|Número de publicación||US3731683 A|
|Tipo de publicación||Concesión|
|Fecha de publicación||8 May 1973|
|Fecha de presentación||4 Jun 1971|
|Fecha de prioridad||4 Jun 1971|
|Número de publicación||US 3731683 A, US 3731683A, US-A-3731683, US3731683 A, US3731683A|
|Cesionario original||Alza Corp|
|Exportar cita||BiBTeX, EndNote, RefMan|
|Citas de patentes (7), Citada por (319), Clasificaciones (13)|
|Enlaces externos: USPTO, Cesión de USPTO, Espacenet|
United States Patent 91 Zalfaroni 51 *May 8,1973
[54) BANDAGE FOR THE CONTROLLED METERING OF TOPICAL DRUGS TO THE SKIN  Inventor: Alejandro Zafiaroni, Atherton,
 Assignee: Alza Corporation Notice: The portion of the term of this patent subsequent to Aug. 10, 1988, has been disclaimed.
 Filed: June 4, 1971  Appl. No.: 150,085
Related US. Application Data  Continuation-impart of Ser. No. 136,981, April 23,
 US. Cl. ..l28/268, 128/156, 424/28  Int. Cl. ..A6lf 7/02  Field of Search ..l28/260, 268, 156,
 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.
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]
|Patente citada||Fecha de presentación||Fecha de publicación||Solicitante||Título|
|US3339546 *||13 Dic 1963||5 Sep 1967||Squibb & Sons Inc||Bandage for adhering to moist surfaces|
|US3444858 *||11 May 1966||20 May 1969||Higham S Russell||Method and means for administering drugs|
|US3536809 *||17 Feb 1969||27 Oct 1970||Alza Corp||Medication method|
|US3551556 *||6 Ene 1967||29 Dic 1970||Ceskoslovenska Akademie Ved||Carriers for biologically active substances|
|US3598122 *||1 Abr 1969||23 Nov 1982||Título no disponible|
|US3598123 *||1 Abr 1969||10 Ago 1971||Alza Corp||Bandage for administering drugs|
|US3632740 *||13 Jun 1968||4 Ene 1972||Johnson & Johnson||Topical device for the therapeutic management of dermatological lesions with steroids|
|Patente citante||Fecha de presentación||Fecha de publicación||Solicitante||Título|
|US3870041 *||16 Ago 1973||11 Mar 1975||Btr Industries Ltd||Surgical dressings|
|US3900027 *||2 Ene 1974||19 Ago 1975||Pall Corp||Process for preparing integral absorbent pad bandages and product|
|US3972995 *||14 Abr 1975||3 Ago 1976||American Home Products Corporation||Dosage form|
|US4031894 *||7 Sep 1976||28 Jun 1977||Alza Corporation||Bandage for transdermally administering scopolamine to prevent nausea|
|US4039653 *||21 Jul 1975||2 Ago 1977||Defoney, Brenman, Mayes & Baron||Long-acting articles for oral delivery and process|
|US4060084 *||28 Ene 1977||29 Nov 1977||Alza Corporation||Method and therapeutic system for providing chemotherapy transdermally|
|US4201211 *||12 Jul 1977||6 May 1980||Alza Corporation||Therapeutic system for administering clonidine transdermally|
|US4226232 *||9 Abr 1979||7 Oct 1980||Spenco Medical Corporation||Wound dressing|
|US4289749 *||9 Jul 1980||15 Sep 1981||Key Pharmaceuticals, Inc.||Polymeric diffusion matrix containing phenylpropanolamine|
|US4291014 *||11 Jul 1980||22 Sep 1981||Key Pharmaceuticals, Inc.||Polymeric diffusion matrix containing estradiol diacetate|
|US4291015 *||26 Jun 1980||22 Sep 1981||Key Pharmaceuticals, Inc.||Polymeric diffusion matrix containing a vasodilator|
|US4292301 *||9 Jul 1980||29 Sep 1981||Key Pharmaceuticals, Inc.||Polymeric diffusion matrix containing ephedrine|
|US4292302 *||9 Jul 1980||29 Sep 1981||Key Pharmaceuticals, Inc.||Polymeric diffusion matrix containing terbutaline|
|US4292303 *||9 Jul 1980||29 Sep 1981||Key Pharmaceuticals, Inc.||Polymeric diffusion matrix containing clonidine|
|US4294820 *||9 Jul 1980||13 Oct 1981||Key Pharmaceuticals, Inc.||Polymeric diffusion matrix containing phenylephrine|
|US4321252 *||17 Dic 1980||23 Mar 1982||Key Pharmaceuticals, Inc.||Polymeric diffusion matrix containing ester derivatives of estradiol|
|US4329333 *||24 Nov 1980||11 May 1982||Arthur Barr||Method for the oral treatment of dogs and other animals|
|US4336243 *||4 May 1981||22 Jun 1982||G. D. Searle & Co.||Transdermal nitroglycerin pad|
|US4340043 *||15 Nov 1979||20 Jul 1982||Smith & Nephew Research Ltd.||Adhesive-coated sheet material incorporating anti-bacterial substances|
|US4363319 *||20 Abr 1981||14 Dic 1982||Applied Medical Devices, Inc.||Ready-to-use bandage incorporating a coagulant composition and method of preparing same|
|US4373519 *||26 Jun 1981||15 Feb 1983||Minnesota Mining And Manufacturing Company||Composite wound dressing|
|US4379454 *||17 Feb 1981||12 Abr 1983||Alza Corporation||Dosage for coadministering drug and percutaneous absorption enhancer|
|US4390520 *||30 Mar 1981||28 Jun 1983||Nitto Electric Industrial Co., Ltd.||Antiphlogistic analgesic adhesive|
|US4455146 *||2 Mar 1982||19 Jun 1984||Hisamitsu Pharmaceutical Co., Ltd.||Novel plasters|
|US4460369 *||21 Dic 1981||17 Jul 1984||Smith & Nephew Research Ltd.||Adhesive-coated sheet material incorporating anti-bacterial substances|
|US4460372 *||1 Abr 1983||17 Jul 1984||Alza Corporation||Percutaneous absorption enhancer dispenser for use in coadministering drug and percutaneous absorption enhancer|
|US4485087 *||12 Mar 1982||27 Nov 1984||Nitto Electric Industrial Co., Ltd.||Process for obtaining composite pharmaceutical preparation|
|US4492685 *||30 Ene 1984||8 Ene 1985||Key Pharmaceuticals, Inc.||Protective skin matrix|
|US4532937 *||28 Nov 1983||6 Ago 1985||Cuderm Corporation||Sebum collection and monitoring means and method|
|US4563184 *||17 Oct 1983||7 Ene 1986||Bernard Korol||Synthetic resin wound dressing and method of treatment using same|
|US4594240 *||7 Sep 1983||10 Jun 1986||Teikoku Seiyaku Kabushiki Kaisha||Sheet-shape adhesive preparation|
|US4597961 *||23 Ene 1985||1 Jul 1986||Etscorn Frank T||Transcutaneous application of nicotine|
|US4614787 *||13 Nov 1984||30 Sep 1986||Thermedics, Inc.||Drug dispensing wound dressing|
|US4631227 *||5 Dic 1983||23 Dic 1986||Kenji Nakamura||Toilet article|
|US4638043 *||23 Ago 1985||20 Ene 1987||Thermedics, Inc.||Drug release system|
|US4655767 *||26 Sep 1985||7 Abr 1987||Dow Corning Corporation||Transdermal drug delivery devices with amine-resistant silicone adhesives|
|US4666441 *||17 Dic 1985||19 May 1987||Ciba-Geigy Corporation||Multicompartmentalized transdermal patches|
|US4690683 *||2 Jul 1985||1 Sep 1987||Rutgers, The State University Of New Jersey||Transdermal varapamil delivery device|
|US4727868 *||20 May 1987||1 Mar 1988||Thermedics, Inc.||Anisotropic wound dressing|
|US4743249 *||10 Jun 1987||10 May 1988||Ciba-Geigy Corp.||Dermal and transdermal patches having a discontinuous pattern adhesive layer|
|US4751133 *||11 May 1987||14 Jun 1988||Thermedics, Inc.||Medical patches and processes for producing same|
|US4767787 *||24 Mar 1986||30 Ago 1988||Kaken Pharmaceutical Co., Ltd.||Sheet-shape adhesive preparation|
|US4830854 *||18 Dic 1987||16 May 1989||James B. Copelan||Chemical splinter removal|
|US4839174 *||5 Oct 1987||13 Jun 1989||Pharmetrix Corporation||Novel transdermal nicotine patch|
|US4844903 *||6 Nov 1987||4 Jul 1989||Mepha Ag||Process for the production of an adhesive plaster|
|US4879275 *||27 May 1988||7 Nov 1989||Nelson Research & Development Co.||Penetration enhancers for transdermal delivery of systemic agent|
|US4880690 *||9 Sep 1988||14 Nov 1989||Thermedics, Inc.||Perfume patch|
|US4889720 *||31 Ago 1987||26 Dic 1989||Teikoku Seiyaku Kabushiki Kaisha||Sustained release dosage form for use with tissues of the oral cavity|
|US4898920 *||15 Oct 1987||6 Feb 1990||Dow Corning Corporation||Adhesive compositions, controlled release compositions and transdermal delivery device|
|US4906475 *||16 Feb 1988||6 Mar 1990||Paco Pharmaceutical Services||Estradiol transdermal delivery system|
|US4908027 *||12 Sep 1986||13 Mar 1990||Alza Corporation||Subsaturated transdermal therapeutic system having improved release characteristics|
|US4920101 *||30 Sep 1987||24 Abr 1990||Nelson Research & Development Co.||Compositions comprising 1-oxo- or thiohydrocarbyl substituted azacycloaklkanes|
|US4943435 *||28 Oct 1988||24 Jul 1990||Pharmetrix Corporation||Prolonged activity nicotine patch|
|US4969871 *||15 Feb 1989||13 Nov 1990||Alza Corporation||Intravenous system for delivering a beneficial agent|
|US4973468 *||22 Mar 1989||27 Nov 1990||Cygnus Research Corporation||Skin permeation enhancer compositions|
|US4985016 *||15 Feb 1989||15 Ene 1991||Alza Corporation||Intravenous system for delivering a beneficial agent|
|US4991574 *||15 Ago 1990||12 Feb 1991||Dow Corning Corporation||Surgical dressing|
|US5004610 *||14 Jun 1990||2 Abr 1991||Alza Corporation||Subsaturated nicotine transdermal therapeutic system|
|US5034386 *||17 Ago 1988||23 Jul 1991||Whitby Research, Inc.||Methods for administration using 1-substituted azacycloalkanes|
|US5035894 *||8 Sep 1989||30 Jul 1991||Dow Corning Corporation||Controlled release compositions and transdermal drug delivery device|
|US5045059 *||15 Ago 1990||3 Sep 1991||Alza Corporation||Intravenous system for delivering a beneficial agent|
|US5053227 *||12 Jun 1990||1 Oct 1991||Cygnus Therapeutic Systems||Skin permeation enhancer compositions, and methods and transdermal systems associated therewith|
|US5059189 *||8 Sep 1987||22 Oct 1991||E. R. Squibb & Sons, Inc.||Method of preparing adhesive dressings containing a pharmaceutically active ingredient|
|US5059426 *||12 Jun 1990||22 Oct 1991||Cygnus Therapeutic Systems||Skin permeation enhancer compositions, and methods and transdermal systems associated therewith|
|US5124157 *||18 Ago 1989||23 Jun 1992||Cygnus Therapeutic Systems||Method and device for administering dexmedetomidine transdermally|
|US5160320 *||14 Feb 1990||3 Nov 1992||Alza Corporation||Intravenous system for delivering a beneficial agent|
|US5173302 *||28 Sep 1990||22 Dic 1992||Medtronic, Inc.||Hydrophilic pressure sensitive adhesive for topical administration of hydrophobic drugs|
|US5176915 *||20 Jun 1991||5 Ene 1993||Lts Lohmann||Plaster 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 *||6 Ago 1990||20 Abr 1993||Whitby Research, Inc.||Penetration enhancers for transdermal delivery of systemic agents|
|US5230896 *||12 Oct 1989||27 Jul 1993||Warner-Lambert Company||Transdermal nicotine delivery system|
|US5250028 *||9 Ago 1991||5 Oct 1993||Alza Corporation||Intravenous system for delivering a beneficial agent using permeability enhancers|
|US5268179 *||14 Feb 1992||7 Dic 1993||Ciba-Geigy Corporation||Ultrasonically sealed transdermal drug delivery systems|
|US5298257 *||19 Mar 1992||29 Mar 1994||Elan Transdermal Limited||Method for the treatment of withdrawal symptoms associated with smoking cessation and preparations for use in said method|
|US5340585 *||17 May 1993||23 Ago 1994||University Of Southern California||Method and formulations for use in treating benign gynecological disorders|
|US5340586 *||17 May 1993||23 Ago 1994||University Of Southern California||Methods and formulations for use in treating oophorectomized women|
|US5342623 *||18 Jun 1993||30 Ago 1994||Alza Corporation||Subsaturated transdermal therapeutic system having improved release characteristics|
|US5422118 *||21 Sep 1992||6 Jun 1995||Pure Pac, Inc.||Transdermal administration of amines with minimal irritation and high transdermal flux rate|
|US5451407 *||21 Jun 1993||19 Sep 1995||Alza Corporation||Reduction or prevention of skin irritation or sensitization during transdermal administration of a irritating or sensitizing drug|
|US5508038 *||16 Abr 1990||16 Abr 1996||Alza Corporation||Polyisobutylene adhesives for transdermal devices|
|US5508039 *||16 Oct 1992||16 Abr 1996||Alza Corporation||Controlled transdermal administration of melatonin|
|US5512292 *||21 Dic 1994||30 Abr 1996||Alza Corporation||Transdermal contraceptive formulations methods and devices|
|US5536263 *||30 Mar 1994||16 Jul 1996||Lectec Corporation||Non-occulusive adhesive patch for applying medication to the skin|
|US5633008 *||12 Ago 1993||27 May 1997||Osborne; James L.||Method of administering nicotine transdermally|
|US5633009 *||12 Nov 1993||27 May 1997||Sano Corporation||Transdermal administration of azapirones|
|US5643596 *||7 Jun 1995||1 Jul 1997||Clarion Pharmaceuticals, Inc.||Hemostatic patch|
|US5645849 *||7 Jun 1995||8 Jul 1997||Clarion Pharmaceuticals, Inc.||Hemostatic patch|
|US5741510 *||8 Abr 1996||21 Abr 1998||Lectec Corporation||Adhesive patch for applying analgesic medication to the skin|
|US5747065 *||29 Sep 1994||5 May 1998||Lee; Eun Soo||Monoglyceride/lactate ester permeation enhancer for oxybutynin|
|US5750137 *||29 Sep 1994||12 May 1998||Taskovich; Lina Tormen||Monoglyceride/lactate ester permeation enhancer|
|US5785991 *||7 Jun 1995||28 Jul 1998||Alza Corporation||Skin permeation enhancer compositions comprising glycerol monolaurate and lauryl acetate|
|US5817331 *||7 Jun 1995||6 Oct 1998||Sano Corporation||Transdermal administration of azapirones|
|US5820876 *||6 Jun 1995||13 Oct 1998||Lts Lohmann Therapie-Systeme Gmbh & Co. Kg||Transdermal therapeutic system|
|US5837280 *||7 Jun 1995||17 Nov 1998||Sano Corporation||Transdermal administration of azapirones|
|US5840327 *||15 Ago 1996||24 Nov 1998||Alza Corporation||Transdermal drug delivery device having enhanced adhesion|
|US5843468 *||13 May 1996||1 Dic 1998||Alza Corporation||Skin permeation enhancer compositions comprising glycerol monolaurate and lauryl acetate|
|US5900250 *||30 Abr 1998||4 May 1999||Alza Corporation||Monoglyceride/lactate ester permeation enhancer for oxybutnin|
|US5919478 *||24 Jun 1994||6 Jul 1999||Alza Corporation||Incorporating poly-N-vinyl amide in a transdermal system|
|US6001390 *||18 Dic 1996||14 Dic 1999||Alza Corporation||Formulations for transdermal delivery of pergolide|
|US6096333 *||8 Oct 1997||1 Ago 2000||Lectec Corporation||Method of forming adhesive patch for applying medication to the skin|
|US6096334 *||14 Dic 1998||1 Ago 2000||Lectec Corporation||Adhesive patch for applying medication to the skin and method|
|US6110488 *||6 Jun 1995||29 Ago 2000||Lts Lohmann Therapie-Systeme Gmbh & Co. Kg||Transdermal therapeutic system, its use and production process|
|US6117448 *||6 Jun 1995||12 Sep 2000||Lts Lohmann Therapie-Systeme Gmbh & Co. Kg||Transdermal therapeutic system, its use and production process|
|US6121289 *||9 Oct 1998||19 Sep 2000||Theramax, Inc.||Method for enhanced brain delivery of nicotinic antagonist|
|US6126963 *||6 Jun 1995||3 Oct 2000||Lts Lohmann Therapie-Systeme Gmbh & Co. Kg||Transdermal therapeutic system, its use and production process|
|US6139868 *||6 Jun 1995||31 Oct 2000||Lts Lohmann Therapie-Systeme Gmbh & Co. Kg||Transdermal therapeutic system, its use and production process|
|US6165497 *||1 Mar 1991||26 Dic 2000||Alza Corporation||Subsaturated nicotine transdermal therapeutic system|
|US6183770 *||15 Abr 1999||6 Feb 2001||Acutek International||Carrier patch for the delivery of agents to the skin|
|US6203817||5 Jun 1998||20 Mar 2001||Alza Corporation||Reduction of skin reactions caused by transdermal drug delivery|
|US6224900||9 Mar 1998||1 May 2001||Lts Lohmann Therapie-Systeme Gmbh & Co. Kg||Sealing bag for a transdermal therapeutic system|
|US6261593||24 Jul 2000||17 Jul 2001||Acutek International||Carrier patch for the delivery of agents to the skin|
|US6264977||28 Oct 1999||24 Jul 2001||Lts Lohmann Therapie-Systeme Gmbh & Co. Kg||Transdermal therapeutic system, its use and production process|
|US6267984||17 Dic 1998||31 Jul 2001||Alza Corporation||Skin permeation enhancer compositions comprising a monoglyceride and ethyl palmitate|
|US6300327||6 Feb 1997||9 Oct 2001||The University Of Southern California||Compositions and methods for potentiation of neurotrophin activity|
|US6348210||10 Nov 1999||19 Feb 2002||Alza Corporation||Methods for transdermal drug administration|
|US6469227||12 May 2000||22 Oct 2002||Lectec Corporation||Antipruritic patch|
|US6479073 *||7 Oct 1996||12 Nov 2002||3M Innovative Properties Company||Pressure sensitive adhesive articles and methods for preparing same|
|US6512010||14 Jul 1997||28 Ene 2003||Alza Corporation||Formulations for the administration of fluoxetine|
|US6572879||7 Jun 1995||3 Jun 2003||Alza Corporation||Formulations for transdermal delivery of pergolide|
|US6592892||29 Ago 2000||15 Jul 2003||Tepha, Inc.||Flushable disposable polymeric products|
|US6660295||29 Sep 1998||9 Dic 2003||Alza Corporation||Transdermal drug delivery device package with improved drug stability|
|US6699497||23 Jul 1999||2 Mar 2004||Alza Corporation||Formulations for the transdermal administration of fenoldopam|
|US6727401||12 Feb 1998||27 Abr 2004||Watson Pharmaceuticals, Inc.||Pressure sensitive adhesive matrix patch for the treatment of onychomycosis|
|US6960353||29 Sep 2003||1 Nov 2005||Alza Corporation||Formulations for the transdermal administration of fenoldopam|
|US6974588||7 Dic 1999||13 Dic 2005||Elan Pharma International Limited||Transdermal patch for delivering volatile liquid drugs|
|US7011844||22 Nov 2002||14 Mar 2006||Alza Corporation||Formulations for the administration of fluoxetine|
|US7267829||23 Abr 2004||11 Sep 2007||Transdermal Technologies, Inc.||Compositions for rapid and non-irritating transdermal delivery of pharmaceutically active agents and methods for formulating such compositions and delivery thereof|
|US7357891||30 Ene 2004||15 Abr 2008||Monosol Rx, Llc||Process for making an ingestible film|
|US7425292||14 Feb 2002||16 Sep 2008||Monosol Rx, Llc||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US7553923||30 Jun 2009||Metabolix, Inc.||Medical devices and applications of polyhydroxyalkanoate polymers|
|US7622136||24 Nov 2009||Alza Corporation||Transparent transdermal nicotine delivery devices|
|US7641825||29 Jul 2005||5 Ene 2010||Tepha, Inc.||Method of making a polyhydroxyalkanoate filament|
|US7666337||28 May 2004||23 Feb 2010||Monosol Rx, Llc||Polyethylene oxide-based films and drug delivery systems made therefrom|
|US7824588||2 Nov 2010||Monosol Rx, Llc||Method of making self-supporting therapeutic active-containing film|
|US7879942||1 Feb 2011||Eastman Chemical Company||Switchable adhesive article for attachment to skin and method of using the same|
|US7910641||14 Dic 2006||22 Mar 2011||Monosol Rx, Llc||PH modulated films for delivery of actives|
|US7943683||17 May 2011||Tepha, Inc.||Medical devices containing oriented films of poly-4-hydroxybutyrate and copolymers|
|US7972618||20 Sep 2007||5 Jul 2011||Monosol Rx, Llc||Edible water-soluble film containing a foam reducing flavoring agent|
|US8017150||13 Sep 2011||Monosol Rx, Llc||Polyethylene oxide-based films and drug delivery systems made therefrom|
|US8017598||16 May 2007||13 Sep 2011||Knopp Neurosciences, Inc.||Compositions of R(+) and S(−) pramipexole and methods of using the same|
|US8034270||30 Abr 2004||11 Oct 2011||Tepha, Inc.||Polyhydroxyalkanoate medical textiles and fibers|
|US8075911||13 Dic 2011||Alza Corporation||Transparent transdermal nicotine delivery devices|
|US8084125||27 Dic 2011||Tepha, Inc.||Non-curling polyhydroxyalkanoate sutures|
|US8124689||6 Jun 2007||28 Feb 2012||Dow Corning Corporation||Silicone acrylate hybride composition and method of making same|
|US8153162||27 Sep 2006||10 Abr 2012||Tissuetech, Inc.||Purified amniotic membrane compositions and methods of use|
|US8182840||22 May 2012||Tissue Tech, Inc.||Amniotic membrane preparations and purified compositions and therapy for scar reversal and inhibition|
|US8182841||27 Sep 2006||22 May 2012||Tissue Tech, Inc.||Amniotic membrane preparations and purified compositions and anti-inflammation methods|
|US8187639||29 May 2012||Tissue Tech, Inc.||Amniotic membrane preparations and purified compositions and anti-angiogenesis treatment|
|US8236288||7 Ago 2012||Skinmedica, Inc.||Melanin modification compositions and methods of use|
|US8361272||27 Jun 2007||29 Ene 2013||Ferring B.V.||Polyurethane elastomers|
|US8361273||29 Ene 2013||Ferring B.V.||Polyurethane elastomers|
|US8420126||16 Abr 2013||Tissue Tech, Inc.||Amniotic membrane preparations and purified compositions and anti-angiogenesis treatment|
|US8440235||14 May 2013||Tissuetech, Inc.||Amniotic membrane preparations and purified compositions and therapy for scar reversal and inhibition|
|US8445474||21 May 2013||Knopp Neurosciences, Inc.||Compositions of R(+) and S(−) pramipexole and methods of using the same|
|US8455009||23 Abr 2012||4 Jun 2013||Tissuetech, Inc.||Amniotic membrane preparations and purified compositions and anti-inflammation methods|
|US8460707||11 Jun 2013||Ferring B.V.||Stabilised prostaglandin composition|
|US8460714||11 Jun 2013||Tissuetech, Inc.||Purified amniotic membrane compositions and methods of use|
|US8475832||7 Ago 2009||2 Jul 2013||Rb Pharmaceuticals Limited||Sublingual and buccal film compositions|
|US8491934||28 Jul 2005||23 Jul 2013||Ferring B.V.||Stabilised prostaglandin composition|
|US8518926||14 Dic 2007||27 Ago 2013||Knopp Neurosciences, Inc.||Compositions and methods of using (R)-pramipexole|
|US8519148||14 Mar 2008||27 Ago 2013||Knopp Neurosciences, Inc.||Synthesis of chirally purified substituted benzothiazole diamines|
|US8524254||15 Oct 2007||3 Sep 2013||Ferring B.V.||Bioresorbable polymers|
|US8524695||14 Mar 2008||3 Sep 2013||Knopp Neurosciences, Inc.||Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same|
|US8557281||13 Jul 2010||15 Oct 2013||Ferring B.V.||Water-swellable polymers|
|US8569416||21 Oct 2011||29 Oct 2013||Dow Corning Corporation||Single phase silicone acrylate formulation|
|US8603514||10 Jul 2007||10 Dic 2013||Monosol Rx, Llc||Uniform films for rapid dissolve dosage form incorporating taste-masking compositions|
|US8614278||29 Nov 2011||24 Dic 2013||Dow Corning Corporation||Silicone acrylate hybrid composition and method of making same|
|US8628798||10 Ago 2012||14 Ene 2014||Ferring B.V.||Water-swellable polymers|
|US8652378||29 Mar 2013||18 Feb 2014||Monosol Rx Llc||Uniform films for rapid dissolve dosage form incorporating taste-masking compositions|
|US8663680||5 Dic 2011||4 Mar 2014||Alza Corporation||Transparent transdermal nicotine delivery devices|
|US8663687||13 May 2010||4 Mar 2014||Monosol Rx, Llc||Film compositions for delivery of actives|
|US8685437||26 Mar 2009||1 Abr 2014||Monosol Rx, Llc||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US8709482||31 May 2013||29 Abr 2014||Ferring B.V.||Stabilised prostaglandin composition|
|US8753555||11 Abr 2011||17 Jun 2014||Tepha, Inc.||Medical devices containing oriented films of poly-4-hydroxybutyrate and copolymers|
|US8758657||16 Jul 2013||24 Jun 2014||Tepha, Inc.||Process of making polyhydroxyalkanoate medical textiles|
|US8765167||8 Sep 2006||1 Jul 2014||Monosol Rx, Llc||Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions|
|US8778315||26 Feb 2013||15 Jul 2014||Allergan, Inc.||Melanin modification compositions and methods of use|
|US8778382||30 Abr 2004||15 Jul 2014||Purdue Pharma L.P.||Tamper resistant transdermal dosage form|
|US8790689||18 Nov 2005||29 Jul 2014||Purdue Pharma L.P.||Tamper resistant transdermal dosage form|
|US8796416||25 Oct 2011||5 Ago 2014||Questcor Pharmaceuticals, Inc||ACTH prophylactic treatment of renal disorders|
|US8900497||23 Ago 2013||2 Dic 2014||Monosol Rx, Llc||Process for making a film having a substantially uniform distribution of components|
|US8900498||23 Ago 2013||2 Dic 2014||Monosol Rx, Llc||Process for manufacturing a resulting multi-layer pharmaceutical film|
|US8906277||23 Ago 2013||9 Dic 2014||Monosol Rx, Llc||Process for manufacturing a resulting pharmaceutical film|
|US8957216||24 Mar 2011||17 Feb 2015||Amitech Therapeutic Solutions, Inc.||Heterocyclic compounds useful for kinase inhibition|
|US8974813||27 Jun 2007||10 Mar 2015||Ferring B.V.||Hydrophilic polyurethane compositions|
|US8974826||10 Jun 2011||10 Mar 2015||Monosol Rx, Llc||Nanoparticle film delivery systems|
|US8999379||27 Feb 2014||7 Abr 2015||Alza Corporation||Transparent transdermal nicotine delivery devices|
|US9044404||26 Feb 2013||2 Jun 2015||Allergan, Inc.||Melanin modification compositions and methods of use|
|US9072636||17 Sep 2012||7 Jul 2015||Kimberly-Clark Worldwide, Inc.||Dynamic fitting body adhering absorbent article|
|US9108340||23 Ago 2013||18 Ago 2015||Monosol Rx, Llc||Process for manufacturing a resulting multi-layer pharmaceutical film|
|US9125719||8 Sep 2011||8 Sep 2015||Tepha, Inc.||Polyhydroxyalkanoate medical textiles and fibers|
|US9161954||12 Mar 2013||20 Oct 2015||Tissuetech, Inc.||Amniotic membrane preparations and purified compositions and anti-angiogenesis treatment|
|US9161955||13 Mar 2013||20 Oct 2015||Tissuetech, Inc.||Amniotic membrane preparations and purified compositions and therapy for scar reversal and inhibition|
|US9161956||13 Mar 2013||20 Oct 2015||Tissuetech, Inc.||Amniotic membrane preparations and purified compositions and anti-inflammation methods|
|US9175066||26 Abr 2010||3 Nov 2015||Tissuetech, Inc.||Compositions containing HC-HA complex and methods of use thereof|
|US9198939||13 Mar 2013||1 Dic 2015||Tissuetech, Inc.||Purified amniotic membrane compositions and methods of use|
|US9205059||23 Feb 2015||8 Dic 2015||Alza Corporation||Transparent transdermal nicotine delivery devices|
|US9212151||12 Feb 2015||15 Dic 2015||Amitech Therapeutic Solutions, Inc.||Heterocyclic compounds useful for kinase inhibition|
|US9260417||7 Feb 2011||16 Feb 2016||Amitech Therapeutic Solutions, Inc.||Therapeutic methods and compositions involving allosteric kinase inhibition|
|US9265749||14 Abr 2015||23 Feb 2016||Patara Pharma, LLC||Methods for the treatment of systemic disorders treatable with mast cell stabilizers, including mast cell related disorders|
|US9273051||14 Sep 2012||1 Mar 2016||Pharmacyclics Llc||Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors|
|US9333066||13 May 2014||10 May 2016||Tepha, Inc.||Method of making a medical textile from polyhydroxyalkanoate fibers|
|US20030107149 *||14 Feb 2002||12 Jun 2003||International Fluidics.||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US20040137047 *||22 Dic 2003||15 Jul 2004||3M Innovative Properties Company||Pressure sensitive adhesive articles and methods for preparing same|
|US20040209907 *||23 Ene 2004||21 Oct 2004||Richard Franklin||Formulation and methods for the treatment of thrombocythemia|
|US20040209909 *||9 Abr 2002||21 Oct 2004||Su Il Yum||Novel formulations for transdermal delivery of pergolide|
|US20040234576 *||30 Abr 2004||25 Nov 2004||Tepha, Inc., State Of Incorporation Delaware||Polyhydroxyalkanoate medical textiles and fibers|
|US20040234585 *||18 Jun 2004||25 Nov 2004||Gale Robert M.||Transparent transdermal nicotine delivery devices|
|US20040258742 *||20 Jul 2004||23 Dic 2004||Van Osdol William Woodson||Transdermal administration of N-(2,5-disubstituted phenyl)-N'-(3-substituted phenyl)-N'-methyl guanidines|
|US20050002997 *||30 Abr 2004||6 Ene 2005||Howard Stephen A.||Tamper resistant transdermal dosage form|
|US20050025809 *||8 Jul 2004||3 Feb 2005||Tepha, Inc.||Poly-4-hydroxybutyrate matrices for sustained drug delivery|
|US20050037055 *||28 May 2004||17 Feb 2005||Monosolrx Llc.||Polyethylene oxide-based films and drug delivery systems made therefrom|
|US20050048104 *||30 Jun 2003||3 Mar 2005||Venkatraman Subramanian S.||Transdermal drug delivery devices comprising a polyurethane drug reservoir|
|US20050065062 *||24 Sep 2003||24 Mar 2005||3M Innovative Properties Company||Method of formulating a pharmaceutical composition|
|US20050142475 *||30 Dic 2003||30 Jun 2005||Moudry Ronald J.||Dry toner comprising encapsulated pigment, methods and uses|
|US20050184427 *||29 Mar 2005||25 Ago 2005||Monosolrx, Llc.||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US20050186277 *||15 Mar 2005||25 Ago 2005||Gale Robert M.||Novel formulations for the administration of fluoxetine|
|US20060008432 *||7 Jul 2004||12 Ene 2006||Sebastiano Scarampi||Gilsonite derived pharmaceutical delivery compositions and methods: nail applications|
|US20060009099 *||12 Jul 2004||12 Ene 2006||Closure Medical Corporation||Adhesive-containing wound closure device and method|
|US20060039958 *||28 Sep 2005||23 Feb 2006||Monosolrx, Llc.||Multi-layer films having uniform content|
|US20060058470 *||29 Jul 2005||16 Mar 2006||Tepha, Inc.||Non-curling polyhydroxyalkanoate sutures|
|US20060121103 *||7 Oct 2005||8 Jun 2006||Kenneth Kirby||Transdermal delivery system|
|US20060147493 *||22 Jul 2003||6 Jul 2006||Yang Robert K||Packaging and dispensing of rapid dissolve dosage form|
|US20060287659 *||20 Ago 2004||21 Dic 2006||Tepha, Inc.||Polyhydroxyalkanoate nerve regeneration devices|
|US20070069416 *||22 Jun 2006||29 Mar 2007||Monosolrx, Llc||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US20070071740 *||27 Sep 2006||29 Mar 2007||Bio-Tissue, Inc.||Purified amniotic membrane compositions and methods of use|
|US20070071828 *||27 Sep 2006||29 Mar 2007||Bio-Tissue, Inc.||Amniotic membrane preparations and purified compositions and anti-angiogenesis treatment|
|US20070086958 *||13 Oct 2006||19 Abr 2007||Medafor, Incorporated||Formation of medically useful gels comprising microporous particles and methods of use|
|US20070122455 *||8 Sep 2006||31 May 2007||Monosolrx, Llc.||Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions|
|US20070149731 *||14 Dic 2006||28 Jun 2007||Monosolrx, Llc.||PH modulated films for delivery of actives|
|US20070154527 *||5 Dic 2006||5 Jul 2007||Monosoirx, Llc||Topical film compositions for delivery of actives|
|US20070172515 *||19 Ene 2007||26 Jul 2007||Monosolrx, Llc||Film bandage for mucosal administration of actives|
|US20070190157 *||19 Ene 2007||16 Ago 2007||Monosoirx, Llc.||Film lined packaging and method of making same|
|US20070202245 *||18 Mar 2005||30 Ago 2007||Gantner David C||Silicone Skin Adhesive Gels With Enhanced Adhesion To Plastic|
|US20070231401 *||27 Sep 2006||4 Oct 2007||Bio-Tissue, Inc.||Amniotic membrane preparations and purified compositions and anti-inflammation methods|
|US20070237812 *||9 Mar 2007||11 Oct 2007||Tyco Healthcare Group||Multi-layer wound dressings|
|US20070258935 *||7 May 2007||8 Nov 2007||Mcentire Edward Enns||Water dispersible films for delivery of active agents to the epidermis|
|US20070259029 *||7 May 2007||8 Nov 2007||Mcentire Edward Enns||Water-dispersible patch containing an active agent for dermal delivery|
|US20070259930 *||10 Abr 2007||8 Nov 2007||Knopp Neurosciences, Inc.||Compositions and methods of using r(+) pramipexole|
|US20070281003 *||13 Feb 2007||6 Dic 2007||Fuisz Richard C||Polymer-Based Films and Drug Delivery Systems Made Therefrom|
|US20080014259 *||16 May 2007||17 Ene 2008||Knopp Neurosciences, Inc.||Compositions of R(+) and S(-) Pramipexole and Methods of Using the Same|
|US20080031933 *||20 Ago 2007||7 Feb 2008||Alza Corporation||Transparent transdermal nicotine delivery devices|
|US20080044454 *||10 Jul 2007||21 Feb 2008||Monosolrx Llc||Uniform films for rapid dissolve dosage form incorporating taste-masking compositions|
|US20080051490 *||9 Ago 2007||28 Feb 2008||Williams Simon F||Medical Devices and Applications of Polyhydroxyalkanoate Polymers|
|US20080057090 *||1 Sep 2006||6 Mar 2008||Mcentire Edward Enns||Wrinkle masking film composition for skin|
|US20080075825 *||20 Sep 2007||27 Mar 2008||Fuisz Richard C||Edible Water-Soluble Film Containing a Foam Reducing Flavoring Agent|
|US20080081071 *||28 Sep 2007||3 Abr 2008||Pradeep Sanghvi||Film Embedded Packaging and Method of Making Same|
|US20080085972 *||5 Oct 2006||10 Abr 2008||O'brien Emmett Patrick||Switchable adhesive article for attachment to skin and method of using the same|
|US20080095823 *||26 Oct 2007||24 Abr 2008||Metabolix, Inc.||Medical Devices and Applications of Polyhydroxyalkanoate Polymers|
|US20080132602 *||31 Oct 2007||5 Jun 2008||Tepha, Inc.||Medical devices containing oriented films of poly-4-hydroxybutyrate and copolymers|
|US20080160065 *||12 Jul 2007||3 Jul 2008||Janet Anne Halliday||Drug delivery polymer with hydrochloride salt of clindamycin|
|US20080227985 *||14 Mar 2008||18 Sep 2008||Knopp Neurosciences, Inc.||Synthesis of chirally purified substituted benzothiazoles|
|US20080255610 *||27 Jun 2008||16 Oct 2008||Closure Medical Corporation||Adhesive-Containing Wound Closure Device and Method|
|US20080260653 *||6 May 2005||23 Oct 2008||Buttar Rashid A||Transdermal Delivery Systems and Transdermal Chelation Preparations|
|US20080260805 *||14 Abr 2008||23 Oct 2008||Monosol Rx, Llc||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US20080260809 *||22 Abr 2008||23 Oct 2008||Monosol Rx, Llc||Polyethylene oxide-based films and drug delivery systems made therefrom|
|US20080299087 *||27 Sep 2006||4 Dic 2008||Bio-Tissue, Inc.|
|US20090042956 *||14 Dic 2007||12 Feb 2009||Knopp Neurosciences, Inc.||Compositions and methods of using (r)-pramipexole|
|US20090054504 *||14 Mar 2008||26 Feb 2009||Knopp Neurosciences, Inc.||Modified Release Formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and Methods of Using the Same|
|US20090076542 *||10 Sep 2008||19 Mar 2009||Jerry Jonn||Adhesive-Containing Wound Closure Device And Method|
|US20090098069 *||12 Sep 2008||16 Abr 2009||Drugtech Corporation||Transdermal, alcohol-free, pharmaceutical compositions|
|US20090181069 *||16 Jul 2009||Monosol Rx, Llc||Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom|
|US20090196911 *||6 Jun 2007||6 Ago 2009||Loubert Gary L||Silicone Acrylate Hybride Composition and Method Of Making Same|
|US20090209983 *||10 Sep 2008||20 Ago 2009||Tepha, Inc.||Polyhydroxyalkanoate nerve regeneration devices|
|US20090286246 *||19 Nov 2009||Wintherix Llc||Methods for Identifying Compounds that Affect Expression of Cancer-Related Protein Isoforms|
|US20090291120 *||27 Jun 2007||26 Nov 2009||Jukka Tuominen||Hydrophilic Polyurethane Compositions|
|US20090324692 *||27 Jun 2007||31 Dic 2009||Controlled Therapeutics (Scotland) Limited||Polyurethane Elastomers|
|US20100021526 *||28 Ene 2010||Monosol Rx, Llc||Ph modulated films for delivery of actives|
|US20100055437 *||27 Ago 2009||4 Mar 2010||Tyco Healthcare Group Lp||Anti-microbial fibers and related articles and methods|
|US20100068708 *||18 Mar 2010||Wintherix Llc||Methods for Identifying Compounds that Modulate WNT Signaling in Cancer Cells|
|US20100093237 *||11 Dic 2009||15 Abr 2010||Tepha, Inc.||Non-curling polyhydroxyalkanoate sutures|
|US20100121304 *||10 Nov 2008||13 May 2010||Kimberly-Clark Worldwide, Inc.||Multifunctional Acrylate Skin-Adhesive Composition|
|US20110009460 *||13 Ene 2011||Valentin Gribkoff||Compositions and methods for treating amyotrophic lateral sclerosis|
|US20110033541 *||7 Ago 2009||10 Feb 2011||Monosol Rx, Llc||Sublingual and buccal film compositions|
|US20110033542 *||10 Feb 2011||Monosol Rx, Llc||Sublingual and buccal film compositions|
|US20110091488 *||21 Abr 2011||Controlled Therapeutics (Scotland) Limited||Water-swellable polymers|
|US20110189475 *||4 Ago 2011||Tepha, Inc.||Medical devices containing oriented films of poly-4-hydroxybutyrate and copolymers|
|US20110190356 *||19 Ago 2009||4 Ago 2011||Knopp Neurosciences Inc.||Compositions and Methods of Using (R)- Pramipexole|
|USRE32991 *||25 Jul 1988||18 Jul 1989||Thermedics, Inc.||Drug dispensing wound dressing|
|USRE35474 *||13 Oct 1994||11 Mar 1997||Dow Corning Corporation||Transdermal drug delivery devices with amine-resistant silicone adhesives|
|USRE37934||3 Feb 2000||10 Dic 2002||Lts Lohmann Therapie-Systeme Ag||Transdermal therapeutic system|
|USRE39588||31 Oct 1990||24 Abr 2007||Alza Corporation||Transdermal drug delivery device|
|DE3208853A1 *||11 Mar 1982||23 Sep 1982||Nitto Electric Ind Co||Verfahren zur herstellung einer pharmazeutischen verbundzubereitung|
|DE3629304A1 *||28 Ago 1986||24 Mar 1988||Lohmann Gmbh & Co Kg||Transdermales therapeutisches system, seine verwendung und verfahren zu seiner herstellung|
|DE102010053792A1||8 Dic 2010||14 Jun 2012||Frank Becher||Device 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|
|DE102013107024A1||4 Jul 2013||15 May 2014||Golden Biotechnology Corporation||Methoden und Zusammensetzungen zum Behandeln, Modifizieren und Handhaben von Knochenkrebsschmerz|
|DE102013107025A1||4 Jul 2013||3 Jul 2014||Golden Biotechnology Corporation||Methoden und zusammensetzungen zur behanldung von diabetis|
|DE102013202928A1||22 Feb 2013||29 Ago 2013||Golden Biotechnology Corporation||Verfahren und Zusammensetzungen zum Behandeln von Krebsmetastasierung|
|EP0236266A1 *||9 Feb 1987||9 Sep 1987||Ciba-Geigy Ag||Dermal and transdermal therapeutic system having a discontinuous-pattern adhesive layer and method of manufacturing thereof|
|EP0273004A2 *||16 Nov 1987||29 Jun 1988||Ciba-Geigy Ag||User-activated therapeutical system|
|EP1399145A2 *||12 Ene 1999||24 Mar 2004||Watson Pharmaceuticals, Inc.||Pressure sensitive adhesive matrix patch for the treatment of onychomycosis|
|EP1674068A1||19 Feb 1997||28 Jun 2006||Acrux DDS Pty Ltd||Dermal penetration enhancers and drug delivery systems involving same|
|EP2158903A2||14 Dic 1999||3 Mar 2010||ALZA Corporation||Transparent Transdermal Nicotine Delivery Devices|
|EP2201840A1||28 Dic 2006||30 Jun 2010||Pharmacyclics, Inc.||Inhibitors of Bruton's Tyrosine Kinase|
|EP2443929A1||28 Dic 2006||25 Abr 2012||Pharmacyclics, Inc.||Inhibitors of Bruton's Tyrosine Kinase|
|EP2526771A1||28 Dic 2006||28 Nov 2012||Pharmacyclics, Inc.||Inhibitors of bruton's tyrosine kinase|
|EP2526933A2||28 Dic 2006||28 Nov 2012||Pharmacyclics, Inc.||Inhibitors of bruton's tyrosine kinase|
|EP2526934A2||28 Dic 2006||28 Nov 2012||Pharmacyclics, Inc.||Inhibitors of bruton's tyrosine kinase|
|EP2529621A1||28 Dic 2006||5 Dic 2012||Pharmacyclics, Inc.||Inhibitors of bruton's tyrosine kinase|
|EP2529622A1||28 Dic 2006||5 Dic 2012||Pharmacyclics, Inc.||Inhibitors of bruton's tyrosine kinase|
|EP2530083A1||28 Dic 2006||5 Dic 2012||Pharmacyclics, Inc.||Inhibitors of bruton's tyrosine kinase|
|EP2532234A1||28 Dic 2006||12 Dic 2012||Pharmacyclics, Inc.||Inhibitors of bruton's tyrosine kinase|
|EP2532235A1||28 Dic 2006||12 Dic 2012||Pharmacyclics, Inc.||Inhibitors of bruton's tyrosine kinase|
|EP2584016A1||19 Oct 2012||24 Abr 2013||Dow Corning Corporation||Single phase silicone acrylate formulation|
|EP2599847A1||29 Nov 2012||5 Jun 2013||Dow Corning Corporation||A Silicone Acrylate Hybrid Composition and Method of Making Same|
|EP2650294A1||12 Oct 2010||16 Oct 2013||Pharmacyclics, Inc.||Inhibitors of Bruton's Tyrosine Kinase|
|EP2664337A1||27 Sep 2006||20 Nov 2013||TissueTech, Inc.||Amniotic membrane preparations and purified compositions and methods of use|
|WO1984002460A1 *||22 Dic 1983||5 Jul 1984||Dermatec Ltd||Sebum collection and monitoring means|
|WO1987000042A1 *||27 Jun 1986||15 Ene 1987||Rutgers, The State University Of New Jersey||Transdermal verapamil delivery device|
|WO1987003477A1 *||12 Dic 1985||18 Jun 1987||Flexcon Company, Inc.||Transdermal methods and adhesives|
|WO1989005582A1 *||30 Nov 1988||29 Jun 1989||Russell Isaac Copelan||Chemical splinter removal|
|WO1999040955A2 *||12 Ene 1999||19 Ago 1999||Watson Pharmaceuticals, Inc.||Pressure sensitive adhesive matrix patch for the treatment of onychomycosis|
|WO2007062266A2||28 Nov 2006||31 May 2007||Marinus Pharmaceuticals||Ganaxolone formulations and methods for the making and use thereof|
|WO2008021368A2||13 Ago 2007||21 Feb 2008||The Johns Hopkins University||Compositions and methods for neuroprotection|
|WO2008039218A2||28 Dic 2006||3 Abr 2008||Pharmacyclics, Inc.||Inhibitors of bruton's tyrosine kinase|
|WO2008066899A2||28 Nov 2007||5 Jun 2008||Marinus Pharmaceuticals||Nanoparticulate formulations and methods for the making and use thereof|
|WO2010071866A2||19 Dic 2009||24 Jun 2010||Nuon Therapeutics, Inc.||Combination therapy for arthritis with tranilast|
|WO2011130689A1||15 Abr 2011||20 Oct 2011||Tracon Pharmaceuticals, Inc.||Potentiation of anti-cancer activity through combination therapy with ber pathway inhibitors|
|WO2011139489A2||11 Abr 2011||10 Nov 2011||Calcimedica Inc.||Compounds that modulate intracellular calcium|
|WO2015084998A1||3 Dic 2014||11 Jun 2015||Pharmacyclics, Inc.||Inhibitors of bruton's tyrosine kinase|
|Clasificación de EE.UU.||424/434, 424/448, 604/304, 424/449|
|Clasificación cooperativa||A61K9/7061, A61K9/7084, A61K9/7069, A61K9/7092|
|Clasificación europea||A61K9/70E2B6B2, A61K9/70E2D, A61K9/70E2B6D, A61K9/70E2K|