CN1479615A - Medicuted tattoos - Google Patents
Medicuted tattoos Download PDFInfo
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- CN1479615A CN1479615A CNA018203957A CN01820395A CN1479615A CN 1479615 A CN1479615 A CN 1479615A CN A018203957 A CNA018203957 A CN A018203957A CN 01820395 A CN01820395 A CN 01820395A CN 1479615 A CN1479615 A CN 1479615A
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- drug substance
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- adhesive layer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
Abstract
A transdermal medicament delivery device in the form of a printed temporary tattoo (2) which conceals the fact that the wearer is taking a drug. The ornamental appearance actually provides an incentive for wear. The medicated tattoo (2) includes a section of cardstock base paper (70), a clear base (50) bearing an ink design on one side, the clear base being attached to the cardstock base paper (70) on the other side by a release base (60) that dissolves when wet to allow detachment of the base paper, and an adhesive layer (20) coated over the ink design on the clear base for adhesion to the skin. A medicament or drug (30) is incorporated into the adhesive layer for diffusion therefrom into the skin of the wearer, and the adhesive layer (20) has predetermined permeability characteristics to ensure effective transdermal delivery of the medicament (30). The process for making the transdermal tattoos includes lithographic printing and silk screen coating to create the necessary layers, inclusive of drug deposition on the control membrane. Th net result is less susceptible to being dislodged, thereby allowing more conventional low-strength skin adhesives to make intentional removal easy and painless. Moreover, the tattoo can provide an outward visual indication of the progress of delivery.
Description
The present invention relates to percutaneous dosing and percutaneous nutrient supply, particularly be the transdermal delivery device of printing the temporary form of tatooing.
Background technology
As everyone knows, topical is used for the treatment of the local skin disease, still the technology that skin is still just grown up recently as the approach that is administered systemically.Up to the present, only allowing to use considerably less several through leathercraft, mainly is because will realize that consistent injection speed is very complicated.Have various changing factors, influence the percutaneous absorption of medicine and enter basic circulation, these factors comprise the biological characteristics of skin, the chemical characteristic of medicine and the interaction between skin and the drug-supplying system.The medicine of collecting has been carried out systematic study through the permeability data scope of skin cutricular plate and skin corium.These transmutabilities that studies show that the most drug process are very big and very slow.Therefore, only have several with the medicine that uses by the dosage form of percutaneous dosing at present.People are making great efforts to improve the method for regulating skin in many ways.For example, people's such as Eppstein US5455611 has instructed, and needs to regulate skin by chemical enhancer and ultrasound wave, renders a service in order that improve percutaneous dosing.
On the other hand, the composing method of doser has multiple.For example, the structure of existing transcutaneous device can make simple two-layer project organization.For example, the US4598004 of Heinecke discloses medicated bandage, is included in the pressure-sensitive adhesive on the liner, and liner firmly is bonded on the administration band successively.
In addition, according to the specific drug of topical application, the percutaneous project organization can comprise that more composite and structure finish administration.
For example, people's such as Andriola US4666441 discloses the initial percutaneous membrane structure with many capsules.
People's such as Chien US5788983 discloses controlled administration through epithelium, and its Chinese medicine is contained in little storage capsule and by permeable membrane and is diffused in the skin.
The microcapsule bag of material is another kind of percutaneous dosing method of generally acknowledging.For example the US4597960 of Cohen has instructed the astringent of the microcapsule of packing into that is used for percutaneous dosing.
All above-mentioned and other known transcutaneous devices are the laminated multi-layer " film " that comprises medicine storing bag.For example, the film more than 75% contains the 3M composition in the world, comprises protectiveness substrate, bottom medicine storing bag, leaches the controlled release film and the bottom skin adhesive of medicine.Can use various contact skin adhesive, comprise the adhesive of siloxanes, acrylate, polyisobutylene (PIB) and rubber-based.3M adopts patent laminating method bonding said structure, and final result brings many significant problems.At first, complicated laminating method is unsuitable for large-scale production, and medicine must be injected in the storage capsule, and such film manufacturing cost is very high.In addition, film is difficult for being shaped on skin, and the influence that is subject to move.Clothes absorbs moisture usually, and this impairs effect and be easy to and moves.Prevent that the universal method that moves too early from being to improve the intensity of adhesive, but be to use the people of nicotine film to represent, this has increased the difficulty of removing intentionally and has brought pain, usually stays hypersensitive skin print.Except cost, also has the shortcoming in some serious application.These films are not attractive in appearance, and shown and therefore, hindered the situation of wearer's drug of topical application and worn.In addition, except blood testing, definitely have no idea to monitor medicine and whether be absorbed.
The another kind of technology that satisfies the needs of consumers of development is rapidly arranged, and this will like never before be of value to the percutaneous industry.Temporary tatooing has the multiple quality that makes percutaneous more practical, as (adopting dressing plate typography and screen printing) low cost of manufacture, alleviates administration misery, temporary effect and excitation people and wears the percutaneous that meets esthetic requirement.US5776586 is an example that adopts the method for tatooing of dressing plate printing and method for printing screen.This method only comprises with the pre-stacked cardstock of water-soluble releasing agent coating, places hyaline membrane, prints the pattern of tatooing on film, and adopts protectiveness to cover.
Print owing to tatoo, therefore be easy to symbol or other labelling that display simulation attracts the child, greatly encouraged child's drug of topical application thus.In addition, by this method, can make tatooing of printing with printing ink, it disappears along with the absorption of medicine or changes, and the actual indication of percutaneous dosing speed and effect is provided first.
Therefore, be beneficial to very much and tatoo and imprint lithography/silk screen manufacture method is used for percutaneous dosing, and in the percutaneous field, obtain thus temporaryly to tatoo that all are potential aesthetic and show advantages temporary.
Summary of the invention
Therefore, the transdermal delivery device that the purpose of this invention is to provide the temporary form of tatooing that is printing.
Another purpose is, do not adopt lamination, forms multilamellar but rely on offset printing and silk screen to apply, and multilamellar comprises the medicine that is deposited on the controlling diaphragm, makes so that simplify.
Another purpose is, a kind of difficult shaping percutaneous dampness and that be easy to remove that do not absorb is provided, and uses more common low-intensity skin adhesive thus and is convenient to the removal of having a mind to and do not feel pain.
Another purpose provides a kind of transdermal delivery device, and it has the outside vision indication that degree is carried out in administration.
Another purpose provides and a kind ofly looks like the transdermal delivery device of tatooing, so that cover the situation of wearer's drug of topical application, in fact this decorative appearance has encouraged and worn.
Another purpose provides a kind of transdermal delivery device, and it shows the attraction child's of (fix, manifest in time or disappear) decoration simulation symbol or other labelling, in order that encourage child's drug of topical application it is not revolted.
According to the present invention,, the temporary transdermal delivery device of tatooing and the manufacture method thereof that are printing realize above-mentioned and other purpose by being provided.Medicuted tattoos comprises one section cardstock base paper (cardstockbase paper); One side scribbles the transparent substrate of ink logo, and described transparent substrate opposite side posts described cardstock base paper by discharging substrate, dissolves when substrate becomes wet when discharging, so that break away from basic paper; Adhesive layer is coated on the ink logo on the described transparent substrate, so that be bonded in skin, described adhesive layer is made of one of the micropore with predetermined Penetration Signature and microchannel.Medicament mixed is in adhesive layer, so that be diffused into thus in wearer's the skin, and adhesive layer has predetermined permeability, so that guarantee effective percutaneous dosing.
The method that the manufacturing percutaneous is tatooed comprises step: at transparent substrate upper flat plate printing-ink pattern; With the drug substance silk screen printing on described transparent substrate and relative with described ink logo; And cardstock base paper is bonded in the drug substance layer.
Brief Description Of Drawings
By below in conjunction with accompanying drawing to preferred embodiment and some improved detailed description thereof, can clearer understanding other purpose of the present invention, feature and advantage, wherein:
Fig. 1 is tatoo 2 a decomposition view of percutaneous of the present invention;
Fig. 2 is that line with rubber adhesive layer 20 is provided with the enforcement illustration that micropore is leached by drug substance layer 30 with the control active medicine specially down;
Fig. 3 and 4 shows and applies the medicine of paste/solution form and adhesive by silk screen printing and stay two steps of medicine pattern deposit 120 on 2 so that tatoo at percutaneous;
Fig. 5 has the colour code 23 of visual contrast so that absorb the percutaneous carry out the degree indication 2 views of tatooing for user provides;
Fig. 6 has the gradual change ratio indication 43 of similar thermometer so that absorb the percutaneous that carries out the degree indication 2 views of tatooing for user provides;
Fig. 7 has the percutaneous of being convenient to the disappearance characteristic point 33 that the child uses 2 views of tatooing.
The preferred embodiment mode
The following describes according to the percutaneous of various embodiments of the invention tatoo structure and preferable production process and various drug candidate materials that can administration.In addition, also tatoo 2 mode of dosing is used in explanation, and explanation can degree be indicated and the child strengthen feature in conjunction with carrying out with selected absorptions that improves effectiveness of the present invention.
1. percutaneous 2 the structure of tatooing
Fig. 1 is tatoo 2 a decomposition view of percutaneous of the present invention.Percutaneous is tatooed and 2 is generally included following seven layers:
20 adhesive layers
30 drug substance layers
40 color layers
50 transparent substrates
60 discharge substrate
70 basic paper
Base is coated with on the paper 70 and discharges substrate 60, dissolves when substrate 60 is soaked when discharging, so that take basic paper 70 off from tatoo 2 function (skin attachment) part of percutaneous.Discharge substrate 60 and preferably include polyoxyethylene sulfate (polyoxyethylene sulfate) and/or polyoxyethylene alkylphenyl ammonium sulfate (ammonium polyoxyethylene alkylphenylether sulfate).As described below, before color layer 40 is stamped, the most handy screen printing will discharge substrate 60 and be imprinted on the basic paper 70, and this helps to prevent colored ink is sucked in the basic paper 70.
By discharging substrate 60 transparent substrate 50 is bonded on the basic paper 70, adheres to bottom so that the cutis elastica of protection ink color layer 40 quality is set.
In either case, in order to ensure the absorbance of skin, must control the desorption of drug substance layer 30 and adhesive layer 20 to every kind of material.
Fig. 2 shows a kind of embodiment that finishes above-mentioned work.Following line with rubber adhesive layer 20 is provided with micropore 32 especially so that control active substance leaching from drug substance layer 30.Should be understood that monolayer micropore adhesive layer can be replaced by the porous membrane that is coated with adhesive.The various porous and absorbent papers that are suitable for contacting skin are arranged, and that uses for this purpose has a Macroflux that is called that Etrans provides
The contact skin surface layer.Should also be noted that and to use microscopic channels or other project organization and do not use the hole, control active medicine leaching in the same way by drug substance layer 30.In these embodiments, hole 22 and or the size of passage and quantity with the major decision active medicine by line with rubber adhesive layer 20 down by the seepage velocity that leaches in the drug substance layer 30.
In another embodiment, drug substance is directly to be mixed into adhesive layer 20 in time so that regularly discharge thus.In this case, by following multitude of different ways, medicine is joined in the adhesive layer 20 with the form of controlled or lasting release.
2. production method
To adopt imprint lithography and screen printing printing administration to tatoo with the common identical mode of tatooing.Below be the special step of this production process:
Step 1: initial picture such as photo, figure and literal are imported and/or scanned in the common computer, adopt existing design software that these contents are merged into the single pattern of tatooing.
Step 2: the film that adopts high-resolution picture type-setting machine output actual size.Can be positive or negative film.
Step 3: adopt known photochemical process to make the printing photographic plate by these films.These plates are arranged to make printing ink only to stick on the image or picture of photographic plate, and this realizes in the following manner,, through making these photographic plates exposures under the high-strength light of film, follows these photographic plates of chemical treatment that is, makes that not imaging district absorbs water.
Step 4: the flexible photoreceptor plate is attached on the photographic plate cylinder of ordinary flat printer and and is printed on the transparent substrate 50 with color layer 40.Imprint lithography is a kind of printing process, by this method only with ink adhesion the printing photographic plate image or pattern on.Make water rinse out except that area of image be printing ink on the extra-regional All Ranges of ink adhesion.Ink logo then be transferred or offset printing the rotation blanket cylinder, this cylinder successively with the direct transfer printing of image on transparent substrate 50.
In the above described manner, in the operation color layer 40 is being printed on the transparent substrate 50 at basic paper 70 back sides for the first time, then in operation for the second time, drug substance layer 60 is coated in or is printed on the opposite side of (above the color layer 40) transparent substrate 50 with screen printing.By using common reverse roll coater, the coating machine as being provided by Kroenert and Egan machine can obtain than high evenness.Silk screen printing is more time-consuming, realizes but can make it pass the net of handling with photographic means by extruding drug substance layer 60 with known manner.
In above-mentioned manufacture process, generally use solvent as retarder usually as required, these solvents comprise butyl cellosolve, ethyl acetate, ethane and toluene etc.
As mentioned above, drug substance layer 30 can comprise individual course shown in Figure 1, so that permeate by microscopic channels or micro-hole shown in Figure 2.In both cases, also carrying out drying subsequently prepares drug substance layer 30 by hybrid medicine in water base paste.
In addition, drug substance can be blended directly in the adhesive layer 30 with the form that various timings discharge.
Provided preparation size and be roughly 3.0 " * 2.5 " the embodiment of above-mentioned two kinds of production methods of Medicuted tattoos, comprise 80mg acetaminophen (N-4 acenol), this is 4 hours a suitable dose of (below 12 years old) child.
Method 1, discontinuous drug substance layer 30 (being used for) by adhesive layer 20 control desorptions
Medicament mixed in water base paste, is carried out drying subsequently, then use adhesive layer 20 to produce the roughly dry film layer of 3.Oml.Because acetaminophen is not water miscible, therefore can make water emulsion, then thicken to and form flowable paste.For acetaminophen is dispersed in the water, need a kind of and compatible surfactant of drug substance (for example lauryl sulfate (lauryl sulfate)).By using the high speed dispersion blender to scatter, this blender makes the micelle (have the structure that the long polymerizable molecular of opposed polarity constitutes by two ends, these two ends are polarity or " hydrophilic " end and nonpolar or " hydrophobic " end) of micron size form and stablize distribution.The hydrophobic side gathers nonpolar core in formation center or chamber.Prostheses can be accepted each organic molecular species to be made in its solution that dissolves in polar solvent.Can add use viscosity and the flowability of thickening agent (several) to obtain to require as colloid, agar, gel, hydroxypropyl cellulose.Follow partially dried drug thing material layer 30, and apply by common reverse roll coater or method for printing screen.Adopt this method, adhesive layer 20 is direct as the permeable films therefrom that discharges drug substance layer 30.The size of micro-hole (Fig. 2) or passage can change, so that the rate of release of control medicine.
Medicine in method 2, the adhesive layer 20
In this case, medicine is by directly being diffused in the skin in the adhesive layer 20.In order to produce the dried adhesive layer in 3.0 Mills (mil) that contains the 80mg drug substance, the adhesive of per 100 pounds (lbs) needs 11.5 pounds acetaminophen.For the dried adhesive layer in 2.0 Mills, per 100 pounds adhesive needs 17.1 pounds acetaminophen.Estimate that it is 0.260 gram that the adhesive weight of layer is done in 2.0 Mills, and to do the adhesive weight of layer be 0.380 gram in 3.0 Mills, so the former drug substance content is approximately 30.25%, the latter's is 20.5%.Acetaminophen is not dissolved in water, but is dissolved in ethyl acetate and butyl cellosolve.Can make the solution that acetaminophen is dissolved in ethyl acetate and/or butyl cellosolve, then (with planetary stirrer or similar agitator) thoroughly is mixed into it in adhesive.Because ethyl acetate also as skin penetration enhancer and be safe, therefore uses the ethyl acetate effect more satisfactory.After part was dried to paste/solution, medicine can directly be discharged by adhesive layer 20, did not therefore need independent drug substance layer 30.
Compare with above-mentioned paste/solution form, be better sustained release speed, can in many ways medicine be injected or be mixed into adhesive layer 20.Adopt the adhesive layer 20 that is provided with micro-hole 22 especially shown in Figure 2, can make in the direct hand-hole 22 of medicine.This preferably realizes by the method for printing screen shown in Fig. 3 and 4.
As shown in Figure 3, percutaneous is tatooed and 2 is comprised transparent substrate 50, and multicolour pattern layer 40 is covered by the silk screen 56 that is coated with Emulsion 54 selectively.On silk screen 56, push the medicine 30 of paste/solution form with squeegee, and make its pattern infiltration silk screen 56 to form by Emulsion 54.
As shown in Figure 4, remove silk screen 56 and Emulsion 54 and, stay medicine pattern deposit 30 on 2 thereby tatoo at percutaneous with product dried.In this embodiment, the size of pattern deposit 30 and quantity are infiltrated the major decision active medicine seepage velocity of skin.Then, by using squeegee or, applying adhesive layer 20, fill empty position around pattern deposit 30 by the reverse roll coating.But as above-mentioned another kind selection scheme, can active medicine be blended in the adhesive layer, comprise i with known form controlled or lasting release) microcapsule; Ii) microemulsion (size range is at the droplet of 100-1000 dust); Iii) liposome; Iv) non-ionic surface active agent capsule; V) hydrogel.For a more detailed description to these selectable forms below.
I microcapsule packing
Microcapsule packing is a kind of the little bag of medicine to be wrapped in method in the capsule, and capsular size is that 1 micron (1/1000 millimeter) is to 7 millimeters.Capsule spreads on the adhesive layer 20 and passs in time and discharge its content.Discharge four kinds of typical mechanism (fusing of the mechanical disruption of cyst wall, the dissolving of wall, wall and see through the distribution of wall) of core material from microcapsule, the present invention needs best timing releasing effect by back three kinds of acquisitions.Cyst material is organic polymer preferably.Particularly, when being applied to acetaminophen of the present invention, medicine can be packed in the capsule that ethyl cellulose or hydroxypropyl cellulose and starch constitutes.Acetaminophen discharges suddenly, but it is discharged by shell with slow and lasting dosage.Other medicines, vitamin and mineral can be contained in the capsule, can control and carry out being applied in this way it.Have and multiple drug substance is contained in prescriptive procedure in the capsule.
Ii. little emulsion
Shown and a small amount of monomer can have been joined in the capsule that is formed by ionic surface active agent, and can not destroy the structure of capsule.John D.Morgan, Christopher A.Johnson, Eric W.Kaler, " Polymerization of Equilibrium Vesicles (polymerization of balanced capsule) ", and Langmuir, 1997, V.13, PP.6447-6451.In case make these polymerisation in solutions, then produce semi-solid hollow polymerization ball and suspend.These balls can be as the nanocapsule spare of percutaneous dosing, and their polymerization property allows desired controlled and lasting drug release.Can make the dissolving of medicine or any bioactive compound, bag carry or be encapsulated in the millimicro particle, or only adsorb in its surface.
Iii. liposome
Liposome is that the lyotropic liquid crystal that mainly is made of the amphipathic bilayer with dissipation capability constitutes.Just begin one's study for the use of the acetominaphensome of the local skin drug of topical application as far back as the eighties.Mezei M.and Gulusekharam V., Liposomes (liposome), a selectivedrug delivery system for the topical route of administration (the selectivity drug-supplying system of topical approach), Life Sci.26:1473-1477 (1980); MezeiM.and Gulusekharam V., Liposomes (liposome), a selective drugdelivery system for the topical route of administration (the selectivity drug-supplying system of topical approach): Gel dosage form (gel dosage form), J Pharm.Pharmacol.34:473-474 (1982).The lipid somatocyst that studies show that subsequently is of value to the treatment imbalance as acne, bald head and various cancer, and facilitates the accelerating system administration by the conveying of alternative pathway.Laucer A.C., Lieb L.M., Ramachandran C., Flynn G.L., andWeiner N.D., Transfollicular Drug Delivery (striding the capsule administration), Pharm.Res.12:179-186 (1995).Liposome vectors has strengthened the clinical efficacy of multiple medicine.These medicines comprise the glucocorticoid of the retinoic acid for the treatment of acne, treatment idiosyncrasy eczema, as narcotic lignocaine and pantocaine.The local liposome medicament Pevaryl Lipogel that at first puts on market is produced by Cliag AG.This medicine contains the 1%enconazole that is the lipidosome gel form.This lipidosome gel form is suitable for directly being used as the drug substance layer 30 of Medicuted tattoos of the present invention.
Have two kinds of liposomees-skin to interact: absorption and the fusion thermodynamic activity and the penetration that cause lipophilic drugs of the capsule of 1) packing on skin surface strengthens; And 2) interaction of capsule in dark horny layer improved the impaired barrier function of these layers to medicine.Liposome-skin that the optimum liposome of the drug of topical application depends on requirement interacts, and it depends on desired pharmacotoxicological effect successively.
Iv. non-ionic surface active agent capsule
Non-ionic surface active agent capsule or non-ionic surface active agent capsule as the liposome alternative have obtained broad research now.Having been found that increasing non-ionic surface active agent forms can wrap the capsule that carries hydrophobic and hydrophilic solute.With regard to its physical characteristic, these non-ionic surface active agent capsules seem identical with liposome, are prepared in the same way and under various conditions, form the single or multiple lift structure.They are a kind of cheap alternatives that are made of abiotic raw material of liposome.
V. hydrogel
Aquogel polymer has the liquid of absorption and expansible ability, when it expands, discharges blended medicine in a controlled manner.By changing physics and the chemical characteristic and the shape of polymer, the control medicine carries out the release of a period of time of several hours to several days.Pass through the scheduled time by hydrogel being immersed drug solution, and accurate medication amount is mixed in the polymer.Then make the hydrogel exsiccation and fix medicine.The aquogel polymer of medicine pack into directly as drug substance layer 30.Got wet when tatooing and when embedding on the skin, begun the release of medicine immediately.When expanding in the water of hydrogel in administration, continue to discharge, transparent substrate 50 sealings are against the aqueous gel drug substance layer 30 of skin.When the drug of topical application finished, exhausted aquogel polymer and color layer 40 were taken off together.These are multiple percutaneous hydrogel pad of commercial use, but adopt methyl salicylate, oxidation body pine and lignocaine to carry out the local pain remissive treatment.But these depend on kidney or vagina body fluid that the water supply gel carries out hydration.The drug of topical application need become wet process owing to tatoo, so Medicuted tattoos of the present invention is applicable to the administration by hydrogel fully.
Under all above-mentioned situations, can also add the dermal osmosis enhancer so that the control absorbance.For example, known infiltration enhancer is disclosed among US4537776, US4973468, US4820720, US5006342 and the US4863970.
Alternative drug substance
Except acetaminophen, can 2 come to carry out the drug of topical application by using percutaneous to tatoo with various drug substances.For example, percutaneous 2 the deposited of cosmetic compounds that can be used for nutriment even skin nutrition and skin is rejuvenated of tatooing are given.Particularly, estimating the local vitamin C administration that prevents owing to Exposure to Sunlight or the old and feeble reverse skin lesion that causes.The proteic generation of collagen in the vitamin C chafe.Percutaneous is tatooed and 2 can be effectively dense vitamin C be applied and be given in the skin.And spontaneous Progesterone can also be sent to the designated receptor position of whole body, alleviate menstrual symptom thus for a long time.
Similarly, need carry out the DNA and oligonucleotide and the prescription anesthesia that comprises Anileridine, Butorphanol, Codeine, Damorphine, Fentanyl, Hydrocodone, Levorphanol, Morphine, Nalbuphine, Oxycodone, Oymorphone Pentazocine, Pethidine (pethidine), Propoxyphene and the percutaneous dosing (comprising many different organic compound) of other medicines such as insulin of some FDA regulating medicine, protein, peptide and macromole, related gene treatment.
Under above-mentioned all situations, 1) viscosity of paste solution form; 2) micropore/microchannel; And/or 3) vehicle that discharges in time of control or its combination will determine medicine to be diffused into speed in the skin by adhesive layer.Infiltration rate in the skin will depend on the Concentraton gradient that forms between the low concentration in medicine saturated solution that arrives skin and skin, this gradient is impelled absorption.Obviously, must do the permeability coefficient (Papp) of diffusion experiment with definite every kind of medicine, because Papp=D*K/h (K is a partition coefficient, and h is a skin thickness), so can determine diffusion coefficient (D) by permeability coefficient (Papp).In patient according to dosage takes medicine, have various variations inevitably, but normal injection speed (per hour 25,50,75 and 100ug) is very accurate.
The Medicuted tattoos drug of topical application
In order to use exquisite percutaneous to tatoo 2, post Medicuted tattoos 2 and water is got basic paper 70 wet and made its deliquescing or dissolving releasing layer 60 against the skin that requires the position.Take basic paper 70 and any residue off, and functional part (layer 20-40) is stayed the original place.In case become dry, the transparent substrate 50 that has multicolour pattern layer 30 and drug substance layer 30 below is bonded on the skin, and the medicine in the drug substance layer 30 begins gradually (directly or by discontinuous adhesive layer 30) and is diffused in the skin.In order to obtain optimum efficiency, should tatoo to percutaneous and 2 carry out drying, the effect that no fur skin (on forearm) generation needs roughly needs 8-12 hour.
The degree indication is carried out in absorption
In use, percutaneous is tatooed and 2 is looked like common tatooing, and color layer 30 can adopt the pattern of wide range of forms.Opposite with common percutaneous, apparatus of the present invention 2 have been covered the situation of wearer's drug of topical application.In fact, ornamental outward appearance impels people to wear.In addition, carry out the degree indication by increase and can further impel people to use, this indication provides administration to carry out the outside vision indication of degree.Adopt any said structure alternative can make up the indication coloring system that will produce change color.By the time of experience or the absorption by drug substance, can make this color change.Because percutaneous is tatooed and 2 can be had indication and take medicine and carry out the monitoring feature voluntarily of degree, therefore all provides great effectiveness under arbitrary situation.
In relying on the embodiment that absorbs, indication pigment is blended in the drug substance layer 30, and moves towards skin with medicine.When indicating dye was shifted to skin and leave multicolour pattern layer 40, it is bright that color layer 40 outward appearances show, and indication absorbs and carries out degree thus.Fig. 5 shows the percutaneous with this feature and tatoos 2, and wherein basic paper 70 prints and indicates colour code, provides reference so that carry out visual comparison to user.When absorbing the drug, faded, by with the simple comparison of colour code 23, tell percentage ratio easily and absorb.By using the complementary color of indicating dye, increased the weight of this effect, translucent multicolour pattern layer 40 as yellow and green, has shown tangible tone variations.
In addition, by using photochromic or fluorescence liquid dyes or liquid crystal, can in drug substance layer 30, realize colored variation characteristic.When solar light irradiation, photochromic dyes works, and the molecular structure change, makes color present (or disappearance).Effect as requested can realize shades of colour or effect.For example, PPG
The Photosol that produces
Photochromic dyes crystal organic dyestuff four primary colours: blue, yellow, purple and orange/red.When mixing, can produce additional color such as green, brown and grey.In addition, fluorescence organic fluorescence group can be used to produce fluorescent effect.Can control these characteristics, make image pass in time and fade or disappear, show the tatoo measurement of 2 effective lifes of percutaneous thus.
In addition, Fig. 6 shows and wears the skin 2 gradient index features of tatooing, wherein, drug substance layer 30 be with dyestuff coding and be contained in the storage capsule, the storage capsule is in abutting connection with the gradual change ratio indication 43 that is similar to thermometer, and it indicates the gradual change ratio 43 for visual comparison, to provide reference to user.When medicine was absorbed, the horizontal plane of medicine in passage 43 descended under capillarity, by with the simple comparison of gradual change ratio, distinguish that at an easy rate percentage ratio absorbs.
Further purpose is to provide a kind of transcutaneous device 2, and it shows the attraction child's of (fix, manifest in time or disappear) decoration simulation symbol (charactor) or other labelling, in order that encourage child's drug of topical application it is not revolted.
The child strengthens
Also adopt above-mentioned colored variation characteristic to stimulate the child to wear this percutaneous greatly and tatoo 2.For example, as shown in Figure 7, can use above-mentioned indicating dye chemical compound, cause that feature manifests in time, or characteristic point 33 disappears reinforcement use thus in time.
In all above-mentioned colored indication embodiment, the colour that uses in drug substance layer 30 produces composition can comprise following list any:
1. liquid crystal
2. thermo-color material
3. photochromic material
4. phosphorescent material
5. radiation therapy printing ink
6. adhesive component
Obviously, can make many changes and not deviate from spirit of the present invention.Therefore, person of skill in the art will appreciate that the special content of describing is implemented the present invention in the scope of accessory claim rather than in by description.
Industrial applicibility
Topical remedy and vitamin administration are the methods for the treatment of as everyone knows the local skin imbalance, with The development of technology, the method becomes the approach of more practicable systematization administration. But, extremely Considerably less several drugs has been used in modern only approval, mainly is because be difficult to realize the consistent approximately speed of giving Degree. There are various changing factors to affect the transdermal absorption of medicine, and at present not monitoring suction The mechanism of yield. But, have the technology of describing in another kind of and this specification in many aspects different But in the relevant technology that satisfies the needs of consumers of material, this technology is of value to through the skin industry. Temporary line Body since its produce various aesthetic and visual effects thereby be popular. Temporary technology and the warp of tatooing The combination of skin medicine-feeding technology has multiple advantage, comprises (adopting the dressing plate art of printing and screen printing The brush art) low cost of manufacture alleviates administration misery, temporary effect and excites people to wear and meets Esthetic requirement through skin. Print owing to tatoo, therefore be easy to make showing mimicry and attract youngster Virgin symbol or other mark. Greatly excited thus the wish of children's topical application of drug. In addition, by this Method can be made tatooing of printing with printing ink, and when absorbing the drug, this is tatooed and disappears or change face Look provides the actual indication of percutaneous dosing speed and effect thereof first. Industrial extensive needs advance The temporary of percutaneous administration tatooed and imprint lithography/silk screen manufacture method, makes thus temporary Tatoo and in the skin field, have various potential aesthetics and showing advantage.
Claims (18)
1. method of making transdermal delivery device comprises step:
At transparent substrate upper flat plate printing-ink pattern;
The cardstock substrate is bonded in a side of described transparent substrate by the water solublity releasing layer; With on drug substance and the described ink logo of skin adhesive applicating on described transparent substrate opposite side.
2. the method for claim 1, the step of wherein said coating drug substance also comprise the described drug substance roll coating in the paste float on transparent substrate and relative with described ink logo.
3. method as claimed in claim 2, wherein said drug substance and skin adhesive are blended in the described paste float.
4. method as claimed in claim 3 wherein is blended in described drug substance in the described paste float that is the controlled release form.
5. method as claimed in claim 4 wherein is blended in described drug substance in the described paste float, and described paste float is any in following group: the micro emulsion of controlled release, liposome, non-ionic surface active agent capsule and hydrogel.
6. the method for claim 1, the step of wherein said coating drug substance and skin adhesive also comprises: first step is coated in drug substance on the described transparent substrate opposite side on the described ink logo; With second step, adhesive layer is coated on the described drug substance.
7. method as claimed in claim 6, wherein said adhesive layer is made of so that control by leaching in the drug substance one of micropore and microchannel.
8. the method for claim 1, the step of wherein said coating drug substance and skin adhesive also comprises: first step is coated in drug substance on the described transparent substrate opposite side on the described ink logo; Second step covers microporous membrane on described drug substance; And third step, adhesive layer is coated on the described microporous membrane.
9. a transdermal drug is tatooed, and comprising:
One side scribbles the transparent substrate of ink logo, and described transparent substrate opposite side posts described cardstock base paper by discharging substrate, dissolves when substrate becomes wet when discharging, so that break away from basic paper;
Adhesive layer is coated on the ink logo on the described transparent substrate, so that be bonded in skin, described adhesive layer has predetermined Penetration Signature;
Medicine is blended in the adhesive layer, so that be diffused into thus in wearer's the skin.
10. transdermal drug as claimed in claim 9 is tatooed, and wherein said drug substance and skin adhesive are made of blended paste float.
11. transdermal drug as claimed in claim 10 is tatooed, and described drug substance is blended in is in the described paste float of controlled release form.
12. transdermal drug as claimed in claim 11 is tatooed, described drug substance is blended in the described paste float, and described paste float is any in following group: the micro emulsion of controlled release, liposome, non-ionic surface active agent capsule and hydrogel.
13. a transdermal drug is tatooed, and comprising:
One section cardstock base paper;
One side scribbles the transparent substrate of ink logo, and described transparent substrate opposite side posts described cardstock base paper by discharging substrate, discharges substrate and dissolves when becoming wet, so that break away from basic paper;
Adhesive layer is coated on the ink logo on the described transparent substrate, so that be bonded in skin, described adhesive layer is made of one of the micropore with predetermined Penetration Signature and microchannel; Medicine is blended in the adhesive layer, so that be diffused into thus in wearer's the skin.
14. a transdermal drug is tatooed, and comprising:
One section cardstock base paper;
One side scribbles the transparent substrate of ink logo, and described transparent substrate opposite side posts described cardstock base paper by discharging substrate, dissolves when substrate becomes wet when discharging, so that break away from basic paper;
The drug substance layer has the medicine in the skin that is mixed in wherein so that is diffused into the wearer;
Adhesive layer, on the coating medicine material layer, so that be bonded in skin, described adhesive layer has predetermined Penetration Signature.
15. transdermal drug as claimed in claim 14 is tatooed, and also is included in the permeable membrane between described drug substance layer and the adhesive layer, so that control the desorption of described medicine by described adhesive layer.
16. transdermal drug as claimed in claim 14 is tatooed, and also comprises the indicating dye that is blended in the drug substance layer, described dyestuff moves so that indication absorbs with described medicine and carries out degree.
17. transdermal drug as claimed in claim 14 is tatooed, and also comprises the indicating dye that is blended in the drug substance layer, indicating dye changes in time so that show expiry date.
18. transdermal drug as claimed in claim 14 is tatooed, and also comprises dyestuff, described dyestuff is blended in the drug substance layer, and is visible together with described multicolour pattern layer, encourages the child to wear so that the change color pattern is provided.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71406000A | 2000-11-16 | 2000-11-16 | |
| US09/714,060 | 2000-11-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1479615A true CN1479615A (en) | 2004-03-03 |
Family
ID=24868618
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA018203957A Pending CN1479615A (en) | 2000-11-16 | 2001-11-16 | Medicuted tattoos |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1341498A4 (en) |
| CN (1) | CN1479615A (en) |
| AU (1) | AU2002246515A1 (en) |
| CA (1) | CA2429181A1 (en) |
| WO (1) | WO2002076379A2 (en) |
Cited By (5)
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| CN102389590A (en) * | 2011-07-11 | 2012-03-28 | 庞彪 | Novel body tattooing technology manifesting natural beauty |
| CN104442166A (en) * | 2014-11-03 | 2015-03-25 | 天津融鑫生物科技有限公司 | Tattoo sticky film used through sunbath |
| CN113069682A (en) * | 2021-04-07 | 2021-07-06 | 济南澜亿未来生物科技有限公司 | Semi-permanent tattoo patch, preparation method and use method thereof |
| CN117462836A (en) * | 2023-12-26 | 2024-01-30 | 山东百多安医疗器械股份有限公司 | Functionalized ultrasonic controlled-release puncture dressing patch and preparation method thereof |
| CN117462836B (en) * | 2023-12-26 | 2024-04-26 | 山东百多安医疗器械股份有限公司 | Functionalized ultrasonic controlled-release puncture dressing patch and preparation method thereof |
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| US7635488B2 (en) | 2001-03-13 | 2009-12-22 | Dbv Technologies | Patches and uses thereof |
| GB0224986D0 (en) | 2002-10-28 | 2002-12-04 | Smith & Nephew | Apparatus |
| GB0325129D0 (en) | 2003-10-28 | 2003-12-03 | Smith & Nephew | Apparatus in situ |
| DE102004019916A1 (en) * | 2004-04-21 | 2005-11-17 | Grünenthal GmbH | Anti-abuse drug-containing patch |
| CA2619929A1 (en) | 2005-09-06 | 2007-03-15 | Tyco Healthcare Group Lp | Self contained wound dressing with micropump |
| US7779625B2 (en) | 2006-05-11 | 2010-08-24 | Kalypto Medical, Inc. | Device and method for wound therapy |
| GB0615429D0 (en) * | 2006-08-03 | 2006-09-13 | Chowdhury Dewan F H | Transdermal drug delivery with temporal control |
| CA2964674A1 (en) | 2006-09-28 | 2008-03-28 | Smith & Nephew, Inc. | Portable wound therapy system |
| GB0722820D0 (en) | 2007-11-21 | 2008-01-02 | Smith & Nephew | Vacuum assisted wound dressing |
| FR2924350B1 (en) | 2007-12-03 | 2010-08-13 | Dbv Tech | METHOD AND COMPOSITIONS FOR SKIN VACCINATION |
| FR2924349B1 (en) | 2007-12-03 | 2010-01-01 | Dbv Tech | ALLERGEN DISENSIBILITY METHOD |
| US9199012B2 (en) | 2008-03-13 | 2015-12-01 | Smith & Nephew, Inc. | Shear resistant wound dressing for use in vacuum wound therapy |
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| RU2615075C2 (en) | 2011-07-14 | 2017-04-03 | СМИТ ЭНД НЕФЬЮ ПиЭлСи | Wound dressing and methods |
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| US10610414B2 (en) | 2014-06-18 | 2020-04-07 | Smith & Nephew Plc | Wound dressing and method of treatment |
| SG11201704254XA (en) | 2014-12-22 | 2017-07-28 | Smith & Nephew | Negative pressure wound therapy apparatus and methods |
| DE102015218193A1 (en) * | 2015-09-22 | 2017-03-23 | Ccl Label Gmbh | Sheet with crosslinked hydrophilic polymer |
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| GB2217206A (en) * | 1988-04-13 | 1989-10-25 | Jeffrey Noble Wilson | First aid dressing |
| US5776586A (en) * | 1996-03-26 | 1998-07-07 | Lipper; Chris | Promotional hang-tag with integral removable tattoo |
| DE19709606C1 (en) * | 1997-03-08 | 1998-10-15 | Beiersdorf Ag | Patches with long afterglow printing and process for its manufacture |
| CN1325290A (en) * | 1998-10-02 | 2001-12-05 | 强生消费者公司 | Decorative adhesive bandage kit |
-
2001
- 2001-11-16 AU AU2002246515A patent/AU2002246515A1/en not_active Abandoned
- 2001-11-16 WO PCT/US2001/043422 patent/WO2002076379A2/en not_active Application Discontinuation
- 2001-11-16 CA CA002429181A patent/CA2429181A1/en not_active Abandoned
- 2001-11-16 CN CNA018203957A patent/CN1479615A/en active Pending
- 2001-11-16 EP EP01994084A patent/EP1341498A4/en not_active Withdrawn
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102389590A (en) * | 2011-07-11 | 2012-03-28 | 庞彪 | Novel body tattooing technology manifesting natural beauty |
| CN104442166A (en) * | 2014-11-03 | 2015-03-25 | 天津融鑫生物科技有限公司 | Tattoo sticky film used through sunbath |
| CN113069682A (en) * | 2021-04-07 | 2021-07-06 | 济南澜亿未来生物科技有限公司 | Semi-permanent tattoo patch, preparation method and use method thereof |
| CN117462836A (en) * | 2023-12-26 | 2024-01-30 | 山东百多安医疗器械股份有限公司 | Functionalized ultrasonic controlled-release puncture dressing patch and preparation method thereof |
| CN117462836B (en) * | 2023-12-26 | 2024-04-26 | 山东百多安医疗器械股份有限公司 | Functionalized ultrasonic controlled-release puncture dressing patch and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002076379A3 (en) | 2003-05-30 |
| CA2429181A1 (en) | 2002-10-03 |
| WO2002076379A2 (en) | 2002-10-03 |
| AU2002246515A1 (en) | 2002-10-08 |
| EP1341498A4 (en) | 2005-01-19 |
| EP1341498A2 (en) | 2003-09-10 |
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