CN1607970B - Dermal patch - Google Patents

Abstract

The invention is generally directed to a kit and patch for transdermal or intradermal delivery of at least one substance into the skin. The kit includes a dermal patch having an electrochemical cell with two electrodes and a retainer for retaining a conductive fluid which further includes an active substance. The conductive fluid can be deposited on at least one of the two electrodes. Alternatively, the conductive fluid can be applied topically to the skin.

Description

Transdermal patches

[0001] the application requires the priority of the submission day of the application No.60/330526 that submits to October 24 calendar year 2001, and its whole technology is as a setting quoted at this.

Technical field

The present invention relates to through skin and/or in skin delivery device, external member and method, more specifically, relate to the transdermal patches that to carry electric current, be used to comprise through skin and in skin electricity carry the material of multiple class, perhaps by electricity irritation be used to improve wound healing, prevent cicatrix, reduce cicatrix, tissue repair and/or tissue regeneration.

Background technology

In technology and patent documentation, taken much count of recently the material such as medicine and other beneficial agent, medicine and cosmetics are transported in the complete skin surface or by complete skin surface by the passive process such as diffusion and infiltration and by the active process such as electric induction iontophoresis, electrophoresis, electric osmose and/or electroporation.The ubiquitous nicotine patch that is designed to aiding smoking cessation made know widely such form through the skin drug conveying.(hereinafter, any term iontophoresis, electrophoresis, electric osmose and/or electroporation will jointly be represented in term " iontophoresis ", and term " iontophoresis " comprises adjective form separately.)

In fact, have at present especially long routinely through skin and/or in skin the inventory of administered agents material, and the similar Changqing of the apparatus and method that are used for administration that are known in the art is single.Brief still vicissitudinous sampling comprises as follows: U.S. Patent No. 6294582, and it has disclosed the device that is used for dermally treating asthma; U.S. Patent No. 5899856, it has disclosed the transdermal patches that is used to detect alcohol consumption; U.S. Patent No. 6291677, its teaching the percutaneous dosing of antiviral protease inhibitors; U.S. Patent No. 6266560, it has disclosed the transdermal therapeutic of erection disturbance; U.S. Patent No. 6238381, it has disclosed antiviral, percutaneous antibiotic and the aging resistance material is carried; And U.S. Patent No. 6288104, it has disclosed the percutaneous dosing of the material that is used for the treatment of congestive heart failure.

Although a lot of materials come administration passively via transdermal patches, a lot of materials are also arranged in skin or the conveying of percutaneous electricity.

Use is known the electricity irritation of body part, and has with isometric and colorful history.In about 20 periods turn of century, there be too much " electrode " that be used for " electricity treatment " is applied to human body.These electrodes are placed on the human body with respect to the organ that will be treated.Like this early stage " electricity treatment " comprises general electricity irritation, and it causes that ionized molecule is driven in the health usually outwardly.Use the iontophoresis or the ion migration of this old model, be used for the beneficial effect of local irritant supposition and the skin that usually simple humidity is incorporated into medicine patient.

The iontophoresis technology is used in medicine gives at present widely, because it is transported to charged medicine electricity in the skin effectively, and enters capillary pipe structure and lymphsystem.This technology has been avoided relevant with the medicine of oral picked-up sometimes gastrointestinal side-effect, and is better than subcutaneous injection because of its optimum and painless relatively characteristic.

The another kind of technology that is known as electroporation promotes percutaneous or the uncharged material of intradermal delivery by the formation of the instantaneous skin micropore of electric induction, and these instantaneous skin micropores allow to move uncharged material by diffusion.

Therefore, iontophoresis, and the technology of other electric induction such as electroporation has been attached in a lot of dermal delivery devices, comprises general transdermal patches.Therefore, the transdermal patches that much is known in the art is at present arranged, it comprises power supply and the circuit that is used for auxiliary percutaneous conveying.

The most of present transdermal patches that comprises those passive effects and electro ultrafiltration comprises the material that is used for the percutaneous conveying.Such paster specifically designs and/or is configured as the particular matter of carrying predetermined close, and this material forms described paster, i.e. the integral part of " nicotine patch ".Like this with predetermined type and wherein have a shortcoming of the transdermal patches of predetermined amount manufacturing to be, in case material exhausts, so whole device is just of no use, and must be dropped.This is disadvantageous, because use the paster of the conveying technology of electric induction must have parts, such as battery, electrode, circuit and other assembly, it may be expensive and/or when abandoning in a large number, is deleterious to environment.In addition, in order to change dosage, must provide the paster of various dose.

At present also know a series of transdermal patches that can utilize once more in the art, be used to keep the container of drug substance before these pasters are included in and give.These transdermal patches generally include the container as the part of one or two electrodes of the skin that conveys electrical current to the experimenter.Such electrode is often referred to bioelectrode.

Bioelectrode has a lot of sizes, shape and structure, assigns to Ioimed company such as following, and it produces the conveyer device of iontophoresis.The example of such bioelectrode is included in the U.S. Patent No. 5037380 and 5248295 that teaching has the paster that can recharge container; Teaching has the U.S. Patent No. 5846217 of the paster of the little access window that is used to recharge; And the medicine that keeps dry of teaching and must being disclosed in the U.S. Patent No. 537424,5730716 and 6223075 of the paster of hydration.All such bioelectrodes are complicated, and comprise a lot of parts, so relative volume is big.Therefore, those parts that are included in the transdermal patches make paster bigger, and relatively costly.In addition, such transdermal patches must charge or loads by the clinician rather than by the experimenter.

Like this, admit need and highly advantageous have thin, flexible and simple electroactive transdermal patches widely, it is simple by experimenter's administration, purposes is many, and can use a series of materials and/or dosage, and is used for various purposes, and its simplicity of design is made cheap.

Summary of the invention

Therefore, one object of the present invention is to provide the multiduty transdermal patches that comprises power supply, and it can be used for carrying through skin or in skin a series of different materials.

Of the present invention also have a purpose to be to provide the multiduty transdermal patches that comprises power supply, and it can be used for for various purposes electric current being introduced parts of skin.

Of the present invention also have a purpose to be to provide the multiduty transdermal patches that comprises thin and flexible power supply, and it can be used for for various purposes electric current being introduced parts of skin and/or its can be used for carrying through skin or in skin a series of different materials.

According to an aspect of the present invention, provide a kind of external member to be used for carrying at least a material through skin or in skin, this external member comprises (a) transdermal patches, and it comprises that having at least two positioning of electrodes is used to form the electrochemical cell that the parts of skin with the experimenter electrically contacts on a side of transdermal patches; And (b) at least one is used to keep comprise the keeper of the conductor fluid of material, and this conductor fluid is used to be deposited at least one electrode, and/or on the partial parts of skin that is applied to the experimenter; This patch design and be configured as and be used to carry electric current, thus with the skin by conductor fluid and experimenter through skin or in skin transportation of substances.

According to another aspect of the present invention, provide a kind of external member to be used for electric current and/or voltage are incorporated into experimenter's parts of skin, this external member comprises (a) transdermal patches, and it comprises that having at least two positioning of electrodes is used to form the electrochemical cell that the parts of skin with the experimenter electrically contacts on a side of transdermal patches; And (b) at least one is used to keep the keeper of conductor fluid, and this conductor fluid is used to be deposited at least one electrode, and/or on the partial parts of skin that is applied to the experimenter; This patch design is used to carry electric current with being configured as, electric current and/or voltage are incorporated into experimenter's parts of skin by conductor fluid.

According to aspect in addition of the present invention, a kind of transdermal patches that mainly comprises electrochemical cell is provided, this electrochemical cell has at least two positioning of electrodes on a side of transdermal patches, be used to form and the electrically contacting of experimenter's parts of skin, this transdermal patches design and being configured as is used for by being deposited at least one electrode and/or the conductor fluid on the partial experimenter's of being applied to the parts of skin is carried electric current.

According to aspect in addition of the present invention, provide a kind of through skin or in skin the method for transportation of substances, it conductor fluid that comprises that (a) will comprise material partly is applied in experimenter's the parts of skin, and/or the conductor fluid that will comprise material is deposited at least one electrode of transdermal patches, and this transdermal patches comprises having the electrochemical cell of at least two positioning of electrodes on a side of transdermal patches; (b) the location transdermal patches makes electrode and experimenter's parts of skin electrically contact; And (c) carry electric current by conductor fluid and parts of skin so that through skin or in skin transportation of substances.

According to aspect in addition of the present invention, a kind of method that electric current and/or voltage is incorporated into experimenter's parts of skin is provided, it comprises that (a) is applied to conductor fluid on experimenter's the parts of skin partly, and/or conductor fluid is deposited at least one electrode of transdermal patches, this transdermal patches comprises having the electrochemical cell of at least two positioning of electrodes on a side of transdermal patches; (b) the location transdermal patches makes electrode and experimenter's parts of skin electrically contact; And (c) by the conductive fluid transport electric current, so that electric current and/or voltage are incorporated into experimenter's parts of skin.

According to the feature in described preferred embodiment, conductor fluid is based on the fluid of water.

According to the feature in described preferred embodiment, conductor fluid is a hydrogel.

According to the feature in described preferred embodiment, conductor fluid is to select from the group that comprises gel, cream, paste, lotion, suspension, Emulsion and solution.

According to the feature in described preferred embodiment, conductor fluid is to be used to be deposited at least one of two electrodes.

According to the feature in described preferred embodiment, conductor fluid is the parts of skin that is used for being applied to partly the experimenter.

According to the feature in described preferred embodiment, material is charged material.

According to the feature in described preferred embodiment, material is uncharged material.

According to the feature in described preferred embodiment, material is to select from comprising that medicine, cosmetics and medicine are made up the group of product.

According to the feature in described preferred embodiment, medicine is to select from comprise therapeutic agent and narcotic group.

According to the feature in described preferred embodiment, electric current is as causing iontophoresis, electrophoresis, electroporation or its any combination.

According to the feature in described preferred embodiment, electric current as cause wound healing, prevent cicatrix, reduce cicatrix, bodily tissue reparation and/or tissue regeneration.

According to the feature in described preferred embodiment, keeper is to select from the group that comprises bucket, pipe, jar, container, allotter and ampoule.

According to the feature in described preferred embodiment, keeper is the separator that is used to be deposited at least one of two electrodes.

According to the feature in described preferred embodiment, electric current is from the separator transportation of substances.Such separator trends towards preventing the contact between electrode and the skin, and the whole lip-deep uniform distribution of electric current at paster is provided.Such separator is the integral part of electrode or is attached to electrode.

According to the feature in described preferred embodiment, this separator is included in the removable lid.

According to the feature in described preferred embodiment, this electrochemical cell is flexible thin layer electrochemistry battery.

According to the feature in described preferred embodiment, this electrochemical cell is the electrochemical cell of the thin layer open liquid state of flexibility, it comprises the insoluble negative pole of ground floor, the insoluble positive pole of the second layer and the 3rd layer of aqueous electrolyte, the 3rd layer is arranged between first and second layers, and comprises that (a) is used for always keeping the deliquescent material of open cell humidity; (b) be used to obtain the electroactive soluble material of required ionic conductivity; And (c) be used to obtain required viscosity can water-soluble polymer, to adhere to the 3rd layer with first and second layers.

According to the feature in described preferred embodiment, at least one in two electrodes is used for moving at least a material.

According to the feature in described preferred embodiment, these at least two electrodes and electrochemical cell are integrally formed.

According to the feature in described preferred embodiment, this electrochemical cell and at least two electrodes constitute paster individually.

According to the feature in described preferred embodiment, transdermal patches also comprises the attachment mechanism of the parts of skin that is used to be attached to the experimenter.

According to the feature in described preferred embodiment, transdermal patches also comprises the circuit that is used to control electric current.

According to the feature in described preferred embodiment, for wound healing applications, prevent that cicatrix from using, reducing cicatrix application, tissue repair application, tissue regeneration application, percutaneous delivery application and intradermal delivery application packages and definite external member.

Carry exercisable multiduty transdermal patches in any amount of material and the dosage by being provided at through skin or in skin, the present invention has successfully solved the shortcoming of present known structure.

Description of drawings

Now at length specifically with reference to the accompanying drawings, be stressed that, the details that show are by example, and only for the schematic discussion of the preferred embodiments of the present invention, and introduce under the situation that the description that is considered to the most useful and easy understanding aspect principle of the present invention and the notion is provided.Aspect this, not to attempt to show in greater detail CONSTRUCTED SPECIFICATION of the present invention, the present invention is necessary for basic comprehension for it, description taken together with the accompanying drawings makes those skilled in the art understand how several form of the present invention can embody in practice.

In the accompanying drawing:

Fig. 1 is the sectional view of the transdermal patches of constructing according to a preferred embodiment of the invention;

Fig. 2 a-g is the view of the keeper of different embodiment according to the subject invention;

Fig. 3 a-d shows according to first open-and-shut embodiment of the present invention;

Fig. 4 a-d shows according to second open-and-shut embodiment of the present invention;

Fig. 5 a-c shows according to the 3rd open-and-shut embodiment of the present invention; And

Fig. 6 is the sectional view according to the different structure of transdermal patches of the present invention.

The specific embodiment

The invention relates to external member, transdermal patches and the method that can be used for percutaneous and/or the multiple material such as medicine, cosmetics and medicine are made up product of intradermal delivery by iontophoresis, electrophoresis and/or electroporation.Transdermal patches of the present invention is multipurpose advantageously on such meaning, that is, single paster is operable as percutaneous and/or a series of multiduty materials of intradermal delivery and/or dosage, and this paster can be charged and administration simply by the experimenter.

Explaining before at least one embodiment, should be appreciated that, the invention is not restricted in this application below description or shown in accompanying drawing in the structure of the parts of illustrating and the details of structure.The present invention can be applicable to other embodiment or can put into practice in a different manner or carry out.In addition, should be appreciated that word used herein and term are for illustrative purposes, should not be considered limiting.

Can understand according to the external member that is used for percutaneous and intradermal delivery material of the present invention better with appended explanation with reference to the accompanying drawings and be used for electric current and/or voltage are incorporated into the principle and the operation of external member of experimenter's parts of skin.

With reference now to Fig. 1,, it shows the transdermal patches according to teaching of the present invention, and it is called paster 10 here below.Paster 10 comprises top surface 12 and contact skin lower surface 13, and it forms paster main body 11 together.Paster 10 is preferably made by flexible material, and when paster 10 is applied on experimenter's the parts of skin, makes surface 12 and/or 13 meet the profile of experimenter's parts of skin.Be appreciated that paster main body 11 can be according to necessary virtually any size of respective application and shape.

Paster 10 preferably also comprises the skin attachment mechanism, and it is adhesive phase 28 preferably, and it is used for paster 10 is attached to experimenter's parts of skin.Adhesive phase 28 covers at least a portion of the lower surface 13 of paster 10.Adhesive phase 28 preferably includes biocompatible permeable pressure-sensitive binding agent, such as the Bio-PSA from Dow Corning.Other example of biocompatible binding agent is to understand easily for those skilled in the art.Adhesive phase 28 can be used for once being attached or repeat to be attached.

Paster 10 is comprising electrochemical cell 14, and it is the thin electrochemical cell of flexibility preferably, most preferably open liquid electrochemical cell.Be appreciated that paster 10 can use any other electrochemical cell, perhaps TRT, it is used to provide the needed electric current of related application.Polytype micro power, disposable and rechargeable, be well known in the art, it can be included in the paster main body 11.

According to a preferred embodiment of the invention, electrochemical cell 14 is the flexible electrochemical cells that approach, and it engages the major part of the whole volume of paster main body 11.In this preferred embodiment, electrochemical cell 14 comprises anodal layer 16, negative electrode layer 18 and between the dielectric substrate between them 20.A suitable example thin and flexible electrochemical cell is for example described in U.S. Patent No. 5652043,5897522 and 5811204, and it passes through reference in this application.Briefly, the electrochemical cell of describing in the United States Patent (USP) of Que Rening is open liquid electrochemical cell in the above, and it can be with the disposable or rechargeable power supply various miniaturizations that act on Compact Design and device portable electric excitation.This battery comprises the insoluble negative pole of ground floor, the insoluble positive pole of the second layer and is arranged on the 3rd layer of aqueous electrolyte between first and second layers, and comprises that (a) is used for always keeping the deliquescent material of open cell humidity; (b) be used to obtain the electroactive soluble material of required ionic conductivity; And (c) be used to obtain required viscosity can water-soluble polymer, to adhere to ground floor with first and second layers.

Some preferred embodiments of the electrochemical cell that discloses comprise that (i) engages dielectric substrate in the porous mass such as, but not limited to filter paper, plastic foil, cellulose membrane and cloth and so on; (ii) make the insoluble positive pole of ground floor comprise manganese dioxide powder and make the insoluble negative pole of the second layer comprise zinc powder; (iii) make insoluble negative pole of ground floor and/or the insoluble positive pole of the second layer also comprise carbon dust; (iv) from zinc chloride, zinc bromide, zinc fluoride and potassium hydroxide, select electroactive soluble; (v) make the insoluble negative pole of ground floor comprise silver oxide powder and make the insoluble positive pole of the second layer comprise zinc powder, and electroactive soluble material is a potassium hydroxide; (vi) make the insoluble negative pole of ground floor comprise cadmium dust and make the insoluble positive pole of the second layer comprise nickel oxide powder, and to select electroactive soluble material be potassium hydroxide; (vii) make the insoluble negative pole of ground floor comprise iron powder and make the insoluble positive pole of the second layer comprise nickel oxide powder, and to select electroactive soluble material be potassium hydroxide; (viii) make insoluble negative pole of ground floor and the insoluble positive pole of the second layer comprise lead oxide powder, battery is charged by the voltage that is applied to these utmost points then, and electroactive soluble material is chosen as sulfacid under these circumstances; (ix) deliquescent material and electroactive soluble material can be identical materials, such as zinc chloride, zinc bromide, zinc fluoride and potassium hydroxide; (x) deliquescent material is selected from the group that comprises calcium chloride, calcium bromide, potassium hydrogen phosphate and potassium acetate; (xi) can water-soluble polymer can be polyvinyl alcohol, polyacrylamide, polyacrylic acid, polyvinylpyrrolidone, polyethylene glycol oxide, agar, agarose, starch, hydroxyethyl-cellulose and their combination and copolymer; (xii) can water-soluble polymer and deliquescent material can be identical materials, such as dextran, sulphuric acid dextran and their combination and copolymer.Electrochemical cell 14 preferably include in the above embodiments any one or a plurality of.Preferred structure according to electrochemical cell 14 of the present invention comprises these combinations, and it does not have toxic compounds.

Electrochemical cell 14 comprises the terminal as electrode, and it is called anelectrode 22 and negative electrode 24 hereinafter, its each electrically contact with anodal layer 16 and negative electrode layer 18 respectively.Electrode 22 and 24 uses known devices, for example prints flexible circuit, metal forming, lead, electroconductive binder or is electrically connected to electrochemical cell 14 by direct contact.Be appreciated that take measures to avoid between the electrode and each electrode and relative utmost point layer between contact.In Fig. 1, the measure of taking is for inserting the insulation component 17 that is formed by dielectric substance.

Electrode 22 and 24 conducts electricity, and can be by metal, and for example metal forming or deposition or the metal that covers on the suitable backing form.The example of suitable metal comprises aluminum, platinum, rustless steel, gold and titanium.Perhaps, electrode 22 and 24 can be formed by the hydrophobic polymer that comprises the conductive filler such as metal dust/fragment, the graphite that dusts, carbon fiber or other known conductive filler material.

Electrode 22 and 24 can be applied on the battery, and whole unit can be for example by making such as, but not limited to the suitable printing technique of silk screen printing, lithographic printing, spray printing, lamination, material evaporation or powder diffusion and so on.Therefore, the electrochemical cell of describing in as mentioned 14 is one of the simplest power supplys.

Be appreciated that each electrode 22 and 24 can be virtually any size and shape, and relative to each other locate, be required to be the parts of skin that covers treatment as possibility with any structure.In fact, according to a preferred embodiment of the invention, electrochemical cell 14 constitutes the independent inner member of paster 10 in conjunction with electrode 22 and 24.Therefore, paster 10 is one of minimum and the thinnest active practices, and the per unit surface area is carried maximum power.

Paster 10 of the present invention is preferably disposed in the removable of protectiveness or the packing that can re-use or liner or the lid 19, so that physical protection is provided before use and prolongs storage life.

Paster 10 designs and is configured as and be at least a, and preferred multiple exterior materials is used together.The such agents design that is described in more detail below also is described in more detail below for being included in the conductor fluid.

Conductor fluid is designed to remain at least one, in preferred a plurality of keepers.Being combined to form of paster 10 and keeper can be by the external member of patient's maintenance, to be used for multiple application.

With reference now to Fig. 2 a-g,, it shows a series of keepers that are used to keep conductor fluid.The formation of such conductor fluid is " medicine is acceptable " and " physiology is acceptable " preparation normally, is used for cosmetics or treatment use.As used herein, term " medicine is acceptable " and " physiology is acceptable " refer to be preferably in not too disadvantageous side effect (for example, for the preparation of topical application, erythra, inflammation etc. under) the situation, can be to the material of experimenter's administration.Concrete preparation comprises aqueous gel, cream, paste, lotion, suspension, Emulsion and solution, perhaps is suitable for other liquid preparation of the topical application that is known in the art.

In this preferred embodiment, conductor fluid conducts electricity, and is to be suitable for use as the contact skin binding agent, especially is suitable for use as the binding agent hydrogel of electrical interface of the electrode of medical apparatus.Hydrogel is a cation acrylic, and for example can preferably be made by the acrylate of ammonium chloride and/or ammonium sulfate or the acrylamide of ammonium chloride.They can be formed by the free radical polymerization in water with initiator and polyfunctional crosslinking agent, preferably by ultraviolet curing.Hydrogel preferably includes buffer system, helping prevent the variable color of hydrogel, and/or the hydrolysis of hydrogel, and/or improve storage life.

Other additive can be combined in (for example, electric conductivity enhancer, medicine, wetting agent, plasticizer etc.) in this hydrogel according to predetermined final use before curing or after curing.The additive that preferably joins in the hydrogel is electroconductive binder material (additive), and it is used to allow conductor fluid both paster 10 to be attached to experimenter's skin, again as the thermal interface between electrode and the skin.Adhesive additive is polymeric binder preferably, and can be that pressure or temperature can be activated, and perhaps it can activate by being exposed to ambient air.

Preferred hydrogel is fully adherent, separates but keep easily.Belong to for example description in U.S. Patent No. 5800685 of further details that is suitable for using hydrogel in the context of the present invention, it is quoted at this by reference.

Under any circumstance, generally include water, spirituosity/aqueous solution, at least a salt or any other charged reagent according to the moisture conductor fluid of teaching of the present invention, and best buffer medium.

Be appreciated that also and can use water-free conductor fluid.

The conductor fluid that uses in conjunction with paster 10 preferably gives by being deposited on one or two electrodes.Be appreciated that conductor fluid can be alternate or give in addition by being applied topically to skin.Here use term " part " to refer to material is administered on the surface of skin or mucosal tissue, it can via porous material that is full of or object, perhaps be used by spraying or atomizing via direct application (for example, diffusion).Be appreciated that that fluid is applied topically to experimenter's skin is normally not too accurate,, may make electrical connection between the electrode unintentionally, make electric current and moving iron not pass through skin directly by conductor fluid if carefully do not carry out.

Therefore, the shape of keeper, size and distribution method can change according to quantity, application and the position relevant with treatment.What show in Fig. 2 b-2g is the keeper that adopts the form of bucket 31, pipe 32, jar 33, container 34, allotter 35 and ampoule 36.Be appreciated that the present invention considers the keeper that all are such, and other keeper of Any shape, size or structure, it is used as and keeps conductor fluid, and distributes conductor fluid to be used for electrode or experimenter's skin as required.

Shown in Fig. 2 a is keeper 30, and it is a separator.The use of term " separator " is intended to describe the keeper of being made by the porous non electrically conductive material, and such as sponge, paper etc., it is as keeping conductor fluid therein.Separator provides the advantage that is better than other keeper to be, they allow accurately location conductor fluid, and they are not in disorder, and they allow to give accurate dose.

Fluid remains in the separator by this way, that is, the object that contacts with separator also contacts the fluid that is included in wherein.Therefore, by between electrode and separator, setting up the physics contact, can electrically contact with the conductor fluid foundation that remains in the separator.

Preferably, separator design and being configured as be assemblied in one or two electrodes 22 and 24 and experimenter's skin between, simple, cleaning and electrode/skin contact surface easily are provided like this, and electric current can flow to area for treatment via conductor fluid by this contact surface.As mentioned above, separator be constructed so that them non-conducting structure not impeded electrode 22 or 24 and conductor fluid wherein between electrically contact.Be appreciated that separator delocalization one-tenth makes itself or its content produce and electrically contacts between electrode 22 and 24.Such location will form the circuit of the skin that does not comprise the experimenter, and can obstruct electric application aims.

Separator can be fabricated to the form of stopper, box or small pieces etc., and it is designed to compatible with difformity, size and the structure of electrode 22 and/or 24.

According to preferred embodiment, as the preferably thin sheet shape keeper of the keeper 30 of separator, it can be required shape in embodiment, with compatible with the electrode of zone for the treatment of and use.Preferably by the thin layer protection, it is peeled off such separator before use.

Can pack separator and be used for storage or use, as can be compatible with the preferred embodiment of external member of the present invention.Separator is packing individually preferably, so that keep storage life, and avoids conductor fluid and/or comprises the evaporation of material wherein.

Above-mentioned keeper, the especially use of separator 30 be intended to make paster 10 in it uses for very user friendly, and almost very simple.The design of the keeper that shows and the extensive variation of shape be for accurately be applied in conductor fluid on the suitable electrode or topical application on experimenter's skin.For example, adopt the keeper of pipe 32 forms to allow accurately a small amount of conductor fluid simply to be deposited on the electrode.The keeper of employing ampoule 36 forms is guaranteed the medicine of correct dose.Allotter 35 allows carefully and accurately conductor fluid is applied to experimenter's parts of skin accurately.The preferred embodiments of the present invention make the vehicle of separator 30 as conductor fluid, and it can accurately be positioned on electrode or experimenter's the skin.

Be appreciated that the effective conduction by experimenter's skin is important for electric current in the accurate location of conductor fluid on relevant electrode or experimenter's skin.Therefore, comprise that the external member of paster 10 and one or more keeper 30 to 36 preferably also comprises any other utensil, indication, labelling, adminicle or device, it is used to help user correctly to use and locate conductor fluid as requested.

Several very simple embodiment about paster 10 of the present invention show in Fig. 3 a-5c.In the embodiment of Fig. 3 a-d, bar 100 is placed on the skin 102, and conduction lotion, gel, cream or analog 104 are applied on the skin 102, make when removing bar 100, formation receives two discontiguous regional 106 according to the paster 108 of teaching structure of the present invention and operation, and paster 108 is applied on the skin 102, makes one of each contact area 106 of its electrode 110, so that avoid short circuit.

In the embodiment of Fig. 4 a-d, having two opens 201 pattern and forms device 200 and be placed on the skin 202, and conduction lotion, gel, cream or analog 204 are applied on the skin 202, make when removing pattern formation device 200, formation receives two discontiguous regional 206 according to the paster 208 of teaching structure of the present invention and operation, and paster 208 is applied on the skin 202, makes one of each contact area 206 of its electrode 210, so that avoid short circuit.

In the embodiment of Fig. 5 a-c, folding paster 308 is placed on the skin 302 with its folding shape, and conduction lotion, gel, cream or analog 304 are applied on the skin 302 of its both sides, make when paster 308 flattens, formation receives 308 two discontiguous regional 306, and paster 308 contact skins 302 make one of each contact area 306 of its electrode 310, so that avoid short circuit.

With reference now to Fig. 6,, it shows the embodiment of paster 10 of the present invention, and wherein, electrode 22 is not integrated with electrochemical cell 14, but by conducting connecting part, is called connector 21 hereinafter and connects.Do not further describe according to embodiments of the invention and its and be similar to the parts of aforesaid paster 10, and determine by aforesaid same numeral.Adapter 21 can print, and perhaps can be any conductive material as known in the art.According to shown in embodiment, for the keeper of separator is deposited on the electrode 24 of electrochemical cell 14.Like this, in this structure, electrode 24 can be called medical electrode, and electrode 22 is called the electroconductive binder electrode.According to this embodiment, contact in the time of skin by electrode 22 and separator 30 and experimenter and can form circuit, it comprises the part of experimenter's skin as conductive path.In such structure, electrochemical cell 14 can produce electric current, its conductive fluid transport by being kept by the keeper 30 with contact skin.Electric current is by skin, and moving belt electron ion or molecule suitably in the conductor fluid that comprises wherein like this are to pass through skin.

A purpose of paster 10 is percutaneous or intradermal delivery drug substance, cosmetic substance or medicine woman's persona product material.As used herein, term " percutaneous " and " Intradermal " with and grammatical variants refer to respectively carry composition by/stride across skin or enter skin.As used herein, term " medicine " refers to therapeutic agent and anesthetis.As used herein, therapeutic agent can be understood as and comprises any material that is used for therapeutic treatment, healing, handles or keep fit.As used herein, anesthetis can be understood as and comprises and be used to cause the material that loses sense of touch, especially pain.Carry for electricity, such material preferably adopts charged molecule, and it can be in response to electric current.Be appreciated that any drug substance, cosmetic substance or medicine make up product material and can carry by invention described herein, it is charged needing only this material, perhaps can be by charged.

At material is not under the charged situation of nature, and it preferably makes up with the charging agent, perhaps experiences environmental condition, and such as special pH environment, its charge inducing forms.The method of charging molecule is known in the art, thereby does not further describe here.Under any circumstance, need to understand, the material that be transferred can or be accompanied by its conveying before it is carried and be recharged.

Therefore, term used herein " material " refers to active substance, and it preferably adopts the form of charged ion or charged molecule, and it can percutaneous or the conveying of Intradermal electricity. is common; The therapeutant that this is included in all primary treatment fields includes but not limited to the anti-infectives such as antibiotic and antivirotic; Comprise too slave of sweet smell; Sufentanil; The anodyne of buprenorphine and analgesic composition; Anesthetic; Anorexigenic; Antiarthritic; Anti-coughing such as Terbutaline breathed heavily agent; Anticonvulsive drug; Antidepressant; The anti-diabetic medicament; Antidiarrheal agent; Antihistaminic; Anti-inflammatory agent; Suppress the antimigraine preparation; The motion sickness agent thing; Preparation such as hyoscine and Ondansetron; Antinauseant; Antineoplastic; Mirapexin; Heart stimulant such as dobutamine; Antipruritic; Antipsychotic drug; Alexipyretic; Comprise stomach and intestine and antispasmodic uropoiesis; Anticholinergic drug; The sympathetic stimulation agent; Xanthine derivative; The cardiovascular preparation that comprises the calcium channel blocker such as nifedipine; Beta receptor blockers; Beta-agonists such as albuterol and ritodrine; Antiarrhythmic; Antihypertensive such as atenolol; Vel-Tyr-Pro-Trp-Thr-Gln-Arg-Phe; Diuretics; Comprise common; Crown; Peripheral and vasodilator brain; Central nervous system stimulant; Cough and cold-treating preparation; Decongestant; The diagnosis medicine; Such as parathyroid hormone; The hormone of auxin and insulin and so on; Hypnotic; Immunosupress; Muscle relaxant; Parasympathomimetic; Parasympathomimetics; Antioxidant; Nicotine; Prostaglandin; Psychostimulant; Anodyne and sedative. The present invention also is useful for carrying cosmetics and medicine to make up the product material.For example, such material comprises such as carotenoid, the skin effect antioxidant of ascorbic acid (vitamin C) and vitamin E and other vitamin preparation and so on and other antioxidant, anti-wrinkle agent such as biostearin, comprise vitamin A (retinol), alpha-hydroxy acid, beta hydroxy acid (being known as salicylic acid), combination hydroxy acid and polyhydroxy acid, and hydrolysis with soluble collagen and other, such as hyaluronic acid and the moisture retention liquid other, such as aminophylline and the anti-liparitosis agent other, such as tretinoin, the Porcelana Skin Bleaching Agent Porcelana of hydroquinone and peroxide and other and so on, such as aloe vera, wild yam, the Hamamelis virginiana tannin, Radix Ginseng, the galenical of green tea and other extract and so on.

Be appreciated that the present invention can be used for carrying in time cycle of requiring above-mentioned and other material of wide region dosage.

The percutaneous of material and intradermal delivery preferably take place by iontophoresis and/or electrophoresis process.Iontophoresis refers to by using the ionic motion that current potential causes.Electrophoresis refers to the charged colloidal particles or the high molecular motion that cause by using electric field.The electric current that is caused by the current potential between electrode 22 and 24 is used for from conductor fluid charge releasing belt isoelectric substance, from the molecular of conductive fluid transport charge species, and molecule is transported to contiguous skin histology.Be deposited on one or two electrodes 22 and 24 and experimenter's skin between conductor fluid in charge species will repel to electrode 22 and electrode 24 or by electrode 22 and electrode 24 according to their charge attraction.For example, if the material positively charged, electrode 22 repels materials, like this it is moved into or passes through skin.In such structure, when electric current from anelectrode 22 when the direction of skin flows, charged material is driven through conductor fluid/skin interface and enters skin.

Must be noted that the reverse ion electric osmose also can be used for from the process of health percutaneous or Intradermal recover materials.Such technology is used the same electrical principle of applied in reverse.The technology of percutaneous or Intradermal recover materials is known in the art.

The percutaneous of material or Intradermal motion also can be assisted by electroporation process.Electroporation is brought execution by the high-tension pulse that is applied to the pair of electrodes that is applied to tissue surface usually.Electric pulse causes through ion and passes organized layer, for charged and uncharged material by new passage is provided.Must be noted that electroporation is not carried charged material, but reduce material by entering the resistance of adjacent tissue.Because it does not provide the driving force that needs, so need be with electroporation and the combination of the conveying technology such as iontophoresis or electrophoresis, so that obtain good infiltration.

The preferred purpose of another of paster 10 be by directly by the dermal application electric current promote wound healing, reduce cicatrix, prevent cicatrix, tissue repair and/or tissue regeneration.Electric current knows already, and be used in the treatment by the electricity irritation that provides with electric pulse form outside promote human body can be excited cell (receptor of neural, muscle and teleneuron) produce electroresponse, so-called action potential.These action potentials are to have the amplitude of qualification and the endocellular electricity pulse of persistent period for the relevant cell type.For example, for nerve, approximately the pulse width of 1ms and about 80mV are typical to the amplitude of 100mV.This cellular-restoring is to its cell membrane voltage, and it has value between 60mV and the 120mV according to cell type when static.This voltage is by producing by the different ion concentration in the space in the isolated extracellular space of cell membrane and the cell.There is more cation in the extracellular.According to definition, the current potential of outside is set to 0V, makes given nagative potential in cell.

In the people of health, action potential is produced by health itself, and is used for the information transmission and triggers cell processes.

In electrotherapy, therapeutic effect is caused by the specific generation of action potential (quantity that limits and in specific place).

Be used for diathermic equipment and use multiple different electric current or impulse form.In order to select to be suitable for most the electrotherapy of specific sign, the therapist should be able to return to the standard of maximum clear definition.These standard sources are from answering, with effectiveness and the tolerance of analyzing various current forms.

The scope of effect comprises, for example, the demulcent zone of pain, striped muscle and non-striped muscle, influences dabbling stimulation, checks the zone of inflammatory process, and promote regenerated detumescence machine-processed (healing acceleration of wound, skeleton etc.).The target of this application always should be for obtaining far-end or the near-end at electrode by correct selection current forms, perhaps the required effect in the influence area of the depths of health.

Basically, electrotherapy apparatus depends on polar " polar stimulation principle " and does not rely on polar " no polar stimulation principle " based on two kinds of stimulating current methods.

Scope is used for " polar stimulation principle " from 0 to 200Hz low frequency ac (LF electric current).Hyperpolarization (rising in membrane voltage) appears at below the anelectrode (anode), makes that the spacing of current potential between the stimulation thresholding in the cell is bigger.On the contrary, the membrane voltage below negative pole (negative electrode) descends.When arriving the stimulation thresholding, the automatic trigger action current potential of cell.

Stimulating current equipment uses in the different pulse shape that approximately＞0 arrives in the low-frequency spectra (LF electric current) of 200Hz.Applicable is for example so-called delta current, rectangle electric current, a streaming current, high-tension current, too drastic stimulating current, faradic currents or the like.Some alternating currents have DC component, and it supports polarity effect extraly.

Two kinds of methods that depend on the current potential of usage operation remedially of frequency are arranged:

Function imitation principle:

Determine to carry out the quantity of the action potential of its task by excitable cell (for example, nerve or muscle) being used to of producing.In treatment, in corresponding cell, produce the pulse of equal number then by stimulation, thereby sustenticular cell is carried out its task.

For example, the stimulus frequency that use to arrive 6Hz produces the contraction that reaches per second 6 times.

Tired principle:

On the contrary, when by producing action potential so that when carrying out the fast slightly frequency stimulation of the desired frequency of its task and impelling cell (nerve or muscle) to produce action potential with higher frequency and than cell, it is tired after the short time.Reverse effect produces.Cell fatigue can be explained by the energy expenditure process in forming action potential.

For example, according to tired principle, stimulate the hardened muscle that to relax by " higher " frequency with for example 100Hz or 200Hz.

In order to produce any action potential fully, intensity must be chosen as enough height certainly, stimulates thresholding to surpass.The rank of the intensity that is set up depends on following factor: be by the position (degree of depth) (leave the distance of electrode) of stimulated cells in tissue, the resistance of the size of electrode and the tissue in the zone that is penetrated by current potential, it is subjected to the parameter influence of current forms again.

In fact, current forms and electrode size are stipulated.In order to stimulate a group cell (for example, in the depths of tissue) apart from electrode a distance, electric current and/or voltage strength continue to increase, and produce up to action potential now.

Along with the increase of intensity, being positioned at deeper and deeper cell or leaving electrode cell far away is day by day successfully stimulated.By no polar stimulation principle, only use alternating current (MF electric current) without any the so-called intermediate frequency of DC component.The meaning of MF electric current is to have＞and 5Hz is to the sinusoidal ac of the frequency of 100000Hz.Monocycle (alternating-current pulse) with sufficient intensity has polarity effect, and it can trigger the action potential in nerve or muscle cell.

Usually, " summation effect " appears.Under the frequency that increases, also need higher day by day intensity, so that can trigger the action potential in cell.Wyss is verified without doubt, the action potential that produces with the MF pulse fully and polarity effect irrespectively carry out.This means that intensity and vibration quantity are enough big anyplace, action potential all can produce, and with moment polarity irrelevant (Wyss, the Oscar A.M. of MF electric current; Prinzipien der elektrischenReizung, [Principle of Electrical Stimulation], Neujahrs-Blatt, publish in 1976 by Natural Research Society in Zurich, Kommissionsverlag Leeman AG, Zurich, 1976,28-34).

The MF pulse＞0 to about 200Hz low frequency repetitive rate and＞5Hz uses under the carrier frequency of 100000Hz.In fact, these great majority are sinusoidal, amplitude modulation MF electric currents (AM-MF electric current).Following principle and being consistent in conjunction with " polar stimulation principle " description.

Function imitation principle:

Synchronous with MF pulse (amplitude modulation), can in the excited cell action potential appear.Thereby cause this cell to carry out its natural functions, it sends from this frequency.

Tired principle:

For make can be excited cell fatigue, use MF pulse with higher amplitude.

When current intensity rose, being positioned at more and more, the cell of dark (farther apart from electrode) was successfully stimulated.

Follow the frequency of increase, need bigger intensity to produce action potential.

Based on the alternating current of intermediate frequency, provide the following extra selection of treatment:

When the MF electric current (constant amplitude) with sufficient intensity stimulates, at first produce action potential.Along with the MF electric current flows the long time, the decay side of action potential remains on unpolarized level (permanent depolarization), and it equals the only about half of of equilibrium potential.When closing the NM electric current, membrane voltage descends, and decays to the level of equilibrium potential then.

Following subitem has been described permanent unpolarized treatment utilization.

Pain relaxes and the influence perfusion:

Because permanent depolarization, depend on the character in the zone of being treated and high strength in the tolerance limit scope causes the neural blocking-up that transmits passage.This real nerve block is (by E.K.University of Ljublijana, Rancho Los Amigos Hospital, Downey, Calif, U.S.A. BOWMAN, Burce is the evidence of the paper foundation in year R.1981) be used for for example blocking in the pain of phantom limb pain, perhaps be used for blocking-up at the Stellatum of blood flow imbalance.

Muscle contraction:

Muscular training in spontaneous innervation deficiency and muscle stretch.

Because the neuromuscular organ is perfect, striped muscle (skeletal muscle) is directly stimulated by permanent depolarization.This causes muscle contraction, and it is used for for example spontaneous innervation deficiency of muscle, perhaps is used to stretch the Antagonistic muscle of spasm muscle.During treating, intensity should be interrupted by short time-out at interval.This intensity also can adjusted value 100% and about 50% between increase and reduce.

Produce strong muscular contraction force:

Very strong muscle contraction can cause under the situation of fatigue phenomenon not having.In the tetanic property contraction that can cause, because the quick decline of muscular contraction force appears in myokinesis unitary fatigue on the contrary by the stimulating current of about 50Hz and Geng Gao.

Cell division

The bone healing of wound healing and acceleration:

Permanent depolarization causes the cell division of healthy cell.Thereby can promote wound healing, quicken the bone healing in the fracture.In addition, under electric alternating-current field effect, the MF electric current causes the reciprocating motion (oscillation action) of the charged molecule in the tissue that electric current penetrates, and is accompanied by rotatablely moving of charged molecule part.Thereby, acquisition be bigger possible " correctly " junction position of enzyme and substrate, it is chemical reaction (metabolism growth encourage) in metabolic processes.This oscillation action is easy to produce level error in concentration, like this, because the diffusion process that existing Concentraton gradient carries out on certain direction is owing to the kinetic energy that additionally gives is accelerated (MF iontophoresis, inhibition inflammation, mitigation pain).

Oscillation action is especially effective under high strength.

The distribution of inflammation and pain amboceptor:

Suppress inflammation and relax pain:

In pain, inflammatory process, in ill tissue, often find the inflammation and the pain amboceptor of high concentration.This high concentration reduces (dispersion) by oscillation action.That caused by high current intensity, identical with frequency should " oscillation intensity " have big meaning (Hans-Jurgens to therapeutic effect, May, Elektrische Differential-Therapie[ElectricalDifferential Therapy], Karlsruhe 1990).

Metabolic influence (diffusion, mitochondrion, circulation A MP):

The growth encourage of metabolic processes and promotion:

As mentioned above, promoted the biochemistry metabolic processes.

Still with MF electric current penetration cell culture, have been found that the quantity of mitochondrion (" the energy factory " of cell) and their size greatly increase.

According to MF electric current and/or voltage, important courier's material of cell, the concentration of circulation A MP also can be subjected to alternating current to influence (Dertinger, 1989, KemforschungszentrumKarlsruhe, Nagy Nemectron GmbH Karlsruhe).

In addition, can cause painless and strong muscle contraction by the MF electric current.

So-called " thresholding division " occurs from 8kHz, just, the thresholding amperage of muscle contraction is lower than the amperage (Edel of sensation thresholding, H.:Fibel der Elektrodiagnostikand Elektrotherapie[Primer of Electrodiagnostics andElectrotherapy, Muller﹠amp; Steinicke Munchen 1983, p.193]).Strong muscle contraction can not have causing of pain.The viewpoint of treatment, thresholding division is interested especially in the reversible process of the muscle contraction that the permanent depolarization of using by the MF electric current causes.

Because the high strength of MF electric current produces heat in the tissue that electric current penetrates.Can comfortable (sensation, muscle, tolerance, pain) but prerequisite is to surpass the thresholding patient.

Be similar to the improvement of metabolic processes, iontophoresis also can be attended by the MF electric current, that is, medicine is given to enter health by skin under the help of electric current.Because concrete condition is compared with galvanic current, use the iontophoresis of MF electric current to require long treatment time and the intensity of Geng Gao.

As mentioned above, and in subsidiary commercial transaction document (handbook " ElektrischeDifferential-Therapie " [Electrical Differential Therapy] byA.Hangsjuorgens and H.U.May, 1990; Nemectron GmbH, Karlsruhe) also find in the scope, according to diagnosis, existing electrotherapy apparatus uses in frequency＞0 to low-frequency current or the amplitude modulation intermediate frequency electric current of 200Hz, perhaps frequency is at＞5Hz intermediate frequency the electric current to 100000Hz, and each has constant amplitude (intensity).

Because any one in the such use and a plurality of expectations transdermal patches of the present invention are used to control the current level of electrochemical cell 14 generations or the circuit of persistent period so paster 10 preferably includes.The on-off switch that such circuit can adopt the drug conveying that is used for " as requested " (for example, patient controls transporting of analgesic and is used to relax pain), intervalometer, fixed or variable resistance, open and close device automatically with the cycle that requires and mate the controller of body's natural or circadian pattern, the perhaps form of the more sophisticated electronic-controlled installation of other that is known in the art.For example, because constant current level is guaranteed the constant rate of speed of mass transport, so carry the predetermined constant level of electric current to expect.The level of electric current can be controlled by multiple known devices, for example, and the simple circuit of resistance or use resistance and field-effect transistor.Circuit also can comprise integrated circuit, and it can be designed as the dosage of the activating agent that control carries, perhaps or even the response sensor signal, so that adjust the regime that dosage is kept predetermined close.Simple relatively circuit can be controlled electric current as the function of time, and if expectation, produce complicated current waveform, such as pulse or sine wave, as above further describe.In addition, circuit can use biological feedback system, and its monitoring bio signal provides the assessment of treatment and regulates active agent delivery.Typical example is the monitoring of blood sugar level, and what be used to control gives insulin to diabetic.The simple still important use of control circuit is to avoid thermal accumlation and final tissue damage.Be appreciated that the ion conveying owing to ion motion produces heat, and conveying is many more, many more at the thermal accumlation of the position of carrying.Same, the electric current that is used for the treatment of can be that patient is controlled, so that find balance between the discomfort of maximum delivery material and minimum temperature increase.

Therefore, external member according to the present invention comprises the transdermal patches that is used for percutaneous and/or at least a material of intradermal delivery, and is used for keeping before use material to leave at least one keeper of paster.This structure allows to carry out multipurpose by single transdermal patches and uses material/dosage.

Therefore, method according to a kind of percutaneous of the present invention or at least a material of intradermal delivery realizes like this, promptly, (a) conductor fluid that will comprise this material partly is applied on experimenter's the parts of skin, and/or the conductor fluid that will comprise material is deposited at least one electrode of transdermal patches, and this transdermal patches comprises having the electrochemical cell of at least two positioning of electrodes on a side of transdermal patches; (b) the location transdermal patches makes electrode and experimenter's parts of skin electrically contact; And (c) by conductor fluid and parts of skin conveying electric current, so that percutaneous or intradermal delivery material.

Therefore, a kind of method that electric current and/or voltage are incorporated into experimenter's parts of skin according to the present invention realizes like this, promptly, (a) partly conductor fluid is applied on experimenter's the parts of skin, and/or conductor fluid is deposited at least one electrode of transdermal patches, this transdermal patches comprises having the electrochemical cell of at least two positioning of electrodes on a side of transdermal patches; (b) the location transdermal patches makes electrode and experimenter's parts of skin electrically contact; And (c) by the conductive fluid transport electric current, so that electric current and/or voltage are incorporated into experimenter's parts of skin.

Be appreciated that conductor fluid can be deposited on be maintained in the keeper or one or two electrodes by any one distribution from described other keeper on.Be further appreciated that above-mentioned application of the present invention can also be by realizing to skin at the position topical application conductor fluid of placing electrode.

Compare with the existing paster that comprises the material of wanting percutaneous or intradermal delivery inherently, the invention provides many advantages, because single transdermal patches can be used to carry any amount of different material/dosage, as long as it is powered, it does not need to be dropped, because it exhausts never.

Those skilled in the art during following Example, can understand other purpose of the present invention, advantage and novel feature in check, these examples be not be intended to restricted.In addition, as description hereinbefore, and find experiment support in claimed in the following claims each different embodiment of the present invention and the aspect example below.

Example

With reference now to following Example,, it has illustrated the present invention with top description with non-limiting way.

The treatment of slight rosacea

The part hyperemia and the telangiectatic slight rosacea that are characterised in that face are general diseases, and it torments a lot of people, mainly from aging population.Unfortunately, the treatment of slight rosacea is limited.

Three patients with slight rosacea participate in pilot study, the inclusion criteria below satisfying:

Patient has slight rosacea, relax the hyperemia of the both sides of face; And

Patient is between 20 to 65 years old.

Research purpose is during treating and the therapeutic effect of congested phenomenon is detected in the treatment back, and detects side effect.

Each research experimenter accepts the treatment of the both sides of face.

On a side of face, " active paster " is connected to power supply by fine rule, so that the big part of paster (main paster) is connected to the positive pole of power supply, the little part of paster (paster relatively) is connected to the negative pole of power supply.

Be free of attachment on experimenter's the opposite side of face that having of power supply identical shaped " passive paster " be used in each test.

Each paster is coated with test formulation (aqueous gel comprises the Radix Hamamelidis Mollis extract).Use and transfer spatula that the test formulation of 0.4ml is applied on the main paster equably, the test formulation of 0.1ml is applied on the relative paster equably.Then, paster is applied on research experimenter's the skin, continues 5 periods of 7 to 20 minutes (treatment period).

After removing paster, immediately, and observed, comprise by patient's subjective assessment with by trained observer not having inclined to one side evaluation at after this 10,25 and 40 minutes.Before treatment and at all points of observation, take a picture.

In all three patients, have significantly in the congested degree of active paster location and telangiectasis scope to reduce.This improvement is at first observed after paster is removed immediately, and further proves period in remaining observation.Passive paster zone presents very small improvement, and it is not thought significant by patient and observer.

Be appreciated that for clear and some feature of the present invention that describe in the content of the embodiment that separates also can make up and be arranged among the single embodiment.On the contrary, the of the present invention various features of describing in the content of single embodiment in order to know also can be provided with dividually or with any suitable recombinant.

Those skilled in the art are appreciated that and the invention is not restricted to hereinbefore specifically to show and describe.On the contrary, scope of the present invention has the accompanying Claim book to limit, and is included in various combination of features and the recombinant of above describing, and those skilled in the art have read its variant and improvement that the description of front can be expected.Therefore, it is intended to comprise the spirit that is arranged in the accompanying Claim book and all such substitutes, improvement and the variant of wide region.

Claims (42)

1. external member that is used for carrying at least a material through skin or in skin, it comprises:

(a) transdermal patches, the profile phase of this transdermal patches and skin surface is fit to, this transdermal patches comprises electrochemical cell and at least two electrodes that are electrically connected with this electrochemical cell, and this electrode comprises negative electrode and anelectrode, and this electrode and experimenter's parts of skin electrically connects;

(b) at least one is used to keep comprise the keeper of the conductor fluid of described at least a material, and described conductor fluid is used to be deposited at least one electrode of described at least two electrodes, and/or on the partial parts of skin that is applied to the experimenter;

Described transdermal patches is designed to and is configured as to be convenient to carry electric current by skin and described conductor fluid, and described electric current is used for carrying through skin or in skin described at least a material;

Wherein said transdermal patches can be folding along two adjacent lines, makes electrode to be folded to leave parts of skin or being flattened on this parts of skin.

2. external member as claimed in claim 1 is characterized in that: described conductor fluid is based on the fluid of water.

3. external member as claimed in claim 1 is characterized in that: described conductor fluid is a hydrogel.

4. external member as claimed in claim 1 is characterized in that: described electric current is as causing iontophoresis, electrophoresis, electroporation or its any combination.

5. external member as claimed in claim 1 is characterized in that: at least one electrode and the described electrochemical cell of described at least two electrodes are integrally formed.

6. external member as claimed in claim 1 is characterized in that: described electrochemical cell and described at least two electrodes are configured to described transdermal patches individually.

7. external member as claimed in claim 1 is characterized in that: described transdermal patches also comprises and is used for described transdermal patches is attached to attachment mechanism on experimenter's the parts of skin.

8. external member as claimed in claim 1 is characterized in that: described transdermal patches also comprises the circuit that is used to control described electric current.

9. external member as claimed in claim 1 is characterized in that: described electrochemical cell is flexible thin layer electrochemistry battery.

10. external member as claimed in claim 1, it is characterized in that: described electrochemical cell is the electrochemical cell of the thin layer open liquid state of flexibility, it comprises the insoluble negative pole of ground floor, the insoluble positive pole of the second layer and the 3rd layer of aqueous electrolyte, described the 3rd layer is arranged between described first and second layers, and comprises:

(a) be used for always keeping the deliquescent material of open cell humidity;

(b) be used to obtain the electroactive soluble material of required ionic conductivity; And

(c) be used to obtain the water-soluble polymer of required viscosity, with described first and the described second layer adhere to described the 3rd layer.

11. external member as claimed in claim 1 is characterized in that: be used for from comprising wound healing applications, prevent the cicatrix application, reducing the application that cicatrix is used, tissue repair is used, tissue regeneration is used and the group of treatment rosacea is selected.

12. external member as claimed in claim 1 is characterized in that: described conductor fluid comprises described at least a material.

13. external member as claimed in claim 1 is characterized in that: described at least a material is to select from comprising that medicine, cosmetics and medicine are made up the group of product.

14. external member as claimed in claim 1, it is characterized in that: described keeper is the separator that is used to be deposited on the parts of skin, make that when contacting described electric current causes that the described of described at least a material carry through skin or in skin by at least one of described separator and described at least two electrodes.

15. external member as claimed in claim 1, it is characterized in that: described keeper is the separator that is used to be deposited at least one of described at least two electrodes, make that when contacting with parts of skin described electric current causes that the described of described at least a material carry through skin or in skin by described separator.

16. as claim 1 or 14 described external members, it is characterized in that: described separator is included in the removable lid.

17. external member as claimed in claim 1 is characterized in that: this transdermal patches is flexible paster.

18. external member as claimed in claim 1 is characterized in that: this transdermal patches also comprises the paster main body, and described electrochemical cell and described at least two electrodes are arranged on this paster main body, avoids the contact between described at least two electrodes.

19. transdermal patches, it comprises and being used for to the electrochemical cell of this transdermal patches power supply and at least two electrodes that are electrically connected with this electrochemical cell, described electrode and experimenter's parts of skin electrically connects, and at least one electrode and described electrochemical cell in wherein said at least two electrodes are integrally formed; In wherein said at least two electrodes at least one is the terminal of electrochemical cell.

20. paster as claimed in claim 19 is characterized in that: its be used for electric current and/at least a conveying that voltage is transported to described experimenter's parts of skin, at least a mass transport is carried, carried and carry in skin through skin to the skin of this parts of skin of described experimenter.

21. paster as claimed in claim 19 is characterized in that: this transdermal patches is flexible paster.

22. paster as claimed in claim 19 is characterized in that: this transdermal patches also comprises the paster main body, and this electrochemical cell and described at least two electrodes are arranged on this paster main body, avoids the contact between described at least two electrodes.

23. paster as claimed in claim 19 is characterized in that: at least one in described at least two electrodes is the terminal of electrochemical cell.

24. paster as claimed in claim 19 is characterized in that: described at least two electrodes are terminals of electrochemical cell.

25. paster as claimed in claim 19 is characterized in that: described electrochemical cell is flexible thin layer electrochemistry battery.

26. paster as claimed in claim 25, it is characterized in that: described electrochemical cell is the electrochemical cell of open liquid state, it comprises the insoluble negative pole of ground floor, the insoluble positive pole of the second layer and the 3rd layer of aqueous electrolyte, described the 3rd layer is arranged between described first and second layers, and comprises:

(a) be used for always keeping the deliquescent material of open cell humidity;

(b) be used to obtain the electroactive soluble material of required ionic conductivity; And

(c) be used to obtain the water-soluble polymer of required viscosity, with described first and the described second layer adhere to described the 3rd layer.

27. paster as claimed in claim 19 is characterized in that: be used for from comprising wound healing applications, prevent the cicatrix application, reducing the application that cicatrix is used, tissue repair is used, tissue regeneration is used and the group of treatment rosacea is selected.

28. paster as claimed in claim 19 is characterized in that: also comprise conductor fluid.

29. paster as claimed in claim 28, it is characterized in that: this conductor fluid comprises at least a material, and this conductor fluid is applied on described two electrodes in advance at least, and when the time by described paster and contact skin, carry electric current by this conductor fluid and experimenter's skin, so that carry described at least a material through skin or in skin.

30. paster as claimed in claim 28 is characterized in that: described conductor fluid is aqueous hydrogel.

31. paster as claimed in claim 20 is characterized in that: described at least a material is to select from comprising that medicine, cosmetics and medicine are made up the group of product and moisture.

32. a transdermal patches, the profile phase of this transdermal patches and skin surface is fit to, and it comprises:

Be used at least two electrodes that the parts of skin with the experimenter electrically connects, described electrode comprises negative electrode and anelectrode;

With the electrochemical cell that described at least two electrodes electrically connect, wherein this electrochemical cell is to this transdermal patches power supply; And

Wherein this transdermal patches can be folding along two adjacent lines, makes electrode to be folded to leave parts of skin or being flattened on this parts of skin.

33. transdermal patches as claimed in claim 32 is characterized in that: described at least one negative electrode, described at least one anelectrode and described electrochemical cell are arranged on the paster main body, avoid the contact between each electrode.

34. transdermal patches as claimed in claim 33 is characterized in that: described at least one negative electrode and described at least one anelectrode are applied on this paster main body by using printing technology.

35. transdermal patches as claimed in claim 32 is characterized in that: also comprise at least a material, described at least a material is to select from comprising that medicine, cosmetics and medicine are made up the group of product and moisture and combination thereof.

36. transdermal patches as claimed in claim 32 is characterized in that: it is used for impelling the parts of skin of active species delivery to the experimenter.

37. transdermal patches as claimed in claim 32 is characterized in that: it is used for current/voltage is transported to experimenter's parts of skin.

38. transdermal patches as claimed in claim 32 is characterized in that: at least one electrode is medical electrode, and at least one electrode is an adhesive electrodes.

39. transdermal patches as claimed in claim 38 is characterized in that: conductor fluid or electrically conductive composition are arranged on these medical electrode.

40. transdermal patches as claimed in claim 32, it is characterized in that: described electrochemical cell comprises flexible electrochemical cell, and electrochemical cell that should flexibility is the electrochemical cell of flexible thin layer open liquid state, it comprises the insoluble negative pole of ground floor, the insoluble positive pole of the second layer and the 3rd layer of aqueous electrolyte, described the 3rd layer is arranged between described first and second layers, and comprises:

(a) be used for always keeping the deliquescent material of open cell humidity;

(b) be used to obtain the electroactive soluble material of required ionic conductivity; And

(c) be used to obtain the water-soluble polymer of required viscosity, with described first and the described second layer adhere to described the 3rd layer.

41. transdermal patches as claimed in claim 32 is characterized in that: this transdermal patches is applicable to active species delivery to parts of skin.

42. an external member that is used for electric current and/or voltage are incorporated into experimenter's parts of skin, this external member comprises:

(a) transdermal patches, the profile phase of this transdermal patches and skin surface is fit to, this transdermal patches comprises electrochemical cell and at least two electrodes that are electrically connected with this electrochemical cell, and described electrode comprises negative electrode and anelectrode, and described electrode and experimenter's parts of skin electrically connects; And

(b) at least one is used to keep the keeper of conductor fluid, and described conductor fluid is used to be deposited at least one electrode of described at least two electrodes, and/or on the partial parts of skin that is applied to the experimenter;

Described transdermal patches is designed to and is configured as to be convenient to carry electric current by skin and described conductor fluid;

Wherein said transdermal patches can be folding along two adjacent lines, makes electrode to be folded to leave parts of skin or being flattened on this parts of skin.

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