Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1994-09-21
1997-08-05
Burn, Brian M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
514 76, 514 78, A61K 31685
Patent
active
056542909
DESCRIPTION:
BRIEF SUMMARY
This is a 371 of PCT/FR93/01158, filed Nov. 24, 1993.
The present invention relates to new drugs based on polyunsaturated fatty acids, and more precisely based on docosahexaenoic acid (also called DHA or 22:6n-3),
It is known that nervous tissues are very rich in essential polyunsaturated fatty acids (1, 2), especially in DHA which can represent 24% of the fatty acids of the phosphatidylethanolamines (PE) of the grey matter (3). Polyunsaturated fatty acids play an important role in normal cerebral development (4). Thus, dietary deficiency of essential unsaturated fatty acids or the disruption of their metabolism during a period of cerebral development might affect myelinization in man (1, 5). As regards more particularly the fatty acids of the n-3 family, it has been shown that a dietary deficiency of these fatty acids results in a faulty pre- and post-natal development of the retina and of the brain in Rhesus monkeys (6, 7) and other animals (8). It seems, in addition, that these fatty acids are involved in the capacity for learning in young rats (9, 10). The brain does not accumulate 18:3n-3, the precursor of 22:6n-3 or DHA, on the one hand because it has the enzymes for elongation and unsaturation necessary for the conversion of 18:3n-3 into 22:6n-3 (11) and, on the other hand, because it can capture the 22:6n-3 attached to the plasma albumin produced by the liver (12, 13) because the brain captures non-esterified fatty acids better if they are unsaturated (14, 15).
On the basis of the oldest of these studies, it has already been proposed to provide the body with essential polyunsaturated fatty acids, in the form of nutrients or preparations which can be administered by other routes. In particular, several documents have insisted on the value of providing, in this manner, essential polyunsaturated acids such as 18:3n-3, arachidonic acid and 22:6n-3. In the preparations envisaged, these fatty acids are present in various forms, in general mixed and especially in the form of triglycerides, phospholipids and also in non-esterified form. Some of these documents underline the value of administering these essential fatty acids in the form of components of phospholipids.
It has, moreover, been shown that diets rich in eicosapentanoic acid (20:5n-3) and in the acid 22:6n-3 decrease the incidence of cardiovascular diseases (16). The mechanisms responsible for the beneficial effects of these fatty acids remain, however, to be specified. Numerous studies have focussed on the effects of these polyunsaturated fatty acids on platelet functions. It has been shown that these fatty acids, like other cis-unsaturated fatty acids, inhibit platelet aggregation induced by a wide variety of platelet activators including U 46.619, an agonist of the receptor for thromboxane (TXA.sub.2) and prostaglandin H.sub.2 (PGH.sub.2) (17-23). The inhibitory effects of 20:5n-3 and 22:6n-3 would be exerted at several levels (17-19, 24-27). Moreover, it has been shown that non-esterified 20:5n-3 and 22:6n-3 competitively inhibit platelet aggregation induced by U 46.619 as well as the specific binding of the latter to washed platelets (28). The incorporation in vitro of 20:5n-3 and of 22:6n-3 into the platelet lipid reserves, by means of albumin, also results in the loss of aggregability of the platelets in response to U 46.619 and a decrease in the affinity of the agonist for its receptor (29). In this study, if 20:5n-3 and 22:6n-3 have been predominantly esterified in the phospholipids, the effects observed can also be attributed to the enrichment of the other lipid fractions in these fatty acids. 20:5n-3 and 22:6n-3 exhibit a certain selectivity of action on the TXA.sub.2 /PGH.sub.2 receptor since none of these fatty acids affects the platelet aggregation induced by thrombin and by the ionophore A 23187, when used at concentrations which do not bring this receptor into play (29). Furthermore, they do not modify binding of yohimbine to the alpha.sub.2 -adrenergic receptor of the platelet membranes (30), which exhibits a certain structural h
REFERENCES:
patent: 5135921 (1992-08-01), Della Valle et al.
Bayon Yves
Chirouze Veronique
Croset Martine
Lagarde Michel
Lecerf Jean
Burn Brian M.
Imedex
Institut National de la Sante et de la Recherche Medicale
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