Use of one or more elements from the group containing yttrium, neodymium and zirconium and pharmaceutical compositions containing said elements

Abstract

A method of treating a patient includes the medical use of one or more of the elements from the group yttrium, neodymium and zirconium, pharmaceutical formulations which contain said elements and implants which are at least region-wise made up of such formulations. It has been found inter alia that a formulation containing one or more of the elements has an action of inhibiting the proliferation of human smooth muscle cells.

Description

BACKGROUND OF THE INVENTION [0001] The invention concerns the medical use of one or more of the elements from the group consisting of yttrium, neodymium and zirconium, pharmaceutical formulations which contain those elements and implants which are at least region-wise made up of such formulations. [0002] Inflammation is used to denote the reaction of the organism, borne by the connective tissue and the blood vessels, to an external or internally triggered inflammation stimulus with the aim of eliminating or inactivating same and repairing the stimulus-induced tissue damage. A triggering action is effected by mechanical stimuli (foreign bodies, pressure, injury) and other physical factors (ionizing rays, UV-light, heat, cold), chemical substances (lyes, acids, heavy metals, bacterial toxins, allergens and immune complexes) as well as pathogens (micro-organisms, worms, insects) or diseased metabolic products (out-of-control enzymes, malignant tumors). The microbiological processes whi...

AI Technical Summary

Problems solved by technology

It will be noted however that, with dilation of the blood vessel, very minor injuries, fissures and dissections occur in the vessel wall, which admittedly frequently heal up without any problem but which in about a third of the cases result in proliferation due to triggered cell growth, which ultimately result in renewed vessel constriction (restenosis).

Dilation also does not eliminate the causes of the stenosis, that is to say, the molecular-pathological changes in the wall of the vessel.

A further cause of restenosis is the elasticity of the expanded blood vessel.

An optimum vessel cross-section can admittedly be achieved by the use of stents, but it will be noted that the use of stents also results in very minor injuries which can induce proliferation and which thus can ultimately trigger restenosis.

In addition, the presence of such a foreign body initiates a cascade of cellular molecular processes which can result in progressive blockage of the stent.

Under the influence of various growth factors, the smooth muscle cells produce a cover layer of neointimal smooth muscle cells and matrix proteins (elastin, collagen and proteoglycans) whose uncontrolled growth can gradually result in constriction of the lumen.

Systemic drug therapy uses provide inter alia the oral administration of calcium antagonists, ACE inhibitors, anticoagulants, antiaggregants, fish oils, antiproliferative substances, antiinflammatory substances and serotonin antagonists, but hitherto significant reductions in the kinds of restenosis have not been achieved in that way.

A possible explanation for the disappointing results of all previous attempts of systemic application of the most widely varying substances is that systemic application cannot take the substance in an adequate level of concentration to the location of the vessel injury.

In the course of time, it has been found however that the material used is admittedly biocompatible but over medium and long periods of time it promoted in part thrombosis formation and in part adhesion of biomolecules to its surface.

A further limitation in terms of biocompatibility of permanent stents is ongoing mechanical stimulus of the vessel wall.

Thus for example, a large number of plastic materials have been proposed as the stent material, which admittedly exhibited good degradation behaviour but which by virtue of their mechanical properties are at most limitedly useful for medical application and—thus at least in the case of synthetic polymers based on PU and LDA derivatives—also cause a severe inflammatory reaction and stimulate neointima proliferation.

Images