Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution... – Containing or obtained from palmaceae
Reexamination Certificate
2002-01-10
2004-07-06
Tate, Christopher R. (Department: 1654)
Drug, bio-affecting and body treating compositions
Plant material or plant extract of undetermined constitution...
Containing or obtained from palmaceae
C424S725000, C424S736000
Reexamination Certificate
active
06759063
ABSTRACT:
TECHNICAL FIELD
The present invention relates to compositions containing
Serenoa repens
for formulation in drug, cosmetic, food, and dietary supplements. The present invention relates to compositions comprising
Serenoa repens
and agents with undesired sympathomimetic activity and the use thereof, in clinical or veterinary applications. The present invention relates to reducing the debilitating, untoward and undesirable side effects associated with use of agents that stimulate adrenergic receptors or display sympathomimetic activity.
BACKGROUND ART
Throughout this application, various publications, patents, and published patent applications are referred to by an identifying citation; full citations for these documents may be found at the end of the specification. The disclosure of the publications, patents, and published patent specifications referred in this application are hereby incorporated by reference into the present disclosure.
Sympathomimetic agents are widely used as pharmacologic agents to control or modulate a variety of physical conditions, including obesity, appetite, sinus congestion, body temperature, thermotolerance, asthma, alertness and physical performance. Examples of sympathomimetic agents are mixtures composed of caffeine and ephedrine, and/or its related alkaloids, over the counter ephedrine drugs, phenylpropanolamine, extracts and concentrates of Ephedra species and
Sida cordifolia
, (plant sources of ephedrine and its related alkaloids), norephedrine (phenylpropanolamine) and pseudoephedrine, and synephrine (either synthetic or derived from plant sources). Commonly, use of these pharmacologic agents is accompanied by undesirable, and often debilitating, side effects. Onset of the adverse side effects can result from both direct stimulation of adrenergic receptor activity, primarily alpha-adrenergic receptor activity, and release of neuronal norepinephrine. See, Lasagno, L. “Phenylpropanolamine. A Review” (1988) John Wiley & Sons, Inc. New formulations of the pharmacologic agents delivering pharmacologically equivalent effects with a mitigation of sympathomimetic effects would be a tremendous improvement over the products presently available.
The sympathomimetic agent ephedrine has potent thermogenic and anti-obesity properties in both rodents and humans. The effect is markedly enhanced by caffeine, while caffeine alone has no effect. Astrup et a. (1992)
Int. J. Obes. Relat. Metab. Disord.
16:269. Reported side effects included tremors, insomnia and dizziness.
Despite its therapeutic efficacy, ephedrine and caffeine (EC) administered in clinically relevant doses produces acute cardiovascular effects. Astrup et al. (1993)
Int. J Obes. Relat. Metab. Disord.
1:S41-3. EC exerts a supra-additive synergism on thermogenesis and systolic blood pressure, without affecting diastolic blood pressure. EC also increases plasma glucose, insulin and C-peptide concentrations. During dietary energy restriction, EC promotes fat loss and preserves fat-free mass, which may contribute to its chronic effect on energy balance. EC also possesses repartitioning properties, which may be useful in the treatment of obesity. During chronic treatment, the effect of EC on energy expenditure is maintained, while side effects subside after tolerance develops to the hemodynamic and metabolic effects.
In separate studies, dexfenfluramine (DF) and EC have been shown to promote weight loss in obese patients. Breum et al. (1994)
Int. J Obes. Relat. Metab. Disord.
18:99. Reported side effects included central nervous system side effects, especially agitation, and gastrointestinal symptoms.
A controlled, clinical study comparing the effects of two anorectic drugs, a prescription containing EC (Elsinore pills) and diethylpropion, with placebo was conducted among obese patients, age 18-60 years and overweight 20-80%. Malchow-Moller et al. (1981)
Int. J Obes.
5:183. Four patients treated with diethylpropion, and four patients treated with EC pills were withdrawn because of complaints of exaltation, tremor and insomnia.
In order to assess the effects of ephedrine hydrochloride on weight loss, a double-blind controlled study was performed in unselected obese outpatients. Pasquali et al. (1985)
Int. J. Obes.
9:93. Patients receiving ephedrine (150 mg/day) suffered from significantly greater adverse side effects than the placebo group. Ephedrine-containing products derived from various sources are popular for multiple uses, including asthma, weight loss/appetite suppression, energy, enhanced physical performance, sexual enhancement, and euphoria. It would be useful to reduce unwanted side effects of ephedrine containing products.
A double-blind, placebo-controlled 8-week trial was conducted for an herbal supplement containing ma huang (Ephedra: as a source of ephedrine) and guarana as a source of caffeine (Metabolife 356™). Nasser et al. (1999) FASEB J. 13:660.7. Of 67 randomized subjects, 7 dropped out of the study before first follow-up. Of these 7 subjects, 5 were taking the supplement, 1 of which developed high blood pressure and 4 of which reported heart palpitations. Of the 60 subjects who returned for at least one follow-up visit, 12 dropped out of the study before week 8. Of these 12, subjects 6 were taking the supplement, 2 of which reported heart palpitations, 1 of which reported irritability and 1 of which developed increased systolic blood pressure. In subjects who completed the study, increases in the following were reported (supplement versus placebo): dry mouth (5 vs 1); heart palpitations (2 vs 2); blood pressure (>20 pts): systolic (2 vs 0), diastolic (1 vs 1); insomnia (9 vs 2); constipation (1 vs 4) and extra-menstrual bleeding (1 vs 2). This study concluded that this herbal supplement promotes weight loss but may also produce undesirable side effects in some subjects and recommended that long term use would require further study.
In order to evaluate the pharmacokinetic properties of a commercially available source of ephedrine contained in an extract of ma huang, heart rate and blood pressure responses to the product were examined in normotensive, healthy adults. White et al. (1997)
J. Clin. Pharmacol.
37:116. Ma haung had variable effects on blood pressure and increased heart rate in healthy, normotensive adults.
Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has only recently been associated with either ephedrine or its plant derivative Ephedra. Evidence of this is provided in a case study where a 39-year-old African American male presented with hypertension and a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. Zaacks et al. (1999)
J Toxicol. Clin. Toxicol.
37:485. He was taking ma huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed that the patient was in mild respiratory distress. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated and one month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal and the patient asymptomatic. Ma huang was the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.
Between December 1993 and September 1995, the Bureau of Food and Drug Safety, Texas Department of Health (TDH), received approximately 500 reports of adverse events in persons who consume
King & Spalding LLP
Tate Christopher R.
LandOfFree
Methods and compositions for reducing... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods and compositions for reducing..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and compositions for reducing... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3253618