Tryptophan source from plants and uses therefor

Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution... – Containing or obtained from cucumbrits

Reexamination Certificate

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C514S023000, C514S419000

Reexamination Certificate

active

06503543

ABSTRACT:

BACKGROUND OF THE INVENTION
Tryptophan is a naturally occurring essential amino acid that has a number of interesting medicinal qualities including treatment of insomnia as well as an adjunct in the treatment of a number of psychiatric disorders. After absorption, tryptophan circulates in the blood (approximately 80% bound to plasma albumin with the remaining 20% circulating as free tryptophan) and under appropriate conditions tryptophan is transported into the brain. Once across the blood brain (BBB), tryptophan becomes available for metabolism into serotonin, a neurotransmitter implicated in mood and sleep regulation (Boman, 1988). Serotonin, in turn, is metabolized to melatonin; a sleep related hormone found in the pineal gland, a small cone-like structure in the epithalamus of the brain that regulates the 24-hour circadian rhythm in humans. Ingestion of a sufficient quantity of tryptophan consistently results in reduced sleep latency (the time from “lights out” to sleep) and an improvement in overall quality of sleep through improved sleep architecture (Boman, 1988). Tryptophan metabolism to serotonin also serves well in conditions where depleted serotonin levels exists such as anxiety disorders, depression, obsessive-compulsive some pain disorders, aggression and eating disorders.
SUMMARY OF THE INVENTION
A naturally derived, tryptophan-rich composition with several unique characteristics has been developed by enriching the tryptophan content of a tryptophan-rich protein source. Compositions of the invention comprise a plant source naturally containing tryptophan, preferably squash seeds, such as butternut squash seeds, peppercorn squash seeds and pumpkin seeds. Preferably, the plant source is at least partially defatted to concentrate the tryptophan content. The composition further comprises a carbohydrate sources such as glucose, in an amount sufficient to facilitate uptake of tryptophan across the blood brain barrier and to circumvent the competition for BBB transport sites into the central nervous system (CNS). The composition can optionally comprise physiologically acceptable vehicle(s), flavorings, colors and other nutrients, such as vitamins, preferably vitamin B3 and/or vitamin B6.
In a preferred embodiment, the composition comprises at least partially defatted squash seeds, particularly butternut squash, pumpkin and peppercorn squash seeds, glucose and vitamins B3 and B6.
The invention further pertains to dietary supplements (e.g., tablet, powder, suspension, liquid, capsule or gel), foods (e.g., dietary bar, cookie, baked good, snack food, candy, candy bars) and beverages comprising the composition of the invention.
The compositions of the invention can be used to induce sleep in an individual in need thereof, such as those suffering from insomnia or condition associated with a sleep disorder. Alternatively, the compositions can be administered to an individual to improve their tryptophan metabolism, such as for those individuals suffering from a condition or disease associated with reduced levels of serotonin. The compositions can be used as a hypnotic, but may also serve a role in clinical states associated with reduced levels of serotonin, a tryptophan metabolite: depression, anxiety states including obsessive-compulsive disorder, eating disorders and chronic pain.
DETAILED DESCRIPTION OF THE INVENTION
It has been discovered, using second derivative spectroscopy, that certain plant sources and specifically plant seeds possess high levels of naturally occurring tryptophan and that these materials can be used as natural sources of tryptophan. Based upon this discovery, a process has been developed to produce compositions having enhanced levels of tryptophan as a natural protein source of tryptophan richer than any known source. Plants that use gramine typically contain high levels of tryptophan and can be used herein as the plant. source. It is desirable, but not essential, that the starting plant material contain at least 200 mg/100 g or at least 0.2% tryptophan, Tryptophan concentration can be determined using known methods including high pressure liquid chromatography (HPLC), second derivative spectroscopy or any other known methodology. Second derivative spectroscopy is the preferred method to quantitatively analyze tryptophan levels as it eliminates background absorbence. See the Examples section.
According to an embodiment of the invention, tryptophan levels present in the plant source are enhanced using a series of steps to extract oil from the plant material, thus rendering the material partially defatted. The plant source can be a seed such as, but not limited to, butternut squash seed, peppercorn squash seed, pumpkin seed, lentil seed, sunflower seed, flax seed, watermelon seed, sisymbrium seed, cotton seed, sesame seed, canola seed, evening primrose seed, barley, safflower seed, alfalfa seed, soy beans and combinations thereof. Preferably, the seed is a butternut squash seed as it is believed to contain the highest ratio of tryptophan to total proteins, relative to other seed types. The plant source can also be a vegetative part of the plant, such as alfalfa, seaweed or kelp. Although it is preferred to partially defat the plant source to enhance tryptophan levels, defatting is not essential to practice the invention.
In the case of seeds, it is not necessary to remove their seed coat or hull to expose the endosperm prior to processing. The seed is first processed (“flaking”) through a series of smooth rollers to produce a thin flake. This step allows the oil cells to at least partially rupture and increases the surface area of the seeds for further treatment.
The flaked seeds are then heat treated (“cooking or conditioning”) to further rupture oil cells and increase the oil viscosity for subsequent defatting. The conditioning step can be performed using for example a microwave, an oven or by indirect steam. The temperature of the conditioning step should be sufficient to rupture the oil cells and increase the viscosity of the oil without detrimentally destroying proteins contained in the plant material. Preferably, the temperature will be from about 40° C. to about 50° C. The conditioning step is performed for a period of time sufficient to achieve the goal temperature.
Prior to cooling, the heated seed flakes are then mechanically pressed (“pressing”) to at least partially remove the oil contained therein. Any known mechanical press or expeller can be used, such as a Gusta Lab Press. The degree of defatting will depend in part on the flaking and cooking steps performed, temperature and oil viscosity and the pressure exerted on the seed. Typically from about two thirds to about three quarters of the oil should be removed.
The pressed plant material can then be further processed depending upon the end user. For example, the plant material can be milled using any conventional means such as but not limited to a disk mill, hammer mill or pin mill. The type of mill selected will depend in part upon the consistency of the product desired. For example, a pin mill will yield a product having a flour-like consistency, while the disk mill or the hammer mill will yield a product with a granular consistency.
The above process yields a natural source of tryptophan having a tryptophan content that is greater than its parent source. Preferably, the material should provide at least 0.2% by weight tryptophan. The resultant, at least partially, defatted seed meal can then be incorporated into compositions useful for inducing sleep.
In addition to the partially defatted meal, the composition should contain a carbohydrate source with a high glycemic index, preferably in the form of glucose, although sucrose and other sugars that breakdown into glucose can be used. Without wishing, to be bound by theory, it is believed that the carbohydrate source facilitates the uptake of tryptophan across the blood brain barrier where it can be made available for metabolism into serotonin. In the human a barrier exists that allows the brain functions to operate in an independent envi

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