Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-06-18
2001-03-27
Goldberg, Jerome D. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S416000, C514S497000, C514S565000, C514S567000
Reexamination Certificate
active
06207699
ABSTRACT:
RELATED APPLICATIONS
None.
BACKGROUND OF THE INVENTION
Numerous studies have documented that medications which increase brain 5-HT, such as fenfluramine, are effective anorectic agents which help obese patients lose weight and which also decrease craving for sweets and carbohydrates (6,23). Evidence from other studies also indicate that increases in brain 5-HT may help decrease craving for alcohol and cocaine (1,8,14,15,18-20,24). 5-hydroxy-L-tryptophan, abbreviated 5-HTP, is the immediate precursor of serotonin (5-HT). A goal of treatment with 5-HTP is to increase brain 5-HT. Previous studies in animals and humans have established that administration of 5-HTP increases brain 5-HT (7,13,21). However, 5-HTP administered systemically (intraperitoneal, oral, intravenous) is rapidly converted to 5-HT by an enzyme called peripheral decarboxylase before it ever gets into the brain. Thus, to achieve the desired effect of increasing brain 5-HT it is necessary to co-administer an inhibitor of the enzyme peripheral decarboxylase along with the 5-HTP. A typical means of doing so is to administer carbidopa along with the 5-HTP.
Increases in synaptic 5-HT decreases the firing rate of 5-HT neurons via stimulation of inhibitory 5-HT1a receptors located on the cell bodies in the raphe. This serves as a negative feedback loop. Administration of 5-HT1a receptor antagonists interrupt this feedback loop, and thereby increase the ability of 5-HT reuptake inhibitors to increase synaptic 5-HT (5,9,17). The clinically available beta adreneric receptor antagonist medication pindolol is also a 5-HT1a antagonist, and can be used to increase the ability of 5-HTP to increase brain 5-HT (4,12).
BRIEF SUMMARY OF THE INVENTION
Medications which increase brain serotonin (5-hydroxytryptamine, 5-HT) decrease hunger, craving for food, especially for carbohydrates and candy (i.e. sweets). Evidence from other studies also indicate that increases in brain 5-HT may help decrease craving for alcohol and cocaine (1,8,14,15,18-20,24).
The biosynthesis of 5-HT in the brain proceeds from the uptake of dietary tryptophan by the neuron, followed by its conversion to 5-hydroxytryptophan (abbreviated 5-HTP) by an enzyme called tryptophan hydroxlyase. 5-HTP is decarboxylated to 5-HT by an enzyme called L-aromatic amino acid decarboxylase. When administered to animals or humans, 5-HTP is rapidly decarboxylated by an enzyme called L-amino acid decarboxylase also commonly called peripheral decarboxylase (11). Thus, when administered via the oral, intravenous and other peripheral routes, 5-HTP is rapidly converted to 5-HT and little if any 5-HTP enters the brain. 5-HT itself does not cross the blood brain barrier and any increase in blood 5-HT is removed by uptake into platelets and metabolism by monamine oxidase. Carbidopa is an inhibitor of Laromatic amino acid decarboxylase. Carbidopa does not enter the brain, and thus administration of carbidopa selectively blocks the conversion of 5-HTP to 5-HT in the periphery, but not the brain. Thus, it is well known that co-administration of carbidopa with 5-HTP can be used to increase brain 5-HT (2,10,11). In addition, administration of 5-HT1a receptor antagonists such as pindolol can be used to increase the ability of 5-HTP to increase brain 5-HT (4,12).
The doses of 5-HTP and carbidopa used in various clinical studies were reviewed by Byerley et al. (2) and van Pragg (22). These reviews demonstrate that 5-HTP was used in doses exceeding 50 mg per day and that when 5-HTP was used in combination with carbidopa, the dose of carbidopa was in excess of 50 mg per day. For example, the study by Ceci et al. (3) administered 560 mg of 5-HTP per day.
There are two novel aspects of the invention. One novel aspect of the invention are the doses of the 5-HTP and carbidopa. I have found much lower daily doses than have been used before to be effective in decreasing appetite, decreasing craving for food and for promoting weight loss. In particular, capsules containing [5-HTP (5 mg) plus carbidopa (5 mg)], [5-HTP (10 mg) plus carbidopa (5 mg)] or 5-HTP (15 mg) plus carbidopa (5 mg)] orally administered one to three time per day are particularly effective. The second novel aspect of the invention relates to the concurrent use of pindolol along with the 5-HTP/Carbidopa. In particular, capsules containing [5-HTP (5 mg) plus carbidopa (5 mg) plus pindolol (2 mg)], [5-HTP (10 mg) plus carbidopa (5 mg) plus pindolol (2 mg)] or 5-HTP (15 mg) plus carbidopa (5 mg) plus pindolol (2 mg)] orally administered one to three time per day are particularly effective.
REFERENCES:
Ceci et al. “The effects of oral 5-hydroxytryptophan administration on feeding behavior in adult female subjects” J.Neural.Transm. 76:109-117, 1989.*
Magnussen et al. “Human pharmacokinetics of long term-hydroxytryptophan combined with decarboxylase inhibitors” Eur. J. Clin. Pharmacolo. 23:81-86, 1982.
Goldberg Jerome D.
Kim Jennifer
LandOfFree
Pharmaceutical combinations for treating obesity and food... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutical combinations for treating obesity and food..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical combinations for treating obesity and food... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2543382