Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1996-07-01
1999-08-10
Kulkosky, Peter F.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424 7814, 424483, 424499, A61K 3133, A61K 31465
Patent
active
059356049
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to compositions for nasal administration and, more particularly, to compositions for nasal administration of nicotine.
Smoking remains the single most important preventable cause of death in modern society. It can be estimated that in the US alone more than 430,000 deaths in 1988 were attributable to cigarette smoking. At least nine out of ten smokers are to some extend dependent upon nicotine and 75% are moderately to strongly dependent and continue smoking despite attempts to stop. In the United States the strong interest in stopping smoking is demonstrated by the fact that nearly 20 million people try to quit smoking each year. Their need for additional help can be seen in the fact that more than 90% fail to maintain their abstinence.
The major problem with nicotine is that it is highly addictive. Nicotine fulfils all criteria of an addictive drug, it is psychoactive, it affects the mood, it can act as a primary reinforcer, it induces tolerance, and physical as well as psychological changes occur on withdrawal.
Importantly, there is no direct evidence that nicotine itself is carcinogenic or mutagenic, nor does it act as a tumour initiator, promoter or co-carcinogen. Similarly, none of the major metabolites of nicotine are known to be carcinogenic. In contrast, tobacco and especially tobacco smoke contains several potent carcinogens.
A major limiting factor in the successful use of nicotine replacement therapy for smoking cessation is the lack of an appropriate delivery system. When a person smokes a cigarette, the level of nicotine rise rapidly in the blood and in the brain with an interval of just 10-20 seconds between taking a puff and the nicotine arriving in the brain. The presently marketed nicotine replacement products, the transdermal nicotine patch and the nicotine chewing gum, are not entirely satisfactory in that they do not provide the patient with the nicotine "buzz" associated with smoking a cigarette, since they are both slowly acting controlled release systems where only low nicotine plasma levels are obtained. Hence clinical trails have shown that only about 20%-30% of those smokers who have used nicotine patches and nicotine chewing gum successfully quit smoking after one year compared to 15% of those smokers receiving behavioural support alone.
Transdermal patches seem to be no more effective than placebo in maintaining smoking cessation in the long term. The long term results after the use of patches alone have not been impressive. Medical Letter (Vol. 34, 37, 1992).
The nicotine chewing gum is a slow release preparation where the rate of release of nicotine will depend on the rate of chewing. It takes 20-30 min of vigorous chewing to release 95% of the nicotine content of the gum. Without chewing or if the gum is accidently swallowed, negligible amounts of nicotine are released. The gum contains 2 or 4 mg of nicotine. A typical smoker needs about 15 pieces of gum a day. The gum has an unpleasant taste and may be irritating to the mouth and throat. Potential side effects are heartburn and hiccups. Tired and aching jaws may be experienced from intensive chewing and users rarely maintain blood nicotine concentrations above one third of their levels from smoking. The chewing gum is contraindicated in individuals with gastritis or active peptic ulcer disease and presents difficulties for those wearing dentures.
U.S. Pat. Nos. 3,877,468, 3,901,248 and 3,845,217 discloses a chewing gum comprising nicotine in the form of a complex with an insoluble cation-exchange base.
The nicotine patch placed on the skin will give a steady release of nicotine over 24 hours and should be changed daily. The patch is available in three sizes delivering about 21, 14 and 7 mg/24 hours. With the patch in place it takes 3-4 hours to attain significant blood levels of nicotine. The continuous dosing provided by patches can disrupt the usual day
ight variation in nicotine intake provided by smoking and can result in a total dose of nicotine per 24 hour exceeding the normal smoking do
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Danbiosyst UK Limited
Kulkosky Peter F.
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