Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Patent
1997-04-29
1999-05-25
Kishore, Gollamudi S.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
424400, 424 43, 424 45, 4284022, 514937, A61K 9127, A61K 910
Patent
active
059068310
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
the present invention is within the field of encapsulating biologically active materials in order to obtain a controlled, or sustained, release thereof as is desirable within many different technical fields, such as for instance to have a longer lasting or delayed effect of a pharmaceutically active material. More specifically the invention is based on a novel encapsulating or carrier material or system which enables a highly reproducible sustained release (reduced biological variability) of biologically active compounds. With reference to last-mentioned property the term "controlled release" will be generally used throughout description and claims to emphasize the fact that by the present invention the desired sustained release of the active compound can be obtained in a controlled way.
BACKGROUND OF THE INVENTION
About thirty years ago one of the inventors, K. Larsson, in Z. phys. Chem. 56 (1967), 173, reported that the aqueous system of monocaproin, which is a lipid the complete name of which is glycerolmonohexanoate or glycerolmonocapronate, forms one single liquid phase at all compositions. At that time this was a unique and remarkable behaviour of a single amphiphilic (surfactant) molecule; only mixtures of surfactants and cosurfactants were known to exceptionally show such lack of a phase transition when the composition was changed from anhydrous towards pure water.
Recent work within the field of drug delivery, with special regard to molecules that need to be protected against enzymatic degradation (like peptides), has shown that so called microemulsions or L2-phases provide a useful carrier system. An example of such an L2-system is disclosed in European patent specification No. 314 689, which discloses the utilization of C.sub.16-22 -monoglycerides interacting with C.sub.16-22 -triglycerides and a polar liquid.
although the phase properties of monocaproin have been known for a very long time, however, it has not been realized earlier that this unusual micellar phase can provide a highly efficient carrier in connection with for instance drug delivery, as far as is known to applicant. The main reason probably is that a molecule with such a short hydrocarbon chain is regarded more as an organic solvent than as a lipid and has, therefore, not been expected to provide efficient solubilization power of drugs into an association-colloid type of structure.
When amphiphilic systems forming ordinary micellar solutions (L1-solution) have been used in drug delivery, relatively long hydrocarbon chains have also been involved; cf. K. A. Johnson, G. B. Westermann-Clark, and D. Shaf, Pharmaceut. Res. 6 (1989), 239.
Furthermore, it can be added that Ericsson and Hegg in Progr. Colloid & Polymer Sci. 70 (1985), 92, have reported a study of the surfactant behaviour of 1-monocaproin and its interaction with ovalbumin in a diluted water solution. The critical micellar concentration (cmc) of monocaproin was found to be 160 mM. Their result demonstrated that there is no molecular interaction between this specific protein and monocaproin. We have now unexpectedly found that the micellar system according to the present invention exhibits full compatibility with any protein also at high concentrations, i.e. even up to and including the region where the L1-type of structure changes to the L2-type of structure.
GENERAL DESCRIPTION OF THE INVENTION
Thus the present invention is based on the unexpected finding that monocaproin is highly efficient in solubilizing amphiphilic biologically active materials, especially drug molecules, and that the successive change from an L2-type of micellar solution into an L1-type thereof without any phase separation provides a useful mechanism for protecting molecules which are sensitive to enzymatic degradation, and also for sustained release, particularly in drug administration, for instance oral administration.
It has also been found that lipase degradation of the new compositions according to the present invention is extremely slow compared to previously disclosed g
REFERENCES:
patent: 5151272 (1992-09-01), Engstrom et al.
Larsson, K.ang.re, "The Structure of Mesomorphic Phases and Micelles in Aqueous Glyceride Systems", Z. Phys. Chem. 56 (1967), pp. 173-198.
Johnson, Keith, et al., "Controlled Release of Steroids Through Microporous Membranes with Sodium Dodecyl Sulfate Micelles", Pharmaceutical Research, vol. 6, No. 3, 1989, pp. 239-243.
Hills, Brian A., The Biology of Surfactant, Cambridge University Press, (1988).
"Surface Behavior of Adsorbed Films from Protein-Amphiphile Mixtures", Progress in Colloid & Polymer Science, vol. 70, B. Ericsson et al., pp. 92-95, 1985.
Larsson K.ang.re
Ljusberg-Wahren Helena
GS Development AB
Kishore Gollamudi S.
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