Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Patent
1997-05-14
1999-11-30
Dees, Jose G.
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
424 111, 424 181, 424 185, 206569, 206223, A61K 5100, A61M 3614
Patent
active
059937769
DESCRIPTION:
BRIEF SUMMARY
This invention has the objective of producing injectable radio-pharmaceutical compositions containing radio-halogenated fatty acids intended for the study of cardiac metabolism problems by scintigraphy.
The functional study of the heart by an external route allows to appraise possible pathological modifications. Hence, the image obtained by the injection of thallium-201 allows the display of the distribution of the blood flow in the myocardium, but it does not give any access to the metabolic condition of the myocardial cell.
The long chain fatty acids constitute one of the principal sources of energy of the cardiac muscle, since they supply 65% of the energy necessary for the functioning of the myocardial cells. As the presence of a halogen in these fatty acids does not modify in any way their metabolic properties, the radio-labelling of the fatty acids by a radioactive halogen therefore leads to an excellent method for exploring metabolic problems of the myocardial cells in man.
At the present time, in order to carry out these examinations, fatty acids labelled with radioactive iodine are used, such as 16-iodo(.sup.123 I) 3-methyl hexadecanoic acid (.sup.123 IAGM). Within the nuclear medical departments, this product is prepared just before injection by labelling the IAGM with the iodine-123. This radio-labelled tracer, insoluble in aqueous solvents, is then dissolved in a liquid constituted by a solution of human blood albumin. The use of human blood albumin poses certain problems for reasons of the very strict control to be exercised on the quality of the human blood albumin so as to avoid any viral contamination of the patient. It would therefore be particularly interesting to use, for the solubilisation, a compound that does not present any contamination risks.
Furthermore, the preparation of the fatty acid labelled with iodine-123 is a rather burdensome method, which requires qualified and trained personnel and a sterile environment to ensure that the final product is innocuous.
It would therefore be of interest, in order to improve the quality of the product, to be able to do this in a pharmaceutical establishment which would be able to distribute the radio-labelled product, both sterile and ready for use.
However, when human blood albumin is used to make the product soluble, sterilisation by heat is impossible since the blood albumin is degraded under these conditions.
Specifically, the object of this invention is to replace human blood albumin with a product that does not have the disadvantages described above, with the purpose of obtaining a radio-pharmaceutical composition of a radio-halogenated fatty acid that, in addition, leads to improved biodistribution of the radio-halogenated fatty acid.
This product that replaces the human blood albumin is a cyclodextrin or one of its derivatives.
Cyclodextrins are cyclic oligosaccharides composed of 6(.alpha.), 7(.beta.) and 8(.gamma.) units of D-glucopyranose linked .alpha.-1,4. In these cyclodextrins, the internal hydrophobic cavity is constituted by protons, while the hydroxyl groups which are directed towards the exterior, generate an external hydrophilic structure. This internal cavity can accept hydrophobic molecules or parts of organic molecules. An inclusion complex is then formed.
This capacity to enclose organic molecules has already been used to solubilise medicines sparingly soluble or insoluble in water, as has been described in U.S. Pat. No. 4,727,064 and EP-A-0 149 197. Hence inclusion complexes have been formed with organic compounds such as hormones, steroids, cardiac glycosides, the derivatives of benzodiazepines, benzimidazoles, piperidines, piperazines, imidazoles etc.
However, as indicated in EP-A-0149197, .beta.-cyclodextrin and its methyl derivatives are not suitable for therapeutic use because of their high toxicity.
Nevertheless, within the field of scintigraphy WO-A-93/15765 describes the use of cyclodextrins as an additive to stabilise certain constituents of a pharmaceutical product kit, notably phosphorated ligands such as
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Djedaini-Pilard Florence
Mauclaire Laurent
Michel Yves
Pasqualini Roberto
Perly Bruno
Cis Bio International
Dees Jos,e G.
Jones Dameron
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