GB2030862A - A composition for treating drug addiction such as smoking nicotine-containing products - Google Patents
A composition for treating drug addiction such as smoking nicotine-containing products Download PDFInfo
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- GB2030862A GB2030862A GB7912389A GB7912389A GB2030862A GB 2030862 A GB2030862 A GB 2030862A GB 7912389 A GB7912389 A GB 7912389A GB 7912389 A GB7912389 A GB 7912389A GB 2030862 A GB2030862 A GB 2030862A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/465—Nicotine; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
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- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Otolaryngology (AREA)
- Pulmonology (AREA)
- Emergency Medicine (AREA)
- Dispersion Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
A composition for treating drug addition such as the smoking of nicotine-containing products or the taking of heroin comprises an aerosol containing the active agent of the addiction-nicotine for tobacco smokers or morphine for heroin addicts.
Description
SPECIFICATION
A treatment for drug addiction such as smoking
nicotine-containing products
This invention relates to methods and products for
use in assisting tobacco smokers to give up smok
ing, and addicts of other drugs such as heroin to give
up their addiction.
E. Gritz and M. Jarvik in Pharmacological Aids for the Cessation of Smoking discuss the use of drugs to treat cigarette smoking. Some of the drugs mentioned include hexamethonium, pentolinium, mecamylamine and lobeline. Reference is made to the belief that nicotine is the chemical constituent of tobacco which produces a craving for cigarettes and other such products and it is noted that few attempts have been made to use nicotine as an anti-smoking aid.
Gritz and Jarvikfurther discuss the development of a nicotine containing chewing gum (Ferno, O.,
Psychopharmacologia 31:201-204, 1973). They conclude that nicotine gum supplement provides only a small advantage over placebo gum in terms of actual smoking consumption. There is also a recent article in the American Journal of Psychiatry (Jarvik et al) 1977 which states that gum is effective in some cases.
Further discussion of nicotine can be found in "The Role of Nicotine in the Smoking Habit" by M.
Jarvik, and related studies are reported in "Effect of
Dose on the Pharmacokinetics of Intravaneous
Nicotine in the Rat", R. Miller et al, Vol. 5 No. 5 Drug
Metabolism and Disposition.
Various proposals have been madeforthe adaptation of smoking techniques using special pipes, imitation cigarettes, or cigarette holders which variously generate, as a result of the usual sucking action in smoking, relatively innocuous vapours having the odour or flavour of tobacco smoke, or which merely dilute the volume of real smoke inhaled with ambient air. In some cases, specially formulated aromatic liquids, or an extract of tobacco smoke from which tars and harmful residues have been removed, are packaged in ampoules, and these can be graded in concentration to provide a regular course for achieving the progressive decline of the patients' addiction to smoking. Examples of the foregoing can be found in U.S. Patents Nos. 2,764,154; 2,809,634; 2,830,597; 3,347,231 and 3,810,476 and in French
Patent No. 1,398,033.
None of these proposals have envisaged the physical administration of nicotine or a nicotinecontaining composition.
It is an object of the invention to provide an improved method of assisting smokers to stop smoking which consists of a technique for administering nicotine to replace the nicotine intake commonly associated with smoking.
Another object is to provide improved techniques for terminating various addictions, such asto heroin by using dilute morphine solutions.
It is also an object to provide nicotine products, for example cotinine, which may reduce symptoms of withdrawal from nicotine and thus aid in smoking
cessation.
According to the present invention, the method of
treating, with a view to curing, an addiction to a drug
such as nicotine or heroin, comprises orally administering to a subject an aerosol containing the active
ingredient of the drug.
In the treatment of a subject addicted to smoking tobacco, it is preferred to administer the aerosol in such an amount as to increase the level of nicotine in the blood of the subject to a value which would be substantially produced by approximately one cigarette with moderate nicotine output.
Advantageously, in the treatment of a tobacco smoker, the aerosol is administered in such an amount and manner as to rapidly increase the nicotine level to a value between 10-20 ng/ml.
Conveniently, the aerosol for smokers is formed from a nicotine-containing saline solution with a particle size of a mean mass diameter of preferably 1 to 4 micrometres. This solution may contain propylene glycol or glycerine, NaH2PO4 and nicotine HCI, and a preferred formulation is a solution of 0.90M NaH2PO4, 42% propylene glycol or glycerine, and 8mg/ml nicotine HCI, each quantity representing the final concentration in solution.
According to another aspect of the invention, the nicotine-containing aerosol is administered over a period of a plurality of days until the serum cotinine and carboxyhaemoglobin levels of the subject drop to an extent indicating substantial reduction of smoking of the nicotine products by the subject.
Levels approaching zero are the goal.
Practical realisation of the invention will be illustrated by the following description, read in conjunction with the accompanying diagrammatic drawing of a known construction of nebulizer, of a series of tests carried out on grqups of tobacco smokers.
A number of nicotine addicts were divided into two groups. One group was treated with a placebo and used as a control group. The placebo was a low-concentration nicotine solution. The other (treated) group inhaled a high-concentration nicotine solution.
In the description of the tests and tabulations of the clinical results which follow, certain symbols and abbreviations are used as follows:
p means probability;
Ss means subjects (identified by letters);
M/F means male or female;
ng/ml means nanograms per milli-litre;
S.D. means standard deviation;
X means mean value;
S.E.M. means standard error of mean;
A means difference;
M means molar.
Data from the placebo-treated control group and the nicotine-treated group were analyzed in detail for changes in smoking indicators. These data include the changes in level in the subjects' blood of cotinine, nicotine and carboxyhaemoglobin (COHG) over a two-week period during which time blood samples were taken three times a week.
In the placebo group, the continine level fell slightly from the pre-treatment level (Table 2). This fall was approximately 35 nanograms per ml., and
was not significant. In addition, there was virtually
no change in the carboxyhaemoglobin (COHG).
Because these individuals were inhaling a very low
concentration of nicotine, the effective uptake of
nicotine proved to be minus 2 nanograms per ml.
indicating continued metabolism of nicotine from cigarette smoking during a ten-minute inhalation
period. In summary, inhalation of low concentrations of nicotine which do not produce positive
increments of blood nicotine levels fail to influence any of the biochemical markers for smoking behaviour.
In contrast, the treated group showed a significant fall in serum cotinine (p < 0.02) from 353 nanograms per ml. to 220 nanograms per ml. at the end of a two-week period (Table 1). There was a substantial decrease in carboxyhaemoglobin, but because of the wide individual variation the change of 8% to 6% was not statistically significant. The uptake of nicotine on an average was only 4 nanograms per ml, with mean uptakes in some individuals as high as7 or8 nanograms/ml. Analysis of the relationship between the intake of nicotine and the percent fall in serumcotinine levels (Table 3) gave a positive correlation of R = 53. A negative correlation was found for the control group.
In the treated subjects, the nicotine aerosol produced a decrease in consumption of cigarettes as judged by the cotinine level and did so by helping the smoker to curtail the use of cigarettes. This fact was indicated by the drop in carboxyhaemoglobin as well as the significant fall in serum-cotinine. The fall in serum-cotinine would not occur unless a drop in consumption of cigarettes had taken place.
Since both the placebo solution and the high concentration nicotine solution are perceived as similar it would appear that nicotine administered in accordance with the invention has a pharmacological action which satisfies the smoker. Subsequent studies in fourteen smokers indicate that five stopped smoking within a 6 to 8 week period of aerosol use. No other treatment, pyschological or otherwise, was offered this group. Each subject had previously been unable to stop smoking using behaviour modification or even hypnosis.
Studies of nicotine inhalation in acute and chronic cases were conducted using a Babington nebulizer (described below). Smokers participated in a programme (not tabulated herein) to evaluate the ability of the nebulizerto produce sufficient nicotine aerosol over each ten minute period to increase nicotine levels in the blood to about those produced by smoking an average cigarette.
Initial studies were conducted for carboxyhaemoglobin and cotinine serum levels to demonstrate that the subjects were smokers. Serum cotinine levels during the initial study gave a base line of approximately 350, with a range of 242 to 403. Carboxyhaemoglobin levels averaged about 5.5 with a range of 7.7 to 1.4 with most values falling in the 5 to 6 range.
The ability of the subjects to use the aerosol nebulizer was measured daily by obtaining samples of blood before and after use of the device. The mean serum nicotine value before nebulizer use ranged between 3 and 4 ng. per ml., falling off during the last four days of the study owing to a directive to use the nebulizer only as needed during those four days.
The mean nicotine value on the last day was found to be below 1 ng. per ml. Immediately after use of the nebulizer mean serum nicotine rose by 9 ng. per ml. However, more than half ofthe subjects were individually able to inhale as much nicotine as that provided by the average cigarette (17 nglml).
TABLE I
Serum nicotine, coboine, COtinine and carboxyhaemoglobin (CHOG) in smokers inhaling
a nicotine-containing aerosol during a 2-week period.
INITIAL LEVEL MEAN LEVELS (+ S. D.) DURING TREATMENT Sb MiF Nicotine (ng/ml) Cotinine (nglml) COHC (%) Nicotine (nglml) Cotinine (nglml) COHG (7r I M 22.7 316 7.0 26.0+ 8.5 317+85 6.7+1.8 B F 17.8 277 6.7 8.8 + 7.0 169 + 16 3.9 + 7.3 T M 37.1 586 8.8 16.0 + 5.6 232 + 60 6.0 + 2.5
C F 12.4 295 14.1 6.1 + 5.0 113 + 52 2.8 + 2.0
N M 14.0 499 11.6 22.0 + 6.2 374 + 70 9.4 + 3.5
H F 1 14.3 228 6.8 26.0+ 13 150 + 62 5.5 + 1.5
B M 22.0 216 6.2 7.5 t 1.0 224+ 10 7.8
G M 29.6 555 8.9 13.0 + 2.5 196 + 56 4.2 + 2.4 W F 3.1 205 3.1 12.0 +.0 0 205 + 99 7.5 + 5.0 X + SE.M. 18.1 + 3.7 353 t 50 8.1 + 1.0 15.0 + 2.5 220 + 27* 5.98+7.0 * p (.02 as compared to initial cotinine.
TABLE 2
Serum nicotine, cotinine and COHG in smokers inhaling "placebo" nicotine aerosol.
INITIAL LEVEL MEAN LEVEL ( + S. D.) DURING TREATMENT Ss M/F Nicotine(ng/ml) Cotinine (ng/ml) COHG (lo) Nicotine (ng/ml) Cotinine (ng/ml) COHG (7c) G M 44.6 364 11.4 9.8+5.4 147t26 5.7t3.1 D M 4.6 174 6.3 11.7+6.0 15826 5.7 +13 G F 16.5 288 3.9 6.4 + 6.0 260 + 43 4.4 + 1.0
L F 11.1 363 8.0 27.0 t9.7 351 + 63 8.25 + 1.3
T F 4.4 84 2.0 8.8+3.8 115+40 5.5+1.0 B F 12.0 161 4.0 4.0 + 5.6 87 + 42 2.2 1.4
S F ' 14.4 225 5.9 24.6 + 6.4 307 14 8.0 + 1.8 De M 23.8 277 13.1 9.6 + 3.9 233 35 9.2 + 5.0 X + SEN. 12.4 + 5.2 242 + 35 6.9 1.3 12.7 + 2.9 207 33 6.16 + 0.8 TABLE 3
Relation between mean serum nicotine produced by aerosol inhalation ( serum nicotine,
ng/ml) and percentage decrease ( A cotinine/cotinine ) x 100 in serum cotinine in treated
and control groups.
1. TREATED Ss MIF Zi Serum nicotine & S.D. Yo decrease ( scot. ratio )
1 M 6.0t2.7 0
B F 4.5t2.3 49
T M 4.66.5 60
C F 7.7 + 3.8 62 N M 6.98 + 5.4 25 H F 1.6* 34
E M o 0
G M unknown 65**
W F 0.4 0
X+ S.E.M. 4.01. Onglml 299.4%
R=0.53
2. CONTROL Ss A Serum nicotine & S.D. % decrease (#cot. ratio )
G - 11.3 59
D + 1.2 9.
G + 2.9 10
L - 3.1 3
T + 0.9 - 36
B + 0.5 46
S - 4.0 - 27
D - 3.0 16 X+S.E.M. - 1.98ing/mI - + 10% * single value
** not included in determination of correlation coefficient.
Some individual values obtained while utilizing the aerosol device show that a number of participants are able to maintain high levels of cotinine without any appreciable amounts of carboxyhaemoglobin indicating the intensive use of the aerosol.
A number of conclusions were drawn from this feasibility study;
(1) nicotine can be taken into the blood stream in concentrations equal to those obtainable from the average cigarette,
(2) the device produces an aerosol which is not unpleasant and can be used over a protracted period of time,
(3) a number of individuals were very successful at maintaining high cotinine levels throughout the trial although on average most participants showed a sharp drop in the use of the nebulizer by comparison
with the cigarette to roughly one-third of cigarette
use.
To obtain a composition for use in treatment
according to the invention, nicotine base obtained
from tobacco is distilled to a colourless or slightly
yellow liquid. This liquid is titrated to pH6 by the
addition of dilute hydrochloric acid to a final con
centration of 100 mg/ml as the base. Propylene
glycol, U.S.P., and 1.8M NaH2PO4 solution in distilled
water are added. The percentage composition is 42%
propylene glycol, 8% nicotine solution, (final con
centration as base is 8 mg/ml) and 50% acid phos
phate solution.
Propylene glycol percentages can be varied between 20% and 60% with a range of 35% to 45% being especially effective in reducing irritation caused by the nicotine without unduly diminishing the production of aerosol particles.
Nicotine hydrochloride, tartrate, sulphate or similar salts can be used as alternatives in the solution in concentrations sufficient to achieve serum levels in venous blood of 10 ng/ml to 20 nglmlfollowing an inhalation period of 10 minutes. The nicotine concentration can be decreased when nebulizer output increases. The range is from 1-10 mg/ml in the phosphate or other buffering medium.
The acid phosphate of sodium is very soluble in water and is the preferred sodium salt. The concentration can range between 0.5 and 2M as the additive.
The final concentration is about one-half of this. The initial experiments used as 1M solution while present applications use a 2M solution which greatly diminishes irritation due to its acidity and buffer capacity. Other useful buffers include acetate, lactate, tartrate, and similar metabolizable substances.
In order to provide rapid uptake of a nicotine aerosol by the lungs, small particles must be generated so that they enter the fine bronchiolar passageways. Particles greater than 10,um in diameter will generally impact on the mucosa of the upper airways and not be absorbed except over a long period. They will also serve to irritate the tissues.
Increased uptake occurs below and above 1 wm. The aqueous solution of acid phosphate, glycol, and nicotine produces particles larger than 1 cm, in the range of 3-4 Fm, using the Babington nebulizer. This device is made of glass or plastic and is able to siphon solution from a reservoir to a point overhanging a hollow glass ball. The ball has a small orifice or pin-hole about 0.1 to 0.3 mm diameter on an equatorial diameter. The solution falls over this ball and air or some gas such as freon is forced into the ball and escapes through the pin-hole. In doing so, it ruptures the film of solution which spreads over the surface of the ball, generating large numbers of fine droplets.Those of large size are blocked by an impactor placed in front of the pin-hole, while the smaller particles are drawn away into the mouth of the user as he or she inhales and thereby draws or
siphons the solution over the ball. When a rubber
squeeze bulb of 70 ml. capacity is used to pressurise the ball and is squeezed vigorously four times during
one inhalation lasting about 2-4 seconds, the output
of the device is about 2.5 ,al. This output can be dou
bled by replacing the squeeze bulb with a freon cannister or an air hose pressurized to 20 psi. Particle size may vary depending on the size of the pin-hole, and to some extent on the viscosity of the liquid.
An alternative to the Babington nebulizer is a de
Vilbiss device. The latter needs to have a 90 bend in the mouthpiece to reduce the number of large particles. The output of the No. 42 Model is about the same as that of the Babington. The de Vilbiss nebulizer is used by first squeezing the bulb and then inhaling.
Referring to the drawing, the Babington nebulizer 10 consists of a container 12 connected to a compartment 14to which a squeeze bulb 16 is attached by a tube 18. The container 12 has an inlet opening 20 and houses a siphon 22 having a discharge neck 24 bent round to overlie a hollow ball or sphere 26 carried on the tube 18. The wall of the sphere 26 has a pin-hole opening 28 on an equatorial diameter of the sphere approximately at right angles to the axis of the outlet from the discharge neck 24. Opposite the pin-hole opening 28 is an impactor 30. The compartment 14 has a mouthpiece 32.
In use, when solution 34 has been introduced into the container 12, it is aspirated, by the suction of the user at the mouthpiece 32, up the siphon 22 and onto the sphere 26, where it spreads in a thin film over the surface and covers the pin-hole opening 28. Operation of the squeeze bulb 16 forces airthrough the pin-hole opening 28, causing the film to break away from the opening in droplets whose size is mainly determined by the size of the pin-hole 28. Droplets which exceed the size range mentioned above strike the impactor 30 and are arrested. Droplets of the required size are inhaled by the subject through the mouthpiece 32.
The Babington nebulizer is described by M. Litt and D. Swift in American Review of Respiratory Disease, Vol. 105, Number 2, February 1972.
Because droplet size is related to the thickness of the dynamic film flowing over the spherical surface, it can be controlled by regulating the velocity of the film and the contour of the surface 26 in conjunction with the atomizing air pressure. By the use of several pin-hole openings in one ball 26, or by using more than one ball, the total output can be greatly increased with little increase in complexity or size of the equipment. By varying the pin-hole size, and the angle of its axis relative to that of the discharge neck 24, in conjunction with air pressure and flow of liquid, a wide range of control of output is possible.
The pin-hole 28 can be rectangular.
According to the present invention, the inhalation of nicotine to provide levels of serum nicotine approximating to those produced by smoking the average cigarette is used as a means of aiding withdrawal from cigarette smoking, either by itself or in conjunction with a smoking behaviour modification
programme. Data indicate that the solution of nicotine and additives, when used in a Babington
nebulizer, will produce adequate serum levels of
nicotine. The data also show that such use enables treated individuals to significantly reduce the use of cigarettes as compared with a group of individuals
using very low or placebo concentrations of nicotine.
The invention is equally applicable to other addiction-causing substance such as heroin and cotinine. Such substances will, according to the invention, be administered orally in aerosol form with particle sizes principally between 1 and 4,um. in diameter and in such amounts as to diminish feelings of withdrawal or craving.
Claims (15)
1. The method of treating an addict to a drug such as nicotine or heroin which consists of the oral administration, at intervals over a period of weeks, of a dilute solution of the active agent or a chemical equivalent thereof which produces the addiction.
2. The method according to claim 1 wherein the solution is orally administered by inhalation thereof in aerosol form.
3. The method according to claim 2 wherein the aerosol is so produced as to consist mainly of droplets in the size range 1-4 m diameter.
4. The method according to claim 2 or 3 for treating a smoker of cigarettes or other nicotine products wherein the aerosol is administered in such an amount as to increase the nicotine blood level of the subject to a value which would be substantially produced by approximately one cigarette.
5. The method according to claim 4 wherein the aerosol is administered in such an amount as to increase the nicotine blood level of the subject to a value of up to about 20 ng/ml.
6. The method according to claim 4 or 5 wherein the aerosol is formed from a nicotine-containing saline solution.
7. The method according to claim 6 wherein the saline solution contains propylene glycol or glycerine, NaH2PO4 and nicotine HCI.
8. The method according to claim 7 wherein the solution is formed of .90M NaH2PO4, 42% propylene glycol or glycerine and 8 mg./ml. nicotine HCI.
9. The method according to any of claims 4-8 wherein the aerosol is administered over a period until the serum cotinine and carboxyhaemoglobin levels in the subject's blood drop to an extent indicating at least a substantial reduction of absorption of nicotine by the addict.
10. The method according to any preceding claim wherein the aerosol is administered in such doses over such a period as to minimise in the subject feelings of craving or withdrawal.
11. A solution for use in the method according to any of claims 4-10 comprising a saline solution including nicotine HCI.
12. Asolution according to claim 11 including propylene glycol or glycerine and NaH2PO4.
13. A solution according to claim 12 including about 50% propylene glycol or glycerine, 0.90M NaH2PO4 and 8 mg./ml. nicotine HCI.
14. The method of treating an addict to a drug substantially as hereinbefore described.
15. A solution capable of producing an aerosol for use in the method claimed in claim 14 substantially as hereinbefore described.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US89525478A | 1978-04-10 | 1978-04-10 |
Publications (1)
Publication Number | Publication Date |
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GB2030862A true GB2030862A (en) | 1980-04-16 |
Family
ID=25404220
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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GB7912389A Withdrawn GB2030862A (en) | 1978-04-10 | 1979-04-09 | A composition for treating drug addiction such as smoking nicotine-containing products |
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Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3401763A1 (en) * | 1983-01-21 | 1984-07-26 | Aktiebolaget Leo, Helsingborg | TOBACCO SMOKING SUBSTANCE PREPARATION FOR ADMINISTRATION BY THE NOSE |
EP0148748A2 (en) * | 1984-01-09 | 1985-07-17 | Ab Leo | Improved snuff and preparation thereof |
GB2191718A (en) * | 1986-06-18 | 1987-12-23 | British American Tobacco Co | Aerosol device simulating a smoking device |
EP0266443A1 (en) * | 1986-11-03 | 1988-05-11 | Allen W. Jacobs | Process for the inclusion of a solid particulate component into aerosol formulations of inhalable nicotine |
WO1989004661A1 (en) * | 1987-11-19 | 1989-06-01 | Indaus International Pty Ltd | Nicotine compositions |
WO1993012764A1 (en) * | 1992-01-03 | 1993-07-08 | The Governors Of The University Of Alberta | Composition to help stop smoking |
US5441060A (en) * | 1993-02-08 | 1995-08-15 | Duke University | Dry powder delivery system |
US5939100A (en) * | 1993-11-01 | 1999-08-17 | Pharmacia And Upjohn Ab | Composition for drug delivery comprising nicotine or a derivative thereof and starch microspheres and method for the manufacturing thereof |
WO2003101454A1 (en) * | 2002-06-03 | 2003-12-11 | Pfizer Health Ab | A buffered, liquid nicotine composition for pulmonary administration |
WO2004002446A1 (en) * | 2002-07-01 | 2004-01-08 | Soderlund Patrick L | Composition and method for cessation of nicotine cravings |
US7767698B2 (en) | 2002-06-03 | 2010-08-03 | Mcneil Ab | Formulation and use thereof |
US7900637B2 (en) | 2001-06-25 | 2011-03-08 | Niconovum Ab | Device and method for the administration of a substance |
US8741348B2 (en) | 2002-12-20 | 2014-06-03 | Niconovum Ab | Physically and chemically stable nicotine-containing particulate material |
WO2015177177A1 (en) * | 2014-05-21 | 2015-11-26 | Mcneil Ab | A liquid formulation comprising nicotine for aerosol administration |
US9402809B2 (en) | 2006-03-16 | 2016-08-02 | Niconovum Usa, Inc. | Snuff composition |
US10213586B2 (en) | 2015-01-28 | 2019-02-26 | Chrono Therapeutics Inc. | Drug delivery methods and systems |
US10258778B2 (en) | 2004-09-13 | 2019-04-16 | Chrono Therapeutics Inc. | Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like |
US10653686B2 (en) | 2011-07-06 | 2020-05-19 | Parkinson's Institute | Compositions and methods for treatment of symptoms in parkinson's disease patients |
US10679516B2 (en) | 2015-03-12 | 2020-06-09 | Morningside Venture Investments Limited | Craving input and support system |
US10716764B2 (en) | 2003-10-27 | 2020-07-21 | Morningside Venture Investments Limited | Transdermal drug delivery method and system |
US11285306B2 (en) | 2017-01-06 | 2022-03-29 | Morningside Venture Investments Limited | Transdermal drug delivery devices and methods |
US11596779B2 (en) | 2018-05-29 | 2023-03-07 | Morningside Venture Investments Limited | Drug delivery methods and systems |
-
1979
- 1979-04-09 GB GB7912389A patent/GB2030862A/en not_active Withdrawn
Cited By (50)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3401763A1 (en) * | 1983-01-21 | 1984-07-26 | Aktiebolaget Leo, Helsingborg | TOBACCO SMOKING SUBSTANCE PREPARATION FOR ADMINISTRATION BY THE NOSE |
EP0148748A3 (en) * | 1984-01-09 | 1988-01-07 | Ab Leo | Improved snuff and preparation thereof |
EP0148748A2 (en) * | 1984-01-09 | 1985-07-17 | Ab Leo | Improved snuff and preparation thereof |
GB2191718B (en) * | 1986-06-18 | 1990-09-05 | British American Tobacco Co | Aerosol device simulating a smoking article |
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