CN117794521A

CN117794521A - Patch for topical use

Info

Publication number: CN117794521A
Application number: CN202280037377.7A
Authority: CN
Inventors: 凯瑟琳·莎查夫
Original assignee: Olangxun Co
Current assignee: Olangxun Co
Priority date: 2021-03-23
Filing date: 2022-03-23
Publication date: 2024-03-29
Also published as: KR20240011668A; EP4313006A1; CA3212391A1; WO2022204234A1

Abstract

The present invention relates to an apparatus and method. The device of the invention comprises a patch comprising: a substrate and an adhesive on the substrate. In addition, the patch is configured to be attached to the skin by an adhesive to form a pocket between the patch and the skin, thereby allowing material to be introduced into the pocket and to be retained within the pocket.

Description

Patch for topical use

RELATED APPLICATIONS

The present application claims priority from U.S. provisional patent application No.63/164,618 entitled "Patch for topical use," filed 3/23 of 2021, the entire contents of which are incorporated herein by reference.

Technical Field

The present invention relates to a device comprising a patch, a method of manufacturing the device and a method of applying the device to skin and providing material to the skin through the patch without damaging the skin surface.

Background

Bandages or patches in medical terms are intended to mean bandaging wounds orA woven material strip for protecting the injured part of the body. Bandages for wounds or burns are generally composed of a sterile absorbent dressing held in place by separate fasteners (e.g., tape, adhesive, compression fabric or tie) ^[1] . These patches typically allow the use of substances, chemicals, compounds, imaging agents or drugs on the skin. Other prior art bandages may be made of air or liquid impermeable materials, however, such bandages are configured to only partially shield the wound to allow air to enter the wound area to provide circulation. Thus, while the bandage material is impermeable to air or liquid, the bandage can breathe when placed over a wound ^[2] 。

WO2016176514 discloses "a bandage comprising a sterile dressing and a conditioning medium applied to the sterile dressing, wherein the conditioning medium is contained in nanocapsules, wherein the nanocapsules are applied to the sterile dressing as an aqueous suspension and air-dried. The method further comprises adding a liquid to the bandage.

US005109874a discloses "a dynamic wound patch having a gas and liquid impermeable member adhesively sealed to the skin surrounding the wound, a temporary barrier formed over the wound to prevent the ingress or egress of gas and liquid through the wound patch, thereby allowing the user to perform physical activities without fear of contaminants entering or exiting the wound area, and a method of creating an in situ non-stick island on the wound patch.

US4776331a discloses "a bandage useful in medical applications comprising a rupturable sheet or strip having an encapsulated fluid (liquid or gas). The sheet or strip is arranged between the body part to be bandaged and the outer surface of the bandage. When the predetermined pressure is exceeded, the sheet or strip breaks, releasing the fluid to indicate that the bandage is too tight. When the fluid is a liquid (e.g., a dye), the released liquid will stain the bandage. When the substance is a gaseous substance, the release of gas will be sensed. When multiple strips are used, one strip may contain a liquid and another strip may contain a gaseous substance, wherein the strips may rupture at different predetermined pressures. In addition, annular decals or patches may be used for imaging.

The embodiment of WO200640773 discloses a "skin tissue inspection (DTI) device comprising a contact surface for close placement on a skin site, multispectral illumination means for illuminating skin tissue at least two different wavelengths through an aperture in the contact surface, digital imaging means for imaging dermis tissue at different imaging depths corresponding to the at least two different wavelengths relative to the surface of the skin site, capturing a digital image of the illuminated dermis tissue through an aperture; and a computing unit for processing the digital image to display information on a clinical display screen including clinical images of different imaging depths relative to the skin site surface. The DTI device is preferably used in combination with a self-adhesive annular sticker for encircling a skin patch at a skin site, which has machine readable identification information for identification purposes.

Nevertheless, the prior art does not disclose a patch that is capable of introducing a material after application of the patch, nor does it disclose a patch that allows for the application of an imaging agent after application of the patch.

The invention allows for the introduction of a material (e.g. a liquid) in a localized manner after application of the patch to the skin. In one embodiment, the activated material is used for imaging.

Disclosure of Invention

The present invention relates to a device comprising a patch having a substrate and an adhesive.

One embodiment relates to a patch that is attached to skin by an adhesive to form a pocket between the patch and the skin. This allows for the introduction of material into the pocket and the retention of material within the pocket.

In an embodiment, the device further comprises a release liner and/or an opening.

In another embodiment, a release liner is positioned under the patch and attached to the patch by an adhesive to form a pocket between the patch and the release liner.

In an embodiment, the opening in the device further comprises a tab.

In one embodiment, the tab is identical to the substrate.

In one embodiment, the tab is different from the base.

In one embodiment, the fins comprise a mesh structure to maintain the surface tension of the liquid.

In one embodiment, the substrate comprises an impermeable material and/or a permeable membrane.

In one embodiment, the substrate and the adhesive are biocompatible and/or compatible with the permeation enhancer.

In one embodiment, the permeation enhancer comprises sulfoxides, azones, pyrrolidones, alcohols and alkanols, glycols, surfactants and/or terpenes or combinations thereof.

In one embodiment, the substrate and the binder are compatible with DMSO.

In one embodiment, the substrate is flexible.

In one embodiment, the material in the pocket includes conditioning fluid, molecular dye, label, nanoparticle, radionuclide, and/or combinations thereof.

In one embodiment, the material in the pocket is configured to be activated and react with the skin under certain conditions.

In one embodiment, the certain conditions include radiation, heating, mixing with the second material, and/or combinations thereof.

In an embodiment, the patch is placed on the unbroken skin surface and/or the broken skin surface.

In an embodiment, the device is configured for imaging purposes or topical administration or a combination thereof.

In one embodiment, the device further comprises a release liner, wherein the release liner is positioned under the patch and attached to the patch by an adhesive to form a pocket between the patch and the release liner.

In one embodiment, the pocket includes a space or pattern.

In one embodiment, the opening comprises a protrusion or tubular structure.

In one embodiment, the protrusion or tubular structure includes a clamp configured to open or close the opening.

In one embodiment, the invention relates to a method comprising:

a. securing a patch of the device to the skin to form a pocket between the skin and the patch;

b. introducing a material into the pocket;

and is also provided with

c. The material is allowed to react with the skin,

wherein the patch comprises a substrate, an adhesive, and an opening in the substrate;

wherein the material in the pocket is activated.

In an embodiment, the material is activated under conditions including radiation, heat, mixing with a second material, and/or combinations thereof.

In an embodiment, the material in the pocket is configured to allow skin material to enter the patch from the skin surface.

In one embodiment, the permeation enhancer comprises a chemical substance configured to activate the material to allow the material to permeate under the skin of the user and react with portions of the biomolecules present under the skin of the user.

In one embodiment, an apparatus includes a patch comprising:

(i) The substrate is provided with a plurality of holes,

(ii) An adhesive on the substrate and a method of forming the same,

(iii) Molecular tags for monitoring physiological conditions of a user wearing a patch, and

(iv) A permeation enhancer comprising a chemical substance configured to activate a material to allow the material to permeate under the skin of a user and react with a portion of a biomolecule present under the skin of the user;

wherein the patch is configured to:

(a) Is attached to the skin by an adhesive to form a pocket between the patch and the skin,

(b) Allowing the introduction of material into the pocket, and

(c) The material is secured within the pocket.

In an embodiment, the patch is configured to activate the material under certain conditions.

In an embodiment, the patch is configured to allow skin material to enter the patch from the skin.

In one embodiment, an imaging system includes:

a patch comprising (i) a substrate, (ii) an adhesive on the substrate, (iii) a molecular tag for monitoring a physiological condition of a user wearing the patch;

a dye; and

a molecular tag;

wherein the patch is configured to:

(b) Allowing the introduction of material into the pocket, and

(c) The material is held within the pocket.

In one embodiment, in the imaging system, the material comprises a skin conditioning fluid.

In one embodiment, the dye comprises a fluorescent dye.

In one embodiment, the imaging system further comprises a fiducial point.

In one embodiment, the imaging system further comprises an imaging agent; wherein the imaging agent comprises radioiodine, a radioactive metal chelate, and a radioisotope.

In one embodiment, the material present within the patch is activated by heat.

In an embodiment, the device, wherein the conditions further comprise heating, mixing with a second material, or a combination thereof.

In an embodiment, the patch is configured to activate the material under conditions including radiation.

In one embodiment, activation by heat does not mean that micro-holes are created to open the passage to the reservoir.

In one embodiment, activating the material by heat does not mean forming holes in the reservoir.

In one embodiment, in the patch, the adhesive layer is not present under the closed reservoir of the patch.

In one embodiment, the adhesive layer surrounds the pocket.

In one embodiment, an apparatus includes a patch comprising:

(i) The substrate is provided with a plurality of holes,

(ii) An adhesive on the substrate and a method of forming the same,

wherein the patch is configured to:

(a) Is attached to the skin by an adhesive to form a pocket between the patch and the skin, wherein a layer of adhesive surrounds the pocket,

(b) The material is allowed to be introduced into the pocket,

(c) Hold the material in the pocket, and

wherein the patch includes an opening and a flap covering the opening.

In one embodiment, the device further comprises a release liner.

In one embodiment, a release liner is positioned under the patch and attached to the patch by an adhesive to form a pocket between the patch and the release liner.

In one embodiment, an apparatus includes a patch comprising:

(i) The substrate is provided with a plurality of holes,

(ii) An adhesive on the substrate and a method of forming the same,

Wherein the patch is configured to:

(b) The material is allowed to be introduced into the pocket,

(c) Hold the material in the pocket, and

(d) Activating the material under conditions including radiation;

wherein the patch includes an opening and a flap covering the opening.

In an embodiment, the conditions further comprise heating, mixing with a second material, or a combination thereof.

Drawings

The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the office upon request and payment of the necessary fee.

The drawings are provided together with the specification to understand the claimed invention and should not be construed as the only way to implement the claimed invention.

Fig. 1 shows an embodiment of a patch (100). The center is the opening (101) of the patch. The area outside the opening depicts the area in which introduced material (e.g., liquid) may be trapped in the pocket (102). Furthermore, the area outside the opening depicts the adhesive (103) and on its outside is the area of the patch remainder beyond the adhesive, called the tab (104). A release liner (105) is attached as a protective surface.

Fig. 2 shows a vertical section of an embodiment of the patch. The first column shows the release liner (105) and the two subsequent boxes show the adhesive (103). Between these boxes there is a pocket (102) which can be pre-filled or filled through an opening (101). The other column is then a patch, with an opening shown in the white box.

Fig. 3A shows an embodiment of the patch without a tubular structure connected to the patch opening.

Fig. 3B shows an embodiment of a patch having a tubular structure connected to a patch opening.

Fig. 4 shows an embodiment of the patch attached to the skin surface.

Fig. 5 shows the embodiment after application of the skin and removal of the patch.

Fig. 6 shows an embodiment of a fluorescence image of skin.

Detailed Description

Definition and general techniques

For simplicity and clarity of illustration, the drawing shows a general manner of construction. Descriptions and details of well-known features and techniques may be omitted to avoid unnecessarily obscuring the disclosure. Additionally, elements in the drawings figures are not necessarily drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help improve the understanding of the embodiments of the present disclosure. Like reference symbols in the various drawings indicate like elements.

The terms "first," "second," "third," "fourth" and the like in the description and in the claims, if any, are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances such that the embodiments described herein are capable of operation in sequences other than those illustrated or otherwise described herein. Furthermore, the terms "comprises," "comprising," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, apparatus or device that comprises a list of elements is not necessarily limited to those elements, but may include other elements not expressly listed or inherent to such process, method, system, article, apparatus or device.

The terms "left," "right," "front," "back," "top," "bottom," "over," "under," and the like in the description and in the claims, if any, are used for descriptive purposes and not necessarily for describing permanent relative positions. It is to be understood that the terms so used are interchangeable under appropriate circumstances such that the embodiments of the apparatus, methods, and/or article of manufacture described herein are capable of operation in other orientations than those illustrated or otherwise described herein.

No element, act, or instruction used herein should be construed as critical or essential unless explicitly described as such. Furthermore, as used herein, the articles "a" and "an" are intended to include the items and may be used interchangeably with "one or more". Furthermore, as used herein, the term "collection" is intended to include items (e.g., related items, unrelated items, combinations of related and unrelated items, etc.), and can be used interchangeably with "one or more. The term "a" or "an" or similar language is used if only one item is referred to. Furthermore, as used herein, the term "having" and the like are open-ended terms. Furthermore, unless explicitly stated otherwise, the phrase "based on" is intended to mean "based, at least in part, on".

The term "coupled" or the like should be construed broadly and refers to connecting two or more elements mechanically and/or otherwise. Two or more electrical components may be electrically coupled together, but not mechanically or otherwise coupled together. The coupling may last any length of time, such as permanent, semi-permanent, or transient only. "electrically coupled" and the like should be construed broadly and include all types of electrical coupling. The absence of words such as "removable" in the vicinity of words such as "coupled" and the like does not imply that the coupling or the like in question is either non-removable.

As defined herein, two or more elements are "unitary" if they are composed of the same piece of material. As defined herein, two or more elements are "non-unitary" if they are each composed of different pieces of material.

As defined herein, in some embodiments, "real-time" may be defined as performing an operation as quickly as practically possible upon occurrence of a triggering event. The trigger event may include receiving data needed to perform a task or otherwise process information. The term "real-time" encompasses operations that occur "near" real-time or slightly delayed from a triggering event due to delays inherent in transmission and/or computation speeds. In various embodiments, "real-time" may refer to subtracting a time delay for processing (e.g., determining) and/or transmitting data in real-time. The particular time delay may vary depending on the type and/or amount of data, the processing speed of the hardware, the transmission capabilities of the communication hardware, the transmission distance, etc. However, in many embodiments, the time delay may be less than about one second, two seconds, five seconds, or ten seconds.

The present invention may be embodied in other specific forms without departing from its spirit or characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.

As defined herein, "about" may mean within plus or minus ten percent of the value in some embodiments. In other embodiments, "about" may mean within plus or minus five percent of the value. In further embodiments, "about" may mean within plus or minus three percent of the value. In other embodiments, "about" may mean within plus or minus one percent of the stated value.

As defined herein, in some embodiments, "about" may mean within plus or minus five units of the value. In other embodiments, "about" may refer to within plus or minus three units of the value. In further embodiments, "about" may refer to within plus or minus two units of the value. In other embodiments, "about" may mean within plus or minus one unit of the value.

Unless defined otherwise herein, scientific and technical terms related to the present invention shall have the meanings commonly understood by one of ordinary skill in the art. Furthermore, unless the context requires otherwise, singular terms shall include the plural and plural terms shall include the singular. Generally, the terms and techniques used in connection with the health monitoring described herein are those well known and commonly used in the art.

Unless otherwise indicated, the methods and techniques of the present invention are generally performed according to conventional methods well known in the art and as described in various general and more specific references cited and discussed throughout the present specification. The terms, processes and techniques used in connection with the embodiments herein and other related fields described herein are those well known and commonly used in the art.

Reference throughout this specification to "various embodiments," "some embodiments," "one embodiment," or "an embodiment," etc., means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, appearances of the phrases "in various embodiments," "in some embodiments," "in one embodiment," or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment.

Furthermore, the features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Thus, a feature, structure, or characteristic shown or described in connection with one embodiment may be combined, in whole or in part, with features, structures, or characteristics of one or more other embodiments without limitation. Such modifications and variations are intended to be included within the scope of the present invention.

Unless otherwise indicated, the following terms and phrases should be understood to have the following meanings.

The term "apparatus" refers to physical hardware or devices or objects that are manufactured or adapted for a specific purpose.

In an embodiment, the device may be adapted for application to a skin surface of a patient and include a transdermal device to introduce a liquid into the patient's skin. In certain embodiments, such devices may include a reservoir containing a fluid drug and a release device for releasing the fluid drug from the reservoir through the transdermal device into the skin of the patient.

In one embodiment, the device may be a medical instrument. The medical device may be any instrument device, tool, machine, appliance, implant, reagent or other similar or related item intended by the manufacturer alone or in combination for medical purposes for use in vitro.

In an embodiment, the device may comprise a transcutaneous device unit and a reservoir unit, the transcutaneous device unit of the device comprising a transcutaneous device and a mounting surface for application to the skin of a patient. The reservoir unit includes a reservoir containing a fluid medicament and a release assembly for cooperating with the reservoir to release the fluid medicament from the reservoir through the transdermal device into the skin of the patient. The transcutaneous device unit and the reservoir unit may also be fixed to each other in use to allow fluid to flow between the reservoir and the transcutaneous device. The transcutaneous device unit and the reservoir unit comprise releasable coupling means allowing the reservoir unit to be secured to the transcutaneous device unit in use. Such a medical device comprising two units is also known as a medical system. Each of the transcutaneous device unit and the reservoir unit comprises a transcutaneous device and a housing, wherein the reservoir and the release assembly are arranged in the housing. The term "release assembly" includes a collection of components or structures that collectively allow release of a liquid from a reservoir. The expelling assembly may be, for example, a mechanical pump (e.g., a diaphragm pump, a piston pump, or a roller pump), a mechanically driven pump (e.g., a spring driven), a gas driven pump, or an osmotic engine driven pump in combination with electronically controlled actuation. The expelling assembly may also be in the form of a collection of assemblies or structures that collectively release fluid from the reservoir when controlled or actuated by a controller external to the assemblies.

In an embodiment, the device may include an image guided robotic device to perform a diagnostic or therapeutic medical procedure. In one embodiment, a robotic device includes an imager, an actuator, and a controller for controlling the actuator. The robotic device may be configured to introduce a tubular device, such as a needle, catheter or cannula, into the anatomy of the human body. The device and its components may be sized to be used as a portable device and/or may be operated by an operator using one hand. The anatomical structure may be any part of the body that has diagnostic or therapeutic significance.

In one embodiment, the device may be in the form of a patch having a plurality of protrusions disposed on a surface of the substrate. The protrusions and base may be formed of any suitable material, but in one example are formed of a silicon-type material, such that the device may be prepared using methods such as vapor deposition, silicon etching, deep Reactive Ion Etching (DRIE), and the like. The protrusions may generally be solid, non-porous, and non-hollow, but this is not required.

The term "patch" is defined by a substrate that is distinguished from the rest by a particular feature.

In one embodiment, the patch may include microneedles. Microneedles are needles of the size of an index of hundred microns that can deliver drugs directly through the stratum corneum. Microneedles are fabricated from a variety of materials including metals, glass, silicon and polymers. The microneedle patch includes: a planar patch layer; and a microneedle disposed on one surface of the patch layer, including an air pocket, and formed as a polymer having at least one of swelling property and solubility. The term "microneedle" has a plurality of protrusions and has a height (h) measured from the inner surface of the middle or substrate layer (if present) to the tip of the microneedle of about 100 μm to 1500 μm, including, for example, about 300 μm to 1000 μm, or about 400 μm to 800 μm, including about 100 μm, 200 μm, 300 μm, 400 μm, 500 μm, 600 μm, 700 μm, 800 μm, 900 μm, 1,000 μm, 1100 μm, 1200 μm, 1300 μm, 1400 μm, and 1500 μm. In other embodiments, the aspect ratio (i.e., height to base ratio) of the microneedles is about 1.0-4.0, including about 1.5-3.5, and 2.0-3.0, including, for example, about 1.0, 1.25, 1.5, 1.75, 2.0, 2.25, 2.5, 2.75, 3.0, 3.25, 3.5, 3.75, and 4.0. In some embodiments, the absolute dimensions of the base of the microneedle are about 50 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, 350 μm, 400 μm, 450 μm, 500 μm, 550 μm, or 600 μm. In other embodiments, the microneedles have an absolute dimension (height to base) of about 400:200 μm, 600:300 μm, or 800:400 μm. The microneedles may be formed in any suitable shape including, for example, conical, diamond, tetrahedral, and pyramidal.

In one embodiment, the patch may be a transdermal patch. The term "transdermal" is a route of administration in which the components are delivered across the skin to distribute throughout the body. Examples include transdermal patches for drug delivery. The drug is administered in the form of a patch or ointment, which delivers the drug into the circulation to produce a systemic effect. Transdermal administration may be achieved by applying, pasting, rolling, attaching, pouring, pressing, rubbing, etc. the transdermal formulation to the skin surface. The term "transdermal patch" refers to a matrix or reservoir type delivery device that is used to transdermally deliver a dose of a substance over a particular administration time.

In one embodiment, the patch may be a peelable pouch comprising a substantially planar enclosure formed by first and second opposed flexible layers. The seal may extend along at least a portion of the perimeter of the opposing layers. A planar, flexible transdermal patch may be disposed in the housing, the patch including a bioactive agent dissolved in an adhesive layer. The release liner may be removably attached to the adhesive layer. The patch and the release liner may together be sufficiently resilient to create a spring force when moved out of the flat configuration. Both the first and second layers may be separated along the seal and may be moved out of the flat configuration. The spring force generated by the patch and the release liner may be sufficient to overcome the adhesive force generated by the adhesive between the patch and one of the layers.

In one embodiment, the patch may typically be a small adhesive bandage containing the drug to be delivered, and these bandages may take a variety of forms. The simplest type is an adhesive monolith that includes a drug-containing reservoir disposed on a backing. The reservoir is typically formed from a pharmaceutically acceptable pressure sensitive adhesive, but in some cases may be formed from a non-stick material, the skin contacting surface of which is provided with a thin layer of a suitable adhesive. Because of the usual person-to-person and skin-to-skin site variability in the permeability of the skin to the drug, the rate of drug administration from these patches to the patient may vary.

In one embodiment, the patch may be a silicon patch, wherein the silicon patch may be referred to as a silicon wafer. It may also be referred to as a medical patch or a medical silicone patch. The medical silica gel patch comprises a silica gel layer, a silica gel layer and a release film, wherein the silica gel layer contains essential oil beta-cyclodextrin inclusion compound particles. The essential oil takes beta-cyclodextrin as essential oil, and is lavender essential oil or essential oil. In addition, vinyl silicone oils may be selected in addition to the essential oils and hydrogenated silicone oils from the beta-cyclodextrin inclusion particles.

In one embodiment, the patch may include a flexible backing and a base layer laminated to the backing. The patch of the present invention is mainly applied to the skin herein, and may include a plaster, a cataplasm, an adhesive tape, a patch, Sheet, wound dressing, facial mask and cosmetic sheetAdhesive tape, and the like. The base layer of the patch may contain SIS block copolymers as an essential ingredient, and preferably also contains tackifiers and plasticizers.

In an embodiment, the patch may also have a plurality of protrusions that are generally urged against the subject's skin such that the protrusions pierce the stratum corneum and into the epidermis to reach the associated target. The protrusion comprises a targeting portion intended to deliver a material or stimulus to a target in the body and a support portion for supporting the targeting portion.

In one embodiment, the patch may be a multi-layer laminate or reservoir patch in which a drug release rate controlling membrane is disposed between the drug reservoir and the skin contact adhesive. The membrane reduces the effects of fluctuations in skin permeability by reducing the in vitro release rate of the patch. This type of patch is generally preferred when administering significantly more potent drugs, but in order to achieve similar drug delivery rates it generally must cover a larger area of skin than an overall patch.

The term "adhesive" refers to any nonmetallic substance that is applied to one or both surfaces of two separate articles to adhere them together and prevent them from separating. Adhesives, also known as glues, glues (glues), mucilage (mucilage) or pastes. There are many types of adhesives suitable for various applications. They can be classified in various ways according to their chemical composition (e.g., epoxy, polyurethane, polyimide), form (e.g., paste, liquid, film, particles, tape), type (e.g., hot melt, reactive hot melt, thermoset, pressure sensitive, contact, etc.), or their load bearing capacity (structural, semi-structural, or non-structural). Any type of adhesive falls within the scope of the present invention. Adhesives based on their function, i.e. core adhesives increase strength when the cloth pad is wet, are known in the art; the structural adhesive adheres the waterproof backsheet to the nonwoven absorbent pad; the elastic adhesive bonds the leg, waist and side panels.

In one embodiment, the adhesive surrounds the pocket of the patch. Surrounding means that (one pattern) is around the other pattern, touching at a point but not cutting. For example: if the pocket has a circular shape, the adhesive will be present at its perimeter.

In one embodiment, the adhesive is disposed on a backing. The backing may be removable (e.g., a release liner, including microstructured release liners or carrier films) or non-removable, such as a polymeric film or a rigid or non-rigid substrate.

In one embodiment, a Pressure Sensitive Adhesive (PSA) composition is well known to those of ordinary skill in the art, having the following properties: (1) aggressive and permanent tack, (2) adhesion not exceeding finger pressure, (3) sufficient ability to hold an adherend, and (4) sufficient cohesive strength. Materials that have been found to function well as PSAs include polymers designed and formulated to exhibit the requisite viscoelastic properties to achieve the desired balance of tack, peel adhesion, and shear holding power. The pressure sensitive adhesive is crosslinked prior to embossing. Examples of suitable adhesives include crosslinked acrylic resins, rubbers, thermoplastic elastomers, silicones, and the like.

In one embodiment, the adhesive may be a "hot melt adhesive". Hot melt adhesives are intended to mean adhesives which are solid at room temperature, melt to a liquid by heating, and when cooled for several minutes by the application of pressure, achieve adhesion and use. It refers to an adhesive coated thereon, such as polyolefin block copolymers (SBS, SIS), ethylene vinyl acetate copolymers (EVA), etc.

In one embodiment, the adhesive may be a "structural adhesive". Structural adhesives are strong structures that can withstand high strength, high yield strength, aging resistance, fatigue resistance, corrosion resistance, and are stable over a defined service life. It refers to an adhesive such as epoxy resin, polyurethane, etc. that can be applied to the adhesion of a vehicle body.

In one embodiment, the pressure sensitive adhesive is based on at least one polymethacrylate (i.e., a methacrylic pressure sensitive adhesive). Particularly preferred polymethacrylates are derived from: (A) At least one monoethylenically unsaturated alkyl methacrylate monomer (i.e., alkyl acrylate and alkyl methacrylate monomers); and (B) at least one monoethylenically unsaturated free radical comonomer. The reinforcing monomer has a homopolymer glass transition temperature (Tg) higher than that of the alkyl methacrylate monomer and is a monomer that increases the glass transition temperature and cohesive strength of the resulting copolymer. Herein, "copolymer" refers to a polymer containing two or more different monomers, including terpolymers, tetrapolymers, and the like.

In one embodiment, the adhesive may be applied using a solvent-based process. For example, the adhesive may be applied by a doctor blade coating, roll coating, gravure coating, bar coating, curtain coating, air knife coating, or the like. The adhesive mixture may also be printed by known methods such as screen printing or ink jet printing. The coated solvent-based adhesive is then dried to remove the solvent. Typically, the coated solvent-based adhesive is subjected to an elevated temperature, such as provided by an oven, to accelerate drying of the adhesive.

In an embodiment, the thickness of the adhesive layer may be at least about 1 micron, at least 5 microns, at least 10 microns, at least 15 microns, or at least 20 microns. The thickness is typically no greater than about 200 microns, no greater than about 175 microns, no greater than about 150 microns, or no greater than about 125 microns. For example, the thickness may be 1 micron to 200 microns, 5 microns to 100 microns, 10 microns to 50 microns, 20 microns to 50 microns, or 1 micron to 15 microns.

In an embodiment, the adhesive may be self-wetting and removable. The adhesive exhibits good compliance, enabling it to spontaneously wet the substrate. The surface characteristics also allow the adhesive to be repeatedly adhered to and removed from the substrate for repositioning or reworking. The strong cohesive strength of adhesives gives them structural integrity limiting cold flow and also has high temperature resistance in addition to permanent removability.

In one embodiment, the adhesive may be a viscoelastic or elastomeric adhesive, a rubber-based adhesive, a silicone-based adhesive. Viscoelastic or elastomeric adhesives also include elastomeric polyurethane or silicone adhesives and viscoelastic optically clear adhesives CEF22, 817x and 818x, all available from 3M company of santalo, minnesota. Other useful viscoelastic or elastomeric adhesives include PSAs based on styrene block copolymers, methacrylic acid block copolymers, polyvinyl ethers, polyolefins, and polymethacrylates.

In one embodiment, the adhesive may contain a tackifier, and is not particularly limited, and for example, alicyclic saturated hydrocarbon resins (synthetic petroleum resins) and rosin ester derivatives, terpene-based resins, phenolic resins, and the like are preferable. The content of the tackifier is not particularly limited, and is preferably 10 to 35wt% based on the entire matrix weight. When the content of the tackifier is too low, the adhesion becomes insufficient. In contrast, when the content of the tackifier is too high, the adhesive force becomes excessive, and thus the user may experience excessive pain when peeling the skin patch from the skin.

In one embodiment, the adhesive may have a microreplicated topography prepared by contacting a microrelief pattern with an adhesive layer. When an adhesive interface is established between the adhesive layer and the support substrate, the topography of the adhesive surface may control the properties of the adhesive interface. Also disclosed herein are articles having microreplicated adhesive surfaces that have the advantage of providing microchannels for fluid egress over an effective period of time. The plurality of micro-embossed patterns create a microreplicated adhesive surface having micro-channels for fluid egress and pegs for improved adhesive performance.

The term "skin": is a generally soft, resilient outer layer of tissue covering the body of a spinal or invertebrate that has three primary functions: protection, regulation and perception. It also refers to the outermost protective layer consisting of cells such as keratinocytes, fibroblasts and melanocytes. The skin includes an outer skin layer and an underlying dermis layer. Skin may also include hair and nails, as well as other types of cells commonly associated with skin, such as muscle cells, merck cells, langerhans cells, macrophages, stem cells, sebocytes, nerve cells, and adipocytes.

In one embodiment, the skin is human skin. Human skin is the outer shell of the body, the largest organ of the crust system. The skin has up to seven layers of ectodermal tissue, protecting the underlying muscles, bones, ligaments and viscera. Skin consists of three main layers: epidermis, dermis, and subcutaneous tissue. Skin with mesodermal cells, pigmentation, such as melanin provided by melanocytes, absorbs some of the potentially dangerous Ultraviolet (UV) rays of sunlight. It also contains DNA repair enzymes, which help to reverse ultraviolet damage, so that individuals lacking these enzyme genes have a high probability of suffering from skin cancer. Malignant melanoma is a form produced mainly by ultraviolet light, which is particularly aggressive, causes it to spread rapidly, and is often fatal. Human skin pigmentation varies significantly among different populations. This results in classifying the person according to skin tone. In terms of surface area, the skin is the second largest organ of the human body (the area inside the small intestine is 15 to 20 times larger). For average adults, the surface area of the skin is between 1.5 and 2.0 square meters (16-22 square feet). Skin thickness varies widely from body part to body part, male and female, young and old. Taking forearm skin as an example, men average 1.3mm and women 1.26mm. The average diameter of human skin cells is about 30 micrometers (μm), but there are many variations. The concentration of skin cells is typically in the range of 25-40 μm2, depending on a number of factors.

In one embodiment, the skin is a complex structure that acts as a barrier to foreign matter from entering the body. Molecules from the environment enter and pass through intact skin must first penetrate the stratum corneum, which is the primary barrier to absorption by topical compositions or transdermally administered drugs (particularly drugs that are insoluble in oil and in ionized salt form).

Pocket: is a small pocket or recess for containing material.

In one embodiment, the patch may have one or more pockets.

In an embodiment, the pocket is preferably made by overlapping in the form of a flat portion of the pocket or base matrix (particularly a portion of the film) or by bending a portion of the film that is part of the pad on the patch.

In one embodiment, the pocket is a recess between the patch and the skin. This allows for the introduction of material into the pocket and the retention of material within the pocket.

In one embodiment, the pocket is a recess between the patch and the release liner.

In one embodiment, the pocket includes a space or pattern.

In one embodiment, the pocket may not open substantially toward the center of the patch to facilitate the introduction of material into the pocket. The depth of the at least one pocket is preferably within a range, wherein the lower limit of the range is selected from 0.5cm, 1cm, 1.5cm, 2cm, 2.5cm, 3cm, 3.5cm, 4.5cm, and the upper limit of the range is selected from 7cm, 8cm, 9cm, 10cm, 11cm, 12cm, 13cm, 14cm, and 15cm.

In an embodiment, a pocket having an opening may have a flap for closing to close such an opening.

In an embodiment, the material may include a drug with or without an excipient.

The term "drug" as used herein generally refers to any substance that alters the physiology of an animal. The term "drug" may be used interchangeably herein with the terms "therapeutic agent," "medicament," "pharmacologically active agent," and the like. It should be understood that a "pharmaceutical" formulation may include more than one therapeutic agent, wherein exemplary combinations of therapeutic agents include combinations of two or more drugs.

For example, pharmaceutical substances suitable for use in the present invention include physiologically active peptides and/or proteins, antineoplastic agents, antibiotics, analgesics, anti-inflammatory agents, muscle relaxants, antiepileptics, antiulcer agents, antiallergic agents, cardiotonic agents, antiarrhythmic agents, vasodilators, antihypertensive agents, antidiabetic agents, hypolipidemic agents, anticoagulants, hemolytic agents, antitubercular agents, hormones, narcotic antagonists, osteoclast inhibitors, osteogenic promoters, angiogenesis inhibitors and various mixtures, salts, prodrugs and combinations thereof, but are not limited thereto.

In one embodiment, the molecular weight of the physiologically active peptide and/or protein is in the range of 200 to 100000, and include, but are not limited to, human growth hormone, growth hormone releasing peptide, interferon, colony stimulating factor, interleukin, macrophage activating factor, macrophage peptide, B-cell factor, T-cell factor, protein a, allergy inhibitor, immunotoxin, lymphotoxin, tumor necrosis factor, tumor suppressor factor, vascular Endothelial Growth Factor (VEGF), fibroblast Growth Factor (FGF), metastatic growth factor, alpha-1 antitrypsin, apolipoprotein-E, erythropoietin, factor VII, factor VIII, factor IX, plasminogen activating factor, urokinase, streptokinase, protein C, C reactive protein, superoxide dismutase, platelet derived growth factor, epidermal growth factor, osteogenic promoting protein, calcitonin, insulin, atrial peptide, cartilage inducing factor, connective tissue activating factor, follicle stimulating hormone, luteinizing hormone releasing hormone, nerve growth factor, parathyroid hormone, relaxin, pancreatic hormone, growth regulator, insulin-like growth factor, adrenocorticotropin, glucagon, contractile hormone, pancreatic hormone, thyroid stimulating hormone, and polyclonal antibody release and polyclonal antibodies thereto. Pegylated forms of proteins, peptides or other biological response modifiers are also suitable for incorporation into the compositions of the invention.

In one embodiment, antiproliferative/antimitotic drugs and prodrugs include natural products such as vinca alkaloids (e.g., vinblastine, vincristine, and vinorelbine), paclitaxel, epipodophyllotoxins (e.g., etoposide, teniposide), antibiotics (e.g., actinomycin, daunorubicin, doxorubicin, and idarubicin), anthracyclines, mitoxantrone, bleomycin, plicamycin (mithramycin), and mitomycin, enzymes (e.g., L-asparaginase); antiplatelet prodrugs; antiproliferative/antimitotic alkylated prodrugs such as nitrogen mustard (dichloromethyl diethylamine, cyclophosphamide and analogues thereof, melphalan, chlorambucil), ethyleneimine and methyl melamine (hexamethylmelamine and thiotepa), alkyl sulfonate-busulfan, nitrosoureas (carmustine (BCNU) and analogues thereof, streptozotocin), triazenes, dacarbazine (DTIC); antiproliferative/antimitotic antimetabolites, such as folic acid analogs (methotrexate), pyrimidine analogs (fluorouracil, fluorouridine and cytarabine), purine analogs and related inhibitors (mercaptopurine, thioguanine, prastatin and 2-chlorodeoxyadenosine (cladribine); platinum coordination complexes (cisplatin, carboplatin), procarbazine, hydroxyurea, mitotane, aminoglutethimide; hormones (e.g., estrogens, progestins), anticoagulants (e.g., heparin, synthetic heparin salts and other thrombin inhibitors), fibrinolytic prodrugs such as tissue plasminogen activator, streptokinase and urokinase, aspirin, dipyridamole, ticlopidine, clopidogrel, acipimab, antimetan, antisecretory agents (ibuprofen Lei Weiding), anti-inflammatory agents such as corticosteroids (cortisol, cortisone, fludrocortisone, fluocinolone, prednisone, prednisolone, methylprednisone, triamcinolone, betamethasone and dexamethasone), NSAIDS (salicylic acid and derivatives thereof), aspirin, acetaminophen, indole and indenacetic acid (indomethacin, sulindac and etodolac), heteroaryl acetic acid (tolmetin, diclofenac and ketorolac), aryl propionic acids (e.g., ibuprofen and derivatives thereof), anthranilic acid (mefenamic acid and meclofenamic acid), enolic acid (piroxicam, tenoxicam, phenylbutazone and hydroxytam), nabumetone, gold compounds (norethide, gold, and thioxofenamic acid) immunosuppressants (e.g., glucopyranoside), tacrolimus (FK-506), sirolimus (rapamycin), azathioprine and mycophenolate; angiogenic agents, such as Vascular Endothelial Growth Factor (VEGF), fibroblast Growth Factor (FGF); angiotensin receptor blockers; a nitric oxide donor; antisense oligonucleotides and combinations thereof; cell cycle inhibitors, mTOR inhibitors, and growth factor signal transduction kinase inhibitors.

In one embodiment, the drug substance is a prodrug or a combination of opioid analgesics or opioid antagonists. Exemplary opioids include morphine and morphine derivatives such as apomorphine, buprenorphine, codeine, dihydrocodeine, dihydroetorphine, diproprphine, etorphine, hydrocodone, hydromorphone, levorphanol, meperidine, metoclopramide, orthomethylnaltrexone, naloxone, naltrexone, normorphine, oxycodone and oxymorphone. In other embodiments, the opioid is fentanyl or a derivative of fentanyl, which can be derivatized to form a prodrug or co-drug, such as β -hydroxy-3-methyl fentanyl. The drug substance may optionally be in the form of a pharmaceutically acceptable salt.

In one embodiment, the drug may be an antioxidant, without particular limitation, such as dibutyl hydroxytoluene, ascorbic acid, tocopherol ester derivatives, butyl hydroxyanisole, 2-mercaptobenzimidazole, and the like.

In one embodiment, the excipient is not particularly limited, and examples thereof include silicon compounds (e.g., silicic anhydride, light silicic anhydride, and hydrated silicic acid), cellulose derivatives (e.g., ethylcellulose, methylcellulose, hydroxypropyl cellulose, and hydroxypropyl methylcellulose), water-soluble polymers (e.g., polyvinyl alcohol), aluminum compounds (e.g., dried aluminum hydroxide gel, hydrated aluminum silicate), kaolin, titanium oxide, and the like.

In one embodiment, the material may include a solubilizing agent and a percutaneous absorption enhancer.

The term "percutaneous absorption enhancer" is also interchangeably referred to as "percutaneous penetration enhancer" or "penetration enhancer". They are also known as enhancers or accelerators. Penetration enhancers are chemical enhancers that help absorb co-administered molecular moieties or drug substances to increase solubility within the stratum corneum. It is believed that the penetration enhancers act primarily in the intercellular spaces of the stratum corneum.

In one embodiment, the permeation enhancer is exemplified by, but not limited to, triacetin, crotamiton, cetyl lactate, diisopropyl adipate, oleic acid and oleyl alcohol, polyethylene glycol (average molecular weight 200 to 30000), polyhydric alcohols such as glycerin, ethylene glycol, fatty acids such as oleic acid, isostearic acid, citric acid, fatty acid esters such as isopropyl myristate, isopropyl palmitate, diisopropyl adipate, fatty acid polyhydric esters such as caprylic acid monoglyceride, caprylic acid triglyceride and sorbitol fatty acid ester, terpenes such as menthol, menthol derivatives, peppermint oil and limonene, N-methyl-2-pyrrolidone, crotamiton, polyvinyl alcohol, and the like. The permeation enhancer may also include benzyl alcohol, propylene glycol monolaurate and C2-C6 alkanediols, 1, 2-propanediol, dipropylene glycol, hexylene glycol, isoparaffins, sodium lauryl sulfate, ethylene oxide adducts of lauryl alcohol, fatty acids, ethanol, polyethylene glycol fatty acid esters, glycerin, polyoxyethylene sorbitan fatty acid esters, propyl carbonate, sodium pyrrolidone carboxylate, urea, lactic acid, sodium lactate, lecithin, dimethyl sulfoxide, pyrrolidone carboxylic acid ester, niacin ester, N-methyl proline ester, amine oxide, and other ingredients formulated as a topical percutaneous absorption enhancer or permeation enhancer.

In one embodiment, the material may include a solubility control agent, such as, but not limited to, a salt.

In one embodiment, the material may include a pH control agent.

In one embodiment, the material may include an imaging agent. Suitable imaging agents together with the medium are radioiodine, or a radiometal chelate, radioisotope (e.g.) ¹⁸ F) Etc.

The term "surface tension" is the tendency of a liquid surface to shrink to the smallest surface area possible. The surface tension is caused by intermolecular forces at the interface. The surface tension depends on the nature of the liquid, the surrounding environment and the temperature. The units are newtons per meter.

In one embodiment, surface tension in the patch blocks the hydrophilic component of the opening. Surface tension typically results in insufficient pore structure at the time of surface sealing. It is believed that the surface tension may further cause critical elements in the patch to clog against each other, thereby causing such a compact seal to block the aperture in the manner of a patch.

In one embodiment, the pocket is capable of retaining material within the pocket due to surface tension.

In one embodiment, the material held within the pocket has a surface tension that enables it to be held within the pocket.

In one embodiment, the surface tension of the liquid is 1nN/m, 2nN/m, 3nN/m, 5nN/m, etc., 1 μN/m, 2 μN/m, 3 μN/m, 5 μN/m, etc., lmN/m, 2mN/m, 3mN/m, 5mN/m, etc.

The term "permeable" refers to a membrane that allows liquid or gas to pass through. The permeable membrane has pores. The flow rate of the liquid through the porous body is proportional to the pressure gradient in the pores. To measure permeability, a pressure differential may be applied across the porous material layer and the flow rate measured. The permeability is measured in cm/s. In other words, a permeable material may refer to any material into which additional substances (e.g., atoms, molecules, or ions) may be introduced.

The term "impermeable" refers to a substance or material that does not allow water or liquid to pass through.

In one embodiment, the patch of the present invention is permeable or impermeable to any liquid or gas or optionally to solids without any external driving force.

In an embodiment, permeable or impermeable when applied through a patch also refers to the permeability or impermeability of the skin to liquids or gases or optionally to solids. Because of the usual person-to-person and skin-to-skin site variability in the permeability of the skin to the drug, the rate of drug administration from these patches to the patient may vary.

In one embodiment, the substrate comprises an impermeable material and/or a permeable material. In one embodiment, the substrate is gas permeable and liquid impermeable; gas permeable and liquid permeable; gas impermeable and liquid permeable; gas impermeable and liquid impermeable; or selectively permeable and may also be solid permeable or impermeable.

In one embodiment, selectively for a solid refers to when the size of the solid is less than 1mm. The size of the solid may be1nm, 2nm, 3nm or 5nm, 1 μm, 2 μm, 3 μm, 5 μm or 1mm.

In one embodiment, the substrate or flap is permeable or impermeable.

In one embodiment, the membrane or material is permeable or impermeable when used passively.

In one embodiment, the membrane or material is permeable or impermeable when actively used.

The term "film" refers to a flexible sheet that forms a barrier, boundary, barrier, or liner. In one embodiment, the membrane is a matrix comprising a polymer substrate. In one embodiment, the polymeric substrate comprises a single polymer. In a specific embodiment, the polymer is selected from insoluble polymers or water soluble polymers. Ethane vinyl acetate and ethyl cellulose are typical insoluble polymers. Polyvinyl alcohol is a typical water-soluble polymer.

In one embodiment, the polymer substrate comprises more than two polymers. In an embodiment, the two or more polymers are selected from insoluble polymers, water soluble polymers, or combinations thereof. In a specific embodiment, the polymeric substrate comprises ethylene vinyl acetate and ethyl cellulose. In another specific embodiment, the polymeric substrate comprises ethylene vinyl acetate and polyvinyl alcohol.

In an embodiment, the membrane is skin or human skin or a substrate or a flap or patch or an entire device or imaging apparatus.

In one embodiment, the membrane is biological or abiotic or natural or synthetic or semi-synthetic.

In one embodiment, the biofilm comprises a cell membrane (the outer layer of a cell or organelle that allows passage of certain components); a nuclear membrane covering the nucleus; and tissue membranes, such as mucous membranes and serosa. Synthetic membranes are manufactured by man for use in laboratory and industry. Semisynthetic films include both natural and non-natural modes.

In one embodiment, the degree of selectivity of the membrane depends on the pore size of the membrane. Depending on pore size, microfiltration (MF), ultrafiltration (UF), nanofiltration (NF) and Reverse Osmosis (RO) membranes can be classified.

In an embodiment, the film may also have various thicknesses, with a homogeneous or heterogeneous structure. The membrane may be neutral or charged and the particle transport may be active or passive. The latter may be facilitated by the pressure, concentration, chemistry or degree of lift of the membrane process.

In one embodiment, the film may be formed of a polymer having at least one of swellability and solubility. Swelling refers to the property of increasing volume by absorbing a liquid such as water. In the present invention, the term "swellable polymer" means a polymer having swelling properties as a main characteristic, and does not mean that the swellable polymer of the present invention does not have other characteristics such as solubility other than swelling properties. That is, the swellable polymer of the present invention has swelling properties as main characteristics, and may exhibit other characteristics. For example, the swellable polymers of the present invention may exhibit both swelling and solubility. The term "soluble polymer" in the present invention refers to a polymer having solubility as a main property, which is a property of being dissolved in a solvent. As described above, the soluble polymer of the present invention may exhibit properties other than solubility. For example, the soluble polymer may exhibit solubility and swelling properties. The polymer of the present invention may be a polymer that can be dissolved by body fluid, or may be a biodegradable polymer that can be decomposed in vivo by body fluid, enzymes, microorganisms, or the like. In addition, the polymer may be a biocompatible polymer that is non-toxic to the human body and suitable for application to a living body. For example, the polymer may be selected from hyaluronic acid, alginic acid, pectin, carrageenan, chondroitin (sulfate), dextran (sulfate), chitosan, polylysine, collagen, gelatin, carboxymethyl chitin, fibrin, agarose, pullulan, cellulose, polyethylene oxide, poly (N-) isopropylacrylamide (PNIPAAm), polyacrylamide (PAAm), polymethacrylic acid, polymaleic acid, polyvinyl alcohol, polymethyl methacrylate (MMA-co-HEMA) (polymethyl methacrylate), polyethylene oxide (PEO) (hydroxyethyl methacrylate copolymer), polyacrylonitrile-aryl sulfonate, poly (glucoxyethyl methacrylate-sulfate) ema (glucoxyethyl methacrylate) oxide (PEO) -poly (PEO-PPO-PEO) terpolymer, polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) terpolymer, N-carboxyanhydride, polystyrene, copolymers of monomers forming such polymers, and the like.

Biocompatibility: biocompatibility relates to the behaviour of biological materials in various situations. The term refers to materials that are capable of exhibiting an appropriate host response under certain conditions. The immune response and repair functions in vivo are very complex and it is difficult to describe the biocompatibility of a single material with a single cell type or tissue. Sometimes, the biocompatibility test is a number of in vitro tests performed according to ISO 10993 (or other similar standard) to determine whether a certain material (or rather a biomedical product) is biocompatible. These tests constitute an important step in animal testing and in final clinical trials, and will determine the biocompatibility of the material in a given application and thus of medical devices such as implants or drug delivery devices.

In one embodiment, the substrate and adhesive of the present invention are biocompatible.

The biocompatible substrate and binder may be organic or inorganic. The organic binder may be from natural or non-natural sources, including vegetable starches (dextrins), natural resins or animals (e.g., milk protein casein and hide-based animal gums). Inorganic binders include non-carbon based binders such as adhesives and mortars.

Some examples of biocompatible substrates include, but are not limited to, polydimethylsiloxane (PDMS), polylactic acid, polycaprolactone (PCL) film, triglycidyl amine. The biocompatible adhesive may be made of epoxy amine.

In one embodiment of the invention, the substrate is a polymeric substrate.

In an embodiment, the substrate is selected from the group consisting of: latex, vinyl-containing polymers, polyurethaneurea, silicone resins, polyvinyl chloride, polypropylene, styrene, polyurethane, polyester, ethylene vinyl acetate copolymer, polystyrene, polycarbonate, polyethylene, polyacrylate, polymethacrylate, acrylonitrile butadiene styrene, polyamide, and polyimide, or mixtures thereof. In another aspect of the invention, the substrate is selected from the group consisting of: natural polymers, degradable polymers, edible polymers, biodegradable polymers, environmentally friendly polymers and medical grade polymers.

Flexibility refers to ease of modification or adjustment.

In one embodiment, the patch is flexible. The patch may include a flexible backing and a base layer laminated to the backing. In one embodiment, the substrate is flexible. The patch is attached to the body surface such that the flexible substrate conforms to the body surface.

In one embodiment, the flexible patch may be flexible, stretchable, and breathable to enhance patient comfort during use. The fabric of the flexible patch may be rolled, crumpled, and folded without affecting its function. The flexible patch may be configured or coated to be fire, water or water resistant.

In one embodiment, the flexible substrate may be formed of a stretchable material to allow the flexible substrate to conform to the head body surface. According to some embodiments, the flexible substrate has a thickness in the range of about 0.001 to 0.100 inches. According to some embodiments, the flexible substrate is selected from the group consisting of: polyethylene, PET, silicone, polyethylene, polyurethane, and polyamide.

Compatibility: in one embodiment, compatibility is defined as being suitable for use together, or to survive or exist or co-exist together. In another embodiment, one material is considered compatible when it has stability when mixed with another material. This property is called compatibility. Two materials are considered incompatible if they mix and chemically react. However, if they do not chemically react, they are said to be compatible. For example, when stirring chemicals, the stirrer must remain stable in the chemical being stirred. One example of incompatibility is: bleaching agents and ammonia, both of which are commonly used as cleaning agents, when combined with each other can undergo dangerous chemical reactions. Although they all have similar uses, care must be taken not to mix these chemicals.

In one embodiment of the invention, compatibility is preferably defined as the absence of chemical reaction of a material when mixed with one or more materials.

In one embodiment, the substrate and the binder are compatible with the permeation enhancer.

In one embodiment, the device or patch is skin compatible. I.e. the patch does not have adverse reactions when applied to the skin.

Skin substance: it is broadly defined as any biochemical entity that is present in the body of a human, animal or any organism for which the invention is intended. Such as but not limited to, those including alpha-1 antitrypsin, anti-angiogenic agents, antisense, butorphanol, calcitonin and analogs thereof, cilexetil, chemokines, chemotactic agents, COX-II inhibitors, dermatological agents, dihydroergotamines, dopamine agonists and antagonists, enkephalins and other opioid peptides, epidermal growth factor, erythropoietin and analogs thereof, follicle stimulating hormone, G-CSF, glucagon, GM-CSF, granisetron, growth hormone and analogs thereof (including growth hormone releasing hormone), growth hormone, irudins and hirudin analogs such as hirudin, igE inhibitors, insulin, insulinotropic and analogs thereof, insulin-like growth factors, interferons, interleukins luteinizing hormone, luteinizing hormone releasing hormone and analogs thereof, low molecular weight heparin, M-CSF, metoclopramide, midazolam, antibodies, oligosaccharides, ondansetron, parathyroid hormone and analogs thereof, parathyroid hormone antagonists, prostaglandin antagonists, prostaglandins, receptor agonists and antagonists, recombinant soluble receptors, scopolamine, serotonin agonists and antagonists, sildenafil, terbutaline, thrombolytics, tissue plasminogen activator, TNFa and TNFa antagonists, proteins, peptides and polysaccharides, polysaccharide conjugates, toxoids, genetic vaccines, attenuated live vaccines, reconstituted vaccines, inactivated vaccines, whole cell vaccines, viruses, bacteria, viruses and bacterial vectors, including but not limited to those derived from adenoviruses, retroviruses and alpha viruses, and are associated with the following diseases: addiction, arthritis, cholera, cocaine addiction, diphtheria, tetanus, HIB, lyme disease, meningococcus, measles, mumps, rubella, varicella, yellow fever, respiratory syncytial virus, tick-borne japanese encephalitis, pneumococci, streptococci, typhoid fever, influenza, hepatitis (including a, b, c and e), otitis media, rabies, poliomyelitis, aids virus, parainfluenza, rotavirus, ai Bashi virus, CMV, chlamydia, non-parting haemophilus, catarrhalis, human papillomavirus, tuberculosis (including bacillus calmette-guerin), gonorrhea, asthma, atherosclerosis, malaria, escherichia coli, alzheimer's disease, helicobacter pylori, salmonella, diabetes, cancer, herpes simplex, human papilloma, and the like, other substances including all major therapeutic agents, such as common cold drugs, anti-addictives, antiallergic drugs, antiemetics, anti-obesity drugs, anti-osteoporosis drugs, anti-infective drugs, analgesics, anesthetics, anorexics, anti-arthritic drugs, anti-asthmatics, anticonvulsants, antidepressants, antidiabetics, antihistamines, anti-inflammatory drugs, antimigraine drugs, anti-motion sickness drugs, anti-nausea drugs, antitumor drugs, antiparkinsonian drugs, antipruritics, antipsychotics, antipyretics, anticholinergic drugs, benzodiazepine antagonists, vasodilators (including coronary, peripheral and cerebral vasodilators), bone stimulating agents, central nervous system stimulants, hormones, hypnotics, immunosuppressants, muscle relaxants, parasympathetic blockers, parasympathetic drugs, prostaglandins, proteins, peptides, polypeptides and other macromolecules, psychostimulants, sedatives, sexual hypofunction and tranquilizer.

In one embodiment, the skin substance may react with the composition of the material.

Imaging refers to the process of visualizing something by scanning with a detector or electromagnetic beam or by radiographic techniques.

In an embodiment, the imaging technique is diagnostic or non-diagnostic or radiographic or magnetic resonance imaging, nuclear medicine, ultrasound, elastography, photoacoustic imaging, tomography, echocardiography, functional near infrared spectroscopy, magnetic particle imaging, electroencephalography (EEG), magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI), positron Emission Tomography (PET), or optical imaging.

In one embodiment, molecular tags may be used for imaging.

In one embodiment of the invention, the patch is configured to perform imaging analysis of a skin layer of the application patch. In another embodiment, an area of the application patch is imaged, but after the patch is removed from the area.

In one embodiment, imaging is a technique whereby an image is taken after application or injection of an imaging agent on or within the skin.

The term "activate" means to turn on, trigger or initiate. "activation" in a chemical sense refers to the reversible transformation of a molecule into nearly identical chemical or physical states, the defining characteristic of which is that the resulting state appears to be more susceptible to a particular chemical reaction.

In one embodiment, the material is activated for imaging purposes.

In an embodiment, the second material is capable of forming a homogeneous or heterogeneous mixture with the material to be activated. The second material is different from the material present in the pocket and to be activated. The second material activates the material present in the pocket. For example: the material in the pocket is a liquid. The second material is also a liquid that is miscible with the material in the pocket and helps activate it.

The term "peel" refers to a removable film or liner without the film or liner breaking or tearing, also known in the food industry as "peeling". The peelability of a film or liner is determined primarily by the properties of the surface layer of the film being sealed. The peelability of the film can be determined relatively easily in the laboratory by a stress strain gauge (e.g., zwick).

In one embodiment, the peelability of the release liner may be easy peelability, medium peelability, and have strong peel resistance (strong peelability). The peel force of the easy peel (easy peel) is about 1 to 4N per 15 mm strip width, the peel force of the firm peel (medium peel) is about 3 to 8N per 15 mm strip width, and the peel force of the strong, peel resistance (strong peel) is greater than 5N per 15 mm strip width.

In one embodiment, the peeling of the patch is performed after the material is applied to the skin and before imaging.

In one embodiment, a release liner is used on the patch.

In one embodiment, a releasable liner having a specific resin composition and laminate structure is capable of achieving both a release force and liner lifting resistance. Further, when the release force of the pressure-sensitive adhesive layer and the release liner has a specific relationship with the rigidity of the release liner, a particularly excellent pressure-sensitive adhesive sheet can be obtained.

The term "sensor" is an apparatus, module, machine or subsystem that is intended to detect events or changes in its environment and to transmit information to other electronic devices, typically computer processors.

In an embodiment, the sensor may be a biosensor. For example, provided herein are sensors integrated in a patch for monitoring glucose concentration in a host and for delivering insulin to the host, the system comprising: a continuous glucose sensor, wherein the continuous glucose sensor is configured to substantially continuously measure glucose concentration in the host and to provide sensor data related to the glucose concentration in the host; an electronic module comprising an on/off controller module configured to iteratively determine insulin therapy instructions in response to an assessment of a relationship of internally derived data and glucose boundaries, wherein the insulin therapy instructions comprise instructions to: opening and closing; and an insulin delivery device configured to deliver insulin to the host, wherein the insulin delivery device is at least one of physically connected to the receiver and operatively connected to the receiver, wherein the insulin delivery device is configured to receive insulin therapy instructions from the controller.

The term "biosensor" is an analytical device for detecting chemical substances that combines biological components with physicochemical detectors. Sensitive biological elements, such as tissues, microorganisms, organelles, cellular receptors, enzymes, antibodies, nucleic acids, etc., are biologically derived materials or biomimetic components that interact, bind or recognize with the analyte of interest.

In one embodiment, the sensors in the patch are wired or wireless. In some applications, the sensor may be wired to a device configured to process and/or display information acquired by the sensor. In another example, there is a wireless sensor that communicates wirelessly with other devices. The wireless sensor may include a storage device configured to store data collected by the sensor device. Additionally or alternatively, the wireless sensor patch may include a transmitter configured to transmit radio signals received by the device (e.g., using bluetooth radio technology). In an embodiment, the receiving device may be a mobile phone or other receiving device capable of relaying information to other locations for processing via satellite. In another example, the wireless sensor patch may include a USB port or other interface that allows for a conventional wired connection with the wireless sensor patch. This allows continuous collection of information synchronized by the device in real time (e.g., via a wireless connection) with the device. Information may be sent to the device periodically while other direct connections are made. Such wired or wireless connections may be used to download information from the wireless sensor patch to the device. In another example, information or instructions may be uploaded from the device to the wireless sensor patch via a wired or wireless connection. For example, instructions to change the operating conditions of the patch may be uploaded to provide information displayed by the patch and/or other functions.

The term "physiological parameter" defines a parameter or condition for knowing the physiological condition of a user. Exemplary physiological parameters include, but are not limited to, subject body temperature, subject heart rate variability, subject blood gas level, subject metabolic rate, subject respiratory rate, subject blood analyte level, subject blood pressure, subject pulse pressure, and the like.

In an embodiment, the invention measures a physiological parameter value of a subject in a selected state (e.g., peak metabolic state, reduced metabolic state, resting state, etc.), including obtaining, by a device attached to the subject, the physiological parameter value of the subject at a particular time of day, and applying, via at least one processor, a time-dependent function to the obtained physiological parameter value to determine the physiological parameter value in the selected state.

In an embodiment, the sensor may include a pulse oximeter, heart rate sensor, ECG sensor, skin sensor, temperature sensor, blood pressure sensor, impedance sensor, tactile sensor, blood pressure sensor, heart rate sensor, etc. According to an embodiment, all types of sensors fall within the scope of the invention.

The invention is explained below by means of various examples.

One embodiment of the invention relates to a patch that is attached to skin by an adhesive to form a pocket between the patch and the skin. This allows for the introduction of material into the pocket and the retention of material within the pocket. The retention of the material may vary depending on the nature of the material and the use and application of the material. For example: the material may be held for about 1 second, about 2 seconds, about 3 seconds, about 4 seconds, about 5 seconds, etc.; about 1 minute, about 2 minutes, about 3 minutes, about 4 minutes, about 5 minutes, etc.; 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, etc.

In one embodiment, the patch may include multiple layers. The multiple layers of the patch may be sequentially applied to the damaged or unbroken skin, or they may be fully or partially adhered to each other with an adhesive prior to application to the skin. In general, the top layer of the patch may be the same size or larger than the underlying layer. The patch may also be in the form of a decal. Furthermore, each layer of the multi-layer patch may be composed of the same substrate or different substrates.

An embodiment of the present invention relates to patches that are either visibly or not visibly adhered to the skin. In order to make the attached portion less noticeable, it is preferable to closely attach the patch along the skin surface having fine irregularities such as skin wrinkles. If the patch is not tightly adhered to the fine uneven surface but is adhered to the skin in a state that appears to be floating out of the skin, the difference in appearance between the patch and the skin surface around it is remarkable, and thus the adhering portion may be remarkable. In order to make the attached portion less conspicuous, it is preferable that the patch is closely adhered to the skin along the uneven surface of skin wrinkles or the like having a fine texture, and the texture appears on the surface (back surface of the base layer) of the patch in a state as if it were transferred to the surface.

In one embodiment, the patch has stretchability. It is also an important subject to avoid causing physical discomfort to the person when the adhesive is applied. If it is difficult for the patch to easily follow the movement of the skin, a feeling of physical discomfort is caused due to the resistance of the patch. In order not to cause a physical uncomfortable feeling upon application, the patch needs to have stretchability in order to easily follow the movement of the skin surface having fine irregularities.

In one embodiment, the patch of the present invention has moderate adhesive strength, and the patch is excellent in a balance between adhesion to the skin surface and peelability after use. If the adhesive strength of the patch is too weak, the patch is simply peeled off from the skin surface or cannot be closely adhered to the skin along the skin surface having fine irregularities such as skin wrinkles. If the adhesive strength of the patch is too strong, rash may be caused or peeling of the patch after use becomes difficult. When the thickness of each of the base layer, the pressure-sensitive adhesive layer, and the patch is thinned, it is easy to hardly obtain moderate adhesive strength.

In one embodiment, the patch has sensors for monitoring various physiological parameters.

In an embodiment, the sensor may include, but is not limited to, a temperature sensor, an Electrocardiogram (ECG) sensor, a Galvanic Skin Response (GSR) sensor, depending on the sensor application.

In one embodiment, the patch used as the adhesive includes a medical patch, such as a dressing for protecting a lesion site, a surgical scar, or the like. And household patches such as emergency band-aid, waterproof patches, and protective patches for protecting skin. These home patches are also used in medical settings because they protect the damaged skin or pinholes that are pierced by syringe needles and the like.

In an embodiment, the patch may have any shape and size, such as, but not limited to, rectangular, triangular, oval, or circular, or any geometric shape.

In one embodiment, the patch includes a substrate.

The substrate may be made of synthetic polymers, purified biopolymers, or a combination thereof.

Suitable synthetic polymers include, but are not limited to, organic and inorganic polymers, polyamides (e.g., nylon, zytel ^TM 、Technyl ^TM 、Winmark ^TM 、Rilsan ^TM 、Rilsamid ^TM 、Radipol ^TM (polyamide); PA 6T, trogamid ^TM 、Amodel ^TM (polyphthalamide); kevlar ^TM 、Nomex ^TM 、Teijinconex ^TM 、Twaron ^TM And Technora ^TM (aromatic polyamides or polyaramides)), polyesters (e.g., polyimide, polysulfone, polyetherketone, polyethylene terephthalate and polybenzimidazole), polystyrene (styrene butadiene rubber, acrylonitrile butadiene styrene), polyacrylate (methacrylate, methyl acrylate, ethyl acrylate, 2-chloroethyl vinyl ether, 2-ethylhexyl acrylate, hydroxyethyl methacrylate, butyl acrylate, butyl methacrylate), vinyl polymers (e.g., polyethylene, polytetrafluoroethylene, polypropylene and polyvinyl chloride), polycarbonate, polyurethane, polydimethylsiloxane, cellulose acetate, polymethyl methacrylate, ethylene vinyl acetate, polysulfone, nitrocellulose, vulcanized rubber, poly 4-hydroxybutyrate (P4 HB), polypropylene fumarate (PPF), polyethylene glycol dimethacrylate (PEG-DMA), beta-tricalcium phosphate (beta-TCP), non-biodegradable Polytetrafluoroethylene (PTFE), polyethylene glycol acrylate (PEG-Ac), polyethylene glycol vinyl sulfone (PEG-VS), polyethylene terephthalate homopolymer, poly (P-phenylene) glycol dimethacrylate (PEG-VS) Ethylene formate copolymers, polybutylene terephthalate, polycyclohexylcyclohexane diformate, polycyclohexyl terephthalate and polytrimethylene terephthalate and similar copolymers, foam backings of urethanes, polyurethanes, and the like may also be used. In one embodiment, the substrate is silicon.

The biopolymer may be naturally occurring or produced in vitro by fermentation or the like. The purified biopolymer may be suitably formed into a substrate by techniques such as braiding, knitting, casting, molding, extrusion, cell alignment, and magnetic alignment. Suitable biopolymers include, but are not limited to, alginate, chitosan, cotton, wool, collagen, elastin, silk, keratin, gelatin, polyamino acids, polysaccharides (e.g., cellulose and starch), proteins, natural rubber, pectin, chitin, polyhydroxyalkanoates, and copolymers thereof. Examples of some other polymers are polylactic acid (PLA), polycaprolactone (PCL), polylactic acid-glycolic acid copolymers (PLGA), PEO, polyvinyl alcohol (PVA), and Polyurethane (PU). Polyglycolic acid (PGA), polyhydroxyalkanoates, natural rubber (isoprene polymer), wood plugs and lignin (complex polyphenol polymer), cutin and glue film (long chain fatty acid complex polymer), melanin, polyethylene. The polymer may also be a nano-polymer of synthetic or natural or semi-synthetic origin.

The synthetic polymers of the present invention may be derived from biological sources by an indirect route involving one or more intermediate compounds.

Furthermore, the synthetic polymer may be biodegradable or non-biodegradable. Biodegradability is also affected by the number of attached synthetic molecules on each protein, as a large number of attached synthetic molecules may mask cleavage sites and thus reduce biodegradability.

The substrate may also comprise a metal. Noble metals such as titanium, stainless steel, gold, silver, cobalt, chromium, and alloys thereof may also be included in the substrate. The substrate may also be tissue. Including, but not limited to, pericardial tissue, for example.

In one embodiment, the substrate comprises an impermeable material and/or a permeable membrane. In one embodiment, the substrate is gas permeable and liquid impermeable; gas permeable and liquid permeable; gas impermeable and liquid permeable; gas impermeable and liquid impermeable; or selectively permeable and may also be solid permeable or impermeable.

In one embodiment, the substrate may be inorganic, organic, synthetic, semi-synthetic, or natural.

The substrate of the patch of the device of the invention may be pure or a mixture of different substrates. The choice of different substrates or their mixture or different variations of the substrates may vary depending on the skin site of topical application, the location in the body (i.e. internal or external), the environmental conditions, the individual requirements.

In one embodiment, the substrate may be inorganic and organic or a mixture of synthetic and natural.

In one embodiment, the adhesive forms an interfacial layer between the skin and the substrate of the patch

In another embodiment, the adhesive forms an interface between the first substrate and the second substrate that has suitable porosity and hydrophilicity. It may be used to fasten the base layers together and/or to adhere the patch to the skin site.

In particular, the adhesive interface should be sufficiently porous such that the adhesive can be incorporated into or with the biocompatible material to achieve a mechanical interlock between the two substrates, which can be skin and substrate or substrates of different compositions, and the adhesive.

To form an adhesive bond between any two substrates, a first substrate associated with the adhesive is typically brought into contact with a second substrate.

In one embodiment, a polyurethane adhesive incorporating an aliphatic polycarbonate polyol derived from the copolymerization of an epoxide and carbon dioxide is used.

In one embodiment, from the viewpoints of transparency, processability, and durability, a pressure-sensitive adhesive, an acrylic pressure-sensitive adhesive, or a polyether pressure-sensitive adhesive is used.

In one embodiment, the adhesive is a UV curable adhesive. The ultraviolet curable adhesive may be a solvent type adhesive or a melt adhesive. The adhesive may adhere to the material at ambient temperature by means of a photoinitiator chemical that converts absorbed light energy (typically UV light) into chemical energy in the form of an initiating species (e.g., a radical or cation) to initiate polymerization in the monomer-containing adhesive.

In one embodiment, the adhesive comprises an acrylate or methacrylate. Examples of acrylates and/or methacrylates which can be used as components of the monomer mixture (i) include: methyl acrylate, ethyl methacrylate, methyl methacrylate, n-butyl acrylate, n-butyl methacrylate, n-pentyl acrylate, n-hexyl acrylate, n-heptyl acrylate, n-octyl acrylate, n-nonyl acrylate, lauryl methacrylate, cyclohexyl acrylate, and branched methacrylic acid isomers such as isobutyl acrylate, isobutyl methacrylate, n-butyl methacrylate, 2-ethylhexyl acrylate, stearyl methacrylate and isooctyl acrylate. Exemplary acrylates and/or methacrylates are monoacrylic monomers and do not include any di-or multi-acrylate monomers.

In one embodiment, the adhesive may also contain various other additives, such as plasticizers, tackifiers, and fillers, all of which are commonly used to prepare photosensitive adhesives (PSAs). As the tackifier or tackifying resin to be added, a known tackifying resin described in the literature can be used. Non-limiting examples include pinene resins, indene resins and their disproportionated, hydrogenated, polymerized and esterified derivatives and salts, aliphatic and aromatic hydrocarbon resins, terpene-phenolic resins, C5 resins, C9 resins and other hydrocarbon resins. Any desired combination of these or other resins may be used to adjust the properties of the resulting adhesive according to the desired final properties.

The acrylic Pressure Sensitive Additive (PSA) may also be blended with one or more additives such as aging inhibitors, antioxidants, light stabilizers, complexing agents and/or accelerators.

The binder may also be mixed with one or more fillers. Fillers are the compound part of the adhesive, the purpose of which is to alter or determine the chemical, physical and mechanical properties of the adhesive, and after selection of monomers and polymers, fillers play an important role in the composition of the adhesive.

In one embodiment, the filler may be fiber, carbon black, zinc oxide, titanium dioxide, solid or hollow glass microspheres, microspheres of other materials, silica, silicate and chalk. In one embodiment, the adhesive may be a double sided self adhesive sheet.

The adhesive may be transparent or opaque.

In one embodiment, the substrate and the binder are compatible with DMSO.

In one embodiment, the substrate and/or adhesive is compatible with the materials present in the patch pocket.

In one embodiment, the substrate and/or the adhesive are compatible with the permeation enhancer.

In one embodiment, the substrate is flexible. The flexible substrate may be a polymeric rubber, paper based such as kraft paper, diamond coated kraft paper, cotton paper, fish paper, vulcanized fiber, polypropylene, PET, polycarbonate, glass epoxy polyimide, elastomeric material, nylon, polyamide, nylon 6, polyamide 6, nylon MXD 6, PVOH, PVC, PVDC, PCTFE, sol gel material, liquid crystal polymer, PA 6, PGA, PHA, PLA, cellulose ester, TPS, PBS, vacuum metal or metal oxide coated flexible material (e.g., al, siOx, alOx), nanoclay coating, paper foil, and blends, combinations thereof. Examples of polymeric rubber substrates include one or more of the following: styrene-isoprene-styrene polymers, styrene-olefin-styrene polymers (including styrene-ethylene/propylene-styrene polymers), polyisobutylene, styrene-butadiene-styrene polymers, polyisoprene, polybutadiene, natural rubber, silicone rubber, acrylonitrile rubber, nitrile rubber, polyurethane rubber, polyisobutylene rubber, butyl rubber, halogenated butyl rubber (including bromobutyl rubber), butadiene-acrylonitrile rubber, polychloroprene, and styrene-butadiene rubber.

The particular substrate used in conjunction with the adhesive may form the entire device or it may form part of the device. Similarly, different substrates may be combined to form a patch. The method of bonding the adhesive to the substrate or substrates selected may affect the type of patch.

In one embodiment, the substrate and the adhesive are biocompatible. The biocompatible substrate and binder may be organic or inorganic. The organic binder may be from natural or non-natural sources, including vegetable starches (dextrins), natural resins or animals (e.g., milk protein casein and hide-based animal gums). Inorganic binders include non-carbon based binders such as adhesives and mortars.

Some examples of biocompatible substrates are Polydimethylsiloxane (PDMS), polylactic acid, polycaprolactone (PCL) film, triglycidyl amine. The biocompatible adhesive may be made of epoxy amine.

In an embodiment of the invention, the device further comprises a release liner and/or an opening.

In one embodiment, the release liner is made of a biocompatible material. The release liner and adhesive may be located on the perimeter or inside of the substrate or the entire area of the patch. The portion of the substrate to which the adhesive or release liner is attached varies depending on the application requirements of the patch. The perimeter forms an outer portion of the patch. The outer portion of the patch may be inferred to cover an area portion outside of the pocket area of the patch. The inside of the substrate may be the portion involved in the formation of the pocket area of the patch.

In one embodiment, the release liner has a similar composition to the substrate.

In an embodiment, the releasable liner exhibits excellent release ability, does not cause lifting of the liner even in the case of storage in a bent state, and exhibits excellent recyclability, and a pressure-sensitive sheet containing the same is provided.

In one embodiment, a releasable liner having a specific resin composition and laminate structure is capable of achieving both a release force and liner lifting resistance. In addition, when the release force of the pressure-sensitive adhesive layer and the release liner has a specific relationship with the rigidity of the release liner, a particularly excellent pressure-sensitive adhesive sheet can be obtained

In one embodiment, the release liner has a layer structure of at least three layers, one skin layer being made of high density polyethylene and the other skin layer being made of low density polyethylene, even substantially low density polyethylene. The present invention provides a release liner having an intermediate layer containing only polyethylene as a resin component.

In one embodiment, the release liner commonly used in the present invention may be a film of polyethylene, polypropylene, ethylene vinyl acetate copolymer, vinyl chloride, or the like, a metal film prepared by aluminum vapor deposition or the like, and the liner surface may be subjected to a mold release treatment such as a silicon treatment or the like. As the releasable liner used in the present invention, for example, a liner having a linear or arcuate cut, two or more liners partially overlapped, having a turning edge, or the like may be considered for facilitating the release.

In one embodiment, the present invention provides a pressure-sensitive adhesive sheet, wherein the pressure-sensitive adhesive layer is a pressure-sensitive adhesive layer containing air bubbles and/or hollow microspheres. The release liner and the pressure-sensitive adhesive sheet of the present invention are excellent in releasability and do not cause the liner to float even when stored in a bent state. In addition, since the structure is simple without polar groups and the like, and each layer is composed of polyethylene, recyclability is also excellent. In the present invention, both the releasable liner and the pressure-sensitive adhesive sheet may be in the form of a tape, i.e., include a release tape material and a pressure-sensitive adhesive tape.

In one embodiment, the release liner may be any shape. The release liner may be attached to substantially the entire interior portion of the patch. The interior portion of the cover pocket is located within the patch. The release liner may also define a plurality of perforations extending therethrough primarily in a central portion of the inner surface such that liquid may freely flow through the perforations.

In one embodiment, the release liner, adhesive is heat or pressure resistant. In another embodiment, the release liner, adhesive, or substrate may be heat or pressure sensitive.

In one embodiment, the opening is a space or gap that allows passage or access in the device. It leads to a pocket in the patch. The size of the opening may vary from picometers (pm) to millimeters (mm) to centimeters (cm).

The openings have a size of about 2pm, about 5pm, about 10pm, about 5nm, about 10nm, about 50nm, about 100nm, about 150nm, about 200nm, about 300nm, about 500nm, about 750nm, about 1 μm, about 2 μm, about 3 μm, about 4 μm, about 5 μm, about 6 μm, about 7 μm, about 8 μm, about 9 μm, about 10 μm, about 15 μm, about 20 μm, about 1mm, about 2mm, about 3mm, about 5mm or more, or within a range therebetween.

In an embodiment, the opening may be any shape, not limited to oval, circular, square, rectangular, or any other shape.

In one embodiment, the opening comprises a protrusion or tubular structure.

In an embodiment, the protrusion or the tubular structure comprises a clamp configured to open or close the opening.

In one embodiment, the clamp may be a roller clamp or a slide clamp. An improved injection molded plastic roller clamp for an Intravenous (IV) set includes a housing having side walls, a bottom wall, a top wall, a flow control region, a roller, and a plastic tube sandwiched between the roller and the bottom wall.

In one embodiment, the roller clamp injects the liquid at a specific flow rate. In one embodiment, the specific flow rate may be about 1 ml/min, about 2 ml/min, about 3 ml/min, about 5 ml/min, etc.

In one embodiment, the slide clamp is used to completely block IV flow without the need to adjust the roller clamp.

In one embodiment, the tab may comprise the same composition as the base of the patch.

In an embodiment, the tab may comprise a different composition than the base of the patch.

In one embodiment, the substrates for patches disclosed herein may be used to fabricate tabs of the patches.

In one embodiment, the fins may be made of synthetic polymers as well as biopolymers or combinations thereof.

The tab may be the same material as the substrate. The tab may also be the same material as the patch. The fins may also comprise metal. Noble metals such as titanium, stainless steel, gold, silver, cobalt, chromium, and alloys thereof may also be used to make the airfoil.

In one embodiment, the tab comprises an impermeable material and/or a permeable membrane.

In one embodiment, the tabs of the patch of the device of the present invention may be pure or a mixture of different polymers.

In one embodiment, the fins may be inorganic and organic or a mixture of synthetic and natural. The choice of different polymers or mixtures thereof or different variants of polymers may vary depending on the skin site of topical application, the location in the body (i.e. internal or external), environmental conditions, personal requirements.

In one embodiment, the tab is the same as the base of the patch.

In another embodiment, the tab is different from the base of the patch.

In one embodiment, the fins may hold liquids at various temperatures, which may cause a change in the surface tension of the liquid.

A liquid is a nearly incompressible fluid that conforms to the shape of its container but that (nearly) maintains a constant volume regardless of pressure. It is a state of a certain volume but not a fixed shape.

Cohesion between the molecules causes the liquid surface to shrink to as small a surface area as possible. This general effect is known as surface tension. Surface tension is the tendency of a liquid surface to shrink to as small a surface area as possible. There are two main mechanisms by which surface tension acts. One is an inward force on the surface molecules, causing the liquid to shrink. The other is a tangential force parallel to the liquid surface. Eventually making the liquid behave as if its surface were covered with a stretched elastic film.

In one embodiment, in the mesh structure, the fibers are laid down in different directions in one plane and in the thickness direction to form a 3D mesh structure. The fibers are comprised of one or more layers of parallel yarns, each of which may be arranged in a different direction. In one embodiment, the mesh structure may be an open mesh fabric that is twisted, knotted, or woven together at regular intervals. The mesh structure may be hand woven, nonwoven, machine manufactured or laser cut.

In various embodiments, the mesh structure may be a homogeneous layer of material. In various embodiments, the mesh structure may be a laminate structure in which at least two layers of material are stacked on top of each other. In various embodiments, the mesh structure may have layers, wherein at least three layers of material are stacked on top of each other.

In various embodiments, the mesh structure may have a laminate structure in which at least four material layers are stacked on top of each other. In various embodiments, one portion of the mesh structure may be a homogenous material layer, while another portion of the same mesh structure may be a laminate structure in which at least two material layers are stacked on top of each other. In various embodiments, the layers of the laminate structure may be at least partially bonded to one another. In various embodiments, the layers of the laminate structure cannot be bonded to one another.

In one embodiment, the web of fins may comprise a composition comprising a patch substrate.

In one embodiment, the web structure of the tab may be made of a variety of materials, such as synthetic fibers (e.g., polyester fibers or polypropylene fibers), natural fibers (e.g., wood fibers or cotton fibers), natural and synthetic fibers, porous foams, reticulated foams, films, apertured plastic films, and the like. Examples of suitable materials include, but are not limited to, rayon, wood, cotton, polyester, polypropylene, polyethylene, nylon or other heatable fibers, bicomponent staple fibers, polyolefins, such as, but not limited to, polypropylene, olefins, aliphatic (acid) ester copolymers of linear low density polyethylene with polylactic acid, fine web fibers, and the like, and combinations thereof.

Skin is a multi-layer tissue and excellent barrier that can evolve to allow anyone to survive in a dry environment. It is the outermost layer, the Stratum Corneum (SC), which is the primary barrier to penetration. The use of penetration enhancers overcomes this obstacle. Skin may refer to the layer that serves as the outermost barrier between the external and internal environment of the body of a living organism. In one embodiment, the patch may be used on any living subject, and is not limited to mammals, such as humans.

In one embodiment, the material is held within a pocket.

In an embodiment, the material may include permeation enhancers, conditioning fluids, molecular dyes, labels, nanoparticles, radionuclides, drugs, solvent enhancers, pH modifiers, and/or combinations thereof.

In one embodiment, the modulator includes, for example, but is not limited to cetostearyl alcohol, PEG 40 and other variants thereof, castor oil, stearylamine chloride.

In one embodiment, the molecular dye includes, for example, but is not limited to, polypropylene, polyurethane, vat dye, acid dye, disperse dye, near infrared-II dye (dye with an operating wavelength of 780nm to 2500 nm), and the like.

In one embodiment, the radionuclides include, for example, but are not limited to, radiouranium, radiothorium, radiobismuth, radioiodine, radiofluorine, and the like.

In one embodiment, the permeation enhancer comprises an alcohol, including short chain alcohols such as ethanol, isopropanol; long chain alcohols such as decyl alcohol, hexyl alcohol, lauryl alcohol, myristyl alcohol, octyl dodecanol, oleyl alcohol; acyl groupAmines, including cyclic amides, such as azo derivatives of azones which are ketones (e.g., laurocapram); esters-alkyl esters, such as ethyl acetate, benzoate esters, such as octyl salicylate, pamoate O, fatty acid esters, such as ethyl oleate, glycerol monooleate, glycerol monocaprate, glycerol trioctanoate, isopropyl myristate, isopropyl palmitate, propylene glycol monolaurate, propylene glycol monocaprylate; ether alcohols, e.g.Fatty acids such as lauric acid, linoleic acid, linolenic acid, myristic acid, oleic acid, palmitic acid, stearic acid, isostearic acid; diols, such as dipropylene glycol, propylene glycol (excipients commonly found in topical dosage forms), 1, 2-butanediol, 1, 3-butanediol; pyrrolidone, an organic compound consisting of a 5-membered lactam, is the simplest gamma-lactam. It is a colorless liquid, miscible with water and most common organic solvents (e.g., N-methyl-2-pyrrolidone, 2-pyrrolidone (2P)); sulfoxides, also known as sulfoxides, are a class of organic compounds containing sulfur and oxygen and having the general formula (RR ') SO, wherein R and R' are groups of carbon and hydrogen atoms, such as: decyl methyl sulfoxide, dimethyl sulfoxide (DMSO).

Surfactants (also common in dosage forms) consist of: anionic surfactants such as sodium lauryl sulfate; cationic surfactants such as alkyl dimethylbenzyl ammonium halides, alkyl trimethyl ammonium halides, alkyl pyridinium halides; nonionic surfactants such as Brij 36T, tween 80; terpenes such as monoterpene eugenol, d-limonene, menthol, menthone sesquiterpene farnesol, nerol.

In one embodiment, the amount of permeation enhancer is about l, about 2, about 5, about 10, about 25, about 50, about 75, about 100, about 200, about 1, about 2, about 3, about 5, or less, and more depending on the size of the pocket can be accommodated within the pocket.

In one embodiment, the pocket has a size of about 2pm, about 5pm, about 10pm, about 5nm, about 10nm, about 50nm, about 100nm, about 150nm, about 200nm, about 300nm, about 500nm, about 750nm, about 1 μm, about 2 μm, about 3 μm, about 4 μm, about 5 μm, about 6 μm, about 7 μm, about 8 μm, about 9 μm, about 10 μm, about 15 μm, about 20 μm, about 1mm, about 2mm, about 3mm, about 5mm or more, or within a range therebetween.

In one embodiment, the material in the pocket comprises a powder, an enzyme, a growth factor, an antiproliferative/antimitotic drug, a gel, an ampoule containing a unit dose, a conditioning fluid, a molecular dye, a tag, a nanoparticle, a radionuclide, a particle, a microorganism, and/or a combination thereof.

In one embodiment, a therapeutically effective amount of the material is present within the pocket.

The term "therapeutically effective amount" refers to the amount of an agent that will elicit the biological or medical response of a cell, tissue, system or subject that is being sought by the user, researcher, veterinarian, medical doctor, clinical medical staff or technician. The term "effective amount" includes an amount of a compound that, when applied, is sufficient to cause, to some extent, one or more binding activities between the compound/material in the liquid and the components (e.g., proteins, DNA, RNA, etc.) in the skin. The effective amount will vary depending on the agent and the condition to be analyzed.

In one embodiment, the material in the pocket is a solid, semi-solid, quasi-solid, or liquid or gas.

In one embodiment, the material is a liquid.

In an embodiment, the enzyme may be a hydrolase, an oxidoreductase, a lyase, a transferase, a ligase, a protease, an isomerase, and/or combinations thereof. The enzyme may be a natural or genetically engineered enzyme. The enzyme may be in an active or pre-active form. The pre-active form of an enzyme, also called a zymogen, is an inactive precursor of the enzyme. The zymogen needs to undergo biochemical changes (e.g., hydrolysis to reveal the active site or change configuration to reveal the active site) to become an active enzyme, e.g., thrombin, fibrinogen.

In one embodiment, wherein the growth factor includes, for example, but is not limited to, adrenomedullin (AM), angiopoietin (Ang), autotaxin, bone Morphogenic Protein (BMP), ciliary neurotrophic factor family, ciliary neurotrophic factor (CNTF), leukemia Inhibitory Factor (LIF), interleukin 6 (IL-6), colony stimulating factor (HDGF), macrophage colony stimulating factor (M-CSF), granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), epidermal Growth Factor (EGF), ephrin, erythropoietin (EPO), fibroblast Growth Factor (FGF), fetal bovine growth hormone (FBS), GDNF ligand family, glial cell line-derived neurotrophic factor (GDNF), neurturin, persephin, neuropsychin, growth differentiation factor-9 (GDF 9), hepatocyte Growth Factor (HGF), liver cancer derived growth factor (HDGF), insulin-like growth factor, interleukin, keratinocyte Growth Factor (KGF), keratinocyte growth factor (MSF), macrophage Stimulating Protein (MSP), also known as hepatocyte growth factor-like protein (HGFLP), myostatin (GDF-8), neuregulin, neurotrophic factor, brain-derived neurotrophic factor (BDNF), nerve Growth Factor (NGF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), placental Growth Factor (PGF), platelet Derived Growth Factor (PDGF), renin (RNLS) -anti-apoptotic survival factor, T Cell Growth Factor (TCGF), thrombopoietin (TPO), transforming growth factor, tumor necrosis factor-alpha (TNF-alpha), vascular Endothelial Growth Factor (VEGF), plant growth factors such as indoleacetic acid, cytokinins, ethylene, gibberellins, abscisic acid.

In an embodiment, wherein the powder or enzyme or microorganism or general material may be lyophilized or in any other form. In one embodiment, the microorganism may be an archaebacteria, a bacterium, a fungus, a protozoan, or the like.

In one embodiment, the conditioning fluid includes, for example, but is not limited to, isopropyl myristate (IPM); sodium dodecyl sulfate (SLS); triethanolamine (TEA); linoleic Acid (LA); sodium Cocoyl Isethionate (SCI); sodium Dodecyl Sulfate (SDS); polyethylene glycol (PEG); sorbitol Sesquioleate (SSO); glycolic Acid (GA); retinaldehyde (RAL); alpha-hydroxy acid (AHA); beta-hydroxy acid (BHA); hydrophobically Modified Polymers (HMPs); natural Moisturizing Factors (NMF), and the like.

In one embodiment, the molecular dye includes, for example, but is not limited to, FITC (fluorescein) dye, PE (R-phycoerythrin) dye, NIR-I (near infrared-I) dye, NIRII dye, polymethine dye, cyanine dye, hydrophilic dye, hydrophobic dye, DNA, RNA or protein dye, inorganic or organic dye, natural or synthetic dye.

In one embodiment, the tags used include any of the well known molecular tags used for imaging.

In one embodiment, the material (e.g., liquid) in the pocket is configured to be activated and react with the skin under certain conditions.

In an embodiment, the conditions for activating the material include, for example, but are not limited to, including chemicals, radiated electromagnetic, ionized, non-ionized, heated, mixed with a second material, and/or combinations thereof.

In an embodiment, the radiation may be any electromagnetic radiation, acoustic radiation, particle radiation, and gravitational radiation. The heat source may be a thermal pocket in the patch using radiation. The temperature of the patch is brought to about 20 c, about 25 c, about 30 c, about 35 c, about 37 c, about 40 c, about 45 c, about 50 c, etc., and ranges therebetween by a heat source.

In an embodiment, the second material is capable of forming a homogeneous or heterogeneous mixture with the material to be activated. The second material is different from the material present in the pocket and to be activated. The second material activates the material present in the pocket. For example: the substance in the pocket is a liquid. The second material is also a liquid that is miscible with the material in the pocket and helps activate it.

In an embodiment, the patch is placed on the unbroken skin surface and/or the broken skin surface. Broken skin refers to skin under conditions of breakage, rupture, injury or tearing.

In one embodiment, the unbroken skin is intact skin and the broken skin is skin in a broken, ruptured, injured tear condition or skin with sutures.

In one embodiment, the invention relates to a method comprising:

b. introducing a material into the pocket; and

c. the material is allowed to react with the skin,

wherein the patch includes a substrate, an adhesive, and an opening in the substrate.

In one embodiment, the material in the pocket is configured to be activated.

In one embodiment, the material is activated under conditions including radiation, heat, chemical reaction, mixing with a second material, and/or combinations thereof.

In one embodiment, the application time of the device is 10 seconds, 20 seconds, 30 seconds, 40 seconds, 50 seconds, etc.; 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, etc.; 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, etc.

In one embodiment, the material is applied to the skin and then rubbed off. The composition of the material may be the same as the composition of the material in the pocket of the patch or different from the composition of the material present in the pocket.

In one embodiment, the material application time is 10 seconds, 20 seconds, 30 seconds, 40 seconds, 50 seconds, etc.; 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, etc.; 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, etc.

In one embodiment, latency is defined as the time between application of the patch and penetration or absorption of the material within the skin. The time may be 10 seconds, 20 seconds, 30 seconds, 40 seconds, 50 seconds, etc.; 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, etc.; 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, etc. The latency period may be symptomatic of penetration of the material into the skin and its reaction with the biomolecular moiety present in the patient.

In one embodiment, the time to image after wiping the material is 10 seconds, 20 seconds, 30 seconds, 40 seconds, 50 seconds, etc.; 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, etc.; 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, etc.

In one embodiment, the device comprises a patch comprising:

(i) The substrate is provided with a plurality of holes,

(ii) An adhesive on the substrate and a method of forming the same,

wherein the patch is configured to:

(b) Allowing the introduction of material into the pocket, and

(c) The material is held within the pocket.

In one embodiment, no adhesive is present under the pocket. In one embodiment, there is no adhesive layer under the pocket.

In one embodiment, the material is activated by heat. Neither the melting process nor the hot tearing or tearing process uses heat to remove the blocking material.

In one embodiment, the material is activated by heat to provide a determined characteristic of the material. For example: if the material is pepsinogen, the patch is configured to activate pepsinogen to pepsin under certain conditions.

In one embodiment, an imaging system includes:

dye, and

a molecular tag;

wherein the patch is configured to:

(b) Allowing the introduction of material into the pocket, and

(c) The material is held within the pocket.

In one embodiment, the dye comprises a fluorescent dye.

In one embodiment, the imaging system further comprises a fiducial point.

In one embodiment, the material present within the patch is activated by heat.

In one embodiment, for the device, wherein the certain conditions further comprise heating, mixing with a second material, or a combination thereof.

In an embodiment, the patch is configured to activate the material under certain conditions including radiation.

In one embodiment, activation by heat does not mean that micro-holes are created to open access to the reservoir.

In one embodiment, activation by heat is not a means of forming holes.

In one embodiment, the adhesive layer surrounds the pocket.

In one embodiment, the device comprises a patch comprising:

(i) The substrate is provided with a plurality of holes,

(ii) An adhesive on the substrate and a method of forming the same,

(iii) Molecular tags for monitoring physiological conditions of a user wearing the patch, and

wherein the patch is configured to:

(a) Is attached to the skin by an adhesive to form a pocket between the patch and the skin, wherein the adhesive layer surrounds the pocket,

(b) It is allowed to introduce the material into the pocket,

(c) Hold the material in the pocket, and

wherein the patch includes an opening and a flap covering the opening.

In one embodiment, the device further comprises a release liner.

In one embodiment, an apparatus includes a patch comprising:

(i) The substrate is provided with a plurality of holes,

(ii) An adhesive on the substrate and a method of forming the same,

wherein the patch is configured to:

(b) It is allowed to introduce the material into the pocket,

(c) Hold the material in the pocket, and

(d) Activating the material under conditions including radiation;

wherein the patch includes an opening and a flap covering the opening.

In one embodiment, the certain conditions further comprise heating, mixing with a second material, or a combination thereof.

Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

The grouping of alternative elements or embodiments of the invention disclosed herein should not be construed as limiting. Each group member may be combined with other members of the group or other elements herein, either alone or in any combination. One or more members of a group may be included in or deleted from the group for convenience and/or patentability reasons.

The invention is further described below in connection with exemplary embodiments and examples. These exemplary embodiments and examples are provided for illustrative purposes only and are not intended to be limiting unless otherwise specified. Thus, the present disclosure should in no way be construed as limited to the following exemplary embodiments and examples, but rather should be construed to cover any and all modifications that are apparent from the teachings provided herein.

Example 1

A silicone patch was placed on the skin over the area to be evaluated. Skin conditioning fluid was applied from the opening for 1 minute. Fluorescent dye was then added to the opening and incubated for an additional 4 minutes.

After the incubation period is over, the patch and fluid are removed and rubbed off.

The fiducial point is placed near the patch placement area as shown in fig. 5. Fiducial markers or fiducials are objects placed in the field of view of the imaging system that appear in the generated image and serve as reference points or measurement points. It may be an object placed in or on the imaging subject, or a marker or set of markers in the optical instrument reticle.

A photograph and fluorescence image of the skin as shown in fig. 6 was taken and used for analysis.

All publications, patents, and patent applications cited in this specification are herein incorporated by reference in their entirety as if each individual publication, patent, or patent application were specifically and individually indicated to be incorporated by reference. Although the foregoing has been described in terms of various embodiments, those skilled in the art will appreciate that various modifications, substitutions, omissions, and changes may be made without departing from the spirit thereof.

Reference to the literature

1.US005109874 A

2.US10,245,272 B2

3.US2009/0043236 A1

4.US10,245,272 B2

5.US20200405331 A1

6.US20030124293 A1

7.US20180161252 A1

8.US10739908 B2

9.US10835672 B2

10.US7395111 B2

11.US7582069 B2

Claim (modification according to treaty 19)

1. A device comprising a patch, the patch comprising:

(i) Substrate and method for manufacturing the same

(ii) An adhesive on the substrate;

(iii) Molecular tags for monitoring the physiological condition of a user wearing the patch, and

(iv) A permeation enhancer comprising a chemical substance configured to activate a material to allow the material to permeate under the skin of the user and react with a portion of a biomolecule present under the skin of the user;

wherein the patch is configured to:

(a) Attaching to the skin by the adhesive to form a pocket between the patch and the skin, wherein the layer of adhesive surrounds the pocket,

(b) Allowing material to be introduced into the pocket, and

(c) Retaining the material within the pocket;

wherein the patch comprises an opening and a flap covering the opening,

wherein the tab is different from the substrate and

wherein the patch is configured to activate the material under certain conditions.

2. The device of claim 1, wherein the device further comprises a release liner.

3. The device of claim 2, wherein the release liner is positioned below the patch and is attached to the patch by the adhesive to form a pocket between the patch and the release liner.

4. The device of claim 1, wherein the fins comprise a mesh structure to maintain the surface tension of the liquid.

5. The device of claim 1, wherein the substrate comprises an impermeable material and/or a permeable membrane.

6. The device of claim 1, wherein the substrate and the adhesive are compatible with a material applied to the patch.

7. The device of claim 6, wherein the material comprises a permeation enhancer.

8. The device of claim 7, wherein the permeation enhancer comprises sulfoxides, azones, pyrrolidones, alcohols and alkanols, glycols, surfactants and/or terpenes or combinations thereof.

9. The device of claim 6, wherein the substrate and the adhesive are compatible with a permeation enhancer.

10. The device of claim 6, wherein the substrate and the adhesive are compatible with DMSO.

11. The device of claim 7, wherein the permeation enhancer comprises a protein or dye.

12. The device of claim 1, wherein the substrate is flexible.

13. The device of claim 1, wherein the material comprises conditioning fluid, molecular dye, label, nanoparticle, radionuclide, and/or combinations thereof.

14. The device of claim 1, wherein the certain condition comprises radiation, heating, mixing with a second material, and/or a combination thereof.

15. The device of claim 1, wherein the patch is placed on a non-damaged skin surface and/or a damaged skin surface.

16. The device of claim 1, wherein the device is configured for imaging purposes or topical administration or a combination thereof.

17. The device of claim 1, wherein the pocket comprises a space or pattern.

18. The device of claim 1, wherein the opening comprises a protrusion or a tubular structure.

19. The device of claim 18, wherein the protrusion or the tubular structure comprises a clamp configured to open or close the opening.

20. The device of claim 1, wherein the patch is configured to allow skin substances to enter the patch from the skin.

21. The apparatus of claim 1, wherein the condition comprises ionizing radiation.

22. The device of claim 1, wherein activation of the material causes the material to react with the skin.

23. The device of claim 1, wherein activation of the material images skin.

Description or statement (modification according to clause 19)

The claims of this application are modified as per patent cooperation treaty 19.

1. Claim 1 adds the following features:

"(iii) molecular tags" for monitoring the physiological condition of the user wearing the patch, the modification being based on paragraphs [061], [324] of PCT application;

"(iv) a permeation enhancer comprising a chemical substance configured to activate a material to allow the material to permeate under the skin of the user and react with a portion of a biomolecule present under the skin of the user, the modification being based on PCT application documents [061], [291], [321], [323] and the original claims 17, 19;

"wherein the layer of adhesive surrounds the pocket", this modification is based on PCT application document [342] paragraph and fig. 1, 2;

"wherein the patch comprises an opening and a flap covering the opening, wherein the flap is different from the substrate", the modification being based on the original claims 4, 6;

"wherein the patch is configured to activate the material under conditions", the modification being based on PCT application document paragraph [338] and the original claims 17, 19.

2. Deleting the "analog" option of claim 14; the method of claim 18, wherein said condition is modified to said certain condition; the method of claim 29 wherein the "material in pocket" is modified to "patch", the modification being based on PCT application documents [045], [178 ].

3. Deleting claims 4-6, 17, 19, 22-25, 30-37.

4. The novel augmentation of claims 21-23.

5. The numbering and citation relationships of the claims are readjusted.

Claims

1. A device comprising a patch, the patch comprising:

(i) Substrate and method for manufacturing the same

(ii) An adhesive on the substrate;

wherein the patch is configured to:

(a) Is attached to the skin by the adhesive to form a pocket between the patch and the skin,

(b) Allowing material to be introduced into the pocket, and

(c) The material is held within the pocket.

2. The device of claim 1, wherein the device further comprises a release liner and/or an opening.

4. The device of claim 2, wherein the opening further comprises a flap.

5. The device of claim 4, wherein the tab is identical to the substrate.

6. The device of claim 5, wherein the tab is different from the substrate.

7. The device of claim 5, wherein the fins comprise a mesh structure to maintain the surface tension of the liquid.

8. The device of claim 1, wherein the substrate comprises an impermeable material and/or a permeable membrane.

9. The device of claim 1, wherein the substrate and the adhesive are compatible with a material applied to the patch.

10. The device of claim 9, wherein the material comprises a permeation enhancer.

11. The device of claim 9, wherein the permeation enhancer comprises sulfoxides, azones, pyrrolidones, alcohols and alkanols, glycols, surfactants and/or terpenes or combinations thereof.

12. The device of claim 9, wherein the substrate and the adhesive are compatible with a permeation enhancer.

13. The device of claim 9, wherein the substrate and the adhesive are compatible with DMSO.

14. The device of claim 10, wherein the permeation enhancer comprises a protein, dye, or the like.

15. The device of claim 1, wherein the substrate is flexible.

16. The device of claim 1, wherein the material comprises conditioning fluid, molecular dye, label, nanoparticle, radionuclide, and/or combinations thereof.

17. The device of claim 1, wherein the material in the pocket is configured to be activated under certain conditions.

18. The device of claim 14, wherein the conditions comprise radiation, heating, mixing with a second material, and/or combinations thereof.

19. The device of claim 14, wherein the material is configured to react with skin.

20. The device of claim 1, wherein the patch is placed on a non-damaged skin surface and/or a damaged skin surface.

21. The device of claim 1, wherein the device is configured for imaging purposes or topical administration or a combination thereof.

22. A method, comprising: securing a patch of the device to the skin to form a pocket between the skin and the patch, introducing a material into the pocket, and allowing the material to react with the skin; wherein the patch comprises a substrate, an adhesive, and an opening in the substrate.

23. The method of claim 22, wherein the material in the pocket is activated.

24. The method of claim 23, wherein the material is activated under conditions comprising radiation, heating, mixing with a second material, and/or combinations thereof.

25. The method of claim 22, wherein the device further comprises a releasable liner, wherein the releasable liner is positioned under the patch and is attached to the patch by the adhesive to form a pocket between the patch and the releasable liner.

26. The device of claim 1, wherein the pocket comprises a space or pattern.

27. The device of claim 2, wherein the opening comprises a protrusion or a tubular structure.

28. The device of claim 27, wherein the protrusion or the tubular structure comprises a clamp configured to open or close the opening.

29. The device of claim 1, wherein the material in the pocket is configured to allow skin substances from the skin to enter the patch.

30. A device comprising a patch, the patch comprising:

(i) The substrate is provided with a plurality of holes,

(ii) The adhesive on the substrate is a mixture of two or more of,

wherein the patch is configured to:

(b) Allowing the material to be introduced into the pocket,

(c) Holding the material within the pocket, and

wherein the patch includes an opening and a flap covering the opening.

31. An imaging system, comprising: a patch comprising (i) a substrate, (ii) an adhesive on the substrate, (iii) a molecular tag for monitoring a physiological condition of a user wearing the patch; a dye; a molecular tag;

wherein the patch is configured to:

(b) Allowing material to be introduced into the pocket, and

(c) The material is held within the pocket.

32. The imaging system of claim 31, wherein the material comprises a skin conditioning fluid.

33. The imaging system of claim 31, wherein the dye comprises a fluorescent dye.

34. The imaging system of claim 31, further comprising a fiducial point.

35. The imaging system of claim 31, further comprising an imaging agent; wherein the imaging agent comprises radioiodine, a radioactive metal chelate, and a radioisotope.

36. A device comprising a patch, the patch comprising:

(i) The substrate is provided with a plurality of holes,

(ii) The adhesive on the substrate is a mixture of two or more of,

Wherein the patch is configured to:

(b) Allowing the introduction of material into the pocket,

(c) Holding the material within the pocket, and

(d) Activating the material under conditions including radiation;

wherein the patch includes an opening and a flap covering the opening.

37. The device of claim 1, wherein the conditions further comprise heating, mixing with a second material, or a combination thereof.