Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-06-01
2003-05-27
Criares, T J (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S213010, C514S646000
Reexamination Certificate
active
06569850
ABSTRACT:
This invention relates to the treatment of Multiple Sclerosis (MS) and other Demyelinating Conditions.
Multiple sclerosis is a common and well known neurological disorder. It is characterised by episodic patches of inflammation and demyelination which can occur anywhere in the central nervous system (CNS) almost always without any involvement of the peripheral nerves. The occurrence of the patches is disseminated in time and space, hence the older alternative name of disseminated sclerosis. It is believed that the pathogenesis involves local disruption of the blood brain barrier, a local immune and inflammatory response, with consequent damage to myelin and hence to neurons.
Clinically, MS can present in both sexes and at any age. However, its most common presentation is in relatively young adults, often with a single focal lesion such as damage to the optic nerve (optic neuritis), an area of anaesthesia or paraesthesia or muscular weakness. Vertigo, nystagmus double vision, pain, incontinence, cerebellar signs, L'Hermitte's sign (paraesthesia or pain in the arms and legs on flexing the neck) and a large variety of less common symptoms may occur. The initial attack is often transient and it may be weeks, months or years before a further attack occurs. Some fortunate individuals may have a stable condition, while other unfortunate ones may have an unrelenting downhill course ending in complete paralysis. More commonly there is a long series of remissions and relapses, each relapse leaving the patient somewhat worse than before. Relapses may be triggered by stressful events or viral infections. Elevated body temperature almost invariably makes the condition worse whereas a reduced temperature, for example induced by a cold bath, may make the condition better. There are no satisfactory treatments for MS. Steroids may produce a temporary improvement but any beneficial effect invariably wears off. Recent clinical trials have shown that interferon may somewhat reduce the risk of relapse. However, the effect is modest and most patients still deteriorate.
I have now developed a new and highly effective treatment for compensating for the effects of nerve damage caused by MS and other demyelinating conditions.
My invention is based on the use of a combination of an antidepressant or a mono-amine oxidase inhibitor in combination with an inducer or precursor of a neurotransmitter. The two compounds may be administered in the same dosage form, or may be in separate dosage forms but a combined pack may be in separate packs for administration at separate times but so as to be effective together in the body.
Lofepramine and related tricyclic and tetracyclic antidepressants work by interfering with the inactivation of substances called neurotransmitters which are required for the normal transmission of nerve impulses from one nerve cell to the next. Such neurotransmitters, among them substances called noradrenaline and serotonin, are released from one nerve cell and activate the next one. They are inactivated by various mechanisms including rapidly being taken up into nerve cells and also enzymic destruction by enzymes known as monoamine oxidase inhibitors (MAOI). Lofepramine is a drug which inhibits neurotransmitter uptake and which is in the class of tricyclic antidepressants and which also has some MAOI activity. Newer drugs to treat depression are more active against serotonin and are known as selective serotonin reuptake inhibitors (SSRIs).
I have discovered that the use of L-phenylalanine (LPA), the precursor of noradrenaline, contributes to the therapeutic effect. In some individuals, however, an alternative may be L-tryptophan which is a precursor of the neurotransmitter, serotonin. Several different antidepressants including tricyclic antidepressants, SSRIs and MAOIs have beneficial effects but have consistently obtained the best results with lofepramine. Detailed information on lofepramine is given in the Merck Index. I have also noted that when the patient receives regular injections of vitamin B
12
the treatment works best.
As an example, a regime of 70 mg lofepramine and 500 mg LPA per day for over a year in my own case completely resolved severe unequivocally diagnosed MS. Over 100 other patients have done well on a similar regime, although some have been given other antidepressants either of the traditional tricyclic class, such as amitriptyline or imipramine, or the newer specialist serotonin uptake inhibitors or monoamine oxidase inhibitors. Four particular instances are given in the appendix. Most have done best on lofepramine. The doses of LPA have also varied from about 100 mg to up to 5 g per day, but best results are obtained with doses in the region of 500-2000 mg/day. The doses of antidepressants (with the proviso that minimum effective and maximum safe levels are determined according to the drug), lie broadly in the range 10 mg to 200 mg per day.
A background course of vitamin B
12
for example by injection, is also preferred and does have a beneficial effect. Daily amounts may for example be the conventional daily requirement for the vitamin.
Four case histories of patients other than myself illustrating the beneficial effects of my invention are given later herein. A total of 126 patients have now been tested and almost all have received benefit. This benefit has reached varying degrees with some only showing a small improvement and others a complete resolution of all symptoms such as I observed in myself.
REFERENCES:
patent: 4409243 (1983-10-01), Lieb
patent: 4650789 (1987-03-01), Pollack
patent: 35 19 687 (1986-12-01), None
patent: 42 04 102 (1993-08-01), None
patent: 1 497 306 (1978-01-01), None
patent: 2 082 910 (1982-03-01), None
patent: 2 129 299 (1984-05-01), None
patent: WO 88/04173 (1988-06-01), None
Abstract of Charles F. Scott, Jr., et al., “Experimental Allergic Encephalitis; Treatment with Drugs Which Alter CNS Serotonin Levels”,Journal of Immunopharmacology, pp. 153-162, 1982-83.
D. Chadwick, et al., “5-Hydroxytryptophan-Induced Myoclonus in Guinea Pigs”Journal of the Neurological Sciences, pp. 157-165, 1976.
Karin N. Westlund, et al., “Serotonin is found in myelinated axons of the dorsolateral funiculus in monkeys”Neuroscience Letters, pp. 35-38, 1992.
E.H. Reynolds, “Multiple sclerosis and vitamin B12 metabolism”,Journal of Neuroimmunology, pp. 225-230, 1992.
Guy M. Goodwin, “Tricyclic and newer antidepressants”,Handbook of Affective Disorders, pp. 327-343, 1992.
Abdulla A.-B. Badawy, et al., “The Effects of Lofepramine and Desmethylimipramine on Tryptophan Metabolism and Disposition in the Rat”, pp. 921-929, 1991.
Criares T J
Foley & Lardner
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