Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Patent
1989-09-25
1994-07-19
Henley, III, Raymond J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
514560, A61K 3122
Patent
active
053310098
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the treatment of adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AMN), and to compositions useful therefor.
ALD is an inherited disease characterised by abnormally high body levels of C24 and C26 saturated fatty acids. It is believed that the reason for these high levels in ALD patients is that the body enzyme which ordinarily breaks down these acids is absent or not functioning properly. The C24 and C26 fatty acids, both saturated rand mono-unsaturated, are synthesised endogenously by the body from corresponding lower fatty acids by the same bifunctional enzyme systems. It has been suggested that, if it were possible to prevent synthesis of the (harmful) saturated fatty acids in ALD patients, then the levels of these acids should drop and so arrest further advance of the disease. With this in mind, Augusto Odone proposed treating ALD patients with a mixture of two fatty acids (in the form of their triglycerides), namely the monounsaturated C20 and C22 fatty acids, the mixture being substantially free from any similar saturated acids and containing the C20:1 and C22:1 acids in a weight ratio of 1:2, respectively. The idea was to provide the body's C24/C26-synthesising enzyme with an abundance of unsaturated acids so that corresponding C24 and C26 unsaturated acids were produced to the exclusion of any C24 and C26 saturated acids.
In the present application applicants have utilized an abbreviation for various long-chain fatty acids. As will be apparent to those of skill in the art, a long-chain fatty acid designated as C18:1 has 18 carbon atoms in the chain, with a single site of unsaturation. A C22:2 long-chain fatty acid has 22 carbons in the chain and is unsaturated at two sites. Where the term erucic acid has been used, that is the common name senoic acid. It has the formula CH.sub.3 (CH.sub.2).sub.7 CH.dbd.CH(CH.sub.2).sub.11 -COOH.
In order to test his theory, we made for Mr. Odone the triglyceride of the following mixture of fatty acids:
______________________________________ C18:1 traces only
C18:2 traces only
C18:3 traces only
C20:0 traces only
C20:1 32.5%
C22:0 traces only
C22:1 65.0%
C22:2 traces only
C24:0 zero
C24:1 1% maximum
C26:0 zero
______________________________________
fatty acid content of the mixture.
When this composition was administered to two ALD patients in their diets, the results were dramatic. Over a period of three weeks, their C24:0 and C26:0 acid levels in total plasma and sphingomyelin were reduced to normal. Evidently, therefore, this is a highly successful way of reducing the damagingly high acid levels in ALD patients and is indeed a major breakthrough in the treatment of the disease.
Unfortunately, however, the manufacture of the above mixture of acids, to exactly the composition indicated, is a long and difficult procedure and, as a result, is very expensive. However, in accordance with a feature of the present invention, it has now been found that the presence of such high levels of C20:1 in the compositions is unnecesary and that it is the C22:1 component which is by far the more important. Indeed, the C20:1 component can be omitted completely. In this way, the compositions can be made more easily and economically.
According to a feature of the present invention, therefore, there is provided a composition for the treatment of ALD and related diseases, which comprises erucic acid (C22:1) and no more than 20% of C20:1, in the substantial absence of C24:0 and C26:0 acids, the composition being in a form suitable for administration to the patient. Normally, the acids in the composition will be in the form of their triglycerides. For simplicity, we refer hereafter to the acids in the compositions, but intend thereby to include reference to physiologically acceptable derivatives, e.g. the triglycerides, as the context determines.
In the treatment of ALD patients, great care has to be taken over their diet because, of course, foodstuffs frequently contain oils and fatty acids. In order to avoid any risk of ingestion
REFERENCES:
patent: 4377526 (1983-03-01), Fujita et al.
patent: 4442125 (1984-04-01), Thiele
patent: 4843095 (1989-06-01), Rubin
Cosco, J. "The Virginia Pilot" No. 17, (1987) pp. A1 and A6.
Nassar et al., Lipids, vol. 21, No. 10 (1986) pp. 652-656.
Coupland Keith
Suddaby Donald
Croda International PLC
Henley III Raymond J.
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