus oil as useful substances.
  • the distance between the emitter 44 and the skin was 1 cm.
  • a voltage of 9,000 volts was applied and each cheek portion included within the funnel shaped spacer 45 was treated for 1 min. and the aggregate time of treatment of each cheek was 5 to 7.5 mins.
  • the treatment was administered every 2-4 days, a total of 10 sessions for each participant. No side effects were observed or reported by the participants .
  • Bacterial population (strain Staph. Epidermidis) was grown on agar during 18 hours. The washing of bacterial population was diluted to a concentration of 10 7 microbes per ml with sterile physiological solution.
  • Petri dishes with Baird-Parker agar were inoculated with bacterial solution. Directly after the inoculation Petri dishes were treated by an apparatus of the kind shown in Figs. 4 and 5. After that treatment petri dishes were placed into an incubator for 24 hours at 37°C. At the next day dishes were checked and zone of sterilization (no growth) and zone of inhibition (slow growth) were measured.

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

Abstract

L'invention concerne l'emploi d'une électrode émettrice entraînée par un champ électrique, pour administrer une substance utile sur une zone cible d'une surface corporelle d'un sujet. Lors de cet emploi, on crée un champ électrique de 1000 à 15000 volts, de manière à ioniser la substance utile. L'électrode émettrice peut contenir une quantité voulue de la substance utile et elle est dotée de tubes capillaires ou tiges servant à l'émission des particules moléculaires ionisées. Le cas échéant, on a monté une contre-électrode.
PCT/IL1998/000395 1998-08-19 1998-08-19 Procede et dispositif d'administration topique de substances WO2000010640A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU88201/98A AU8820198A (en) 1998-08-19 1998-08-19 Method and device for topical administration of substances
PCT/IL1998/000395 WO2000010640A1 (fr) 1998-08-19 1998-08-19 Procede et dispositif d'administration topique de substances

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IL1998/000395 WO2000010640A1 (fr) 1998-08-19 1998-08-19 Procede et dispositif d'administration topique de substances

Publications (1)

Publication Number Publication Date
WO2000010640A1 true WO2000010640A1 (fr) 2000-03-02

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ID=11062352

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IL1998/000395 WO2000010640A1 (fr) 1998-08-19 1998-08-19 Procede et dispositif d'administration topique de substances

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AU (1) AU8820198A (fr)
WO (1) WO2000010640A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU750912B2 (en) * 1999-05-25 2002-08-01 Iomed, Inc Methods and apparatus for ocular iontophoresis
EP1454652A1 (fr) * 2003-03-07 2004-09-08 M & T S.r.l. Dispositif pour l'administration transcutanée de substances en utilisant l'iontophorèse
EP1800711A4 (fr) * 2004-09-07 2008-04-02 Yugen Kaisha Beauty Clinical Appareil cosmétique
US7522954B2 (en) 2004-06-01 2009-04-21 M & T S.R.L. Device for the transcutaneous administration of substances by means of iontophoresis
EP2384789A1 (fr) * 2010-04-13 2011-11-09 Tolykorea. Inc Appareil de massage capable d'iontophorèse
WO2013118114A1 (fr) * 2012-02-08 2013-08-15 Gurovich, Martin Dispositif d'administration transdermique
WO2024218387A1 (fr) * 2023-04-20 2024-10-24 Wetling Ip Aeam Ltd Utilisation d'ions d'air chargés dans des traitements esthétiques

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990006153A1 (fr) * 1988-11-28 1990-06-14 Innofinance Általános Innovációs Pénzintézet Rt. Appareil d'iontophorese
EP0678337A1 (fr) * 1994-03-25 1995-10-25 Zeneca Limited Aérosol ophthalmologique aqueux
WO1996017648A1 (fr) * 1994-12-09 1996-06-13 Novartis Ag Systeme transdermique

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990006153A1 (fr) * 1988-11-28 1990-06-14 Innofinance Általános Innovációs Pénzintézet Rt. Appareil d'iontophorese
EP0678337A1 (fr) * 1994-03-25 1995-10-25 Zeneca Limited Aérosol ophthalmologique aqueux
WO1996017648A1 (fr) * 1994-12-09 1996-06-13 Novartis Ag Systeme transdermique

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU750912B2 (en) * 1999-05-25 2002-08-01 Iomed, Inc Methods and apparatus for ocular iontophoresis
EP1454652A1 (fr) * 2003-03-07 2004-09-08 M & T S.r.l. Dispositif pour l'administration transcutanée de substances en utilisant l'iontophorèse
US7522954B2 (en) 2004-06-01 2009-04-21 M & T S.R.L. Device for the transcutaneous administration of substances by means of iontophoresis
EP1800711A4 (fr) * 2004-09-07 2008-04-02 Yugen Kaisha Beauty Clinical Appareil cosmétique
EP2384789A1 (fr) * 2010-04-13 2011-11-09 Tolykorea. Inc Appareil de massage capable d'iontophorèse
WO2013118114A1 (fr) * 2012-02-08 2013-08-15 Gurovich, Martin Dispositif d'administration transdermique
US9522267B2 (en) 2012-02-08 2016-12-20 Derma Dream Group Ltd Transdermal delivery device
WO2024218387A1 (fr) * 2023-04-20 2024-10-24 Wetling Ip Aeam Ltd Utilisation d'ions d'air chargés dans des traitements esthétiques

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