Anti-cavity toothpaste Design

1. Anti-cavity toothpaste Design By Michele Johnson, Bonnie Grider

2. Anti-Cavity Toothpaste

3. Anti-Cavity Toothpaste

4. Background on Cavities • Also known as Dental Caries • Most prevalent and costly infectious disease in the U.S. • $78 billion spent on dental services/year in U.S. • Occur when tooth enamel and the underlying tooth decay • Cause - mainly Streptococcus mutans • Prevention – Inhibition of S. mutansalong with regular cleaning of teeth

5. Mouth Chemistry • Natural cycle of tooth remineralization/demineralization • Saliva is a buffer and, among many other compunds, contains fluoride and calcium, which promote remineralization • Oral bacteria use food carbohydrates to produce polysaccharides, building blocks of plaque • Biofilm formation leads to anaerobic fermentation, acid build-up • Switches cycle toward demineralization (pH < 5.5)

6. Anti-Cavity Toothpaste

7. Novel Active Ingredient • Red Wine Pomace Phenolic Extract • Grape pomace – waste byproduct of winemaking, mostly skins and seeds • Rich in polyphenols, currently under research for various health benefits • Polyphenols extracted through solvent-solid leaching, purification, and evaporation • Abundance of raw material: 3.239 million tons in California grapes • No adverse effects from high dietary intake Catechin

8. Extract activity against S. mutans • Inhibits virulence factors of S. mutans • Prevents synthesis of extracellular polysaccharides • Lowers activity of glucosyltransferases (GTFs), enzymes which transfer glucose into glucans • Lowers bacteria’s ability to produce and tolerate acids • Lowers activity of F-ATPase, which protects S. mutans against environmental acid stress • Shows no antibacterial activity • Would be a precise and selective preventative strategy for dental caries • No risk of disrupting the other oral flora and, even more important, of consumer allergic reactions and bacterial resistance

9. In Vitro Studies with Extract • % GTF B activity shows the activity of the enzyme to produce glucans in comparison to the control • Cultures of S. mutans exposed to varying concentrations of polyphenolic extract • Thimothe et al., J. Agr. Food Chem. 2007, 55, 10200-10207.

10. In Vivo Studies with Extract • Study on Sprague-Dawley rats using different polyphenol: apigenin • Quantified both GTF B % activity as well as dental caries • Koo H et al. Oral Microbiol Immunol 2002: 17: 337-343.

11. In Vivo Studies with Extract %C – percent less dental caries mFP – mass of Pinot Noir fruit pomace

12. Anti-Cavity Toothpaste

13. Objective • To use red wine pomace extract to create a toothpaste to prevent cavities by preventing S. mutans virulence • Through Consumer Modeling

14. Consumer Modeling for Product Design • Use consumer survey to find a product formulation with the highest consumer preference • Maximize preference by maximizing preference of each property weight • yi – preference for property i • wi - property weight of i • S - preference

15. Consumer Modeling: Survey • Ranked importance of key characteristics on 1-100 scale • Effectiveness Sweetness • Thickness Foaminess • Cooling Effect Creaminess • Abrasiveness • Chose preferred variation of each key characteristic • Degree of Sweetness (i.e. like candy, chewing gum, little sweet) • Identified the importance of effectiveness based upon number of cavities that could be prevented

16. Consumer Modeling: Survey

17. Consumer & Business Modeling • Designing the product • Connect consumer preference to consumer related property (effectiveness, toxicity, etc). • Correlate the consumer related property with known engineering/scientific properties (viscosity, PH, etc) • Correlate engineering/scientific properties with proportion of ingredients. • Maximize consumer preference by varying the composition. • Optimize the economics by targeting different consumer satisfaction levels.

18. Effectiveness: Active Ingredient • Average American has 1 cavity every 4 years • Or 11.6 cavities, total • Have surveyors rank “happiness” for: • A. Never having another cavity • B. Having a cavity (on average) once every 20 years • C. Having a cavity (on average) once every 10 years • D. Having a cavity (on average) once every 6 years

19. Effectiveness of Active Ingredient

20. Effectiveness

21. Sweetness • Related Ingredients: Sorbitol, Sodium Saccharine, Xylitol • Sweetness α Equivalent Sucrose

22. Sweetness

23. Cooling Effect • The cooling effect in the mouth during is due to menthol in mint oils used as flavoring as well as lower temperature due to negative heat of solution. • Cooling effect caused by both menthol and cold is mediated by Ca+ ion channels • The greater the Ca+ current, the greater the sensation

24. Cooling Effect David D. McKemy et al., NATURE, Volume 416, March 2002

25. Cooling Effect David D. McKemy et al., NATURE, Volume 416, March 2002

26. Cooling Effect

27. Thickness • Consumer assessment of thickness is the consumer assessment of “viscous” • (assessments of “viscous”) α to force applied • A is constant and • But • Then assessments of “viscous” α • Thickness αF α (Viscosity)1/2 F= force upon substance µ= viscosity of substance ν= velocity of substance h = layer height

28. Thickness • Dispersion: solids (abrasives) in liquid continuous phase (mainly water) • Empirical formula from E. Barnea and J. Mizrahi: • Works best for fluids with low Reynolds numbers (our case)

29. Thickness

30. Abrasion • Abrasion α Relative Dentin Abrasion (RDA) • Used in dental care to quantify abrasion of toothpaste • Set relative to a standard abrasive, usually calcium carbonate • Usual toothpaste values should be between 60 and 150

31. Abrasion

32. Foaminess

33. Foaminess • Difficult to predict, based on many factors • Mainly amount surfactant

34. Creaminess • Creaminess in toothpaste is related to the smoothness (abrasion) and the thickness • Determined by surveying consumers and having them arbitrarily assign a value for “thickness”, “smoothness”, and “creaminess” to a standard and the experimental semisolids and liquids • COF = coefficient of friction • µ = viscosity of mixture Kokini, JL, and E L Cussler, Journal of Food Science, 48 (1983), 1221-1225.

35. Creaminess COF = coefficient of friction of toothpaste Φ = percentage solids in toothpaste Lewis, R and R S Dwyer-Joyce. Proc. IMechE Vol. 220 Part J: J. Engineering Tribology. 2006

36. Creaminess

37. Optimal Product

38. Consumer Satisfaction

39. Anti-Cavity Toothpaste

40. ADA Seal of Approval • The ADA Seal of Acceptance is a registered certification mark. • Products Considered for Approval • Evaluation • Submitted upon request of manufacturer or distributor. • ADA Criteria • Safety • Composition, Nature, and Function • Labeling (Name) • Package Inserts (preferably biodegradable and recyclable) • Advertising Standards

41. Toothpaste Manufacturing Process The following steps are the mixing procedure according to the Personal Care formulation section of the Rheology Modifiers Handbook (Braun and Rosen 2000): • Slowly add the deionized water and the sorbitol aqueous solution (70%) until uniform. • Mix this solution with the xanthan gum. Mix until the gum is completely dissolved in the solution. • Add the calcium carbonate and hydrated silica to the solution until it is uniform. • Add the flavoring, xylitol to the mixture until it is uniform and follow by the addition of the active ingredient, polyphenolic extract. Mix until it is uniform. • Add the sweetener, sodium saccharin (10%) aqueous solution until it is uniform in the mixture. • Add the preservative, sodium benzoate and the pH adjuster, trisodium phosphate until it is uniform. • Add the titanium dioxide until it is uniform in the mixture and then add sodium lauryl sulfate (30%) aqueous solution to the mixture until it is completely incorporated into the toothpaste mixture.

42. Contra Rotating Mixer • Contra Rotating Mixer • Ideal for viscous product • Stainless Steel material • Two Different Shafts • Solid shaft paddle blades rotate clockwise • Hollow shaft with anchor scrapper blades rotate counter-clockwise • Homogenous mixing achieved from contra rotary motion of two different blades and high speed homogenizer • Jacked mixer for heating during mixing • Mixing products under vacuum • In built homogenizer allows for emulsification

43. Anti-Cavity Toothpaste

44. Extraction Process – $10.1 Million Equipment Piping, Installation, etc. Indirect Costs Toothpaste Manufacturing – No investment cost Utilize an existing process line at the existing toothpaste production facility. Economics: Investment

45. Total Capital Investment

46. Extraction Process • Modeled after extraction used in research paper • Could be optimized for bulk extraction Homogenizer Freeze Dryer Decanter Centrifuge Evaporators PBA Chromatography Column Delivery Truck

47. Extraction Equipment Cost

48. Extraction Piping Network

49. Piping Network Summary • Network Cost --$185,000 • Pipe Composition– Stainless Steel • Number of Streams –17 streams • Piping Length –72.92 feet • Maximum Flow rate – 28.4 ft3/hr (3.54 gpm)

50. Economics: Total Annual Product Cost