Surgery: light – thermal – and electrical application – Light – thermal – and electrical application – Electrical therapeutic systems
Reexamination Certificate
1999-09-14
2001-05-15
Jastrzab, Jeffrey R. (Department: 3762)
Surgery: light, thermal, and electrical application
Light, thermal, and electrical application
Electrical therapeutic systems
C128S898000
Reexamination Certificate
active
06233489
ABSTRACT:
FIELD OF THE INVENTION
This invention pertains to a method for enhancing serum levels of neurotensin in human beings without administration of exogenous neurotensin or salts thereof.
BACKGROUND OF THE INVENTION
Neurotensin, an endogenous tridecapeptide found in the central nervous system, has been postulated to be a neurotransmitter or neuromodulator found in synapsomes in the hypothalamus, amygdala, basal ganglia, and dorsal gray matter of the spinal cord. Neurotensin plays a role in pain perception, but its analgesic effects are not blocked by opioid antagonists. It also affects pituitary hormone release and gastrointestinal function. Though a wide range of pharmacological effects have been attributed to neurotensin, discussion of neurotensin is generally associated with its gastrointestinal activity.
Two important aspects of neurotensin actions on the central nervous system are its possible involvement in the etiology of schizophrenia and its analgesic properties. Nemeroff, et al., Neuropsychopharm 1991; 4:27. Thus, it has been suggested that neurotensin may have neuroleptic-like activity within the central nervous system. Researchers have reported data that showed diminished availability of neurotensin in some psychotic patients with increases in neurotensin early in neuroleptic treatment. These results suggest that neurotensin would be useful as an anti-psychotic agent. Garver, et al., Am. J. Psychiatry 1991; 148:484-8.
Furthermore, it has been reported that neurotensin has analgesic effects when administered intracisternally to rodents. These results suggest that neurotensin would be useful as an analgesic agent. Clineschmidt, et al., European Journal of Pharmacology 1979; 54:129-139.
The C-terminal hexapeptide fragment of neurotensin (NT(8-13)) has been shown to retain much of the activity found in the native peptide. Indeed, neurotensin or NT(8-13) has been shown to possess activity in pre-clinical antinociceptive tests and in animal behavior tests indicative of anti-psychotic efficacy. Irvin, et al., Nature 1981; 29:73-76. NT(8-13) is metabolically unstable and this would diminish its potency as a therapeutic agent. Studies of the catabolism of NT(8-13) in various brain regions have revealed several key amide bonds which are most susceptible to proteolytic degradation. Davis, et al., Journal of Neurochemistry 1992; 58:608-617. Compounds, when administered peripherally, generally do not have sufficient metabolic stability to remain intact long enough to diffuse or to be transported across the blood brain barrier and interact with central neurotensin receptors. As a result, neurotensin has a broad distribution but a very short half-life in blood.
It has been discovered that, when a patient is pretreated with neurotensin, somatostatin inhibits glucagon secretion. At low glucose levels, neurotensin stimulates release of insulin, glucagon, and somatostatin while release of these peptides stimulated by glucose or arginine is inhibited by neurotensin. There is a close similarity between the metabolic effects of neurotensin and those of histamine, and neurotensin effects are reversed by H
1
and H
2
histamine receptor blockers. Berelowitz, et al., Annals of New York Academy of Science, 1982, Vol. 400, pp. 150-182.
U.S. Pat. No. 3,929,756 to Leeman, et al. discloses the hypothalamically derived substance (and a synthetically prepared tridecapeptide) designated as “neurotensin”. The biological activity of neurotensin was described by observing the vassal dilation in rats and was observed to cause a marked increase in vascular permeability following the intravenous injection or interdermal administration.
Forman, et al. studied an interaction of neurotensin with substance P, and suggested that neurotensin is a partial agonist at the substance P receptors on rat mast cells, and in human skin. Br. J. Pharmac. 1982; 77:531-539.
Some other members of the neurotensin family, all of which are strikingly similar in their C-terminal regions, are described by Carraway and Reinecke in their article “Neurotensin and Related Peptides”, which appears as Chapter 4 in
The Comparative Physiology of Regulatory Peptides
(Holmgren, editor, Chapmann and Hall, London, 1989). As noted by Carraway and Reinecke, structure and function studies have indicated a strong dependence on the five or six residues of the C-terminal portion of neurotensin and related peptides, and it appears that the C-terminal portion of these peptides is highly conserved in evolution.
In addition, neurotensin, and related peptides, act as anti-inflammatory agonists and, like Corticotrophin-releasing factor, actively shut off the response of tissues to virtually all known inflammatory mediators.
Therefore, there is an existing need to harness the anti-diabetic, anti-inflammatory, anti-psychotic, neuroleptic and analgesic activity of neurotensin despite the extremely short half-life of neurotensin in the body. It would be most beneficial to achieve this objective without the administration of exogenous neurotensin due to the side effects that exogenous sources may cause.
SUMMARY OF THE INVENTION
The present invention provides a method for enhancing or restoring neurotensin in a living human being. Because neurotensin is a naturally occurring neuropeptide, in accordance with the present invention endogenous production of the hormone may be stimulated without requiring the use of exogenous dietary supplements or pharmaceutical preparations containing neurotensin, neurotensin analogs, neurotensin agonists, or salts thereof.
Serum neurotensin levels in human beings may be raised without the use of dietary supplements or pharmaceuticals by applying electrical stimulation to specific epidermal points of the individual's body for a period of time, preferably daily. The electrical stimulation is preferably applied to specific locations on the individual's body which correspond to thirteen well-known acupuncture points. The electrical stimulation can be applied to these acupuncture points over a number of weeks to achieve a significant increase in serum neurotensin levels within the patient. Preferably, electrical stimulation is applied for a minimum period of two to four weeks.
It has been found that the greatest increase in serum neurotensin levels occurred in patients treated with daily electrical stimulation applied to the specific acupuncture points. This electrical stimulation, applied to an individual on a daily basis for a period of several weeks, was effective in elevating neurotensin levels in patient's serum by as much as 500 percent.
Further objects, features and advantages of the invention will be apparent from the following detailed description taken in conjunction with the accompanying drawings.
REFERENCES:
patent: 3929756 (1975-12-01), Leeman et al.
patent: 5109847 (1992-05-01), Liss et al.
patent: 5374621 (1994-12-01), Wei
patent: 5407916 (1995-04-01), Wise et al.
patent: 5609617 (1997-03-01), Shealy et al.
Liss Cranial Stimulator—Professional Instrument Manual, 1994, pp. 1-11.
Myss Caroline M.
Shealy C. Norman
Wisneski Leonard
Biogenics II, LLC
Foley & Lardner
Jastrzab Jeffrey R.
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