Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-01-26
1998-07-21
Kight, John
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
53612312, 5361231, 536124, C07H 100, C08B 3700, A61K 31715
Patent
active
057835691
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
In the early 1960's, zymosan, a crude insoluble yeast extract prepared by boiling yeast before and after trypsin treatment, was noted to produce marked hyperplasia and functional stimulation of the reticuloendothelial system in rodents. In animal studies, zymosan preparations were shown to inactivate complement component C3, to enhance antibody formation, to promote survival following irradiation, to increase resistance to bacterial infections, to inhibit tumor development, to promote graft rejection, and to inhibit dietary-induced hypercholesterolemia and cholesterosis. Zymosan was shown to consist of polysaccharides, proteins, fats, and inorganic elements; however, subsequent studies identified the active components of the yeast cell wall as a pure polysaccharide, specifically .beta.-glucan. In conventional nomenclature, the polysaccharide .beta.-glucan is known as poly-(1-6)-.beta.-D-glucopyranosyl-(1-3)-.beta.-D-glucopyranose (PGG). Repetition of biological assays with .beta.-glucan indicated that most of the above functional activities identified with zymosan were retained by the purified .beta.-glucan preparation.
The properties of .beta.-glucan are quite similar to those of endotoxin in increasing nonspecific immunity and resistance to infection. The activities of .beta.-glucan as an immune adjuvant and hemopoietic stimulator compare to those of more complex biological response modifiers (BRMs), such as bacillus Calmette-Guerin (BCG) and Corynebacterium parvum. The functional activities of yeast .beta.-glucan are also comparable to those structurally similar carbohydrate polymers isolated from fungi and plants. These higher molecular weight (1-3)-.beta.-D-glucans such as schizophyllan, lentinan, krestin, grifolan, and pachyman exhibit similar immunomodulatory activities. A common mechanism shared by all these .beta.-glucan preparations is their stimulation of cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF). Lentinan has been extensively investigated for its antitumor properties, both in animal models at 1 mg/kg for 10 days and in clinical trials since the late 1970s in Japan for advanced or recurrent malignant lymphoma and colorectal, mammary, lung and gastric cancers. In cancer chemotherapy, lentinan has been administered at 0.5-5 mg/day, intramuscularly (I.M.) or intravenously (I.V.), two or three times per week alone, or in combination with antineoplastic drugs. In addition to the activities ascribed to yeast glucans, studies suggest lentinan acts as a T-cell immunopotentiator, inducing cytotoxic activities, including production of interleukins 1 and 3 and colony-stimulating factors (CSF). (Chihara et al., 1989, Int. J. Immunotherapy, 4:145-154; Hamuro and Chihara, In Lentinan. An Immunopotentiator)
Various preparations of both particulate and soluble .beta.-glucans have been tested in animal models to evaluate biological activities. The use of soluble and insoluble .beta.-glucans alone or as vaccine adjuvants for viral and bacterial antigens has been shown in animal models to markedly increase resistance to a variety of bacterial, fungal, protozoan and viral infections. The hemopoietic effects of .beta.-glucan have been correlated with increased peripheral blood leukocyte counts and bone marrow and splenic cellularity, reflecting increased numbers of granulocyte-macrophage progenitor cells, splenic pluripotent stem cells, and erythroid progenitor cells, as well as, increased serum levels of granulocyte-monocyte colony-stimulating factor (GM-CSF). Furthermore, the hemopoietic and anti-infective effects of .beta.-glucan were active in cyclophosphamide-treated immunosuppressed animals. .beta.-glucan was shown to be beneficial in animal models of trauma, wound healing and tumorigenesis. However, various insoluble and soluble preparations of .beta.-glucan differed significantly in biological specificity and potency, with effective dosages varying from 25 to 500 mg/kg intravenously or intraperitoneally (I.P.) in models for protection against infectio
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Easson, Jr. D. Davidson
Jamas Spiros
Ostroff Gary R.
Alpha-Beta Technology, Inc.
Kight John
White Everett
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