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Publication numberUS3731683 A
Publication typeGrant
Publication dateMay 8, 1973
Filing dateJun 4, 1971
Priority dateJun 4, 1971
Publication numberUS 3731683 A, US 3731683A, US-A-3731683, US3731683 A, US3731683A
InventorsA Zaffaroni
Original AssigneeAlza Corp
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Bandage for the controlled metering of topical drugs to the skin
US 3731683 A
Abstract
Bandage for the topical administration of controlled therapeutically effective quantities of topically active drugs has a backing member, a pressure-sensitive adhesive, and a reservoir layer containing a topically active drug confined within a wall member. The wall member is formed from drug release rate controlling material to continuously meter the flow of a therapeutically effective amount of the drug through the wall to the skin at a controlled and predetermined rate over a period of time.
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Description  (OCR text may contain errors)

United States Patent 91 Zalfaroni 51 *May 8,1973

[54) BANDAGE FOR THE CONTROLLED METERING OF TOPICAL DRUGS TO THE SKIN [75] Inventor: Alejandro Zafiaroni, Atherton,

Calif.

[73] Assignee: Alza Corporation Notice: The portion of the term of this patent subsequent to Aug. 10, 1988, has been disclaimed.

[22] Filed: June 4, 1971 [21] Appl. No.: 150,085

Related US. Application Data [63] Continuation-impart of Ser. No. 136,981, April 23,

[52] US. Cl. ..l28/268, 128/156, 424/28 [51] Int. Cl. ..A6lf 7/02 [58] Field of Search ..l28/260, 268, 156,

[56] References Cited UNITED STATES PATENTS 3,339,546 9/1967 Chen ..l28/268 X 3,444,858 5/1969 Russell ..l28/268 X 3,536,809 10/1970 Applczweig ..424l28 3,551,556 12/1970 Kliment et al. ..424 22 3,598,122 3 1971 Zaffaroni ..l28/268 3,598,123 8/1971 Zaffaroni .....l28/268 3,632,740 1 1972 Robinson et a1 ..424 28 Primary Examiner-Charles F. Rosenbaum Attorney-Steven D. Goldby, Edward L. Mandell and Paul L. Sabatine 57 ABSTRACT Bandage for the topical administration of controlled therapeutically effective quantities of topically active drugs has a backing member, a pressure-sensitive adhesive, and a reservoir layer containing a topically active drug confined within a wall member. The wall member is formed from drug release rate controlling material to continuously meter the flow of a therapeutically effective amount of the drug through the wall to the skin at a controlled and predetermined rate over a period of time.

14 Claims, 5 Drawing Figures BANDAGE FOR THE CONTROLLED METERING OF TOPICAL DRUGS TO THE SKIN RELATED APPLICATIONS This application is a continuation-in-part of Ser. No. 136,981, filed Apr. 23, 1971, (Docket No. LR. 165A- CIP; Dl), entitled Therapeutic Adhesive Tape, of Alejandro Zaffaroni.

BACKGROUND OF THE INVENTION This invention relates to a device for the administration of drugs and more particularly to a medical bandage for the predetermined controlled metering of the flow of topically active drugs to the skin over a period of time. Topically active drugs, as that term is used in this specification and the appended claims, are agents which primarily cause a pharmacological or physiological response at or near the site of their application. They are to be distinguished from systemically active drugs which are transported from their site of application by the recipients circulatory system or lymphatic system, to cause a pharmacologic or physiologic response at a remote site in the body.

A large number of locally acting drugs are available to treat skin disorders or other conditions which manifest themselves in a manner such that they are susceptible to treatment via the skin. These drugs can be broadly classified as astringents, irritants, sclerosing agents, caustics, melanizing and demelanizing agents, keratolytics, mucolytics, antibacterials, anti-fungals, anti-inflammatories, antiporasitics, antiperspirants and deodorants, and the like. These drugs are conventionally topically administered to the skin with the active agent carried in the form of ointments, creams, salves, liniments, powders, dressings, and the like. The popularity of these types of formulations resides in the fact that it is quite easy to topically apply the agent to the skin in this manner. In most cases, however, it is not possible to determine how much of the preparation has been taken up or effectively administered to the skin since only non-uniform levels of the agent are available. A further undesirable feature is the unsightliness of these formulations which often discourage patients from using them during their waking hours of the day when they are most likely to be seen by others. Further, the preparations are subject to rub off onto clothing, thus causing much inconvenience and annoyance to the user.

In order to obviate some of these undesirable effects, it has been proposed to provide medicinal bandages wherein the absorbent portion to be applied to the area to be treated is further provided with drug material adhered thereto. The advantage of a bandage construction of this type, of course, resides in the elimination of the intermediate step of applying the drug. A further advantage is realized by the elimination of the possibility that the drug which is often in a liquid formulation will be lost by run-off or leakage. A significant disadvantage, however, also exists with these prior art devices for the administration of topically active drugs in that the amount of medication applied to the affected areas cannot be accurately controlled, nor is there any assurance that sufficient medication will be available for the duration of periods that it is required.

It has also been proposed to admix certain topical drugs in the adhesive materials of bandages to treat various skin conditions with improved convenience; see for example British Pat. No. l,2l6,908. Further, it is known that medicaments can be incorporated into certain types of crushable microcapsules which are then incorporated in bandages; see for example Goldfarb US. Pat. No. 3,464,4l3. The microcapsules, however, merely function as drug carriers releasing the drug by rupture of the microcapsules. Therefore, these bandages are not suitable for continuously controlling the dosage of the drug administered, which is a most desirable objective of drug therapy.

SUMMARY OF THE INVENTION Accordingly, an object of this invention is to provide a bandage for the improved continuous administration of predetermined controlled quantities of topically active drugs to the skin over a period of time.

In accomplishing these objects, this invention in its broadest aspects resides in a medicated bandage for the continuous administration of controlled quantities of topically active drugs to the skin of a patient by direct application to the affected skin area. The bandage is comprised of a laminate of: l a backing member defining one face surface of the bandage; (2) a pressure-sensitive adhesive adapted for contact with the skin or mucosa, the external surface of said pressuresensitive adhesive defining the other face surface of the bandage and disposed between the face surfaces defined by l) and (2); (3) at least one reservoir comprised of a topically active drug formulation confined within a wall member, said wall member being formed from drug release rate controlling material to continuously meter the flow of drug from the said reservoir to the skin or mucosa at a controlled and predetermined rate over a prolonged period of time.

The termreservoir as used herein refers both to microcapsules as well as distinct reservoir compartments or matrix layers.

An embodiment of the invention described above resides in a bandage comprised of a laminate of: (l) a backing member; bearing (2) a discrete middle reservoir layer containing a topically active therapeutic agent confined within a wall member, said wall member being formed from drug release rate controlling material permeable to the passage of agent, to continuously meter the flow of a therapeutically effective amount of the agent to the skin from the reservoir at a controlled and predetermined rate over a period of time; and (3) a pressure-sensitive adhesive surface adapted for contact with the skin and positioned on one wall of the reservoir remote from the backing member.

Another aspect of this invention resides in a bandage as described immediately above including a solubility membrane interposed between the wall of the reservoir and the pressure-sensitive adhesive layer.

Still, another embodiment of this invention resides in a medicated adhesive bandage comprising a laminate of: l a backing member; bearing (2)'a pressure-sensitive adhesive on one surface thereof adapted for contact with the skin, said pressure-sensitive adhesive having distributed therethrough, (3) a plurality of discrete microcapsules, each of which microcapsules comprise a topically active therapeutic agent confined within a wall member, the wall member being formed from drug release rate controlling material, to continuously meter the flow of a therapeutically effective amount of the agent to the skin from the microcapsules at a controlled and predetermined rate over a period of time.

Other objects, features and advantages of the invention will become more apparent from the following description when taken in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS In the drawings:

FIG. 1 is a perspective view of the medical adhesive bandage of the invention wherein the topically active agent is microencapsulated with a material permeable to the passage of those agents and the microcapsules are uniformly distributed throughout the pressure-sensitive adhesive coating;

FIG. 2 is a cross-sectional view of the bandage of the invention shown in FIG. 1;

FIG. 3 is a cross-sectional view of another embodiment of the invention wherein the topically active agent is uniformly distributed throughout a matrix of material permeable to the passage of those agents and the material is laminated to a backing member. The matrix material which acts as a reservoir for the agent bears a coating of the pressure-sensitive adhesive thereon;

FIG. 4 is a cross-sectional view of still another embodiment of the invention wherein the adhesive bandage of the invention is comprised of a backing member having a reservoir on one surface thereof of topically active agent uniformly distributed throughout a matrix of material permeable to passage of agent, and on the surface of the reservoir remote from the backing member bearing a pressure-sensitive adhesive coating. A solubility membrane is interposed between the reservoir layer and the pressure-sensitive adhesive coating;

FIG. 5 is a cross-sectional view of another embodiment of the invention wherein the reservoir laminated to the backing member is a hollow container permeable to passage of agent and having the agent confined within the interior chamber thereof.

DETAILED DESCRIPTION OF THE INVENTION In accordance with this invention there is provided a v medicated bandage containing a topically active drug therein for the predetermined controlled metering of the flow of topically active drugs to the skin over a period of time.

FIG. 1 illustrates an adhesive tape 10 of the invention including a backing member 11 bearing a pressure-sensitive adhesive coating 12 on one surface thereof. Ad-. hesive coating 12 has uniformly distributed therethrough microcapsules 13 of topically active agent encapsulated with a material permeable to passage of the drug.

Materials used to encapsulate the drug and form the microcapsules to be distributed throughout the adhependent on the particular drug used in the bandage. By varying the encapsulating material and the wall thickness, the dosage rate per area of bandage can be controlled and movement of drug to the adhesive regulated.

Suitable materials for use in encapsulating the drug include hydrophobic polymers such as polyvinylchloride either unplasticized or plasticized with long-chain fatty amides or other plasticizer; plasticized nylon; unplasticized soft nylon; silicone rubber; polyethylene, and polyethylene terephthalate; and hydrophilic polymers such as esters of acrylic and methacrylic acid (as described in US. Pat. Nos. 2,976,576 and 3,220,960 and Belgian Pat. No. 701,813); modified collagen; cross-linked hydrophilic polyether gels (as described in US. Pat. No. 3,419,006); cross-linked polyvinylalcohol; and crosslinked partially hydrolyzed polyvinylacetate.

To provide the microcapsules, the encapsulating material can be uniformly impregnated with the drug to form microcapsules which are a matrix having the drug distributed therethrough. Alternatively, particles of drug can be encapsulated with thin coatings of the encapsulating material to form microcapsules having an interior chamber containing the drug. If desired, parti cles of a matrix, such as starch, gum acadia, gum tragacanth, and polyvinylchloride, can be impregnated with the drug and encapsulated with other materials such as the encapsulating materials previously described which function as a solubility membrane to .meter the flow of drug to the adhesives; use of a matrix and a different solubility membrane coating can slow the passage of the drug from the microcapsules which is desirable with drugs that are released too rapidly from available encapsulating materials.

Airy of the encapsulation or impregnation techniques known in the art can be used to prepare the microcapsules to be incorporated into the pressure-sensitive adhesive in accord with the embodiment of FIGS. 1 and 2. Thus, the drug can be added to the encapsulating material in liquid form and uniformly distributed therethrough by mixing and subsequently converting to a solid by curing or cooling; or solid encapsulating material can be impregnated with a drug by immersion in a bath of the drug to diffuse into the material. Subsequently, the solid material can be reduced to fine microcapsules by grinding, each of the microcapsules comprising drug coated with and distributed throughout the encapsulating material. Alternatively, fineparticles of the drug can be encapsulated with the coating. One suitable technique comprises suspending dry particles of the drug in an air stream and contacting that stream with a stream containing the encapsulating material to coat the drug particles. Usually, the microcapsules have an average particle size of from I to l ,000 microns, although this is not critical to the invention.

Further embodiments of the adhesive bandage of the invention are illustrated in FIGS. 3, 4 and 5. As illustrated in FIG. 3, adhesive bandage 20 of the invention is comprised of topically active agent 24 uniformly distributed in a reservoir 22 which is a polymeric matrix material. The matrix material is laminated to backing member 21 and bears a pressure-sensitive adhesive coating 23 thereon. The polymeric matrix material has a release rate for the particular drug used which continuously controls the releasing drug.

FIG. 4 illustrates a further modified form of the invention wherein the adhesive bandage 30 of the invention is comprised of a backing member 21 having a reservoir 32 on one surface thereof. A solubility member 35 is interposed between the reservoir 32 and a pressure-sensitive adhesive coating 23. Topically active agent 24 is confined in polymeric matrix material 32 which acts as the reservoir for the drug.

FIG. 5 illustrates a further form of the bandage 40 including a backing member 21 and a reservoir 42 in the form of a hollow container having an interior chamber 43 containing topically active agent 34. Wall 45 of reservoir 42, remote from backing member 21, is permeable to passage of drug 34, as by diffusion, to meter the flow of drug to pressure-sensitive adhesive layer 23 on the outer surface thereof. This form of the bandage is less preferred since it cannot conveniently be cut to fit precisely the size of skin lesions to which applied. However, it is satisfactory for application to large areas of skin.

Suitable materials for forming the reservoir, whether of the matrix or hollow container type, are those materials permeable to passage of the drug previously described as suitable encapsulating materials. The reservoir can be formed by molding into the form of a hollow container with the drug trapped therein. Alternatively, the reservoir can bein the form of an envelope formed from sheets of polymeric material permeable to passage of the drug and enclosing the drug. While the walls of the reservoir can be of any convenient thickness, usually they have a thickness of from 0.01 to 7 millimeters. When the reservoir comprises a matrix with the drug distributed therethrough, it can be prepared by adding the drug to the matrix material in liquid form or solvent solution form and subsequently converting the matrix to a solid by curing, cooling or evaporation of solvent.

Thus, the reservoir of the bandage is a hollow drug container or a solid matrix. Drug is metered from the reservoir to the adhesive layer, at a rate controlled by the composition and thickness of the reservoir or of the reservoir wall. From the adhesive layer, drug is directly transmitted to the skin to which the bandage is applied.

In the embodiment of the invention illustrated in FIG. 4, metering of the drug from the reservoir to the adhesive is further controlled by interposing a further solubility membrane therebetween. The solubility membrane is formed ofa material in which the drug is soluble and capable of diffusing through. Any of the materials previously mentioned for use in microencapsulation may be used as the solubility membrane. Of course, in each instance, the solubility membrane will have different characteristics than the reservoir wall of the particular device. This use of a pair of solubility membranes, that is, the reservoir wall and the further solubility membrane, allows for precise metering of drug to the adhesive layer; for the thickness and composition of both membranes can be varied to provide for wide range of dosage levels for a given area of bandage. It will be appreciated that this solubility membrane can be used with either the matrix or container type of reservoir.

In practicing this invention one can employ a wide variety of topically active drugs consistent with their known dosages and uses. Suitable drugs include, without limitation: Antiperspirants, e.g. aluminum chloride; Deodorants, e.g. hexachlorophene, methylbenzethonium chloride; Astringents, e.g. tannic acid; Irritants, e.g. methyl salicylate, camphor, cantharidin; Keratolytics, e.g. benzoic acid, salicylic acid, resorcinol, iodochlorhydroxyguin; Antifungal Agents such as tolnaftate, griseofulvin, nystatin and amphotericin; Anti-Inflammatory Agents, such as corticosteroids, e.g. hydrocortisone, hydrocortisone acetate, prednisolone, methylprednisolone, triamcinolone acetonide, fluidrocortisone, flurandrenolone, fiumethasone, dexamethasone sodium phosphate, bethamethasone valerate, fluocinolone acetonide; fluorometholone; and pramoxine HCl; and Antibacterial Agents, such as bacitracin, neomycin, erythromycin, tetracycline HCI, chlortetracycline HCI, chloramphenicole, oxytetracycline, polymyxin B, nitrofurazone, mafenide (aamino-p-toluenesulfonamide), hexachlorophene, benzalkonium chloride, cetalkonium chloride, methylbenzethonium chloride, and neomycin sulfate.

In addition to the aforementioned drugs, simple pharmacologically acceptable derivatives of the drugs, such as ethers, esters, amides, acetals, salts, etc., or formulations of these drugs, having the desired polymeric permeability or transport properties can be prepared and used in practicing the invention. Drugs mentioned above can be used alone or in combination with others and each other.

The amount of topically active agent to be incorporated in the bandage to obtain the desired therapeutic effect will vary depending upon the desired dosage, the permeability of the polymeric materials of the bandage which are employed to the particular agent to be used, and the length of time the bandage is to remain on the skin. The effective rate or release of the active agent to the skin can be in the range of from 0.5 to 1,000 micrograms per square centimeter of bandage per day. The exact amount will depend on the desired dosage as well as the area of the skin to be treated. These effective rates of release of active agent to the skin can be obtained by altering the permeability and thickness of the release rate controlling barrier. In the case of the microencapsulated active agent, the release rate can also be controlled by varying the number of microcapsules present in a given volume of the matrix of the device. This is a particular desirable feature of this aspect of the invention. Additionally, the duration of action of the device can be altered by controlling the amount of active agent initially incorporated consistent with the release rate. Further, the release rate of drug as well as the duration of release of the drug from the device can be predetermined to be in consonance with the optimum therapeutic values. Once this dosage level in micrograms per square centimeter of bandage has been determined, the total amount of drug to be incorporated in the bandage can be established by obtaining the release rate of the agent in the particular material or materials which are to be used.

Those skilled in the art can readily determine the rate of permeation of agent through a polymeric material or selected combinations of polymeric materials. One method that has been found to be eminently well suited is to cast or hot press a film of the material to a thickness in the range of 2 to 60 mils. The film is used as a barrier between a rapidly stirred (e.g. 150 r.p.m.) saturated solution of the drug containing excess solid drug (or a concentrated solution of the drug) and a rapidly stirred solvent bath, both maintained at :constant temperature (typically 37 C). Samples are periodically withdrawing from the solvent bath and analyzed for drug concentration. By plotting drug concentration in the solvent bath versus time, the permeability constant P of the membrane is determined by the Ficks First Law of Diffusion.

Slope of plot Q, Q /t z =p (AC/h) I wherein Q' cumulative amount of drug in solvent in micrograms at t Q cumulative amount of drug in solvent in microgram at 1 t, elapsed time to first sample i.e. Q

t elapsed time to second sample i.e. Q

A area of membrane in cm C saturation concentration of drug in solution h thickness of membrane in cm.

By determining the slop of the plot i.e. Q Q /t t and solving the equation using the known or measured values of A, C, and h, the permeability P constant in cm /time of the material or membrane for a given compound is readily determined. Of course, this permeability constant is an inherent characteristic of the material for a given compound.

Using the above technique, the permeability constant P of hydrocortisone from isotonic solution through different membranes into isotonic solution at 37 C was found to be:

Membrane Permeability Constant (cm lhr) Silicone Rubber 835 Aromatic Polyamide 2 Down Corning- HH07l7 2 Allied Chemical Capran Using the abovetechnique and data, the permeability constant P for a select membrane and drug can be determined. These data can then be employed to design a device of the invention to release the agent to the skin in the desired dosage range. Similarly, this experimental procedure or others known to those skilled in the art can be used to determine release rates for the suitable polymeric materials as above disclosed in order to design the bandage of this invention.

Other methods of the determining passage of drugs by diffusion through drug permeable polymeric material are available. See Dziuk, P. J. and Cook, 3., Passage of Steroids Through Silicone Rubbers, Endocrinology, 78:208, 1966; U.S. Pat. No. 3,279,996; Folkman and Edmonds, Circulation Research 10:632, l962; Folkman and Long, J. Surg. Res. 432139, 1964; Powers, J. Parasitology 51 :53 April, 1965), No. 2 Section 2.

Any of the well-known dermatologically acceptable permeable pressure-sensitive adhesives which permit drug migration can be used in practicing this invention. Exemplary adhesives include acrylic or methacrylic resins such as polymers of esters of acrylic or methacrylic acid with alcohols such as n-butanol, npentanol, isopentanol, 2-methyl butanol, l-methyl butanol, l-methyl pentanol, 2-methyl pentanol, 3-methyl pentanol, 2-ethyl butanol, isooctanol, n-decanol, or ndodecanol, alone or copolymerized with ethylenically unsaturated monomers such as acrylic acid, methacrylic acid, acrylamide, methacrylamide, N-alkoxymethyl acrylamides, N-alkoxymethyl methacrylamides, N-tert. butylacrylamide, itaconic acid, vinylacetate, N- branched alkyl maleamic acids wherein the alkyl group has l0 to 24 carbon atoms, glycol diacrylates, or mixtures of these; natural or synthetic rubbers such as silicone rubber, styrene-butadiene, butyl-ether, neoprene, polyisobutylene, polybutadiene, and polyisoprene; polyurethane elastomers; vinyl polymers, such as polyvinylalcohol, polyvinyl ethers, polyvinyl pyrrolidone, and polyvinylacetate; ureaformaldehyde resins; phenolformaldehyde resins; resorcinol formaldehyde resins; cellulose derivatives such as ethyl cellulose, methyl cellulose, nitrocellulose, cellulose acetatebutyrate, and carboxymethyl cellulose; and natural gums such as guar, acacia, pectins, starch, dextrin, albumin, gelatin, casein, etc. The adhesives may be compounded with tackifiers and stabilizers as is well known in the art.

Various occlusive and non-occlusive, flexible or nonflexible backing members can be used inthe adhesive bandageof the invention. Suitable backings include cellophane, cellulose acetate, ethylcellulose plasticized vinylacetate-vinylchloride copolymers, polyethylene terephthalate, nylon, polyethylene,

polypropylene, polyvinylidenechloride, paper, cloth, and aluminum foil. Preferably, a flexible occlusive backing is employed to conform to the shape of the body member to which the adhesive tape is applied and to enhance administration of the agent to the skin.

To prevent passage of the drug away from the exposed surface of the pressure-sensitive adhesive prior to use, the adhesive surface of the tape generally is covered with a protective release film or foil, such as waxed paper. Alternatively, the exposed rear surface of the backing member can be coated with a low-adhesion backsize and the bandage rolled about itself. To enhance stability of the active compounds, the therapeutic bandage usually is packaged between hermetically sealed polyethylene terephthalate films under an inert atmosphere, such as gaseous nitrogen.

To use the adhesive bandage of the invention, it is applied directly to skin, to release a therapeutically effective amount of the agent to the affected area. By use of this invention, one ensures that an accurately measured quantity of the active drug is available when the bandage is applied to the skin.

The following examples will serve to illustrate the invention without in any way being limiting thereon.

EXAMPLE I Z-hydroxyethyl methacrylate (100 grams) is diluted with water (100 grams) and mixed with tertiary butyl peroctoate (0.20 gram). Ethylene glycol dimethacrylate (0.20 gram) is added along with 4 grams of sodium bicarbonate as a foaming agent. The mixture is heated to C under an atmosphere of nitrogen and the resulting solid, friable polymeric foam is ground into fine powder of 20 micron average particle size. The polymeric powder (10 grams) is mixed with neomycin (2 grams) dissolved in a mixture of ethyl alcohol: water (50:50) and the resultant mixture placed on a mechanical roller until the polymeric powder has absorbed the drug. The solution is then filtered.

The resulting microcapsules of neomycin are mixed with 100 grams of a 22 percent solution in hexane: isopropylacetate (70:30) of a viscoelastic copolymer of isooctyl acrylate and acrylic acid (94:6) adhesive to uniformly distribute the microcapsules throughout the adhesive solution. The resulting slurry is coated onto a cellophane sheet 10 centimeters in width by 100 centimeters in length and the solvent removed by evaporation from the coated film.

When applied to the infected skin area of a subject, the resulting bandage is effective to control the continuous administration of a daily therapeutically effective dosage of neomycin to the skin.

EXAMPLE ll Liquid dimethyl silicone polymeric rubber 100 grams, Dow-Corning Silastic) is mixed with 5 grams of nitrofurazone. After uniformly mixing the drug with unvulcanized silicone rubber, 0.5 gram of stannous octoate catalyst is added and the rubber cured at room temperature. The resulting silicone rubber body is reduced to an average particle size of 100 microns. Pressure-sensitive adhesive composition is prepared by adding to 100 milliliters of hexane the following:

grams of polyvinylethyl ether (reduced visosity= 5.0 i 0.5)

4 grams of polyvinylethylether (reduced viscosity= 0.3 i 0. l

4 grams of glycerol ester of hydrogenated rosin and 2 grams polyethylene glycol 400 Ten grams of the resulting nitrofurazone capsules are mixed with pressure-sensitive adhesive prepared above to uniformly distribute the microcapsules throughout the adhesive. Immediately thereafter, the adhesive mixture is coated onto one surface of a 1,000 square centimeter Mylar sheet. The resulting bandage can be used for control of skin infections.

EXAMPLE lll Ten milligrams of betamethasone is placed on a sheet of dimethyl silicone rubber having a thickness of 0.13 millimeters. The sheet is folded to provide a surface area of 100 square centimeters on each face and the flaps sealed with silicone adhesive to provide a thin envelope containing the drug.

Pressure-sensitive adhesive is prepared by mixing together, 90 grams of polyacrylate solution (ethylacetate: hexane/5:1) containing percent nonvolatile matter, (obtained by the catalytic polymerization of isoamylacrylatc and acrylic acid in the ratio of 95:5 in ethylacetatc and then diluting with hexane), 5 grams polyvinylethylether (reduced viscosity= 0.3 i 0.1), l gram castor oil (USP) and 4 grams polyethyleneglycol 400.

One face surface of the envelope is bonded to a sheet of cellophane while the other is coated with adhesive prepared above to a thickness of2 millimeters. The adhesive face surface of the bandage has an area of 100 square centimeters. The bandage is effective to release a therapeutically effective daily dosage of the drug when applied to the skin for control of psoriasis.

Thus, this invention provides a reliable and easy to use device for administering topically active drugs directly to the skin. Uncertainties resulting from topical application of these agents, from creams and solutions, are not encountered; and a precisely determined amount of the drug is applied in a controlled manner.

Although the product of this invention has been referred to as an adhesive bandage, those skilled in the art will appreciate that the term adhesive bandage as used herein includes any product having a backing member and a pressure-sensitive adhesive face surface. Such products can be provided in various sizes and configurations, including tapes, bandages, sheets, plasters, and the like.

While there have been shown and described and pointed out the fundamental novel features of the invention as applied to the preferred embodiment, it will be understood that various omissions and substitutions and changes in the form and details of the adhesive tape illustrated may be made by those skilled in the art without departing from the spirit of the invention. It is the intention, therefore, to be limited only as indicated by the scope of the following claims.

What is claimed is:

l. A medical bandage for the continuous administration to the skin or mucosa of controlled quantities of topically active drugs over a prolonged period of time, said bandage comprising a laminate of (1) a backing member defining one face surface of the bandage; (2) a pressure-sensitive adhesive adapted for contact with the skin or mucosa, the external surface of said pressure-sensitive adhesive defining the other face surface of the bandage and disposed between the face surfaces defined by (l) and (2); (3) at least one reservoir comprised of a topically active drug formulation confined within a wall member, said wall member being formed from drug release rate controlling material to continuously meter the flow of drug from the said reservoir to the skin or mucosa at a controlled and predetermined rate over a prolonged period of time.

2. The medical bandage of claim 1, wherein said bandage comprises a laminate of: (l) a backing member; bearing (2) a pressure-sensitive adhesive on one surface thereof adapted for contact with the skin, said pressure-sensitive adhesive having distributed therethrough; (3) a plurality of discrete microcapsules, each of which microcapsules comprises a topically active drug formulation confined within a wall member, said wall member being formed from drug release rate controlling material to continuously meter the flow of a therapeutically effective amount of the drug in the skin through the wall of said microcapsules at a controlled and predetermined rate over a period of time.

3. The bandage as defined by claim 2, wherein each of said microcapsules (3) is comprised of topically active drug formulation microencapsulated with the drug release rate controlling material.

4. The bandage as defined by claim 2, wherein each of said microcapsules (3) is comprised of a matrix of the drug release rate controlling wall material, said matrix having the topically active drug formulation distributed therethrough.

5. The bandage as defined by claim 2, wherein the drug formulation includes a pharmacologically acceptable solvent.

6. The medical bandage of claim 1, wherein said bandage comprises a laminate of: (l) a backing member; bearing (2) a discrete, middle reservoir layer, which reservoir layer is comprised of topically active drug formulation confined within a wall member, said wall member being formed from drug release rate controlling material to continuously meter the flow of a therapeutically effective amount of the drug to the skin through the wall at a controlled and predetermined rate over a period of time; and (3) a pressure-sensitive adhesive adapted for contact with the skin and carried by the reservoir remote from the backing member.

7. The bandage as defined by claim 6, wherein the reservoir layer (2) is comprised of a walled container having an interior chamber containing the topically active drug formulation.

8. The bandage as defined by claim 6, wherein the reservoir layer (2) is comprised of a matrix of the drug release rate controlling wall material, said matrix having the topically active drug formulation distributed therethrough.

9. The bandage as defined by claim 6, wherein the drug formulation includes a pharmacologically acceptable solvent.

10. The bandage as defined by claim 6, further comprising a solubility membrane (4) interposed between said reservoir layer (2) and said surface of pressuresensitive adhesive (3).

11. The bandage as defined by claim 2, wherein the rate release controlling material is silicone rubber.

12. The bandage as defined by claim 6, wherein the rate release controlling material is silicone rubber.

13. The bandage as defined by claim 2, wherein the rate release controlling material is a hydrophilic polymer of an ester of an olefinic acid.

14. The bandage as defined by claim 6, wherein the rate release controlling material is a hydrophilic polymer of an ester of an olefinic acid.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,731, 3 Dated May 8l975 It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 3, lines 33, 34, and 35, "...agent, and on the surface of the reservoir remote from the backing member bearing a..." should read ...a ent, and bearing on the surface of the reservoir remote rom the backing member a.

Column 4, line 27, "acadia" should read -acacia-; Column 5, line 7, "member" should read --membrane--; Column 5, line 54, add after "and" and before "capable" the following: -through which the drug is-; same column and line, delete the word "through" after the word "diffusing"; Column 7, line 8, "withdrawing" should read --withdrawn-. I

' Signed and sealed this 17th day of September 1974.

(SEAL) Attest:

McCOY M. GIBSON JR. C. MARSHALL DANN Attesting Officer Commissioner of Patents USCOMM-DC 60376-P69 u 5. GOVERNMENT PRINTING OFFICE: I969 o-aes-aaa FORM O-1050 (10-69]

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3339546 *Dec 13, 1963Sep 5, 1967Squibb & Sons IncBandage for adhering to moist surfaces
US3444858 *May 11, 1966May 20, 1969Higham S RussellMethod and means for administering drugs
US3536809 *Feb 17, 1969Oct 27, 1970Alza CorpMedication method
US3551556 *Jan 6, 1967Dec 29, 1970Ceskoslovenska Akademie VedCarriers for biologically active substances
US3598122 *Apr 1, 1969Nov 23, 1982 Title not available
US3598123 *Apr 1, 1969Aug 10, 1971Alza CorpBandage for administering drugs
US3632740 *Jun 13, 1968Jan 4, 1972Johnson & JohnsonTopical device for the therapeutic management of dermatological lesions with steroids
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3870041 *Aug 16, 1973Mar 11, 1975Btr Industries LtdSurgical dressings
US3900027 *Jan 2, 1974Aug 19, 1975Pall CorpProcess for preparing integral absorbent pad bandages and product
US3972995 *Apr 14, 1975Aug 3, 1976American Home Products CorporationDosage form
US4031894 *Sep 7, 1976Jun 28, 1977Alza CorporationBandage for transdermally administering scopolamine to prevent nausea
US4039653 *Jul 21, 1975Aug 2, 1977Defoney, Brenman, Mayes & BaronBreath deodorants, sustained release
US4060084 *Jan 28, 1977Nov 29, 1977Alza CorporationMethod and therapeutic system for providing chemotherapy transdermally
US4201211 *Jul 12, 1977May 6, 1980Alza CorporationTherapeutic system for administering clonidine transdermally
US4226232 *Apr 9, 1979Oct 7, 1980Spenco Medical CorporationWound dressing
US4289749 *Jul 9, 1980Sep 15, 1981Key Pharmaceuticals, Inc.Polar plasticizer, polyvinyl alcohol, polyvinylpyrrolidone; sustained release of bronchodilator and decongestant through skin
US4291014 *Jul 11, 1980Sep 22, 1981Key Pharmaceuticals, Inc.Polymeric diffusion matrix containing estradiol diacetate
US4291015 *Jun 26, 1980Sep 22, 1981Key Pharmaceuticals, Inc.Polymeric diffusion matrix containing a vasodilator
US4292301 *Jul 9, 1980Sep 29, 1981Key Pharmaceuticals, Inc.Polymeric diffusion matrix containing ephedrine
US4292302 *Jul 9, 1980Sep 29, 1981Key Pharmaceuticals, Inc.Comprising plasticized polyvinyl alcohol and polyvinylpyrrolidone; bandages; sustained release
US4292303 *Jul 9, 1980Sep 29, 1981Key Pharmaceuticals, Inc.Polymeric diffusion matrix containing clonidine
US4294820 *Jul 9, 1980Oct 13, 1981Key Pharmaceuticals, Inc.Polymeric diffusion matrix containing phenylephrine
US4321252 *Dec 17, 1980Mar 23, 1982Key Pharmaceuticals, Inc.Polymeric diffusion matrix containing ester derivatives of estradiol
US4329333 *Nov 24, 1980May 11, 1982Arthur BarrMethod for the oral treatment of dogs and other animals
US4336243 *May 4, 1981Jun 22, 1982G. D. Searle & Co.Transdermal nitroglycerin pad
US4340043 *Nov 15, 1979Jul 20, 1982Smith & Nephew Research Ltd.Adhesive-coated sheet material incorporating anti-bacterial substances
US4363319 *Apr 20, 1981Dec 14, 1982Applied Medical Devices, Inc.Ready-to-use bandage incorporating a coagulant composition and method of preparing same
US4373519 *Jun 26, 1981Feb 15, 1983Minnesota Mining And Manufacturing CompanyHighly absorbent particles, non-adherent to wound
US4379454 *Feb 17, 1981Apr 12, 1983Alza CorporationDosage for coadministering drug and percutaneous absorption enhancer
US4390520 *Mar 30, 1981Jun 28, 1983Nitto Electric Industrial Co., Ltd.Indomethacin and acrylic-vinyl copolymer
US4455146 *Mar 2, 1982Jun 19, 1984Hisamitsu Pharmaceutical Co., Ltd.Novel plasters
US4460369 *Dec 21, 1981Jul 17, 1984Smith & Nephew Research Ltd.Adhesive-coated sheet material incorporating anti-bacterial substances
US4460372 *Apr 1, 1983Jul 17, 1984Alza CorporationPercutaneous absorption enhancer dispenser for use in coadministering drug and percutaneous absorption enhancer
US4485087 *Mar 12, 1982Nov 27, 1984Nitto Electric Industrial Co., Ltd.Laminate containing a medicine which migrates through a polymer film
US4492685 *Jan 30, 1984Jan 8, 1985Key Pharmaceuticals, Inc.Portection of burned or wounded patients
US4532937 *Nov 28, 1983Aug 6, 1985Cuderm CorporationSebum collection and monitoring means and method
US4563184 *Oct 17, 1983Jan 7, 1986Bernard KorolSynthetic resin wound dressing and method of treatment using same
US4594240 *Sep 7, 1983Jun 10, 1986Teikoku Seiyaku Kabushiki KaishaSheet-shape adhesive preparation
US4597961 *Jan 23, 1985Jul 1, 1986Etscorn Frank TTranscutaneous application of nicotine
US4614787 *Nov 13, 1984Sep 30, 1986Thermedics, Inc.Drug dispensing wound dressing
US4631227 *Dec 5, 1983Dec 23, 1986Kenji NakamuraToilet article
US4638043 *Aug 23, 1985Jan 20, 1987Thermedics, Inc.Drug release system
US4655767 *Sep 26, 1985Apr 7, 1987Dow Corning CorporationReduced sensitivity to amino-functional drugs
US4666441 *Dec 17, 1985May 19, 1987Ciba-Geigy CorporationMulticompartmentalized transdermal patches
US4690683 *Jul 2, 1985Sep 1, 1987Rutgers, The State University Of New JerseyTransdermal varapamil delivery device
US4727868 *May 20, 1987Mar 1, 1988Thermedics, Inc.Anisotropic wound dressing
US4743249 *Jun 10, 1987May 10, 1988Ciba-Geigy Corp.Dermal and transdermal patches having a discontinuous pattern adhesive layer
US4751133 *May 11, 1987Jun 14, 1988Thermedics, Inc.Medical patches and processes for producing same
US4767787 *Mar 24, 1986Aug 30, 1988Kaken Pharmaceutical Co., Ltd.Containing prostaglandin
US4830854 *Dec 18, 1987May 16, 1989James B. CopelanChemical splinter removal
US4839174 *Oct 5, 1987Jun 13, 1989Pharmetrix CorporationNovel transdermal nicotine patch
US4844903 *Nov 6, 1987Jul 4, 1989Mepha AgProcess for the production of an adhesive plaster
US4879275 *May 27, 1988Nov 7, 1989Nelson Research & Development Co.Penetration enhancers for transdermal delivery of systemic agent
US4880690 *Sep 9, 1988Nov 14, 1989Thermedics, Inc.Perfume patch
US4889720 *Aug 31, 1987Dec 26, 1989Teikoku Seiyaku Kabushiki KaishaAdhesive, reservoir and control release layer
US4898920 *Oct 15, 1987Feb 6, 1990Dow Corning CorporationAdhesive compositions, controlled release compositions and transdermal delivery device
US4906475 *Feb 16, 1988Mar 6, 1990Paco Pharmaceutical ServicesEstradiol transdermal delivery system
US4908027 *Sep 12, 1986Mar 13, 1990Alza CorporationSubsaturated transdermal therapeutic system having improved release characteristics
US4920101 *Sep 30, 1987Apr 24, 1990Nelson Research & Development Co.For enhancing penetration of physiologically active agents through skin or other membranes
US4943435 *Oct 28, 1988Jul 24, 1990Pharmetrix CorporationTransdermal drug delivery, polyethylene membrane
US4969871 *Feb 15, 1989Nov 13, 1990Alza CorporationIntravenous system for delivering a beneficial agent
US4973468 *Mar 22, 1989Nov 27, 1990Cygnus Research CorporationSkin permeation enhancer compositions
US4985016 *Feb 15, 1989Jan 15, 1991Alza CorporationIntravenous system for delivering a beneficial agent
US4991574 *Aug 15, 1990Feb 12, 1991Dow Corning CorporationSurgical dressing
US5004610 *Jun 14, 1990Apr 2, 1991Alza CorporationSubsaturated nicotine transdermal therapeutic system
US5034386 *Aug 17, 1988Jul 23, 1991Whitby Research, Inc.Fungicides
US5035894 *Sep 8, 1989Jul 30, 1991Dow Corning CorporationControlled release compositions and transdermal drug delivery device
US5045059 *Aug 15, 1990Sep 3, 1991Alza CorporationIntravenous system for delivering a beneficial agent
US5053227 *Jun 12, 1990Oct 1, 1991Cygnus Therapeutic SystemsTransmittance of drug in mixture of diethylene glycol ethyl and/or methyl ether and ester
US5059189 *Sep 8, 1987Oct 22, 1991E. R. Squibb & Sons, Inc.Method of preparing adhesive dressings containing a pharmaceutically active ingredient
US5059426 *Jun 12, 1990Oct 22, 1991Cygnus Therapeutic SystemsSkin permeation enhancer compositions, and methods and transdermal systems associated therewith
US5124157 *Aug 18, 1989Jun 23, 1992Cygnus Therapeutic SystemsUsing adhesive skin patch
US5160320 *Feb 14, 1990Nov 3, 1992Alza CorporationIntravenous system for delivering a beneficial agent
US5173302 *Sep 28, 1990Dec 22, 1992Medtronic, Inc.2-acrylamido-2-methyl propanesulfonic acid copolymer, ethylene /propylene oxide derivative humectant, crosslinking monomer, initiator
US5176915 *Jun 20, 1991Jan 5, 1993Lts LohmannPlaster used as therapeutic system for the administration of active substances to the skin which exhibits a graduated active substance release, process for the production of the plaster and the use thereof
US5204339 *Aug 6, 1990Apr 20, 1993Whitby Research, Inc.Penetration enhancers for transdermal delivery of systemic agents
US5230896 *Oct 12, 1989Jul 27, 1993Warner-Lambert CompanyTransdermal nicotine delivery system
US5250028 *Aug 9, 1991Oct 5, 1993Alza CorporationIntravenous system for delivering a beneficial agent using permeability enhancers
US5268179 *Feb 14, 1992Dec 7, 1993Ciba-Geigy CorporationUltrasonically sealed transdermal drug delivery systems
US5298257 *Mar 19, 1992Mar 29, 1994Elan Transdermal LimitedControlled transdermal nicotine delivery; anti-irritant
US5340585 *May 17, 1993Aug 23, 1994University Of Southern CaliforniaMethod and formulations for use in treating benign gynecological disorders
US5340586 *May 17, 1993Aug 23, 1994University Of Southern CaliforniaSlow release formulations of estrogens and androgens
US5342623 *Jun 18, 1993Aug 30, 1994Alza CorporationSubsaturated transdermal therapeutic system having improved release characteristics
US5422118 *Sep 21, 1992Jun 6, 1995Pure Pac, Inc.Transdermal administration of amines with minimal irritation and high transdermal flux rate
US5451407 *Jun 21, 1993Sep 19, 1995Alza CorporationReduction or prevention of skin irritation or sensitization during transdermal administration of a irritating or sensitizing drug
US5508038 *Apr 16, 1990Apr 16, 1996Alza CorporationDrug delivery patches having mixture of high and low molecular weight polymers as adhesives which dissolve active agents, free of plasticizers and tackifiers
US5508039 *Oct 16, 1992Apr 16, 1996Alza CorporationControlled transdermal administration of melatonin
US5512292 *Dec 21, 1994Apr 30, 1996Alza CorporationTransdermal contraceptive formulations methods and devices
US5536263 *Mar 30, 1994Jul 16, 1996Lectec CorporationNon-occulusive adhesive patch for applying medication to the skin
US5633008 *Aug 12, 1993May 27, 1997Osborne; James L.Method of administering nicotine transdermally
US5633009 *Nov 12, 1993May 27, 1997Sano CorporationTransdermal administration of azapirones
US5643596 *Jun 7, 1995Jul 1, 1997Clarion Pharmaceuticals, Inc.Hemostatic patch
US5645849 *Jun 7, 1995Jul 8, 1997Clarion Pharmaceuticals, Inc.Containing thrombin and epsilon aminocaproic acid; accelerates clot formation at wound surface
US5741510 *Apr 8, 1996Apr 21, 1998Lectec CorporationTransdermal delivery
US5747065 *Sep 29, 1994May 5, 1998Lee; Eun SooMonoglyceride/lactate ester permeation enhancer for oxybutynin
US5750137 *Sep 29, 1994May 12, 1998Taskovich; Lina TormenDrug delivery, permeability, glycerides and lactates
US5785991 *Jun 7, 1995Jul 28, 1998Alza CorporationTransdermal drug delivery
US5817331 *Jun 7, 1995Oct 6, 1998Sano CorporationAbsorption; drug delivery device
US5820876 *Jun 6, 1995Oct 13, 1998Lts Lohmann Therapie-Systeme Gmbh & Co. KgButadiene-acrylonitrile-methyl acrylate terpolymer, paper, and aluminum sealing bag containing a nicotine patch
US5837280 *Jun 7, 1995Nov 17, 1998Sano CorporationTransdermal administration of azapirones
US5840327 *Aug 15, 1996Nov 24, 1998Alza CorporationTransdermal drug delivery device having enhanced adhesion
US5843468 *May 13, 1996Dec 1, 1998Alza CorporationSkin permeation enhancer compositions comprising glycerol monolaurate and lauryl acetate
US5900250 *Apr 30, 1998May 4, 1999Alza CorporationMonoglyceride/lactate ester permeation enhancer for oxybutnin
US5919478 *Jun 24, 1994Jul 6, 1999Alza CorporationIncorporating poly-N-vinyl amide in a transdermal system
US6001390 *Dec 18, 1996Dec 14, 1999Alza CorporationFormulations for transdermal delivery of pergolide
US6096333 *Oct 8, 1997Aug 1, 2000Lectec CorporationMethod of forming adhesive patch for applying medication to the skin
US6096334 *Dec 14, 1998Aug 1, 2000Lectec CorporationSelf-supporting flexible sheet; fluid adhesive
US6110488 *Jun 6, 1995Aug 29, 2000Lts Lohmann Therapie-Systeme Gmbh & Co. KgApplying a polymeric acrylic pressure sensitive adhesive to a detacable protective layer, applying absorbent factric to the adhesive, applying a drug and laminating a backing layer to the fabric material
US6117448 *Jun 6, 1995Sep 12, 2000Lts Lohmann Therapie-Systeme Gmbh & Co. KgConsists of a layer of backing material which is substantially impermeable to nicotine and a matrix of nicotine in a body of pressure sensitive acrylate copolymer which is laminated to a protective layer, used for transdermal drug delivery
US6121289 *Oct 9, 1998Sep 19, 2000Theramax, Inc.Treating addiction to tobacco by intranasally administering a nicotinic antagonist such as mecamylamine, and carrier
US6126963 *Jun 6, 1995Oct 3, 2000Lts Lohmann Therapie-Systeme Gmbh & Co. KgBags for transdermal drug therapy
US6139868 *Jun 6, 1995Oct 31, 2000Lts Lohmann Therapie-Systeme Gmbh & Co. KgTransdermal therapeutic system, its use and production process
US6165497 *Mar 1, 1991Dec 26, 2000Alza CorporationSubsaturated nicotine transdermal therapeutic system
US6183770 *Apr 15, 1999Feb 6, 2001Acutek InternationalDelivery of agents to the skin for local skin treatment may be desirable to improve the health and appearance of the skin.
US6203817Jun 5, 1998Mar 20, 2001Alza CorporationReduction of skin reactions caused by transdermal drug delivery
US6224900Mar 9, 1998May 1, 2001Lts Lohmann Therapie-Systeme Gmbh & Co. KgNicotine barrier layer of nitrile rubber and degradation agent
US6261593Jul 24, 2000Jul 17, 2001Acutek InternationalSupplying petroleum jelly
US6264977Oct 28, 1999Jul 24, 2001Lts Lohmann Therapie-Systeme Gmbh & Co. KgTransdermal therapeutic system, its use and production process
US6267984Dec 17, 1998Jul 31, 2001Alza CorporationImproved transdermal drug delivery
US6300327Feb 6, 1997Oct 9, 2001The University Of Southern CaliforniaNeurotropin inhibitors
US6348210Nov 10, 1999Feb 19, 2002Alza CorporationMethods for transdermal drug administration
US6469227May 12, 2000Oct 22, 2002Lectec CorporationAntipruritic patch
US6479073 *Oct 7, 1996Nov 12, 20023M Innovative Properties CompanyPressure sensitive adhesive articles and methods for preparing same
US6512010Jul 14, 1997Jan 28, 2003Alza CorporationFormulations for the administration of fluoxetine
US6572879Jun 7, 1995Jun 3, 2003Alza CorporationFormulations for transdermal delivery of pergolide
US6592892Aug 29, 2000Jul 15, 2003Tepha, Inc.Flushable disposable polymeric products
US6660295Sep 29, 1998Dec 9, 2003Alza CorporationA pouch containing (a) a transdermal drug delivery device comprising a drug reservoir layer positioned between a release liner and a backing alyer, one of the layer being non-occlusive, (b) oxybutynin as antioxidant and desiccant
US6699497Jul 23, 1999Mar 2, 2004Alza CorporationPermeation enhancer
US6727401Feb 12, 1998Apr 27, 2004Watson Pharmaceuticals, Inc.Occlusive backing layer; antifungal fluconazole, terbinafine, clotrimazole, miconazole and ketoconazole, salts or mixtures thereof; nail infections
US6960353Sep 29, 2003Nov 1, 2005Alza CorporationFormulations for the transdermal administration of fenoldopam
US6974588Dec 7, 1999Dec 13, 2005Elan Pharma International LimitedTransdermal patch for delivering volatile liquid drugs
US7011844Nov 22, 2002Mar 14, 2006Alza CorporationFormulations for the administration of fluoxetine
US7267829Apr 23, 2004Sep 11, 2007Transdermal Technologies, Inc.Compositions for rapid and non-irritating transdermal delivery of pharmaceutically active agents and methods for formulating such compositions and delivery thereof
US7357891Jan 30, 2004Apr 15, 2008Monosol Rx, LlcProcess for making an ingestible film
US7425292Feb 14, 2002Sep 16, 2008Monosol Rx, LlcThin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom
US7553923Oct 26, 2007Jun 30, 2009Metabolix, Inc.Medical devices and applications of polyhydroxyalkanoate polymers
US7622136Jun 18, 2004Nov 24, 2009Alza CorporationTransparent transdermal nicotine delivery devices
US7641825Jul 29, 2005Jan 5, 2010Tepha, Inc.Method of making a polyhydroxyalkanoate filament
US7666337May 28, 2004Feb 23, 2010Monosol Rx, LlcPolyethylene oxide-based films and drug delivery systems made therefrom
US7824588Apr 14, 2008Nov 2, 2010Monosol Rx, LlcWater degradation; controlled drying; digestible film containing water soluble polymer
US7879942Oct 5, 2006Feb 1, 2011Eastman Chemical CompanySwitchable adhesive article for attachment to skin and method of using the same
US7910641Dec 14, 2006Mar 22, 2011Monosol Rx, LlcPH modulated films for delivery of actives
US7943683Oct 31, 2007May 17, 2011Tepha, Inc.Thin bioabsorbable materials; toughness, low modulus, tensile strength; tissue repair, drug delivery and support; solvent casting or melt extrusion continuous production
US7972618Sep 20, 2007Jul 5, 2011Monosol Rx, LlcEdible water-soluble film containing a foam reducing flavoring agent
US8017150Apr 22, 2008Sep 13, 2011Monosol Rx, LlcPolyether combined with hydrophilic cellulosic material; demonstrates non-self-aggregating, uniform heterogeneity; mucosally adhesive water soluble product containing analgesic opiate; preventing air pocket formation during production
US8017598May 16, 2007Sep 13, 2011Knopp Neurosciences, Inc.Compositions of R(+) and S(−) pramipexole and methods of using the same
US8034270Apr 30, 2004Oct 11, 2011Tepha, Inc.Absorbable polyesters; surgery meshes
US8075911Aug 20, 2007Dec 13, 2011Alza CorporationTransparent transdermal nicotine delivery devices
US8084125Dec 11, 2009Dec 27, 2011Tepha, Inc.Non-curling polyhydroxyalkanoate sutures
US8124689Jun 6, 2007Feb 28, 2012Dow Corning CorporationSilicone acrylate hybride composition and method of making same
US8153162Sep 27, 2006Apr 10, 2012Tissuetech, Inc.Purified amniotic membrane compositions and methods of use
US8182840Sep 27, 2006May 22, 2012Tissue Tech, Inc.Amniotic membrane preparations and purified compositions and therapy for scar reversal and inhibition
US8182841Sep 27, 2006May 22, 2012Tissue Tech, Inc.Amniotic membrane preparations and purified compositions and anti-inflammation methods
US8187639Sep 27, 2006May 29, 2012Tissue Tech, Inc.Amniotic membrane preparations and purified compositions and anti-angiogenesis treatment
US8236288Jan 6, 2012Aug 7, 2012Skinmedica, Inc.Melanin modification compositions and methods of use
US8361272Jun 27, 2007Jan 29, 2013Ferring B.V.Polyurethane elastomers
US8361273Sep 6, 2012Jan 29, 2013Ferring B.V.Polyurethane elastomers
US8420126Apr 23, 2012Apr 16, 2013Tissue Tech, Inc.Amniotic membrane preparations and purified compositions and anti-angiogenesis treatment
US8440235Apr 23, 2012May 14, 2013Tissuetech, Inc.Amniotic membrane preparations and purified compositions and therapy for scar reversal and inhibition
US8445474Aug 5, 2011May 21, 2013Knopp Neurosciences, Inc.Compositions of R(+) and S(−) pramipexole and methods of using the same
US8455009Apr 23, 2012Jun 4, 2013Tissuetech, Inc.Amniotic membrane preparations and purified compositions and anti-inflammation methods
US8460707Mar 26, 2012Jun 11, 2013Ferring B.V.Stabilised prostaglandin composition
US8460714Apr 3, 2012Jun 11, 2013Tissuetech, Inc.Purified amniotic membrane compositions and methods of use
US8475832Aug 7, 2009Jul 2, 2013Rb Pharmaceuticals LimitedSublingual and buccal film compositions
US8491934Jul 28, 2005Jul 23, 2013Ferring B.V.Stabilised prostaglandin composition
US8518926Dec 14, 2007Aug 27, 2013Knopp Neurosciences, Inc.Compositions and methods of using (R)-pramipexole
US8519148Mar 14, 2008Aug 27, 2013Knopp Neurosciences, Inc.Synthesis of chirally purified substituted benzothiazole diamines
US8524254Oct 15, 2007Sep 3, 2013Ferring B.V.Bioresorbable polymers
US8524695Mar 14, 2008Sep 3, 2013Knopp Neurosciences, Inc.Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same
US8557281Jul 13, 2010Oct 15, 2013Ferring B.V.Water-swellable polymers
US8569416Oct 21, 2011Oct 29, 2013Dow Corning CorporationSingle phase silicone acrylate formulation
US8603514Jul 10, 2007Dec 10, 2013Monosol Rx, LlcUniform films for rapid dissolve dosage form incorporating taste-masking compositions
US8614278Nov 29, 2011Dec 24, 2013Dow Corning CorporationSilicone acrylate hybrid composition and method of making same
US8628798Aug 10, 2012Jan 14, 2014Ferring B.V.Water-swellable polymers
US8652378Mar 29, 2013Feb 18, 2014Monosol Rx LlcUniform films for rapid dissolve dosage form incorporating taste-masking compositions
US8663680Dec 5, 2011Mar 4, 2014Alza CorporationTransparent transdermal nicotine delivery devices
US8663687May 13, 2010Mar 4, 2014Monosol Rx, LlcFilm compositions for delivery of actives
US8685437Mar 26, 2009Apr 1, 2014Monosol Rx, LlcThin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom
US8709482May 31, 2013Apr 29, 2014Ferring B.V.Stabilised prostaglandin composition
US8753555Apr 11, 2011Jun 17, 2014Tepha, Inc.Medical devices containing oriented films of poly-4-hydroxybutyrate and copolymers
US8758657Jul 16, 2013Jun 24, 2014Tepha, Inc.Process of making polyhydroxyalkanoate medical textiles
US8765167Sep 8, 2006Jul 1, 2014Monosol Rx, LlcUniform films for rapid-dissolve dosage form incorporating anti-tacking compositions
US8778315Feb 26, 2013Jul 15, 2014Allergan, Inc.Melanin modification compositions and methods of use
US8778382Apr 30, 2004Jul 15, 2014Purdue Pharma L.P.Tamper resistant transdermal dosage form
US8790689Nov 18, 2005Jul 29, 2014Purdue Pharma L.P.Tamper resistant transdermal dosage form
US8796416Oct 25, 2011Aug 5, 2014Questcor Pharmaceuticals, IncACTH prophylactic treatment of renal disorders
USRE32991 *Jul 25, 1988Jul 18, 1989Thermedics, Inc.Drug dispensing wound dressing
USRE35474 *Oct 13, 1994Mar 11, 1997Dow Corning CorporationTransdermal drug delivery devices with amine-resistant silicone adhesives
USRE37934Feb 3, 2000Dec 10, 2002Lts Lohmann Therapie-Systeme AgTransdermal therapeutic system
USRE39588Oct 31, 1990Apr 24, 2007Alza CorporationDelays onset of drug administration; does not deliver an initial burst of drug, less likely to cause irritation; stabilizes an active drug by storing it within a transdermal therapeutic system, in form suitable for storage
DE3208853A1 *Mar 11, 1982Sep 23, 1982Nitto Electric Ind CoVerfahren zur herstellung einer pharmazeutischen verbundzubereitung
DE3629304A1 *Aug 28, 1986Mar 24, 1988Lohmann Gmbh & Co KgTransdermales therapeutisches system, seine verwendung und verfahren zu seiner herstellung
DE102010053792A1Dec 8, 2010Jun 14, 2012Frank BecherDevice for germ-free keeping of surfaces, such as door handles, handrails, grip bars, handles of shopping carts and toilet seating surfaces, has flat support material and self-adhesive portion formed on one side of flat support material
DE102013107024A1Jul 4, 2013May 15, 2014Golden Biotechnology CorporationMethoden und Zusammensetzungen zum Behandeln, Modifizieren und Handhaben von Knochenkrebsschmerz
DE102013107025A1Jul 4, 2013Jul 3, 2014Golden Biotechnology CorporationMethoden und zusammensetzungen zur behanldung von diabetis
DE102013202928A1Feb 22, 2013Aug 29, 2013Golden Biotechnology CorporationVerfahren und Zusammensetzungen zum Behandeln von Krebsmetastasierung
EP0236266A1 *Feb 9, 1987Sep 9, 1987Ciba-Geigy AgDermal and transdermal therapeutic system having a discontinuous-pattern adhesive layer and method of manufacturing thereof
EP0273004A2 *Nov 16, 1987Jun 29, 1988Ciba-Geigy AgUser-activated therapeutical system
EP1399145A2 *Jan 12, 1999Mar 24, 2004Watson Pharmaceuticals, Inc.Pressure sensitive adhesive matrix patch for the treatment of onychomycosis
EP1674068A1Feb 19, 1997Jun 28, 2006Acrux DDS Pty LtdDermal penetration enhancers and drug delivery systems involving same
EP2158903A2Dec 14, 1999Mar 3, 2010ALZA CorporationTransparent Transdermal Nicotine Delivery Devices
EP2201840A1Dec 28, 2006Jun 30, 2010Pharmacyclics, Inc.Inhibitors of Bruton's Tyrosine Kinase
EP2443929A1Dec 28, 2006Apr 25, 2012Pharmacyclics, Inc.Inhibitors of Bruton's Tyrosine Kinase
EP2526771A1Dec 28, 2006Nov 28, 2012Pharmacyclics, Inc.Inhibitors of bruton's tyrosine kinase
EP2526933A2Dec 28, 2006Nov 28, 2012Pharmacyclics, Inc.Inhibitors of bruton's tyrosine kinase
EP2526934A2Dec 28, 2006Nov 28, 2012Pharmacyclics, Inc.Inhibitors of bruton's tyrosine kinase
EP2529621A1Dec 28, 2006Dec 5, 2012Pharmacyclics, Inc.Inhibitors of bruton's tyrosine kinase
EP2529622A1Dec 28, 2006Dec 5, 2012Pharmacyclics, Inc.Inhibitors of bruton's tyrosine kinase
EP2530083A1Dec 28, 2006Dec 5, 2012Pharmacyclics, Inc.Inhibitors of bruton's tyrosine kinase
EP2532234A1Dec 28, 2006Dec 12, 2012Pharmacyclics, Inc.Inhibitors of bruton's tyrosine kinase
EP2532235A1Dec 28, 2006Dec 12, 2012Pharmacyclics, Inc.Inhibitors of bruton's tyrosine kinase
EP2584016A1Oct 19, 2012Apr 24, 2013Dow Corning CorporationSingle phase silicone acrylate formulation
EP2599847A1Nov 29, 2012Jun 5, 2013Dow Corning CorporationA Silicone Acrylate Hybrid Composition and Method of Making Same
EP2650294A1Oct 12, 2010Oct 16, 2013Pharmacyclics, Inc.Inhibitors of Bruton's Tyrosine Kinase
EP2664337A1Sep 27, 2006Nov 20, 2013TissueTech, Inc.Amniotic membrane preparations and purified compositions and methods of use
WO1984002460A1 *Dec 22, 1983Jul 5, 1984Dermatec LtdSebum collection and monitoring means
WO1987000042A1 *Jun 27, 1986Jan 15, 1987Univ New JerseyTransdermal verapamil delivery device
WO1987003477A1 *Dec 12, 1985Jun 18, 1987Flexcon Co IncTransdermal methods and adhesives
WO1989005582A1 *Nov 30, 1988Jun 29, 1989Russell Isaac CopelanChemical splinter removal
WO1999040955A2 *Jan 12, 1999Aug 19, 1999Theratech IncPressure sensitive adhesive matrix patch for the treatment of onychomycosis
WO2007062266A2Nov 28, 2006May 31, 2007Marinus PharmaceuticalsGanaxolone formulations and methods for the making and use thereof
WO2008021368A2Aug 13, 2007Feb 21, 2008Norman HaugheyCompositions and methods for neuroprotection
WO2008066899A2Nov 28, 2007Jun 5, 2008Marinus PharmaceuticalsNanoparticulate formulations and methods for the making and use thereof
WO2010071866A2Dec 19, 2009Jun 24, 2010Nuon Therapeutics, Inc.Combination therapy for arthritis with tranilast
Classifications
U.S. Classification424/434, 424/448, 604/304, 424/449
International ClassificationA61K9/70
Cooperative ClassificationA61K9/7061, A61K9/7084, A61K9/7069, A61K9/7092
European ClassificationA61K9/70E2B6B2, A61K9/70E2D, A61K9/70E2B6D, A61K9/70E2K