JP2004512907A - Device and method for smoking cessation - Google Patents

Abstract

The present invention is directed to an oral nicotine delivery device and a method of using this device to reduce a person's smoking frequency. The device includes a tubular chamber having a first end suitable for taking in a liquid or gas from an external source, and a second end suitable for performing oral inhalation. The chamber includes nicotine and a maintenance device to prevent release of nicotine from the first end of the chamber. This device supplies nicotine in a non-irritating solution form.

Description

[0001]
Background of the Invention
Field of the invention
The field of the invention is pharmacology. Specifically, the present invention relates to a smoking cessation method and a smoking cessation aid that provides a non-irritating form of nicotine to a user and provides oral and tactile stimulation of smoking.
[0002]
Overview of related technologies
Smoking is a leading cause of preventable illness and death in the United States. Each year, more than 400,000 adults die from tobacco-related illnesses (Report of the Secretary of Defense, Rockville, MD: Public Health Service (2000)). There is increasing attention to the nuisance and harm of secondary smoking, as well as the health problems faced by the smokers themselves. Although smoking is often prohibited on aircraft, at work, and in restaurants, nearly 88% of non-smokers have detectable blood levels of nicotine metabolites (Morbidity and Mortality Weekly, November 5, 1999). Tobacco smoke in the environment remains a preventable health problem for smokers' colleagues and families (A Report of the Surgeon General, Rockville, MD: Public Health Service) (2000)).
[0003]
Unfortunately, 48 million adults in the United States, or 24.7% of the total population, continue to smoke. Despite guidance from the Health and Safety Administration, smoking prevalence in adults during the 1999s has not changed much (Morbidity and Mortality Weekly, November 5, 1999). Most smokers in the United States want to quit, and over one-third attempt to quit each year, but only about 2.5% have succeeded. Report of the Surgeon General, Rockville, MD: Public Health Service (2000)).
[0004]
Various technologies have been developed to help quit smoking. The five main medications that treat tobacco dependence include nicotine gum (see, eg, US Pat. No. 3,845,217), nicotine transdermal patches (see, eg, US Pat. No. 4,915,950), nicotine nasal sprays (eg, AU66441), nicotine inhalers (eg, US Pat. Nos. 4,209,899 and 4,953,572), sustained release bupropion hydrochloride (eg, Jorenby et al.,N. Engl. J. Med.340: 685-91 (1999)). Other examples of smoking cessation aids include nasal drops (see, for example, US Pat. No. 4,579,858), nicotine lozenges (see, for example, US Pat. Nos. 4,080,635 and 5,549,906), and smokeless tobacco (see, US Pat. , 089,4,676,259,4,736,755,4,813,437,5,284,163 and 6,041,789), nicotine metabolites (See, eg, US Pat. No. 5,869,505), and drinkable nicotine solutions (see, eg, WO 99/55371).
[0005]
Studies show that smokers using nicotine gum, patches, nasal sprays, inhaled nicotine, or nicotine tablets are about 1.5 to 2 times more likely to quit than smokers without cessation aids And there is some evidence that bupropin is much more effective (Siragy et al.,Cochrane Database Syst. Rev .., No. 2, p. CD000146 (2000)). However, each of the existing smoking cessation aids has drawbacks and there is no means to prove it is effective enough.
[0006]
For example, nicotine gum and lozenges have locally high levels of nicotine in the mouth, making them less appealing, and nicotine gum is difficult to chew. In addition, chewing gum and eating troches may look non-professional. Nicotine patches can irritate the skin, and some smokers are dissatisfied with the slow absorption of nicotine from the patches. Nicotine nasal spray can irritate the nose and throat. More importantly, none of these smoking cessation aids stimulates tactile or hand-to-mouth movements that form an important part of smoker addiction.
[0007]
Studies have shown that, like nicotine intake, sensory aspects also affect smoking behavior and attachment to tobacco. In fact, smokers who have attempted to smoke have complained that they not only experienced nicotine withdrawal symptoms, but also lost their senses and hand-to-mouth movements associated with smoking (Rose,Ann. Rev .. Med., 47: 493-507 (1996)). In a study conducted with the American Lung Association, the most recent attempt to quit smoking by 41% of smokers was reported to be unsuccessful due to feeling abandoned (Smoking Survey, Yankelorich Partners, 1998). (July 27). Smoking involves hand-to-mouth movements that are repeated more than 70,000 times per year. Effective smoking cessation aids should address the behavioral component of smoking, as well as giving nicotine replacement therapy, because smoking requires not only cessation of nicotine but also cessation of habitual movements It is. Smoking cessation aids should provide ritual comfort to the smoker's mouth and touch while supplying nicotine. However, smoking cessation devices that are too similar to conventional cigarettes and provide mouth and tactile stimuli that are too similar to smoking are not ideal. Smokers using such devices easily resume smoking (see, for example, Schneider et al., Addiction, 91: 1293-1306 (1996)), thus synergizing nicotine with mouth and tactile stimuli. A smoking cessation aid that is not too close to conventional cigarettes while providing a natural combination is most desirable.
[0008]
Among the existing smoking cessation aids, patches do not irritate the mouth or touch, gums, troches, and drinking solutions irritate the mouth only, and nasal sprays irritate only the respiratory tract. These aids lack the important synergistic combination of nicotine, mouth irritation, and hand-to-mouth movements that smokers desire.
[0009]
Some existing smoking aids, such as nicotine inhalers and various smokeless cigarettes, provide nicotine and address certain behavioral aspects of smoking. However, these products have significant disadvantages. For example, U.S. Pat. No. 4,953,572 (Rose et al.) Discloses a nicotine aerosol spray designed to stimulate the sensation of inhaling tobacco smoke. The spray can be administered by inhalation from a hand-held nebulizer. However, the amount of nicotine in the spray is limited by the volatility of the nicotine groups in the inhaler at room temperature and is small compared to the amount of nicotine in cigarette smoke and is therefore insufficient for many smokers. In addition, such sprays can cause irritation to the oral cavity.
[0010]
U.S. Patent No. 5,284,163 (Knudsen et al.) Discloses a smokeless tobacco replacement that includes nicotine granules in a tubular sleeve. The end of the sleeve includes a gum plug that is bitten off and held as chewing gum in the mouth. When this cigarette is smoked, the nicotine granules are drawn into the mouth and chewed into a gum, thus supplying nicotine into the oral cavity. This product may have the disadvantages of nicotine chewing gum described above. In addition, like smokeless tobacco, using this product will approximate the behavioral aspects of smoking, thus making smoking cessation more difficult.
[0011]
U.S. Pat. Nos. 4,284,089 and 4,813,437 (Ray) disclose non-woven fabrics having a regular cigarette-like shape and including a porous polymer plug that retains volatile liquid nicotine. A pyrolysis device is disclosed. When inhaled with this device, nicotine vapors are delivered to the lungs. However, such devices cannot supply a sufficiently uniform amount of nicotine. Furthermore, the taste of evaporable nicotine is unfavorable and unstable, so the useful life of this device is very short.
[0012]
U.S. Patent No. 6,041,789 (Banker et al.) Discloses that some of these problems are addressed by non-pyrolytic tobacco alternatives that provide a mixture of nicotine and irritating vapors having a tobacco-like taste and aroma. Are dealing with. The device comprises volatile nicotine-like agonists and volatile flavor enhancers, rather than evaporable nicotine. However, this device does not actually supply nicotine. In addition, due to the tobacco-like structure, taste, and aroma, this device is very similar to conventional tobacco, and therefore, a smoker using this device as a smoking cessation aid may be able to resume smoking Is high.
[0013]
Japanese Patent No. 02190178 (Akimichi et al.) Discloses a smokeless tobacco "perfume solution" that can be vaporized and administered through a "tubular flexible casing." However, this solution can be detrimental to health due to carcinogens and irritating particles contained in tobacco. Further, like other smokeless cigarettes, using this device will approximate the actual taste, aroma, and behavior of smoking, thus making smoking more difficult.
[0014]
U.S. Pat. No. 5,293,883 (Edwards) discloses two cigarette filling chambers containing unburned and unburned cigarettes, and a user's mouth when chewed or squeezed out by hand crushing. A non-pyrolytic cigarette is disclosed that includes a mouse filter holding a nicotine-filled ampoule that releases liquid nicotine that is highly pure. This device provides nicotine and tobacco-like taste, but may have the disadvantages of liquid nicotine described above. Furthermore, as mentioned above, this device poses a health problem with cigarettes and may make smoking cessation more difficult by approximating actual cigarettes.
[0015]
Therefore, there is still a need for new and improved smoking cessation aids that will help reduce the existing public health problems associated with smoking and secondary smoking. A smoking cessation aid that provides an easily adjustable amount of nicotine in a non-irritating form and synergistically provides a delivery device that provides the mouth and tactile sensations desired by the smoker without excessively approximating actual smoking Means are particularly needed.
[0016]
Summary of the Invention
The present invention solves the foregoing problems by providing nicotine in a non-irritating solution form and providing a smoking cessation aid that provides the mouth and tactile sensations desired by the smoker. Withdrawing a nicotine solution into the mouth through this device is analogous to the habitual hand-to-mouth movement of smoking. However, because nicotine is supplied as a solution rather than inhaled vapor, using the smoking cessation aid of the present invention is not sufficient to ensure that the smoker does not resume smoking due to similarities in behavior. And different. Nicotine supplied as a solution does not irritate the oral cavity as does the vapor inhaled from a nicotine spray.
[0017]
Accordingly, the present invention provides, in one aspect, an oral nicotine delivery device that includes a tubular chamber, nicotine granules contained within the chamber, and a maintenance device within the chamber. The chamber has a first end suitable for taking in liquid from an external source, and a second end suitable for performing oral inhalation. The maintenance device prevents the release of nicotine granules and liquid from the first end of the chamber. When oral inhalation occurs at the second end of the chamber, liquid enters the chamber from an external source through the first end of the chamber, and then liquid and nicotine are supplied through the second end of the chamber. Is done. As used herein, the term “comprise” means, but is not limited to, “include”.
[0018]
In one aspect, the tubular chamber of the device approximates the size and shape of a conventional cigarette. In another aspect, the tubular chamber approximates the size and shape of a conventional drinking straw.
[0019]
In some aspects, the maintenance device is secured proximate the first end of the chamber. In another aspect, the maintenance device is movable with the nicotine granules and liquid toward the second end of the chamber when inhalation is performed from the second end of the chamber.
[0020]
In some aspects, the nicotine granules comprise coated powdered nicotine particles. In certain embodiments, the nicotine particles are coated for improved palatability. In some embodiments, the nicotine granules form a sphere comprising at least one material selected from the group consisting of sugar, starch, acacia, sodium alginate, carbomer, cellulose, dextrotes, ethylcellulose, methylcellulose, and povidone. Includes particles of powdered nicotine that are taken up.
[0021]
In another aspect, the tubular chamber contains about 1 mg to about 40 mg of nicotine. In another aspect, the tubular chamber contains about 4 mg to about 12 mg of nicotine. Nicotine is preferably selected from the group consisting of levonicotine, dextronictine, racemic mixtures thereof, and pharmaceutically acceptable salts thereof.
[0022]
In some embodiments, a nicotine solution is formed when a liquid enters the chamber and contacts nicotine. In certain embodiments, the solution is a suspension.
[0023]
In another aspect, the invention provides a method of reducing a person's smoking frequency. The method comprises the step of orally administering nicotine to a human using a device according to the above aspects of the invention. A person performs an oral inhalation from the second end of the chamber and liquid enters the chamber from an external source through the first end of the chamber. The liquid and nicotine are then supplied into the mouth of the person through the second end of the chamber.
[0024]
In one aspect of the method, the single dose of nicotine administered to the human is from about 1 mg to about 40 mg. In certain aspects, the dosage is from about 4 mg to about 12 mg. In a preferred embodiment, the total amount of nicotine administered to a human per day is from about 4 mg to about 144 mg. In some aspects, the nicotine blood level of the human after administration of nicotine is at least about 5 ng / ml blood. In some preferred embodiments, the nicotine concentration in the blood of the person after nicotine administration is from about 10 ng to about 50 ng / ml of blood.
[0025]
In some aspects of the method, a nicotine solution is formed when the liquid enters the chamber and contacts the nicotine. In certain aspects, the solution has an acidic pH.
[0026]
In another aspect, the invention provides an oral nicotine delivery device that includes a tubular chamber, a nicotine solution contained within the chamber, and a maintenance device. The chamber has a first end suitable for inhaling a liquid or gas from an external source, and a second end suitable for performing oral inhalation. The maintenance device prevents the release of the nicotine solution from the first end of the chamber. The nicotine solution is supplied through the second end of the chamber when oral inhalation occurs at the second end of the chamber.
[0027]
In some aspects of the device of the present invention, when oral inhalation occurs at the second end of the chamber, liquid enters the chamber from an external source through the first end of the chamber. A liquid and nicotine solution are then supplied from the device through the second end of the chamber.
[0028]
In another aspect, when oral inhalation occurs at the second end of the chamber, gas enters the chamber from an external source through the first end of the chamber. A nicotine solution is then supplied from the device through the second end of the chamber.
[0029]
In some aspects, the tubular chamber approximates the size and shape of a conventional cigarette. In another aspect, the tubular chamber approximates the size and shape of a conventional drinking straw.
[0030]
In some preferred embodiments, the maintenance device is movable with the nicotine solution toward the second end of the chamber when inhalation is performed from the second end of the chamber.
[0031]
In certain aspects, the nicotine solution is a nicotine suspension. In a preferred embodiment, the nicotine suspension comprises nicotine granules. In some embodiments, the nicotine granules comprise coated powdered nicotine particles, and in some embodiments, the nicotine granules are coated for better palatability. In some embodiments, the nicotine granules are incorporated into a sphere comprising at least one material selected from the group consisting of sugar, starch, acacia, sodium alginate, carbomer, cellulose, dextrothes, ethylcellulose, methylcellulose, and povidone. Contains particles of powdered nicotine.
[0032]
In a preferred embodiment, the nicotine solution contains about 1 mg to about 40 mg of nicotine. In another aspect, the nicotine solution contains about 4 mg to about 12 mg of nicotine. In certain aspects, the chamber contains about 1 ml to about 5 ml of the nicotine solution. Nicotine in the nicotine solution is preferably selected from the group consisting of levonicotine, dextronicotine, their racemic mixtures, and their pharmaceutically acceptable salts. In some aspects, the nicotine solution has an acidic pH. In some embodiments, the nicotine solution further comprises a flavor.
[0033]
In another aspect, the invention provides a method of reducing a person's smoking frequency. The method comprises the step of orally administering nicotine to a human using a device according to the above aspects of the invention. A person performs an oral inhalation at the second end of the chamber, and a nicotine solution is supplied from the chamber through the second end of the chamber into a person's mouth.
[0034]
In some preferred embodiments of this aspect of the invention, the single dose of nicotine administered to the human is from about 1 mg to about 40 mg. In certain aspects, the dosage is from about 4 mg to about 12 mg. In some preferred embodiments, the total amount of nicotine administered to a human per day is from about 4 mg to about 144 mg. In some aspects, the human nicotine blood concentration after administration of the nicotine solution is at least about 5 ng / ml blood. In some preferred embodiments, the nicotine concentration in the blood of the human after administration of the nicotine solution is from about 10 ng to about 50 ng / ml of blood. In a preferred embodiment, the nicotine solution is a nicotine suspension.
[0035]
Detailed description
Published U.S. patents, published patent applications, and references cited herein are each to the same extent as if each were specifically and individually indicated to be incorporated herein by reference. , Incorporated herein by reference. Contradictions between these documents and the present disclosure shall be resolved by giving priority to the present disclosure.
[0036]
The present invention provides a smoking cessation method and a smoking cessation aid that supplies a nicotine solution to a user through a tubular device. The advantage of delivering nicotine via a tubular device is that the mouth sensation and tactile sensation experienced by the user is close to the hand-to-mouth stains associated with smoking. Thus, the device of the present invention reduces tobacco attachment by concentrating the smoker on mouth and hand work, thereby giving the smoker the purpose of operating and chewing the device.
[0037]
As shown in FIG. 1, the device of the present invention can approximate the size and shape of a conventional drinking straw. Alternatively, as shown in FIG. 2, the device can approximate the size and shape of a conventional cigarette. The term "close" means that the device includes an elongate tubular chamber 10 including a first end 12 adapted for inhaling air or liquid from an external source, and a second end 14 adapted for oral inhalation. Including means that the dimensions of the device are similar to the dimensions of a conventional drinking straw or a conventional cigarette. In some preferred embodiments, as shown in FIG. 1, the device approximates the shape and size of a conventional drinking straw. Chamber 10 is preferably about 13 cm to about 20 cm in length and about 4 mm to about 8 mm in diameter. More preferably, chamber 10 is about 15 cm to about 17 cm in length and about 6 mm to about 7 mm in diameter. Alternatively, as shown in FIG. 2, the device approximates the shape and size of a conventional cigarette. In these embodiments, chamber 10 is preferably about 7 cm to about 11 cm in length and about 7 mm to about 10 mm in diameter. More preferably, chamber 10 is about 8 cm to about 10 cm in length and about 8 mm in diameter. Examples of tubular feeders of the present invention include U.S. Patent No. 5,718,681 (Manning) and U.S. Patent Nos. 5,780,058, 5,985,324, and 5,989,590. No. 6,024,721, and 6,106,845 (Wong et al.), But are not limited thereto.
[0038]
Materials for making the tubular chamber 10 of the present invention may include, but are not limited to, paper, plastics such as propylene / styrene copolymer, polypropylene, high density polyethylene, low density polyethylene, ethylene vinyl acetate copolymer, and the like. .
[0039]
The tubular device 10 of the device of the present invention includes nicotine 16 that is supplied to a user. Nicotine 16 may be in any useful form, such as levonicotine, dextronicotine, or a racemic mixture thereof. Nicotine in a pharmaceutically acceptable salt form is also suitable for use in the present invention. Non-limiting examples of such suitable salt forms of nicotine include dihydrochloride, sulfuric acid, bitartrate, salicylic acid, hydrogen tartrate, and hemisulphate. Nicotine and its salt forms are commercially available, for example, from Sigma-Aldrich of St. Louis, MO.
[0040]
Preferably, nicotine 16 is in granular form. The term "granules" means that the nicotine is in the form of particles, such as granules or beads. The size of the granules or beads is preferably small enough not to be felt as discrete particles in the mouth, preferably smaller than about 200 μm in diameter.
[0041]
In some preferred embodiments, nicotine granules are produced using standard techniques known in the art (eg, Deasy, Crit Rev. Ther., “Drug Carrier System”, 8: 39-89 (1991). )), Powdered nicotine particles. The term “powder” means composed of fine particles. Glatt Air Technologies (Ramsey, NJ) and Particle and Coating Technologies, Inc., St. Louis, MO provide particle coating services. Suitable coatings include, but are not limited to, hydroxypropylcellulose, sugar, starch, polymers, resins, gums, waxes, and fats. The diameter of the nicotine particles before coating is preferably less than about 200 μm, more preferably about 20 μm to about 100 μm, and even more preferably about 40 μm to about 60 μm.
[0042]
In some preferred embodiments, the nicotine granules comprise powdered nicotine particles incorporated into microspheres that can be coated as described above. Suitable materials for the microspheres include, but are not limited to, sugar, starch, acacia, sodium alginate, carbomer, cellulose, dextrothes, ethylcellulose, methylcellulose, povidone, and mixtures thereof. For example, the microspheres may include a degradable composition. The diameter of the microspheres is between about 300 μm and about 1000 μm, preferably between about 500 μm and about 600 μm. U.S. Patent No. 5,939,100 (Albrechtson et al.) Discloses another example of nicotine microspheres.
[0043]
The coating on the nicotine particles or microspheres is preferably configured to mask the taste of nicotine and thus enhance the taste of the device itself. Most preferably, the coating is formulated to mask most, if not all, of the nicotine taste. The advantage of such a composition is that the taste of nicotine is masked to an extent that the taste of nicotine is felt good, but enough nicotine taste remains to allow the user to recognize that nicotine is being taken. is there. Thus, in some preferred embodiments, the composition may include both coated and uncoated particles. The coating on the particles or microspheres may be designed to perform other functions, including, but not limited to, preventing aggregation and preventing water absorption.
[0044]
Preferably, a single dose of nicotine 16 from the device of the present invention comprises a therapeutically effective amount of nicotine. The term “single dose” means the amount of nicotine provided to the chamber 10 and provided to the user when oral inhalation is performed at the second end 14 of the chamber 10. The term “therapeutically effective amount” means an amount sufficient to reduce the need for a smoker for nicotine from burned tobacco. This amount can be determined by the user's physician. An advantage of the smoking cessation device of the present invention is that it can supply a large amount of nicotine as needed or a small amount of nicotine. Preferably, the device provides from about 1 mg to about 40 mg of nicotine. Useful amounts include about 1 mg to about 5 mg, about 4 mg to about 12 mg, about 4 mg to about 20 mg, about 5 mg to about 15 mg, about 5 mg to about 20 mg, and about 20 mg to about 40 mg supplied at a time by the device. Contains nicotine. Smokers attempting to quit smoking may use the device of the present invention daily, such that a total of about 1 mg to about 480 mg, preferably about 5 mg to about 480 mg, of nicotine is supplied per day as perceived need. It can be used from 1 to about 12 times, preferably about 5 to about 12 times a day. Useful total daily amounts include about 1 mg to about 60 mg, about 4 mg to about 144 mg, about 4 mg to about 240 mg, about 5 mg to about 180 mg, about 5 mg to about 240 mg, and about 240 mg to about 480 mg of nicotine. . The term "total amount per day" means the amount of nicotine supplied to a user during a 24 hour period.
[0045]
Preferably, such dosing regimens have a blood nicotine concentration of at least about 5 ng / ml of blood and a maximum peak nicotine amount of about 60 ng / ml of blood. Preferably, the blood nicotine concentration of the user of the device is from about 10 ng to about 50 ng / ml of blood. More preferably, the user's blood nicotine concentration is about 20 ng / ml of blood.
[0046]
Blood nicotine levels are described, for example, in Jacob et al. It can be measured by gas chromatography described in Chromatography, 222: 61-70 (1981) with nitrogen and phosphorus detection. Dosage frequency can be adjusted to achieve steady-state nicotine blood levels. The steady-state blood nicotine concentration is preferably within the preferred blood concentration ranges described above. The amount of nicotine described above is sufficient to provide a therapeutically effective amount of nicotine to the user's metabolism, even after initial absorption by the liver. It will be understood by those skilled in the art that the preferred amount of nicotine and blood nicotine concentration will vary depending on the preferences, metabolism, and previous smoking habits of the individual user of the smoking cessation aid of the present invention.
[0047]
In one device included in the present invention, nicotine granules are provided to a user as a nicotine solution. The term "solution" as used herein refers to a liquid in which nicotine is dissolved, or a suspension or emulsion of nicotine in a liquid. Supplying nicotine as a solution has several advantages. Swallowing the solution provides the mouth irritation desired by the smoker. However, the solution is not as irritating to the oral cavity as nicotine gum. In addition, nicotine in solution form is absorbed more slowly into the body than nicotine from nasal sprays. Such slow absorption can reduce the number of doses and reduce the potential for abuse. Finally, supplying the liquid with nicotine prevents local nicotine concentrations from being reduced, thus preventing convulsions, for example when swallowing a nicotine capsule.
[0048]
In some devices, a first end 12 of the chamber 10 is positioned to contact an external liquid source, and a user performs oral inhalation at a second end 14 of the chamber 10. According to one method of the present invention, liquid is drawn into the first end 12 of the chamber 10 from an external source. The liquid then forms a suspension of nicotine 16 granules as it is drawn through the chamber 10, and the suspension is supplied into the mouth of the user through the second end 14 of the chamber 10. Some or all of the nicotine 16 granules can be dissolved in a liquid such that the nicotine 16 is provided as a solution. WO 99/55371 (Westman et al.) Discloses a non-limiting nicotine solution having properties that are desirable for use with the present invention.
[0049]
The external liquid source drawn into the tubular chamber 10 of the device of the present invention is preferably a beverage. Most preferably, the beverage includes a flavoring that helps improve the taste of the nicotine solution. This is not important if the taste of nicotine is already masked by coating the particles of nicotine granules. The term "tasting good" means that the taste of the solution is tolerable to the user. The beverage may include, but is not limited to, coffee, soda, sugar, fruit juice, carbonated water, or ethyl alcohol such as wine, beer, whiskey and the like. Preferably, the beverage is free of solids such as pulp. The nicotine solution preferably has an acidic pH to enhance palatability. The term "acidic pH" means a pH of less than about 6.9. More preferably, the pH of the nicotine solution is less than about 5.5. Most preferably, the pH of the nicotine solution is from about 2.0 to about 4.0. The flavor of the nicotine solution can be adjusted using flavorings such as coffee, alcohol, fruit juices, and the like. For example, lime juice, cranberry juice, grapefruit juice, orange juice, quinine water, soda, and wine have a pH of about 2.0 to about 4.0 and beer, celtua water, and coffee have a pH of about 2.0 to about 4.0. It is less than 6.9.
[0050]
An advantage of the smoking cessation device of the present invention is that it is compatible with acidic beverages, as well as most common beverages. Existing smoking cessation devices, such as nicotine gum and nicotine inhalers, cannot be used in combination with acidic beverages due to the need for an alkaline environment to absorb the nicotine supplied by such devices from the mouth . When using smoking cessation devices that rely on the absorption of nicotine by mouth, the consumption of acidic beverages must be avoided for about an hour before and after. Thus, smokers attempting to quit using such devices must avoid consuming most of the beverages for many hours. In contrast, smokers using the nicotine supply device of the present invention, in which nicotine is orally ingested, can always consume acidic beverages.
[0051]
The tubular chamber 10 of the device of the present invention may include two or more lumens. The plurality of lumens provide a plurality of flow paths having a relatively small cross-section, helping to optimize the flow rate and flow rate of liquid from an external source, and thus speeding up nicotine 16 contained within chamber 10. Can be supplied uniformly and completely. Nicotine 16 may be in one lumen or multiple lumens. The plurality of lumens may be the same size or different sizes.
[0052]
Alternatively, the chamber 10 of the device of the present invention contains a pre-composed nicotine 16 solution, such as a nicotine suspension. About 1 ml to about 40 ml of the nicotine solution can be prepared in the chamber. Preferably, about 1 ml to about 10 ml, most preferably about 1 ml to about 5 ml of solution is provided. Preferred single doses of nicotine, total amount of nicotine per day, and nicotine blood concentration are as described above for nicotine granules.
[0053]
In another method of the present invention, a user performs an oral inhalation at the second end 14 of the chamber 10 of the device and a gas, such as air, is drawn into the device through the first end 12 of the chamber 10. As the air is drawn into the chamber 10, the nicotine 16 solution contained in the chamber 10 is supplied through the second end 14 of the chamber 10 into the mouth of the user.
[0054]
Alternatively, the user places the first end 12 of the chamber 10 into contact with an external liquid source and performs an oral inhalation at the second end 14 of the chamber 10 such that liquid is supplied from the external source to the chamber 10. It is drawn into the first end 12. As the liquid is drawn through the chamber 10, it mixes with the solution of nicotine 16 contained in the chamber 10, and the mixture is supplied through the second end 14 of the chamber 10 into the mouth of the user. The external liquid source is preferably a beverage, as described above for the device in which chamber 10 contains nicotine 16 granules. Most preferably, the beverage is flavored and has the pH range described above.
[0055]
The nicotine 16 solution itself contained in the chamber 10 may include the flavoring described above. Preferably, the solution is pre-formed to fall within the aforementioned pH levels, for example, by using an acid such as carbonic acid, citric acid, acetic acid, maleic acid, ascorbic acid, adipic acid, or a combination thereof. Such a pre-composition that optimizes flavoring and pH allows the user to inhale air rather than liquid through the first end of the chamber, and thus the nicotine 16 solution contained within the chamber 10 enhances taste. It is particularly desirable when supplied without liquid from an external source where possible.
[0056]
The chamber 10 of the device of the present invention further includes a maintenance device 18 that prevents the release of nicotine 16 from the first end 12 of the chamber 10. The term “maintenance device” refers to a disc, float, plug, or other restraining member that blocks the diameter of chamber 10 so that nicotine 16 contained within chamber 10 cannot be released from first end 12 of chamber 10. Point to. The maintenance device 18 allows gas or liquid from an external source to enter the first end 12 of the chamber 10, but prevents release of nicotine 16 from the first end 12 of the chamber 10. The maintenance device 18 may release liquid drawn into the chamber 10 from an external source or liquid contained in the chamber 10 as part of a pre-composed solution of nicotine 16 from the first end 12 of the chamber 10. It also prevents you from being done.
[0057]
The maintenance device 18 can be fixed proximate to the first end 12 of the chamber 10. “Proximal position” to the first end 12 of the chamber 10 means a position at or near the first end 12 of the chamber 10. Alternatively, the maintenance device 18 may be movable toward the second end 14 of the chamber 10. For example, the maintenance device 18 is transferred toward the second end 14 of the chamber 10 when a user inhales at the second end 14 of the chamber 10. Gas or liquid from an external source is drawn into the device through the first end 12 of the chamber 10 and the nicotine 16 solution in the chamber 10 is supplied into the user's mouth. As the movable retainer 18 is retracted toward the second end 14 of the chamber 10 behind the nicotine 16 solution, the retainer 18 causes all nicotine 16 in the chamber 10 to smoothly move to the second end of the chamber 10. Through the end 14 of the user. The second end 14 of the chamber 10 is constructed such that the maintenance device 18 itself is blocked from entering the user's mouth. For example, the maintenance device 18 can move from the first end 12 of the chamber 10 to the second end 14 of the chamber 10 but pass through the second end 14 of the chamber 10 and into the mouth of the user. The diameter of the second end 14 of the chamber 10 may be smaller than the diameter of other locations within the chamber 10 and smaller than the diameter of the maintenance device 18 so that the diameter of the maintenance device 18 cannot be reduced. The diameter of the second end 14 of the chamber 10 may be crimping of the chamber 10, a series of indentations in the circumference of the chamber 10, or continuous in the circumference of the chamber 10 at the second end 14 of the chamber 10. The indentation can be smaller than the diameter at other locations within the chamber 10. The moveable maintenance device 18 is particularly useful when the device is pre-filled with liquid, ie, contains a pre-composed nicotine 16 solution.
[0058]
The maintenance device 18 may include constraints and plugs. The term “constrained” refers to the diameter of the plug near the first end 12 of the chamber 10 such that the plug is contained within the chamber 10 and prevents release of nicotine 16 from the first end 12 of the chamber 10. Is smaller than the diameter of the other location in the chamber 10 and smaller than the diameter of the plug. The constraint may be obtained, for example, by crimping the chamber 10, a series of depressions in the circumference of the chamber 10, or a continuous depression in the circumference of the chamber 10 near the first end 12 of the chamber 10.
[0059]
The retention device 18 may include a particle barrier having an opening or slit that allows liquid to pass through the barrier when oral suction is performed at the second end of the chamber 10. A cap can be placed on the first end 12 of the chamber 10 prior to use to avoid loss of nicotine 16 or to prevent ingress of contaminants through the particle barrier openings or slits. The openings must be so small that nicotine 16 cannot pass through them and cannot be released from the first end 12 of the chamber 10. The slit is easier to manufacture than the opening and seals the chamber 10 more completely than the opening before use. Alternatively, the barrier is made of a material such as a fine mesh or perforated paper that holds the nicotine 16 within the chamber 10 but does not require barrier openings or slits to allow liquid to be drawn into the chamber. The barrier is preferably conical and is located at the first end 12 of the chamber 10 to facilitate construction.
[0060]
Alternatively, maintenance device 18 includes a one-way plug or valve. This plug or valve seals the first end 12 of the chamber 10 at atmospheric pressure. However, when suction occurs at the second end 14 of the chamber 10, the plug deforms and liquid from an external source flows around the plug and into the chamber 10 through the first end 12 of the chamber 10. Can flow in. The plug is preferably inhaled at the second end 14 of the chamber 10 and toward the second end 14 of the chamber 10 when the nicotine 16 contained in the chamber 10 is supplied into a user's mouth. Has a density of less than 1 as drawn by When the suction from the second end 14 of the chamber 10 stops, the plug relaxes, sealing the chamber 10 and remaining stationary. By moving the plug to the second end 14 of the chamber 10, it can be seen that the entire amount of nicotine 16 contained in the chamber 10 has been supplied.
[0061]
Alternatively, the maintenance device 18 includes a cylindrical body having at least one protrusion on an outer surface. Liquid from an external source is drawn into the chamber 10 through or around the maintenance device 18, but the protrusions cause the nicotine 16 solution to leak from or around the side of the maintenance device 18, and the chamber 10 Is prevented from leaking from the first end 12. This protrusion acts as a seal for the chamber 10 and also creates friction or resistance between the retainer 18 and the chamber 10, after the liquid passes through or around the retainer 18. Fins, ridges, or rings that give time to mix with nicotine 16.
[0062]
The maintenance device 18 of the present invention may be made from thermoplastic materials, such as, but not limited to, ethylene vinyl acetate copolymers, polyolefins such as polyethylene and polypropylene, closed cell foams, and the like, or low or high density foam materials. Can be. Alternatively, the retention device 18 may include a compressible plug of bonded fibers, for example. The fibers may be polymeric fibers, such as polyolefin fibers, with or without polyester core, polyester, cellulose acetate, nylon, felt, cotton. The uncompressed fiber plug preferably has a diameter slightly larger than the diameter of the chamber 10. Thus, after being inserted into chamber 10, the plug prevents nicotine 16 from being released from chamber 10, but still allows liquid to enter chamber 10 when oral aspiration is performed at second end 14 of chamber 10. Allow to withdraw.
[0063]
In some aspects, the chamber 10 of the device of the present invention preferably includes a removable end cap 20 or seal located at the second end 14 of the chamber 10. The removable end cap 20 or seal allows the nicotine 16 granules or pre-formed nicotine 16 solution contained within the chamber 10 to be released from the second end 14 of the chamber 10 during shipping and storage of the device. To prevent The user may supply the nicotine 16 granules or pre-composed nicotine 16 solution contained in the chamber 10 into the mouth of the user through the second end 14 of the chamber 10 before using the device. Remove the end cap 20 or seal from the second end 14 of the end cap. Materials from which the end cap 20 or seal of the present invention is made may include, but are not limited to, paper, foil, propylene / styrene copolymer, polypropylene, high density polyethylene, low density polyethylene, ethylene vinyl acetate copolymer, and the like. .
[0064]
In some examples, the device itself may include flavoring before and after the nicotine is supplied, so as to make the device more chewable. The flavoring can be, for example, sugar, cinnamon, spearmint, peppermint, wintergreen, bubble gum, fruit, chocolate, anise, nuts, coffee, tobacco, or a combination thereof. Preferably, the flavor is selected from the group consisting of spearmint, peppermint, wintergreen, and cinnamon.
[0065]
The device described in detail above provides a novel synergistic combination of mouth and tactile stimuli with a controlled amount of nicotine in a non-irritating solution form. Smokers trying to quit smoking can satisfy this desire for nicotine, while at the same time providing an alternative to the hand-to-mouth movement element of the smoker, as an aid to preventing attachment to tobacco. Can be used. The synergistic combination of the present invention provides an important new way of understanding the health problems of smoking and reducing the number of smokers who want to quit.
[0066]
The following non-limiting examples further illustrate certain preferred embodiments of the present invention.
[0067]
Example 1 : Safety and pharmacokinetic studies
1 . apparatus
Nicotine is administered orally using the straw-shaped smoking cessation device of the present invention shown in FIG. The chamber 10 is a drinking straw made of plastic. The retaining device 18 is a filter at the first end 12 of the straw. The user places the first end 12 of the device in a glass of apple juice and makes an oral inhalation at the second end 14 of the device, so that the juice and nicotine 16 are delivered into the user's mouth.
[0068]
Nicotine 16 in the device is in the form of a nicotine bitartrate coated sugar sphere having a diameter of about 500 μm. Nicotine spheres are made by spraying dihydrated nicotine bitartrate with a binder onto sugar spheres and applying a film coating. Using a Wurster processing unit, the particles are suspended in air using a controlled airflow system and the coating suspension is added at a controlled rate via a pneumatic spray nozzle. When the spray droplets of the coating solution come into contact with the particles, they spread and collect on the surface of the particles. The excess moisture of the added liquid evaporates in the apparatus, leaving a coated and dry substance. Mixing of the coating suspension is performed throughout the manufacturing process so that the suspension is uniform.
[0069]
2 . Administration
Healthy adult smokers who wish to stop smoking are given a single dose of nicotine or placebo on day 1 after smoking overnight. As known in the art, smokers are randomly assigned to each dose group by a double-blind method. The following data is collected before dosing, every 30 minutes for the first 2 hours after dosing, and every hour for the next 6 hours: plasma nicotine and cotinine levels, vital signs, Assessment of adverse events and patient attachment to tobacco. Baseline and endpoint clinical chemistry data, hematology data, urine analysis data, and ECG are also monitored.
[0070]
The same patient is given an equal dose of nicotine or placebo on day 8 after smoking again overnight. This dose is repeated periodically throughout the day. As described above, the following data is collected before the first dose and one hour after each dose: plasma nicotine and cotinine levels, vital signs, adverse events, assessment of the patient's attachment to tobacco. Baseline and endpoint clinical chemistry data, hematology data, urine analysis data, and ECG are also monitored. These data are used to evaluate the safety and pharmacokinetics of the nicotine supply by this smoking cessation device.
[0071]
Example 2 : Effectiveness study
In a double-blind study, 300 healthy adult smokers wishing to quit smoking will be given nicotine or a placebo over 10 weeks using the smoking cessation device described in Example 1. Each device contains 5-10 mg of nicotine or placebo. Patients are instructed to use the device in response to their desire to smoke and are instructed to use no more than 12 times per day. Patients are simultaneously included in a counseling program to obtain behavioral support for smoking. As a primary endpoint, smoking cessation data will be collected during the last 8 weeks of treatment. Smoking cessation is defined as abstinence from smoking for 4 consecutive weeks during the study period. Patients are examined weekly by a clinician to monitor plasma nicotine and cotinine levels, vital signs, adverse events, and assessment of the patient's attachment to tobacco. Baseline and endpoint clinical chemistry data, hematology data, urine analysis data, and ECG are also monitored.
[0072]
Equivalent
While the foregoing invention has been described in some detail for purposes of clarity and understanding of the description, various modifications in form and detail may be made by reading this disclosure without departing from the scope of the invention and the appended claims. Will be understood by those skilled in the art.
[Brief description of the drawings]
FIG. 1 is a schematic front view of a nicotine supply device of the present invention, which is close to the shape and size of a conventional drinking straw.
FIG. 2 is a schematic front view of the nicotine supply device of the present invention, which is close to the shape and size of a conventional cigarette.

Claims (41)

An oral nicotine supply device,
(A) a tubular chamber having a first end suitable for taking in liquid from an external source, and a second end suitable for performing oral inhalation;
(B) nicotine granules contained within the tubular chamber, and (c) a maintenance device within the tubular chamber to prevent release of nicotine granules and liquid from the first end of the chamber;
When oral inhalation is performed from the second end of the chamber, liquid enters the chamber from an external source through the first end of the chamber, and then liquid and nicotine pass through the second end of the chamber. Equipment supplied. The device of claim 1, wherein the tubular chamber is close in size and shape to a conventional cigarette. The device of claim 1, wherein the tubular chamber approximates the size and shape of a conventional drinking straw. The apparatus of claim 1, wherein the maintenance device is secured proximate the first end of the chamber. The device of claim 1, wherein the maintenance device is movable with the nicotine granules and liquid toward the second end of the chamber when inhalation occurs at the second end of the chamber. The device of claim 1, wherein the nicotine granules comprise coated powdered nicotine particles. 7. The device of claim 6, wherein the nicotine particles are coated for improved palatability. The nicotine granules comprise powdered nicotine particles incorporated into a sphere comprising at least one material selected from the group consisting of sugar, starch, acacia, sodium alginate, carbomer, cellulose, dextrotes, ethylcellulose, methylcellulose, and povidone. The device of claim 1, comprising: The device of claim 1, wherein the tubular chamber contains about 4 mg to about 12 mg of nicotine. The device of claim 1, wherein a nicotine solution is formed when the liquid enters the chamber and contacts the nicotine. The device according to claim 10, wherein the solution is a suspension. The device of claim 1, wherein the nicotine is selected from the group consisting of levonicotine, dextronicotine, racemic mixtures thereof, and pharmaceutically acceptable salts thereof. A method of reducing a person's smoking frequency, comprising the step of orally administering nicotine to a person using an oral nicotine delivery device, the device comprising:
(A) a tubular chamber having a first end suitable for taking in liquid from an external source, and a second end suitable for performing oral inhalation;
(B) nicotine granules contained within the tubular chamber, and (c) a maintenance device within the tubular chamber to prevent release of nicotine granules or liquid from the first end of the chamber;
Oral administration involves a person performing an oral inhalation at a second end of the chamber, wherein liquid enters the chamber from an external source through the first end of the chamber, and then liquid and nicotine are applied to the chamber. A method of delivering into a person's mouth through a second end. 14. The method of claim 13, wherein the amount of nicotine administered to the human in a single dose is from about 4 mg to about 12 mg. 14. The method of claim 13, wherein the total amount of nicotine administered to the human per day is from about 4 mg to about 144 mg. 14. The method of claim 13, wherein the blood nicotine concentration of the person after nicotine administration is at least about 5 ng / ml of blood. 17. The method of claim 16, wherein the blood nicotine concentration of the person after nicotine administration is from about 10 ng to about 50 ng / ml of blood. 14. The method of claim 13, wherein a nicotine solution is formed when the liquid enters the chamber and contacts the nicotine. 19. The method according to claim 18, wherein the solution has an acidic pH. An oral nicotine supply device,
(A) a tubular chamber having a first end suitable for taking in a liquid or gas from an external source, and a second end suitable for performing oral inhalation;
(B) a nicotine solution contained within the tubular chamber, and (c) a maintenance device within the chamber to prevent release of the nicotine solution from the first end of the chamber;
A device wherein the nicotine solution is supplied through the second end of the chamber when oral inhalation is performed at the second end of the chamber. When oral inhalation occurs at the second end of the chamber, liquid enters the chamber from an external source through the first end of the chamber, and then liquid and nicotine solution are applied to the second end of the chamber. 21. The device of claim 20, which is fed through a section. When oral inhalation occurs at the second end of the chamber, gas enters the chamber from an external source, through the first end of the chamber, and then a nicotine solution passes through the second end of the chamber. 21. The device of claim 20, supplied through. 21. The device of claim 20, wherein the tubular chamber is close to the size and shape of a conventional cigarette. 21. The device of claim 20, wherein the tubular chamber is similar in size and shape to a conventional drinking straw. 21. The device of claim 20, wherein the maintenance device is movable with the nicotine solution toward the second end of the chamber when inhalation occurs at the second end of the chamber. 21. The device of claim 20, wherein the nicotine solution is a nicotine suspension. 27. The device of claim 26, wherein the nicotine suspension comprises nicotine granules. 28. The device of claim 27, wherein the nicotine granules comprise coated powdered nicotine particles. 29. The device of claim 28, wherein the nicotine particles are coated for improved palatability. The nicotine granules comprise powdered nicotine particles incorporated into a sphere comprising at least one material selected from the group consisting of sugar, starch, acacia, sodium alginate, carbomer, cellulose, dextrotes, ethylcellulose, methylcellulose, and povidone. 28. The apparatus of claim 27. 21. The device of claim 20, wherein the nicotine solution has an acidic pH. 21. The device of claim 20, wherein the nicotine solution comprises about 4 mg to about 12 mg of nicotine. 21. The device of claim 20, wherein the chamber contains about 1 ml to about 5 ml of the nicotine solution. 21. The device of claim 20, wherein the nicotine in the nicotine solution is selected from the group consisting of levonicotine, dextronicotine, racemic mixtures thereof, and pharmaceutically acceptable salts thereof. 21. The device of claim 20, wherein the nicotine solution further comprises a flavor. A method of reducing a person's smoking frequency, comprising the step of orally administering nicotine to a person using an oral nicotine delivery device, the device comprising:
(A) a tubular chamber having a first end suitable for taking in a liquid or gas from an external source, and a second end suitable for performing oral inhalation;
(B) a nicotine solution contained within the tubular chamber, and (c) a maintenance device within the chamber to prevent release of the nicotine solution from the first end of the chamber;
Oral administration includes the step of a person performing an oral inhalation at the second end of the chamber, wherein the nicotine solution is supplied into the mouth of the person through the second end of the chamber. 37. The method of claim 36, wherein the amount of nicotine administered to the human in a single dose is from about 4 mg to about 12 mg. 37. The method of claim 36, wherein the total amount of nicotine administered to the human per day is from about 4 mg to about 144 mg. 37. The method of claim 36, wherein the human nicotine blood concentration after administration of the nicotine solution is at least about 5 ng / ml of blood. 40. The method of claim 39, wherein the human peak blood nicotine concentration after administration of the nicotine solution is from about 10 ng to about 50 ng / ml of blood. 37. The method of claim 36, wherein the nicotine solution is a nicotine suspension.

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