JP2007529502A - Means for transdermal administration of nicotine - Google Patents

Abstract

  Device for transdermal administration of nicotine providing basic and additional user-activatable nicotine administration, and use of such a device.

Description

  The present invention relates to a device for transdermal administration of nicotine, and more particularly to a device that provides basic and additional user-activatable nicotine administration. The invention also relates to the use of the device.

Tobacco addiction and its reduction Recently a campaign by government agencies and various health organizations and other relevant organizations to disseminate information about the adverse health effects of tobacco smoking, as well as the harmful effects of tobacco smoking. And the number of programs is increasing. In addition, and as a result of the perception of this adverse effect, there are a growing number of programs aimed at reducing smoking rates.

  Nicotine is an organic compound and the major alkaloid of tobacco. Nicotine is the main dwarf component of tobacco used in cigarettes, cigars, snuff, and others. Nicotine is also an addictive drug, but smokers are characterized by a strong tendency to revert after a period of successful cessation. Nicotine is the second most used drug in the world after caffeine from coffee and tea.

  The main problem with cigarette smoking is a very significant health implication. Smoking is estimated worldwide to be associated with a disease that causes approximately 3-4 million deaths annually. According to the US Centers for Disease Control and Prevention, "Cigarette Smoking in Adults-USA, 1995", MMWR 1997; 46: 1217-1220, approximately 500,000 people die in the United States each year as a result of tobacco use. ing. In fact, excessive smoking is now recognized as one of the major health problems around the world. This terrible consequence of tobacco smoking has been a recommendation that many medical associations and health authorities take very strong actions against tobacco use.

  Tobacco smoking is decreasing in many developed countries today, but it is difficult to find out how society can expel the second most used drug in the world. is there.

  The most advantageous thing a heavy smoker can do is reduce smoking, or preferably just stop completely. However, experience has shown that this is very difficult for most smokers, as tobacco smoking in most cases results in addiction or craving. WHO has a diagnosis called tobacco dependence in its international disease classification. Others, such as the American Psychiatric Association, call it habitual nicotine addiction. It is generally accepted that these difficulties in quitting smoking result from the fact that these heavy smokers are nicotine dependent. However, the most important risk factors are substances formed during tobacco combustion, such as carbon monoxide, tar products, aldehydes and hydrocyanic acid.

Effects of nicotine Administration of nicotine can be satisfactory and its usual method is by any smoking, for example by smoking cigarettes, cigars or pipe tobacco. However, smoking is harmful to health and therefore can be used to make it easier to stop smoking and / or can be used as a substitute for smoking in a fun way. It is desirable to formulate alternative methods of administration.

  When smoking a cigarette, nicotine is quickly absorbed into the smoker's blood and reaches the brain within approximately 10 seconds after inhalation. The rapid uptake of nicotine gives the consumer instant satisfaction or excitement. Satisfaction then continues during the cigarette smoking time and for some time thereafter. The toxic, toxic, carcinogenic and fertile nature of smoking has led to efforts to methods, compositions and devices that help to break the habit of smoking cigarettes.

Nicotine is a toxic alkaloid addiction from tobacco plants _{C 5 H 4 NC 4 H 7} NCH 3. Nicotine is also used as an insecticide.

Nicotine replacement products One way to reduce smoking is to provide nicotine in a form or method other than smoking, and several products have been developed to meet this demand. Nicotine-containing formulations are currently the predominant treatment for tobacco addiction.

  Achieving reductions in smoking rates has been relatively unsuccessful with currently known products. The state of the art at the present time includes both habitual and pharmacological attempts. After using some habitual or pharmacological attempts to simply reduce smoking rates, more than 80% of tobacco smokers who initially quit smoking generally had their original The smoking rate reverts to smoking habits.

  There are several methods and forms of commercially available nicotine substitutes, such as nicotine chewing gum, to help people who are willing to stop smoking. For example, described in US Pat. No. 5,810,018 (oral nicotine spray), US Pat. No. 5,939,100 (nicotine-containing microspheres) and US Pat. No. 4,967,773 (nicotine-containing troches). Several methods and means have been described for reducing the desire of a subject to use tobacco, including administering nicotine or a derivative thereof to the subject.

  Nicotine-containing nasal drops have been reported (Russell et al., British Medical Journal, Vol. 286, p. 683 (1983); Jarvis et al., Brit. J. of Addiction, Vol. 82, p. 983 (1987)). However, nasal drops are difficult to administer and are inconvenient during work or other public conditions. Methods for administering nicotine by delivery directly into the nasal cavity by spray are known from US Pat. No. 4,579,858, German Patent 3241437 and WO 93/12764. However, they can have local nasal irritation associated with the use of nasal nicotine formulations. The difficulty of administration also results in an unpredictable single dose of nicotine being administered.

  Inhalation devices similar to cigarettes are also known for the uptake of nicotine vapor, as suggested in US Pat. No. 5,167,242.

  One attempt to date that has been successful in reducing smoking rates relies on nicotine-containing chewing gums designed to reduce smoking withdrawal symptoms. The reported success rate is approximately twice that of placebo.

  One successful product based on nicotine, used as a smoking substitute and / or as a smoking cessation aid, is the chewing gum “Nicolet®”. This product is one of the first nicotine replacement forms approved by the US Food and Drug Administration (FDA) and still one of the most used nicotine replacement products. Nicolet® chewing gum has been marketed in about 60 countries over the years. In this chewing gum, nicotine is present in the form of a complex with an insoluble cation exchanger (Polacrilex) dispersed in a gum base. Nicotine is slowly released from the gum by chewing and reaches a plasma level similar to that of smoking a cigarette after about 30 minutes, depending on how it is chewed, ie slowly or quickly. Patents relating to this product are, for example, US Pat. No. 3,877,468, US Pat. No. 3,901,248 and US Pat. No. 3,845,217.

Nicotine Transdermal Patches The use of skin patches for transdermal administration of nicotine has been reported for many years (Rose, in Pharmacologic Treatment of Tobacco Dependence, (1986) pp. 158-166, Harvard Univ. Press). A number of patents have been issued relating to devices for transdermal delivery of nicotine. For example,
US Pat. No. 5,120,546 discloses a transdermal delivery system in which nicotine is complexed with a cyclic compound, US Pat. No. 5,230, discloses a transdermal delivery system using an acrylic polymer adhesive. 896, U.S. Pat. No. 4,943,435, which discloses a transdermal patch that uses a rate-limiting membrane to deliver nicotine in 12-24 hours, whereby a nicotine-containing transdermal delivery device is produced. U.S. Pat. No. 4,915,950, which discloses a method of printing on an adsorbent fabric layer, U.S. Pat. US Pat. No. 5,533,995, US Pat. No. 5,135,753, which discloses a transdermal device for nicotine administration in combination with a nicotine-containing troche, nicotine in combination with a nasal spray for nicotine administration US Pat. No. 5,721,257 discloses a transdermal device for delivery, WO 0164149 discloses the use of a device for transdermal administration of nicotine in combination with heat, and uses electrical pulses , WO 9600111, which discloses transdermal delivery of drugs such as nicotine.

Prior art and its problems It is known to provide an essentially constant baseline plasma level of nicotine, supplemented with elevated doses of nicotine, as desired by the patient. These methods to date involve the use of two different dosage forms for nicotine delivery in combination. For this purpose, for example, there may be the use of a nicotine patch in combination with a nicotine troche (see US Pat. No. 5,135,753) or the use of a nicotine patch in combination with a nicotine nasal spray (US patent). No. 5,721,257). For the convenience of the user, a single dosage form that can provide an essentially constant baseline plasma level of nicotine and an additional elevated dosage of nicotine when desired by the patient / user. There is a demand to provide.

  The present invention relates to a solution to the title problem by providing a single device consisting of a basic and additional, user-activatable transdermal delivery of nicotine.

  Developing a means and method of administering nicotine that gives satisfaction to smoking without smoking, which can satisfy those who are craving for nicotine or avoid the problems associated with prior art means and methods, Considering the above problems, it is highly desirable. In this respect, the present invention addresses this need and interest.

The definition “basic transdermal administration of nicotine in any form” and similar expressions are used herein to administer nicotine continuously during the intended application of the claimed device to the skin, By transdermal delivery of nicotine performed by a portion of the claimed device.

  “Additional transdermal administration of nicotine in any form” and similar expressions are used herein for transdermal performed by a portion of the claimed device that provides basic administration of any form of nicotine. In addition to mechanical nicotine transport, it refers to transdermal nicotine transport performed by a portion of the claimed device that additionally administers nicotine upon user activation.

  When attempting to deliver nicotine to a subject in order to provide the subject with nicotine at different delivery rates, the present invention is fundamental and additional in view of the aforementioned disadvantages known in the art. A novel device is provided that combines transdermal delivery of nicotine that can be activated by.

  In addition, the present invention provides for the use of nicotine to manufacture a device, and for smoking cessation, to aid in temporary smoking cessation, and / or by transdermal administration of nicotine using such a device. To help reduce the urge to smoke or otherwise use tobacco-containing substances and / or consist of Alzheimer's disease, Crohn's disease, Parkinson's disease, Tourette's syndrome, ulcerative colitis and post-smoking cessation weight control Methods are provided for treating conditions suitable for treatment with nicotine, such as conditions selected from the group. Nicotine transdermal delivery methods include the use of tobacco, oral sprays, nasal sprays, transdermal patches, inhalation devices, troches, tablets, as well as parenteral, subcutaneous, intravenous, It can also be carried out in combination with means for delivering nicotine selected from rectal administration, vaginal administration and transmucosal administration.

Transdermal Device Classification Any form of transdermal administration of nicotine can be classified in many different ways. The overall classification of transdermal devices useful in the present invention can be divided into four main groups:
• Reservoir type : The drug is placed in a liquid or gel and delivered to the skin through a rate regulating membrane;
Matrix Type: drug non-adhesive polymeric material, typically are located in the hydrogel or soft polymer;
• Drug type in adhesive: the drug is in the adhesive polymer;
Multi-layered : Similar to the drug-in-adhesive type, but incorporates an additional layer of pressure sensitive adhesive to cover the entire device and stick it to the skin The membrane can also be incorporated into a multi-stack type.

The means of regulating the transdermal flow of nicotine active substances that can be activated by the user can be classified into many different ways. One such classification is set forth in Table 2 below.

  Many of the means listed in Table 2 are very suitable for use in the additional transdermal administration of nicotine in the present invention because they are designed to be both activated and deactivated by the user. Means that are particularly suitable for the user to start and stop, and therefore preferred for use in the additional transdermal administration of the nicotine of the present invention, include iontophoresis (including electromigration and electroosmosis), Includes but is not limited to sonophoresis, microneedles, jet injections or combinations thereof.

表２の手段は、技術的にはそれ自体公知である。

The means of Table 2 are known per se in the art.

Active ingredient According to the present invention, the claimed device comprises nicotine in any form.
Nicotine includes basic forms of nicotine and 3- (1-methyl-2-pyrrolidinyl) -pyridine, synthetic nicotine and tobacco plants or parts thereof, such as nicotine extracts from genus Nicotiana and their singly or It is intended to encompass combinations thereof.

  Any form of nicotine includes nicotine salts, nicotine free base form, nicotine cation exchanger, nicotine inclusion complex or any non-covalent nicotine; nicotine bound to zeolite; Selected from the group consisting of bound nicotine or nicotine bound to starch microspheres; and mixtures thereof.

Many nicotine salts are known, for example, the salts presented in Table 3 below can be used.

The cation exchanger is preferably a polyacrylate.
The inclusion complex is preferably a complex with a cyclodextrin such as β-cyclodextrin.
The nicotine salt is preferably tartrate, bitartrate, citrate, maleate or hydrochloride.
The form of nicotine provided through basic administration may be different from that provided when administered additionally.

Other additives Other additives may also optionally be added to the device according to the invention.
Optional additives preferably comprise one or more additives selected from the group consisting of stabilizers, enhancers and anti-irritants.

  Stabilizers include vitamin E, antioxidants including tocopherol, ascorbic acid, sodium pyrosulfite, or butylated hydroxytoluene (BHT), butylated hydroxyanisole, edetic acid and edetate; and citric acid, tartaric acid And preservatives including lactic acid, malic acid, acetic acid, benzoic acid and sorbic acid. Preferred embodiments include antioxidants as stabilizers, and more preferably vitamin E and / or butylated hydroxytoluene (BHT).

The enhancer can be selected from the group consisting of:
Alcohols , for example, short chain alcohols such as ethanol, long chain aliphatic alcohols such as lauryl alcohol, and polyalcohols such as propylene glycol and glycerin;
Amides , for example amides having a long aliphatic chain, or aromatic amides such as N, N-diethyl-m-toluamide;
Amino acids ;
-Azone and azone-like compounds ;
-Essential oils , i.e. essential oils such as 1-carvone, 1-menton etc. or their constituents;
Fatty acids and fatty acid esters , for example fatty acids such as oleic acid, lauric acid, further esters of fatty acids such as isopropyl myristate, and various esters such as lauric acid and oleic acid;
Macrocyclic compounds such as cyclopentadecanone and cyclodextrins;
Phospholipids and phosphate compounds , such as phospholipids;
2-pyrrolidone compounds ; and- Various compounds , for example sulfoxides such as dimethyl sulfoxide, and fatty acid ethers such as laureth-9 and polyoxylauryl ether.

A combination of enhancers from different groups will demonstrate utility and efficiency.
An example of a useful anti-irritant is vitamin E.

  The following examples are illustrative and non-limiting. Numbers in parentheses represent numbers corresponding to the drawing.

This is illustrated schematically in FIG.
Basic administration from the matrix part and additional administration from the iontophoresis part A device in the form of a transdermal patch consisting of two different nicotine delivery systems:
One system in which transdermal administration of nicotine is delivered from the polymer matrix compartment (11). The mechanism of transdermal nicotine delivery of this system is passive diffusion along a concentration gradient. The delivery rate is defined by the nature of the matrix polymer and the concentration of nicotine loaded into the matrix. Matrix nicotine exists in its neutral basic form.

One system in which transdermal administration of nicotine is delivered from a compartment where the mechanism of nicotine delivery is iontophoresis, ie, the driving force is supplied by current (12, 13). In this system, positively charged nicotine is loaded into a drug compartment (12) with an electrode (anode). The system is completed by a compartment (13) with a second electrode (cathode) loaded with a negatively charged counterion. The counter ion is preferably a chloride ion, but other biocompatible negatively charged ions can also be used. The electrode (14) is preferably of the Ag / AgCl type. A disposable battery (14) in contact with the skin and capable of outputting current up to 0.5 mA / cm ^{2 in the} drug compartment area is connected to the electrodes. When the iontophoresis system is activated, the skin tissue at the application site completes the electrical circuit. The nicotine delivery rate of this system is defined by the magnitude of the current between the electrodes (14).

The above two systems, the size is housed alongside in a thin patch-like device of 20 to 50 cm ^2. The device is secured to the application site by an adhesive layer that covers the bottom of the device. The device is lined with a flexible nonwoven material that provides structural support. Immediately below the nonwoven material is a thin aluminum layer that acts as a barrier to nicotine that diffuses through the backing material of the device. The device is also provided with a start button (15) for starting iontophoretic current drive. The passive diffusion system provides basic administration of nicotine. The user can activate the iontophoresis system by pressing the activation button (15), thereby releasing an additional dose of nicotine. The iontophoresis system is stopped by the timer function. Alternatively, the user can stop the additional administration of nicotine at any time by pressing the activation button (15) a second time.

This is illustrated schematically in FIG.
Basic administration from reservoir portion and additional administration from microneedle portion Device configured in transdermal patch consisting of two different nicotine delivery systems:
One system in which transdermal administration of nicotine is delivered from the reservoir compartment through a rate limiting membrane (21). The mechanism of transdermal nicotine delivery of this system is passive diffusion along a concentration gradient. The delivery rate is defined by the nature of the rate limiting membrane and the concentration of nicotine loaded into the compartment. Matrix nicotine exists in its neutral basic form.

  Transdermal administration of nicotine is delivered from a reservoir compartment lined with one side of a microneedle that has the ability to perforate the stratum corneum of the skin, thereby increasing the transdermal delivery rate of nicotine (22) One system. The microneedle is suspended at a short distance from the skin surface, and the user can bring the microneedle into contact with the skin by pressing the backing of the patch. The delivery rate is defined by the nature of the microneedles and the concentration of nicotine loaded into the compartment. Nicotine in the microneedle reservoir compartment exists in its neutral basic form.

The above two systems, the size is housed alongside in a thin patch-like device of 20 to 50 cm ^2. The device is lined with a flexible nonwoven material that provides structural support. Immediately below the nonwoven material is a thin aluminum layer that acts as a barrier to nicotine that diffuses through the backing material of the device. The device is secured to the application site by an adhesive layer covering the bottom of the device. The adjacent area surrounding the microneedle portion of the device bends the microneedle so that it touches or does not contact the stratum corneum (24) as directed by the user by pressing the backing of the device directly behind the microneedle. Made of semi-rigid flexible polymer. The passive diffusion system provides basic administration of nicotine. The user can add additional doses of nicotine by pushing the backing of the device so that the microneedles can pierce the stratum corneum (24) of the skin and guide nicotine through the stratum corneum (24) to the underlying tissue. Can be activated.

This is illustrated schematically in FIG.
Basic administration from the matrix part and additional administration from the ultrasound part A device in the form of a transdermal patch consisting of two different nicotine delivery systems:
One system in which transdermal administration of nicotine is delivered from the polymer matrix compartment (31). The mechanism of transdermal nicotine delivery of this system is passive diffusion along a concentration gradient. The delivery rate is defined by the nature of the matrix polymer and the concentration of nicotine loaded into the matrix. Matrix nicotine exists in its neutral basic form.

  Transdermal administration of nicotine from the polymer matrix compartment (32), where the mechanism of nicotine delivery is sonophoresis, ie the ultrasound device (33) heats the skin, resulting in reversible damage to the stratum corneum structure. One system to be delivered. The nicotine delivery rate of this system is defined by the intensity of the ultrasonic vibration. Nicotine in the matrix exists in its neutral basic form.

The above two systems, the size is housed alongside in a thin patch-like device of 20 to 50 cm ^2. The device is secured to the application site by an adhesive layer that covers the bottom of the device. The device is also fitted with an activation button (34) for initiating ultrasonic vibrations. The passive diffusion system provides basic administration of nicotine. The user can activate the sonophoresis system by pressing the activation button (34), thereby releasing an additional dose of nicotine. The sonophoresis system is stopped by the timer function. Alternatively, the user can stop the additional administration of nicotine at any time by pressing the activation button (34) a second time.

This is illustrated schematically in FIG.
Basic administration from an iontophoresis part for additional administration and a matrix part sharing space A device configured in a transdermal patch consisting of two different nicotine delivery systems:
One system in which transdermal administration of nicotine is delivered from a compartment where the mechanism of nicotine transport is iontophoresis, ie, the driving force is supplied by an electric current. In this system, positively charged nicotine is loaded into a drug compartment (41) fitted with an electrode (anode). This system is completed by a compartment (42) fitted with a second electrode (cathode) loaded with a negatively charged counterion. This compartment also contains the neutral basic nicotine of the passive diffusion system, described in detail below. A battery (43) supplies the necessary power. The rate of nicotine delivery to this system is defined by the magnitude of the current between the electrodes.

  One system in which transdermal administration of nicotine is delivered from the polymer matrix compartment (42). This compartment contains both the neutral, basic form of nicotine, and the negatively charged counterion required for the iontophoretic system. The mechanism of transdermal nicotine delivery of this system is passive diffusion along a concentration gradient. The rate of nicotine delivery is defined by the nature of the matrix polymer and the concentration of nicotine loaded on the matrix.

The above two systems, the size is housed in a thin patch-like device of 20 to 50 cm ^2. The device is secured to the application site by an adhesive layer that covers the bottom of the device. The device is lined with a flexible nonwoven material that provides structural support. Immediately below the nonwoven material is a thin aluminum layer that acts as a barrier to nicotine that diffuses through the backing material of the device. The apparatus is also provided with a start button (44) for starting iontophoretic current drive. A passive diffusion moiety located in the iontophoresis cathode compartment (42) provides basic administration of nicotine. The user can activate the iontophoresis system by pressing the activation button (44) to release a positively charged additional dose of nicotine from the iontophoresis anode compartment (41). The iontophoresis system is stopped by the timer function. Alternatively, the user can stop additional administration of nicotine at any time by pressing the activation button (44) a second time.

FIG. 5 is a diagrammatic illustration.
A basic administration from the reservoir part and an additional administration from the iontophoresis part , comprising the construction of a transdermal patch consisting of two different nicotine delivery systems in which the two parts are applied separately to the skin. Equipment:
One system in which transdermal administration of nicotine is delivered from the reservoir compartment through a rate limiting membrane (51). The mechanism of transdermal nicotine delivery of this system is passive diffusion along a concentration gradient. The delivery rate is defined by the nature of the rate limiting membrane and the concentration of nicotine loaded into the compartment. Matrix nicotine exists in its neutral basic form.

  One system in which transdermal administration of nicotine is delivered from a compartment where the mechanism of nicotine delivery is iontophoresis, ie, the driving force is supplied by an electric current. In this system, positively charged nicotine is loaded into a drug compartment (52) with electrodes. The system is completed by a compartment (53) with a second electrode loaded with a negatively charged counterion. A battery (54) provides the necessary power. The nicotine delivery rate for this system is defined by the magnitude of the current between the electrodes.

The above two systems, the size is housed alongside in a thin patch-like device of 20 to 50 cm ^2. The device is secured to the application site by an adhesive layer that covers the bottom of the device. The device is lined with a flexible nonwoven material that provides structural support. Immediately below the nonwoven material is a thin aluminum layer that acts as a barrier to nicotine that diffuses through the backing material of the device. The two systems are separated by a perforation (55), allowing the one system to be torn from the other system to place the two parts individually on the body. An activation button (56) for starting current drive of the iontophoresis system is also attached to the iontophoresis portion of the apparatus. The passive diffusion system provides basic administration of nicotine. The user can activate the iontophoresis system by pressing the activation button (56) and release an additional dose of nicotine. The iontophoresis system is stopped by the timer function. Alternatively, the user can stop the additional administration of nicotine at any time by pressing the activation button (56) a second time.

This is illustrated schematically in FIG.
Basic administration from the matrix portion and additional multi-level administration from the iontophoresis portion Device configured in a transdermal patch consisting of two different nicotine delivery systems:
One system in which transdermal administration of nicotine is delivered from the polymer matrix compartment (61). The mechanism of transdermal nicotine delivery of this system is passive diffusion along a concentration gradient. The delivery rate is defined by the nature of the matrix polymer and the concentration of nicotine loaded into the matrix. Matrix nicotine exists in its neutral basic form.

  One system in which transdermal administration of nicotine is delivered from a compartment where the mechanism of nicotine delivery is iontophoresis, ie, the driving force is supplied by an electric current. In this system, positively charged nicotine is loaded into a drug compartment (62) with an electrode (anode). The system is completed by a compartment (63) with a second electrode (cathode) loaded with a negatively charged counterion. A battery (64) supplies the necessary power. The nicotine delivery rate of this system is defined by the magnitude of the current between the electrodes.

The above two systems, the size is housed alongside in a thin patch-like device of 20 to 50 cm ^2. The device is secured to the application site by an adhesive layer that covers the bottom of the device. The device is lined with a flexible nonwoven material that provides structural support. Immediately below the nonwoven material is a thin aluminum layer that acts as a barrier to nicotine that diffuses through the backing material of the device. The passive diffusion system provides basic administration of nicotine. The device also includes a set of activation buttons (65, 66, 67) to start driving the iontophoretic current. The user can activate the iontophoresis system by pressing one of the activation buttons (65, 66, 67) and release an additional dose of nicotine. The amount of additional nicotine administered ranges from low to high depending on the button pressed by the user. Each button corresponds to a preset dose. The iontophoresis system is stopped by the timer function. Alternatively, the user can stop the additional administration of nicotine at any time by pressing the activation button a second time.

Further Embodiments Combinations of the means disclosed herein for obtaining each of the basic and additional dosages other than those disclosed in the examples are readily anticipated and useful. .
The device of the present invention should preferably be hermetically sealed.
The device of the present invention is capable of delivering nicotine for a predetermined period of time, preferably 12, 16, 24 or 48 hours.

  At least one portion for performing basic transdermal administration, as well as at least one portion for performing transdermal administration that can be activated by the user may be combined in different ways. For example, the part may have at least one common feature, such as a general adhesive layer and / or a general drug reservoir. The parts may also be combined so that they do not have common features.

1 is a schematic diagram of an embodiment described in Example 1. FIG. 2 is a schematic diagram of an embodiment described in Example 2. FIG. 2 is a schematic diagram of an embodiment described in Example 3. FIG. 2 is a schematic view of an embodiment described in Example 4. FIG. 6 is a schematic diagram of an embodiment described in Example 5. FIG. FIG. 7 is a schematic diagram of an embodiment described in Example 6.

Claims (15)

  A device for transdermal administration of nicotine in any form, comprising at least a first part for performing a basic administration of nicotine in any form, and an additional administration of nicotine in any form The apparatus of claim 1, wherein the apparatus includes at least one second portion for activation of the at least one second portion by a user.   At least one first part for performing basic administration is preferably a reservoir-type, matrix-type, adhesive-in-adhesive and / or multi-layered transdermal patch, more preferably in an adhesive The device for transdermal administration according to claim 1, which is a transdermal patch of a drug type or a reservoir type or a combination of these two types.   The at least one second part for performing additional administration comprises means of iontophoretic delivery, sonophoresis, jet injection and / or microneedle, according to claim 1 or 2. Device for transdermal administration.   4. A device for transdermal administration according to claim 3, characterized in that at least one second part for performing additional administration comprises means for iontophoretic delivery.   5. Transdermal administration according to any one of claims 1 to 4, characterized in that at least one first part and at least one second part have at least one common feature. Equipment.   6. The method according to claim 1, wherein the at least one first part and the at least one second part are removable from each other and / or are individually applicable. The device for transdermal administration described.   The form of nicotine is nicotine free base; a salt of nicotine such as tartrate, bitartrate, citrate, maleate or hydrochloride; a nicotine inclusion complex such as a complex with cyclodextrin; Nicotine cation exchangers such as nicotine or any non-covalently bound nicotine; nicotine bound to zeolite, nicotine bound to cellulose or nicotine bound to starch microspheres; and mixtures thereof The device for transdermal administration according to any one of claims 1 to 6, wherein:   The device for transdermal administration according to claim 7, wherein the form of nicotine is nicotine free base.   At least one portion for performing basic administration of nicotine is for delivering a form of nicotine different from at least one portion for performing additional administration of nicotine The device for transdermal administration according to claim 7 or 8.   10. Device for transdermal administration according to any one of claims 1 to 9, characterized in that the device delivers nicotine for a predetermined period of time, preferably 12, 16, 24 or 48 hours. The device preferably comprises vitamin E, an antioxidant including tocopherol, ascorbic acid, sodium pyrosulfite, butylated hydroxytoluene (BHT), butylated hydroxyanisole, edetic acid and edetate; and citric acid, One or more stabilizers selected from the group consisting of: tartaric acid, lactic acid, malic acid, acetic acid, benzoic acid and sorbic acid; more preferably vitamin E and / or butylated hydroxytoluene ( BHT); and / or one or more substances wherein the device enhances transdermal penetration, preferably
Alcohols, for example, short chain alcohols such as ethanol, long chain aliphatic alcohols such as lauryl alcohol, and polyalcohols such as propylene glycol and glycerin;
Amides, for example amides having a long aliphatic chain, or aromatic amides such as N, N-diethyl-m-toluamide;
Amino acids;
-Azone and Azone-like compounds;
Essential oils, ie essential oils such as 1-carvone, 1-menton and the like or their constituents;
Fatty acids and fatty acid esters, for example oleic acid, lauric acid and similar fatty acids, further esters of fatty acids such as isopropyl myristate, and various esters such as lauric acid and oleic acid;
Macrocyclic compounds such as cyclopentadecanone and cyclodextrins;
Phospholipids and phosphate compounds, such as phospholipids;
2-pyrrolidone compounds; and various compounds, for example sulfoxides such as dimethyl sulfoxide, and fatty acid ethers such as laureth-9 and polyoxylauryl ether;
11. The method further comprising: a compound selected from the group consisting of; and / or the device further comprises one or more substances, preferably vitamin E, that reduce the stimulus response. The apparatus of any one of these.   The device according to claim 1, wherein the device is sealed.   To help quit smoking, to help with temporary smoking cessation, and / or to help reduce the urge to smoke or use tobacco-containing substances separately, and / or to Alzheimer's disease, clones 13. For treating a condition suitable for treatment with nicotine, such as a condition selected from the group consisting of Parkinson's disease, Tourette syndrome, ulcerative colitis and weight control after smoking cessation Use of nicotine for the manufacture of a device according to any one of the preceding claims.   A transdermal administration of nicotine using the device according to any one of claims 1 to 12 to aid in smoking cessation, to aid in temporary cessation of smoking, and / or to smoke or otherwise. To help alleviate the urge to use tobacco-containing substances and / or to be selected from the group consisting of Alzheimer's disease, Crohn's disease, Parkinson's disease, Tourette's syndrome, ulcerative colitis and weight control after smoking cessation Thus, a method for treating a condition suitable for treatment with nicotine.   Oral sprays, nasal sprays, transdermal patches, inhalation devices, troches, from tablets, including the use of tobacco, and parenteral, subcutaneous, intravenous, rectal, vaginal and Useful for temporary smoking cessation to help quit smoking by transdermal administration of nicotine using a device according to any one of claims 1 to 12, in combination with means selected from transmucosal administration methods And / or to help reduce the urge to smoke or otherwise use tobacco-containing materials and / or Alzheimer's disease, Crohn's disease, Parkinson's disease, Tourette's syndrome, ulcerative colitis and A method for treating a condition suitable for treatment with nicotine, such as a condition selected from the group consisting of weight control after smoking cessation.

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