Quality of life for hepatitis C patients with a formulation for administration to the oral mucosa including Lactobacillus delbrueckii subsp. bulgaricus and N-acetyl D-glucosamine

#Lactobacillus delbrueckii subsp bulgaricus (LBD) is a gram-positive homofermentative lactic acid bacteria which metabolizes carbohydrates with lactic acid as the major end product (Salminen, S., and von Wright, A., “Current Probiotics-Safety Assured?” Microbial Ecology in Health and Disease (1998)10:68-77).

#LBD is well known as a food additive and dietary supplement, and is one of the components that are required by the FDA to be included in any product identified as “yogurt.” LBD is a gram positive, non-motile, non-spore forming bacilli, which is homofermentative, and is almost exclusively present in milk (Germond, et al., Evoluton of the bacterial species Lactobacillus delbrueckii: A partial genomic study with reflections on prokaryotic species concept, Mol. Biol. Evol., 20(1):93-104, 2003; Pelczar, M. J. and Reid, R. D., Microbiology of Milk, Microbiology 2nd Edition, p. 534, McGraw Hill, NY, N.Y., 1965). For patients with hepatitis C, there are reports that administering LBD improves quality of life, and can even lower viral load.

#In fact, it has been postulated that LDB may work therapeutically by improving the immunologic barrier of the intestine through stimulating the immunoglobulin A response or by alleviating the inflammatory response (Isolaurie et al., Probiotics: effect on immunity, Amer. J. Clin. Nutr. (2001) 73(suppl):444S-450S). Anti-inflammatory properties of fermented milk on the intestine may be derived from their ability to inhibit platelet activating factor (P AF), a potent phospholipids mediator secreted by pro inflammatory cells. LDB was found to be a critical component in the biosynthesis of quantities of P AF inhibitors (Heyman, M., Effect of Lactic Acid Bacteia on Diarrheal Diseases, J Amer College of Nutr (2000) 19(2):137S-146S). Studies have reported the increase in cytokines such as the cytokines I1-10 and I1-4 in mice (Ghosh et al., Probiotics in inflammatory bowel disease: is it all gut flora modulation?, Gut (2004) 53:620-622) as well as activation of macrophages following the oral introduction of LDB (Isolauri, E. et al., supra) and the stimulation of IFN-alpha/beta following intraperitoneal injection of LDB in animal studies (Pereyra et al., Interferon induction by Lactobacillus bulgaricus and Streptococcus thermophilus in mice, Eur Cytokine News (1991) 2(4):299-303). LDB has also been investigated in vivo and in vitro for toxicity towards the carcinogens MNNG and H202. Acetone extracts of LDB as well as lactic acid metabolites that were expected to be in the gut lumen as fermentation products were examined. LDB (but not the metabolites) was determined to be antigenotoxic (Wollowski et al., Bacteria Used for the Production of Yogurt Inactivate Carcinogens and Prevent DNA Damage in the Colon of Rats, J. Nutr (1999) 129:77-82).

#In order to generate the formulation described herein suitable for therapy, which is capable of dissolving on the oral mucosa in less than about one minute and releasing the active ingredients, the following exemplary procedure may be followed, although there are a number of other processes which could also generate a suitable formulation. The process consists of three steps of processing the active ingredients and two steps involving formulation and tablet making.

#1. Active Ingredient Process

#Fermentation