CA2046921A1 - Device for the transdermal delivery of nicotine - Google Patents
Device for the transdermal delivery of nicotineInfo
- Publication number
- CA2046921A1 CA2046921A1 CA002046921A CA2046921A CA2046921A1 CA 2046921 A1 CA2046921 A1 CA 2046921A1 CA 002046921 A CA002046921 A CA 002046921A CA 2046921 A CA2046921 A CA 2046921A CA 2046921 A1 CA2046921 A1 CA 2046921A1
- Authority
- CA
- Canada
- Prior art keywords
- nicotine
- patch
- transdermal
- antipruritic
- transdermal patch
- 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.)
- Abandoned
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/465—Nicotine; Derivatives thereof
Abstract
A transdermal nicotine patch comprising an antipruritic to counteract pruritis observed with the transdermal administration of nicotine is disclosed. The patch can be any conventional patch type, e.g., reservoir, adhesive or polymeric matrix.
Description
2~4~21 WO~0/09808 . ` .; " ~ PCI`/US90/00805 -1 ~
DEVI CE FOR THE
. ~ ~
TRANSDERMAL DELIVERY OF NICOTINE
BACKGROUND OF THE INVENTION
This invention relates to a transdermal drug delivery patch, in particular, a patch useful for the transdermal delivery of nicotine. The patch is useful in that it delivers an amount of nicotine which achieves a physiological effect, curbing the urge to smoke tobacco, and thus easing the physiological symptoms of nicotine withdrawal.
A long felt need has existed in the medical art for a transdermal nicotine patch. In the past, nicotine has been administered orally, for example by chewing a resin gum containing nicotine such as that sold commercially under the trade name NICORETTE.
Several transdermal nicotine products have recently been disclosed. One such transdermal delivery device is disclosed by Lohmann & Co. GmbH in WO 8801-516-A, filed August 28, 1986. Lohmann describes a controlled release transdermal delivery system with an active substance, e.g., nicotine, in a depot formed by a reservoir contained between an adhesive layer and a backing layer. A dispersion device is connected to the depot which is spatially defined from the matrix.
Von Tilly, Ger. Offen. DE 3,438,284 similarly discloses a nicotine-reservoir containing transdermal preparation which is alleged to deliver approximately 20 to 30 ~g/day from a 10/20 cm2 patch.
Rose, et al. I~Transdermal nicotine reduces cigarette craving and nicotine preference", Clin.
Phar~,acol. Ther., Vol. 38, No. 4, pp 450-456 (Oct., 1985) discloses that transdermal nicotine base (8 mg) applied -in 30 percent aqueous solution under a polyethylene patch was helpful in reducing the urge to smoke tobacco.
It has been determined that a relatively constant nicotine blood level may help to curb the urge to smoke. Hence, one objective of the invention is to provide a transdermal nicotine patch which will deliver nicotine transdermally over an extenced perioc of time, e.g., 16 to 24 hours. ~ further objective is to provide a trans2ermal nicotine patch which causes a minimum of local pruritis or discom~ort where applied and worn on the skin. These obiectives, as well as others, will become more readily apparent from the following detailed description taken in conjunction with the drawings wherein:
Fig. 1 is a cross-sectional schematic view of a transdermal nicotine patch in an adhesive matrix form;
Fig. 2 is a cross-sectional view of an alternative embodiment of a transdermal nicotine patch, i.e., a polymeric matrix patch; and Fig. 3 is a cross-sectional view of a seconu alternative embodiment of a transdermal nicotine patch, i.e., a reservoir patch.
During testing of the transaermal nicotine patch describec herein, it was ~iscovered that nicotine delivered trans~ermally causes severe pruritis with practically no local erythema or inflammation. This pruritic reaction appears to be a pharmacological response to nicotine rather than a component of a general inflammatory reaction, since little if any erythema or inflammation are observed.
204~92~
~90/09808 3 ~ T/US90/00805 SUMMARY OF THE INVENTION
A transdermal nicotine patch is disclosed, comprising (a) an amount of nicotine or a salt or solvate thereof effective for treating the s~mptoms associated with tobacco smoking cessation, said nicotine to be transdermally delivered to a patient in need of such treatment and (b) an effective amount of a topical antipruritic. A preferred antipruritic is bisabolol, in an amount ranging from about 0.10 to about 2 percent of the total weight of the nicotine, antipruritic and carrier.
The transdermal patch may comprise an adhesive matrix, a reservoir or a polymeric matrix for containing the nicotine and/or antipruritic, and the transdermal patch preferably further comprises an easily removed release liner to protect the patch prior to application, and may further comprise a rate-limiting membrane.
The invention further includes a method of treating the urge to smoke tobacco and/or nicontine withdrawal, which method comprises transdermally delivering to a patient in need of such treatment an effective amount of nicotine in combination with the topical or transdermal use of an antipruritic such as bisabolol.
DETAILED DESCRIPTION
The invention described herein involves in its preferred embodiment the incorporation in a transdermal device for administering nicotine and at least one antipruritic compound useful for reducing or eliminating itching caused by the transdermal penetration of nico~ine.
The active ingredient in the patch described herein is nicotine or a pharmacologically and W090/09808 2 0 ~ 6 9 2 1 PCT/US90/00805 pharmaceutically acceptable salt or solvate thereof.
Typical salts and solvates include the hydrochlor~ide, dihydrochloride, sulfate, tartrate, bitartarate, zinc chloride double salt monohydrate and salicylate. The concentration of nicotine in the patch generally ranges from about 5 to about 40 percent of the total weight o~
the nicotine, antipruritic and carrier (e.g., the weight of the adhesive matrix, the polymeric matrix or the contents of the reservoir, but not including the weight of the backing material, release liner or rate controlling membrane) on a (w/w) basis. The preferred active ingredient is nicotine free base, and the preferred concentration of active ingredient is about 10 to about 20%.
The antipruritic used in the transdermal nicotine patch is included to counter the pruritic effects experienced when delivering nicotine transdermally. As such, it is referred to herein as the antipruritic, rather than as the nactive ingredient" even though it is clearly "active" in the sense that it reduces itching. The antipruritic is without pharmacological effect with respect to the nicotine withdrawal symptoms that are being treated.
One such preferred antipruritic compound is bisabolol, also known as 2-(4-methyl-3-cyclohexenyl)-6-methyl-5-hepten-2-ol, and more preferably a(-)bisabolol. Such a compound has not previously been used to effectuate the transdermal delivery of drugs, and in particular, nicotine, although it has been used as a cosmetic adjuvant. It is commercially available from BASF ~yandotte Corp., Parsippany, NJ. a(-)bisabolol is present in an amount ranging from about 0.10 to about 2%, more preferably about 0.1 to about 1% of the total weight of the nicotine, antipruritic and carrier.
, . 204~921 Examples of topical antipruritics effective in reducing itching during transdermal nicotine delivery other than bisabolol, mentioned above, are oil of chamomile, chamazulene, allantoin, D-panthenol glycyrrhetenic acid, corticosteroids, antihistamines, and combinations thereof. ANTIPHLOGISTICUM "ARO", commercially available from Novarom GmbH, Holzminder, Germany, comprising a combination of 18-B-glycyrrhetenic acid and D-panthenol, is a particularly useful combination.
Other ingredients useful in preparing the carrier for the transdermal nicotine patches described herein include conventional adhesives, solvents, co-solvents, plasticizers, polymeric matrices, stabilizers, thickeners, preservatives, etc.
Examples of pharmaceutically acceptable pressure sensitive adhesives useful in delivery devices for nicotine include acrylic, silicone, vinyl acetate and synthetic or natural rubber adhesives as well as other adhesives useful in transdermal drug delivery. The adhesives may be .used alone or in combination to prepare an adhesive drug matrix or may be applied to the skin-contacting surface of a polymeric matrix or reservoir patch to adhere said patch to the skin. Examples of-adhesives are acrylic adhesives such as RA 2484, RA 2333, RA 2397, R 363 and R 362 from Monsanto Co. Other acrylic adhesives, such as Durotak, manufactured by ~lorton Thiokol, Inc., and Neocryl XA5210 by Polyvinyl Chemicals, Ltd. may be utilized. Vinyl acetate adhesives include Flexcryl-161~, 1617, 1618 and 1625 from Air Products.
Numerous silicone based adhesives may be used, such as Q72929, Q27406, X72920 and 355, each manufactured by Dow-Corning. Natural and synthetic rubbers include polyisobutylenes, neoprenes, polybutadienes and polyisoprenes.
: 2ff~`69~1 WO90/09808 6 PCT/US90/0080~ -Polymeric matrix-forming agents include pharmaceutically acceptab~e-polymers such-as polyvinyl alcohol, polyvinylpyrolidones, gelatin and partially hydrolyzed polyvinyl alcohols.
Examples of solvents useful for effecting the transdermal delivery of nicotine include aqueous and organic solvents. As used herein the term solvent differs from the term co-solvent only in the most general sense. A co-solvent is a liquid which generally is a non-solvent, in which the active ingredient becomes soluble upon the addition of a small amount of a true solvent. Water is a typical solvent used in the transdermal nicotine patch. Polar organic solvents, such as ethanol, may also be useful.
Co-solvents useful in the transdermal nicotine patch include, for example, mineral oil, silicone-based liquids, and low molecular weight polyisobutylenes.
Suitable preservatives, antioxidants and chelating agents can be included in the transdermal nicotine patch, such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfate, a-tocopherol, maleic acid, ethylenediaminetetraacetic acid (EDTA), and cysteine hydrochloride.
Components useful for~imparting the desired wear and pharmacokinetic characteristics to the transdermal nicotine patch include, for example, polymeric matrix-forming materials added to facilitate curing of the adhesives, for example Aerotex Resin 3730 (American Cyanamid) and a thickener may be added to adjust the viscosity of the polymer mixture to the desired viscosity for coating on a backing material. The thickener can be an acrylic polymer thickener such as AMSCO 6038A (Unocal), methyl cellulose and hydroxypropyl-methyl cellulose. Plasticizers may be added to impart softness and flexibility to the adhesive, a typical , 2046~1 plasticizer being glycerin. Stabiliziers~ àdded to prevent degradation by heat and light and to improve aging characteristics, include polyvinylpyrolidone, Examples of formulations are shown below in Table 1.
Formulae 1-3 are adhesive formulations, Formula 4 is a reservoir formulation, and Formula 5 is a polymeric matrix formulation.
WO 90t098081`' ' ` ` -8- PCI-/US90/00805 204~921 Ul 5 I I I I ~ g r~ ~ ~ olo q~ .
U) o l ~o~
_l 1 ~ I I I o ~ o 1 c ~ 5~ ~ I I I I I I g I u~ o ~3 ~; ~ ~ _ E~
~ -'I
X
V V .rl V V ~ ~, ~ C Ll & C N
-- V X ~ ~
E~ ~n u~ u~ O O v E ~ r r v s C Y Y ~ " V ~ V V ~
2 ~ n ,~ c, ~' ~c 3 ~ O Q~
g ~ o ~ C
~ g O h ~ s ~ æ
~ a ~ o C~ S.l Q) ~ V ~ ~ 0~ ~ O ~
~ O ~V ~C ~ S ~ ~ C~ ~V ~ O
~ ~ O ~ U~ ~ ~ OS~ ~1 ~ .r~ ~a ,~ .
~1 --~ U) O Ul ~--1 h ~V
:~ C ~ C ~ U~ O 0 7 ~ ~, ,5, z ~ 3 I ~ . 20~6921 ) 90/09808 -9- ' - PC~r/US9~/00805 The transdermal nicotine patch described herein can be in any conventional patch form, such as a polymeric matrix type, a reservoir type or an adhesive type, with the adhesive type being preferred.
As shown in each of the Figures, an impermeable -backing layer 10 is typically included to render the contents of the patch impervious to the outside environment during use. Suitable components for use as an impermeable backing material include such materials as foam, metal foili polyester, low density polyethylene, copolymers of vinyl chloride and polyvinylidene chloride (e.g. Saran), and laminates thereof. A preferred backing material is a metallized plastic such as metallized polypropylene.
A protective release liner 17, also shown in each of the figures, i- typically included. The release liner is removed prior to application and use; it is typically present to protect the patch, e.g. by preventing dirt from sticking to the patch adhesive during shipment and storage. Examples of materials suitable for release 1iners are polyethylene and polyethylene-coated paper, preferably silicon-coated to facilitate removal.
The patch shown in cross-section in Figure 1 exemplifies an adhesive/nicotine/antipruritic combination 11 applied to the backing layer during manufacture. The combination 11 may also include therein other components such as a polymeric matrix-forming material.
The patch exemplified in Figure 2 illustrates elements of a a matrix-type patch, wherein distinct portions of the patch contain the active ingredient and the adhesive; the matrix 19 comprises the nicotine or salt or solvate thereof and an antipruritic compound, which is separated from the backing layer 10 by a paper foil baseplate 18 and an absorbant pad 13. The baseplate WO90/09808 2 ~ ~ 6 9 2 1 -lo- PCTtUS90/00805 18 prevents the migration of the active into the absorbant pad 13, while the pad absorbs moisture from the adhesive, which in turn absorbs moisture from the skin.
The adhesive 16 is peripheral to the matrix and keeps the matrix in contact with the skin surface. The patch preferably also comprises a release liner covering the adhesive, the drug matrix and the baseplate.
~ igure 3 shows a cross-section of a reservoir type patch wherein a reservoir 12 is formed, which reservoir contains the nicotine/antipruritic combination and may also contain one or more additional components such as preservatives or thickeners. A rate-controlling membrane 14 may be included to effect controlled release of the nicotine/antipruritic from the patch.
Alternatively, the nicotine may be contained in a distinct section of the patch such as reservoir 12, and the antipruritic may be contained in a separate layer 15 when it is not desirable to mix the two components.
Materials suitable for rate-controlling membranes include ethylene-vinyl acetate (EVA) copolymer membranes (e.g. 1-20% vinyl acetate), polyvinylalcohol (PVA) gels and silicone films.
The adhesive, poly~eric and reservoir patches are all made by methods well known in the art.
The transdermal nicotine patch is used by simply removing the protective layer to expose the adhesive surface, and applying the patch to the skin of a patient in need of such treatment so that the patch adheres to the skin.
Transdermal delivery of an effective amount of nicotine thereby occurs over an extended period of time. The patch described herein provides adequate serum levels of nicotine which are useful for a period of from about 4 to about 24 hours, after which the patch is replaced. Preferably the patch is used for about 12 to 24 hours and then replaced.
. .
20~6921 ~'~0/09808 ~ PCT/US90/00805 Effectiveness of the antipruritic in the transdermal nicotine patch is measured in terms of reduced itching as noted from the data below in Table 2. An adhesive-type transdermal nicotine patch comprising nicotine and bisabolol was used to test -itching in patients. The concentration of antipruritic and nicotine was varied, and the number of patients complaining of itching was evaluated, along with the severity of the itching experienced.
WO 90/09808 20 4~9~ -12- PCI`/US90/00805 O ~r c~ ~ ~
O æ o ~ _ O _ _ o o -~ o _~
c .~
~1 ~c ~ ~ ~ r~ _ ~ ~. ~ ~ ~.
nl ~- ~
:n S
~ ~ t) 0 o7 W
h ~ _ _ r ~ ~ c~
~ ~ ~
O ~n) .
0 dO
m'' O O o ~ g O ~ O dO _~
~ ~ i O
S C
~V ~
0 S~ ~ ~
~.~ G~
dP dP d~ ~ dP dP OP dP oO ~ V
O O O ~ O O O O O O ~~ O
Z ~ ~ -~ V ~ ~ ~ ~ _ _ ~ ~1-~ C
~ ~ O ~ ~
2o~692l ~'~90/Og808 -13- PCT/US90/00805 As is seen from Table 2 a~ove','thè~ formulations containing 0.5 to 1 percent ~(-)bisabolol caused fewer itching side effects than those without the antipruritic, and also fewer side effects than those patches which contain 5 to 10 percent of the antipruritic.
Additionally, severity of the itching side effect is greatly reduced in the formulations containing 0.5 to 1 percent antipruritic. ~ence it is concluded that a transdermal nicotine patch containing ~(-)bisabolol is effective in treating nicotine withdrawal symptoms with a minimum of adverse itching side effects.
While certain specific embodiments of the transdermal nicotine patch have been described herein, numerous modifications are possible and within the scope of the invention. Consequently, interpretation of the claims is not to be limited thereby.
DEVI CE FOR THE
. ~ ~
TRANSDERMAL DELIVERY OF NICOTINE
BACKGROUND OF THE INVENTION
This invention relates to a transdermal drug delivery patch, in particular, a patch useful for the transdermal delivery of nicotine. The patch is useful in that it delivers an amount of nicotine which achieves a physiological effect, curbing the urge to smoke tobacco, and thus easing the physiological symptoms of nicotine withdrawal.
A long felt need has existed in the medical art for a transdermal nicotine patch. In the past, nicotine has been administered orally, for example by chewing a resin gum containing nicotine such as that sold commercially under the trade name NICORETTE.
Several transdermal nicotine products have recently been disclosed. One such transdermal delivery device is disclosed by Lohmann & Co. GmbH in WO 8801-516-A, filed August 28, 1986. Lohmann describes a controlled release transdermal delivery system with an active substance, e.g., nicotine, in a depot formed by a reservoir contained between an adhesive layer and a backing layer. A dispersion device is connected to the depot which is spatially defined from the matrix.
Von Tilly, Ger. Offen. DE 3,438,284 similarly discloses a nicotine-reservoir containing transdermal preparation which is alleged to deliver approximately 20 to 30 ~g/day from a 10/20 cm2 patch.
Rose, et al. I~Transdermal nicotine reduces cigarette craving and nicotine preference", Clin.
Phar~,acol. Ther., Vol. 38, No. 4, pp 450-456 (Oct., 1985) discloses that transdermal nicotine base (8 mg) applied -in 30 percent aqueous solution under a polyethylene patch was helpful in reducing the urge to smoke tobacco.
It has been determined that a relatively constant nicotine blood level may help to curb the urge to smoke. Hence, one objective of the invention is to provide a transdermal nicotine patch which will deliver nicotine transdermally over an extenced perioc of time, e.g., 16 to 24 hours. ~ further objective is to provide a trans2ermal nicotine patch which causes a minimum of local pruritis or discom~ort where applied and worn on the skin. These obiectives, as well as others, will become more readily apparent from the following detailed description taken in conjunction with the drawings wherein:
Fig. 1 is a cross-sectional schematic view of a transdermal nicotine patch in an adhesive matrix form;
Fig. 2 is a cross-sectional view of an alternative embodiment of a transdermal nicotine patch, i.e., a polymeric matrix patch; and Fig. 3 is a cross-sectional view of a seconu alternative embodiment of a transdermal nicotine patch, i.e., a reservoir patch.
During testing of the transaermal nicotine patch describec herein, it was ~iscovered that nicotine delivered trans~ermally causes severe pruritis with practically no local erythema or inflammation. This pruritic reaction appears to be a pharmacological response to nicotine rather than a component of a general inflammatory reaction, since little if any erythema or inflammation are observed.
204~92~
~90/09808 3 ~ T/US90/00805 SUMMARY OF THE INVENTION
A transdermal nicotine patch is disclosed, comprising (a) an amount of nicotine or a salt or solvate thereof effective for treating the s~mptoms associated with tobacco smoking cessation, said nicotine to be transdermally delivered to a patient in need of such treatment and (b) an effective amount of a topical antipruritic. A preferred antipruritic is bisabolol, in an amount ranging from about 0.10 to about 2 percent of the total weight of the nicotine, antipruritic and carrier.
The transdermal patch may comprise an adhesive matrix, a reservoir or a polymeric matrix for containing the nicotine and/or antipruritic, and the transdermal patch preferably further comprises an easily removed release liner to protect the patch prior to application, and may further comprise a rate-limiting membrane.
The invention further includes a method of treating the urge to smoke tobacco and/or nicontine withdrawal, which method comprises transdermally delivering to a patient in need of such treatment an effective amount of nicotine in combination with the topical or transdermal use of an antipruritic such as bisabolol.
DETAILED DESCRIPTION
The invention described herein involves in its preferred embodiment the incorporation in a transdermal device for administering nicotine and at least one antipruritic compound useful for reducing or eliminating itching caused by the transdermal penetration of nico~ine.
The active ingredient in the patch described herein is nicotine or a pharmacologically and W090/09808 2 0 ~ 6 9 2 1 PCT/US90/00805 pharmaceutically acceptable salt or solvate thereof.
Typical salts and solvates include the hydrochlor~ide, dihydrochloride, sulfate, tartrate, bitartarate, zinc chloride double salt monohydrate and salicylate. The concentration of nicotine in the patch generally ranges from about 5 to about 40 percent of the total weight o~
the nicotine, antipruritic and carrier (e.g., the weight of the adhesive matrix, the polymeric matrix or the contents of the reservoir, but not including the weight of the backing material, release liner or rate controlling membrane) on a (w/w) basis. The preferred active ingredient is nicotine free base, and the preferred concentration of active ingredient is about 10 to about 20%.
The antipruritic used in the transdermal nicotine patch is included to counter the pruritic effects experienced when delivering nicotine transdermally. As such, it is referred to herein as the antipruritic, rather than as the nactive ingredient" even though it is clearly "active" in the sense that it reduces itching. The antipruritic is without pharmacological effect with respect to the nicotine withdrawal symptoms that are being treated.
One such preferred antipruritic compound is bisabolol, also known as 2-(4-methyl-3-cyclohexenyl)-6-methyl-5-hepten-2-ol, and more preferably a(-)bisabolol. Such a compound has not previously been used to effectuate the transdermal delivery of drugs, and in particular, nicotine, although it has been used as a cosmetic adjuvant. It is commercially available from BASF ~yandotte Corp., Parsippany, NJ. a(-)bisabolol is present in an amount ranging from about 0.10 to about 2%, more preferably about 0.1 to about 1% of the total weight of the nicotine, antipruritic and carrier.
, . 204~921 Examples of topical antipruritics effective in reducing itching during transdermal nicotine delivery other than bisabolol, mentioned above, are oil of chamomile, chamazulene, allantoin, D-panthenol glycyrrhetenic acid, corticosteroids, antihistamines, and combinations thereof. ANTIPHLOGISTICUM "ARO", commercially available from Novarom GmbH, Holzminder, Germany, comprising a combination of 18-B-glycyrrhetenic acid and D-panthenol, is a particularly useful combination.
Other ingredients useful in preparing the carrier for the transdermal nicotine patches described herein include conventional adhesives, solvents, co-solvents, plasticizers, polymeric matrices, stabilizers, thickeners, preservatives, etc.
Examples of pharmaceutically acceptable pressure sensitive adhesives useful in delivery devices for nicotine include acrylic, silicone, vinyl acetate and synthetic or natural rubber adhesives as well as other adhesives useful in transdermal drug delivery. The adhesives may be .used alone or in combination to prepare an adhesive drug matrix or may be applied to the skin-contacting surface of a polymeric matrix or reservoir patch to adhere said patch to the skin. Examples of-adhesives are acrylic adhesives such as RA 2484, RA 2333, RA 2397, R 363 and R 362 from Monsanto Co. Other acrylic adhesives, such as Durotak, manufactured by ~lorton Thiokol, Inc., and Neocryl XA5210 by Polyvinyl Chemicals, Ltd. may be utilized. Vinyl acetate adhesives include Flexcryl-161~, 1617, 1618 and 1625 from Air Products.
Numerous silicone based adhesives may be used, such as Q72929, Q27406, X72920 and 355, each manufactured by Dow-Corning. Natural and synthetic rubbers include polyisobutylenes, neoprenes, polybutadienes and polyisoprenes.
: 2ff~`69~1 WO90/09808 6 PCT/US90/0080~ -Polymeric matrix-forming agents include pharmaceutically acceptab~e-polymers such-as polyvinyl alcohol, polyvinylpyrolidones, gelatin and partially hydrolyzed polyvinyl alcohols.
Examples of solvents useful for effecting the transdermal delivery of nicotine include aqueous and organic solvents. As used herein the term solvent differs from the term co-solvent only in the most general sense. A co-solvent is a liquid which generally is a non-solvent, in which the active ingredient becomes soluble upon the addition of a small amount of a true solvent. Water is a typical solvent used in the transdermal nicotine patch. Polar organic solvents, such as ethanol, may also be useful.
Co-solvents useful in the transdermal nicotine patch include, for example, mineral oil, silicone-based liquids, and low molecular weight polyisobutylenes.
Suitable preservatives, antioxidants and chelating agents can be included in the transdermal nicotine patch, such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfate, a-tocopherol, maleic acid, ethylenediaminetetraacetic acid (EDTA), and cysteine hydrochloride.
Components useful for~imparting the desired wear and pharmacokinetic characteristics to the transdermal nicotine patch include, for example, polymeric matrix-forming materials added to facilitate curing of the adhesives, for example Aerotex Resin 3730 (American Cyanamid) and a thickener may be added to adjust the viscosity of the polymer mixture to the desired viscosity for coating on a backing material. The thickener can be an acrylic polymer thickener such as AMSCO 6038A (Unocal), methyl cellulose and hydroxypropyl-methyl cellulose. Plasticizers may be added to impart softness and flexibility to the adhesive, a typical , 2046~1 plasticizer being glycerin. Stabiliziers~ àdded to prevent degradation by heat and light and to improve aging characteristics, include polyvinylpyrolidone, Examples of formulations are shown below in Table 1.
Formulae 1-3 are adhesive formulations, Formula 4 is a reservoir formulation, and Formula 5 is a polymeric matrix formulation.
WO 90t098081`' ' ` ` -8- PCI-/US90/00805 204~921 Ul 5 I I I I ~ g r~ ~ ~ olo q~ .
U) o l ~o~
_l 1 ~ I I I o ~ o 1 c ~ 5~ ~ I I I I I I g I u~ o ~3 ~; ~ ~ _ E~
~ -'I
X
V V .rl V V ~ ~, ~ C Ll & C N
-- V X ~ ~
E~ ~n u~ u~ O O v E ~ r r v s C Y Y ~ " V ~ V V ~
2 ~ n ,~ c, ~' ~c 3 ~ O Q~
g ~ o ~ C
~ g O h ~ s ~ æ
~ a ~ o C~ S.l Q) ~ V ~ ~ 0~ ~ O ~
~ O ~V ~C ~ S ~ ~ C~ ~V ~ O
~ ~ O ~ U~ ~ ~ OS~ ~1 ~ .r~ ~a ,~ .
~1 --~ U) O Ul ~--1 h ~V
:~ C ~ C ~ U~ O 0 7 ~ ~, ,5, z ~ 3 I ~ . 20~6921 ) 90/09808 -9- ' - PC~r/US9~/00805 The transdermal nicotine patch described herein can be in any conventional patch form, such as a polymeric matrix type, a reservoir type or an adhesive type, with the adhesive type being preferred.
As shown in each of the Figures, an impermeable -backing layer 10 is typically included to render the contents of the patch impervious to the outside environment during use. Suitable components for use as an impermeable backing material include such materials as foam, metal foili polyester, low density polyethylene, copolymers of vinyl chloride and polyvinylidene chloride (e.g. Saran), and laminates thereof. A preferred backing material is a metallized plastic such as metallized polypropylene.
A protective release liner 17, also shown in each of the figures, i- typically included. The release liner is removed prior to application and use; it is typically present to protect the patch, e.g. by preventing dirt from sticking to the patch adhesive during shipment and storage. Examples of materials suitable for release 1iners are polyethylene and polyethylene-coated paper, preferably silicon-coated to facilitate removal.
The patch shown in cross-section in Figure 1 exemplifies an adhesive/nicotine/antipruritic combination 11 applied to the backing layer during manufacture. The combination 11 may also include therein other components such as a polymeric matrix-forming material.
The patch exemplified in Figure 2 illustrates elements of a a matrix-type patch, wherein distinct portions of the patch contain the active ingredient and the adhesive; the matrix 19 comprises the nicotine or salt or solvate thereof and an antipruritic compound, which is separated from the backing layer 10 by a paper foil baseplate 18 and an absorbant pad 13. The baseplate WO90/09808 2 ~ ~ 6 9 2 1 -lo- PCTtUS90/00805 18 prevents the migration of the active into the absorbant pad 13, while the pad absorbs moisture from the adhesive, which in turn absorbs moisture from the skin.
The adhesive 16 is peripheral to the matrix and keeps the matrix in contact with the skin surface. The patch preferably also comprises a release liner covering the adhesive, the drug matrix and the baseplate.
~ igure 3 shows a cross-section of a reservoir type patch wherein a reservoir 12 is formed, which reservoir contains the nicotine/antipruritic combination and may also contain one or more additional components such as preservatives or thickeners. A rate-controlling membrane 14 may be included to effect controlled release of the nicotine/antipruritic from the patch.
Alternatively, the nicotine may be contained in a distinct section of the patch such as reservoir 12, and the antipruritic may be contained in a separate layer 15 when it is not desirable to mix the two components.
Materials suitable for rate-controlling membranes include ethylene-vinyl acetate (EVA) copolymer membranes (e.g. 1-20% vinyl acetate), polyvinylalcohol (PVA) gels and silicone films.
The adhesive, poly~eric and reservoir patches are all made by methods well known in the art.
The transdermal nicotine patch is used by simply removing the protective layer to expose the adhesive surface, and applying the patch to the skin of a patient in need of such treatment so that the patch adheres to the skin.
Transdermal delivery of an effective amount of nicotine thereby occurs over an extended period of time. The patch described herein provides adequate serum levels of nicotine which are useful for a period of from about 4 to about 24 hours, after which the patch is replaced. Preferably the patch is used for about 12 to 24 hours and then replaced.
. .
20~6921 ~'~0/09808 ~ PCT/US90/00805 Effectiveness of the antipruritic in the transdermal nicotine patch is measured in terms of reduced itching as noted from the data below in Table 2. An adhesive-type transdermal nicotine patch comprising nicotine and bisabolol was used to test -itching in patients. The concentration of antipruritic and nicotine was varied, and the number of patients complaining of itching was evaluated, along with the severity of the itching experienced.
WO 90/09808 20 4~9~ -12- PCI`/US90/00805 O ~r c~ ~ ~
O æ o ~ _ O _ _ o o -~ o _~
c .~
~1 ~c ~ ~ ~ r~ _ ~ ~. ~ ~ ~.
nl ~- ~
:n S
~ ~ t) 0 o7 W
h ~ _ _ r ~ ~ c~
~ ~ ~
O ~n) .
0 dO
m'' O O o ~ g O ~ O dO _~
~ ~ i O
S C
~V ~
0 S~ ~ ~
~.~ G~
dP dP d~ ~ dP dP OP dP oO ~ V
O O O ~ O O O O O O ~~ O
Z ~ ~ -~ V ~ ~ ~ ~ _ _ ~ ~1-~ C
~ ~ O ~ ~
2o~692l ~'~90/Og808 -13- PCT/US90/00805 As is seen from Table 2 a~ove','thè~ formulations containing 0.5 to 1 percent ~(-)bisabolol caused fewer itching side effects than those without the antipruritic, and also fewer side effects than those patches which contain 5 to 10 percent of the antipruritic.
Additionally, severity of the itching side effect is greatly reduced in the formulations containing 0.5 to 1 percent antipruritic. ~ence it is concluded that a transdermal nicotine patch containing ~(-)bisabolol is effective in treating nicotine withdrawal symptoms with a minimum of adverse itching side effects.
While certain specific embodiments of the transdermal nicotine patch have been described herein, numerous modifications are possible and within the scope of the invention. Consequently, interpretation of the claims is not to be limited thereby.
Claims (9)
1. An adhesive, polymeric matrix or reservoir transdermal delivery patch for the controlled release of nicotine comprising an amount of nicotine or a pharmaceutically acceptable salt or solvate thereof effective to treat symptoms associated with tobacco smoking cessation and an amount of an antipruritic effective to treat the pruritis associated with transdermal delivery of nicotine, in a pharmaceutically acceptable carrier.
2. A transdermal patch of claim 1 wherein the salts and solvates of nicotine are selected from the group consisting of the hydrochloride, dihydrochloride, sulfate, tartrate, bitartarate, zinc chloride double salt monohydrate and salicylate.
3. A transdermal patch of claim 1 or 2 wherein the nicotine or salt or solvate thereof comprises 5 to 40% of the total weight of the nicotine or salt or solvate thereof, antipruritic and carrier.
4. A transdermal patch of claim 1,2, or 3 wherein the antipruritic is selected from the group consisting of bisabolol, oil of chamomile, chamazulene, allantoin, D-panthenol, glycyrrhetenic acid, corticosteroids and antihistamines.
5. A transdermal patch of claims 1-3 wherein the antipruritic is .alpha.(-)bisabolol and wherein .alpha.(-)bisabolol comprises about 0.1 to about 2% of the total weight of the nicotine or salt or solvate thereof, .alpha.(-)bisabolol and carrier.
6. A transdermal patch of claims 1-5 wherein the carrier comprises a pharmaceutically acceptable pressure sensitive adhesive selected from the group consisting of acrylic, silicone and polyisobutylene adhesive.
7. A transdermal patch of claims 1-5 wherein the carrier comprises a polymeric-matrix forming agent.
8. An adhesive transdermal patch of claims 1 or 6 comprising 20% nicotine free base and 1% .alpha.(-)bisabolol, and wherein the carrier comprises 71.5% acrylic pressure sensitive adhesive, 4% water, 2.5% butylated hydroxyanisole and 1% acrylic polymer thickner.
9. A method for treating the symptoms associated with tobacco smoking cessation comprising applying a transdermal patch of claims 1 or 8 to the skin of a human in need of such treatment.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/313,103 US4908213A (en) | 1989-02-21 | 1989-02-21 | Transdermal delivery of nicotine |
| US313,103 | 1989-02-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2046921A1 true CA2046921A1 (en) | 1990-08-22 |
Family
ID=23214398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002046921A Abandoned CA2046921A1 (en) | 1989-02-21 | 1990-02-20 | Device for the transdermal delivery of nicotine |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US4908213A (en) |
| EP (2) | EP0384386A1 (en) |
| JP (1) | JPH04503357A (en) |
| AU (1) | AU5106890A (en) |
| CA (1) | CA2046921A1 (en) |
| WO (1) | WO1990009808A1 (en) |
Families Citing this family (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU682813B2 (en) * | 1988-06-14 | 1997-10-23 | Alza Corporation | Subsaturated transdermal delivery device |
| NZ237241A (en) * | 1990-03-02 | 1993-11-25 | Pharmetrix Corp | Method for increasing the storage stability of physostigmine |
| US5130139A (en) * | 1990-07-06 | 1992-07-14 | Alza Corporation | Reduction or prevention of skin irritation by drugs |
| US5160741A (en) * | 1990-07-06 | 1992-11-03 | Alza Corporation | Reduction or prevention of skin irritation by drugs |
| US5135753A (en) * | 1991-03-12 | 1992-08-04 | Pharmetrix Corporation | Method and therapeutic system for smoking cessation |
| US5486362A (en) * | 1991-05-07 | 1996-01-23 | Dynagen, Inc. | Controlled, sustained release delivery system for treating drug dependency |
| US5403595A (en) * | 1991-05-07 | 1995-04-04 | Dynagen, Inc. | Controlled, sustained release delivery system for smoking cessation |
| TW221970B (en) * | 1991-06-26 | 1994-04-01 | Tbs Lab Inc | |
| 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 |
| US5780051A (en) * | 1992-04-02 | 1998-07-14 | Dynagen, Inc. | Methods and articles of manufacture for nicotine cessation and monitoring nicotine use |
| JPH08502727A (en) * | 1992-08-25 | 1996-03-26 | シグナス セラピューティック システムズ | Printed transdermal drug delivery device |
| DE4230588C1 (en) * | 1992-09-12 | 1993-10-07 | Lohmann Therapie Syst Lts | Dexpanthenol-containing plaster for the transdermal application of steroid hormones and process for its production |
| US5762952A (en) * | 1993-04-27 | 1998-06-09 | Hercon Laboratories Corporation | Transdermal delivery of active drugs |
| US5549906A (en) * | 1993-07-26 | 1996-08-27 | Pharmacia Ab | Nicotine lozenge and therapeutic method for smoking cessation |
| US5362496A (en) * | 1993-08-04 | 1994-11-08 | Pharmetrix Corporation | Method and therapeutic system for smoking cessation |
| US5547681A (en) * | 1994-07-14 | 1996-08-20 | Union Carbide Chemicals & Plastics Technology Corporation | Dermal patch |
| US5716635A (en) * | 1995-07-19 | 1998-02-10 | M. E. Cody Products, Inc. | Plantago major transdermal patch for use in treating a tobacco or nicotine habit |
| US5730721A (en) * | 1996-01-25 | 1998-03-24 | Vesture Corporation | Medical applicator and method |
| SE9703458D0 (en) * | 1997-09-25 | 1997-09-25 | Pharmacia & Upjohn Ab | Nicotine compositions and methods of formulation thereof |
| US6063401A (en) * | 1998-05-06 | 2000-05-16 | M.E. Cody Products, Inc. | Plantago major and hypericum perforatum compound for use in treating a tobacco or nicotine habit |
| US6045825A (en) | 1998-06-17 | 2000-04-04 | M. E. Cody Products, Inc. | Plantago major and Piper methysticum compound for use in treating a tobacco or nicotine habit |
| DE19833177A1 (en) * | 1998-07-23 | 2000-01-27 | Labtec Gmbh | Rapidly acting plaster preparation for treating irritation due to nettle stings or insect bites, preferably containing menthol and benzocaine |
| KR100603168B1 (en) * | 1998-12-18 | 2006-07-24 | 알자 코포레이션 | Transparent transdermal nicotine delivery devices |
| US6242473B1 (en) | 1999-01-08 | 2001-06-05 | Maxim Pharmaceuticals, Inc. | Treatment and prevention of reactive oxygen metabolite-mediated cellular damage |
| US6270781B1 (en) | 1999-01-08 | 2001-08-07 | Maxim Pharmaceuticals, Inc. | Method and compositions for topical treatment of damaged tissue using reactive oxygen metabolite production or release inhibitors |
| US6682757B1 (en) * | 2000-11-16 | 2004-01-27 | Euro-Celtique, S.A. | Titratable dosage transdermal delivery system |
| US6479076B2 (en) * | 2001-01-12 | 2002-11-12 | Izhak Blank | Nicotine delivery compositions |
| CA2461661A1 (en) * | 2001-10-19 | 2003-05-01 | Maxim Pharmaceuticals, Inc. | Use of histamine to treat liver disease |
| JP2005508366A (en) * | 2001-11-06 | 2005-03-31 | マキシム ファーマシューティカルス，インコーポレイテッド | Composition for the treatment of infectious diseases |
| CA2733212C (en) * | 2002-08-22 | 2014-01-07 | Nutrition 21, Inc. | Arginine silicate inositol complex and use thereof |
| US20040086551A1 (en) * | 2002-10-30 | 2004-05-06 | Miller Kenneth J. | Fentanyl suspension-based silicone adhesive formulations and devices for transdermal delivery of fentanyl |
| US8758804B2 (en) * | 2002-11-05 | 2014-06-24 | Fadim S.R.L. | Controlled and continued delivery of rifaximin and/or other substances |
| US20050037194A1 (en) * | 2003-08-15 | 2005-02-17 | Kimberly-Clark Worldwide, Inc. | Thermoplastic polymers with thermally reversible and non-reversible linkages, and articles using same |
| DE10353629A1 (en) * | 2003-11-17 | 2005-06-16 | Lts Lohmann Therapie-Systeme Ag | Device for the transdermal administration of active substances |
| US20050171192A1 (en) * | 2003-12-11 | 2005-08-04 | Gehlsen Kurt R. | Use of histamine to treat bone disease |
| US20060002913A1 (en) * | 2004-06-22 | 2006-01-05 | Gehlsen Kurt R | Use of histamine and related compounds to treat disorders affecting muscle function |
| US7399493B2 (en) * | 2004-07-16 | 2008-07-15 | Wille John J | Anti-irritant botanicals |
| US8252321B2 (en) | 2004-09-13 | 2012-08-28 | Chrono Therapeutics, Inc. | Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like |
| CA2580329C (en) | 2004-09-13 | 2015-01-06 | Chrono Therapeutics Inc. | Biosynchronous transdermal drug delivery |
| WO2006066244A2 (en) | 2004-12-17 | 2006-06-22 | Cash Alan B | Method for extending lifespan and delaying the onset of age-related disease |
| US20070042026A1 (en) * | 2005-03-17 | 2007-02-22 | Wille John J | Prophylactic and therapeutic treatment of topical and transdermal drug-induced skin reactions |
| EP3056200B1 (en) | 2005-05-23 | 2023-09-06 | President and Fellows of Harvard College | Huperzine for use in treating seizure |
| WO2006127905A2 (en) | 2005-05-24 | 2006-11-30 | Chrono Therapeutics, Inc. | Portable drug delivery device |
| JP5000932B2 (en) * | 2005-06-21 | 2012-08-15 | 日東電工株式会社 | Nicotine-containing transdermal preparation |
| DE102005033543A1 (en) * | 2005-07-14 | 2007-01-18 | Grünenthal GmbH | A fragrance-containing transdermal therapeutic system |
| US20070098772A1 (en) * | 2005-09-23 | 2007-05-03 | Westcott Tyler D | Transdermal norelgestromin delivery system |
| EP2308480B1 (en) | 2005-09-23 | 2014-08-13 | ALZA Corporation | High Enhancer-Loading Polyacrylate Formulation for Transdermal Applications |
| US7888422B2 (en) * | 2005-11-09 | 2011-02-15 | Mylan Technologies Inc. | Long-wearing removable pressure sensitive adhesive |
| US20090246264A1 (en) * | 2005-12-08 | 2009-10-01 | Fertin Pharma | Transdermal Tobacco Alkaloid Patch |
| JP5010829B2 (en) * | 2005-12-28 | 2012-08-29 | 帝國製薬株式会社 | Patch |
| JP4769575B2 (en) * | 2005-12-28 | 2011-09-07 | 帝國製薬株式会社 | Patch and method for producing the same |
| DE102006026060B4 (en) * | 2006-01-12 | 2013-01-31 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing as active ingredient nicotine and method for producing such systems |
| US20100197625A1 (en) | 2006-12-21 | 2010-08-05 | D Alarcao Marc | Synthetic lipophilic inositol glycans for treatment of cancer and glucose-metabolism disorders |
| DE112008001135A5 (en) * | 2007-06-08 | 2010-04-15 | Bayer Consumer Care Ag | Anti-inflammatory drug combinations for the treatment of diseases of the skin and mucous membranes |
| US9017301B2 (en) * | 2007-09-04 | 2015-04-28 | Mylan Technologies, Inc. | Transdermal drug delivery systems comprising a coated release liner |
| EP2328584A4 (en) * | 2008-09-04 | 2012-01-18 | Harvard College | Treatment of neurological disorders using huperzine |
| US9168232B2 (en) | 2009-09-07 | 2015-10-27 | Nipro Patch Co., Ltd. | Transdermally absorbable preparation |
| JP5412323B2 (en) * | 2010-02-26 | 2014-02-12 | 日東電工株式会社 | Patch preparation |
| JP5776079B2 (en) * | 2010-02-26 | 2015-09-09 | 日東電工株式会社 | Patch preparation containing bisoprolol |
| US20140017296A1 (en) * | 2011-04-04 | 2014-01-16 | Coloplast A/S | Adhesive Patch |
| WO2013006643A1 (en) | 2011-07-06 | 2013-01-10 | The Parkinson's Institute | Compositions and methods for treatment of symptoms in parkinson's disease patients |
| CN105073102B (en) | 2012-10-01 | 2018-06-19 | 香港科技大学 | Transdermal label apparatus |
| US10105487B2 (en) | 2013-01-24 | 2018-10-23 | Chrono Therapeutics Inc. | Optimized bio-synchronous bioactive agent delivery system |
| KR20160019944A (en) | 2013-06-13 | 2016-02-22 | 마이크로데믹스 인코퍼레이티드 | Metallic microneedles |
| US10213586B2 (en) | 2015-01-28 | 2019-02-26 | Chrono Therapeutics Inc. | Drug delivery methods and systems |
| AU2016228779A1 (en) | 2015-03-12 | 2017-09-07 | Chrono Therapeutics Inc. | Craving input and support system |
| US11191735B2 (en) | 2015-03-13 | 2021-12-07 | Nutrition 21, Llc | Arginine silicate for periodontal disease |
| US20170135969A1 (en) | 2015-11-12 | 2017-05-18 | Jds Therapeutics, Llc | Topical arginine-silicate-inositol for wound healing |
| JP2019526638A (en) | 2016-09-01 | 2019-09-19 | ジェイディーエス・セラピューティクス、エルエルシー | Magnesium biotinate composition and method of use |
| BR112019005581A2 (en) | 2016-09-22 | 2019-06-11 | B Cash Alan | Premenstrual Syndrome Symptom Relief Method |
| US11285306B2 (en) | 2017-01-06 | 2022-03-29 | Morningside Venture Investments Limited | Transdermal drug delivery devices and methods |
| DE102017104026A1 (en) | 2017-02-27 | 2018-08-30 | Lts Lohmann Therapie-Systeme Ag | Nicotine containing transparent transdermal therapeutic system |
| JP7420797B2 (en) | 2018-05-29 | 2024-01-23 | モーニングサイド ベンチャー インベストメンツ リミテッド | Drug delivery methods and systems |
| AU2019371825B2 (en) | 2018-11-02 | 2023-07-27 | Nutrition 21, Llc | Compositions containing inositol-stabilized arginine silicate complexes and inositol for improving cognitive function in video gamers |
| WO2021127048A1 (en) | 2019-12-16 | 2021-06-24 | Nutrition 21, Llc | Methods of production of arginine-silicate complexes |
| JP2024503435A (en) | 2021-01-14 | 2024-01-25 | アラン ビー． キャッシュ， | Treatment of pathological fatigue with oxaloacetate |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3438284A1 (en) * | 1984-10-16 | 1985-03-07 | Hans-Harald von 2400 Lübeck Tilly | Nicotine-containing depot plaster |
| US4597961A (en) * | 1985-01-23 | 1986-07-01 | Etscorn Frank T | Transcutaneous application of nicotine |
| DE3629304A1 (en) * | 1986-08-28 | 1988-03-24 | Lohmann Gmbh & Co Kg | TRANSDERMAL THERAPEUTIC SYSTEM, ITS USE AND METHOD FOR THE PRODUCTION THEREOF |
| IL86170A (en) * | 1987-05-01 | 1992-12-01 | Elan Transdermal Ltd | Preparations and compositions comprising nicotine for percutaneous administration |
| US4839174A (en) * | 1987-10-05 | 1989-06-13 | Pharmetrix Corporation | Novel transdermal nicotine patch |
-
1989
- 1989-02-21 US US07/313,103 patent/US4908213A/en not_active Expired - Fee Related
-
1990
- 1990-02-20 EP EP90103221A patent/EP0384386A1/en not_active Ceased
- 1990-02-20 AU AU51068/90A patent/AU5106890A/en not_active Abandoned
- 1990-02-20 WO PCT/US1990/000805 patent/WO1990009808A1/en not_active Application Discontinuation
- 1990-02-20 EP EP90903557A patent/EP0471668A1/en active Pending
- 1990-02-20 CA CA002046921A patent/CA2046921A1/en not_active Abandoned
- 1990-02-20 JP JP2503778A patent/JPH04503357A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO1990009808A1 (en) | 1990-09-07 |
| AU5106890A (en) | 1990-09-26 |
| US4908213A (en) | 1990-03-13 |
| JPH04503357A (en) | 1992-06-18 |
| EP0384386A1 (en) | 1990-08-29 |
| EP0471668A1 (en) | 1992-02-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4908213A (en) | Transdermal delivery of nicotine | |
| JP4511691B2 (en) | Matrix patch for transdermal administration | |
| US4690683A (en) | Transdermal varapamil delivery device | |
| KR100483476B1 (en) | A dual adhesive transdermal drug delivery system | |
| RU2449766C2 (en) | Composition for transcutaneous delivery of medication | |
| US6316022B1 (en) | Transdermal compositions containing low molecular weight drugs which are liquid at room temperatures | |
| JP5069402B2 (en) | Silicone-based adhesive formulation based on fentanyl suspension and device for transdermal delivery of fentanyl | |
| US5879701A (en) | Transdermal delivery of basic drugs using nonpolar adhesive systems and acidic solubilizing agents | |
| JP4629578B2 (en) | Percutaneous absorption preparation for treatment of eye diseases | |
| JPH04507256A (en) | Biphasic transdermal drug delivery device | |
| CA2233334A1 (en) | Transdermal administration of ropinirole and analogs thereof | |
| JPS63233916A (en) | Elastic transdermal drug supply device, composition of fatty acid ester/ether of alkanediol as transdermally absorption promoter and device | |
| KR20080077998A (en) | Method of transdermally administering an indole serotonin receptor agonist and transdermal compositions for use in the same | |
| JPH08502727A (en) | Printed transdermal drug delivery device | |
| JPH0424324B2 (en) | ||
| JP3525391B2 (en) | Surface stabilized preparations for skin application | |
| JP2004002465A (en) | Device for treatment of tobacco addiction | |
| CA2064845A1 (en) | Transdermal nitroglycerin patch with penetration enhancers | |
| WO2021037199A1 (en) | Transdermal amide local anesthetic-containing pharmaceutical composition and preparation method therefor | |
| WO2004019892A2 (en) | Drug delivery system for treating urinary incontinence | |
| KR100446416B1 (en) | Transdermal system for local anesthesia | |
| KR20020037616A (en) | Transdermal ketorolac formulation for increasing transdermal absorption of ketorolac | |
| KR20100095059A (en) | Transdermal formulation comprising sibutramine | |
| MXPA01000527A (en) | Transdermal patch and topical compositions comprising propylnorapomorphine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |