Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Patent
1996-01-02
1999-03-09
Bawa, Raj
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
514937, 264 41, A61K 9127, A61K 9107
Patent
active
058797033
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD OF THE INVENTION
This invention relates to a system for delivering vaccines to mucosal sites for the stimulation of immunoglobulin production and to the production of vaccines and lipid-encapsulated active ingredients.
BACKGROUND OF THE INVENTION
The route of administration of a particular vaccine is dependent upon several factors. Factors to be considered include locus of initiation of infection, locus of disease progression, systemic or nonsystemic involvement, pathogenicity of the particular vaccine used, and type of immunity desired to be induced. Vaccines have been given orally, parenterally, and through inhalation. Oral and inhalation administration of vaccines is preferable when it is desirous to stimulate production of secretory immunoglobulin as a first line of defense against infection. Oral administration of vaccines may also be preferable in the instance of a particularly pathogenic organism, even though the organism has been attenuated prior to administration.
As the pathogenicity of the particular organism administered as a vaccine increases, so do concerns regarding incomplete attenuation. Alternatives have been developed which utilize protein subunits of antigenic molecules expressed on the surface of the organisms instead of the complete organism. However, although such materials are generally antigenic, they are not always immunogenic. Immunogenicity depends upon, among other factors, size. Several attempts have been made to address the antigen immunogen dichotomy in particularly pathogenic organisms. In that regard, various adjuvants were developed to augment the immunogenicity of a particular antigen and include such materials as keyhole limpet hemocyanin, aluminum hydroxide gels, sodium alginate, synthetic polynucleotides, muramyl dipeptide, Bordetella pertussis, Freund's Complete Adjuvant (emulsion of mineral oil, water, and mycobacterial extracts, and Freund's Incomplete Adjuvant (emulsion of water and oil only). Liposomes have also been used as adjuvants.
A liposome is a lipid-containing vesicle capable of entrapping various molecules of interest. Previously, most liposome vesicles functioned as adjuvants on the principle of entrapment of the antigen within a central core. However, liposomes have been developed which attempt to integrate the antigen within the lipid bi-layer.
U.S. Pat. No. 5,100,662 issued to Bolcsak et al. on Mar. 31, 1992 describes liposomes or liposome-like structures comprising sterols either alone or in combination with additional liposome-forming lipids. Liposome structures such as micelles, reverse micelles, hexagonal phases, multilamellar vesicles, or unilamellar vesicles are described. The liposomes may be prepared with or without the use of an organic solvent and may function as vaccines after entrapment or association of an immunogen.
While not specifically addressed to vaccine preparations, U.S. Pat. No. 5,049,388 issued to Gilbert et al. on Sep. 17, 1991 describes small particle aerosol liposomes and liposome-drug combinations for medical use and discloses that the drug or medication is interactive with the liposome membrane so that, on its rupture, the drug or medication is not lost from the liposome. Before aerosolization, the liposomes are heterogenous in size.
U.S. Pat. No. 4,900,549 issued to de Vries on Feb. 13, 1990, relates to a process for preparing immunogenic complexes. The patent describes an amphipathic antigenic protein or peptide contacted with a solution containing a detergent, a sterol, and a glycoside comprising hydrophobic and hydrophilic regions. Subsequently, the detergent is removed and the immunogenic complex is purified. Optionally, the solution further comprises a phospholipid, preferably phosphatidylethanolamine. The structure is described as consisting of cage-like or two-dimensional aggregates, depending upon whether phospholipid is or is not present, respectively.
The incorporation of pathogen subunits into liposome preparations for stimulation of immune response has been described previously. More specif
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Guzman, et al., "Antibody responses in the serum and respiratory tract of mice following oral vaccination with liposomes coated with filamentous hemagglutinin and pertussis toxoid," Infect Immun 61:573-579 (1993).
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Bawa Raj
Fountain Pharmaceuticals, Inc.
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