CA2294067C - Device for delivery of dermatological ingredients - Google Patents
Device for delivery of dermatological ingredients Download PDFInfo
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- CA2294067C CA2294067C CA002294067A CA2294067A CA2294067C CA 2294067 C CA2294067 C CA 2294067C CA 002294067 A CA002294067 A CA 002294067A CA 2294067 A CA2294067 A CA 2294067A CA 2294067 C CA2294067 C CA 2294067C
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- skin
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- shell
- transfer pad
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/12—Keratolytics, e.g. wart or anti-corn preparations
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
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- Veterinary Medicine (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Media Introduction/Drainage Providing Device (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
A novel device and method for delivering a liquid containing an active ingredient to a treatment site on the skin is disclosed. The device is useful for treating lesions or abnormal skin features such as corns, warts, calluses, bunions, actinic keratoses and hard hyperkeratotic skin as is often found on the face, arms, legs or feet.
Description
Title: DEVICE FOR DELIVERY OF DERMATOLOGICAL INGREDIENTS
BACICGROUND OF THE INVENTION
Devices for transdermal or percutaneous drug delivery are known, such as described in U.S. Patent Re. 34,692 to Becher; U.S.
Patent 2,561,071 to Prisk; U.S.Patents 3,598,122 and 3,797,494 and 3,948,262 to Zaffaroni; U.S. Patent 3,923,939 to Baker et al.; U.S.
Patent 4,031,894 to Urquhart et al.; U.S. Patent 4,176,664 to Kalish; U.S. Patent 4,379,454 to Campbell; U.S. Patent 4,466,953 to Keith et al.; U.S. Patents 4,573,996 and 4,710,191 to Kwiatek et al.; U.S.Patent 4,597,961 to Etscorn; U.S. Patent 4,605,548 to Ushiyama et al.; U.S. Patent 4,638,043 to Szycher et al.; U.S.
Patents 4,687,481 and 4,810,499 to Nuwayser; U.S. Patent 4,762,124 to Kerch et. al.; U.S. Patent 4,784,857 to Berry et al.; U.S.
Patent 4,812,305 to Vocal; U.S. Patent 4,816,258 to Nedberge et al.; U.S. Patent 4,830,854 to Copelan; U.S. Patent 4,830,856 to Peppers; U.S. Patent 4,904,475 to Gale et al.; U.S. Patent 4,917,676 to Heiber et al.; U.S. Patent 5,028,435 to Katz et. al.;
U.S. Patent 5,112,618 to Cartmell et al.; U.S. Patent 5,128,137 to Muller et al.; U.S. Patent 5,141,750 to Lee et. al.; U.S. Patent 5,296,222 to Petersen et al.; and WO 96/19205.
Such devices are typically characterized by delivering an amount of a drug, e.g. nitroglycerin, estrogen, estradiol, corticoid, levonorgestrel, etc. to the patient's skin at a rate controlled by the device. Subsequently, the drug is delivered systemically to the intended site of treatment within the body.
Although effective for their intended use, such controlled release devices have limited utility for providing the kind of treatment which requires maximum delivery of the drug or active ingredient for local skin conditions, for example, lesions or abnormal skin features such as corns, warts, calluses, bunions, actinic keratoses and hard hyperkeratotic skin as is often found on the face, arms, legs or feet. Other types of delivery devices such as medicated plasters have been used for corns, warts, calluses, etc. However, the amount of active ingredient that can be delivered by such plasters is limited by the dimensions of the plaster and solubility of the active ingredient in the plaster. Consequently, repetitive applications are required for effect~_ve treatment. It would be desirable to provide a device which would provide maximum delivery of dermatological ingredients for local skin conditions as described above.
SUMMARY OF THE INVENTION
In one embodiment, the present invention is directed toward a device for delivering a liquid containing an active ingredient to a treatment site on the skin, comprising:
a) a reservoir for holding said liquid, wherein said reservoir has sufficient interior surface area to retain said liquid against a gravitational force;
b) a shell impermeable to said liquid, wherein said shell has an upper portion within which said reservoir is disposed, and an underneath side having an opening, wherein said reservoir, said shell or the combination of said reservoir and said shell is capable of retaining said liquid against a compressive force of one psi or less;
c) a transfer pad having an upper side and an lower side, wherein at least a portion of the upper side of said transfer pad contacts said reservoir at the opening of said shell, and at least a portion of the lower side of said transfer pad contacts the treatment site on the skin, wherein said transfer pad is conformable to the skin and readily transfers liquid from the reservoir, through itself and onto the skin treatment site; and d) means for attaching said device to the skin to maintain said transfer pad in intimate contact with the treatment site.
In another embodiment, the present invention is directed toward a device whose reservoir of active ingredient is located remote from the skin treatment site. The remote delivery device comprises:
i) a reservoir for holding said liquid, wherein said reservoir has sufficient interiorsurface area to retain said liquid against a gravitational force;
ii) a shell impermeable to said liquid, wherein said shell has an upper portion within which said reservoir is disposed, and an underneath side having an opening, wherein said reservoir, said shell or the combination of said reservoir and said shell is capable of retaining said liquid against a compressive force of one psi or less;
iii) a connector strip having a first end and a second end, wherein the first end of the connector strip contacts said reservoir through said shell opening ;
iv) a transfer pad having an upper side and an lower side, wherein said second end of said connector strip contacts said upper side of said transfer pad, and at least a portion of the lower side of said transfer pad contacts the treatment site on the skin, wherein said transfer pad is conformable to the skin and readily transfers liquid from the connector strip, through itself and onto the skin treatment site; and v) an elongated connector which surrounds said connector strip to prevent loss of liquid from said strip; and vi) means for attaching said device to the skin to maintain said transfer pad in intimate contact with the treatment site:
Preferably, the liquid is an aqueous solvent, a water miscible organic solvent or mixtures thereof. A preferred water miscible organic solvent is ethanol. Also preferred is that the active ingredient can be used to treat corns, warts or calluses.
Preferably the active ingredient is a keratolytic agent such as active salicylic acid or salt thereof.
Optionally and preferably, the d) or vi) means for attaching said device to the skin also seals said device on the skin to prevent lateral leaching of the liquid from the treatment site, preferably using a pressure sensitive adhesive.
Optionally, the device further comprises e) means for sealing said device on the skin to prevent lateral leaching or migration, of the liquid from the treatment site, preferably using a pressure sensitive adhesive.
Optionally and preferably, the device further comprises a release liner in contact with any one or all of said transfer pad, said attaching means and said sealing means.
In another embodiment, the present invention is directed toward a method for treating corns, warts or calluses comprising attaching either of the above device to the skin, wherein the active ingredient in the device can be used to treat corns, warts or calluses.
The present delivery device has the advantage of utilizing a low viscosity liquid, which can permeate into the treatment site significantly faster than high viscosity formulations, thus ensuring maximum delivery of the active ingredient to the treatment site.
BACICGROUND OF THE INVENTION
Devices for transdermal or percutaneous drug delivery are known, such as described in U.S. Patent Re. 34,692 to Becher; U.S.
Patent 2,561,071 to Prisk; U.S.Patents 3,598,122 and 3,797,494 and 3,948,262 to Zaffaroni; U.S. Patent 3,923,939 to Baker et al.; U.S.
Patent 4,031,894 to Urquhart et al.; U.S. Patent 4,176,664 to Kalish; U.S. Patent 4,379,454 to Campbell; U.S. Patent 4,466,953 to Keith et al.; U.S. Patents 4,573,996 and 4,710,191 to Kwiatek et al.; U.S.Patent 4,597,961 to Etscorn; U.S. Patent 4,605,548 to Ushiyama et al.; U.S. Patent 4,638,043 to Szycher et al.; U.S.
Patents 4,687,481 and 4,810,499 to Nuwayser; U.S. Patent 4,762,124 to Kerch et. al.; U.S. Patent 4,784,857 to Berry et al.; U.S.
Patent 4,812,305 to Vocal; U.S. Patent 4,816,258 to Nedberge et al.; U.S. Patent 4,830,854 to Copelan; U.S. Patent 4,830,856 to Peppers; U.S. Patent 4,904,475 to Gale et al.; U.S. Patent 4,917,676 to Heiber et al.; U.S. Patent 5,028,435 to Katz et. al.;
U.S. Patent 5,112,618 to Cartmell et al.; U.S. Patent 5,128,137 to Muller et al.; U.S. Patent 5,141,750 to Lee et. al.; U.S. Patent 5,296,222 to Petersen et al.; and WO 96/19205.
Such devices are typically characterized by delivering an amount of a drug, e.g. nitroglycerin, estrogen, estradiol, corticoid, levonorgestrel, etc. to the patient's skin at a rate controlled by the device. Subsequently, the drug is delivered systemically to the intended site of treatment within the body.
Although effective for their intended use, such controlled release devices have limited utility for providing the kind of treatment which requires maximum delivery of the drug or active ingredient for local skin conditions, for example, lesions or abnormal skin features such as corns, warts, calluses, bunions, actinic keratoses and hard hyperkeratotic skin as is often found on the face, arms, legs or feet. Other types of delivery devices such as medicated plasters have been used for corns, warts, calluses, etc. However, the amount of active ingredient that can be delivered by such plasters is limited by the dimensions of the plaster and solubility of the active ingredient in the plaster. Consequently, repetitive applications are required for effect~_ve treatment. It would be desirable to provide a device which would provide maximum delivery of dermatological ingredients for local skin conditions as described above.
SUMMARY OF THE INVENTION
In one embodiment, the present invention is directed toward a device for delivering a liquid containing an active ingredient to a treatment site on the skin, comprising:
a) a reservoir for holding said liquid, wherein said reservoir has sufficient interior surface area to retain said liquid against a gravitational force;
b) a shell impermeable to said liquid, wherein said shell has an upper portion within which said reservoir is disposed, and an underneath side having an opening, wherein said reservoir, said shell or the combination of said reservoir and said shell is capable of retaining said liquid against a compressive force of one psi or less;
c) a transfer pad having an upper side and an lower side, wherein at least a portion of the upper side of said transfer pad contacts said reservoir at the opening of said shell, and at least a portion of the lower side of said transfer pad contacts the treatment site on the skin, wherein said transfer pad is conformable to the skin and readily transfers liquid from the reservoir, through itself and onto the skin treatment site; and d) means for attaching said device to the skin to maintain said transfer pad in intimate contact with the treatment site.
In another embodiment, the present invention is directed toward a device whose reservoir of active ingredient is located remote from the skin treatment site. The remote delivery device comprises:
i) a reservoir for holding said liquid, wherein said reservoir has sufficient interiorsurface area to retain said liquid against a gravitational force;
ii) a shell impermeable to said liquid, wherein said shell has an upper portion within which said reservoir is disposed, and an underneath side having an opening, wherein said reservoir, said shell or the combination of said reservoir and said shell is capable of retaining said liquid against a compressive force of one psi or less;
iii) a connector strip having a first end and a second end, wherein the first end of the connector strip contacts said reservoir through said shell opening ;
iv) a transfer pad having an upper side and an lower side, wherein said second end of said connector strip contacts said upper side of said transfer pad, and at least a portion of the lower side of said transfer pad contacts the treatment site on the skin, wherein said transfer pad is conformable to the skin and readily transfers liquid from the connector strip, through itself and onto the skin treatment site; and v) an elongated connector which surrounds said connector strip to prevent loss of liquid from said strip; and vi) means for attaching said device to the skin to maintain said transfer pad in intimate contact with the treatment site:
Preferably, the liquid is an aqueous solvent, a water miscible organic solvent or mixtures thereof. A preferred water miscible organic solvent is ethanol. Also preferred is that the active ingredient can be used to treat corns, warts or calluses.
Preferably the active ingredient is a keratolytic agent such as active salicylic acid or salt thereof.
Optionally and preferably, the d) or vi) means for attaching said device to the skin also seals said device on the skin to prevent lateral leaching of the liquid from the treatment site, preferably using a pressure sensitive adhesive.
Optionally, the device further comprises e) means for sealing said device on the skin to prevent lateral leaching or migration, of the liquid from the treatment site, preferably using a pressure sensitive adhesive.
Optionally and preferably, the device further comprises a release liner in contact with any one or all of said transfer pad, said attaching means and said sealing means.
In another embodiment, the present invention is directed toward a method for treating corns, warts or calluses comprising attaching either of the above device to the skin, wherein the active ingredient in the device can be used to treat corns, warts or calluses.
The present delivery device has the advantage of utilizing a low viscosity liquid, which can permeate into the treatment site significantly faster than high viscosity formulations, thus ensuring maximum delivery of the active ingredient to the treatment site.
The present delivery device has the further advantage of being a maximum release° device as compared to the typical "controlled release" device. Since the present device release or delivers the active ingredient to the skin at a rate at least as great or even greater than the skin can absorb, since the rate limiting step for delivery of the active ingredient using the present device is the rate of uptake by the skin, not the rate of delivery or release by the device. Thus, the present device ensures maximum delivery of the active ingredient to the treatment site on the skin.
The present delivery device has the further advantage of usually being able to achieve effective treatment of local skin conditions with a single application, as compared to multiple or repetitive applications required with plasters.
The present delivery device has the further advantage of being able to reduce the time for treatment due to its ability to deliver higher dosages of the active ingredient compared to plasters and other known delivery devices.
The present delivery device has the further advantage of being able to deliver the active ingredient to the skin treatment site more efficiently and continuously compared to plasters and other known delivery devices.
BRIEF DESCRIPTION OF THE DRAWINGS
Figs. 1, 2, and 3 are schematic, cross sectional side views of the device for delivering a liquid to a treatment site on the skin using a box-type shell.
Figs. 4, 5 and 6 are schematic, cross sectional side views of the device for delivering a liquid to a treatment site on the skin using a box-type shell in combination with a specialized means for preventing migration of the liquid from the skin treatment site.
Figs. 7 and 8 are schematic, cross sectional side views of the device for delivering a liquid to a treatment site on the skin using a hat-type shell.
Fig. 9 is a schematic, cross sectional side view of the device for delivering a liquid to a treatment site on the skin using a hat-type shell in combination with a specialized means for sealing the liquid on the skin.
Fig. 10 is a schematic, cross sectional side view of the device for delivering a liquid to a skin treatment site that is remote from the shell and reservoir.
DETAILED DESCRIPTION OF THE DRAWINGS
In Fig. 1, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an interior surface (2b).
Reservoir (4), which holds a liquid containing an active 5 ingredient, is disposed within the interior of shell (2). Transfer pad (6), which occupies opening (10) of shell (2), does not impede the flow of liquid through the opening (10). In this embodiment, the upper surface (6a) of transfer pad (6) is substantially flush with the lower interior surface (2b) of shell (2) and upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Skin adhesive also serve as the means for sealing the liquid on the skin. A
release liner (not shown) contacts adhesive (8b) and the lower surface (6b) of transfer pad (6) .
In Fig. 2, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an interior surf ace (2b).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad (6), which occupies opening (10) of shell (2), does not impede the flow of liquid through the opening (10). In this embodiment, a portion of transfer pad (6) rests upon the lower interior surface (2b) of shell (2) so that the upper surface (6a) of transfer pad (6) is not flush with the lower interior surface (2b) of shell (2) and upper surface (6a) is in direct contact with reservoir (4).
Means ( 8 ) f or attaching device ( 1 ) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Skin adhesive also serve as the means for sealing the liquid on the skin. A release liner (not shown) contacts adhesive (8b) and the lower surface (6b) of transfer pad (6) .
In Fig. 3, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an exterior surface (2c).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad ( 6 ) , which covers opening ( 10 ) of shell ( 2 ) , does not impede the flow of liquid through the opening (10). In this embodiment, a portion of transfer pad (6) rests against the lower exterior surface (2c) of shell (2) so that. the upper surface (6a) of transfer pad (6) is flush with the lower exterior surface (2c) of shell (2) and upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Skin adhesive (8b) also serve as the means for sealing the liquid on the skin. A release liner (not shown) contacts adhesive (8b) and the lower surface (6b) of transfer pad (6) .
In Fig. 4, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an interior surface (2b).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the Interior of shell (2). Transfer pad (6), which occupies opening (10) of shell (2), does not impede the flow of liquid through the opening. In this embodiment, the upper surface (6a) of transfer pad (5) is substantially flush with the lower interior surface (2b) of shell (2) and upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Specialized sealing means (9) is interposed between attaching means (8) and transfer pad (6) to seal the liquid on the skin, either by itself or in conduction with adhesive (8b). A release liner (not shown) contacts adhesive (8b), sealing means (9) and lower surface (6b) of transfer pad ( 6 ) .
In Fig. 5, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an interior surface (2b).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad (6), which occupies opening (10) of shell (2), does not impede the flow of liquid through the opening (10). In this embodiment, a portion of transfer pad (6) rests upon the lower interior surface (2b) of shell (2) so that the upper surface (6a) of transfer pad (6) is not flush with the lower interior surface (2b) of shell (2) and upper surface (6a) is in direct contact with reservoir (4).
Means ( 8 ) for attaching device ( 1 ) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Specialized sealing means (9) is interposed between attaching means (8) and tranfer pad (6) to seal the liquid on the skin, either by itself or in conduction with adhesive (8b). A
release liner (not shown) contacts adhesive (8b), sealing means (9) and lower surface (6b) of transfer pad (6).
In Fig. 6, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an exterior surface (2c).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad (6), which covers opening (10) of shell (2), does not impede the flow of liquid through the opening (10). In this embodiment, a portion of transfer pad (6) rests against the lower exterior surface (2c) of shell (2) so that the upper surface (6a) of transfer pad (6) is flush with the lower exterior surface (2c) of shell (2) and upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Specialized sealing means (9) is interposed between attaching means (8) and tranfer pad (6) to seal the liquid on the skin, either by itself or in conduction with adhesive (8b). A
release liner (not shown) contacts adhesive (8b), sealing means (9) and lower surface (6b) of transfer pad (6).
In Fig. 7, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an exterior surface (2c).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad (6), which occupies opening (10) of shell (2), does not impede the flow of liquid through the opening (10). In this embodiment, the upper surface (6a) of transfer pad (6) is substantially flush with the lower exterior surface (2c) of shell (2). The edge of transfer pad (6) abuts against sealing means (8) so that the edge aligns with interior wall of shell (2). The entire upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Skin adhesive also serve as the means for sealing the liquid on the skin. A
release liner (not shown) contacts adhesive (8b) and the lower surface (6b) of transfer pad (6).
In Fig. 8, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an exterior surface (2c).
Reservoir (4), which holds a li~.~uid containing an active ingredient, is disposed within the interior of shell (2).
Transfer pad (6), which covers opening (10) of shell (2), does i not impede the flow of liquid through opening (10). In this embodiment, a portion of transfer pad (6) rests against the lower exterior surface (2c) of shell (2) and only a portion of upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b).
Skin adhesive (8b) also serve as the means for sealing the liquid on the skin. A release liner (not shown) contacts adhesive (8b) and the lower surface (6b) of transfer pad (6).
In Fig. 9, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an exterior surface (2c).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad (6); which covers opening (10) of shell (2), does not impede the flow of liquid through opening (10). In this embodiment, a portion of transfer pad (6) rests against the lower exterior surface (2c) of shell (2) and only a portion of upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on t:he skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Specialized sealing means (9) is interposed between attaching means (8) and transfer pad (6) to seal the liquid on the skin, either by itself or in conjuction with adhesive (8b). A release liner (not shown) contacts adhesive (8b), sealing means (9) and lower surface (6b) of transfer pad (6) .
In Fig. 10, device (1) has a shell (2) having an upper portion (2a) which is connected to elongated connector (17). Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Connector strip (15) or wick (15), disposed within elongated connector (17), has a first end (15a) in direct contact with reservoir (4) and second end (15c) in direct contact with the upper sur~ace (6a) of transfer pad (6).
In this embodiment, transfer pad (~~) occupies opening (10) of connector (17) and does not impede the flow of liquid through the opening. Transfer pad (6) can be sized dimensionally to accomodate the size of the lesion. Means (8) for attaching device (1) to the treatment site on the skin is joined to the other end of elongated connector. Means (8) is comprised of skin attaching layer (8a) and skin adhesive (8b). Means (8) also includes a skin adhesive on shell (2). Skin adhesive (8b) also serve as the means for sealing the liquid on the skin. Release liners (not shown) contact adhesive (8b), the lower surface (6b) of transfer pad (6) and skin adhesive (8) on shell (2).
DETAILED DESCRIPTION OF THE EMBODIMENTS
The Shell The shell should be impermeable or impervious to the liquid being delivered to the treatment site, in order to prevent loss by evaporation or wetting. The shell may also protect the active ingredient and/or liquid against radiant energy sources such as ultraviolet and visible light. '~he shell can be either dimensionally stable or dimensionally non-stable, preferably dimensionally non-stable. A dimensionally stable shell is capable of resisting a compressive force of one pound per square inch (psi) (703 kilogram/square meter) or less. A dimensionally non-stable shell is not capable of withstanding a compressive force of one psi or less, i.e. will at least partially crush or collapse. Suitable materials for the shell can include but are not limited to ceramics, metals such as titanium, aluminum or steel, plastics such as polyolefins, barex, styrene, polyesters, polyacrylics, vinylpolymers, polyamides, polyfluorocarbons, polyimides, polylactams, polyaramides, polycarbonates, polysulfones, polyethylene, polypropylene, nylon, polyvinyl chloride or composites thereof.
The Reservoir The reservoir is a structure having Buff icient interior surface area to retain the liquid against a gravitational force by means of surface energy to prevent the liquid from readily draining out of the reservoir. The reservoir can be either dimensionally stable or dimensionally non-stable, as discussed for the shell, above. The reservoir should also be resistant to dissolution by the liquid, especially where water-miscible organic solvents are employed.
Suitable materials for the reservoir can include but are not limited to sintered glass; sintered metals; ceramics; porous polyethylene; porous ultrahigh molecular weight polyethylene;
porous polyvinylidene fluoride polymer; porous polypropylene polymer; fiberglass; natural and synthetic fibers such as cotton fibers and cotton gauze, polyester fibers, nylon fibers, polyamide fibers, polyolefin fibers, and hollow fiber materials; porous materials such as sponges, either natural or synthetic; and compacted powder matrices such as compacted amorphous silica.
In order to retain the liquid in the reservoir, it is important 5 that either the reservoir, the shell or the combination of the reservoir and the shell is capable of retaining said liquid against a compressive force of one pound per square inch psi or less. For example, a dimensionally non-stable reservoir should use a dimensionally stable shell. Similarly, a dimensionally non-stable 10 shell should use a dimensionally stable reservoir.
The reservoir and the shell are generally separate components.
However, where feasible, the reservoir and the shell could be formed into an integral unit, such as by molding porous polyethylene or by scintering the exterior of a porous ceramic.
The Transfer Pad The transfer pad establishes an intimate interface between the reservoir and the treatment site on the skin, i.e. directly contacts both the reservoir and skin treatment site. The transfer pad should conform to the skin and readily transfer liquid from the reservoir to the skin treatment site. That is, the liquid from the reservoir should readily pass through the transfer pad. Generally, the transfer pad should have a surface energy greater than the surface energy of the reservoir surface, so that when the device is applied to the skin, the transfer pad wicks and/or promotes liquid flow from the reservoir, through itself and onto the skin treatment site. Suitable materials for the transfer pad include synthetic or natural fibers such cottons or polyesters; or non-woven materials such as polyesters. A preferred non-woven polyester is Veratec #140060. Veratec is a division of International Paper, Walpole, Massachusetts.
Means for Attaching the Device to the Skin The means for attaching and securing the device to the skin ensures that transfer pad remains ~_n intimate contact with the treatment site. Suitable material: for the attaching means can include waterproof tape or other materials that have an adhesive underside. Where an adhesive is employed, a pressure sensitive adhesive is preferred. The adhesive should be resistant to permeation and/or dissolution by the liquid. Suitable adhesives may include but are not limited to the following:
The present delivery device has the further advantage of usually being able to achieve effective treatment of local skin conditions with a single application, as compared to multiple or repetitive applications required with plasters.
The present delivery device has the further advantage of being able to reduce the time for treatment due to its ability to deliver higher dosages of the active ingredient compared to plasters and other known delivery devices.
The present delivery device has the further advantage of being able to deliver the active ingredient to the skin treatment site more efficiently and continuously compared to plasters and other known delivery devices.
BRIEF DESCRIPTION OF THE DRAWINGS
Figs. 1, 2, and 3 are schematic, cross sectional side views of the device for delivering a liquid to a treatment site on the skin using a box-type shell.
Figs. 4, 5 and 6 are schematic, cross sectional side views of the device for delivering a liquid to a treatment site on the skin using a box-type shell in combination with a specialized means for preventing migration of the liquid from the skin treatment site.
Figs. 7 and 8 are schematic, cross sectional side views of the device for delivering a liquid to a treatment site on the skin using a hat-type shell.
Fig. 9 is a schematic, cross sectional side view of the device for delivering a liquid to a treatment site on the skin using a hat-type shell in combination with a specialized means for sealing the liquid on the skin.
Fig. 10 is a schematic, cross sectional side view of the device for delivering a liquid to a skin treatment site that is remote from the shell and reservoir.
DETAILED DESCRIPTION OF THE DRAWINGS
In Fig. 1, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an interior surface (2b).
Reservoir (4), which holds a liquid containing an active 5 ingredient, is disposed within the interior of shell (2). Transfer pad (6), which occupies opening (10) of shell (2), does not impede the flow of liquid through the opening (10). In this embodiment, the upper surface (6a) of transfer pad (6) is substantially flush with the lower interior surface (2b) of shell (2) and upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Skin adhesive also serve as the means for sealing the liquid on the skin. A
release liner (not shown) contacts adhesive (8b) and the lower surface (6b) of transfer pad (6) .
In Fig. 2, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an interior surf ace (2b).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad (6), which occupies opening (10) of shell (2), does not impede the flow of liquid through the opening (10). In this embodiment, a portion of transfer pad (6) rests upon the lower interior surface (2b) of shell (2) so that the upper surface (6a) of transfer pad (6) is not flush with the lower interior surface (2b) of shell (2) and upper surface (6a) is in direct contact with reservoir (4).
Means ( 8 ) f or attaching device ( 1 ) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Skin adhesive also serve as the means for sealing the liquid on the skin. A release liner (not shown) contacts adhesive (8b) and the lower surface (6b) of transfer pad (6) .
In Fig. 3, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an exterior surface (2c).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad ( 6 ) , which covers opening ( 10 ) of shell ( 2 ) , does not impede the flow of liquid through the opening (10). In this embodiment, a portion of transfer pad (6) rests against the lower exterior surface (2c) of shell (2) so that. the upper surface (6a) of transfer pad (6) is flush with the lower exterior surface (2c) of shell (2) and upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Skin adhesive (8b) also serve as the means for sealing the liquid on the skin. A release liner (not shown) contacts adhesive (8b) and the lower surface (6b) of transfer pad (6) .
In Fig. 4, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an interior surface (2b).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the Interior of shell (2). Transfer pad (6), which occupies opening (10) of shell (2), does not impede the flow of liquid through the opening. In this embodiment, the upper surface (6a) of transfer pad (5) is substantially flush with the lower interior surface (2b) of shell (2) and upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Specialized sealing means (9) is interposed between attaching means (8) and transfer pad (6) to seal the liquid on the skin, either by itself or in conduction with adhesive (8b). A release liner (not shown) contacts adhesive (8b), sealing means (9) and lower surface (6b) of transfer pad ( 6 ) .
In Fig. 5, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an interior surface (2b).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad (6), which occupies opening (10) of shell (2), does not impede the flow of liquid through the opening (10). In this embodiment, a portion of transfer pad (6) rests upon the lower interior surface (2b) of shell (2) so that the upper surface (6a) of transfer pad (6) is not flush with the lower interior surface (2b) of shell (2) and upper surface (6a) is in direct contact with reservoir (4).
Means ( 8 ) for attaching device ( 1 ) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Specialized sealing means (9) is interposed between attaching means (8) and tranfer pad (6) to seal the liquid on the skin, either by itself or in conduction with adhesive (8b). A
release liner (not shown) contacts adhesive (8b), sealing means (9) and lower surface (6b) of transfer pad (6).
In Fig. 6, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an exterior surface (2c).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad (6), which covers opening (10) of shell (2), does not impede the flow of liquid through the opening (10). In this embodiment, a portion of transfer pad (6) rests against the lower exterior surface (2c) of shell (2) so that the upper surface (6a) of transfer pad (6) is flush with the lower exterior surface (2c) of shell (2) and upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Specialized sealing means (9) is interposed between attaching means (8) and tranfer pad (6) to seal the liquid on the skin, either by itself or in conduction with adhesive (8b). A
release liner (not shown) contacts adhesive (8b), sealing means (9) and lower surface (6b) of transfer pad (6).
In Fig. 7, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an exterior surface (2c).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad (6), which occupies opening (10) of shell (2), does not impede the flow of liquid through the opening (10). In this embodiment, the upper surface (6a) of transfer pad (6) is substantially flush with the lower exterior surface (2c) of shell (2). The edge of transfer pad (6) abuts against sealing means (8) so that the edge aligns with interior wall of shell (2). The entire upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Skin adhesive also serve as the means for sealing the liquid on the skin. A
release liner (not shown) contacts adhesive (8b) and the lower surface (6b) of transfer pad (6).
In Fig. 8, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an exterior surface (2c).
Reservoir (4), which holds a li~.~uid containing an active ingredient, is disposed within the interior of shell (2).
Transfer pad (6), which covers opening (10) of shell (2), does i not impede the flow of liquid through opening (10). In this embodiment, a portion of transfer pad (6) rests against the lower exterior surface (2c) of shell (2) and only a portion of upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on the skin is comprised of skin attaching layer (8a) and skin adhesive (8b).
Skin adhesive (8b) also serve as the means for sealing the liquid on the skin. A release liner (not shown) contacts adhesive (8b) and the lower surface (6b) of transfer pad (6).
In Fig. 9, device (1) has a shell (2) having an upper portion (2a) and a lower portion having an exterior surface (2c).
Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Transfer pad (6); which covers opening (10) of shell (2), does not impede the flow of liquid through opening (10). In this embodiment, a portion of transfer pad (6) rests against the lower exterior surface (2c) of shell (2) and only a portion of upper surface (6a) is in direct contact with reservoir (4). Means (8) for attaching device (1) to the treatment site on t:he skin is comprised of skin attaching layer (8a) and skin adhesive (8b). Specialized sealing means (9) is interposed between attaching means (8) and transfer pad (6) to seal the liquid on the skin, either by itself or in conjuction with adhesive (8b). A release liner (not shown) contacts adhesive (8b), sealing means (9) and lower surface (6b) of transfer pad (6) .
In Fig. 10, device (1) has a shell (2) having an upper portion (2a) which is connected to elongated connector (17). Reservoir (4), which holds a liquid containing an active ingredient, is disposed within the interior of shell (2). Connector strip (15) or wick (15), disposed within elongated connector (17), has a first end (15a) in direct contact with reservoir (4) and second end (15c) in direct contact with the upper sur~ace (6a) of transfer pad (6).
In this embodiment, transfer pad (~~) occupies opening (10) of connector (17) and does not impede the flow of liquid through the opening. Transfer pad (6) can be sized dimensionally to accomodate the size of the lesion. Means (8) for attaching device (1) to the treatment site on the skin is joined to the other end of elongated connector. Means (8) is comprised of skin attaching layer (8a) and skin adhesive (8b). Means (8) also includes a skin adhesive on shell (2). Skin adhesive (8b) also serve as the means for sealing the liquid on the skin. Release liners (not shown) contact adhesive (8b), the lower surface (6b) of transfer pad (6) and skin adhesive (8) on shell (2).
DETAILED DESCRIPTION OF THE EMBODIMENTS
The Shell The shell should be impermeable or impervious to the liquid being delivered to the treatment site, in order to prevent loss by evaporation or wetting. The shell may also protect the active ingredient and/or liquid against radiant energy sources such as ultraviolet and visible light. '~he shell can be either dimensionally stable or dimensionally non-stable, preferably dimensionally non-stable. A dimensionally stable shell is capable of resisting a compressive force of one pound per square inch (psi) (703 kilogram/square meter) or less. A dimensionally non-stable shell is not capable of withstanding a compressive force of one psi or less, i.e. will at least partially crush or collapse. Suitable materials for the shell can include but are not limited to ceramics, metals such as titanium, aluminum or steel, plastics such as polyolefins, barex, styrene, polyesters, polyacrylics, vinylpolymers, polyamides, polyfluorocarbons, polyimides, polylactams, polyaramides, polycarbonates, polysulfones, polyethylene, polypropylene, nylon, polyvinyl chloride or composites thereof.
The Reservoir The reservoir is a structure having Buff icient interior surface area to retain the liquid against a gravitational force by means of surface energy to prevent the liquid from readily draining out of the reservoir. The reservoir can be either dimensionally stable or dimensionally non-stable, as discussed for the shell, above. The reservoir should also be resistant to dissolution by the liquid, especially where water-miscible organic solvents are employed.
Suitable materials for the reservoir can include but are not limited to sintered glass; sintered metals; ceramics; porous polyethylene; porous ultrahigh molecular weight polyethylene;
porous polyvinylidene fluoride polymer; porous polypropylene polymer; fiberglass; natural and synthetic fibers such as cotton fibers and cotton gauze, polyester fibers, nylon fibers, polyamide fibers, polyolefin fibers, and hollow fiber materials; porous materials such as sponges, either natural or synthetic; and compacted powder matrices such as compacted amorphous silica.
In order to retain the liquid in the reservoir, it is important 5 that either the reservoir, the shell or the combination of the reservoir and the shell is capable of retaining said liquid against a compressive force of one pound per square inch psi or less. For example, a dimensionally non-stable reservoir should use a dimensionally stable shell. Similarly, a dimensionally non-stable 10 shell should use a dimensionally stable reservoir.
The reservoir and the shell are generally separate components.
However, where feasible, the reservoir and the shell could be formed into an integral unit, such as by molding porous polyethylene or by scintering the exterior of a porous ceramic.
The Transfer Pad The transfer pad establishes an intimate interface between the reservoir and the treatment site on the skin, i.e. directly contacts both the reservoir and skin treatment site. The transfer pad should conform to the skin and readily transfer liquid from the reservoir to the skin treatment site. That is, the liquid from the reservoir should readily pass through the transfer pad. Generally, the transfer pad should have a surface energy greater than the surface energy of the reservoir surface, so that when the device is applied to the skin, the transfer pad wicks and/or promotes liquid flow from the reservoir, through itself and onto the skin treatment site. Suitable materials for the transfer pad include synthetic or natural fibers such cottons or polyesters; or non-woven materials such as polyesters. A preferred non-woven polyester is Veratec #140060. Veratec is a division of International Paper, Walpole, Massachusetts.
Means for Attaching the Device to the Skin The means for attaching and securing the device to the skin ensures that transfer pad remains ~_n intimate contact with the treatment site. Suitable material: for the attaching means can include waterproof tape or other materials that have an adhesive underside. Where an adhesive is employed, a pressure sensitive adhesive is preferred. The adhesive should be resistant to permeation and/or dissolution by the liquid. Suitable adhesives may include but are not limited to the following:
A. Solvent-based acrylic adhesives such as:
Monsanto GMS 737, trademark of Monsanto Corporation, St. Louis, Missouri;
National Starch Durotak 72-9720 and 80-1197, trademark of National Starch & Chemical Corp., Bridgewater, New Jersey;
Ashland~s AROSET 11 13-AD-40 and 1085-Z-45, trademark of Ashland Oil Co., Ashland, Kentucky. -B. Solvent-based rubber adhesives such as:
National Starch 36-6172 C. Acrylic emulsion adhesives such as:
Monsanto GME 2397 Rohm & Haas N580, trademark of Rohm & Haas Co., Philadelphia, Pennsylvania;
Unocal 76 RES 9646, trademark of Unocal Corp., Los Angeles, California; and Ashland's AROSET 2022-W-50.
C. Adhesive Transfer Tapes such as:
3M F-9465 PC, trademark of 3M Co., St. Paul, Minnesota Avery-benison MED 1116, trademark of Avery Dennison Corp., Pasedena, California;
ARCare 7530, trademark of Adhesive Research Inc., Glen Rock, Pennsylvania; and RX230U, trademark of Coating Science Inc., Bloomfield, Connecticut.
A tackifier is a substance which enhances the property of tack of a pressure sensitive adhesive. Suitable tackifiers include rosin acid derivatives, terpene based derivatives and synthetic C-5 tackifiers such as Escorez 1310 of the Exxon Corporation, Irving, Texas. The amount of~ tackifier ir.. the adhesive can range from about 10 to about 60% by weight of the adhesive, preferably from about 20 to about 40%. The means for attaching said device to the skin can also seal the device on the skin to prevent lateral leaching or migration of the liquid from the treatment site.
Sealing Means Optionally and preferably, a means for sealing the device on the skin to prevent lateral leaching and migration of the liquid from the treatment site can be employed. Such means for sealing the liquid to prevent lateral leaching or migration can be the attaching means cited above, a s~=parate sealing means, or a combination of the attaching means and the sealing means. Such sealing means serves as a gasket to confine the liquid so that liquid flow is restricted to the transfer pad and the skin treatment site. Thus, the sealing means should be substantially impermeable or impervious to the liquid. Suitable materials for the sealing means can include waxes, polymers, adhesive coated tapes, and pressure sensitive adhesives.
The Liquid The liquid employed in the present device can be an aqueous solvent (i.e. water), a water miscible organic solvent or mixtures thereof. The water miscible organic solvent can include but is not limited to ethanol, acetone, ethers, ketones such as methylethylketone (MEK), dimethlysulfoxide, polyethylene glycol (PEG) and propylene glycol. Preferably the water miscible organic solvent is ethanol or a water-containing ethanol solution, wherein the amount of water in the liquid solution can range from about 1 to about 50%. The liquid should have a low viscosity, i.e. about 3000 centipoise (cPs) or less, preferably about 1000 cPs or less.
The liquid may include other excipients such as thickeners and permeation enhance~rs such as propylene glycol, oleic acid, isopropyl myristate and dimethylisosorbide (DMI).
Active Ingredient The active ingredient preferably is one which can treat corns, warts or calluses. Preferably the active ingredient is a keratolytic agent such as salicylic acid or salts or esters thereof, glacial acetic acid, glycolic acid, phenoxyacetic acid, ascorbic acid, retinoic acid (tretinoin), fluorouracil, calcium pantothenate, cantharidin, podophyllum, phenol, zinc chloride, tannic acid, castor oil, or mixtures thereof. The amount of active ingredient in the liquid can range from about 1 to about 40% by weight, preferably from about 5 to about 30%. Preferably, the active ingredient is salicylic acid or a salt or ester thereof.
Suitable salts include the sodium, potassium, calcium or magnesium salts thereof. Suitable esters include the C-1 to C-4 esters thereof, such as methyl salicylate. Other esters include.salsalate (salicylsalicylic acid), the sali-.:ylate ester of salicylic acid.
Most preferably the acid form is employed as the active ingredient.
Release Liner Optionally and preferably, a release liner is used to contact the attaching means, the sealing means and/or the transfer pad.
The release liner prevents contamination of the attaching means or sealing means, especially where an adhesive is employed. The release liner also serves to prevent loss of liquid through the transfer pad prior to application of the device to the skin treatment site. Upon removal of the release liner, the device can be applied to the skin treatment site. Suitable release liners include high density polyethylene (HDPE), polyester (i.e. Mylar°), polyethylene terephthalate (PET) and the like, preferably 7 mil high density polyethylene film.
The Connector Strip & Elongated Connector The connector strip or wick enables the liquid to move from a remotely located reservoir (i.e, not directly above the treatment site) to the transfer pad which is directly above the treatment site. Suitable materials for the connector strip can include any of the non-dimensionally stable materials cited for the reservoir, such as woven polyester cloth, bonded nylon fibers, cotton gauze, fiberglass, polyester fibers and cotton fibers. An elongated connector is used to surround or encase the connector strip to prevent loss of liquid through evaporation or wetting. The elongated connector can be a non-absorbent or impermeable material such as those described for the shell.
The following examples how the present invention may be practised, and should not be construed as limiting the its overall scope.
Example 1: A delivery device as illustrated in Fig. 1 is used to remove a wart. The reservoir is bonded nylon 3 x 5x 15 mm in dimension covered with a polyethylene shell. The protective cover is Johnson & Johnson 1" waterproof tape. The transfer pad is a 5 mm x 5 mm strip of Sontara~ by Dupont. The device is applied over the wart on the skin surface. The following liquid wart removal formula (0. 1 80 milliliters) (mL) is injected into the reservoir.
Ingredient Percent by Weight Salicylic acid 20.1 Propylene glycol 42.6 Deionized Water 10.7 Anhydrous Alcohol 26.6 After 6 hours, the device is removed. The wart has a white appearance and completely sloughs off in 6 days without additional treatment.
Example 2: Five milliters of the formula of Example 1 is used in conjunction with a modified version of Fig. 10 embodiment to treat rough hardened skin on the heel. In this particular example, the transfer pad is much larger than shown in Figure 10 and the remote device was wrapped on the extremity or limb with a non occlusive bandage. The transfer pad is a 6 inch x 2 inch piece of DuPont Sontara #8423 (rayon 700, polyester 30%). The transfer pad is attached to a Transorb polyester reservoir (American Filtrona) via a 3 inch polyethylene covered 6 mm wide strip of Sontara. The entire assembly is attached or secured to the skin with adhesive tape. After 4 hours, all of the skin in contact with the transfer pad is white in color. In 6 days the entire area of skin sloughs off, revealing a layer of soft pink skin. No irritation or untoward effect is observed.
Example 3: Eight milliliters of the following formula was used in conjunction with a modified version of the Fig. 10 embodiment to treat a chronic case of athlete's foot. The transfer pad is a 12 cm x 4 cm strip of Sontara. The res::rvoir is a 1 mm x 1 mm x 5 mm strip of American Filtrona's nylon fiber block. The rod-shaped connector strip is woven polyester cloth having dimension of 6 cm x 1 millimeter (mm) diameter.
~ Ingredient Percent by Weight Salicylic acid 21.7 Dimethyl Isorbide 34.8 Anydrous Alcohol 43.5 'TABLE 2 The area between the toes is infected with fissures and red itchy skin. One 4 hour treatment is used. The intense itching stops on contact. The entire stratum corneum sloughs off in 7 days, leaving healthy skin with with no evidence of infection. Reeamination after 60 days reveals normal skin.
Example 4: One-hundred fifty microliters (ul) of 50% lactic acid is absorbed on a 1 0 mm x 70 mm piece of Sontara (Dupont) used as the connector strip as shown in Fig. 1 0. At the time of use, a 10 mm x 15 mm x 5 mm nylon reservoir (American Filtrona) is filled with water and placed in contact with the above connector strip.
The water migrates from the reservoir through the connector strip and transfers the lactic acid quantitatively to a 3 mm x 5 mm transfer pad of Sontara. The transfer pad is totally wetted in 5 about 1 0 minutes. This illustrates that all the ingredients of the treatment liquid need not be placed in the reservoir. Although this Example illustrates impregnating the connector strip with a liquid, the connector strip could also be impregnated with a solid that is not stable in solution. The reservior would then be filled 10 with a solution capable of dissolving the solid impregnated in the connector strip and carrying it, in solution, to the transfer pad.
Example 5: One-hundred eighty microliters (ul) of 1 percent fluorouracil is added to the reservoir of the device in Fig. 1 to treat a lesion on the face. The reservoir is a light density 15 polyethylene by Porex Technologies. The transfer pad of polyester cellulose (Veratec) is cut to fit the size of the lesion. The device is attached to the face for 12 hours. Redness appears in one day, followed by scaling and healing in one week.
Example 6: The device of Fig. 7 is used to bathe a wound to enhance healing time. The reservoir is filled with 10 mL of antibiotics which continuously bathes the wound to enhance healing time. The reservoir is a medium density polyethylene by Porex Technologies, the transfer pad is polypropylene, and the collection reservoir is a medium density polyethylene product.
Example 7: The device of Fig. 1 is used to treat age spots.
One hundred microliters of 4 percent hydroquinone, a depigmenting solution, is added to the reservoir. The transfer pad is cut to fit the size of the age spot. The reservoir is a polyethylene product by Porex Technologies, and the transfer pad is a polyester/cellulose product by Veratec. The device is attached to the skin at the age spot daily for four hours until the age spot disappears.
Example 8: Insect bites are treated using the device of Fig.
1. A sufficient quantity of the following liquid is placed into the reservoir.
i Ingredient Percent by Weight Benzocaine 4.0 Propylene glycol 20.0 Deionized Water 76.0 The transfer pad is placed directly over the insect bite for treatment. The reservoir is HPDE (Porex product with a 45% pore volume), 6 mm diameter by 1 mm thick, and the transfer pad is a Veratec product classified as #1308221 which is a polyester/cotton material.
Example 9: A study is conducted to determine the drug substance release rate characteristics for the device in Fig. 1. In that device, the shell is a rubber type polymer film known as Parafilm (trademark of American Natural Can, Greenwich, Conneticut) , the reservoir is porous polypropylene, the transfer pad is a non-woven polyester fiber and the attachment means is a double sided adhesive tape. To the reservoir is added 150 microliters of the liquid formulation described in Example 1.
The device is placed on a subject s forearm for a predetermined time. Upon removal, the device is assayed for remaining drug substance and the release rate is calculated.
For comparison, the release rate of Estraderm°, estradiol transdermal system of Ciba Pharmaceutical Company, Summit, N.J., which also uses ethanol as the solvent, is shown. Estraderm releases 17B-estradiol through a rate-limiting membrane continuously upon application to the skin. The Estraderm system comprises four layers: (1) a transparent polyester film, (2) a drug reservoir of estradiol USP and alcohol USP gelled with hydroxypropyl cellulose, (3) an ethylene-vinyl acetate co-polymer membrane and (4) an adhesive formulation of light mineral oil and polyisobutylene. Results indicated total cumulative amount of active ingredient released after a given time.
Monsanto GMS 737, trademark of Monsanto Corporation, St. Louis, Missouri;
National Starch Durotak 72-9720 and 80-1197, trademark of National Starch & Chemical Corp., Bridgewater, New Jersey;
Ashland~s AROSET 11 13-AD-40 and 1085-Z-45, trademark of Ashland Oil Co., Ashland, Kentucky. -B. Solvent-based rubber adhesives such as:
National Starch 36-6172 C. Acrylic emulsion adhesives such as:
Monsanto GME 2397 Rohm & Haas N580, trademark of Rohm & Haas Co., Philadelphia, Pennsylvania;
Unocal 76 RES 9646, trademark of Unocal Corp., Los Angeles, California; and Ashland's AROSET 2022-W-50.
C. Adhesive Transfer Tapes such as:
3M F-9465 PC, trademark of 3M Co., St. Paul, Minnesota Avery-benison MED 1116, trademark of Avery Dennison Corp., Pasedena, California;
ARCare 7530, trademark of Adhesive Research Inc., Glen Rock, Pennsylvania; and RX230U, trademark of Coating Science Inc., Bloomfield, Connecticut.
A tackifier is a substance which enhances the property of tack of a pressure sensitive adhesive. Suitable tackifiers include rosin acid derivatives, terpene based derivatives and synthetic C-5 tackifiers such as Escorez 1310 of the Exxon Corporation, Irving, Texas. The amount of~ tackifier ir.. the adhesive can range from about 10 to about 60% by weight of the adhesive, preferably from about 20 to about 40%. The means for attaching said device to the skin can also seal the device on the skin to prevent lateral leaching or migration of the liquid from the treatment site.
Sealing Means Optionally and preferably, a means for sealing the device on the skin to prevent lateral leaching and migration of the liquid from the treatment site can be employed. Such means for sealing the liquid to prevent lateral leaching or migration can be the attaching means cited above, a s~=parate sealing means, or a combination of the attaching means and the sealing means. Such sealing means serves as a gasket to confine the liquid so that liquid flow is restricted to the transfer pad and the skin treatment site. Thus, the sealing means should be substantially impermeable or impervious to the liquid. Suitable materials for the sealing means can include waxes, polymers, adhesive coated tapes, and pressure sensitive adhesives.
The Liquid The liquid employed in the present device can be an aqueous solvent (i.e. water), a water miscible organic solvent or mixtures thereof. The water miscible organic solvent can include but is not limited to ethanol, acetone, ethers, ketones such as methylethylketone (MEK), dimethlysulfoxide, polyethylene glycol (PEG) and propylene glycol. Preferably the water miscible organic solvent is ethanol or a water-containing ethanol solution, wherein the amount of water in the liquid solution can range from about 1 to about 50%. The liquid should have a low viscosity, i.e. about 3000 centipoise (cPs) or less, preferably about 1000 cPs or less.
The liquid may include other excipients such as thickeners and permeation enhance~rs such as propylene glycol, oleic acid, isopropyl myristate and dimethylisosorbide (DMI).
Active Ingredient The active ingredient preferably is one which can treat corns, warts or calluses. Preferably the active ingredient is a keratolytic agent such as salicylic acid or salts or esters thereof, glacial acetic acid, glycolic acid, phenoxyacetic acid, ascorbic acid, retinoic acid (tretinoin), fluorouracil, calcium pantothenate, cantharidin, podophyllum, phenol, zinc chloride, tannic acid, castor oil, or mixtures thereof. The amount of active ingredient in the liquid can range from about 1 to about 40% by weight, preferably from about 5 to about 30%. Preferably, the active ingredient is salicylic acid or a salt or ester thereof.
Suitable salts include the sodium, potassium, calcium or magnesium salts thereof. Suitable esters include the C-1 to C-4 esters thereof, such as methyl salicylate. Other esters include.salsalate (salicylsalicylic acid), the sali-.:ylate ester of salicylic acid.
Most preferably the acid form is employed as the active ingredient.
Release Liner Optionally and preferably, a release liner is used to contact the attaching means, the sealing means and/or the transfer pad.
The release liner prevents contamination of the attaching means or sealing means, especially where an adhesive is employed. The release liner also serves to prevent loss of liquid through the transfer pad prior to application of the device to the skin treatment site. Upon removal of the release liner, the device can be applied to the skin treatment site. Suitable release liners include high density polyethylene (HDPE), polyester (i.e. Mylar°), polyethylene terephthalate (PET) and the like, preferably 7 mil high density polyethylene film.
The Connector Strip & Elongated Connector The connector strip or wick enables the liquid to move from a remotely located reservoir (i.e, not directly above the treatment site) to the transfer pad which is directly above the treatment site. Suitable materials for the connector strip can include any of the non-dimensionally stable materials cited for the reservoir, such as woven polyester cloth, bonded nylon fibers, cotton gauze, fiberglass, polyester fibers and cotton fibers. An elongated connector is used to surround or encase the connector strip to prevent loss of liquid through evaporation or wetting. The elongated connector can be a non-absorbent or impermeable material such as those described for the shell.
The following examples how the present invention may be practised, and should not be construed as limiting the its overall scope.
Example 1: A delivery device as illustrated in Fig. 1 is used to remove a wart. The reservoir is bonded nylon 3 x 5x 15 mm in dimension covered with a polyethylene shell. The protective cover is Johnson & Johnson 1" waterproof tape. The transfer pad is a 5 mm x 5 mm strip of Sontara~ by Dupont. The device is applied over the wart on the skin surface. The following liquid wart removal formula (0. 1 80 milliliters) (mL) is injected into the reservoir.
Ingredient Percent by Weight Salicylic acid 20.1 Propylene glycol 42.6 Deionized Water 10.7 Anhydrous Alcohol 26.6 After 6 hours, the device is removed. The wart has a white appearance and completely sloughs off in 6 days without additional treatment.
Example 2: Five milliters of the formula of Example 1 is used in conjunction with a modified version of Fig. 10 embodiment to treat rough hardened skin on the heel. In this particular example, the transfer pad is much larger than shown in Figure 10 and the remote device was wrapped on the extremity or limb with a non occlusive bandage. The transfer pad is a 6 inch x 2 inch piece of DuPont Sontara #8423 (rayon 700, polyester 30%). The transfer pad is attached to a Transorb polyester reservoir (American Filtrona) via a 3 inch polyethylene covered 6 mm wide strip of Sontara. The entire assembly is attached or secured to the skin with adhesive tape. After 4 hours, all of the skin in contact with the transfer pad is white in color. In 6 days the entire area of skin sloughs off, revealing a layer of soft pink skin. No irritation or untoward effect is observed.
Example 3: Eight milliliters of the following formula was used in conjunction with a modified version of the Fig. 10 embodiment to treat a chronic case of athlete's foot. The transfer pad is a 12 cm x 4 cm strip of Sontara. The res::rvoir is a 1 mm x 1 mm x 5 mm strip of American Filtrona's nylon fiber block. The rod-shaped connector strip is woven polyester cloth having dimension of 6 cm x 1 millimeter (mm) diameter.
~ Ingredient Percent by Weight Salicylic acid 21.7 Dimethyl Isorbide 34.8 Anydrous Alcohol 43.5 'TABLE 2 The area between the toes is infected with fissures and red itchy skin. One 4 hour treatment is used. The intense itching stops on contact. The entire stratum corneum sloughs off in 7 days, leaving healthy skin with with no evidence of infection. Reeamination after 60 days reveals normal skin.
Example 4: One-hundred fifty microliters (ul) of 50% lactic acid is absorbed on a 1 0 mm x 70 mm piece of Sontara (Dupont) used as the connector strip as shown in Fig. 1 0. At the time of use, a 10 mm x 15 mm x 5 mm nylon reservoir (American Filtrona) is filled with water and placed in contact with the above connector strip.
The water migrates from the reservoir through the connector strip and transfers the lactic acid quantitatively to a 3 mm x 5 mm transfer pad of Sontara. The transfer pad is totally wetted in 5 about 1 0 minutes. This illustrates that all the ingredients of the treatment liquid need not be placed in the reservoir. Although this Example illustrates impregnating the connector strip with a liquid, the connector strip could also be impregnated with a solid that is not stable in solution. The reservior would then be filled 10 with a solution capable of dissolving the solid impregnated in the connector strip and carrying it, in solution, to the transfer pad.
Example 5: One-hundred eighty microliters (ul) of 1 percent fluorouracil is added to the reservoir of the device in Fig. 1 to treat a lesion on the face. The reservoir is a light density 15 polyethylene by Porex Technologies. The transfer pad of polyester cellulose (Veratec) is cut to fit the size of the lesion. The device is attached to the face for 12 hours. Redness appears in one day, followed by scaling and healing in one week.
Example 6: The device of Fig. 7 is used to bathe a wound to enhance healing time. The reservoir is filled with 10 mL of antibiotics which continuously bathes the wound to enhance healing time. The reservoir is a medium density polyethylene by Porex Technologies, the transfer pad is polypropylene, and the collection reservoir is a medium density polyethylene product.
Example 7: The device of Fig. 1 is used to treat age spots.
One hundred microliters of 4 percent hydroquinone, a depigmenting solution, is added to the reservoir. The transfer pad is cut to fit the size of the age spot. The reservoir is a polyethylene product by Porex Technologies, and the transfer pad is a polyester/cellulose product by Veratec. The device is attached to the skin at the age spot daily for four hours until the age spot disappears.
Example 8: Insect bites are treated using the device of Fig.
1. A sufficient quantity of the following liquid is placed into the reservoir.
i Ingredient Percent by Weight Benzocaine 4.0 Propylene glycol 20.0 Deionized Water 76.0 The transfer pad is placed directly over the insect bite for treatment. The reservoir is HPDE (Porex product with a 45% pore volume), 6 mm diameter by 1 mm thick, and the transfer pad is a Veratec product classified as #1308221 which is a polyester/cotton material.
Example 9: A study is conducted to determine the drug substance release rate characteristics for the device in Fig. 1. In that device, the shell is a rubber type polymer film known as Parafilm (trademark of American Natural Can, Greenwich, Conneticut) , the reservoir is porous polypropylene, the transfer pad is a non-woven polyester fiber and the attachment means is a double sided adhesive tape. To the reservoir is added 150 microliters of the liquid formulation described in Example 1.
The device is placed on a subject s forearm for a predetermined time. Upon removal, the device is assayed for remaining drug substance and the release rate is calculated.
For comparison, the release rate of Estraderm°, estradiol transdermal system of Ciba Pharmaceutical Company, Summit, N.J., which also uses ethanol as the solvent, is shown. Estraderm releases 17B-estradiol through a rate-limiting membrane continuously upon application to the skin. The Estraderm system comprises four layers: (1) a transparent polyester film, (2) a drug reservoir of estradiol USP and alcohol USP gelled with hydroxypropyl cellulose, (3) an ethylene-vinyl acetate co-polymer membrane and (4) an adhesive formulation of light mineral oil and polyisobutylene. Results indicated total cumulative amount of active ingredient released after a given time.
Active Ingredient % Active Ingredient Cumulative Time Released by Device Released by Known of Present I.ZVentionDevice Device is on Skin (salicylic acid) (17B-estradiol) 1.5 hours 6.1 -3.0 hours 10.4 - -5.0 hours 17.8 -8 hours 60.8 -12 hours 83.9 -.
24 hours >83.9 1.25 The above table shows that the device of the present invention delivers at least 83.9% of the active ingredient after only 12 hours. In contrast, after 24 hours, a known device which also uses an alcohol solvent delivers only 1.25%, indicating the much higher rate of delivery rate of active ingredient for the delivery device of the present invention.
24 hours >83.9 1.25 The above table shows that the device of the present invention delivers at least 83.9% of the active ingredient after only 12 hours. In contrast, after 24 hours, a known device which also uses an alcohol solvent delivers only 1.25%, indicating the much higher rate of delivery rate of active ingredient for the delivery device of the present invention.
Claims (14)
1. A device for delivering a liquid containing an active ingredient to a treatment site on the skin, comprising:
(a) a reservoir for holding said liquid, wherein said reservoir has sufficient interior surface area to retain said liquid against a gravitational force;
b) a shell impermeable to said liquid, wherein said shell has an upper portion within which said reservoir is disposed, and an underneath side having an opening, wherein said reservoir, said shell or the combination of said reservoir and said shell is capable of retaining said liquid against a compressive force of one psi or less;
c) a transfer pad having an upper side and an lower side, wherein at least a portion of the upper side of said transfer pad contacts said reservoir at the opening of said shell, and at least a portion of the lower side of said transfer pad contacts the treatment site on the skin, wherein said transfer pad is conformable to the skin and readily transfers liquid from the reservoir, through itself and onto the skin treatment site; and d) means for attaching said device to the skin to maintain said transfer pad in intimate contact with the treatment site.
(a) a reservoir for holding said liquid, wherein said reservoir has sufficient interior surface area to retain said liquid against a gravitational force;
b) a shell impermeable to said liquid, wherein said shell has an upper portion within which said reservoir is disposed, and an underneath side having an opening, wherein said reservoir, said shell or the combination of said reservoir and said shell is capable of retaining said liquid against a compressive force of one psi or less;
c) a transfer pad having an upper side and an lower side, wherein at least a portion of the upper side of said transfer pad contacts said reservoir at the opening of said shell, and at least a portion of the lower side of said transfer pad contacts the treatment site on the skin, wherein said transfer pad is conformable to the skin and readily transfers liquid from the reservoir, through itself and onto the skin treatment site; and d) means for attaching said device to the skin to maintain said transfer pad in intimate contact with the treatment site.
2. The device of Claim 1 wherein said liquid is an aqueous solvent, a water miscible organic solvent or mixtures thereof.
3. The device of Claim 2 wherein the water miscible organic solvent is ethanol.
4. The device of Claim 1 wherein the active ingredient is used to treat corns, warts or calluses.
5. The device of Claim 1 wherein the active ingredient is a keratolytic agent.
6. The device of Claim 1 wherein the active ingredient is salicylic acid or a salt or ester thereof.
7. The device of Claim 1 wherein raid d) means for attaching said device to the skin also seals said device on the skin to prevent lateral leaching of the liquid from the treatment site.
8. The device of Claim 1 wherein said d) means for attaching said device to the skin uses a pressure sensitive adhesive.
9. The device of Claim 1 further comprising e) means for sealing said device on the skin to prevent lateral leaching of the liquid from the treatment site.
10. The device of Claim 9 wherein said e) means for sealing said device on the skin to prevent lateral leaching of the liquid from the treatment site uses a pressure sensitive adhesive.
11. The device of Claim 1 further comprising a release liner.
12. A device for delivering a liquid containing an active ingredient to a treatment site on the skin, comprising:
a) a reservoir for holding said liquid, wherein said reservoir has sufficient interior surface area to retain said liquid against a gravitational force, said liquid having a viscosity no greater than about 3000 centipoises.
b) a shell impermeable to said liquid, wherein said shell has an upper portion within which said reservoir is disposed, and an underneath side having an opening, wherein said reservoir, said shell or the combination of said reservoir and said shell is capable of retaining said liquid against a compressive force of one psi or less;
c) a connector strip having a first end and a second end, wherein the first end of the connector strip contacts said reservoir through said shell opening;
d) a transfer pad having an upper side and an lower side, wherein said second end of said connector strip contacts said upper side of said transfer pad, and at least a portion of the lower side of said transfer pad contacts the treatment site on the skin, wherein said transfer pad is conformable to the skin and readily transfers liquid from the connector strip, through said transfer pad and onto the skin treatment site; and e) an elongated connector which surrounds said connector strip to prevent loss of liquid from said strip; and f) means for attaching said device to the skin to maintain said transfer pad in intimate contact with the treatment site.
a) a reservoir for holding said liquid, wherein said reservoir has sufficient interior surface area to retain said liquid against a gravitational force, said liquid having a viscosity no greater than about 3000 centipoises.
b) a shell impermeable to said liquid, wherein said shell has an upper portion within which said reservoir is disposed, and an underneath side having an opening, wherein said reservoir, said shell or the combination of said reservoir and said shell is capable of retaining said liquid against a compressive force of one psi or less;
c) a connector strip having a first end and a second end, wherein the first end of the connector strip contacts said reservoir through said shell opening;
d) a transfer pad having an upper side and an lower side, wherein said second end of said connector strip contacts said upper side of said transfer pad, and at least a portion of the lower side of said transfer pad contacts the treatment site on the skin, wherein said transfer pad is conformable to the skin and readily transfers liquid from the connector strip, through said transfer pad and onto the skin treatment site; and e) an elongated connector which surrounds said connector strip to prevent loss of liquid from said strip; and f) means for attaching said device to the skin to maintain said transfer pad in intimate contact with the treatment site.
13. The use of the device of any one of claims 1 to 3 for treating corns, warts or calluses wherein the device is attached to the skin, at the appropriate location so that the active ingredient in the device can treat the corn, wart or callus.
14. The use of the device of any one of claims 5 to 12 for treating corns, warts or calluses wherein the device is attached to the skin, at the appropriate location so that the active ingredient in the device can treat the corn, wart or callus.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1997/011062 WO1998058631A1 (en) | 1997-06-24 | 1997-06-24 | Device for delivery of dermatological ingredients |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2294067A1 CA2294067A1 (en) | 1998-12-30 |
| CA2294067C true CA2294067C (en) | 2005-11-15 |
Family
ID=22261154
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002294067A Expired - Lifetime CA2294067C (en) | 1997-06-24 | 1997-06-24 | Device for delivery of dermatological ingredients |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0991404A1 (en) |
| AU (1) | AU3791997A (en) |
| CA (1) | CA2294067C (en) |
| WO (1) | WO1998058631A1 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2311892C2 (en) * | 2001-08-29 | 2007-12-10 | КАРВАЛХО Рикардо А. П. ДЕ | Implantable sealable system for one-way delivery of therapeutic preparations to tissues |
| US8870876B2 (en) | 2009-02-13 | 2014-10-28 | Tarsus Medical Inc. | Methods and devices for treating hallux valgus |
| US8277459B2 (en) | 2009-09-25 | 2012-10-02 | Tarsus Medical Inc. | Methods and devices for treating a structural bone and joint deformity |
| US8652141B2 (en) | 2010-01-21 | 2014-02-18 | Tarsus Medical Inc. | Methods and devices for treating hallux valgus |
| US8696719B2 (en) | 2010-06-03 | 2014-04-15 | Tarsus Medical Inc. | Methods and devices for treating hallux valgus |
| KR102232806B1 (en) | 2013-02-28 | 2021-03-29 | 더미라, 인코포레이티드 | Glycopyrrolate salts |
| US8558008B2 (en) | 2013-02-28 | 2013-10-15 | Dermira, Inc. | Crystalline glycopyrrolate tosylate |
| US9006462B2 (en) | 2013-02-28 | 2015-04-14 | Dermira, Inc. | Glycopyrrolate salts |
| US11607026B2 (en) | 2014-05-30 | 2023-03-21 | Johnson & Johnson Consumer Inc. | Device for delivery of skin care composition |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4597961A (en) * | 1985-01-23 | 1986-07-01 | Etscorn Frank T | Transcutaneous application of nicotine |
| CA1280111C (en) * | 1985-04-03 | 1991-02-12 | Richard E. Reever. | Composition for transdermal drug delivery |
| US5045553A (en) * | 1987-06-24 | 1991-09-03 | Fujisawa Pharmaceutical Company, Ltd. | Pharmaceutical composition for percutaneous drug absorption and percutaneous drug absorption promoter |
| EP0601058A4 (en) * | 1991-08-27 | 1995-05-31 | Cygnus Therapeutic Systems | Transdermal formulations for administering prazosin. |
| US5460620A (en) * | 1992-07-31 | 1995-10-24 | Creative Products Resource, Inc. | Method of applying in-tandem applicator pads for transdermal delivery of a therapeutic agent |
| WO1996032142A1 (en) * | 1995-04-12 | 1996-10-17 | Hopp Robert B | Skin patch for use in contact immunotherapy |
-
1997
- 1997-06-24 CA CA002294067A patent/CA2294067C/en not_active Expired - Lifetime
- 1997-06-24 WO PCT/US1997/011062 patent/WO1998058631A1/en not_active Application Discontinuation
- 1997-06-24 AU AU37919/97A patent/AU3791997A/en not_active Abandoned
- 1997-06-24 EP EP97934853A patent/EP0991404A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP0991404A1 (en) | 2000-04-12 |
| CA2294067A1 (en) | 1998-12-30 |
| AU3791997A (en) | 1999-01-04 |
| WO1998058631A1 (en) | 1998-12-30 |
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| Date | Code | Title | Description |
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| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20170627 |