7.1. Effects of postirradiation carboxymethylglucan administration in mice (Hofer et al. 1995).
The haemopoiesis-enhancing ability of a soluble glucan derivative, i.e. carboxymethylglucan (CMG), was investigated in gamma-irradiated mice. CMG was administered i.p. at (a) single dose of 6 mg 2 h postirradiation, (b) four 6 mg doses in the first 4 days postirradiation, (c) four 1.5 mg doses at the same time intervals. Indications of granulopoiesis and inflammatory side effects (liver weight increase and hepatic granulomas) were investigated in mice irradiated with a sublethal dose of 7 Gy. All three CMG-treated groups of mice were found to exhibit enhanced haemopoietic recovery in comparison with the controls. The mice repeatedly given the 6 mg CMG doses (group b) showed the most rapid recovery of all the evaluated parameters of granulopoiesis, but also the most pronounced hepatic side effects were found in these mice. When survival of mice was recorded in lethally (9 Gy) irradiated animals, the best protective response were obtained following the repeated administration of the 1.5 mg CMG dose, the survival by day 30 in this group being significantly higher not only in comparison with the controls but also with the mice repeatedly given the 6 mg dose of CMG. The results suggest that the postirradiation CMG administration can be useful for enhancing radiation-suppressed haemopoiesis. However, repeated larger CMG doses may produce side effects that compromise the overall survival of irradiated mice.
7.2. Isolation, physicochemical characterization and preclinical efficacy evaluation of soluble scleroglucan (Pretus et al. 1991).
Alkaline extraction of insoluble S. glucanicum exopolymers produced a soluble scleroglucan composed of a triple-helical beta-1,3-linked glucopyranose backbone with single beta-1,6-linked glucopyranosyl branches every third subunit. Scleroglucan has a weight average molecular mass of 1.56 x 10(6) Da, a weight average root mean square distance from the center of gravity of the molecule to its farthest elements of 51.8 nm, a polydispersity (weightaverage molecular mass/number average molecular mass) of 1.83 and intrinsic viscosity of 3.081 dl/g. Scleroglucan (250 mg/kg, intravenously) stimulated in vivo murine macrophage phagocytic activity (66%, P less than .001) and increased in vitro macrophage tumor cytotoxicity against syngeneic tumor targets by 124% (P less than .05). Scleroglucan enhanced (P less than .001) murine bone marrow proliferation in a biphasic manner by up to 328%.
Scleroglucan therapy increased survival of mice challenged with syngeneic lymphoma, melanoma or adenocarcinoma. AKR/J mice bearing syngeneic lymphoma (1 x 10(3) cells, intraperitoneally) demonstrated increased (P less than .001) long-term survival (100% vs. 0%, greater than 64 days). C57Bl/6J mice bearing syngeneic melanoma B16 (5 x 10(5) cells, subcutaneously) demonstrated increased long-term survival (64% vs. 0%, P less than .05). C57Bl/6J mice bearing syngeneic adenocarcinoma BW10232 (1 x 10(5) cells, subcutaneously) demonstrated increased (P less than .05) median survival time. In addition, scleroglucan prophylaxis increased resistance of mice to challenge with Staphylococcus aureus, Candida albicans and mouse hepatitis virus A-59. Scleroglucan did not induce toxicity or hepatomegaly. It was concluded that the water-soluble beta-1,3-linked scleroglucan stimulates immunity, modifies experimental neoplastic disease and increases resistance to microbial challenge.
7.3. Development, physicochemical characterization and preclinical efficacy, evaluation of a water-soluble glucan sulphate derived from Saccharomyces cerevisiae (Williams et al. 1992).
This report describes the development, characterization and preclinical efficacy evaluation of water-soluble glucan sulphate. Glucan sulphate was derived from insoluble beta-1,3-D-glucan isolated from Saccharomyces cerevisiae. The proposed repeating unit empirical formula of glucan sulphate is [(C6H10O5)5.3H2SO4]n. Two polymer peaks were resolved by aqueous high-performance size exclusion chromatography (HPSEC) with on-line multi-angle laser light scattering (MALLS) photometry and differential viscometry. Peak 1 (MW = 1219697 Da) represents approximately 1% of the total polymers, while peak 2 (MW = 8884 Da) accounts for approximately 99% of polymers. 13C-NMR spectroscopy suggests that glucan sulphate polymer strands may be partially cross-linked. Glucan sulphate (250 mg/kg, i.v.) increased (P less than 0.01) macrophage vascular clearance of 131Ireticuloendothelial emulsion by 42% (P less than 0.01) and in vitro bone marrow proliferation by 46% (P less than 0.05). Glucan sulphate (250 mg/kg, i.v.) increased (P less than 0.05) median survival time of C57B1/6J mice with syngeneic melanoma B16 or sarcoma M5076. In addition, glucan sulphate immunoprophylaxis increased resistance of mice to challenge with Escherichia coli, Candida albicans or Mouse Hepatitis Virus strain A-59. It was concluded that glucan sulphate activates macrophages, stimulates bone marrow, exerts anti-tumor therapeutic activity, and modifies the course of experimental infectious disease.
7.4. Tumor regression after treatment with aminated beta 1-3D polyglucose is initiated by circulatory failure (Seljelid 1989).
Meth A sarcoma grew progressively when inoculated intradermally in CB6 mice. When the mice were treated on day 7 after inoculation with 10 mg aminated polyglucose (AG) [Bogwald, J., Hoffman, J. & Seljelid, R. Carbohydrate Res. 148, 101, 1986], the tumors regressed completely in over 90% of the cases. During the first hours after AG treatment, tumor thymidine incorporation decreased, adenosine triphosphate (ATP) content decreased, and there were indications of circulatory disturbance as shown by decreased deposition of dye (trypan blue) in the tumor tissue after intravenous injection. Histological examination demonstrated a conspicuous thickening of the walls of small tumor vessels, statis of red blood cells, and perivascular collections of mononuclear cells only hours after AG treatment. In thymectomized animals, where regression does not occur after AG treatment [Seljelid, R. Bioscience Reports 6, 845, 1986], there was no evidence of circulatory failure, no tumor diameter reduction, and no decrease in colouring following intravenous injection of trypan blue. On the basis of these findings, we conclude that the early phase of events after AG treatment leading to tumor regression involves a vascular phenomenon that causes circulatory disturbance and necrosis. The data also indicate that this initial circulatory failure requires the involvement of functional T cells.
7.5. Soluble yeast beta-1,3/1,6-glucan in cosmetic formulations (patents WO 0054734, WO 0054742 and WO 0054739)
A soluble beta-1,3/1,6-glucan preparation (patent EPO: application no. 95914485.8) has been the active ingredient in various cosmetic formulations for humans. According to the data presented in these documents the soluble beta-1,3/1,6-glucan protects against skin cell damage caused by UV-light (WO 0054734), causes reduction in wrinkle depth of skin (WO 0054742) and counteracts gum infection (WO 0054739).