Drug – bio-affecting and body treating compositions – Nonspecific immunoeffector – per se ; or nonspecific...
Patent
1991-12-13
1997-03-04
Woodward, Michael P.
Drug, bio-affecting and body treating compositions
Nonspecific immunoeffector, per se ; or nonspecific...
514 54, 53612312, A61K 4736, A61K 31715, C07H 100
Patent
active
056076770
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE DISCLOSURE
Advances in biotechnology and immunology have presented new challenges for obtaining safe and effective drugs, such as vaccines. For example, new generation subunit and antiidiotype antigens yield very safe vaccines; however, these vaccines, in general, provide poor immune stimulation and prophylactic effects. Therefore, an important aspect of any new drug or vaccine formulation is a component that enhances its safety and efficacy by providing a delivery mechanism and, in the case of vaccines, by boosting the immune response to the antiget. Adjuvants can generally be categorized as components that boost the immune response, and as delivery systems that enhance antigen presentation, provide sustained release of the drug or antiget for extended periods, or target the drug or antiget to specific immune cells.
Serious drawbacks exist in many of today's adjuvants and delivery systems. Most are crude preparations of bacterial or plant origin, or oil emulsion systems, the active components and modes of action of which are unknown. In addition, these compounds are usually toxic and cannot be used safely, especially for human applications. Some preparations of the yeast cell wall component. .beta.-glucan, have been shown to provide enhanced resistance to several infectious diseases when given in conjunction with viral vaccines or killed infected cells. Reynolds et al., 1980, Infect. Immunity, 30:51-57; Holbrook et al., 1981, Infect. Immunity, 35:534-546; Benach et al., 1982, Infect. Immunity, 36:947-951. Some of the adverse effects of administering other .beta.-glucan preparations are described by Williams et al. in U.S. Pat. No. 4,761,402. These effects include anaphylaxis, granuloma development, hypotension development and a high degree of acute toxicity.
SUMMARY OF THE INVENTION
The invention relates to a novel pharmaceutical composition which is a drug delivery vehicle and which nonspecifically enhances the immune response. The composition comprises whole glucan particles and a pharmacologically active substance, such as a drug or antigert. The drug or antigen can be contained within, uniformly dispersed with, or chemically linked to the whole glucan particles.
Methods for utilizing whole glucan particles in pharmaceutical formulations which provide, in combination, (1) the prolonged release of the drug; (2) longer half-life of the drug by protecting it from proteolytic, hydrolyric and other clearance mechanisms; (3) targeted delivery of the drug to macrophages; and (4) stimulation of the immune response are also the subject of the present invention.
When the present composition is administered to an individual the entrapped drug is released through the glucan matrix into the physiological environment. Where the drug is an antigen, the .beta.-glucan component simultaneously acts as an adjuvant to the antigen by enhancing the immune response in the individual.
Whole glucan particles are very pure preparations of .beta.-glucan molecules which avoid many of the undesirable side effects associated with less pure preparations. Whole glucan particles retain the in vivo three-dimensional morphology of the yeast cell walls from which they are derived. Thus, the particles are hollow, which allows the drug or antiget to be incorporated into the cavity. Whole glucan particles have a higher water-holding capacity than .beta.-glucans prepared by other methods which disrupt the cell walls. The water-holding capacity can be controlled by modifying the .beta.-glucan structure, for example, by modifying the amount of branching.
The invention further provides a method for providing a drug or antigen to an individual while simultaneously providing an adjuvant to boost the immune response to the drug or antigen, by administering to the individual a drug contained within (e.g., encapsulated or entrapped), or uniformly dispersed in, or chemically linked to whole glucan particles. For example, a vaccine can be incorporated into a whole glucan particle, and the particle administered to an individual to
REFERENCES:
patent: 4705780 (1987-09-01), Massot et al.
patent: 4739046 (1988-05-01), DiLuzio
patent: 4741872 (1988-06-01), DeLuca et al.
patent: 4761402 (1988-05-01), Williams et al.
patent: 4810646 (1989-03-01), Jamas et al.
patent: 4857505 (1989-05-01), Arendt
J. K. Czop, Pathology and Immunopathology Research, 5:286-296 (1986).
J. A. Cook et al., Survey of Immunology Research, 2:243-245 (1983).
W. Browder, Survey of Immunology Research, 2:299-301 (1983).
M. L. Patchen, Survey Immunology Research, 2:237-242 (1983).
J. A. Reynolds et al., Infection and Immunity, 30(1):51-57 (1980).
T. W. Holbrook et al., Infection and Immunity, 32(2):542-546 (1981).
J. L. Benach et al., Infection and Immunity, 35 (3):947-951 (1982).
E. R. Sherwood et al., International Journal of Immunopharmacology 9 (3):261-267 (1987).
J. A. Cook et al., Infection and Immunity, 37 (3):1261-1269 (1982).
T. W. Holbrook et al., American Journal of Tropical Medical Hygiene, 32(1):51-53 (1983).
T. W. Holbrook et al., American Journal of Tropical Medical Hygiene, 30 (4):762-768 (1981).
J. A. Cook et al., Infection and Immunity, 40 (3):1038-1043 (1983).
M. A. Chirigos et al., Cancer Research, 38:1085-1091 (1978).
S. James et al., Biotech. Bioeng., 28:769-784 (1986).
Patent Abstracts of Japan, vol. 8, No. 279 (Dec., 1984) Masumoto.
International Search Report for International Application No. PCT/USPO/03440.
Easson, Jr. D. Davidson
Jamas Spiros
Ostroff Gary R.
Alpha-Beta Technology, Inc.
Woodward Michael P.
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