Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Patent
1994-05-16
1996-02-13
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
424489, 424490, 424497, A61K 914
Patent
active
054909864
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to a microcapsule composition for the delivery of an oxygen and carbon dioxide carrying compound through the vascular system. In particular, the microencapsulated composition is useful as an artificial blood substitute.
BACKGROUND
A specific type of microcapsulant material and a method of making such material is disclosed in U.S. Pat. No. 3,959,457 (of common assignment and partial common inventorship herewith). This material is comprised of the reaction product produced at the interface boundary of a finely dispersed emulsion, comprising a water immiscible solution of a Lewis base and an aqueous solution of a partially hydrophilic, partially lipophilic Lewis acid.
An improvement in the invention of the '457 patent is disclosed in a presently pending U.S. application (also of common assignment herewith and partial common inventorship), at least one foreign counterpart of the parent of which has been published prior to the conception of the present invention (see European Patent Application, Publication Number 0 299 205, Publication Date, Jan. 18, 1989). According to specific aspects of this prior improvement, polyoxethylene-polyoxypropylene or block copolymers thereof comprise a core-forming adjuvant and/or ethylene oxide adducts of ethylenediamine ("tetronomers") comprise a wall-forming adjuvant for use in systems of the '457 patent type. The resultant microcapsules are more robust and more stable physically than the non-adjuvant microcapsules disclosed in the '457 patent.
Perfluorocarbons are known to be useful as blood substitutes but only in the form of dispersions or emulsions. One such known prior art emulsion of perfluorocarbons is marketed under the trade name Fluosol DA. It is understood that this and similar dispersed emulsions exhibit low stability and must be stored at -40.degree. C. Microspheres containing cross-linked hemoglobin and encapsulated hemoglobin have also been prepared for use as a blood substitute. (See U.S. Pat. No. 3,875,510 Kitajima et al., U.S. Pat. No. 4,133,874--Miller et al. and U.S. Pat. No. 4,376,059--Davis et al.)
Encapsulated fluorocarbons have previously been disclosed as tracers for use in the petroleum and petrochemical fields, but the known encapsulants (see U.S. Pat. No. 4,520,109--Simmonds et al. and U.S. Pat. No. 3,964,294-- Shair et al.) are quite .different from those used in the present invention.
Heretofore, such perfluorocarbons have been considered poor candidates for encapsulation in systems of the '457 type because their polar character would be expected to destabilize the capsule wall structure.
The extremely low polarity of perfluorocarbons causes them to be incapable of solvating the regions of high charge density associated with ionic centers in systems of the '457 type or of forming hydrogen bonds with water solvating those ionic centers. As a practical result, it has heretofore been impossible to capture perfluorocarbons in charged film microcapsules of the type produced by '457. A technique is described in '457, currently pending U.S. application Ser. No. 07/417,590 and European Patent Application 0 299 205, by which nonpolar materials may be utilized as the dispersed phase and encapsulated. In this technique a solvent of intermediate polarity, such as chloroform, is added to a core material of low polarity, such as light liquid petrolatum, to increase polarity of the dispersed phase. This technique is not applicable to perfluorocarbons because they exhibit such low polarity that they are immiscible with solvents such as chloroform or the even less polar material light liquid petrolatum.
Three other references identified as of possible interest in a patentability search on the present invention are U.S. Pat. No. 4,107,288--Oppenheim et al., U.S. Pat. No. 4,512,762--Spears and U.S. Pat. No. 4,812,445--Eden et al. The first and third of these pertain to encapsulation techniques different from that used in the present invention and the second, at column 2, lines 37-42, makes reference (though negative)
REFERENCES:
patent: 5284663 (1994-02-01), Speaker
Benston, Jr. William E.
Page Thurman K.
Temple University Of The Commonwealth System Of Higher Education
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