RU2320378C2 - Cutaneous applicator - Google Patents

Abstract

FIELD: medicine, medicinal equipment.

SUBSTANCE: the present innovation deals with devices and methods for perosseous and/or intraosseous injection of medicinal substances. The kit for delivering electric current and/or voltage to a part of skin and/or for perosseous or intraosseous injection of substances contains a cutaneous applicator that contains a power pack and, at least, two electrodes being electrically connected with the power pack and indicated for electric connection with a patient's part of skin and, at least, one separator for keeping electroconductive flowing medium. The latter is indicated to be applied onto, at lest, one electrode and/or locally applied onto a patient's part of skin. In one variant, a thin elastic cutaneous applicator has got a thin elastic power pack and thin chamber that contains electroconductive flowing medium/composition, in which a thin chamber is located in, at least, one mentioned negative electrode and, at least, on one positive electrode. The innovation enables to increase the universality of cutaneous applicators due to introducing any desired number of substances in any desired dosages.

EFFECT: higher efficiency.

85 cl, 6 dwg

Description

The date of the convention priority of this application is October 24, 2001 according to the application No. 60/330526, which is included in its entirety as the basis for this application.

FIELD OF THE INVENTION

The present invention relates to devices, kits and methods for transdermal and / or intradermal administration of medicinal substances and, in particular, to a cutaneous applicator capable of supplying electric current to electrically induce transdermal and intradermal administration of various substances or enhance wound healing, prevent and reduce scarring , restore the skin and / or regenerate the skin by electrical exposure.

Modern technical and patent literature pays much attention to the administration of pharmaceutical and cosmetic substances, for example, drugs and other useful preparations, into or through intact skin surfaces using passive methods such as diffusion and osmosis and active methods such as electrically induced iontophoresis, electrophoresis, electroosmosis and / or electroporosis. The widespread anti-nicotine patch, created to combat smoking, uses the above mechanisms of percutaneous administration of well-known medications. (The term "iontophoresis" is collective for terms such as iontophoresis, electrophoresis, electroosmosis and / or electrophoresis, and the term "iontophoresis" is collective for the corresponding adjectives).

Currently, there is an exceptionally long list of pharmaceutical substances that, in accordance with established practice, are administered by the transdermal and / or intradermal route, and an equally long list of known devices and methods for administering such substances. An incomplete but diverse list includes the following examples: US patent No. 6294582, which contains a description of a device for percutaneous treatment of asthma; US patent No. 5899856, which contains a description of the device of the cutaneous applicator for detecting alcohol consumption; US patent No. 6291677, which offers the transdermal administration of antiviral protease inhibitors; US patent No. 6266560, which contains a description of percutaneous treatment of erectile dysfunction; US patent No. 6238381, which contains a description of the transdermal administration of antiviral, antibacterial and anti-aging drugs; and US patent No. 6288104, which contains a description of the transdermal administration of substances for the treatment of heart failure with congestive phenomena.

Many substances are administered passively through the cutaneous applicator, but there are many such substances that are administered intracutaneously or transdermally electrically.

The use of electrical stimulation of body parts is well known and has a long and varied history. Around the middle of the 20th century, many “electrodes” were proposed for the “electrical treatment” of the human body. Electrodes were applied to the body depending on the organ to be treated. Initially, the “electrical treatment” consisted of a well-known galvanic stimulation, which caused the ionized molecules to move inside the body, as a rule, not deeply. This early method of iontophoresis or ion transfer was used to obtain the proposed surface results of localized irritation and the administration of medications, often simply moisture, to the patient’s skin.

The method of iontophoresis is currently widely used for the administration of drugs, since it effectively delivers electrically charged drugs through the skin and into the capillary structure and lymphatic system. This method eliminates the adverse gastrointestinal effects, sometimes caused by orally taken medicinal substances, therefore, it is advisable to make a subcutaneous injection due to its relatively less danger and pain.

Another method, known as electroporosis, facilitates the transdermal or intradermal administration of uncharged substances by electrically inducing the formation of temporary skin micropores, which allow uncharged substances to travel through diffusion.

Accordingly, iontophoresis, as well as other electrically induced methods, for example, electrophoresis, have been used in many devices for transdermal administration of drugs, including well-known cutaneous applicators. Therefore, at present, in the art there are many cutaneous applicators that contain a power source and an electrical circuit to accelerate percutaneous administration.

Most modern cutaneous applicators, including passive and electrical applicators, contain a substance for transdermal administration. Such applicators are specially designed and configured to introduce a predetermined dosage of a specific substance, which is an integral part of a particular applicator, such as a “nicotine patch”. One of the drawbacks of these cutaneous applicators, which are made with a predetermined amount of a given type of substance, is that after a depletion of the supply of matter, the entire device becomes useless and must be sent to waste. This is a serious drawback because applicators using electrically induced administration methods inevitably contain components, such as batteries, electrodes, electrical circuits, and other components that can be expensive and / or dangerous to the environment when emitted into it in large quantities. In addition, to change the dosage, it is required to produce applicators with different dosages.

A group of reusable cutaneous applicators that contain a container for storing a drug substance prior to administration is also currently known in the art. These cutaneous applicators typically contain a capacitance in the form of an integral part of one or both electrodes that supply current to the patient’s skin. These electrodes are commonly referred to as bioelectrodes.

Commercially available bioelectrodes vary in size, shape, and configuration according to Ioimed, Inc., which manufactures devices for iontophoretic drug administration. The electrodes mentioned include, for example, the electrodes described in US Pat. Nos. 5,037,380 and 5,248,295, which offer an applicator with a rechargeable container; in US patent No. 5846217, which offers an applicator with a small hole for recharging; and US Pat. Nos. 5,37424, 5,730,716 and 6,222,075, which offer an applicator containing a dry drug substance and requiring hydration. All of these bioelectrodes have a complex structure and many components and therefore occupy a relatively large volume. Therefore, when embedding bioelectrodes in cutaneous applicators, the latter are large and of high cost. Moreover, it is the doctor, not the patient, who should charge or download the data of cutaneous applicators.

For the above reasons, it is generally agreed that a thin, flexible and simple electric active cutaneous applicator, which provides a simple solution to the problem of administering drugs by the patient himself, is universal and allows the use of various substances and / or dosages for various purposes, and also has a simple design and low manufacturing cost.

SUMMARY OF THE INVENTION

In accordance with the foregoing, the present invention is the creation of a universal cutaneous applicator, which contains a power source and can be used for transdermal or intradermal administration of many different substances.

Another objective of the present invention is the creation of a universal cutaneous applicator that contains a power source that can be used to supply electric current to the skin area for various purposes.

Another objective of the present invention is to provide a universal cutaneous applicator that contains a thin and elastic power source that can be used to supply electric current to a skin area for various purposes and / or which can be used for transdermal or intradermal administration of many different substances.

In accordance with one aspect of the present invention, there is provided a kit for transdermal or intradermal administration of at least one substance comprising (a) a cutaneous applicator that comprises an electrochemical cell with at least two electrodes located on one side of the cutaneous applicator for creating electrical contact with a portion of the skin of the patient, and (b) at least one chamber for storing a substance-containing conductive fluid, wherein the conductive fluid is intended ene for applying at least one of the electrodes and / or for topical application to the skin of the patient, and the applicator is designed and configured so as to supply electric current for transdermal or intradermal administration of substance through the conductive fluid and the skin of the patient.

In accordance with another aspect of the present invention, there is provided a kit for applying current and / or voltage to a portion of a patient’s skin, comprising (a) a cutaneous applicator that comprises an electrochemical cell with at least two electrodes located on one side of the cutaneous applicator to create an electrical contact with the patient’s skin area; and (b) at least one chamber for storing an electrically conductive fluid intended to be applied to at least one of the electrodes and / or to be applied locally to a portion of the patient’s skin, the applicator being designed and configured to form an electrical current for supplying current and / or voltage to a portion of the patient’s skin through an electrically conductive fluid.

In accordance with another aspect of the present invention, there is provided a skin applicator comprising a substantially electrochemical cell with at least two electrodes located on one side of the skin applicator to create electrical contact with a portion of a patient’s skin, the applicator being designed and configured to in order to supply electric current through an electrically conductive fluid applied to at least one of the electrodes and / or locally applied to a portion of the skin of the patient.

In accordance with another aspect of the present invention, there is provided a method for transdermally or intradermally administering a substance, comprising the steps of: (a) locally applying a substance containing a conductive fluid to a region of a patient’s skin and / or applying a substance containing a conductive fluid of at least on one electrode of the cutaneous applicator, which contains an electrochemical cell with at least two electrodes located on one side of the cutaneous applicator; (b) positioning the cutaneous applicator so that the electrodes are in electrical contact with a portion of the skin of the patient; and (c) supplying electric current through an electrically conductive fluid and a skin region of a patient for transdermal or intradermal administration of a substance.

In accordance with another aspect of the present invention, there is provided a method for applying current and / or voltage to a portion of a patient’s skin, comprising the steps of: (a) applying an electrically conductive fluid locally to a patient’s skin region and / or applying an electrically conductive fluid, at least one electrode of the cutaneous applicator, which contains an electrochemical cell with at least two electrodes located on one side of the cutaneous applicator; (b) positioning the cutaneous applicator so that the electrodes are in electrical contact with a portion of the skin of the patient; and (c) passing an electric current through an electrically conductive fluid to supply current and / or voltage to a portion of the skin of the patient.

In accordance with the features obvious from the descriptions of the preferred embodiments, the electrically conductive fluid is a water-based liquid.

In accordance with the features obvious from the descriptions of the preferred embodiments, the electrically conductive fluid is a hydrogel.

In accordance with the features obvious from the descriptions of the preferred embodiments, the electrically conductive fluid is selected from the group consisting of gel, cream, paste, lotion, suspension, emulsion and solution.

In accordance with the features apparent from the descriptions of the preferred embodiments, the conductive fluid is intended to be applied to at least one of the two electrodes.

In accordance with the features obvious from the descriptions of the preferred embodiments, the electrically conductive fluid is intended to be applied locally to a patient’s skin area.

In accordance with the features obvious from the descriptions of the preferred embodiments, the substance is a charged substance.

In accordance with the features apparent from the descriptions of the preferred embodiments, the substance is an uncharged substance.

In accordance with the distinguishing features obvious from the descriptions of the preferred embodiments, the substance is selected from the group consisting of pharmaceutical, cosmetic and therapeutic cosmetic substances.

In accordance with the features obvious from the descriptions of the preferred embodiments, the pharmaceutical substance is selected from the group consisting of therapeutic and analgesic substances.

In accordance with the features obvious from the descriptions of the preferred embodiments, the electric current is used to conduct iontophoresis, electrophoresis, electrophoresis, or any combination of these effects.

In accordance with the features obvious from the descriptions of the preferred embodiments, the electric current is intended to accelerate wound healing, prevent and reduce scarring, restore body tissue and / or tissue regeneration.

In accordance with the features obvious from the descriptions of the preferred embodiments, the chamber is selected from the group consisting of vessels, tubes, cans, containers, dispensers and ampoules.

In accordance with the features apparent from the descriptions of the preferred embodiments, the chamber is a separator for applying to at least one of the two electrodes.

In accordance with the features apparent from the descriptions of the preferred embodiments, an electric current introduces matter from the separator. This separator is designed to prevent contact between the electrode and the skin and ensure uniform distribution of electric current over the entire surface of the applicator. This separator either forms an integral part of the electrode or is attached to it.

In accordance with the features apparent from the descriptions of the preferred embodiments, the separator is enclosed in a removable lid.

According to features that are apparent from the descriptions of the preferred embodiments, the electrochemical cell is an elastic thin layer electrochemical cell.

In accordance with the features apparent from the descriptions of the preferred embodiments, the electrochemical cell is an elastic thin layer open liquid electrochemical cell that contains a first layer constituting an insoluble negative pole, a second layer constituting an insoluble positive pole, and a third layer of aqueous electrolyte, wherein , the third layer is located between the first and second layers and contains (a) moisture-absorbing material for constant support tions open cell in a liquid state; (b) electroactive soluble material to provide the necessary ionic conductivity; and (c) a water-soluble polymer to provide the viscosity necessary to adhere the first and second layers to the third layer.

In accordance with the features obvious from the descriptions of the preferred embodiments, at least one of the two electrodes is designed to impart mobility to at least one substance.

In accordance with the features obvious from the descriptions of the preferred embodiments, at least two electrodes are made as an integral part of the electrochemical cell.

In accordance with the features obvious from the descriptions of the preferred embodiments, the applicator contains only an electrochemical cell and at least two electrodes.

In accordance with the features obvious from the descriptions of the preferred embodiments, the cutaneous applicator further comprises a fastening device for attaching to the patient’s skin area.

In accordance with the features obvious from the descriptions of the preferred embodiments, the cutaneous applicator further comprises circuits for adjusting the electric current.

In accordance with the features apparent from the descriptions of the preferred embodiments, the kit is packaged and labeled as intended for use in wound healing, prevention and reduction of scarring, skin repair, skin regeneration, transdermal administration and intradermal administration.

The present invention effectively overcomes the disadvantages and limitations of previously known configurations with a universal cutaneous applicator capable of providing transdermal and / or intradermal administration of any number of substances in any dosage.

Brief Description of the Drawings

The following are specific references to the detailed drawings, however, it should be borne in mind that the details are shown only as an example and illustrate the description of the preferred embodiment of the invention and are presented in the context of the presentation of the material, which the authors consider the most useful and easily understandable description of the principles and conceptual features of the present invention. In this regard, the description does not contain more detailed construction details of the present invention than is necessary to understand the essence of the invention, and it is obvious from the description and the accompanying drawings for those skilled in the art how certain embodiments of the invention can be practiced.

In the drawings:

Figure 1 is a cross section of a cutaneous applicator constructed in accordance with a preferred embodiment of the present invention,

Figa-g - cameras in accordance with different variants of implementation of the present invention,

Figa-d is the first protected from mishandling an embodiment of the present invention,

Figa-d is a second protected from mishandling an embodiment of the present invention,

Figa-c is a third protected from mishandling an embodiment of the present invention,

6 is a cross section of a cutaneous applicator of a different configuration in accordance with the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION

The present invention relates to kits, cutaneous applicators and methods that can be used for transdermal and / or intradermal administration of various substances, for example, pharmaceutical, cosmetic and therapeutic cosmetics, by means of iontophoresis, electrophoresis and / or electrophoresis. The dermal applicator in accordance with the present invention has the advantage of versatility in that the only applicator is suitable for transdermal and / or intradermal administration of many different substances in different dosages, and that the applicator can be simply charged and used by the patient.

Before a detailed consideration of at least one embodiment of the present invention, it should be understood that the invention is not limited within the scope of the application by structural elements and configuration included in the following description or shown in the drawings. The invention may be carried out in other embodiments or applied and carried out in other fields. In addition, it should be understood that the wording and terms used in the text serve the purpose of the description and do not limit the present invention.

A more complete understanding of the principles and functioning of the kit for transdermal and / or intradermal administration of a substance and a kit for supplying current and / or voltage to a patient’s skin area in accordance with the present invention can be achieved from the above description with reference to the accompanying drawings.

Figure 1 shows the cutaneous applicator in accordance with the principles of the present invention, indicated below as the applicator 10. The applicator 10 includes an upper surface 12 and a lower surface 13 in contact with the skin, which together form the applicator shell 11. In a preferred embodiment, the applicator 10 is made of elastic materials that allow the surface 12 and / or 13 to take shape in accordance with the contours of the skin areas of the patient to which the applicator is applied. Obviously, the applicator shell 11 may be of any size and shape necessary for the respective application.

In a preferred embodiment, the applicator 10 further comprises a device for attaching to the skin, which in a preferred embodiment is an adhesive coating 28 for attaching the applicator 10 to a portion of a patient’s skin. Adhesive coating 28 covers at least a portion of the bottom surface 13 of applicator 10. Adhesive coating 28 in a preferred embodiment comprises a biocompatible permeable self-adhesive material, such as Dow Corning's Bio-PSA. Professionals with a medium level of competence in the art will appreciate the existence of other examples of biocompatible adhesive materials. Adhesive coating 28 may allow both single and multiple attachment.

The applicator 10 contains inside the electrochemical cell 14, which in a preferred embodiment is a thin elastic electrochemical cell, most preferably an open liquid electrochemical cell. It will be apparent to those skilled in the art that the applicator 10 may comprise any other electrochemical cell or power source designed to generate the electric current necessary for the respective application. In the art there are well-known many types of both single-use and rechargeable miniature power supplies that can be integrated into the shell 11 of the applicator.

According to a preferred embodiment of the present invention, the electrochemical cell 14 is a thin elastic electrochemical cell that occupies most of the total volume of the applicator shell 11.

In the present preferred embodiment, the electrochemical cell 14 comprises a positive pole layer 16, a negative pole layer 18 and an electrolyte layer 20 interposed therebetween. A suitable thin elastic electrochemical cell is described, for example, in US Pat. Nos. 5,652,043, 5,897,522 and 5,811,204, which are incorporated herein by reference. The electrochemical cell described in the aforementioned US patents is an open liquid electrochemical cell that can be used as a primary or rechargeable battery for various miniature and portable electrical devices of a compact design. The cell contains a first layer constituting an insoluble negative pole, a second layer constituting an insoluble positive pole, and a third layer of aqueous electrolyte located between the first and second layers and containing (a) easily absorbing moisture material to constantly maintain the open cell in a liquid state; (b) electroactive soluble material to provide the necessary ionic conductivity; and (c) a water-soluble polymer to provide the viscosity necessary to adhere the first and second layers to the third layer.

Some preferred embodiments of the described electrochemical cell are that (i) feed an electrolyte layer into a porous material, for example, but without limitation, filter paper, plastic membrane, cellulose membrane and fabric; (ii) ensure that the first layer constituting the insoluble positive pole contains magnesium dioxide powder, and the second layer constituting the insoluble negative pole contains zinc dust; (iii) ensure that the first layer constituting the insoluble negative pole and / or the second layer constituting the insoluble positive pole further comprises carbon powder; (iv) electrically soluble material is selected from the group consisting of zinc chloride, zinc bromide, zinc fluoride and potassium hydroxide; (v) ensure that the first layer constituting the insoluble negative pole contains silver oxide powder, and the second layer constituting the insoluble positive pole contains zinc powder, and potassium hydroxide is selected as the electroactive soluble material; (vi) ensure that the first layer comprising the insoluble negative pole contains cadmium powder and the second layer comprising the insoluble positive pole contains nickel oxide powder and potassium hydroxide is selected as the electroactive soluble material; (vii) ensure that the first layer constituting the insoluble negative pole contains iron powder, and the second layer constituting the insoluble positive pole contains nickel oxide powder, and potassium hydroxide is selected as the electroactive soluble material; (viii) ensure that the first layer constituting the insoluble negative pole and the second layer constituting the insoluble positive pole contain lead oxide powder, then the element is charged with voltage applied to the poles, and sulfuric acid is selected as the electroactive soluble material; (ix) a moisture-absorbing material and an electroactive soluble material may be the same material, for example zinc chloride, zinc bromide, zinc fluoride and potassium hydroxide; (x) the moisture-absorbing material is selected from the group consisting of calcium chloride, calcium bromide, primary acidic potassium phosphate and calcium acetate; (xi) the water-soluble polymer may be polyvinyl alcohol, polyacrylamide, polyacrylic acid, polyvinylpyrrolidone, polyoxyethylene, agar, agarose, starch, hydroxyethyl cellulose and any combinations and copolymers thereof; (xii) the water-soluble polymer and the moisture-absorbing material may be the same material, for example, dextran, dextran sulfate and any combinations and copolymers thereof. The electrochemical cell 14 in a preferred embodiment includes one or more of the above-described embodiments. In preferred configurations of the electrochemical cell 14 according to the present invention, combinations which do not contain toxic preparations are used.

The electrochemical cell 14 contains leads serving as electrodes, hereinafter referred to as the positive electrode 22 and the negative electrode 24, each of which has electrical contact, respectively, with the positive pole layer 16 and the negative pole layer 18. The electrodes 22 and 24 are electrically connected to the electrochemical cell 14 by well-known means, for example, flexible printed circuits, metal foil, wires, electrically conductive adhesives or by direct contact. Obviously, measures have to be taken to prevent contact between the electrodes and between each electrode and the opposite pole layer. 1, said measures consist in introducing an intermediate insulating element 17 of dielectric material.

The electrodes 22 and 24 are electrically conductive and can be made of metal, for example a metal foil or metal deposited or applied in the form of paint on a suitable base. Suitable metals are, for example, aluminum, platinum, stainless steel, gold and titanium. In accordance with another embodiment, the electrodes 22 and 24 may be made of a hydrophobic polymer binder material containing an electrically conductive filler, for example metal powder and / or plates, powdered graphite, carbon fibers or other known electrically conductive fillers.

The electrodes 22 and 24 can be deposited on the element, and the entire element can be made, for example, using appropriate printing technology, for example, but without limitation, silk-screen printing, offset printing, inkjet printing, lamination, spraying or spraying of materials. In accordance with the foregoing, the electrochemical element 14 of the above construction is one of the simplest power sources.

It will be apparent to those skilled in the art that each of the electrodes 22 and 24 can be of any size and shape and is positioned relative to the other electrode in any pattern that may be required to be applied to the area of skin to be treated. In fact, in accordance with a preferred embodiment of the present invention, the internal elements of the applicator 10 are only the electrochemical element 14 and the related electrodes 22 and 24. In accordance with the foregoing, the skin applicator 10 is one of the smallest and thinnest in existing practice and provides maximum power per unit surface area.

The cutaneous applicator 10 in accordance with the present invention, in a preferred embodiment, is released in a protective removable or reusable container, or package insert or case 19, which provide mechanical protection and a long shelf life before use.

The cutaneous applicator 10 is designed and configured to work with at least one externally applied substance, and, in a preferred embodiment, with a large number of these substances. It is assumed that these substances, the detailed description of which is given below, should be contained in an electrically conductive liquid, a detailed description of which is also given below.

The electrically conductive fluid in accordance with the construction must be stored in at least one, and in the preferred embodiment, multiple chambers. The cutaneous applicator 10 and the camera in combination form a kit that can be stored by the patient for use for various purposes.

2a-g illustrate a plurality of chambers for storing an electrically conductive fluid. This electrically conductive fluid will usually be formulated according to “pharmaceutically approved” or “cosmetologically authorized” formulations intended for cosmetic or therapeutic use. Used in the description, the terms "permitted in pharmacy" or "permitted in cosmetology" refer to substances that can be administered to a patient, in a preferred embodiment, without unnecessarily harmful side effects (in relation to locally applied formulations, for example, without skin rashes, irritation). Specific formulations include aqueous gels, creams, pastes, lotions, suspensions, emulsions and solutions, or other liquid formulations suitable for topical application and known in the art.

In accordance with the present preferred embodiment, the electrically conductive fluid is an electrically conductive and adhesive hydrogel suitable for use as a skin contact adhesive, and in particular suitable for use as an electrical contact surface of electrodes of a medical device. Hydrogels are cationic acrylates and can be, for example, in a preferred embodiment made from acrylic esters of quaternary salts of hydrochloric acid and / or hydrochloric acid or acrylamides of quaternary salts of hydrochloric acid. These esters can be prepared by polymerizing free radicals in water, in a preferred embodiment, with ultraviolet curing, an initiating catalyst and a multifunctional builder. In a preferred embodiment, the hydrogel may comprise a buffer system to prevent discoloration of the hydrogels and / or hydrolysis of the hydrogels, and / or to extend the shelf life.

Other additives (for example, conductivity enhancers, pharmaceuticals, moisture-retaining agents, plasticizers) may be added to these hydrogels before or after curing, depending on the intended end use. The additive, which is expediently introduced into the hydrogel, is an electrically conductive adhesive substance (additive), which allows the electrically conductive fluid to both attach the cutaneous applicator 10 to the patient’s skin and to act as an electrical contact surface between the electrode and the skin. In a preferred embodiment, the adhesive additive is a polymer adhesive and can be activated by pressure or temperature, or by exposure to the surrounding atmosphere.

In a preferred embodiment, the hydrogel provides sufficient adhesion and can easily come off. Additional data regarding hydrogels applicable in the context of the present invention are contained, for example, in US Pat. No. 5,800,685, which is incorporated herein by reference.

In any case, the aqueous electrically conductive fluid in accordance with the essence of the present invention usually contains water, aqueous alcoholic solutions, at least one salt or any other charged means and, in a preferred embodiment, a buffer medium.

It will be apparent to those skilled in the art that non-aqueous, electrically conductive fluids can also be used.

The electrically conductive fluids used in combination with the cutaneous applicator 10 are advantageously applied to one or both of the electrodes. It will be apparent to those skilled in the art that an electrically conductive fluid can be additionally applied topically to the skin in accordance with other embodiments. The term "local" in the present description is used to apply the substance to the surface of the skin or mucous membranes, and the application can be performed directly (for example, by spreading), by means of an impregnated porous material or object, or by spraying or spraying. It will be apparent to those skilled in the art that the accuracy of local application of fluid to a patient’s skin is usually small and, if not performed accurately, can erroneously create an electrical connection directly between the electrodes through an electrically conductive fluid, as a result of which an electric current will not flow through the skin and mobile ions.

In accordance with the foregoing, the chambers will vary in shape, size and method of dosing, depending on the medical purpose and the corresponding amount, application and location. 2b-g show chambers in the form of a vessel 31, a tube 32, a can 33, a container 34, a dispenser 35 and an ampoule 36. It will be apparent to those skilled in the art that the present invention involves the use of said chambers, as well as other chambers of any shape, sizes or configurations that are used to store and dispense an electrically conductive fluid for application to the electrodes or skin of the patient as needed.

On figa shows a chamber 30, which is a separator. The term "separator" is used to refer to a chamber made of a porous non-conductive material, such as a sponge, paper, which serves to hold an electrically conductive fluid in its volume. The advantage of separators compared to other chambers is that the separators allow the precise application of an electrically conductive fluid, eliminate contamination and provide an accurate dosage during administration.

The fluid is stored in the separator in such a way that objects that are in contact with the separator are also in contact with the fluid contained in the separator. In accordance with the foregoing, electrical contact with the electrically conductive fluid contained in the separator can be established by creating a mechanical contact between the electrode and the separator.

It is advisable to design and configure the separators so that they enter between one or both of the electrodes 22 and 24 and the skin of the patient and thereby create between the electrode and the skin a simple, clean and convenient electrical contact surface through which electricity can flow through the electrically conductive fluid to the treatment area . According to the previous information, the separators are designed so that their non-conductive structure does not interfere with the electrical contact between the electrode 22 or 24 and the electrically conductive fluid in the separator. It is clear that the separator will not be placed so that it or its contents creates an electrical contact between the electrodes 22 and 24. This placement would form an electric circuit that does not contain the patient’s skin and does not allow to achieve the goal of electrical exposure.

The separators can be made in the form of tampons, cartridges or tablets and similar products that are designed to be compatible with electrodes 22 and / or 24 that are different in shape, size and configuration.

According to a preferred embodiment, the chamber 30 in the form of a separator is preferably a thin layered container, which may have a predetermined shape in order to be compatible with both the treatment area and the electrode used. In a preferred embodiment, these separators, it is advisable to protect the thin-film layer, which will be torn off immediately before use.

The separators may be packaged for storage or use, if possible, for compatibility with the preferred embodiment of the kit of the present invention. It is advisable to pack the separators separately to ensure a predetermined shelf life and to prevent evaporation of the electrically conductive fluid and / or the substance contained therein.

The use of the above-described chambers, in particular, the separator 30, is intended to give the cutaneous applicator 10 qualities such as user-friendliness and practical protection from rough handling during use. The significant design and configuration differences between the chambers described are due to the desire to accurately apply the electrically conductive fluid either to the corresponding electrode or locally to the patient’s skin. For example, a tube-shaped chamber 32 will make it easy to apply a drop of an electrically conductive fluid precisely onto an electrode. An ampoule-shaped chamber 36 will provide an accurate dosage of the drug. Dispenser 35 will allow accurately and accurately applying an electrically conductive fluid to a portion of a patient’s skin. In a preferred embodiment of the invention, the separator 30 will function as a carrier of electrically conductive fluid that can be accurately placed on the electrode or skin of the patient.

It will be apparent to those skilled in the art that the precise placement of an electrically conductive fluid on an appropriate electrode or skin of a patient is essential for efficiently conducting electric current through the skin of the patient. In accordance with the foregoing, a kit comprising a cutaneous applicator 10 and one or more chambers 30-36, in a preferred embodiment, will also contain any other devices, instructions, markings, aids or devices that will assist the user correctly, as required, apply and place electrically conductive fluid.

A series of anti-abuse embodiments of the present invention as applied to the cutaneous applicator 10 are shown in FIGS. 3a-5c. In the embodiment shown in FIGS. 3a-d, a strip 100 is applied to the skin 102 and an electrically conductive lotion, gel, cream or the like is applied to the skin 102 so that after removing the strip 100 two non-contacting zones 106 are formed to be placed on of them of the skin applicator 108, designed and functioning in accordance with the principles of the present invention, and then the skin applicator 108 is placed on the skin 102 so that each of the electrodes 110 of the skin applicator is in contact with one of the zones 10 6 with the exception of a short circuit.

In the embodiment shown in FIGS. 4a-d, a patterning device 200 containing two holes 201 is applied to the skin 202, and an electrically conductive lotion, gel, cream or the like 204 is applied to the skin 202 so that after removal of the forming apparatus 200 two non-contacting zones 206 were formed to accommodate the cutaneous applicator 208, designed and functioning in accordance with the principles of the present invention, and then the skin applicator 208 was placed on the skin 202 so that each the first electrode 210 Cutaneous applicator is in contact with one of zones 206, except in this case the short-circuit.

In the embodiment shown in FIGS. 5a-c, the collapsible skin applicator 308 is folded onto the skin 302 and an electrically conductive lotion, gel, cream or the like 304 is applied to the skin 302 on both sides of the skin applicator so that after alignment of the skin applicator 308, two non-contacting zones 306 were formed to accommodate the skin applicator 308 on them, and the skin applicator 308 was in contact with the skin 302 so that each of the electrodes of the skin applicator 310 was in contact e from one of the zones 306 with the exception of a short circuit.

6 shows an embodiment of a cutaneous applicator 10 in accordance with the present invention, where the electrode 22 is not an integral part of the electrochemical cell 14, but is connected by an electrically conductive connector, hereinafter referred to as a connector 21. Next, a description will be made of the components of the cutaneous applicator 10 in accordance with the present embodiment inventions that are similar to those described above, and similar numeric positions are used to designate them. The connector 21 may be made by printing technology or from any electrically conductive material known in the art. According to the embodiment shown, a chamber, which is a separator, is placed on the electrode 24 of the electrochemical cell 14. Accordingly, in this configuration, the electrode 24 can be called a treatment electrode, and electrode 22 is called an electrically conductive adhesive electrode. In accordance with the present embodiment of the invention, the simultaneous contact of the electrode 22 and the separator 30 with the skin of the patient will ensure the formation of an electric circuit, one of the conductive sections of which is the skin of the patient. In this configuration, the electrochemical cell 14 will generate an electric current, which will be supplied through an electrically conductive fluid held by the camera 30 in contact with the skin. An electric current will pass through the skin and, therefore, will impart mobility to respectively charged ions or molecules inside the electrically conductive fluid and force them to move through the skin.

One of the tasks of creating a cutaneous applicator 10 is the transdermal or intradermal administration of a pharmaceutical, cosmetic or therapeutic and prophylactic cosmetic substance. In the context of the present description, the terms "percutaneous" and "intradermal" and their grammatical modifications refer to the introduction of drugs, respectively, through / through the skin and into the skin. In the context of the present description, the term "pharmaceutical" refers to therapeutic or analgesic substances. In the present description, therapeutic substances include any substance intended for the treatment, healing, medical treatment or maintenance of health. In the present description, anesthetics include any substance intended to weaken tactile sensitivity, in particular pain. For electrical introduction, these substances in a preferred embodiment should be in the form of charged molecules that will respond to electric current. Specialists in the art it is obvious that the invention in accordance with the present description allows you to enter any pharmaceutical, cosmetic or therapeutic cosmetic substance, if this substance is present in the form of charged particles or can be charged.

If a substance in a free state is not charged, it is advisable to combine it with a charging device or expose it to external factors, for example, a medium with a special pH value, which initiates the formation of charged particles. Methods of communicating an electric charge to molecules are well known in the art, and therefore their description is not given. In any case, it is understood that the substance to be administered can be charged before or simultaneously with the administration.

Therefore, the term "substance" in the context of the present description refers to active substances that, in a preferred embodiment, are present in the form of charged ions or charged molecules, and which can be administered transdermally or intradermally by electrical means. In general, this term encompasses therapeutic agents used in all major areas of therapy, including, without limitation, anti-infective drugs such as antibiotics and antiviral drugs, analgesics, including fentanyl, sufentanil, buprenorphine and painkillers, painkillers, appetite-lowering drugs, anti-arthritis and anti-asthma drugs, for example terbutaline, anticonvulsants, antidepressants, anti-diabetic drugs, anti-inflammatory drugs, antihistamines, anti-inflammatory drugs TWA, headache medications, anti-agonist drugs such as scopolamine and ondansetron, antiemetics, antitumor drugs, drugs for tremor palsy, pacemakers like dobutamine, antipruritic drugs, antipsychotics, antipyretic drugs, antispasmodics, including gastrointestinal and genitourinary drugs, anticholinergics, sympathonetic drugs, xanthine derivatives, cardiovascular drugs, including block calcium channel inhibitors such as nifedipine, beta-blockers, beta-agonists such as salbutamol and ritodrin, antiarrhythmic drugs, antihypertensive drugs such as atenolol, angiotensin-I-converting enzyme (ACE) inhibitors, diuretics, vasodilators, including those common for coronary peripheral and cerebral vessels, stimulants of the central nervous system, cough and cold preparations, decongestants, diagnostic tools, hormones such as parathyroid hormone, growth hormone and insulin, hypnotics means, immunosuppressive agents, muscle relaxants, parasympatholytics, parasympathomimetics, anti-oxidants, nicotine, prostaglandins, psychostimulants, sedatives and tranquilizers. The invention is also suitable for the introduction of cosmetic and therapeutic cosmetic substances. These substances include, for example, skin antioxidants such as carotenoids, ascorbic acid (vitamin C) and vitamin E, as well as other vitamin preparations and other antioxidants, anti-wrinkles, such as retinoids, including retinol (vitamin A alcohol) ), alpha hydroxy acids, beta hydroxy acids, commonly known as salicylic acid, complex hydroxy acids, polyoxy acids and hydrolyzed and soluble collagen, moisturizers such as hyaluronic acid, type a anti-cellulite minofillins, skin whitening agents such as retinoic acid, hydroquinone, peroxides, etc., herbal preparations such as extracts of aloe vera, wild potato, witch hazel, ginseng, green tea.

It should be understood that the invention is applicable for the introduction of the above and other substances with the possibility of a wide change in dosage and over a given period of time.

Percutaneous or intradermal administration of a substance, in a preferred embodiment, occurs as a result of iontophoresis and / or electrophoresis. Iontophoresis involves the movement of ions caused by the application of an electric potential. Electrophoresis involves the movement of charged colloidal particles or macromolecules under the influence of an electric field. The electric current induced by the electric potential between the electrodes 22 and 24 leads to the release of a charged substance from the electrically conductive fluid and the introduction of molecules and / or ions of a charged substance contained in the electrically conductive fluid into the adjacent skin tissue. A charged substance contained in an electrically conductive fluid that is applied to one of the electrodes or both electrodes 22 and 24 and to the patient’s skin will be attracted or repelled by electrode 22 and electrode 24, depending on their charge. For example, if the substance carries a positive charge, then the electrode 22 will repel the substance and thereby force it to move into the skin or through the skin. In this configuration, when current flows from the positive electrode 22 in the direction of the skin, the charged substance moves inside the electrically conductive fluid and through the electrical contact surface into the skin.

It should be noted the possibility of using reverse iontophoresis for the process of percutaneous or intradermal excretion of substances from the body. This method is based on similar electrical principles, but used for reverse action. Methods for percutaneous or intradermal excretion of substances are well known in the art.

The process of electroporosis can intensify the percutaneous or intradermal movement of substances. Electroporosis is usually carried out by applying high voltage pulses to a pair of electrodes that are applied to the surface of the tissue. Electric impulses force ions to punch holes in the tissue layer and thereby create new paths for the movement of both charged and uncharged substances. It should be noted that electroporosis does not introduce a charged substance, but significantly reduces the resistance to movement of substances into adjacent tissues. Since electroporosis does not provide the necessary driving force, it is advisable to combine electroporosis with such methods of administration as iontophoresis or electrophoresis in order to ensure effective implementation.

Another important task of creating a cutaneous applicator 10 is to stimulate wound healing, prevent and reduce scarring, restore skin and / or regenerate the skin by passing an electric current directly through the skin. In therapy, the ability of an electric current to compel excitable cells (nerve and muscle cells and receptors of nerve endings) of the human body is known and applied, when external electrical stimulation in the form of electrical impulses is applied to them, to form an electrical response called action potentials. These action potentials are intrinsic electrical impulses of a cell with a certain amplitude and duration in cells of the corresponding type. For example, typical values of the width and amplitude of a pulse of one nerve are about 1 ms and about 80 mV-100 mV. The cell returns to the voltage of its cell membrane, which at rest, depending on the type of cell, has a value of 60 mV-120 mV. This voltage is due to the difference between extracellular and intracellular ionic concentrations. In the extracellular space there are more positive ions. According to the definition, the extracellular space potential is taken equal to 0 V, therefore, the intracellular potential has a negative sign.

A healthy organism itself forms action potentials that serve to transmit information and enable cellular processes.

In electrotherapy, the therapeutic effect is obtained by the specific formation of action potentials (a certain number and in a specific place).

Electrotherapy devices allow the use of many different forms of electric currents or pulses. To select the most effective electrotherapy method for a specific indication, the doctor should be able to address the criteria for the clearest definition. These criteria follow from answers to questions regarding the efficiency and admissibility of various forms of current.

The range of results includes, for example, zones of anesthesia, irritation of striated and smooth muscles, effects on perfusion, detumescence mechanisms, zones of control of inflammatory processes and stimulation of regeneration (wounds, accelerated restoration of bone tissue, etc.). The objective of the application should always be to achieve the desired effect in the impact zone due to the correct choice of the current shape either at a distance, or near the electrode, or in the depths of the body.

The operation of electrotherapy devices is based essentially on two methods of electric shock, the polar-dependent "principle of polar irritation" and the polar-independent "principle of apolar irritation."

The "principle of polar irritation" is based on the use of low-frequency alternating currents (LF current) in the frequency range 0-200 Hz. Under the positive electrode, which is an anode, there is hyperpolarization (increased transmembrane voltage), which increases the difference between the intracellular potential and the threshold of irritation. On the contrary, under the negative electrode, which is a cathode, the transmembrane voltage decreases. When the threshold of irritation is reached, the cell automatically turns on the action potential.

Irritation current generators emit pulses of various shapes in the low-frequency spectral range from approximately> 0 to 200 Hz (LF current). You can use, for example, the so-called delta currents, rectangular currents, diadynamic currents, high voltage currents, super-irritating currents, Faraday currents, where only a small number of possible currents are listed. Some alternating currents have a constant component, which further enhances the effects of polarization.

There are two frequency-dependent ways to use action potentials for therapeutic purposes:

The principle of functional imitation:

Set the number of action potentials formed by an excitable cell (for example, a nerve or muscle) to perform its functions. During therapy, the same number of impulses is formed in the corresponding cell by means of stimulation and thereby help the cell to fulfill its functions.

For example, to cause compression at a frequency of 6 compressions per second, an annoying signal is applied at a frequency of up to 6 Hz.

The principle of fatigue:

On the contrary, when a (nerve or muscle) cell is forced to form action potentials by stimulation with a higher frequency, significantly higher than the frequency that would be required for the cell to function, the latter quickly becomes tired. The impact is in the opposite direction. Fatigue of the cell can be explained by the processes of energy consumption for the formation of action potentials.

For example, in accordance with this principle of fatigue, hardened muscle can be relaxed with irritation of a "higher" frequency, for example 100 Hz-200 Hz.

In any case, in order to form action potentials, a sufficiently high intensity should be prescribed to exceed the threshold of irritation. The level of intensity to be determined is determined by the following factors: the location (depth) of the tissue to be irritated (the distance from the electrode), the size of the electrodes, and the resistance of the tissues in the region in which the electric potential propagates and which, in turn, is influenced by the current shape parameters.

In practice, the current shape and electrode size are predetermined parameters. Then, to irritate a group of cells at a certain distance from the electrode (for example, deep in the tissue), the current strength and / or voltage level is increased until action potentials arise.

Simultaneously with an increase in current strength, cells located more and more deeply or even more distant from the electrodes are sequentially irritated. The principle of apolar irritation involves the use of only the so-called mid-frequency alternating currents (MF currents) without any constant component. The concept of mid-frequency currents (MF currents) is applied to sinusoidal alternating currents with a frequency of> 5 Hz to 100,000 Hz. A single cycle (sinusoidal impulse) of sufficient intensity has a polar effect, which can include the action potential in a nerve or muscle cell.

Often there is a "summation effect". To include action potentials in cells with increasing frequency, it is also necessary to increase intensities. Weiss indisputably proved that the formation of action potentials by mid-frequency pulses occurs completely independently of polar effects. This means that whenever the intensity and number of oscillations are sufficiently large, action potentials will be formed regardless of the instantaneous polarity of the mid-frequency current (Wyss, Oscar AM; Prinzipien der elektrischen Reizung, [Principle of Electrical Stimulation], Neujarhrs-Blatt, published by Natural Research Society in Zurich for the year 1976, Kommissionsverlag Leeman AG, Zurich, 1976, 28-34).

Mid-frequency pulses are applied with a low repetition rate from> 0 Hz to approximately 200 Hz, with carrier medium frequencies from> 5 Hz to 100,000 Hz. In practice, a sinusoidal amplitude modulated mid-frequency current (AM-mid-frequency current) is usually used. The following are principles consistent with those set forth in conjunction with the “principle of polar irritation”.

The principle of functional imitation:

The action potentials arise in excitable cells synchronously with mid-frequency (amplitude-modulated) pulses. Thus, the cell is stimulated to perform its natural functions originating from a given frequency.

The principle of fatigue:

To tire an excitable cell, mid-frequency pulses with higher amplitudes are used.

With an increase in current strength, cells located more and more deeply (more distant from the electrodes) are sequentially irritated.

To form action potentials with increasing frequency, it is necessary to increase the intensity.

The use of mid-frequency alternating current provides the following additional therapeutic options:

When stimulated by the mid-current (constant amplitude) of sufficient strength, the action potential is first formed. When stimulated by the mid-frequency current, which takes a longer time, the action potential on the damping side remains at the level of depolarization (constant depolarization), which is about half the equilibrium potential. After turning off the MF current, the transmembrane voltage drops, then decays to the equilibrium potential level.

The following is a description of the therapeutic use of permanent depolarization.

Pain relief and effect on perfusion:

High intensities, which, depending on the properties of the treated zone, change to an acceptable limit, cause blocking of the nerve pathways due to constant depolarization. This true neural blockade (as shown by BOWMAN, Bruce R., 1981, dissertation EK University of Ljubljana, Rancho Los Amigos Hospital, Downey, Calif, USA) is used, for example, to block phantom pain or block the stellate ganglion in case of blood flow disorders .

Muscle contractions:

Muscle training with intentional insufficient innervation and muscle tension.

With an intact neuromuscular mechanism, the striated (skeletal) muscle is directly irritated by constant depolarization. As a result, the muscle contracts, which is used, for example, with deliberate insufficient innervation of muscles or for stretching the muscles antagonists of spastic muscles. During treatment, the intensity should be turned off by pauses at short intervals. The intensity can also be increased and decreased in the range from 100% to approximately 50% of the adjusted value.

The formation of great muscle contraction efforts:

Very strong muscle contractions can be caused without signs of fatigue. With a tetanic contraction, which can be caused by current irritation with a frequency of about 50 Hz or more, the muscle contraction force, on the contrary, quickly decreases due to fatigue of myokinetic nodes.

Cell division:

Wound healing and accelerated bone repair:

Constant depolarization causes cell division of healthy cells. Thus, it is possible to stimulate wound healing and accelerate the restoration of bone tissue in fractures. Moreover, the MF currents cause a reciprocating motion (vibration effect) of charged molecules in the tissue permeable by the action of an alternating electric field, accompanied by rotational movements of the charged parts of the molecules. This increases the likelihood of a "right" on-site arrangement of the enzyme and substrate, which chemically interact during metabolic processes (facilitating metabolism). The mentioned vibration effect seeks to balance the differences in concentrations by accelerating these diffusion processes, which, due to existing concentration gradients, proceed in certain directions due to the additional kinetic energy supplied (mid-range iontophoresis, suppression of inflammation, and pain relief).

The effect of vibrations is especially enhanced at high intensities.

Distribution of mediators of inflammation and pain:

Suppression of inflammation and pain relief:

With the occurrence of painful inflammatory processes in diseased tissues, a high concentration of inflammatory and pain mediators is periodically detected. The effect of vibration reduces (disperses) this high concentration. "Vibration intensity" due to strong currents and having the same frequency is of great importance for obtaining therapeutic results (Hans-Jurgens, May, Elektrische Differential-Therapie [Electrical Differential Therapy], Karlsrune 1990).

The effect of metabolism (diffusion, mitochondria, cyclic adenosine-5'-monophosphate (AMP)):

Acceleration and stimulation of metabolic processes:

In accordance with the foregoing, there is an acceleration of biochemical metabolic processes.

In addition, when passing the MF current through cell cultures, a significant increase in the number and size of mitochondria (cellular "energy systems") was noted.

The concentration of an important cellular informational substance, cyclic adenosine-5'-monophosphate (AMP) can also be changed by exposure to alternating current, depending on the mid-frequency current and / or voltage (Dertinger, 1989, Kemforschungszentrum Karlsruhe, Nagy Nemectron GmbH Karlsruhe).

In addition, MF currents can cause painless, strong muscle contraction.

The so-called "threshold separation" begins with 8 kHz, i.e. the threshold current strength, in amperes, for muscle contraction is less than the threshold current strength corresponding to the sensitivity threshold (Edel, H .: Fibel der Elektrodiagnostik and Elektrotherapie [Primer of Electrodiagnostics and Electrotherapy], Muller & Steinicke Munchen 1983, p.193). Strong muscle contractions can be caused without pain. From a therapeutic point of view, the separation of thresholds is of particular interest for using the reversible process of muscle contraction, which is caused by constant depolarization upon application of the MF current.

A strong mid-frequency current causes heat to be released into the tissues, allowing current to pass through. However, it is mandatory that the patient should not feel unwell due to exceeding thresholds (sensitivity, muscle contraction, tolerable, painful).

Similarly, stimulating metabolic processes, the MF current can contribute to iontophoresis, namely, percutaneous administration of drugs using current into the body. Due to physical conditions, iontophoresis using MF current requires more treatment time and stronger currents than galvanic currents.

In accordance with the above information and data published in the relevant commercial literature (see the book "Elektrische Differential-Therapie" [Electrical Differential Therapy] by A. Hansjuorgens and HUMay, 1990; Nemectron GmbH, Karlsrune), the first electrotherapy devices were used, depending on the diagnosis, low-frequency currents or amplitude-modulated mid-frequency currents with frequencies from> 0 Hz to 200 Hz, or mid-frequency currents with frequencies from> 5 Hz to 100,000 Hz, in each case with a constant amplitude (force).

Since it is assumed that the cutaneous applicator in accordance with the present invention will find one or more of any of the above applications, the applicator 10 in a preferred embodiment contains electrical circuits for controlling the level or duration of the current generated by the electrochemical cell 14. Such circuits can be made in the form of a two-position switch for on-demand inclusion of a drug administration process (eg, a patient-controlled pain administration process a means for relieving headaches), a timer, constant or variable electrical resistance, a controller that automatically turns the device on and off at the required frequency to meet the natural or daily characteristics of the body, or other more complex electronic control devices known in the art . For example, it may be necessary to supply an electric current of a given constant level, since a constant current level provides a constant rate of introduction of the substance. The current level can be adjusted by many known means, for example, a resistor or a simple circuit that contains a resistor and a field effect transistor. The circuits may also contain an integrated microcircuit, which can be designed to adjust the dosage of the active agent supplied, or even respond to sensor signals to adjust the dosage to comply with a given dosing schedule. A relatively simple circuit can control the current depending on time and, if necessary, generate complex currents according to the type of signal, for example, pulses or sine waves in accordance with the above description. In addition, the circuits may include a biofeedback system that monitors the biosignal, evaluates the treatment, and adjusts the administration of the active agent accordingly. A characteristic example is that in which blood sugar levels are controlled to regulate the administration of insulin to a patient with diabetes mellitus. A simple but important application of the regulatory scheme is to eliminate heat generation and tissue damage caused by it. It is clear that the introduction of ions is accompanied by heat release due to the movement of ions, and the faster the introduction, the more intense the heat release at the injection site. The current used for treatment, as such, can be regulated by the patient in such a way that a balance can be found between the intensification of the administration of the substance and the weakening of the malaise with increasing temperature.

Therefore, the kit in accordance with the present invention will contain a cutaneous applicator for transdermal and / or intradermal administration of at least one substance and at least one chamber for storing substances (a) separately from the applicator before use. The proposed design allows the universal administration of various substances and / or dosages with a single cutaneous applicator.

As a result, the method of transdermal or intradermal administration of at least one substance in accordance with the present invention is carried out as a sequence of steps consisting in (a) locally applying the substance containing the conductive fluid to the patient’s skin area and / or applying the conductive substance containing the substance fluid, at least one electrode of the cutaneous applicator, which contains an electrochemical cell with at least two electrodes located on one side of the skin burn applicator; (b) positioning the cutaneous applicator so that the electrodes are in electrical contact with a portion of the skin of the patient; and (c) supplying electric current through an electrically conductive fluid and a portion of the patient’s skin for transdermal or intradermal administration of the substance.

As a result, the method of applying current and / or voltage to a patient’s skin area in accordance with the present invention is carried out as a sequence of steps in which (a) a conductive fluid is applied locally to the patient’s skin area and / or a conductive fluid is applied at least at least one electrode of the cutaneous applicator, which contains an electrochemical cell with at least two electrodes located on one side of the cutaneous applicator; (b) positioning the cutaneous applicator so that the electrodes are in electrical contact with a portion of the skin of the patient; and (c) passing an electric current through an electrically conductive fluid to supply current and / or voltage to a portion of the skin of the patient.

It should be understood that an electrically conductive fluid can be applied to one or both of the electrodes either held in a chamber or dispensed from any other described chamber. In addition, it should be understood that the aforementioned applications of the present invention can also be realized by local application of the conductive fluid to the skin at the place where the electrode will be located.

The present invention provides numerous advantages over existing applicators, which essentially contain substances to be administered percutaneously or intradermally, since a single skin applicator can be used to administer any number of different substances / dosages while it is receiving food, without the need for waste since it is never depleted.

Additional objectives, advantages and new features of the present invention are obvious to specialists with an average level of competence in the art from consideration of the following examples, to which the invention is not limited. In addition, the following are examples experimentally confirming each of the various embodiments and each feature of the present invention defined in the above description and the following examples.

Examples

The following are examples that, together with the above description, illustrate the present invention without limiting it.

Rosacea Treatment

Rosacea, characterized by redness of the face and telangiectasia, is a common disease that affects many people, mostly of the aging generation. Rosacea treatment options are limited.

Three patients with rosacea who met the following selection criteria were enrolled in an experimental study:

Patients had mild to moderate redness on both sides of the face and patients were aged 20-65 years.

The objectives of the study were to determine the therapeutic effect on the phenomenon of redness during and after treatment, and to determine side effects.

Each test patient received treatment on both sides of the face.

A “active applicator” was applied on one side of the face, connected by thin wires to the power source so that most of the applicator (main applicator) was connected to the positive pole of the power source, and a smaller part of the applicator (counterpplicator) was connected to the negative pole of the power source.

On the other side of the face of each subject, a “passive applicator” of a similar shape was applied without connecting to a power source.

Each applicator was coated with a test preparation (aqueous gel containing witch hazel extract). 0.4 ml of the test preparation was evenly applied with a spatula to the main applicator, and 0.1 ml of the test preparation was applied to the contrapplicator. Then the applicators were applied to the skin of the studied patients for 7-20 minutes (treatment period).

Immediately after removing the applicators and then after 10, 25 and 40 minutes, visual observations were performed, including subjective assessment by the patient and covert assessment by a trained observer. Before treatment and at each observation, photographs were taken.

All three patients showed a marked decrease in the degree of redness and spread of telangiectasia at the sites of application of the active applicator. This improvement was noted at the first observation immediately after removal of the applicator and then was recorded during the rest of the observation period. The passive applicator gave only slightly noticeable improvements, which neither the patient nor the observer did not assess as significant.

Those skilled in the art will appreciate that certain features of the invention, which are described for clarity in connection with individual embodiments of the invention, may also be combined in one embodiment of the invention. Conversely, various features of the invention, the description of which for brevity is given in connection with one embodiment of the invention, may also be presented separately or in any suitable subcombination.

Those skilled in the art will appreciate that the present invention is not limited to the above specific embodiments. On the contrary, the scope of the present invention is determined by the attached claims and includes both combinations and subcombinations of the various above features, as well as their changes and additions, which are obvious to specialists in this field of technology after reading the above description. In accordance with the foregoing, all such variations, changes and additions can be made to the invention that do not go beyond the essence and wide scope of the attached claims.

Claims (85)

1. A kit for supplying electric current and / or voltage to a skin site and / or percutaneous or intradermal injection of substances containing (a) a cutaneous applicator comprising a power source and at least two electrodes electrically connected to a power source, said electrodes being designed to electrically connect to a portion of a patient’s skin, and (b) at least one separator for storing an electrically conductive fluid, wherein said electrically conductive fluid is intended to be applied to at least one of said at least two electrodes and / or to be applied locally to a portion of a patient’s skin wherein said separator is designed to prevent contact between at least one of said at least two electrodes and a skin region, said applicator being designed and configured to conduct electrical of current through the skin and said conductive fluid. 2. The kit according to claim 1, in which the aforementioned conductive fluid is a liquid based on water. 3. The kit according to claim 1, wherein said conductive fluid is a hydrogel. 4. The kit according to claim 1, wherein said electrically conductive fluid is selected from the group consisting of gel, cream, paste, lotion, suspension, emulsion and solution. 5. The kit according to claim 1, in which the aforementioned electric current is designed to provide iontophoresis, electrophoresis, electroporosis, or any combination thereof. 6. The kit according to claim 1, in which said at least two electrodes are made as an integral part of said power source. 7. The kit according to claim 1, in which said power source and said at least two electrodes are components of the applicator. 8. The kit according to claim 1, in which the said cutaneous applicator further comprises a mounting device for attaching to the patient’s skin area. 9. The kit according to claim 1, wherein said cutaneous applicator further comprises a circuit for regulating said electric current. 10. The kit according to claim 1, wherein said power source is an elastic thin-layer electrochemical cell. 11. The kit of claim 10, wherein said electrochemical cell is an elastic thin layer open liquid electrochemical cell that comprises a first layer constituting an insoluble negative pole, a second layer constituting an insoluble positive pole, and a third layer of aqueous electrolyte, wherein the third layer is located between the aforementioned first and second layers and contains: (a) a moisture-absorbing material for continuously maintaining an open element in a liquid state, (b) electroactive soluble material to provide the necessary ionic conductivity, (c) a water-soluble polymer to provide the viscosity necessary to adhere said first and second layers to said third layer. 12. The kit according to claim 1, packaged and labeled as intended for use with a target selected from the group consisting of wound healing, prevention and reduction of scarring, skin repair, skin regeneration, muscle stimulation, muscle contraction, acceleration of bone healing, suppression of inflammatory processes, relief and acceleration of metabolic processes, pain relief, treatment of rosacea and telangiectasia. 13. The kit according to claim 1, in which the kit is intended for transdermal or intradermal administration of at least one substance. 14. The kit according to item 13, in which the aforementioned conductive fluid contains at least one substance. 15. The kit of claim 14, wherein said at least one substance is a charged substance. 16. The kit of claim 14, wherein said at least one substance is an uncharged substance. 17. The kit of claim 14, wherein said at least one substance is selected from the group consisting of pharmaceutical, cosmetic, therapeutic and cosmetic substances and moisturizers. 18. The kit according to 17, in which the aforementioned pharmaceutical substance is selected from the group consisting of therapeutic and analgesic substances. 19. The kit of claim 14, wherein said separator is intended to be applied to a skin site so that, when said separator contacts at least one of said at least two electrodes, said electric current causes said transdermal or intradermal administration of said at least one substance. 20. The kit of claim 14, wherein said separator is intended to be applied to at least one of said at least two electrodes so that, when said separator contacts a skin site, said electric current causes said transdermal or intradermal administration of said at least one substance. 21. The kit according to claim 19, in which said separator is enclosed in a removable cover. 22. The kit according to item 13, in which at least one electrode of the aforementioned at least two electrodes is designed to impart mobility to at least one substance. 23. The kit according to claim 1, in which the said kit is designed to supply current and / or voltage to the skin area of the patient. 24. The kit according to item 23, in which the said separator is intended for application to a skin site. 25. The kit according to item 23, in which the said separator is designed for applying at least one of the aforementioned at least two electrodes. 26. The kit according to claim 1, in which the said cutaneous applicator is a thin elastic applicator. 27. The kit according to claim 1, in which the said cutaneous applicator further comprises an applicator shell, and in which the electrochemical cell and said at least two electrodes are located on the applicator shell at a distance from each other with the formation of a gap between the at least , two electrodes. 28. The kit of claim 14, wherein said at least one substance is at least one antibiotic. 29. The kit according to claim 1, in which at least one substance is at least one of the following: anti-infective agents, antibiotics, antiviral drugs, analgesics, fentanyl, sufentanil, buprenorphine, painkillers, pain relievers, appetite-lowering , anti-arthritis and anti-asthma drugs, terbutaline, anticonvulsants, antidepressants, antidiabetic drugs, antidiarrheal, antihistamines, anti-inflammatory drugs, headache drugs, anti-contraceptives drugs, scopolamine, ondansetron, antiemetics, antitumor drugs, drugs for tremor palsy, pacemakers, dobutamine, antipruritic drugs, antipsychotics, antipyretic drugs, antispasmodics, gastrointestinal and genitourinary drugs, anticholinergics, sympathy , cardiovascular drugs, calcium channel blockers, nifedipine, beta-blockers, beta-agonists, salbutamol, rhytod rin, antiarrhythmics, antihypertensives, atenolol, angiotensin-1-converting enzyme (ACE) inhibitors, diuretics, vasodilators common to the coronary, peripheral and cerebral vessels, central nervous system stimulants, cough and cold preparations, decongestants, diagnostic tools, hormones such as parathyroid hormone, growth hormone and insulin, hypnotics, immunosuppressive drugs, muscle relaxants, parasympatholytic drugs, parasympathomimetic drugs, antioxidants, nicotine, prostaglandins, psychostimulants, sedatives, tranquilizers, cosmetic and therapeutic cosmetics, skin antioxidants, carotenoids, ascorbic acid (vitamin C) and vitamin E, vitamin preparations, antioxidants, anti-aging agents wrinkles, retinoids, retinol (vitamin A alcohol), alpha hydroxy acids, beta hydroxy acids, salicylic acid, complex hydroxy acids, polyoxy acids and hydrolyzed and soluble collagen, moisturize s agent, hyaluronic acid, anti-cellulite agents, aminophylline, agents for skin whitening, retinoic acid, hydroquinone, peroxides, herbal preparations, extracts of aloe vera, wild potato gamamelitanin, ginseng, hamamelis and green tea. 30. The kit according to claim 9, in which said electric current is direct current. 31. The kit according to claim 9, in which the aforementioned circuit includes at least one on-off switch, a timer, constant or variable resistance, a field effect transistor, an integrated circuit for controlling the dosage of the active agent introduced and a controller. 32. A method of using a cutaneous applicator containing at least one power source to power the applicator and at least two electrodes electrically connected to the power source, and a storage chamber for the substance and to prevent contact between at least one of two electrodes and a skin area, the method consisting in the fact that: (a) positioning said cutaneous applicator so as to electrically connect the electrodes to a portion of the patient’s skin, and (b) passing an electric current to a portion of the skin of the patient. 33. The method of claim 32, further comprising administering at least one substance to a portion of a patient’s skin, wherein said at least one substance is contained in said electrically conductive fluid. 34. The method of claim 33, wherein said at least one substance is administered transdermally or intradermally. 35. A cutaneous applicator comprising at least one power source for powering the applicator and at least two electrodes electrically connected to a power source, said electrodes being used to electrically connect to a patient’s skin area, and a substance storage chamber, and to prevent contact between at least one of the at least two electrodes and the skin area. 36. The applicator according to clause 35, designed to supply current and / or voltage to the patient’s skin area. 37. The applicator according to clause 35, intended for the introduction of at least one substance into the skin area of the patient by at least one skin, transdermal and intradermal injection, or a combination thereof. 38. The applicator according to clause 35, in which the said applicator is made thin and elastic. 39. The applicator according to clause 35, in which said at least two electrodes are made as an integral part of said power source. 40. The applicator according to clause 35, in which the applicator further comprises an applicator shell, and in which said power source and at least two electrodes are located on the applicator shell at a distance from each other with the formation of a gap between the said at least two electrodes. 41. The applicator according to clause 35, in which the applicator further comprises a mounting device for attaching to the patient’s skin area. 42. The applicator according to clause 35, in which the applicator further comprises a circuit for regulating electric current. 43. The applicator according to clause 35, in which said power source is an elastic thin-layer electrochemical cell. 44. The applicator according to item 43, in which the said elastic thin-layer electrochemical cell is an elastic thin-walled open liquid electrochemical cell that contains a first layer constituting an insoluble negative pole, a second layer constituting an insoluble positive pole, and a third layer of aqueous electrolyte, the third layer is located between the first and second layers and contains: (a) moisture-absorbing material for continuous maintenance open element in a liquid state, (c) electroactive soluble material to provide the necessary ionic conductivity, and (c) a water soluble polymer to provide the viscosity necessary for adhesion of the first and second layers with the third layer. 45. The applicator according to clause 35, packaged and labeled as intended for use with a purpose selected from the group consisting of wound healing, skin repair, skin regeneration, muscle stimulation, muscle contraction, accelerate bone healing, suppress inflammatory processes, facilitate and accelerate metabolic processes, pain relief, treatment of rosacea and telangiectasia. 46. The applicator of claim 35, further comprising an electrically conductive fluid. 47. The applicator according to item 46, in which the aforementioned conductive fluid further comprises at least one substance, and in which the conductive fluid is pre-applied to the aforementioned at least two electrodes, and the applicator in contact with the skin provides passage electric current through the electrically conductive fluid and the patient’s skin for transdermal or intradermal administration of at least one substance. 48. The applicator according to item 46, in which the aforementioned conductive fluid is a hydrogel. 49. The applicator according to clause 47, in which at least one substance is selected from the group consisting of pharmaceutical, cosmetic, therapeutic and cosmetic substances and moisturizers. 50. The applicator of claim 47, wherein said at least one substance is at least one antibiotic. 51. The applicator according to clause 35, in which the substance is at least one of the following: anti-infective agents, antibiotics and antiviral drugs, analgesics, fentanyl, sufentanil, buprenorphine, painkillers, pain relievers, reduce appetite, anti-arthritis and anti-asthma drugs, terbutaline, anticonvulsants, antidepressants, antidiabetic agents, antidiarrheal, antihistamines, anti-inflammatory drugs, headache medications, anti-contraceptives, scop amine, ondansetron, antiemetics, antitumor drugs, drugs for tremor palsy, pacemakers, dobutamine, antipruritic drugs, antipsychotics, antipyretic drugs, antispasmodics, gastrointestinal and genitourinary drugs, anticholinergics, sympathy antagonists, cardiovascular drugs, calcium channel blockers, nifedipine, beta blockers, beta agonists, salbutamol, and ritodrin, antiarrhythmic drugs, antihypertensives, atenolol, angiotensin-1-converting enzyme (ACE) inhibitors, diuretics, vasodilators common to the coronary, peripheral and cerebral vessels, central nervous system stimulants, cough and cold preparations, decongestants, diagnostic tools , hormones such as parathyroid hormone, growth hormone and insulin, hypnotics, immunosuppressive drugs, muscle relaxants, parasympatolytic drugs, parasympathomimetic drugs, an thioxidants, nicotine, prostaglandins, psychostimulants, sedatives and tranquilizers, cosmetic and therapeutic cosmetics, skin antioxidants, carotenoids, ascorbic acid (vitamin C) and vitamin E, vitamin preparations, antioxidants, anti-wrinkle agents, retinoids , retinol (vitamin A alcohol), alpha hydroxy acids, beta hydroxy acids, salicylic acid, complex hydroxy acids, polyoxy acids and hydrolyzed and soluble collagen, moisturizers, hydrants luronovaya acid, anti-cellulite agents, aminophylline, agents for skin whitening, retinoic acid, hydroquinone, peroxides, herbal preparations, extracts of aloe vera, wild potato gamamelitanin, ginseng, hamamelis and green tea. 52. A thin elastic skin applicator comprising: at least one negative electrode and at least one positive electrode for electrically connecting to a patient’s skin area, a thin elastic power source electrically connected to at least one negative electrode and at least one positive electrode, wherein said thin elastic power source is capable of driving the applicator, and a thin chamber containing an electrically conductive fluid / composition in which the thin chamber is located at least on one of the at least negative electrode and at least one positive electrode. 53. The applicator according to paragraph 52, in which said at least one negative electrode, said at least one positive electrode and said thin elastic power source are located on the applicator shell at a distance from each other to prevent contact between each from the electrodes. 54. The applicator of claim 52, wherein said at least one negative electrode and said at least one positive electrode are applied to the applicator shell. using printing technology. 55. The applicator according to paragraph 52, placed in the package insert. 56. The applicator according to paragraph 52, in which the electrically conductive fluid / composition contains at least one active substance. 57. The applicator according to item 56, in which the active substance is selected from the group consisting of pharmaceutical, cosmetic, therapeutic and cosmetic substances, moisturizers and their combination. 58. The applicator according to paragraph 52, designed to ensure the introduction of the active substance into the skin area of the patient. 59. The applicator according to paragraph 52, designed to supply electric current / voltage to the skin area of the patient. 60. The applicator according to paragraph 52, in which at least one electrode is a treatment electrode and at least another electrode is an electrically conductive adhesive electrode. 61. The applicator of claim 56, wherein said conductive fluid / composition is applied to said treatment electrode. 62. The applicator according to paragraph 52, in which the aforementioned power source contains a thin elastic electrochemical cell, and in which the thin elastic electrochemical cell is a thin elastic open liquid electrochemical cell, which contains a first layer constituting an insoluble negative pole, a second layer constituting insoluble a positive pole and a third layer of aqueous electrolyte, wherein said third layer is located between said first and second layers and contains: moisture-absorbing material for constant maintenance of an open element in a liquid state, electroactive soluble material to provide the necessary ionic conductivity, a water-soluble polymer to provide the viscosity necessary to adhere said first and second layers to said third layer. 63. The applicator of claim 56, wherein said at least one substance is at least one antibiotic. 64. The applicator according to item 56, in which at least one substance contains salicylic acid. 65. Kit for supplying electric current and / or tension to the area of the skin and / or percutaneous or intradermal introducing substances containing (a) a thin elastic skin applicator comprising a power source and at least two electrodes electrically connected to a power source, said electrodes being designed to electrically connect to a portion of a patient’s skin, and (b) at least one chamber for storing an electrically conductive fluid, wherein said electrically conductive fluid is intended to be attached to at least one of said at least two electrodes and / or to be applied locally to a patient’s skin area , wherein said applicator is designed and configured to conduct electric current through the skin and said electrically conductive fluid, said electric current being used to supply current and / or voltage to said skin region and / or for transdermal or intradermal administration of at least one substance . 66. The kit according to item 65, in which at least one substance contains an analgesic. 67. The kit according to item 65, in which at least one substance contains an anesthetic. 68. The kit according to item 65, in which at least one substance contains hormones. 69. The kit according to item 65, in which at least one substance contains muscle relaxants. 70. The kit according to item 65, in which at least one substance contains an agent that prevents the formation of wrinkles. 71. The kit according to item 65, in which at least one substance contains a moisturizer. 72. The kit according to item 65, in which at least one substance contains an anti-cellulite agent. 73. The kit according to item 65, in which at least one substance contains a means for whitening the skin. 74. The kit according to item 65, in which at least one substance contains an antibiotic. 75. The kit according to item 65, in which at least one substance contains an anti-infective agent. 76. The kit according to item 65, which is used for wound healing. 77. The kit according to item 65, which is used to reduce inflammation. 78. The kit according to item 65, which is used to reduce pain. 79. The kit according to item 65, in which at least one substance contains salicylic acid. 80. A thin elastic skin applicator comprising at least one thin elastic power source for supplying the applicator and at least one positive electrode and one negative electrode are electrically connected to a power source, said electrodes being intended for electrical connection with area of the patient’s skin. 81. The applicator according to claim 80, which is used to isolate substances from the body. 82. The applicator according to claim 80, which is used for wound healing. 83. The applicator according to claim 80, which is used to reduce inflammation. 84. The applicator according to claim 80, which is used to reduce pain. 85. A thin elastic skin applicator comprising at least one power source for powering the applicator and at least two electrodes electrically connected to a power source, said electrodes being designed to electrically connect to a portion of a patient’s skin, in which at least one of the at least two electrodes is made as an integral part of said power source.

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