Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
1999-04-30
2001-05-29
Kulkosky, Peter F. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
C514S813000, C514S879000, C424S468000, C424S482000
Reexamination Certificate
active
06238689
ABSTRACT:
The present invention relates to the use of nicotine composition delivered for absorption from the intestine, particularly the ileum and colon, for the treatment of nicotine responsive conditions particularly schizophrenia, Alzheimer's disease, Tourette's syndrome, Parkinson's disease, depression (particularly associated with cessation of smoking), inflammatory skin conditions, and as an aid to cease smoking.
Cigarette smoking has been reported as altering the inflammatory response in the skin following application of irritants and rubefacients (Mills et al, BMJ 1993;307:911). In a follow up study, Mills administered nicotine via a transdermal delivery system and was found to suppress the cutaneous inflammatory response to sodium lauryl sulphate (irritant) and UVB radiation, as well as reactive hyperaemia following arterial occlusion (Workshop on Nicotine as a Therapeutic Agent—May 15, 1996, Frankfurt, Germany). In the same workshop, Sandberg et al reported that administration of nicotine (either 2 mg nicotine gum or 7 mg transdermal nicotine patch) along with neuropleptics produce a decrease in tic symptoms in patients suffering from Tourette's syndrome. A beneficial response of Alzheimer's and Parkinson's disease patients to nicotine was also reported at the workshop.
However, nicotine has a substantial effect on the cardiovascular system including increased heart rate and blood pressure resulting in greater myocardial work and oxygen requirement and coronary vasocontriction. Nicotine has also be purported to activate platelets and to adversely affect blood lipids, thereby promoting atherosclerosis and increasing the risk of acute coronary events. Furthermore nicotine from tobacco products has also been associated with an increased risk of cancer and cerebral haematoma.
Known delivery routes for nicotine are via cigarette smoking, inhalers, nasal spray, polyacrylic gum and transdermal patch. Inhalers and nasal sprays deliver nicotine rapidly to the blood plasma in high peak concentrations and can therefore give rise to addictive cravings similar to cigarette smoking. The use of nicotine gum and transdermal patches are reported at the aforementioned Nicotine Workshop, and are used extensively to aid in the cessation of smoking. However long term administration of a nicotine patch is limited by a relatively high rate of dermatological side effects, especially in the elderly. Patients have also reported side effects such as nausea, headaches, tremor and vomiting, thereby again limiting patient compliance. Polyacrylic gum again relies heavily on good patient compliance. The amount of nicotine delivered depends on the rate and length of chewing and therefore it is difficult to achiever a controlled uniform plasma concentration of nicotine.
It is an object of the present invention to obviate or mitigate the aforesaid disadvantages.
It is a further object to provide for delivery of nicotine which is convenient and where side effects of nicotine is limited, while still providing a beneficial effect on conditions susceptible to treatment with nicotine.
The inventors have now found that the blood plasma concentration of nicotine can be controlled to therapeutic levels while limited the adverse side-effects if nicotine is absorbed from the small or large intestine. For example nicotine can be delivered rectally, such as by an enema, to the large intestine or as a post-gastric delayed release oral (DRO) composition to the small and/or large intestine. In this way the nicotine is absorbed more slowly into the blood plasma over a sustained time period thereby decreasing the peak plasma concentrations which typically induces nicotine dependency. It also avoids the dermatological side-effects of a transdermal patch, and the uncertain effectiveness of nicotine chewing gum. Thus therapeutic levels of nicotine can be delivered to treat the aforementioned conditions while reducing the adverse side-effects normally associated with nicotine.
Accordingly in a first aspect of the invention there is provided the use of nicotine or a pharmacologically acceptable derivative or metabolite thereof in the preparation of a medicament which is adapted for absorption from the small and/or large intestine for the treatment or prophylaxis of inflammatory skin conditions, schizophrenia, Alzheimer's disease, Parkinson's disease, Tourette's syndrome, depression, or to assist in the cessation of smoking. In fact, nicotine could be used therapeutically in any disease state in which an association with non-smoking or smoking status would suggest a therapeutic role for nicotine. For the avoidance of doubt, absorption from the small and/or large intestine includes from the pylorus to the anus.
Examples of inflammatory skin conditions susceptible to the invention are acne, reigacne vulgaris and rosacea. With Alzheimer's patients, the invention will typically improve their attentional function. Depression, particularly associated with the cessation of smoking, is susceptible to treatment with the invention.
A further aspect of the invention comprises a method for the treatment of nicotine responsive condition, disclosed herein, comprising administering to the patient an effective amount of a rectally administrable or delayed release oral (DRO) DRO composition as defined in the first aspect of the invention.
Co-pending International No. PCT/GB97/00369 and U.S. application Ser. Nos. 08/605,319 and 08/794,668 relate to the use of nicotine delivered for sustained release from the colon for the treatment of inflammatory bowel disease, and therefore this nicotine responsive condition is not within the scope of the present condition.
Although there is some benefit in having absorption of nicotine from anywhere in the small or large intestine, it is most preferred that absorption occurs predominantly in the colon. This in the case of a post-gastric delayed release oral (DRO) composition, the composition will pass through the small intestine in about 4 to 8 hours and will then reside in the colon for about 48 hours. Furthermore nicotine is absorbed more slowly in the colon than in the small intestine. Therefore nicotine delivered for absorption predominantly in the colon will be absorbed more slowly over a sustained period and will give rise to a more uniform blood plasma concentration, and will reduce the peak concentration of nicotine which otherwise cause dependence and adverse side-effects.
By predominant absorption from the colon, we mean to include at least 70%, more preferably at least 80%, such as at least 85% or at least 90% of the total dose of nicotine.
In a preferred embodiment, a DRO composition is delivered for dissolution in the ileum, more particularly the terminal ileum so that most of the nicotine would be released and absorbed in the colon.
The most preferred form of the invention is a sustained and post-gastric delayed released composition. In this form, the effect of the nicotine being absorbed more slowly and at more uniform concentration levels into the bloodstream from the small and/or large intestine, is enhanced because the composition also controls the release of the nicotine over a sustained time interval. This form of the invention is of particular benefit, where most of the nicotine is released and absorbed in the colon i.e. the composition resides here for the longest time period. Thus in a preferred embodiment the invention relates to use of nicotine given orally as a sustained release DRO composition (advantageously having an enteric coating) for the treatment of nicotine responsive conditions.
Various sustained release compositions of nicotine are described later and include nicotine being present as a nicotine-polyacrylate complex, nicotine is an ampiphilic polyglycolized glyceride matrix, and using various enteric coated microgranules containing nicotine in an enteric coated capsule. A preferred form of saturated polyglycolized glyceride is Gelucire™, particular Gelucire 44/14 and 53/10.
By pharmacologically acceptable derivatives and metabol
Evans Brian K.
Rhodes John
Rhodes Peter
Sandborn William J.
Kulkosky Peter F.
Mayo Foundation for Medical Education and Research
LandOfFree
Intestinal absorption of nicotine to treat nicotine... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Intestinal absorption of nicotine to treat nicotine..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Intestinal absorption of nicotine to treat nicotine... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2462829