1. PROBIOTICS IN HEALTH & DISEASE www.triphasepharma.com 1 An ISO9001:2008 Certified Company

2. What are Probiotics? Potential Mechanisms of Action Therapeutic Targets of Probiotics Strain Specificity Quality Control Private & Confidential 2

3. 3 PROBIOTICS “ Live microorganisms which when administered in adequate amounts confer a health benefit on the host” Probiotic microorganisms can be found in both supplement form and as components of foods and beverages.

4. Private & Confidential 4 TYPES OF PROBIOTIC Lactobacillus - Most available are species are, - L.acidophilus - L.casei - L.reuterii - L.rhamnosus - L.bulgaricus - L.plantarum Bifidobacteria - Most available are species are, - B.infantis - B.longum - B.bifidum - B.lactis Saccharomyces boulardii – Widely studied probiotic yeast Saccharomyces cerevisiae- Most used probiotic strain for varied applications

5. 5 MECHANISM OF ACTION

6. 6 THERAPEUTIC TARGETS OF PROBIOTICS Gut Function Acute Diarrhea AAD, Travelers diarrhea C. difficile Inf Lactose Indigestion IBS symptoms Gut pain sensation Inflammatory bowel Oral Care Dental caries Colds Respiratory Infections Skin Microbiology, Inflammation Metabolic Syndrome Obesity, Diabetes Allergy Atopic dermatitis Asthma Vaginal Infection

7. S. boulardii Is Effective in Patients with Recurrent C. difficile Disease CDD=Clostridium difficile-associated disease McFarland L, et al. JAMA. 1994;271:1913-1918. Initial CDD CDD recurrence, % S. boulardii (n=31) Placebo (n=33 ) P=NS Recurrent CDD Control (n=34) P=0.04 Patients received standard antibiotics (vancomycin or metronidazole) and S. boulardii 1 g/day or placebo for 4 weeks. CDD recurrence, % S. boulardii (n=26)

8. Mixtures included: Lactinex = L. acidophilus and L. bulgaricus; Lactobacillus acidophilus and Bifidobacterium lactis; Lactobacillus acidophilus and Bifidobacterium infantis. McFarland, Am J Gastroenterol 2006; 101(4): 812-822. PROBIOTICS FOR PREVENTION OF ANTIBIOTIC ASSOCIATED DIARRHEA

9.  Probiotics are live active cultures  More is not better  Dose (1 billion vs 10 billion vs 450 billion)  Number of strains  The effect of probiotics is genus specific MISCONCEPTIONS ABOUT PROBIOTICS

10. DOSAGE & STRAINS OF PROBIOTICS 10 The dose of probiotics is usually expressed as the number of colony forming units (CFUs) The required dose of probiotics may vary greatly for different strains and the specific health effect under investigation Probiotic effects should be considered dose-specific Dose listed on the label must be based on studies that show a health effect in humans Different strains of the same species can be different Clinical support to substantiate claims must be for each probiotic strain

11. PROBIOTICS -QUALITY CONTROL 11 Source (Animal vs Human; Normal vs Diseased) Safety (in at risk populations) Characterization (strain purity) Viability (Cfu Delivered) Dose (Dose-response studies) Combinations/cocktails (Different effects of different Bacterial,yeast strains)

12. AWARENESS OF PROBIOTICS

13. PROBIOTICS IN THE CURRENT MARKET PLACE 13

14. ADVANTAGES OF YEAST PROBIOTIC COMPARE TO BACTERIAL PROBIOTICS 14 Probiotic Characteristics Yeast Probiotic Bacterial Probiotic Unique Advantage Viable at a lower pH to survive gastric digestion YesLimited Resistance to AntibioticsYesNo Reaches colon in an active stateYesLimited Safety Does not lead to permanent intestinal colonization Yes Appropriate for ages 2 months and upYesLimited Toxin neutralization Neutralization of EnterotoxinYesNo Temperature stability Required RefrigerationNoYes

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