阅读说明：本技术 增加通过使用者的皮肤的药物和药妆品的吸收的方法和装置 (Method and device for increasing the absorption of drugs and cosmeceuticals through the skin of a user ) 是由 斯科特·N·谢夫特尔 杰弗里·B·斯基巴 于 2019-06-07 设计创作，主要内容包括：本发明提供一种用于增加通过动物或人的皮肤的物质的吸收的装置,该装置包括：织物或基底；作为特定图案中的多条线或点放置在织物或基底表面的至少一部分上或通过织物或基底表面的至少一部分暴露的金属颗粒,特定图案将金属颗粒离散地定位在相距一定距离的电隔离位置,其中,织物或基底被配置为使得所述金属颗粒接触人或动物的皮肤表面,其中多条间隔的线彼此基本上均匀地间隔开；以及适于容纳物质的层；其中所述织物或基底形成空气-金属电池的多个半电池,用于与人或动物的皮肤进行离子交换,于是,通过离子电渗疗法驱动位于装置和皮肤之间的物质。(The present invention provides a device for increasing the absorption of a substance through the skin of an animal or human, the device comprising: a fabric or substrate; metal particles placed on or exposed through at least a portion of the fabric or substrate surface as a plurality of lines or dots in a specific pattern, the specific pattern discretely locating the metal particles at electrically isolated locations at a distance, wherein the fabric or substrate is configured such that the metal particles contact a skin surface of a human or animal, wherein the plurality of spaced lines are substantially evenly spaced from each other; and a layer adapted to contain a substance; wherein the fabric or substrate forms a plurality of half-cells of an air-metal battery for ion exchange with human or animal skin, whereupon substances located between the device and the skin are driven by iontophoresis.)

1. A device for increasing the absorption of a substance through the skin of an animal or human, comprising in order:

a base layer;

a therapeutic substance bearing layer that holds a therapeutic substrate, the therapeutic substance bearing layer bearing on the substrate layer; and

a cover layer disposed on or exposed through at least a portion of the cover layer, the cover layer having metal particles disposed on or exposed through at least a portion of the cover layer in a plurality of lines or dots in a particular pattern that discretely locates metal particles at electrically isolated locations that are a distance apart or disposed in or on an adhesive coating on the cover layer in a plurality of lines or dots in a particular pattern that discretely locates metal particles at electrically isolated locations that are a distance apart, wherein the cover layer is configured such that the metal particles are at least partially exposed, wherein the metal particles on or supported by the adhesive coating on the cover layer form a plurality of half-cells of an air or oxygen-metal cell, for ion exchange with human or animal skin, so that the therapeutic substance can enter the skin by iontophoresis.

2. The device according to claim 1, wherein the pattern corresponds to a blood circulation pattern and/or a nerve or underlying muscle pattern of a human or animal.

3. The device according to claim 1, wherein the lines or dots are evenly spaced from each other at an interval of 0.1 to 3mm, preferably 0.2 to 2mm, more preferably 0.3 to 1.5mm, most preferably 0.5 to 1 mm.

4. The device according to claim 1, wherein the line or line has a dot width of 0.1mm to 5mm, preferably about 0.1 to 3mm, more preferably 0.2 to 2mm, even more preferably 0.3 to 1mm, most preferably 0.4 to 0.5 mm.

5. The device of claim 1, wherein the pattern covers about 10% to 90%, preferably about 15% to about 75%, more preferably about 25% to about 50%, most preferably about 30% to about 40% of the surface of the cover layer.

6. The device of claim 1, wherein the metal particles comprise a metal, metal oxide or metal salt, wherein the metal particles are preferably selected from the group consisting of elemental zinc particles, zinc oxide particles and zinc salt particles or elemental aluminum, iron, copper or magnesium particles, aluminum, iron, copper or magnesium oxide particles, or aluminum, iron, copper or magnesium salt particles.

7. The device of claim 1, further comprising an adhesive pad or adhesive tab adapted to secure the substrate layer.

8. A method for increasing the absorption of a substance through the skin of a human or animal comprising:

providing a device according to claim 1, wherein the substance is retained by a gauze layer; and

the device is placed in contact with the skin of a person or animal, wherein the metal particles on the cover layer or adhesive coating together with the skin of the person or animal form a plurality of half cells of an air or oxygen-metal battery, whereupon the metal particles form a first half cell of a battery circuit and the body of the person or animal together with the oxygen forms a second half cell of the battery circuit, whereupon the substance is driven into the skin of the person or animal by iontophoresis.

9. The method according to claim 8, wherein the pattern corresponds to a blood circulation pattern and/or a nerve or underlying muscle pattern of a human or animal.

10. The method according to claim 8, wherein the lines or dots are evenly spaced at intervals of 0.1 to 3mm, preferably 0.2 to 2mm, more preferably 0.3 to 1.5mm, most preferably 0.5 to 1 mm.

11. The method according to claim 8, wherein the line or line has a dot width of 0.1mm to 5mm, preferably about 0.1 to 3mm, more preferably 0.2 to 2mm, even more preferably 0.3 to 1mm, most preferably 0.4 to 0.5 mm.

12. The method of claim 8, wherein the pattern covers from about 10% to 90%, preferably from about 15% to about 75%, more preferably from about 25% to about 50%, most preferably from about 30% to about 40% of the surface of the cover layer.

13. The method of claim 8, wherein the metal particles comprise a metal, metal oxide or metal salt, preferably wherein the metal particles are selected from the group consisting of elemental zinc particles, zinc oxide particles, and zinc salt particles or elemental aluminum, iron, copper, or magnesium particles, aluminum, iron, copper, or magnesium oxide particles, or aluminum, iron, copper, or magnesium salt particles.

14. The method of claim 8, further comprising securing the device to the skin of the animal or human using an adhesive.

Technical Field

The present invention relates to a method and device for increasing the absorption of a substance through the skin of a user. The invention has particular utility in increasing the absorption of drugs through the skin and will be described in connection with such utility, but other utilities, such as increasing the rate or depth of absorption of other substances including, for example, cosmeceuticals, are also contemplated.

Background

Skin includes epidermis, dermis and subcutaneous adipose tissue. When a drug is applied to the skin, the epidermis, the upper layer of the skin, often treats the drug as a foreign body and hinders absorption of the drug. As a result, the amount of drug actually absorbed into the skin is very small due to the influence of molecular size, biological properties, biochemical phenomena, and the like.

To overcome this problem, iontophoresis has been developed to increase the absorption of drugs through the skin. Iontophoresis involves generating a minute electric current to flow through the skin, thereby effectively increasing the absorption of components contained in a drug having an electrical affinity with the skin by an electrical repulsive force. For example, iontophoresis may be used to absorb vitamin C into the skin as an antioxidant and cofactor in skin growth, thereby providing cell stimulation and antioxidant protection. Topical vitamin C is used for skin health and wrinkle improvement. Other uses of iontophoresis may range from drug delivery (e.g., prescription drugs) to local administration without systemic side effects.

Current iontophoresis devices induce an electric field on and around the skin by attaching a patch to the skin and allowing a micro-current to flow from the patch into the skin. However, current iontophoresis devices require a power source, e.g., a battery or connection to a power source, wires, circuitry, etc., which are expensive and bulky and inconvenient to use, thereby reducing patient compliance. Thus, there is a need for a self-contained, low cost method and device for delivering drugs for absorption through the skin. In addition to iontophoresis of the skin, directed microcurrents can stimulate the skin, enhance blood flow and tissue oxygenation, and enhance cellular responses by increasing protein synthesis, amino acid transport, and increasing ATP (mitochondrial energy) synthesis. The net effect is local collagen stimulation, which can solve wrinkles, skin tone and skin health.

In our previous us patent nos. 9,192,761 and 9,707,172, we describe methods and devices for treating hyperhidrosis and other conditions (e.g. neuropathic pain, peripheral arterial disease and neuropathy); for surgical rehabilitation and surgical recovery, including joint surgical rehabilitation and soft tissue healing; and for physical therapy including muscle and tendon healing and stroke rehabilitation by applying it to the skin surface of a patient in need of said treatment, the device comprising a fabric containing elemental zinc particles, the fabric being arranged such that the fabric forms half-cells of an air zinc cell, thereby producing ion exchange with the skin of the patient. As described in our above patents, the action of elemental or zinc salt particles on the skin will lead to side reactions, forming zinc complexes that are beneficial to the host (host). The ability to deliver topical zinc to the skin surface can produce beneficial effects as long as the topical zinc is in the correct elemental form, availability and configuration.

The unique therapeutic value of zinc, zinc oxide and zinc salts in cosmetic and pharmaceutical ointments and creams, i.e. for the treatment of a variety of skin disorders, is well documented in the art. Also, as reported in our co-pending U.S. application serial No. 15/823,076, many of the same benefits of zinc containing creams or ointments applied directly to the skin can be obtained by contacting the fabric with elemental zinc particles printed thereon with the skin of a patient, i.e., as described in our above-mentioned '761 and' 172 patents.

Disclosure of Invention

We have now found that metal particle loaded fabrics such as those described in our above ' 761 and ' 172 patents and in our above ' 076 co-pending application can be advantageously used as half cells in oxidation/reduction reactions in contact with the skin to generate an electrical current which, when introduced into the skin, alters the permeability of the skin membrane to make it easier for substances such as drugs to enter the skin. That is, the electric field generated by the contact of the metal particle loaded fiber with the skin provides the direction of the electric field, i.e., negative in the ionic fabric and positive in the tissue. As a result, similar to iontophoresis, substances on the fabric or skin can be absorbed onto the skin by electrical repulsive forces, i.e., negative to positive attraction, towards positive attraction to the patient's tissue. The present invention therefore essentially provides a self-contained, external battery-less iontophoresis device for driving substances, such as drugs, into the skin of a wearer.

One aspect of the invention provides a device for increasing the absorption of a substance through the skin of an animal or human, the device comprising: a fabric or substrate; metal particles placed on or exposed through at least a portion of the fabric or substrate surface as a plurality of lines or dots in a specific pattern that discretely positions the metal particles in electrically isolated locations at a distance, wherein the fabric or substrate is configured such that the metal particles contact the skin surface of a human or animal, wherein the plurality of spaced lines are substantially evenly spaced from each other; and a layer adapted to contain a substance; wherein the fabric or substrate forms a plurality of half-cells of an air-metal battery for ion exchange with human or animal skin, followed by iontophoresis of a substance located between the device and the skin of the animal or human into the skin.

In one aspect, these patterns conform to blood circulation patterns and/or nerve or underlying muscle patterns of a human or animal.

In another aspect, the lines or dots are evenly spaced at intervals of 0.1 to 3mm, preferably 0.2 to 2mm, more preferably 0.3 to 1.5mm, most preferably 0.5 to 1 mm.

In a further aspect, the line or line has a dot width of 0.1mm to 5mm, preferably about 0.1 to 3mm, more preferably 0.2 to 2mm, even more preferably 0.3 to 1mm, most preferably 0.4 to 0.5 mm.

In another aspect, the pattern covers from about 10% to 90%, preferably from about 15% to about 75%, more preferably from about 25% to about 50%, and most preferably from about 30% to about 40% of the surface of the fabric or substrate.

In a preferred aspect, the metal particles comprise metals, metal oxides or metal salts, preferably elemental zinc particles, zinc oxide particles and zinc salt particles, or aluminium, iron, copper and magnesium and oxides or salts thereof.

In yet another aspect, the device comprises an adhesive or adhesive tab (tab) adapted to secure the device to the skin of an animal or human. In the case of a device which is fixed to the skin by means of an adhesive, the metal particles can be incorporated directly into the adhesive.

The invention also provides a method for increasing the absorption of a substance through the skin of a human or animal, the method comprising placing a substrate in the vicinity of the skin of the human or animal; and on the skin of a human or animal placed over the substrate, a device comprising: a fabric or substrate; metal particles arranged in the form of a plurality of lines or dots in a specific pattern on at least a part of the surface of a fabric or substrate, which specific pattern discretely positions the metal particles in electrically isolated positions at a distance, wherein the fabric or substrate is configured such that the metal particles contact the skin surface of a human or animal, wherein the plurality of isolated lines are substantially evenly spaced from each other, wherein the fabric or substrate forms a plurality of half-cells of an air-metal cell which alters the permeability of the skin membrane and drives the substance into the skin.

In one aspect of the method, the patterns conform to a blood circulation pattern and/or a neural or underlying muscle pattern of the human or animal.

In another aspect of the method, the lines or dots are evenly spaced at intervals of 0.1 to 3mm, preferably 0.2 to 2mm, more preferably 0.3 to 1.5mm, most preferably 0.5 to 1 mm.

In a further aspect of the method, the line or line has a dot width of 0.1mm to 5mm, preferably about 0.1 to 3mm, more preferably 0.2 to 2mm, even more preferably 0.3 to 1mm, most preferably 0.4 to 0.5 mm.

In yet another aspect of the method, the pattern covers from about 10% to 90%, preferably from about 15% to about 75%, more preferably from about 25% to about 50%, and most preferably from about 30% to about 40% of the surface of the fabric or substrate.

In a preferred aspect of the method, the metal particles comprise metals, metal oxides or metal salts, preferably elemental zinc particles, zinc oxide particles and zinc salt particles, or aluminum, iron, copper and magnesium, and oxides or salts thereof.

In yet another aspect of the method, the device is secured to the skin of the animal or human using an adhesive or adhesive tabs. In the case of using an adhesive to secure the device to the skin, the metal particles may be incorporated directly into the adhesive.

The present invention also provides a method of increasing the absorption of a substance through the skin of a human or animal comprising: contacting the substance with human or animal skin; and covering the substance with a fabric device comprising: a fabric or substrate; metal particles arranged in the form of a plurality of lines or dots in a specific pattern on at least a part of the surface of a fabric or substrate, which specific pattern discretely positions the metal particles in electrically isolated positions at a distance, wherein the fabric or substrate is configured such that the metal particles contact the skin surface of a human or animal, wherein the plurality of spaced lines are substantially evenly spaced from each other, wherein the fabric or substrate and the skin of the human or animal form a plurality of half-cells of an air-metal cell, whereupon the metal particles in the fabric form a first half-cell of a battery circuit, while in the body of the human or animal a second half-cell of the battery circuit is formed with oxygen in the body, whereupon the substance enters the skin of the human or animal by iontophoresis.

In one aspect of the latter method, the pattern corresponds to a blood circulation pattern and/or a nerve or underlying muscle pattern of the human or animal. Alternatively, these patterns may also conform to asian medically defined meridians and meridian foci.

In another aspect of the latter method, the lines or dots are evenly spaced at intervals of 0.1 to 3mm, preferably 0.2 to 2mm, more preferably 0.3 to 1.5mm, most preferably 0.5 to 1 mm.

In a further aspect of the latter method, the line or line has a dot width of from 0.1mm to 5mm, preferably from about 0.1 to 3mm, more preferably from 0.2 to 2mm, even more preferably from 0.3 to 1mm, most preferably from 0.4 to 0.5 mm.

In yet another aspect of the latter method, the pattern covers from about 10% to 90%, preferably from about 15% to about 75%, more preferably from about 25% to about 50%, most preferably from about 30% to about 40% of the surface of the fabric or substrate.

In a preferred aspect of the latter method, the metal particles comprise metals, metal oxides or metal salts, preferably elemental zinc particles, zinc oxide particles and zinc salt particles, or aluminum, iron, copper and magnesium, and oxides or salts thereof.

In yet another aspect of the latter method, an adhesive or adhesive tab is used that is adapted to secure the device to the skin of an animal or human.

Drawings

Other features and advantages of the present invention will become apparent from the following detailed description taken in conjunction with the accompanying drawings, in which

FIG. 1 is a top plan view, partially in cross-section, of a self-contained iontophoresis pad according to the present invention;

FIG. 2 is a flow chart schematically illustrating a process for forming a self-contained iontophoresis pad in accordance with the present invention; and

fig. 2A is an enlarged view of an intermediate product formed by the process of fig. 2.

Detailed Description

In the following description, the term "metal particles" may include elemental metal particles of metals capable of forming metal-air electrochemical cells, as well as oxides and salts thereof. Zinc metal particles and their oxides and salts are preferred, although other metals and oxides including aluminum, iron, copper or magnesium and their salts may be used.

Although synthetic fibres are preferred, particularly fibres formed from thermoplastic or thermosetting plastics materials and/or fibres coated with a binder, the term "fibres" may include natural and synthetic fibres, filaments and threads.

Referring to fig. 1, a self-contained, battery-less iontophoresis device or apparatus 10 according to the present invention takes the form of a patch (patch) including a flexible substrate 12, a sandwich (sandwich) of a drug carrier such as gauze 14 and a cover 16, the flexible substrate 12 being formed of a sheet material such as an air-permeable or air-impermeable textile or fabric which may include an adhesive coated textile or fabric, the cover 16 being formed of a second sheet carrying a plurality of spaced apart lines or dots of metal particles, for example as described in our aforementioned ' 761 and ' 172 patents, or in our ' 076 co-pending application. Preferably, the metal particles are zinc particles and have an average particle size of between 1 and 100 nanometers, more preferably between 1 and 10 microns, even more preferably about 5 microns. As taught in our above-mentioned patents and pending applications, the metal particles can be printed on the substrate 16 or extruded or melt spun as the fibers are formed. Polyethylene is the material of choice for forming fibers that release zinc ions. The amount of zinc used and the surface area of the zinc or other metal used is a function of the particle size and the availability to manufacture the cell. The total amount of zinc per unit volume will determine the capacity of the cell. When the zinc is depleted, the battery will also be depleted unless charging continues, for example due to ions present in the skin.

Preferably, but not necessarily, the fabric 16 comprises a woven fabric, although the fabric 16 may be a nonwoven fabric, a web of fibers, a non-fibrous web, which may comprise a textile or fabric, a web, or the like, coated with an adhesive.

Preferably, but not necessarily, the opposite end of the device 10 may include an adhesive or adhesive tab, shown in phantom at 20, so that the iontophoresis device may be secured to the user's skin. Alternatively, the iontophoresis device 10 may be held in place by a wrap or the like.

As taught in our aforementioned ' 761 and ' 172 patents, or as described in our ' 076 co-pending application, and as shown in fig. 1, the metal particles are discontinuously and substantially uniformly distributed on the surface of the fabric 16 in imaginary lines of spaced lines or points, at least partially across the surface area of the fabric 16. Typically, the lines or dots of lines are evenly spaced at intervals of 0.1 to 3mm, preferably 0.2 to 2mm, more preferably 0.3 to 1.5mm, most preferably 0.5 to 1.0 mm. The concentration of metal, such as zinc, in the binder or extruded fibers forming the lines or dots determines the amount of metal available for the "battery". The preferred concentration is 30% of the fabric surface area; however, the concentration of zinc may range from about 1% to about 99%. The mixture of binder and zinc metal can be made into a paste and applied by screen printing, for example, as described in our aforementioned '761 and' 172 patents. For this purpose, 30% by weight of zinc binder is preferred. The width and length of the line or dot also determines the amount of metal in the deposit, as the wider and longer the line, the more metal is available. The preferred dot width is 1mm wide, but the width may vary from 0.1mm to 5mm wide. The amount of binder/metal may also vary, as the deposit is deposited on the fabric or carried in the binder. In certain embodiments, the coated fabric may be coated two or more times in the same pattern, thereby increasing the thickness of the deposit as desired. In certain embodiments, the pattern of metal deposition areas covers from about 10% to about 90% of the surface area of the fabric. In other embodiments, the metal deposition area covers from about 20% to about 80%, from about 15% to about 75%, from about 25% to about 50%, or from about 30% to about 40% of the surface area of the fabric or anywhere therebetween. Although fig. 1 shows a plurality of metal deposition areas 18 substantially uniformly distributed over the surface of the fabric, in other embodiments, the plurality of metal deposition areas may be randomly distributed over the surface of the fabric. Typically, the thickness of the wire is from 0.1 to 3mm, preferably from 0.2 to 2mm, more preferably from 0.3 to 1.0, most preferably from 0.4 to 0.5 mm. The spaced lines may be continuous and may take various forms including straight, curved and various angled shapes as shown, such as straight continuous lines; straight line breakage; continuous sawing; a continuous wavy line; broken wavy lines, etc., as described in our above-referenced ' 761 and ' 172 patents and our ' 076 pending application. The actual shape of the wire is not important. Preferably, but not necessarily, the wires are approximately equal in thickness and are evenly spaced.

Referring to fig. 2 and 2A, a self-contained external batteryless iontophoresis device according to the present invention was formed in accordance with the teachings of our above-mentioned' 076 application, as follows: metal particles, in particular elemental zinc particles, which have been preformed by grinding or precipitation from suspension and have an average particle size of 1 to 100 nanometers, more preferably 1-10 microns, even more preferably about 5 microns, are mixed with a thermoplastic material, such as polyethylene, in a heated mixing barrel 30 to melt the material, and the mixture is extruded or melt spun at a spinning station 32 to form fibers 34, which contain metal particles 36. Polyethylene is the polymer of choice for releasing electrons from metals. The porosity of the fibers is also believed to play a role. Polypropylene or polyester fibers may also be used, but the result is slower ion release. The metal-containing fibers may then be cabled or twisted at a cabling station 38 and woven into a sheet or cloth at a weaving or knitting station 40. The resulting sheet or cloth impregnated with metal particles is cut to size at a cutting station 42, assembled with the gauze pad impregnated with the drug and the substrate 12 as previously described at an assembly station 44, and the assembled packaging is laminated together to form a self-contained, battery-less iontophoresis device at a lamination station 46. Lamination may be performed by applying glue to the border of the substrate 12 and the metal containing fabric 16 or by melting the edges of the fused assembly.

Thus, a self-contained external batteryless iontophoresis device is provided.

Various changes may be made to the invention described above without departing from the spirit and scope of the invention. For example, the amount of zinc in the fabric or adhesive coating can be increased or decreased to alter the cell capacity. Adding too much zinc to the fiber may weaken the fiber, so we can use a bicomponent concept where only the outer layer has zinc and the inner core is polyester or other stronger polymer. By this method we can treat the fibres differently from polyethylene fibres where only zinc is added.