Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – Molecular bilayer structure
Patent
1989-01-19
1994-05-17
Waddell, Frederick E.
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
Molecular bilayer structure
424 9, A61K 4904, A61K 4900
Patent
active
053126157
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to an aqueous composition which can be injected into the circulatory system of a patient and the purpose of which is to opacify certain organs with a view to their diagnostic examination with X-rays. This composition is formed of a suspension, in a physiologically acceptable aqueous medium, of liposomes as vesicles with a phospholipidic membrane containing, encapsulated in these vesicles, an aqueous solution of at least one iodinated compound which is opaque to the X-rays.
It is known to use suspensions of liposomes as vehicles for the transportation, in certain organs which are to be studied, of opacifying agents intended for radioscopic examinations. Thus, the specification of U.S. Pat. No. 4,192,859 describes such a suspension of liposomes constituted of lecithin and sterols and containing about 20 to 60% by weight of a contrast agent intended for the examination of organs, particularly of organs in relation with the reticuloendothelial and cardiovascular systems, as well as lymphographic examinations. Among such contrast agents, the following compounds are referred to in this specification:
N,N'-bis[2-hydroxy-1-(hydroxymethyl)-ethyl]-5-[(2-hydroxy-1-oxopropyl)-amin o]-2,4,6-triiodo-1,3-benzene-dicarboxyamide (iopamidol); metrizamide; diatrizoic acid; sodium diatrizoate; meglumine diatrizoate; acetrizoic acid and its soluble salts; diprotrizoic acid; iodamide, sodium iodipamide, meglumine iodipamide, iodohippuric acid and the soluble salts thereof; iodomethamic acid; iodopyracetiodo-2-pyridone-N-acetic acid, 3,5-diiodo-4-pyridone-N-acetic acid (Iodopyracet); the diethylammonium salt of the preceding acid; iothalmic acid; metrizoic acid and the salts thereof, the ipanoic, iocetamic, iophenoxic acids and their soluble salts; sodium tyropanoate, sodium ipodate and also other similar iodised compounds. The lipidic membrane of the liposomes which are used in accordance with this document mainly contains phospholipids, a sterol, lecithin, dicetyl phosphate or stearyl amine, and an organic solvent. Always in accordance with this document, it is possible to prepare such liposomes by the selected lipidic components being mixed in a container with an organic solvent, such as chloroform, dichloromethane, ethyl ether, carbon tetrachloride, ethyl acetate, dioxane, THF, etc. After having evaporated the volatile compounds under reduced pressure, the lipidic mixture is dispersed in a buffering solution containing a measured quantity of an opacifying agent. The whole is then stirred for several hours, this causing the formation of liposomes, a part of the dispersion liquid (containing the opacifying agent) then being encapsulated in the liposomic vesicles which are thus produced. The dispersion is then subjected to a sonication in order to reduce the size of these liposomes and the viscosity of the dispersion.
There are other documents which are concerned with the preparation of liposomes which contain opacifying agents.
For example, the specification of FR-A-2,561,101 describes a process for the preparation of liposomes which may contain X-ray opacifying agents. According to this specification, there are first of all prepared "precursors" of liposomes in organic solution, from which then the solvent is partially separated, this solution containing a proportion of lipids which are adapted to convert the monomolecular membrane of the precursors into bimolecular membrane. This solution is then dispersed in an aqueous medium and the residual solvent is completely eliminated.
The specification of U.S. Pat. No. 4,567,034 describes X-ray opacifiers and the incorporation thereof into the liposomes as vector of a contrast product.
The specification of GB-A-134,869 describes a technique for the preparation of liposomes, in accordance with which particles (10 .mu.m) of a hydrosoluble carrier agent (NaCl, saccharose, lactose, etc.) are coated with an amphipatic agent, the subsequent dissolution of the carrier in an aqueous medium yielding the liposomes. The coating is effected by dispersing the solid
REFERENCES:
patent: 4192859 (1980-03-01), Mackaness et al.
patent: 4599227 (1986-08-01), Dees et al.
patent: 4647447 (1987-03-01), Gries et al.
patent: 4744989 (1988-05-01), Payne et al.
Chemical Abstracts: (106:125855w) 1987.
Lamy Bernard
Schneider Michel
Tournier Herve
Bracco - Industria Chimica S.p.A.
Waddell Frederick E.
Weddington K.
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