Drug – bio-affecting and body treating compositions – Inorganic active ingredient containing – Heavy metal or compound thereof
Reexamination Certificate
1999-09-13
2001-03-13
Henley, III, Raymond (Department: 1614)
Drug, bio-affecting and body treating compositions
Inorganic active ingredient containing
Heavy metal or compound thereof
C424S648000, C514S249000, C514S345000, C514S355000, C514S567000
Reexamination Certificate
active
06200607
ABSTRACT:
The invention herein relates to the treatment of Parkinson's disease and/or depression.
Parkinson's disease is a medical disorder whose characteristic symptoms are due to excessive muscle contraction. This often begins as a tremor, which can develop into muscle rigidity, and then to a complete lack of physical movement. Usually, it does not develop until adulthood and becomes progressively more common with age.
It is caused by the insufficient action of dopamine, which normally acts by preventing excessive muscle contraction. Although dopamine is produced in the dopaminergic neurons in the brain, it is not normally administered to treat the disorder since dopamine does not easily pass between the blood brain barrier.
Some existing methods of treating Parkinson's disease make use of dopamine agonists, which mimic the action of dopamine. However, though the use of dopamine agonists can be effective for a while they can cause side effects, and their long term use leads to the progressive desensitisation of the receptors that respond to them.
L-Tyrosine was compared against the use of prominent products for Parkinson's disease and was found to be more effective (Comples Rendus Academie des sciences (III) [1989] 309 (2):43-47). The use of iron in the treatment of Parkinson's disease was compared against existing methods of treatment and was found to be beneficial in all patients tested (Journal of Neural Transmission [1986] 67:287-292). Zinc deficiency has been shown to lead to, amongst other things, symptoms of Parkinson's disease. It has been reported that nicotinamidadenine dinucleotide (NADH) can be beneficial in the treatment of Parkinson's disease (Annals of Clinical and Laboratory Science [1989] 19 (1):38-43). Tetrahydrobiopterin (BH
4
) was also found to have a therapeutic effect on Parkinson's disease patients. (Advances in Neurology 40:463-466 and Proceedings Japan Academy series B [1982] 58:283-287).
In the early 1940's a number of studies were reported to have been carried out primarily in the USA in which pyridoxine was linked to improvements in Parkinson's disease. (Minnesota Medical Association [1940] 23:542, Journal of the American Medical Association [1940] 115:839, Minnesota Medicine [1940] 23:542, Journal of the American Medical Association [1941] 116:1895, and New York State Medical Journal [1941] 41:461).
Mental depression (depressive disorders, depressive illnesses) and manic depressive disorders consist of a group of common psychiatric disorders characterised by both mental and somatic symptoms. Treatment includes psychotherapy, electroconvulsive therapy (ECT) and antidepressant drugs such as the manoamine oxidase inhibitors, serotonin reuptake inhibitors and noradrenaline reuptake inhibitors.
It has been reported that a lack of dopamine will cause mental depression. Nicotinamide and similar substances such as nicotinic acid have been used with a fair degree of success in the treatment of depression (Canadian Psychiatric Association [1971] 16:413). Pyridoxine has been used in the treatment of depression, and was shown in certain types of cases to be successful (The Lancet [1973]:897). The deficiency of folic acid folates has been shown to result in depression (Psychological Medicine [1992] 22:871).
At present, the most common basis for the treatment of Parkinson's disease is the administration of L-dopa. L-dopa is metabolised to dopamine in vivo and, unlike dopamine, L-dopa can pass the blood brain barrier. However, its administration, via feedback inhibition causes a correspondingly reduced production of the body's own dopamine. Therefore although the use of L-dopa can initially be effective in treating Parkinson's disease, over time it leads to the condition becoming progressively worse. There are also side effects caused by the use of L-dopa.
It is an object of the inventions to provide an effective treatment for Parkinson's disease and depression, and particularly more effective than L-dopa.
It is a further object to obviate or mitigate the disadvantages of treatment with L-dopa.
According to the first aspect of the present invention there is provided the use of a combination pharmaceutical product of at least tyrosine or a pharmacologically acceptable derivative thereof and an iron containing compound in the preparation of medicament for the treatment or prophylaxis of Parkinson's disease and depression. The combination can be given separately, sequentially, simultaneously or as a combined unitary drug product. Thus for example, a blister pack containing iron and tyrosine as separate tablets to be given together would be within the scope of the invention. However a unitary tablet or capsule containing the combination is preferred.
A second aspect of the invention provides a pharmaceutical product comprising tyrosine or a pharmacologically acceptable derivative thereof together with an iron containing compound for combined, separate, sequential or simultaneous administration for the treatment or prophylaxis of Parkinson's disease or depression.
Unlike L-dopa, the invention can be used long term without significant side effects since it enables the natural biosynthesis, secretion, transport and action of the body's own dopamine.
By pharmacologically acceptable derivative of tyrosine, we mean to include any precursor which will metabolise to tyrosine in vivo such as phenylalanine (typically the L-phenylalanine). Ideally, L-tyrosine or DL-tyrosine and salts is administered in accordance with the invention. A suitable daily dosage of tyrosine (typically L-tyrosine) or derivative in accordance with the invention is 240 mg to 6000 mg, preferably 1200 mg to 3600 mg, typically about 2400 mg.
Iron should also be available in vivo with tyrosine and so any compounds or element which delivers iron in vivo is an iron containing compound in accordance with the invention. Preferably the iron containing compound contains ferrous iron (e.g. ferrous sulphate or a ferri-ferro complex e.g. oxyferriscarbone™) since this appears to be absorbed better by the body. Ferrous iron is used in the biosynthesis of dopamine. Suitable total daily dosage of iron in an iron containing compound is 2 mg to 100 mg, preferably 10 mg to 30 mg, typically about 20 mg iron. If the iron is present as iron sulphate then the weight of iron containing compound would be higher such as 54 mg ferrous sulphate (corresponding with 20 mg Fe
3+
)
Preferably the combination product of the invention also comprises for separate, sequential, simultaneous administration or administration as a combined preparation, at least one of a vitamin B6 (e.g. pyridoxine), a folate (e.g. folic acid), a vitamin B3 (e.g. nicotinamide) or a zinc containing compound.
Advantageously, the combination of the invention comprises at least one vitamin B6 such as pyridoxal and pyridoxamine. However, most preferably the vitamin B6 is substantially pryridoxine or a pharmacologically acceptable salt thereof such as pyridoxine hydrochloride. Suitably the total daily dose of vitamin B6 (such as pyridoxine) is 0.2 mg to 240 mg, more preferably 1.2 mg to 3.6 mg, typically about 2.4 mg.
It is further preferred that a folate is administered in the combination of the invention. Most preferably folic acid is used. A suitable total daily dose of folate (such as folic acid) is 0.04 mg to 10 mg, preferably 0.2 mg to 0.8 mg, typically 0.4 mg.
Further preferably at least one vitamin B3 such as nicotinic acid is present in the combination of the invention, but ideally nicotinamide is present. A suitable total daily dose of vitamin B3 (such as nicotinamide) is 2 mg to 500 mg, preferably 10 mg to 30 mg, typically 20 mg.
Yet further preferably, a zinc containing compound such as zinc sulphate is also present in the combination of the invention, so as to deliver Zn
2+
in vivo. A suitable daily dose of a zinc containing compound is 2 mg to 80
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