WO2021224334A1 - Combinaison contenant deux médicaments contenant de la nicotine pour le traitement de la covid-19 - Google Patents

Combinaison contenant deux médicaments contenant de la nicotine pour le traitement de la covid-19 Download PDF

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Publication number
WO2021224334A1
WO2021224334A1 PCT/EP2021/061876 EP2021061876W WO2021224334A1 WO 2021224334 A1 WO2021224334 A1 WO 2021224334A1 EP 2021061876 W EP2021061876 W EP 2021061876W WO 2021224334 A1 WO2021224334 A1 WO 2021224334A1
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Prior art keywords
nicotine
drug
day
patient
combination
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Application number
PCT/EP2021/061876
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German (de)
English (en)
Inventor
Thomas Hille
Gerhard Ritzdorf
Original Assignee
Lts Lohmann Therapie-Systeme Ag
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Publication of WO2021224334A1 publication Critical patent/WO2021224334A1/fr

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Classifications

    • 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
    • A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
    • A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
    • A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
    • A24B15/10—Chemical features of tobacco products or tobacco substitutes
    • A24B15/16—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
    • A24B15/167—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes in liquid or vaporisable form, e.g. liquid compositions for electronic cigarettes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A61K9/007—Pulmonary tract; Aromatherapy
    • 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

Definitions

  • the invention relates to a combination of nicotine-containing medicaments for use in the prevention and / or treatment of Covid-19.
  • Covid-19 is a viral disease that leads to partially fatal pneumonia and threatens the entire world population. Despite intensive medical research, it is at least doubtful whether a vaccine with which the entire world population can be vaccinated will be available within a period of a few years, especially since it is still unclear how long vaccination protection will be effective.
  • the extremely short biological half-life of nicotine is known.
  • long-lasting nicotine concentrations are required not only in the lungs, but in almost all parts of the body. Because of the high toxicity of the cell toxin nicotine, the nicotine concentration used may only be very low.
  • the invention is therefore based on the object of providing a medicament which, at least over a very short period of time, provides a high nicotine concentration in the organ most affected by the virus, i.e. the lungs, but at the same time in the rest of the body Effecting a concentration of nicotine that only affects or kills the virus but can be tolerated by the patient.
  • the present invention relates to a combination of at least two medicaments for use in the prevention and / or treatment of Covid-19, characterized in that the at least two medicaments comprise a first medicament and a second medicament, the first medicament as active ingredient nicotine and / or contains one or more pharmaceutically acceptable salts thereof and the second drug contains nicotine as active ingredient and / or one or more pharmaceutically acceptable salts thereof and the drug form of the first drug differs from the drug form of the second drug.
  • the combination according to the invention makes it possible to achieve the actually conflicting requirements with regard to the nicotine concentration in the body.
  • the second drug for example an aerosol containing nicotine
  • the first drug for example a nicotine TTS
  • the combination according to the invention can bind the SARS-CoV-2 virus, for example via its spike proteins, to cell receptors such as ACE2 receptors, prevented or at least reduced. At the same time, the nicotine can affect or kill the virus.
  • the drug can also be used for prophylactic purposes, for example when doctors or nurses look after Covid 19 patients but have not yet been vaccinated.
  • the invention does not describe a combination preparation, because combination preparations (Composita) are drugs that contain several active ingredients, but the teaching of the invention describes the combination of at least two nicotine-containing drug forms, e.g. in secondary packaging.
  • the invention aims at a combination therapy for the prevention and / or treatment of Covid-19 with two or more common therapies based on at least two drugs that contain the same active ingredient but have a different drug form.
  • FIGS 1 and 2 show schematic representations of a divisible transdermal therapeutic system (TTS).
  • TTS divisible transdermal therapeutic system
  • the invention relates to a combination of at least two medicaments for use in the prevention and / or treatment of Covid-19.
  • Covid-19 is an abbreviation for "Corona Virus Disease 2019”.
  • Covid-19 is an infectious disease, especially an acute respiratory illness, that can be serious and is caused by a newly identified coronavirus officially known as SARS-CoV-2.
  • the combination comprises a first medicament and a second medicament, both the first medicament and the second medicament containing nicotine and / or one or more pharmaceutically acceptable salts thereof as the active ingredient.
  • the first medicament contains nicotine as active ingredient and / or one or more pharmaceutically acceptable salts thereof and the second medicament also contains nicotine and / or one or more pharmaceutically acceptable salts thereof as active ingredient.
  • Nicotine is the base 3 - [(2S) -l-methylpyrrolidin-2-yl] pyridine. Under this IUPAC name, the active ingredient nicotine has entered the European Pharmacopoeia Ph.Eur. found. However, nicotine can also be bound to an acidic ion exchange resin in the form of a salt.
  • Examples of pharmaceutically acceptable salts of this alkaloid are nicotine sulfate and nicotine tartrate. These and other pharmaceutically acceptable salts are listed with their molecular formula and molecular mass in the following table so that the nicotine base can be converted into the salt equivalents.
  • nicotine-containing is understood here to mean that nicotine and / or one or more pharmaceutically acceptable salts thereof is or are contained, unless explicitly stated otherwise.
  • a drug is a substance or a composition of substances that is intended to cure or prevent human or animal diseases or is suitable for influencing physiological functions or enables a medical diagnosis.
  • Medicines are usually not used as a pure substance, but rather prepared in a special dosage form.
  • the dosage form also depends on the intended mode of administration.
  • Examples of dosage forms for a drug containing nicotine and / or one or more pharmaceutically acceptable salts thereof as active ingredient are tablets, capsules, injections, continuous infusions, active ingredient-containing patches, which are also referred to as transdermal therapeutic systems (TTS), or aerosols and Inhalation solutions.
  • TTS transdermal therapeutic systems
  • other medicinal forms such as lozenges or chewing gum, which are regarded as exotic in the pharmaceutical treasury, can also be used.
  • nicotine base which are about the size of a peach stone, essentially consist of water-insoluble polymethacrylate and contain the active ingredient nicotine base.
  • the size of the drug prevents swallowing, so that the nicotine base is delayed in the oral cavity and can only be absorbed through the oral mucosa.
  • polymethacrylates without limiting the invention, in particular polymers from Evonik in question under the trade name Eudragit RL ® marketed - are used and already as an adjuvant in the manufacture of tablets.
  • these buccal dosage forms contain 2.5 mg or 5 mg or 10 mg or 20 mg or 30 mg nicotine base or the amounts of nicotine salts shown in Table 1, whereby in the case of nicotine salts a weakly basic salt, for example calcium levulinate, which can be incorporated into the buccal dosage form.
  • a weakly basic salt for example calcium levulinate
  • a drug form for a drug that contains nicotine and / or one or more pharmaceutically acceptable salts thereof as the active ingredient is a buccal drug form based on water-insoluble polymethacrylate, e.g. a buccal tablet or a buccal film, the largest dimension of which (linear distance ) is preferably in the range from 2 to 4 cm. It can contain, for example, 2.5 to 30 mg nicotine base or the equivalent amount of nicotine salt.
  • a buccal pharmaceutical form based on water-insoluble polymethacrylate the proportion of water-insoluble polymethacrylate is, for example, at least 80% by weight, preferably at least 90% by weight.
  • Means insoluble in water here according to the definition of the European Pharmacopoeia for practically insoluble a solubility of less than 0.1 g / L water at 20 ° C.
  • the dosage form should allow safe dosing in use and optimize the action of the active ingredient.
  • nicotine when nicotine is administered for the prevention and / or treatment of patients who are sick with Covid-19 or who are to be protected from it, this is not possible through the use of a single dosage form. Rather, nicotine must be given by combining at least two drug forms, both of which contain nicotine as the active ingredient and / or one or more pharmaceutically acceptable salts thereof.
  • the drug form of the first drug differs from the drug form of the second drug.
  • Suitable dosage forms have been mentioned above.
  • One drug or the first drug is used in particular to provide a long-lasting but low nicotine concentration in the blood and brain, while the other drug or the second drug is used in particular to provide a short-term but high nicotine concentration, especially in the lungs , serves.
  • a medicament or the first medicament is administered transdermally, transmucosally, sublingually and / or buccally.
  • a medicament or the second medicament is administered nasally, by inhalation and / or by atomization, preferably by inhalation.
  • the first medicament is administered transdermally, transmucosally, sublingually and / or buccally
  • the second medicament is administered nasally, inhalatively and / or by atomization, preferably inhalatively.
  • the second medicament is, comprises and / or generates a nicotine-containing aerosol in order to generate a uniquely high nicotine concentration in the lungs and / or in the pharynx.
  • the nicotine-containing aerosol contains nicotine and / or one or more pharmaceutically acceptable salts thereof.
  • An aerosol is a heterogeneous mixture (dispersion) of solid suspended particles, e.g. nicotine salts, or liquid suspended particles, e.g. nicotine (base), in a gas, e.g. water vapor.
  • the nicotine-containing aerosol is used in particular by inhalation.
  • the nicotine-containing aerosol can be generated from a liquid, preferably an aqueous liquid, which contains nicotine and / or one or more pharmaceutically acceptable salts thereof, by an evaporator device.
  • An electronic cigarette for example, which is also referred to as an e-cigarette, is suitable as a vaporizer device.
  • the liquid for generating the nicotine-containing aerosol generally also contains water.
  • the liquid can also contain one or more additives, e.g. selected from propylene glycol, glycerine and / or flavorings.
  • E-cigarettes generally comprise a mouthpiece for inhalation, a vaporizer head, a battery carrier, a rechargeable battery and a container for holding a nicotine-containing liquid.
  • OTC evaporator devices are sold under the Flandelsnamen JustFog ® or VaptioCosmo ® for example. Inhaling the nicotine-containing vapors enables a very high concentration of nicotine in the lungs, which kills Covid 19 viruses. The effect only lasts for a short time.
  • the first medicament is therefore a transdermal therapeutic system (TTS), also referred to as an active ingredient-containing patch, or an oral film (OTF, "oral thin film”) or an orodispersible tablet containing nicotine.
  • TTS transdermal therapeutic system
  • OTF oral thin film
  • a buccal drug form based on water-insoluble polymethacrylate is also conceivable as the first drug.
  • a suitable TTS contains nicotine and / or one or more pharmaceutically acceptable salts thereof.
  • a TTS is used for transdermal administration ("through the doldrums").
  • a suitable OTF contains nicotine and / or one or more pharmaceutically acceptable salts thereof.
  • An OTF is used in particular for transmucosal, sublingual and / or buccal administration, but can also effect oral administration.
  • Transdermal therapeutic systems are special drug preparations for the transdermal administration of active substances.
  • a plaster containing the active ingredient is stuck on the flaut; thereafter the active ingredient diffuses into the body through the skin over several hours or days.
  • I.a. Nicotine is administered to quit smoking using TTS.
  • a nicotine-containing TTS generally includes a backing layer that is impermeable to nicotine, a layer containing the active ingredient which contains nicotine as active ingredient and / or one or more pharmaceutically acceptable salts thereof, and a removable protective layer.
  • the TTS also usually contains one or more polymers, usually in the active ingredient-containing layer, which act as pressure-sensitive adhesives and optionally as a matrix for the active ingredient.
  • the nicotine and / or one or more pharmaceutically acceptable salts thereof for example Habitrol ®, ® Niquitin, Nicotinell ®, ® Nicoderm and Nicorette ®, are known. TTS are described, for example, in the following patent applications: DE 36 29 304, DE 10110 391, EP 708 627, EP 366 240, US 5,364,630, WO 95/24172, WO 00/33812, WO 88/01516, US 5,236,896 and US 6,165,497.
  • suitable TTSs are those which can be subdivided in order to obtain subunits of the TTS for administration. This is advantageous because it enables TTS subunits with different dose amounts to be obtained in a simple manner as required.
  • a TTS that has bulges on the longitudinal sides and / or printed, dashed cutting lines is particularly suitable as a divisible TTS. Such a TTS can be cut in order to obtain subunits of the TTS with the desired dosage for transdermal nicotine administration.
  • Oral films are drug forms similar to TTS, but they are applied in the oral cavity, whereby the active ingredient is not absorbed through the skin, but through the oral mucosa.
  • the polymer that contains the active ingredient is not a pressure-sensitive adhesive.
  • Niquitin ® was commercially available as a preparation. OTF are described, for example, in the following patent: US Pat. No. 5,948,430.
  • Oral films also known as oral drug films, are thin, flexible drug carriers. You put them on or under your tongue, for example, and let them melt. With transmucosal films, the active ingredient is applied directly into the body through the oral mucosa.
  • OTF for example, have a size in the range from 2 to 10 cm 2 . They are very thin, for example in the range from 20 to 500 ⁇ m.
  • An OTF can be single or multi-layer System. The layers are usually formed by one or more polymeric matrices, the active ingredient being contained in one or more of the layers.
  • the invention relates to a combination of at least two drugs, preferably two drugs, for use in the prevention and / or treatment of Covid-19.
  • the combination is formed from the first and the second medicament.
  • the combination can, however, optionally also comprise one or more further medicaments.
  • the first drug delivers at least 5 mg and at most 30 mg nicotine base transdermally, transmucosally, sublingually or buccally per day and / or the second drug delivers up to 0.5 mg nicotine base or the equivalent amount of nicotine salt pulmonarily per application.
  • the second medicament for example 1 to 30, preferably 1 to 10, more preferably 1 to 5 applications per day, e.g. 3 applications per day, can be carried out.
  • the first drug delivers at least 5 mg and at most 30 mg nicotine base transdermally per day and / or the second drug delivers up to 0.5 mg nicotine base or the equivalent amount of nicotine salt pulmonarily per application.
  • the second medicament for example 1 to 30, preferably 1 to 10, more preferably 1 to 5 applications per day, e.g. 3 applications per day, can be carried out.
  • the combination according to the invention of at least two medicaments for the prevention and / or treatment of Covid-19 can, for example, be administered to a patient over a period of 1 to 40 days.
  • the known duration of Covid-19 disease is up to about 40 days, in particular up to about 14 days, so that this is also a suitable treatment period.
  • a patient is initially administered the second drug nasally, inhalatively and / or by atomization over a period of 1 to 2 days, preferably 1 day, in particular as a shock therapy, the second drug preferably comprising a nicotine-containing aerosol and / or generated, for example by a vaporizer device, in particular an e-cigarette, and then the first drug is administered transdermally, transmucosally, sublingually and / or buccally to the patient over a period of 1 to 14 days, the first drug preferably being a TTS for the transdermal dose is.
  • the combination according to the invention is used for the prevention and / or treatment of a patient, preferably a patient who has tested positive for Covid-19, according to the following treatment regime.
  • shock therapy is carried out by means of 1 to 5 times, preferably 1 to 3 times, pulmonary administration per day of the second drug, which comprises a nicotine-containing aerosol and / or that releases up to 0.5 mg of nicotine base or the equivalent amount of nicotine salt per application.
  • the nicotine-containing aerosol is preferably produced by an e-cigarette.
  • a transdermal, transmucosal, sublingual or buccal administration of at least 5 mg and a maximum of 30 mg nicotine base per day takes place through the first drug, preferably over a period of 1 to 14 days, the first drug preferably being a TTS.
  • the dosage for pulmonary administration in shock therapy is preferably based on the severity of the patient's disease.
  • the dosage for transdermal, transmucosal, sublingual or buccal administration following the shock therapy is preferably based on the patient's body weight.
  • the following recommendations apply to the dosages. However, these dosage criteria can also be useful in general for any other treatment regimen.
  • An appropriate dosage for pulmonary administration, especially for shock therapy, depending on the severity of the patient's disease is as follows: If the patient has tested positive for Covid-19 but shows no symptoms, the nicotine-containing aerosol is administered once a day, if the patient has tested positive for Covid-19, shows symptoms such as fever, but does not require hospitalization If the patient has tested positive for Covid-19 and a hospital stay is necessary due to pronounced symptoms, the aerosol is administered 3 times a day.
  • transdermal, transmucosal, sublingual or buccal administration is as follows:
  • Body weight under 50 kg 5-8 mg / day, e.g. 7 mg / day,
  • Body weight 50 - 60 kg 8-15 mg / day, e.g. 10 mg / day,
  • Body weight 60 - 90 kg 15-25 mg / day, e.g. 20 mg / day,
  • Body weight over 90 kg 25-30 mg / day, e.g. 30 mg / day.
  • a secondary packaging can contain, for example, 10 to 20 TTS, e.g. about 14 TTS, and e cigarettes for up to 60 repeated nicotine doses, e.g. 20 to 60 nicotine doses, e.g. to provide patient care for up to 14 days, of the known duration the Covid-19 disease.
  • the combination according to the invention of at least two medicaments for the prevention and / or treatment of Covid-19 is suitable for administration to a patient who is a non-smoker.
  • the following examples show combinations of nicotine-containing TTS with e-cigarettes to generate nicotine-containing aerosols for the prevention and / or treatment of Covid-19.
  • Covid-19 begins with a nicotine application three times a day (as a nicotine-containing aerosol by inhalation) using an e-cigarette from example 1-3.
  • the patient receives a nicotine-containing TTS from example 1 -3 glued to the flood every day until the symptoms of the disease, in particular fever, subsided - or until antibodies to the Covid-19 virus can be detected in an appropriate concentration.
  • patient groups are defined using different - including clinical conditions.
  • the medicaments according to the teaching of the invention are, as mentioned above, particularly suitable for non-smokers.
  • the nicotine-containing aerosol for example an e-cigarette
  • Table 2 lists the treatment regimens according to the severity of the disease.
  • Table 2 Dosage information for the nicotine-containing aerosol according to the severity of the Covid 19 symptoms
  • a nicotine-containing drug is administered to maintain low but constant nicotine plasma concentrations.
  • nicotine-containing transdermal therapeutic systems are proposed for this treatment purpose.
  • the amount of nicotine to be applied transdermally does not depend on the symptoms, but on the patient's body weight.
  • the duration of treatment is generally up to 14 days, which corresponds to the mean duration of a Covid 19 disease.
  • Table 3 lists the recommended nicotine delivery rates according to the body weights of the patients and recommends, without restricting the invention, approved drugs with which these delivery rates can be achieved.
  • Table 3 Dosage information for nicotine-containing TTS according to body weight of Covid 19 patients
  • transdermal nicotine administration by means of a TTS with bulges on the long sides and / or printed dashed cutting lines, as is shown by way of example in FIGS. 1 and 2.
  • Fig. 1 shows schematically a divisible TTS in plan view with bulges according to the parallel dashed lines in the longitudinal direction.
  • the TTS should be 8 cm long and 4.5 cm wide at the widest points.
  • the distance between the parallel dashed lines should be 2 cm.
  • the TTS is wrapped in a protective film with a length of 8.5 cm and a width of 5.5 cm, which is shown as an outer rectangle.
  • the vertical dashed line in the upper part of the TTS perpendicular to the dashed lines running in the longitudinal direction represents a pull-off aid for removing the protective film.
  • a TTS of FIG. 1 can deliver 40 mg of nicotine as an entire system.
  • Figure 2 shows the same system with printed symbols - scissors - indicating that the system can be divided into sub-units by cutting. By cutting along the dashed lines and / or from bulge to bulge, either 4 TTS with 10 mg nicotine release or 2 TTS with 20 mg nicotine release or 10 mg and 30 mg nicotine release are possible from this system. Of course, even larger systems with more subunits are also conceivable.

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  • Animal Behavior & Ethology (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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Abstract

L'invention concerne une combinaison d'au moins deux médicaments destinés à être utilisés dans la prévention et/ou le traitement de la Covid-19, les premiers médicaments ainsi que le second médicament contenant de la nicotine et/ou un ou plusieurs sels pharmaceutiquement actifs de ceux-ci en tant que principe actif et la forme posologique du premier médicament étant différente de la forme posologique du second médicament.
PCT/EP2021/061876 2020-05-05 2021-05-05 Combinaison contenant deux médicaments contenant de la nicotine pour le traitement de la covid-19 WO2021224334A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102020112143.1A DE102020112143B4 (de) 2020-05-05 2020-05-05 Nicotin - Corona
DE102020112143.1 2020-05-05

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WO2021224334A1 true WO2021224334A1 (fr) 2021-11-11

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Citations (11)

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Publication number Priority date Publication date Assignee Title
WO1988001516A1 (fr) 1986-08-28 1988-03-10 Lohmann Gmbh & Co. Kg. Systeme therapeutique transdermique, son utilisation et son procede de fabrication
US4920989A (en) * 1985-04-25 1990-05-01 Regents Of The University Of California Method and apparatus for aiding in the reduction of incidence of tobacco smoking
EP0366240A1 (fr) 1988-10-28 1990-05-02 Pharmacia AB Pansement de nicotine à activité prolongée
US5236896A (en) 1990-10-08 1993-08-17 Sumitomo Electric Industries, Ltd. Superconducting device having an extremely thin superconducting channel formed of oxide superconductor material
US5364630A (en) 1988-06-14 1994-11-15 Alza Corporation Subsaturated nicotine transdermal therapeutic system
WO1995024172A1 (fr) 1994-03-07 1995-09-14 Theratech, Inc. Systeme d'apport medicamenteux transdermique, composite et adhesif, contenant un medicament
EP0708627A1 (fr) 1993-07-09 1996-05-01 Cygnus, Inc. Procede et dispositif therapeutique d'administration de substitut de la nicotine par voie transcutanee ou buccale
US5948430A (en) 1996-11-11 1999-09-07 Lts Lohmann Therapie-Systeme Gmbh Water soluble film for oral administration with instant wettability
WO2000033812A2 (fr) 1998-12-07 2000-06-15 Elan Corporation, Plc Timbre transdermique pour administrer des medicaments liquides volatiles
US6165497A (en) 1988-06-14 2000-12-26 Alza Corporation Subsaturated nicotine transdermal therapeutic system
DE10110391A1 (de) 2001-03-03 2002-09-26 Lohmann Therapie Syst Lts Hochflexibles Nikotin transdermales therapeutisches System mit Nikotin als Wirkstoff

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4920989A (en) * 1985-04-25 1990-05-01 Regents Of The University Of California Method and apparatus for aiding in the reduction of incidence of tobacco smoking
WO1988001516A1 (fr) 1986-08-28 1988-03-10 Lohmann Gmbh & Co. Kg. Systeme therapeutique transdermique, son utilisation et son procede de fabrication
DE3629304A1 (de) 1986-08-28 1988-03-24 Lohmann Gmbh & Co Kg Transdermales therapeutisches system, seine verwendung und verfahren zu seiner herstellung
US5364630A (en) 1988-06-14 1994-11-15 Alza Corporation Subsaturated nicotine transdermal therapeutic system
US6165497A (en) 1988-06-14 2000-12-26 Alza Corporation Subsaturated nicotine transdermal therapeutic system
EP0366240A1 (fr) 1988-10-28 1990-05-02 Pharmacia AB Pansement de nicotine à activité prolongée
US5236896A (en) 1990-10-08 1993-08-17 Sumitomo Electric Industries, Ltd. Superconducting device having an extremely thin superconducting channel formed of oxide superconductor material
EP0708627A1 (fr) 1993-07-09 1996-05-01 Cygnus, Inc. Procede et dispositif therapeutique d'administration de substitut de la nicotine par voie transcutanee ou buccale
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