WO1993000057A1 - Procede et unite de dosage d'absorption de nicotine transdermique - Google Patents

Procede et unite de dosage d'absorption de nicotine transdermique Download PDF

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Publication number
WO1993000057A1
WO1993000057A1 PCT/US1992/005271 US9205271W WO9300057A1 WO 1993000057 A1 WO1993000057 A1 WO 1993000057A1 US 9205271 W US9205271 W US 9205271W WO 9300057 A1 WO9300057 A1 WO 9300057A1
Authority
WO
WIPO (PCT)
Prior art keywords
nicotine
dosage unit
transdermal
layer
skin
Prior art date
Application number
PCT/US1992/005271
Other languages
English (en)
Inventor
Chin-Chih Chiang
Jhili Wu
Original Assignee
Tbs Laboratories, Inc.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Tbs Laboratories, Inc. filed Critical Tbs Laboratories, Inc.
Publication of WO1993000057A1 publication Critical patent/WO1993000057A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A61K9/7061—Polyacrylates
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions

Definitions

  • This invention relates to a novel transdermal absorp ⁇ tion dosage unit adapted for administration of nicotine wherein adverse reaction in the skin at the site of the absorption, such as a reddening of the absorption site, caused by said transdermal administration of nicotine, is prevented or substantially reduced.
  • Incorporated into the dosage unit is an agent which is also transdermally absorbed, which reduces or prevents this adverse reaction to the transdermal absorption of nicotine.
  • Also preferably included in the dosage unit is an ingredient which increases skin wearability of the dosage units and desirably also reduces the amount of nicotine lost during the production of the dosage units and preferably a further ingredient is dis ⁇ persed in the dosage unit which will reduce any oxidation of nicotine during storage.
  • this invention relates to a method for reducing the desire by those persons who smoke or have smoked tobacco to continue that smoking habit.
  • Nicotine has been introduced into the body by various means, such as by oral administration. Also, cer ⁇ tain administration has been proposed by transdermal admin ⁇ istration of nicotine. However, there have been certain side-effects that have been caused by certain of these pro ⁇ posed means of nicotine administration by transdermal means, such as reddening of the skin at the absorption site.
  • transdermal dosage unit for administration of nicotine which would substantially reduce or prevent such side-effects. It would also be highly advisable and desired to have such improved transdermal dosage units for administration of nicotine which would provide an improved means to help a human subject to cease the habit of smoking tobacco.
  • transdermal nicotine absorption dosage unit which has the advantage of providing very substantial reduction or prevention of the side-effect of reddening of the skin site at which the nicotine is transdermally absorbed.
  • the nicotine transdermal dosage units of this invention comprise the following elements: 1) a backing layer substantially impervious to the ingre ⁇ histch of the dosage unit;
  • the nicotine be released from the dosage unit and transdermally absorbed on a continuous basis throughout a 24-hour period in order to provide consistent systemic levels of nicotine effective to reduce the desire for the subject to smoke.
  • the amount of salicylate ester, suitably methyl salicy ⁇ late, to be present in the dosage unit will vary depending upon the particular dosage unit, the length of time the dosage unit is designed for administering nicotine and other factors. Ordinarily, a continuously delivered amount of methyl salicylate in the range of about 5 mg to about 20 mg has been found effective and an amount presently preferred is i n the range of about 10 mg to about 15 mg per day.
  • isopropyl myristate and certain other agents providing the properties in the dosage units as provided by isopropyl myristate have increased or contributed to high wearability of the dosage units. It has been found that such agents as isopropyl myristate also provide the added property of reducing loss of nicotine through volatilization during the production of the transdermal dosage units of this invention.
  • this invention is a method to assist humans having the desire or craving to smoke caused by smoking or exposure to smoking to reduce the desire or craving to smoke and thus to assist in breaking the so- called smoking habit.
  • the backing layer can be made of any suitable material which is impermeable to the nicotine and other components dispersed within the adjacent adhesive layer or the optional polymer matrix layer.
  • the backing layer serves as a protec- tive cover for the dosage unit and provides also a support function.
  • the backing layer can be formed so that it is essentially the same size layer as the nicotine-containing layer or it can be of larger dimension so that it can extend beyond the side of the nicotine-containing layer or overlay the side or sides of the nicotine-containing layer and then can extend outwardly in a manner that the surface of the extension of the backing layer can be a base for an adhesive to hold the dosage unit in intimate contact with subjects being treated.
  • the composition containing the nicotine can readily be coated onto a nicotine impermeable backing layer such as a composite sold under the designation Scotch Pak 1109 by 3M Company.
  • a coating equipment unit can be used to coat the backing layer to the desired thickness.
  • a coater which can be used is the Warner-Mathis Laboratory Coater Type LTSV with built-in laboratory dryer LTF.
  • the thickness of the nicotine-adhesive layer can be accurately controlled to desired thickness such as to 400 microns, using such a designed coater-dryer.
  • the amount of nicotine added to the adhesive solution used for coating can vary so long as there is provided an effective amount of nicotine for transdermal absorption. Ordinarily it has been found that about a 5 percent amount of nicotine based upon the total weight of the coating ix- ture of adhesive, nicotine and isopropyl myristate, provides an effective amount of transdermal absorption of nicotine.
  • the amount of nicotine can be varied depending upon the rate of absorption desired, the particular adhesive or polymer material used in making the dosage unit and other factors.
  • the effective amount can be selected from a range of from about 1 to about 20 percent based upon the weight of the coating mixture used to make the dosage unit, a more prefer ⁇ able range being from about 3 to about 10 percent based on said weight.
  • the amount of methyl salicylate or other effective salicylate ester can also be varied so long as an effective amount is utilized to reduce greatly or eliminate the red ⁇ dening of the absorption site of nicotine from the trans- dermal dosage units. It has been found that an effective amount of a salicylate ester can be incorporated into the adhesive solution in making the adhesive layer or into the polymer mixture used in making a polymer matrix storage reservoir, if that is selected. It has been found prefer ⁇ able to use methyl salicylate, however, other effective and biocompatible esters can be selected such as other lower alkyl esters, such as ethyl salicylate, glycol salicylate, benzyl salicylate and the like esters.
  • a biocompatible agent for enhancing skin wearability of the dosage unit. It is preferable that said agent also reduces the amount of loss through volatilization of nicotine in the production of the transdermal dosage units.
  • isopropyl myristate It presently is preferred to use isopropyl myristate. Other agents providing the proper ⁇ ties of isopropyl myristate can also be used for this pur ⁇ pose.
  • Other effective agents can be selected as the skin wearability enhancer, for example, it can be selected from other effective and biocompatible fatty acid compounds such as other esters, alcohols and the like. Lauryl alcohol, diethyl tartrate, diethyl citrate and isopropyl adipate, have been found in illustration to be effective.
  • an anti- oxidant agent to preclude any substantial amount of oxida- tion of the nicotine of the dosage units. It has been found successful and effective to use such biocompatible anti- oxidant agents as BHT (butylated hydroxy toluene) and AAP
  • the amount utilized will vary as desired so long as there is an effective reduction or pre- vention of nicotine oxidation. It has been found suitable to utilize about one percent or an effective amount in the range of about 1 mg to about 8 mg and more preferably within
  • Examples of materials suitable for making the backing layer are films of high and low density polyethylene, poly ⁇ propylene, polyurethane, polyvinylchloride, polyesters such as poly(ethylene phthalate) , metal foils, metal foil lami ⁇ nates of such suitable polymer films, and the like.
  • the materials used for the backing layer are laminates of such polymer films with a metal foil such as aluminum foil. In such laminates, a polymer film of the laminate will usually be in contact with the adhesive layer.
  • the backing layer can be any appropriate thickness which will provide the desired protective and support functions. A suitable thickness will be from about 10 to about 200 microns.
  • the thickness will be from about 20 to about 150 microns, and preferably be from about 30 to about 100 microns.
  • the adhesive polymer used must be biologically acceptable and compatible with the nicotine and salicylate ester and other ingredients used.
  • Certain polyacrylic adhesive polymers (in the form of an alkyl ester, amide, free acid, or the like) are suitable and are presently preferred.
  • Illustrative of suitable poly- acrylic adhesives for use in making the adhesive layer are represented by the following formula:
  • x represents the number of repeating units suffi ⁇ cient to provide the desired properties in the adhesive polymer and R is H or lower alkyl including ethyl, butyl and 2-ethylhexyl.
  • hypoallergenic pressure-sensitive con ⁇ tact adhesive compositions can also be used.
  • a preferred adhesive layer is pressure-sensitive.
  • the adhesive means can extend in the form of a ring attached, for example, to an extended portion of the backing layer so that the adhesive layer is adjacent to the sidewall of the nicotine-containing disc layer.
  • the width of such adjacent adhesive ring must be adequate to hold the dosage unit securely to the subject being treated.
  • a suitable width of such adhesive ring can be about 0.1 to about 1.0 cm, preferably about 0.2 to about 0.8 cm.
  • a releasable protective film layer which is made from mate- rials which are substantially impermeable to nicotine, the salicylate ester, wearability enhancer, and any other compo- nents of the dosage unit.
  • the polymer materials and metal foil laminates used for the backing layer may also be used to make the protective layer, provided the layer is made strippable or releasable such as by applying conventional siliconizing or Teflon coating.
  • a suitable releasable mate- rial is Scotchpak 1022 material sold by the 3M Company or
  • poly- acrylic adhesive polymers as described above can also be used, such as sold under the designation Duro-Tak, and other biocompatible adhesive polymers which provide a stable environment for nicotine and the salicylate ester and permit their release, can suitably be used.
  • those polymers and adhesive polymers can be used to form the polymer matrix layer which are capable of forming thin walls or coatings through which nicotine and the salicylate ester are stable and can pass at desired controlled rates.
  • Suit ⁇ able polymers and adhesive polymers are biologically and pharmaceutically compatible, non-allergenic and insoluble in and compatible with body fluids or tissues with which the device is contacted.
  • soluble polymers are to be avoided since dissolution or erosion of the matrix would affect the release rate of the components as well as the capability of the dosage unit to remain in place for con ⁇ venience of removal.
  • the amount of the components used depends upon the dosage rate of nicotine and other components, especially the salicylate ester, and the duration of treatment desired in each dosage unit and the amount which can be incorporated into the polymer matrix layer to retain suitable structural, diffusion and other properties in the final polymer matrix layer. It has been found, for example, that nicotine can be satisfactorily added to the polymer used in making the poly ⁇ mer layer, such as polyacrylic adhesive polymer.
  • the nicotine and salicylate ester used in an amount of a selected adhe ⁇ sive polymer solution It has been found to be preferable to add and disperse the nicotine and salicylate ester used in an amount of a selected adhe ⁇ sive polymer solution.
  • the mixture of the polymer and com- ponents is then thoroughly mixed to form a homogeneous solu ⁇ tion or microdispersion of the nicotine in the polymer.
  • the composition can be subjected, if desired, to vacuum to remove any entrapped air.
  • the mixture is then applied as by solvent casting tech- nique, to a suitable substrate, like backing laminate or release liner or other suitable substrate as described above with regard to making the adhesive layer.
  • the polymer matrix sheet desirably is about 10 to 400 microns, prefer ⁇ ably about 20 to about 300 microns, in thickness.
  • the resulting polymer matrix sheet is removed from the casting machine and another layer of medicated polymer, can be further coated on the first medicated polymer layer formed by direct casting or lamination.
  • the dosage units either with or without the optional polymer matrix layer are then covered with a transparent low-adhesion release liner (e.g., Scotch-Pak 1022/3M) .
  • the completed dosage layers are then cut into dosage units having various shapes and sizes by using a specially- designed device cutter, such as a 10 cm 2 or 20 cm 2 rectangu ⁇ lar shape.
  • the dosage units can be tested for the effectiveness in protecting against skin irritation as caused by nicotine transdermal absorption.
  • An acute skin irritation test can be conducted. The results are expressed in a score in the Primary Dermal Irritation Index (PDII) .
  • the test is con ⁇ ducted by utilizing young female New Zealand white rabbits. The dosage units are applied to the skin of the rabbits and the absorption sites are observed during the test period for any occurrence of skin reddening.
  • the control dosage units utilizing a controlled amount of nicotine such as 5 percent showed no acute skin irritation upon a one-day testing.
  • the scoring system is as follows:
  • a composition for use in making dosage units of this invention is made by following the procedure described. An amount of 82.93 grams of material Duro-Tak solution (Duro-
  • Tak 80-1054 used is added to a 4 oz. Ouorpak bottle. To that solution there is also added to the bottle 4.04 grams of nicotine, 4.49 grams of isopropyl myristate, 8.09 grams of methyl salicylate and 0.4 grams of butylated hydroxy- toluene. The mixture is mixed for ten hours to obtain a homogeneous formulation.
  • the composition is coated on a backing layer.
  • the backing layer is made of Scotch Pak 1109 sold by 3M Corpora- tion.
  • the oven temperature of the coating machine is set at
  • a coating frame number 1 is installed onto the machine.
  • the Scotch Pak 1109 backing material is mounted on the coating frame of the machine and the position of the doctor knife is adjusted to provide a thickness of 400 microns onto the backing layer.
  • About 20 grams of the homogeneous formulation is poured onto the backing layer and the doctor knife is pulled toward the operator to coat a thin film of formulation upon the Scotch Pak backing layer.
  • the doctor knife is removed and the control button is activated to advance the coating frame into the drying chamber of the coating machine.
  • the frame holding the backing layer bearing the coating is automati- cally released from the drying chamber and the coated film is removed from the coating frame.
  • a coating frame number 2 is then installed into the coating machine.
  • Release liner material is mounted onto a coating frame number 2.
  • About 20 grams of the homogeneous nicotine formulation is poured upon the release liner and the doctor knife is pulled toward the operator to coat a thin film of the formulation upon the release liner.
  • the doctor knife is again removed and the controlling button is activated to advance the coating frame bearing the release liner having coated upon it the layer of formulation into the drying chamber.
  • the number 2 frame bearing the coated release layer is automatically released from the drying chamber of the coating machine.
  • the coating frame number 2 with the coated release liner is removed from the frame.
  • Coating frame number 1 bearing the backing layer with the nicotine coating layer is reinstalled into the machine with the nicotine coating facing upward. Also, the release liner with the coated formulation from coating frame number
  • the two layers then become laminated to provide a backing layer having adhered thereto the nicotine adhesive layer having 9 percent nicotine, 10 percent isopropyl myristate, 18 percent of methyl salicylate and 1 percent of butylated hydroxytoluene.
  • the final lami ⁇ nated layer then also has on the opposite side from the backing layer a release layer adhered to the adhesive nico ⁇ tine containing layer.
  • the laminated sheet containing a backing layer the nicotine adhesive layer and the release layer are formed into 5 cm or 10 cm transdermal dosage units by using a cutting press.
  • Chien et al. referred to herein above was used to evaluate the permeability of nicotine across human cadaver skin. Skin permeation flux measurements were made at 37°C. The nicotine concentration in the receptor medium (40% aqueous- polyethylene glycol solution) was measured at various time intervals. The skin flux or transmission of the nicotine through the cadaver skin was determined and calculated for various time intervals.
  • the skin permeation rate of nicotine is relatively high, for example, about 13 mcg/cm /hr from a polyacrylate adhesive matrix with 5% nicotine concentration. It was determined that the addition of certain of the ingredients, such as isopropyl myristate or methyl salicylate has little or no effect on the skin permeation rate of nicotine as shown in the following Table 1:
  • the addition of isopro ⁇ pyl myristate up to 20 percent did not substantially affect nicotine skin permeation.
  • the slight increase in nicotine skin permeation from the patch formulation containing 30% isopropyl myristate was the result of the protective proper ⁇ ty of isopropyl myristate to prevent nicotine from evapora ⁇ tion during the drying of the dosage unit sheets as described in Example 1 and the dilution result of isopropyl myristate to the polyacrylate adhesive matrix, causing a high nicotine diffusivity in a less viscous adhesive matrix.
  • the following experiments show that the nicotine con ⁇ centration can be varied from 2.5 to 10 percent.
  • Nicotine Skin micromol/5 cm 2 Flux (mcg/cm 2 /hr
  • Example 1 The dosage units made following the procedure of Example 1 which contain methyl salicylate with or without nicotine, placebo dosage units or active dosage units, respectively, were tested on six young female New Zealand white” rabbits to study the protective effect of salicylate ester against skin irritation (redenning) normally caused by nicotine transdermal absorption.
  • Table 4 shows the low amount of skin irritation of the dosage units of the invention having methyl salicylate in the Primary Dermal Irritation Index (PDII) .
  • Table 4 shows the low amount of skin irritation of the dosage units of the invention having methyl salicylate in the Primary Dermal Irritation Index (PDII) .
  • Table 4 shows the low amount of skin irritation of the dosage units of the invention having methyl salicylate in the Primary Dermal Irritation Index (PDII) .
  • Table 4 shows the low amount of skin irritation of the dosage units of the invention having methyl salicylate in the Primary Dermal Irritation Index (PDII) .
  • methyl salicylate containing dosage units showed little or no skin irritation at the various concentrations of nicotine.
  • the methyl sali ⁇ cylate containing dosage units showed substantially the same skin irritation level exhibited by placebo dosage units, in contrast to the positive control using the standard test material dinitrochlorobenzene in 95% ethanol solution.
  • the scoring system is as follows:
  • Dosage units were made containing different concentra ⁇ tions of isopropyl myristate.
  • the presence of isopropyl myristate and other like agents increase the wearability or adhesion of the dosage units upon the skin of the subject undergoing nicotine transdermal absorption.
  • isopropyl myristate reduces loss of nicotine during the production of the nicotine containing dosage units, such as those described in Example 1.
  • Dosage units made by the general procedure as described in Example 1 having a size of 5 cm were extracted with solvent to remove nicotine.
  • Dosage units containing no iso ⁇ propyl myristate and dosage units containing both the 10% nicotine and 20% isopropyl myristate were extracted to determine the amount of nicotine present and the protective effect of isopropyl myristate.
  • Table 6 shows that isopropyl myristate substantially improved the preven ⁇ tion of loss of nicotine during the preparation procedure for making the nicotine containing dosage units.
  • Formulation Ingredients Amount of Nicotine Recovered NCT IPM Polyacrylate (mg/5 cm 2 Patch)
  • Dosage units were made containing zero and various amounts of an antioxidant, ascorbic acid palmitate or buty ⁇ lated hydroxytoluene. Long term stability tests were car ⁇ ried out. These tests showed that at high storage te pera- tures nicotine was stabilized in the presence of butylated hydroxytoluene as compared to corresponding dosage unit containing no butylated hydroxytoluene.
  • Table 7 shows the loss of nicotine in the absence of the antioxi ⁇ dant butylated hydroxytoluene.
  • Corresponding dosage units were made incorporating 1% butylated hydroxytoluene based on the weight of the nicotine composition used to make up the nicotine containing adhesive layer. The following data show that presence of butylated hydroxytoluene acted to protect nicotine against oxidative degradation. Table 8. Recovery of Nicotine from Patches with 1% BHT.
  • the above dosage units are repeated using ethyl salicy- late or glycol salicylate as the anti-reddening agent.
  • the above dosage units can be made using other antioxidation agents, such as ascorbic acid palmitate and other wear ⁇ ability enhancers instead of isopropyl myristate, which provide the benefits of isopropyl myristate.
  • Effective and biocompatible nicotine salts, solvates and the like nicotine compounds which are transdermally absorbed can be used in making the dosage units described in the above Example.
  • other effective and biocompatible salicylate esters, isopropyl myristate substitutes, other bioacceptable antioxidants or other components can be used, so long as the resulting dosage units are effective and have the desired properties.
  • dosage units which comprise a backing layer-polymer matrix-adhesive- release liner: 1) Mount Scotch Pak 1109 on the coating frame and adjust the position of the doctor knife to provide a thickness of 400 microns (above the Scotch Pak) .
  • Scotch Pak from the machine and place it aside. 5) Install the coating frame No. 2 onto the machine.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
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  • General Health & Medical Sciences (AREA)
  • Dermatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne une unité de dosage transdermique permettant d'administrer de la nicotine afin de réduire le désir ou l'envie de fumer du tabac. L'unité de dosage réduit ou élimine sensiblement le rougissement de la peau au niveau du site d'absorption de nicotine, rougissement généralement associé à l'absorption transdermique de nicotine. L'invention concerne également une unité de dosage dans laquelle est incorporé un agent d'augmentation de l'aptitude de la peau à porter une unité de dosage transdermique. De plus, l'invention concerne un procédé de réduction du désir ou de l'envie d'un sujet à fumer du tabac en utilisant l'unité de dosage transdermique décrite par l'invention.
PCT/US1992/005271 1991-06-26 1992-06-24 Procede et unite de dosage d'absorption de nicotine transdermique WO1993000057A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US72112991A 1991-06-26 1991-06-26
US721,129 1991-06-26

Publications (1)

Publication Number Publication Date
WO1993000057A1 true WO1993000057A1 (fr) 1993-01-07

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PCT/US1992/005271 WO1993000057A1 (fr) 1991-06-26 1992-06-24 Procede et unite de dosage d'absorption de nicotine transdermique

Country Status (6)

Country Link
EP (1) EP0544900A4 (fr)
CN (1) CN1067811A (fr)
AU (1) AU2294192A (fr)
CA (1) CA2094913A1 (fr)
TW (1) TW221970B (fr)
WO (1) WO1993000057A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5603947A (en) * 1993-07-09 1997-02-18 Cygnus Terapeutic Systems Method and device for providing nicotine replacement therapy transdermally/transbuccally
US20060286160A1 (en) * 2005-06-21 2006-12-21 Shiro Satoda Nicotine transdermal delivery system
EP1774964A1 (fr) * 2005-10-13 2007-04-18 Nitto Denko Corporation Système therapeutique transdermique comprenant de nicotine et sa méthode de production
WO2011120704A1 (fr) * 2010-03-31 2011-10-06 Hexal Ag Timbre transdermique contenant du 17-désacétyl-norgestimate

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4933184A (en) * 1983-12-22 1990-06-12 American Home Products Corp. (Del) Menthol enhancement of transdermal drug delivery

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH672888A5 (fr) * 1986-11-07 1990-01-15 Mepha Ag
US4908213A (en) * 1989-02-21 1990-03-13 Schering Corporation Transdermal delivery of nicotine
DE4020144A1 (de) * 1990-06-25 1992-01-09 Lohmann Therapie Syst Lts Pflaster mit hohem gehalt an weichmachenden inhaltsstoffen

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4933184A (en) * 1983-12-22 1990-06-12 American Home Products Corp. (Del) Menthol enhancement of transdermal drug delivery

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP0544900A4 *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5603947A (en) * 1993-07-09 1997-02-18 Cygnus Terapeutic Systems Method and device for providing nicotine replacement therapy transdermally/transbuccally
US20060286160A1 (en) * 2005-06-21 2006-12-21 Shiro Satoda Nicotine transdermal delivery system
EP1736146A1 (fr) * 2005-06-21 2006-12-27 Nitto Denko Corporation Système de délivrance transdermal de nicotine
JP2007031427A (ja) * 2005-06-21 2007-02-08 Nitto Denko Corp ニコチン含有経皮吸収製剤
TWI412380B (zh) * 2005-06-21 2013-10-21 Nitto Denko Corp 尼古丁經皮傳輸系統
EP1774964A1 (fr) * 2005-10-13 2007-04-18 Nitto Denko Corporation Système therapeutique transdermique comprenant de nicotine et sa méthode de production
TWI383794B (zh) * 2005-10-13 2013-02-01 Nitto Denko Corp 尼古丁經皮吸收製劑及其製造方法
US8506991B2 (en) 2005-10-13 2013-08-13 Nitto Denko Corporation Nicotine transdermal preparation and production method thereof
KR101317053B1 (ko) * 2005-10-13 2013-10-11 닛토덴코 가부시키가이샤 니코틴 경피 제제 및 이의 제조 방법
WO2011120704A1 (fr) * 2010-03-31 2011-10-06 Hexal Ag Timbre transdermique contenant du 17-désacétyl-norgestimate
EP2377540A1 (fr) * 2010-03-31 2011-10-19 Hexal AG Timbre transdermique contenant du norgestimate 17-deacetyl

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Publication number Publication date
CN1067811A (zh) 1993-01-13
EP0544900A4 (en) 1993-12-01
EP0544900A1 (fr) 1993-06-09
TW221970B (fr) 1994-04-01
CA2094913A1 (fr) 1992-12-27
AU2294192A (en) 1993-01-25

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