CA1261702A - Therapeutic device for the administration of medicaments - Google Patents
Therapeutic device for the administration of medicamentsInfo
- Publication number
- CA1261702A CA1261702A CA000525383A CA525383A CA1261702A CA 1261702 A CA1261702 A CA 1261702A CA 000525383 A CA000525383 A CA 000525383A CA 525383 A CA525383 A CA 525383A CA 1261702 A CA1261702 A CA 1261702A
- Authority
- CA
- Canada
- Prior art keywords
- layer
- active agent
- backing layer
- reservoir
- release layer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
Abstract
ABSTRACT OF THE DISCLOSURE
A device for the administration of an active agent to the skin or mucosa of a host is provided, said device comprising a reservoir containing said active agent therein, said reservoir having an inner surface and an outer surface, a release layer formed on said inner surface of said reservoir, an active agent impermeable backing layer formed on said outer surface of said reservoir, said release layer underlying said backing layer and sealed thereto about a circumferential sealed area so as to enclose said reservoir, said backing layer and said release layer extending peripherally beyond said sealed area about the entire periphery thereof so as to create an extended peripheral area, and adhesive means disposed between said backing layer and said release layer in said extended peripheral area and thereby separated from said reservoir by said sealed area, said adhesive means adapted to adhere said device to the skin or mucosa of said host upon removal of said release layer, whereby said active agent is released from said reservoir to provide a dose of said active agent.
A device for the administration of an active agent to the skin or mucosa of a host is provided, said device comprising a reservoir containing said active agent therein, said reservoir having an inner surface and an outer surface, a release layer formed on said inner surface of said reservoir, an active agent impermeable backing layer formed on said outer surface of said reservoir, said release layer underlying said backing layer and sealed thereto about a circumferential sealed area so as to enclose said reservoir, said backing layer and said release layer extending peripherally beyond said sealed area about the entire periphery thereof so as to create an extended peripheral area, and adhesive means disposed between said backing layer and said release layer in said extended peripheral area and thereby separated from said reservoir by said sealed area, said adhesive means adapted to adhere said device to the skin or mucosa of said host upon removal of said release layer, whereby said active agent is released from said reservoir to provide a dose of said active agent.
Description
71~32 The present invention relates in general to a therapeutic device for the administration of a medicament or active agent to a host upon adhesion thereto by an adhesive layer. More particularly, the therapeutic device allows for topical or systemic administration to the host, or administration through the skin or mucosa of the host over a period of time, while isolating the medicament or active agent contained within a reservoir from the adhesive layer during storage and administration of the medicament or active agent to prevent the contamination of the active agent, to prevent deterioration of the adhesive and to avoid trapping of the drug within the device itself.
Transdermal administration systems are known in the art and have been approved for transdermal administration of nitroglycerin and scopolamine. ~uch devices are described, for example, in U.S. Patent Nos. 4,460,368, 4,460,370, 4,460,372, 4,379,454, 4,4~6,194 and 3,972,995.
Characteristically, those controlled continuous transdermal devices known before the present invention contained a backing member which defined the outer surface of the device, a membrane sealed to the backing member to create a reservoir therebetween containing the active agent, and an active agent permeable adhesive layer on the membrane defining the other face. Alternatively, the active agent, rather than being in one separate reservoir, is contained in a plurality of microcapsules distributed throughout the permeable adhesive layer. In either case, the active agent is delivered continuously from the reservoir or microcapsules through the membrane into the active agent permeable adhesive, which contacts the skin or mucosa of the recipient. Thus, in such devices, substantially the entire face, or surface, in contact with the skin or mucosa consists of the active agent permeable adhesive through which the active agent is administered. While such devices 7~3~
have a number of advantages, including full contact to the skin, certain potential disadvantages are apparent therewith.
For example, unless due care is exercised, contamination of the permeable adhesive layer can easily occur by finger contact when a user applies the device to the skin. Thus, where the fingers are sufficiently contaminated with perspiration, body oils and foreign matter, the resulting contamination of the permeable adhesive layer may adversely affect its permeable nature and cause a deterioration of its adhesive nature. This can also adversely affect the desired predetermined rate of transport of the active agent to the recipient, loss of its effectiveness, and can potentially cause infection to occur.
Moreover, finger contact with the permeable adhesive layer will contaminate the finger with the active agent. This is undesirable, for example, where the active agent is an eye irritant such as scopolamine, subsequent contact of the contaminated finger to the eye may result in irritation.
In addition, contact between the adhesive layer and the active agent can also result in contamination of the active agent itself, with obvious deleterious effects, including loss of its effectiveness and the potential to cause infection or other such adverse effects upon the recipient. E'urthermore, the construction of the known devices generally maintain the permeable adhesive layer in contact with the active agent contained within the reservoir during storage of the device from the time of its manufacture. Thus, there is a need for the permeable adhesive layer to be formulated specifically to match the drug or active agent, i.e., so that it will permit the drug to pass therethrough without trapping the drug 9 or becoming a "sink" therefor.
In accordance with the present invention, there is provided a device for the administration of an active agent to the skin or mucosa of a host, the device including a reservoir containing the active agent therein, the reservoir ~2~7~
having an inner surface and an outer surface, a release layer formed on the inner surface of the reservoir, an active agent impermeable backing layer formed on the outer surface of the reservoir, the release layer underlying the backing layer and sealed thereto about a circumferential sealed area so as ko enclose the reservoir, the backing layer and the release layer extending peripherally beyond the sealed area about the entire periphery thereof so as to create an extended peripheral area, and adhesive means disposed between the backing layer and the release layer in the extended peripheral area and thereby separated from the reservoir by the sealed area, the adhesive means adapted to adhere the device to the skin or mucosa of the host upon removal of the release layer, whereby the active agent is released from the reservoir to provide a dose of the active agent.
In order that the present invention may be more fully understood, it will now be described with reference to the accompanying drawings, in which:
FIGo 1 is a side, elevational, cross-sectional view of one embodiment of a therapeutic device constructed in accordance with the present invention;
FIG~ 2 is a side, elevational, cross-sectional view of another embodiment of a therapeutic device constructed in accordance with the present invention; and FIG. 3 is a side, elevational, cross-sectional view of another embodiment of a therapeutic device constructed in accordance with the present invention.
Referring now to the drawings, wherein like reference numerals represent like elements, there is shown in FIG. 1 one embodiment of a therapeutic device constructed in accordance with the present invention a~d designated generally by reference numeral 100. The device 100 is constructed of a plurality of layers including an active asent impermeable heat sealable release layer 102 which is coated with a release coating 104 on the inner surface thereof (e.g., a silicone release coated polyethylene film), 7~
an active agent impermeable backing layer 106 co-extruded with a heat sealable layer 108, and an outer backing layer 110 supporting an active agent impermeable pressure sensitive adhesive layer 112. A distinct reservoir 11~ is formed by heat sealing the backing layer 106 about its entire perimeter to the underlying release layer 102 by means o~ the interposed heat sealable layer 108.
In a preferred embodiment, the release coating 104, coated on the inner surface of the release layer 102, renders the heat sealed area 118 peelable by weakening the thermal bond created therein. However, one alternative for achieving that result is to employ two different materials as the release layer 102 and the heat sealable layer 108, such as polyethylene and polypropylene. In that case, no release coating 104 is required, and a weakened seal is created at 118 by the nature of the differences in physical properties as between these two layers. In any event, it is most important that this heat sealed area 118 circumferentially separate the reservoir 114 from an extended peripheral area 120 of the release layer 102. The outer backing layer 110 and supported adhesive layer 112 have a sufficient surface area and are of a shape so that, when they are attached to the backing layer 106, they overlie at least a portion of the extended peripheral area 120. Thus, the adhesive layer 112 circumferentially surrounds the reservoir 114 and is isolated therefrom by the peelable heat sealed area 118. A medicament or active agent 122 is retained within the reservoir 114 by means of a sterile synthetic sponge 124 which facilitates the administration of the active agent to the skin or mucosa of a host. The sponge 124 is secured to the heat sealable layer 10~ by means of, for example, one or more strips 126 of hot melt adhesive, or by other means of sealing, such as by ultrasonic welding, etc., or by applying strips of tape or the like. It can also be seen that the extended peripheral area 120 of release layer 102 extends outwardly beyond the outer backing layer 110 and its associated adhesive layer 112. This is done in this embodiment for the purpose of providing the equivalent of a tab for removal of the release layer 102 from the device.
During storage of the device 100, the active agent 122 within the reservoir 114 is isolated from the contact with the adhesive layer 112 by means o~ heat sealed area 118. In this manner, as discussed above, contamination or deterioration of the adhesive layer 112 is prevented, as is contamination of the active agent by the adhesive layer.
Furthermore, entrapment of the active agent within the adhesive layer during storage is also eliminated. However, the embodiment shown in FIG. 1 is particularly applied to use in connection with an active agent which will not migrate through or penetrate the heat sealed area 118.
That, however, is not always the case, and where such migration or penetration is a potential problem for the particular active agent in question, the use o~ embodiments of this invention as shown, for example, in FIGS. 2 and 3 hereo~, is utilized in order to insure isolation of the active agent in the reservoir from the adhesive layer.
These embodiments, and the use of an annular gap 140 for this purpose, are discussed more fully below. In adhering the device 100 to the skin or mucosa of a host, the release layer 102 is removed so as to expose the adhesive layer 112 as well as the sponge 124 containing the active agent 122.
In this regard, the release coating 104 facilitates separation of the release layer 102 from the adhesive layer 112 and the heat sealed area 118. When the device 100 is adhered to the skin or mucosa by the surrounding adhesive layer 112, the active agent 122 within the sponge 124 is released to provide a direct continuous dose without having to permeate through the adhesive layer. Furthermore 7 by employing an active agent impermeable adhesive layer, there will continue to be no contamination or deterioration of the adhesive layer, or any contamination of the active agent after the device has been so applied.
7~3~
Turning now to FIG. 2, there is disclosed another embodiment of a therapeutic device constructed in accordance with the present invention, and in this case generally designated by reference numeral 128. The device 128 differs primarily from that shown in FIG. 1 by the inclusion of a heat sealable permeable membrane 130, and by the inclusion of annular gap or space 140 between the heat sealed area 118 and the adhesive layer 112. The membrane 130 is provided between the release layer 102 and the reservoir 114, and is heat sealed about its perimeter within peelable heat sealed area 118 between the peripheral portion of release layer 120 and heat sealable layer 108. Thus, once again this portion of heat sealed area 118 between the release layer 102 and the membrane 130 is peelable by virtue of the presence of release coating 104 therebetween, and its effect upon weakening of the thermal bond produced therebetween or by use of other methods for achieving this result, such as the use of differing thermoplastic layers as is discussed above.
In any event, the thermal bond produced in heat sealed area 118 between the membrane 130 and the heat sealable layer 108 is not weakened in such manner, and is therefore a permanent bond or seal. The pressure sensitive adhesive layer 112 is interposed between the outer backing layer 110 and release layer 102 within the extended peripheral area 120 circumscribing the heat sealed area 118. In this case an annular gap 140 is also provided between the heat sealed area 118 and the adhesive layer 112. Upon removal of the release layer 102 from the adhesive layer 112 and membrane 130, which is facilitated by the release coating 10~, the active agent 122 can now be released through the membrane 130 to provide a continuous dose directly to the skin or mucosa of a host.
The membrane 130, in addition to being permeable, may be either microporous or macroporous, and the pores thereof therefore become filled with the active agent 122 from the reservoir 11~. The membrane 130 may also function in any other way as long as the active agent 122 can 7~
permeate through the membrane, and this can occur at either a controlled (as with a microporous membrane) or a noncontrolled rate, as with a microporous membrane which merely permits the active agent to pass freely therethrough at a suitable rate. Materials suitable for use as the membrane 130 are conventional in the art and need not be discussed in detail here. Some preferred materials for the membrane 130 may be, for example r polypropylene, polycarbonates, polyvinyl chloridel cellulose acetate, cellulose nitrate, and polyacrylonitrile. It shall be noted that the use of such a membrane 130 itself necessitates the use of annular gap 140 to isolate the reservoirs in accordance with this invention~ since by its very nature this membrane 130 must be permeable, and this will also be permeable to the active agent within the heat sealed area 118. Thus, without the presence of annular gap 1~0, the undesirable contact between the active agent and the adhesive layer 112 would take place.
Turning to FIG. 3, this embodiment of a therapeutic device constructed in accordance with the present invention is generally designated by reference numeral 142 The device 142 differs primarily Erom that shown in FIG. 1 by elimination of the portion of the adhesive layer 112 covering the entire inner surface of outer backing layer 110. Thus, the adhesive layer 112 is limited in this case to the outer peripheral area thereof, i.e., outside of heat sealed area 118. Furthermore, annular gap 1~0 is again provided between the heat sealed area 118 and the adhesive layer 112 so as to further isolate the adhesive itself from the active agent.
In connection with these various embodiments, the backing layer 106 is preferably made of a material or combination of materials which are substantially impermeable to the layer or layers with which it can be in contact, i~e., to the active agent 122, the adhesive layer 112, etc.
However, a primary purpose of the backing layer 106 is to 7~3~
prevent seepage of the active agent 122 from the reservoir 114. If the backing layer 106 is coated on its surface in contact with the active agent 122, such as by co-extrusion with the heat sealable layer 10~, this co-extruded heat sealable layer will perform this purpose even if the backing layer per se is not totally impermeable to the active agent~
Suitable materials for the heat sealable layer 108 include those polymers known as polyolefins, for example, polyethylene and polypropylene, and preferably an ethylene-vinyl acetate copolymer. Thus, it is not necessary in all instances that the backing layer 106 be impermeable to the active agent, although in most instances it normally is.
This similarly applies to the outer backing layer 110 where that is utilized, which layer in FI~. 1 is rendered impermeable by its coating with the impermeable adhesive layer 112. By substantially impermeable, it is meant that the other components in contact with the layer or component ~nder consideration will not appreciably permeate through such layer or component for the normal period of use and storage of the device.
The actual material used for the backing layer 106 and outer backing layer 108 will depend on the properties of the materials in contact therewith. Some suitable materials include, for example, cellophane, cellulose acetate, ethyl cellulose, plasticized vinyl acetate-vinyl chloride copolymers, ethylene-vinyl acetate copolymer, polyethylene terephthalate, nylon, polyethylene, polypropylene, polyvinylidene chloride, and aluminum foil.
Preferably, the material which forms the backing layer 106 and heat sealable layer 108 are co-extruded to form an integral layer. The composite can be a metallized (e.g., aluminized) film or a laminate of two or more films or a combination thereof. For example, a laminate of polyethylene terephthalate and polyethylene or a polyethylene/metallized po'yethylene terephthalate/poly-ethylene laminate can be employed. The preferred polymers . . .
include polyethylene, polypropylene, polyvinyl chloride and polyethylene terephthalate.
A primary purpose of the adhesive layer 112 is to provide adhesion to the skin or mucosa, and the degree of impermeability of the adhesive layer 112 to the active agent 122 may vary, depending upon the active agent, carrier, transporting agent, etc. Preferably, the adhesive layer 112 is a pressure sensitive adhesive suitable for contact with the skin or mucosa, e.g., dermatologically acceptable.
Examples of suitable pressure sensitive adhesives for use in the present invention as the active agent impermeable adhesive layer 112 include natural rubber adhesives, acrylic adhesives and synthetic rubber adhesives, all of which are commercially available.
The active agents 122 suitable for use in the present invention may be, for example, systemic or topical drugs. Individual active agents 122 or mixtures thereof, if desired, can be employed. Any drug which passes through the skin or mucosa can be employed for internal administration in the devices 100, 128 and 142 of the present invention, so long as the drug will pass through the sponge 124, as shown in FIGS. 1 and 3, and/or the material forming the membrane 130, as shown in FIGo 2~ Suitable systemic drugs for administration by the devices 100, 128 and 142 include those useful in treating emesis and nausea as is described in U.S.
Patent No. ~,031,894, e.g., preferably, scopolamine. Other suitable drugs include the coronary vasodilators described in U.S. Patent NoO 3,742,951, such as compounds having nitrate moiety. Still other suitable systemic drugs are disclosed in U.S. Patent No. 3,996,934. Some examples of topical drugs suitable for use in the present inYention include, for example, the folic acid antagonists, anti-neoplastic agents r and antimitotic agents described in U.S.
Paten~ No. 3,732,097.
The active agent 122 may be present in the reservoir 114 either alone or in combination with other active agents and/or a pharmaceutically acceptable carrier.
.. -.. :.. - ~
7~3~
Some suitable agent 122, whether in the presence or absence of a carrier, may also be combined in the reservoir 114 with a transporting agent which assists the drug delivery device to achieve the administration of a drug to a receptor such as by enhancing penetration through the skin. Some transporting agents suitable for use in the present invention include those described in U.S. Patent No.
3,996,934.
The host to which an active agent 122 is administered by means of the therapeutic device 10~, 128 may be any host on which a drug or other active agent has the desired effect. The host may be, for example, a mammal such as a human being, or, for that matter, any warm blooded or cold blooded animal. The advantage of administering the active agent 122 may be therapeutic or experimental. The devices 100, 128 and 142 of this invention may also be for any other advantageous purpose.
The degree of impermeability (for the impermeable adhesive layer 112 and for that matter the other elements of the devices ~00, 12~ and 142 which are desired to be impermeable to the active agent 122), is that degree which prevents the active agent from permeating or oozing away from the device during normal periods of use. The device preferably remains therapeutically effective for at least two years, more preferably at least five years, and most preferably at least ten years.
It will be understood that the embodiments described herein are merely exemplary and that a person skilled in the art may make many variations and modiications without departing from the spirit and scope of the invention All such modifications and variations are intended to be included within the scope of the invention as described in the appended claims.
Transdermal administration systems are known in the art and have been approved for transdermal administration of nitroglycerin and scopolamine. ~uch devices are described, for example, in U.S. Patent Nos. 4,460,368, 4,460,370, 4,460,372, 4,379,454, 4,4~6,194 and 3,972,995.
Characteristically, those controlled continuous transdermal devices known before the present invention contained a backing member which defined the outer surface of the device, a membrane sealed to the backing member to create a reservoir therebetween containing the active agent, and an active agent permeable adhesive layer on the membrane defining the other face. Alternatively, the active agent, rather than being in one separate reservoir, is contained in a plurality of microcapsules distributed throughout the permeable adhesive layer. In either case, the active agent is delivered continuously from the reservoir or microcapsules through the membrane into the active agent permeable adhesive, which contacts the skin or mucosa of the recipient. Thus, in such devices, substantially the entire face, or surface, in contact with the skin or mucosa consists of the active agent permeable adhesive through which the active agent is administered. While such devices 7~3~
have a number of advantages, including full contact to the skin, certain potential disadvantages are apparent therewith.
For example, unless due care is exercised, contamination of the permeable adhesive layer can easily occur by finger contact when a user applies the device to the skin. Thus, where the fingers are sufficiently contaminated with perspiration, body oils and foreign matter, the resulting contamination of the permeable adhesive layer may adversely affect its permeable nature and cause a deterioration of its adhesive nature. This can also adversely affect the desired predetermined rate of transport of the active agent to the recipient, loss of its effectiveness, and can potentially cause infection to occur.
Moreover, finger contact with the permeable adhesive layer will contaminate the finger with the active agent. This is undesirable, for example, where the active agent is an eye irritant such as scopolamine, subsequent contact of the contaminated finger to the eye may result in irritation.
In addition, contact between the adhesive layer and the active agent can also result in contamination of the active agent itself, with obvious deleterious effects, including loss of its effectiveness and the potential to cause infection or other such adverse effects upon the recipient. E'urthermore, the construction of the known devices generally maintain the permeable adhesive layer in contact with the active agent contained within the reservoir during storage of the device from the time of its manufacture. Thus, there is a need for the permeable adhesive layer to be formulated specifically to match the drug or active agent, i.e., so that it will permit the drug to pass therethrough without trapping the drug 9 or becoming a "sink" therefor.
In accordance with the present invention, there is provided a device for the administration of an active agent to the skin or mucosa of a host, the device including a reservoir containing the active agent therein, the reservoir ~2~7~
having an inner surface and an outer surface, a release layer formed on the inner surface of the reservoir, an active agent impermeable backing layer formed on the outer surface of the reservoir, the release layer underlying the backing layer and sealed thereto about a circumferential sealed area so as ko enclose the reservoir, the backing layer and the release layer extending peripherally beyond the sealed area about the entire periphery thereof so as to create an extended peripheral area, and adhesive means disposed between the backing layer and the release layer in the extended peripheral area and thereby separated from the reservoir by the sealed area, the adhesive means adapted to adhere the device to the skin or mucosa of the host upon removal of the release layer, whereby the active agent is released from the reservoir to provide a dose of the active agent.
In order that the present invention may be more fully understood, it will now be described with reference to the accompanying drawings, in which:
FIGo 1 is a side, elevational, cross-sectional view of one embodiment of a therapeutic device constructed in accordance with the present invention;
FIG~ 2 is a side, elevational, cross-sectional view of another embodiment of a therapeutic device constructed in accordance with the present invention; and FIG. 3 is a side, elevational, cross-sectional view of another embodiment of a therapeutic device constructed in accordance with the present invention.
Referring now to the drawings, wherein like reference numerals represent like elements, there is shown in FIG. 1 one embodiment of a therapeutic device constructed in accordance with the present invention a~d designated generally by reference numeral 100. The device 100 is constructed of a plurality of layers including an active asent impermeable heat sealable release layer 102 which is coated with a release coating 104 on the inner surface thereof (e.g., a silicone release coated polyethylene film), 7~
an active agent impermeable backing layer 106 co-extruded with a heat sealable layer 108, and an outer backing layer 110 supporting an active agent impermeable pressure sensitive adhesive layer 112. A distinct reservoir 11~ is formed by heat sealing the backing layer 106 about its entire perimeter to the underlying release layer 102 by means o~ the interposed heat sealable layer 108.
In a preferred embodiment, the release coating 104, coated on the inner surface of the release layer 102, renders the heat sealed area 118 peelable by weakening the thermal bond created therein. However, one alternative for achieving that result is to employ two different materials as the release layer 102 and the heat sealable layer 108, such as polyethylene and polypropylene. In that case, no release coating 104 is required, and a weakened seal is created at 118 by the nature of the differences in physical properties as between these two layers. In any event, it is most important that this heat sealed area 118 circumferentially separate the reservoir 114 from an extended peripheral area 120 of the release layer 102. The outer backing layer 110 and supported adhesive layer 112 have a sufficient surface area and are of a shape so that, when they are attached to the backing layer 106, they overlie at least a portion of the extended peripheral area 120. Thus, the adhesive layer 112 circumferentially surrounds the reservoir 114 and is isolated therefrom by the peelable heat sealed area 118. A medicament or active agent 122 is retained within the reservoir 114 by means of a sterile synthetic sponge 124 which facilitates the administration of the active agent to the skin or mucosa of a host. The sponge 124 is secured to the heat sealable layer 10~ by means of, for example, one or more strips 126 of hot melt adhesive, or by other means of sealing, such as by ultrasonic welding, etc., or by applying strips of tape or the like. It can also be seen that the extended peripheral area 120 of release layer 102 extends outwardly beyond the outer backing layer 110 and its associated adhesive layer 112. This is done in this embodiment for the purpose of providing the equivalent of a tab for removal of the release layer 102 from the device.
During storage of the device 100, the active agent 122 within the reservoir 114 is isolated from the contact with the adhesive layer 112 by means o~ heat sealed area 118. In this manner, as discussed above, contamination or deterioration of the adhesive layer 112 is prevented, as is contamination of the active agent by the adhesive layer.
Furthermore, entrapment of the active agent within the adhesive layer during storage is also eliminated. However, the embodiment shown in FIG. 1 is particularly applied to use in connection with an active agent which will not migrate through or penetrate the heat sealed area 118.
That, however, is not always the case, and where such migration or penetration is a potential problem for the particular active agent in question, the use o~ embodiments of this invention as shown, for example, in FIGS. 2 and 3 hereo~, is utilized in order to insure isolation of the active agent in the reservoir from the adhesive layer.
These embodiments, and the use of an annular gap 140 for this purpose, are discussed more fully below. In adhering the device 100 to the skin or mucosa of a host, the release layer 102 is removed so as to expose the adhesive layer 112 as well as the sponge 124 containing the active agent 122.
In this regard, the release coating 104 facilitates separation of the release layer 102 from the adhesive layer 112 and the heat sealed area 118. When the device 100 is adhered to the skin or mucosa by the surrounding adhesive layer 112, the active agent 122 within the sponge 124 is released to provide a direct continuous dose without having to permeate through the adhesive layer. Furthermore 7 by employing an active agent impermeable adhesive layer, there will continue to be no contamination or deterioration of the adhesive layer, or any contamination of the active agent after the device has been so applied.
7~3~
Turning now to FIG. 2, there is disclosed another embodiment of a therapeutic device constructed in accordance with the present invention, and in this case generally designated by reference numeral 128. The device 128 differs primarily from that shown in FIG. 1 by the inclusion of a heat sealable permeable membrane 130, and by the inclusion of annular gap or space 140 between the heat sealed area 118 and the adhesive layer 112. The membrane 130 is provided between the release layer 102 and the reservoir 114, and is heat sealed about its perimeter within peelable heat sealed area 118 between the peripheral portion of release layer 120 and heat sealable layer 108. Thus, once again this portion of heat sealed area 118 between the release layer 102 and the membrane 130 is peelable by virtue of the presence of release coating 104 therebetween, and its effect upon weakening of the thermal bond produced therebetween or by use of other methods for achieving this result, such as the use of differing thermoplastic layers as is discussed above.
In any event, the thermal bond produced in heat sealed area 118 between the membrane 130 and the heat sealable layer 108 is not weakened in such manner, and is therefore a permanent bond or seal. The pressure sensitive adhesive layer 112 is interposed between the outer backing layer 110 and release layer 102 within the extended peripheral area 120 circumscribing the heat sealed area 118. In this case an annular gap 140 is also provided between the heat sealed area 118 and the adhesive layer 112. Upon removal of the release layer 102 from the adhesive layer 112 and membrane 130, which is facilitated by the release coating 10~, the active agent 122 can now be released through the membrane 130 to provide a continuous dose directly to the skin or mucosa of a host.
The membrane 130, in addition to being permeable, may be either microporous or macroporous, and the pores thereof therefore become filled with the active agent 122 from the reservoir 11~. The membrane 130 may also function in any other way as long as the active agent 122 can 7~
permeate through the membrane, and this can occur at either a controlled (as with a microporous membrane) or a noncontrolled rate, as with a microporous membrane which merely permits the active agent to pass freely therethrough at a suitable rate. Materials suitable for use as the membrane 130 are conventional in the art and need not be discussed in detail here. Some preferred materials for the membrane 130 may be, for example r polypropylene, polycarbonates, polyvinyl chloridel cellulose acetate, cellulose nitrate, and polyacrylonitrile. It shall be noted that the use of such a membrane 130 itself necessitates the use of annular gap 140 to isolate the reservoirs in accordance with this invention~ since by its very nature this membrane 130 must be permeable, and this will also be permeable to the active agent within the heat sealed area 118. Thus, without the presence of annular gap 1~0, the undesirable contact between the active agent and the adhesive layer 112 would take place.
Turning to FIG. 3, this embodiment of a therapeutic device constructed in accordance with the present invention is generally designated by reference numeral 142 The device 142 differs primarily Erom that shown in FIG. 1 by elimination of the portion of the adhesive layer 112 covering the entire inner surface of outer backing layer 110. Thus, the adhesive layer 112 is limited in this case to the outer peripheral area thereof, i.e., outside of heat sealed area 118. Furthermore, annular gap 1~0 is again provided between the heat sealed area 118 and the adhesive layer 112 so as to further isolate the adhesive itself from the active agent.
In connection with these various embodiments, the backing layer 106 is preferably made of a material or combination of materials which are substantially impermeable to the layer or layers with which it can be in contact, i~e., to the active agent 122, the adhesive layer 112, etc.
However, a primary purpose of the backing layer 106 is to 7~3~
prevent seepage of the active agent 122 from the reservoir 114. If the backing layer 106 is coated on its surface in contact with the active agent 122, such as by co-extrusion with the heat sealable layer 10~, this co-extruded heat sealable layer will perform this purpose even if the backing layer per se is not totally impermeable to the active agent~
Suitable materials for the heat sealable layer 108 include those polymers known as polyolefins, for example, polyethylene and polypropylene, and preferably an ethylene-vinyl acetate copolymer. Thus, it is not necessary in all instances that the backing layer 106 be impermeable to the active agent, although in most instances it normally is.
This similarly applies to the outer backing layer 110 where that is utilized, which layer in FI~. 1 is rendered impermeable by its coating with the impermeable adhesive layer 112. By substantially impermeable, it is meant that the other components in contact with the layer or component ~nder consideration will not appreciably permeate through such layer or component for the normal period of use and storage of the device.
The actual material used for the backing layer 106 and outer backing layer 108 will depend on the properties of the materials in contact therewith. Some suitable materials include, for example, cellophane, cellulose acetate, ethyl cellulose, plasticized vinyl acetate-vinyl chloride copolymers, ethylene-vinyl acetate copolymer, polyethylene terephthalate, nylon, polyethylene, polypropylene, polyvinylidene chloride, and aluminum foil.
Preferably, the material which forms the backing layer 106 and heat sealable layer 108 are co-extruded to form an integral layer. The composite can be a metallized (e.g., aluminized) film or a laminate of two or more films or a combination thereof. For example, a laminate of polyethylene terephthalate and polyethylene or a polyethylene/metallized po'yethylene terephthalate/poly-ethylene laminate can be employed. The preferred polymers . . .
include polyethylene, polypropylene, polyvinyl chloride and polyethylene terephthalate.
A primary purpose of the adhesive layer 112 is to provide adhesion to the skin or mucosa, and the degree of impermeability of the adhesive layer 112 to the active agent 122 may vary, depending upon the active agent, carrier, transporting agent, etc. Preferably, the adhesive layer 112 is a pressure sensitive adhesive suitable for contact with the skin or mucosa, e.g., dermatologically acceptable.
Examples of suitable pressure sensitive adhesives for use in the present invention as the active agent impermeable adhesive layer 112 include natural rubber adhesives, acrylic adhesives and synthetic rubber adhesives, all of which are commercially available.
The active agents 122 suitable for use in the present invention may be, for example, systemic or topical drugs. Individual active agents 122 or mixtures thereof, if desired, can be employed. Any drug which passes through the skin or mucosa can be employed for internal administration in the devices 100, 128 and 142 of the present invention, so long as the drug will pass through the sponge 124, as shown in FIGS. 1 and 3, and/or the material forming the membrane 130, as shown in FIGo 2~ Suitable systemic drugs for administration by the devices 100, 128 and 142 include those useful in treating emesis and nausea as is described in U.S.
Patent No. ~,031,894, e.g., preferably, scopolamine. Other suitable drugs include the coronary vasodilators described in U.S. Patent NoO 3,742,951, such as compounds having nitrate moiety. Still other suitable systemic drugs are disclosed in U.S. Patent No. 3,996,934. Some examples of topical drugs suitable for use in the present inYention include, for example, the folic acid antagonists, anti-neoplastic agents r and antimitotic agents described in U.S.
Paten~ No. 3,732,097.
The active agent 122 may be present in the reservoir 114 either alone or in combination with other active agents and/or a pharmaceutically acceptable carrier.
.. -.. :.. - ~
7~3~
Some suitable agent 122, whether in the presence or absence of a carrier, may also be combined in the reservoir 114 with a transporting agent which assists the drug delivery device to achieve the administration of a drug to a receptor such as by enhancing penetration through the skin. Some transporting agents suitable for use in the present invention include those described in U.S. Patent No.
3,996,934.
The host to which an active agent 122 is administered by means of the therapeutic device 10~, 128 may be any host on which a drug or other active agent has the desired effect. The host may be, for example, a mammal such as a human being, or, for that matter, any warm blooded or cold blooded animal. The advantage of administering the active agent 122 may be therapeutic or experimental. The devices 100, 128 and 142 of this invention may also be for any other advantageous purpose.
The degree of impermeability (for the impermeable adhesive layer 112 and for that matter the other elements of the devices ~00, 12~ and 142 which are desired to be impermeable to the active agent 122), is that degree which prevents the active agent from permeating or oozing away from the device during normal periods of use. The device preferably remains therapeutically effective for at least two years, more preferably at least five years, and most preferably at least ten years.
It will be understood that the embodiments described herein are merely exemplary and that a person skilled in the art may make many variations and modiications without departing from the spirit and scope of the invention All such modifications and variations are intended to be included within the scope of the invention as described in the appended claims.
Claims (13)
1. Device for the administration of an active agent to the skin or mucosa of a host, said device comprising a reservoir containing said active agent therein, said reservoir having an inner surface and an outer surface, a release layer formed on said inner surface of said reservoir, an active agent impermeable backing layer formed on said outer surface of said reservoir, said release layer underlying said backing layer and sealed thereto about a circumferential sealed area so as to enclose said reservoir, said backing layer and said release layer extending peripherally beyond said sealed area about the entire periphery thereof so as to create an extended peripheral area, and adhesive means disposed between said backing layer and said release layer in said extended peripheral area and thereby separated from said reservoir by said sealed area, said adhesive means adapted to adhere said device to the skin or mucosa of said host upon removal of said release layer, whereby said active agent is released from said reservoir to provide a dose of said active agent.
2. The device of Claim 1, further including an annular gap in said extended peripheral area between said sealed area and said adhesive means so as to further separate said adhesive means from said reservoir.
3. The device of Claim 1, wherein said sealed area comprises a peelable heat seal, whereby the removal of said release layer from said device can be facilitated.
4. The device of Claim 1, 2 or 3, wherein said release layer extends outwardly beyond said backing layer so as to act as a tab for removal of said release layer.
5. The device of Claim 1, 2 or 3, further including a release coating provided on the inner surface of said release layer facing said reservoir and extending at least within said sealed area, whereby said release layer may be removed from said device for adhering said device to the skin or mucosa of said host by said adhesive means.
6. The device of Claim 1, 2 or 3, further including a release coating provided on the inner surface of said release layer facing said reservoir and extending at least within said sealed area, whereby said release layer may be removed from said device for adhering said device to the skin or mucosa of said host by said adhesive means, said release coating extending within said extended peripheral area to facilitate the removal of said release layer from said adhesive means.
7. The device of Claim 1, 2 or 3, wherein said backing layer includes a primary backing layer impermeable to said active agent and extending at least to said sealed area and a secondary outer backing layer overlying said primary backing layer and said extended peripheral area.
8. The device of Claim 1, 2 or 3, wherein said backing layer includes a primary backing layer impermeable to said active agent and extending at least to said sealed area and a secondary outer backing layer overlying said primary backing layer and said extended peripheral area, said secondary outer backing layer including an inner surface and an outer surface, and said adhesive means comprising an adhesive layer extending over the entire inner surface of said secondary outer backing layer.
9. The device of Claim 1, 2 or 3, wherein said backing layer includes a primary backing layer impermeable to said active agent and extending at least to said sealed area and a secondary outer backing layer overlying said primary backing layer and said extended peripheral area, said secondary outer backing layer including an inner surface and an outer surface, and said adhesive means comprising an adhesive layer extending over the entire inner surface of said secondary outer backing layer, said adhesive layer comprising an adhesive substantially impermeable to said active agent.
10. The device of Claim 1, 2 or 3, wherein said backing layer comprises a coextruded layer of a primary backing layer impermeable to said active agent and a heat sealable layer in contact with said release layer within said sealed area.
11. The device of Claim 1, 2 or 3, wherein said adhesive means comprises an adhesive layer comprising an adhesive substantially impermeable to said active agent.
12. The device of Claim 1, 2 or 3, further including an active agent permeable membrane disposed between said inner surface of said reservoir and said release layer, and extending at least to said sealed area so as to be sealed between said backing layer and said release layer.
13. The device of Claim 1, 2 or 3, further including a sponge within said reservoir for retaining said active agent therein.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/809,483 US4710191A (en) | 1985-12-16 | 1985-12-16 | Therapeutic device for the administration of medicaments |
| US809,483 | 1985-12-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1261702A true CA1261702A (en) | 1989-09-26 |
Family
ID=25201450
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000525383A Expired CA1261702A (en) | 1985-12-16 | 1986-12-15 | Therapeutic device for the administration of medicaments |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4710191A (en) |
| JP (1) | JP2527547B2 (en) |
| BE (1) | BE905928A (en) |
| CA (1) | CA1261702A (en) |
| CH (1) | CH670393A5 (en) |
| DE (1) | DE3642600C2 (en) |
| FR (1) | FR2591493A1 (en) |
| GB (1) | GB2184016B (en) |
| IT (1) | IT1199760B (en) |
| NL (1) | NL8603204A (en) |
| SE (1) | SE500637C2 (en) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5910304A (en) * | 1982-12-13 | 1999-06-08 | Texas A&M University System | Low-dose oral administration of interferons |
| DE3762480D1 (en) * | 1986-08-23 | 1990-06-07 | Arno W Latzke | AGENT FOR APPLICATION OF TRANSDERMAL RESORBABLE ACTIVE SUBSTANCES. |
| GB8622698D0 (en) * | 1986-09-20 | 1986-10-29 | Smith & Nephew Ass | Dispenser |
| ZA878295B (en) * | 1986-11-06 | 1988-05-03 | Amarillo Cell Culture Co. Inc. | Treatment of immuno-resistant disease |
| CA1320905C (en) * | 1986-11-06 | 1993-08-03 | Joseph M. Cummins | Treatment of immuno-resistant disease |
| US4849224A (en) * | 1987-11-12 | 1989-07-18 | Theratech Inc. | Device for administering an active agent to the skin or mucosa |
| US4983395A (en) * | 1987-11-12 | 1991-01-08 | Theratech Inc. | Device for administering an active agent to the skin or mucosa |
| US4906475A (en) | 1988-02-16 | 1990-03-06 | Paco Pharmaceutical Services | Estradiol transdermal delivery system |
| US4877618A (en) * | 1988-03-18 | 1989-10-31 | Reed Jr Fred D | Transdermal drug delivery device |
| CH678151A5 (en) * | 1988-07-13 | 1991-08-15 | Heinz Hermann Weick | Self-medication nasal dispenser |
| US5139023A (en) * | 1989-06-02 | 1992-08-18 | Theratech Inc. | Apparatus and method for noninvasive blood glucose monitoring |
| NO894195L (en) * | 1989-06-05 | 1990-12-06 | Bertek Inc | DEVICE FOR APPLICATION OF A THIN FILM. |
| US5087242A (en) * | 1989-07-21 | 1992-02-11 | Iomed, Inc. | Hydratable bioelectrode |
| US5374241A (en) * | 1989-07-21 | 1994-12-20 | Iomed, Inc. | Electrodes for iontophoresis |
| US5328455A (en) * | 1989-07-21 | 1994-07-12 | Iomed, Inc. | Rehydratable product and method of preparation thereof |
| US5230896A (en) * | 1989-10-12 | 1993-07-27 | Warner-Lambert Company | Transdermal nicotine delivery system |
| US5088978A (en) * | 1990-01-26 | 1992-02-18 | Gensia Pharmaceuticals, Inc. | Apparatus and method for iontophoretic transfer |
| US5227169A (en) * | 1991-05-17 | 1993-07-13 | Theratech, Inc. | Sorbitan esters as skin permeation enhancers |
| US5120325A (en) * | 1991-06-12 | 1992-06-09 | Fleshtones Products Co., Inc. | Color-matched sterile adhesive bandages containing melanin-like pigment composition |
| CA2075517C (en) * | 1992-04-01 | 1997-03-11 | John Wick | Transdermal patch incorporating a polymer film incorporated with an active agent |
| US6010715A (en) * | 1992-04-01 | 2000-01-04 | Bertek, Inc. | Transdermal patch incorporating a polymer film incorporated with an active agent |
| US5503844A (en) * | 1993-05-18 | 1996-04-02 | Mli Acquisition Corp. Ii | Foam laminate transdermal patch |
| US5962011A (en) * | 1993-12-06 | 1999-10-05 | Schering-Plough Healthcare Products, Inc. | Device for delivery of dermatological ingredients |
| GB9409281D0 (en) | 1994-05-10 | 1994-06-29 | Svedman Paul | Transdermal device |
| CA2208132A1 (en) * | 1994-12-21 | 1996-06-27 | Theratech, Inc. | Transdermal delivery system with adhesive overlay and peel seal disc |
| TW592729B (en) * | 1995-04-06 | 2004-06-21 | Janssen Pharmaceutica Nv | Rate-controlled transdermal administration of risperidone |
| US5840056A (en) * | 1995-06-15 | 1998-11-24 | Empi, Inc. | Iontophoresis electrode |
| US5788666A (en) * | 1995-06-15 | 1998-08-04 | Empi, Inc. | Iontophoresis electrode |
| US5730721A (en) * | 1996-01-25 | 1998-03-24 | Vesture Corporation | Medical applicator and method |
| US7150881B2 (en) | 1997-06-26 | 2006-12-19 | Mylan Technologies, Inc. | Adhesive mixture for transdermal delivery of highly plasticizing drugs |
| US6163720A (en) * | 1997-12-18 | 2000-12-19 | Alza Corporation | Layered rate controlling membranes for use in an electrotransport device |
| JP4864204B2 (en) | 1998-12-18 | 2012-02-01 | アルザ・コーポレーション | Transparent transdermal nicotine delivery device |
| US6277401B1 (en) | 1999-05-07 | 2001-08-21 | U.S. Dermatologics, Inc. | Drug delivery device |
| SE518097C2 (en) * | 2000-10-03 | 2002-08-27 | Ellen Ab | Process for the preparation of an absorbent sanitary article comprising lactic acid producing bacteria as well as such |
| DE10127455A1 (en) * | 2001-06-07 | 2002-12-19 | Hexal Ag | Transdermal therapeutic system, preferably of reservoir or matrix type, has peelable film with reduced tear strength in one dimension |
| CA2457114C (en) | 2001-09-21 | 2010-11-23 | Coloplast A/S | Device for the administration of an active agent to the human skin |
| US7169823B2 (en) * | 2003-03-10 | 2007-01-30 | Air Products And Chemicals, Inc. | Tertiary alkanolamine polyurethane catalysts derived from long chain alkyl and fatty carboxylic acids |
| US6998508B2 (en) * | 2003-03-10 | 2006-02-14 | Air Products And Chemicals, Inc. | Tertiary alkanolamines containing surface active alkyl groups |
| US6747069B1 (en) | 2003-03-10 | 2004-06-08 | Air Products And Chemicals, Inc. | Tertiary alkanolamine polyurethane catalysts derived from long chain alkyl and fatty carboxylic acids |
| US20060210615A1 (en) * | 2003-08-07 | 2006-09-21 | Frank Theobald | Dermal or transdermal therapeutic system comprising an ormocer with barrier effect on a cover foil |
| EP1747033A1 (en) | 2004-04-30 | 2007-01-31 | Burrell E. Clawson | Apparatus and methods for isolating human body areas for localized cooling |
| US8252319B2 (en) | 2004-10-21 | 2012-08-28 | Durect Corporation | Transdermal delivery system for sufentanil |
| CN102085198B (en) | 2004-10-21 | 2014-06-04 | 杜雷科特公司 | Transdermal delivery systems |
| JP2007254435A (en) * | 2006-03-27 | 2007-10-04 | Takaoka Kasei Kogyo Kk | Anticancer functional water |
| WO2009009651A1 (en) * | 2007-07-10 | 2009-01-15 | Agile Therapeutics, Inc. | Dermal delivery device with ultrasonic weld |
| US20100178323A1 (en) * | 2007-07-10 | 2010-07-15 | Agis Kydonieus | Dermal Delivery Device |
| BRPI0814697B8 (en) * | 2007-07-10 | 2021-05-25 | Agile Therapeutics Inc | drug delivery device |
| DE102008060203A1 (en) * | 2008-12-07 | 2010-06-10 | Dietrich Wilhelm Schacht | Sheet-like device, useful for transdermal administration of e.g. rotigotine to treat Parkinson's disease, comprises an active ingredient containing layer, an active agent impermeable backing layer and a removable protective layer |
| DE102009056745A1 (en) * | 2009-12-04 | 2011-06-09 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system for the administration of peptides |
| DE102010064358A1 (en) * | 2010-12-29 | 2012-07-05 | Acino Ag | Transdermal application system with protruding baking foil |
| EP2682113B1 (en) * | 2012-07-02 | 2018-10-31 | Luye Pharma AG | Sealing laminates containing agents |
| US20140155827A1 (en) * | 2012-12-03 | 2014-06-05 | Mylan, Inc. | Medicament information system and method |
| EP3067050A1 (en) * | 2015-03-13 | 2016-09-14 | Acino AG | Transdermal therapeutic system with an overtape comprising two adhesive layers |
| DE102018130469A1 (en) * | 2018-11-30 | 2020-06-04 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system with diffusion barrier |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE8424387U1 (en) * | 1984-11-15 | Allpack Industrielle Lohnverpackung GmbH & Co KG, 7050 Waiblingen | Pharmaco adhesive plaster | |
| US2235436A (en) * | 1939-11-03 | 1941-03-18 | Stanley V Laub | Medical appliance |
| US2561071A (en) * | 1949-09-21 | 1951-07-17 | Prisk Howard Conley | Holder for subcutaneous administration of medicaments |
| US3797494A (en) * | 1969-04-01 | 1974-03-19 | Alza Corp | Bandage for the administration of drug by controlled metering through microporous materials |
| US3814095A (en) * | 1972-03-24 | 1974-06-04 | H Lubens | Occlusively applied anesthetic patch |
| US3972995A (en) * | 1975-04-14 | 1976-08-03 | American Home Products Corporation | Dosage form |
| US4052505A (en) * | 1975-05-30 | 1977-10-04 | Alza Corporation | Ocular therapeutic system manufactured from copolymer |
| GB1510569A (en) * | 1976-07-02 | 1978-05-10 | American Home Prod | Dosage form for the administration of a medicament to a moist body surface |
| US4117841A (en) * | 1977-02-07 | 1978-10-03 | Anthony Perrotta | Medicated bandage pocket |
| US4176664A (en) * | 1978-03-13 | 1979-12-04 | Stanley Kalish | Impregnated bandage |
| BR7905505A (en) * | 1978-08-28 | 1980-05-13 | Kemicron Oy | DISPOSABLE NUT PACKING |
| EP0010987B1 (en) * | 1978-11-07 | 1983-10-05 | Beecham Group Plc | Device for oral administration to a ruminant animal |
| IL59063A (en) * | 1979-01-11 | 1983-12-30 | Key Pharma | Polymeric diffusion matrix for release of pharmaceutical dosage |
| DE2902183A1 (en) * | 1979-01-20 | 1980-07-31 | Geb Schmidt Beate D Ringwelski | Device for applying nitrate and nitrite cpds. to skin - for treating heart disorders, consists of porous layer between skin and drug |
| US4402696A (en) * | 1979-10-15 | 1983-09-06 | Gulko Bruce N | Folded applicator |
| US4297995A (en) * | 1980-06-03 | 1981-11-03 | Key Pharmaceuticals, Inc. | Bandage containing attachment post |
| US4341208A (en) * | 1980-07-14 | 1982-07-27 | Whitman Medical Corporation | Moisture-retentive covering for ointment application |
| US4460372A (en) * | 1981-02-17 | 1984-07-17 | Alza Corporation | Percutaneous absorption enhancer dispenser for use in coadministering drug and percutaneous absorption enhancer |
| US4379454A (en) * | 1981-02-17 | 1983-04-12 | Alza Corporation | Dosage for coadministering drug and percutaneous absorption enhancer |
| US4725272A (en) * | 1981-06-29 | 1988-02-16 | Alza Corporation | Novel bandage for administering beneficial drug |
| US4486193A (en) * | 1981-07-22 | 1984-12-04 | Alza Corporation | Method for treating ischemic conditions by administering drug by two routes |
| US4460368A (en) * | 1981-10-29 | 1984-07-17 | Almedco, Inc. | Trans-dermal medication system |
| US4460370A (en) * | 1981-10-29 | 1984-07-17 | Almedco, Inc. | Trans-dermal medication application cell |
| US4468194A (en) * | 1983-03-24 | 1984-08-28 | Marathon Oil Company | Automatic flame snuffer for storage tank vent lines with manual override |
| US4573996A (en) * | 1984-01-03 | 1986-03-04 | Jonergin, Inc. | Device for the administration of an active agent to the skin or mucosa |
| DE3430250C1 (en) * | 1984-08-17 | 1986-04-24 | Allpack Industrielle Lohnverpackung GmbH & Co KG, 7050 Waiblingen | Medicinal adhesive plaster |
| ES8608895A1 (en) * | 1984-08-17 | 1986-07-16 | Allpack Ind Lohnverpackung | Therapeutical adhesive plaster and process for its manufacture. |
| US4692462A (en) * | 1985-03-18 | 1987-09-08 | Menley & James Laboratories, Ltd. | Compositions and method of controlling transdermal penetration of topical and systemic agents |
| GB8512358D0 (en) * | 1985-05-16 | 1985-06-19 | Euro Celtique Sa | Transdermal delivery system |
-
1985
- 1985-12-16 US US06/809,483 patent/US4710191A/en not_active Expired - Lifetime
-
1986
- 1986-12-09 GB GB8629406A patent/GB2184016B/en not_active Expired
- 1986-12-10 CH CH4921/86A patent/CH670393A5/fr not_active IP Right Cessation
- 1986-12-11 SE SE8605320A patent/SE500637C2/en unknown
- 1986-12-12 DE DE3642600A patent/DE3642600C2/en not_active Expired - Lifetime
- 1986-12-15 CA CA000525383A patent/CA1261702A/en not_active Expired
- 1986-12-15 FR FR8617617A patent/FR2591493A1/en active Granted
- 1986-12-15 JP JP61298583A patent/JP2527547B2/en not_active Expired - Lifetime
- 1986-12-15 IT IT22683/86A patent/IT1199760B/en active
- 1986-12-16 NL NL8603204A patent/NL8603204A/en not_active Application Discontinuation
- 1986-12-16 BE BE0/217532A patent/BE905928A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| US4710191A (en) | 1987-12-01 |
| GB8629406D0 (en) | 1987-01-21 |
| SE8605320L (en) | 1987-06-17 |
| SE8605320D0 (en) | 1986-12-11 |
| CH670393A5 (en) | 1989-06-15 |
| GB2184016B (en) | 1989-11-15 |
| BE905928A (en) | 1987-04-16 |
| NL8603204A (en) | 1987-07-16 |
| IT1199760B (en) | 1988-12-30 |
| DE3642600A1 (en) | 1987-06-19 |
| IT8622683A1 (en) | 1988-06-15 |
| FR2591493B1 (en) | 1995-03-31 |
| FR2591493A1 (en) | 1987-06-19 |
| JP2527547B2 (en) | 1996-08-28 |
| GB2184016A (en) | 1987-06-17 |
| IT8622683A0 (en) | 1986-12-15 |
| JPS62195326A (en) | 1987-08-28 |
| DE3642600C2 (en) | 1997-02-06 |
| SE500637C2 (en) | 1994-08-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1261702A (en) | Therapeutic device for the administration of medicaments | |
| US4573996A (en) | Device for the administration of an active agent to the skin or mucosa | |
| EP0356614B1 (en) | Dermal applicator | |
| EP0316168B1 (en) | Device for administering an active agent to the skin or mucosa | |
| KR960005143B1 (en) | Transdermal patch incorporation a polymer film incorporated with an active agent | |
| CA2053272C (en) | Device for administering an active agent to the skin or mucosa | |
| KR101035041B1 (en) | Two-sided non-stick release film | |
| US5064422A (en) | Twin patch applicator | |
| JP4388068B2 (en) | Transdermal patch comprising an active agent transfer barrier layer | |
| SI8810781A (en) | Plaster with an active substance for a controlled application of the active substance to the skin. | |
| EP0401949A2 (en) | Thin film applicator | |
| JPH08252299A (en) | Package for patch |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |