Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
1999-06-25
2001-08-21
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S443000, C514S903000, C514S944000, C514S946000, C604S109000
Reexamination Certificate
active
06277402
ABSTRACT:
BACKGROUND
a. Field of the Invention
The present invention relates generally to methods for the treatment of multiple sclerosis and related disease states, and, more particularly, to a method for alleviating/controlling the symptoms associated with multiple sclerosis and related disease states, by administration of compositions which induce an increased presence of cyclic AMP in the body so as to reduce or reverse demyelination of the nervous system.
b. Related Art
Multiple sclerosis (referred to from time-to-time hereinafter as “MS”) is a chronic degenerative disease of the central nervous system, characterized by demyelination of the nerve axons. Symptoms include varying degrees of fatigue, numbness, tremors/muscle spasms and paralysis, coupled with a heightened susceptibility to heat and other environmental stressors. Currently, approximately 2,500,000 people worldwide have been diagnosed as having multiple sclerosis. Onset of the disease usually occurs between 20 and 40 years of age.
It is recognized that MS occurs in at least two general types, i.e., “remissive-relapsive”, in which acute exacerbations are separated by periods of partial recovery, and “chronic-progressive”, in which the symptoms continue generally unrelieved and there is a progressive deterioration of the patient's condition that may eventually result in total debilitation.
Efforts at treatment of MS have heretofore concentrated almost entirely on the body's autoimmune response system. The prevailing theory has been that some agent causes the myelin sheath to be attacked by the immune system, resulting in destruction of the myelin and creation of the lesions. It is also believed that certain viruses may play a role in causing or precipitating MS: In particular, the measles virus may be involved in the disease, in that studies have not only found that people suffering from MS almost invariably possess the measles antigen, but also that MS patients generally have higher than normal levels of measles antibodies in their serum and cerebrospinal fluid. One theory has been that the measles or other virus triggers the T-cells to attack and destroy the myelin sheath.
Proceeding on the theory that MS is the result of an autoimmune response triggered by measles or another virus, most conventional treatment techniques have involved the use of Betaseron, Avonex and/or other anti-viral substances, generally referred to collectively as “Interferon”. The intended purpose of these materials is to impede the RNA-DNA transcription process in the T-cells which are believed to be triggered by the virus into attacking the myelin. While interferon has demonstrated some positive results when treating remissive-relapsive type MS, it is proven almost entirely ineffective against the chronic-progressive type.
Another treatment method which has yielded a limited degree of success involves the injection of adenosine monophosphate. This material is not readily absorbed, in part because it is ordinarily available only in an oil-based solution, and is not “friendly” to the patient's tissues. The tissues have a tendency to wall off the material and form a small abscess capsule around it, and with each injection the material becomes harder and harder to absorb. In order for the material to be absorbed, most patients must walk vigorously on a tread mill for 20-30 minutes or engage in other strenuous exercise, or else the material will simply remain at the injection site with the result that the patient becomes extremely sore and the symptoms do not improve. Most people suffering from MS, however, are not mobile and are simply incapable of engaging in such exercise. Consequently, while many individuals experience significant benefits at the beginning of adenosine monophosphate treatments, these results eventually fade as the person's body becomes unable to absorb the material.
As will be described in greater detail below, the present invention is not postulated on conventional autoimmune theories, and instead employs application of histamine phosphate or other histamine H2 analogue to prevent/repair self-degeneration of the myelin. With the exception of experimental studies by Hinton D. Jonez, M. D. (Jonez, “Management of Multiple Sclerosis”,
Postgraduate Medicine,
May 1952) and certain methods described in patents to John McMichael (U.S. Pat Nos. 4,521,405 and 4,705,685), histamine phosphate (which is most commonly employed for diagnosis of stomach conditions) has not been used in connection with multiple sclerosis and related disorders.
The work of both Jonez and McMichael is founded on conventional autoimmune response theories. Dr. Jonez's experiments in the early 1950's attempted to manipulate the body's allergic responses using histamine phosphate, and also used the material as a vasodilator to get more blood to the brain and other parts of the nervous system. In this context, it should be understood that the present invention employs histamine phosphate to mimic histamine H2, the functions of which are confined mainly to the central nervous system, whereas the primary agent in allergic reactions is in fact histamine H1. At the time of Dr. Jonez's work, however, this distinction (between histamine H1 and histamine H2) was not fully appreciated.
McMichael's method involves the injection of a small amount of an “immunogen” consisting of viral fragments or other antigens (under the theory known as “provocative neutralization”), together with a small amount of histamine phosphate. McMichael identifies histamine phosphate as a vasodilator, and theorizes that the histamine phosphate reacts with the immunogen to form an “active complex” which affects absorption of the material. In any event, the amounts of histamine phosphate which are involved in McMichael's treatment are far too small to have any significant impact on overall levels of histamine H2 in the body.
Accordingly, there exists a need for a treatment method which effectively alleviates the symptoms of multiple sclerosis and related disease conditions. Furthermore, there exists a need for such a method which provides an effective treatment for both the remissive-relapsive and chronic-progressive forms of the disease. Still further, there exists a need for such a method in which the treatment compositions are readily absorbed into the patient's body, without requiring resort to physical exercise for effective absorption. Still further, there exists a need for such a method which is sufficiently economical to be widely available to the great number of individuals who suffer from MS and related diseases.
SUMMARY OF THE INVENTION
The present invention has solved the problems cited above, and is a method for treatment of multiple sclerosis and related disease states.
Broadly, the method comprises administering a composition comprising a histamine H2 mimicking agent, in an amount effective to stimulate production of cyclic AMP at a level which is adequate to maintain the patient's myelin against self degeneration. The treatment composition may further comprise a phosphodiesterase inhibitor, administered in an amount effective for conservation of the increased levels of cyclic AMP in the patient's body.
The histamine H2 mimicking agent may comprise histamine phosphate, or may comprise a selected beta adrenergic agent which mimics histamine H2. The phosphodiesterase inhibitor may comprise a methylxanthine agent; the methylxanthine agent may comprise caffeine, or may comprise theophylline or a theophylline derivative.
The method may comprise administering histamine phosphate transdermally at a rate in the range of about 0.06 mg/hr to about 0.50 mg/hr, and administering caffeine transdermally at a rate in the range from about 2 mg/hr to about 25 mg/hr.
The present invention also provides a treatment method which comprises administering histamine phosphate and caffeine simultaneously using a transdermal patch. In a preferred embodiment, the histamine phosphate is administered transdermally at a rate in the range from about 0.1
Ghali Isis
Hathaway Todd N.
Page Thurman K.
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