Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1990-11-15
1993-11-23
Husarik, Nancy S.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 56, 514572, 514589, 514613, 514642, 514643, 536 21, 536 54, 536 55, 558276, A61K 31725, A61K 3173, C07C 6996, C08B 3710
Patent
active
052644251
DESCRIPTION:
BRIEF SUMMARY
The present invention refers to glycosaminoglycan salts which are able to induce therapeutically effective blood levels of the glycosaminoglycanic polyanion even when administered orally or rectally.
Proteoglycans are macromolecules characterized by a proteic core to which different polysaccharides are covalenty bound. They differentiate by the nature of the proteins and that of the saccharidic side chains and constitute the major part of some mammalian tissues.
By suitable hydrolytic methods (e.g. by means of proteases) it is possible to separate the proteic part from the saccharidic part, commonly known as glycosaminoglycans, because of their content in aminosugars.
The glycosaminoglycans known as chondroitin-4- or 6-sulfate, heparan sulfate, heparin, dermatan sulfate, hyaluronic acid etc., are characterized, in each single family, by polydispersion of molecular weight and also by heterogenity in the saccharidic compositions, and are thus obtained, also industrially.
Due to their highly hydrophilic, polyanionic nature, glycosaminoglycans are able to interact with various chemical species, such as divalent cations or plasmatic basic proteins, often aspecifically and sometimes (such as in the case of the heparin - anti-thrombin III complex or of the dermatan sulfate - cofactor III complex) with a certain specificity, whose degree is higher or lower according to the ligand or to the binding agent.
Interactions occur also with chemical species bound to cell membrane structures such as those constituting the blood vessels.
Due to said interactions, glycosaminoglycans are interesting therapeutic agents, because they allow to control of pathological conditions wherein either the activation or the inhibition of certain plasma factors (such as anti-thrombin III or the activated factor X) are highly useful.
The glycosaminoglycans used for the preparation of the salts of the invention are the following: extractive source (porcine, bovine or ovine intestinal mucosa, lung etc.) or on the extraction and purification methods; charge value, which is not dependent on the preparation and isolation methods; operations ("supersulfated"); N-desulfation (10-100%) of heparins and then subjected to hemisuccinylation.
Heparin is extracted from tissues of different origin: bovine or porcine intestinal mucosa, lung etc. Chemically heparin, as well as its fractions or fragments, is a mixture having polydispersed molecular weight ranging from 1,000 to 30,000 D.
Under the biological profile, heparin itself, its fragments and fractions show different pharmacological activities, particularly anticoagulant, anti-thrombotic, antiangiogenetic and antilipemic activities. Said activities are connected with the ability of developing interactions with different factors either plasmatic or extra-plasmatic (anti-thrombin III, activated factor X, heparin cofactor II, plasminogen activator, lipoproteinlipase in addition to platelet factors) According to the use of heparin as such or of its fragments or fractions (having low molecular weight: 3500-9000 D), one mechanism of action may overcome another one or prolonged or decreased pharmacokinetics may result.
The salts of these polyanions most frequently used in human therapy are the sodium, calcium or magnesium salts.
Dermatan sulfate may be obtained from mammalian tissues such as skin, bowels, tendons etc. by means of enzymatic and controlled chemical hydrolysis.
It is also known as chondroitin sulfate B and shows an anti-thrombotic activity unrelated to the anticoagulant activity, so as to be considered a therapeutic agent safer than heparin. The anti-thrombotic activity seems to be due, according to the present knowledge, to the ability of catalyzing the reaction between heparin - cofactor III and thrombin with consequent inactivation of the latter.
Also for said polyanion the used salts are the sodium and calcium salts.
Heparan sulfate is obtainable from connective tissues such as lungs, basal membranes, walls of blood vessels, pancreas etc.
Even though exhibiting poor in vitro pharmacological
REFERENCES:
patent: 2830932 (1958-04-01), Cushing et al.
patent: 3162673 (1964-12-01), Brotherton et al.
patent: 3244594 (1966-04-01), Csaba et al.
patent: 4324739 (1982-04-01), Zondler et al.
patent: 4352913 (1982-10-01), Zondler et al.
patent: 4478822 (1984-10-01), Haszam et al.
patent: 4506081 (1985-03-01), Fenyes et al.
patent: 4510135 (1985-04-01), Teng
patent: 4581058 (1986-04-01), Fenyes et al.
patent: 4591638 (1986-05-01), Ahrgren et al.
patent: 4604376 (1986-08-01), Teng
patent: 4654327 (1987-03-01), Teng
patent: 4703042 (1987-10-01), Bodor
patent: 4727063 (1988-02-01), Naggi et al.
patent: 4783447 (1988-11-01), Del Bono et al.
patent: 4910142 (1990-03-01), Schwengers et al.
patent: 4981955 (1991-01-01), Lopez
patent: 4985410 (1991-01-01), Conti
Tadolini et al; Chem. Ab. 99:209189g (1983).
Tadolini et al; Chem. Ab. 101:35516d (1984).
Tadolini et al; Chem. Ab. 103:192661f (1985).
Ehrenpreis et al; Biochim. Biophys. Acta 44:577-585 (1960).
Acquasaliente Maurizio
Dal Pozzo Alma
De Santis Francesco
Ferruti Paolo
Sarret Monique
Husarik Nancy S.
Italfarmaco S.p.A.
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