Table 6. Examples of citric acid-sodium bicarbonate in effervescent formulations from Mohrle.(39)
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Product Citric Acid (g) Sodium Product Weight (g) Bicarbonate (g) _______________________________________________________________________ antacid 1.180 0.875 3.100 antacid- analgesics 1.060 1.700 3.250 flavored beverage 1.300 0.815 2.230 decongestant 0.650 0.550 1.330 denture cleanser 0.575 0.800 3.354 _______________________________________________________________________ average 0.953 (36%) 0.948 (36%) 2.654 (100%) _______________________________________________________________________
Results of Study
Of 70 treatment courses used by 55 individuals in 34 families, 63 (33 zinc and 30 placebo) could be evaluated, in that they used medication at least four times daily for at least 3 days (average utilization of 6 lozenges daily for 5.4 days). Effervescent lozenges required 10 minutes to dissolve. Placebo blinding was shown adequate by statistical analysis. Whereas 60 percent of the placebo-treated colds lasted 7 days or less, only 42 percent of the zinc-treated colds did so, and 24 percent of the zinc-treated colds versus 13 percent of the placebo-treated colds lasted more than 12 days. One zinc-treated cold lasted 53 days.
Mean number of days of respiratory nasal and cough symptoms were appreciably higher for effervescent tartarate-bicarbonate chelated zinc lozenge treatment compared to placebo treatment. Mean severity point score was higher for nasal and cough symptoms. The observed duration, as opposed to the calculated duration of colds, in the zinc-treated group averaged 12.1 days versus 7.7 days in placebo-treated group.(37) No salivary protein precipitate in zinc-laden saliva was noted, suggesting Zn2+ ions were absent. The amount of zinc-laden saliva generated was high at 44 ml per lozenge.
The pH of tartaric acid in distilled water at the above concentration was 2.0. Zinc acetate totally dissociates in solution releasing 100 percent Zn2+ ion.(40) Tartaric acid was present in considerable excess, and it has a first stability constant for zinc of log K1 = 2.2.(41) Negatively charged zinc tartarate complexes are relatively stable, and few solution Zn2+ ions are available at physiologic pH 7.4.
Zinc acetate vigorously reacts with sodium bicarbonate, producing insoluble zinc carbonate precipitate, eliminating all Zn2+ ions, and leaving neutral and negatively charged zinc species.
The ZIA value for tartarate and carbonate complexed zinc acetate lozenges is estimated to be negative 55 from linear ZIA relationships found in the Figure 19 equation to project the value from the 4.4 day increase in duration, and because negative zinc species are present.
The finding of sharp increases in duration of colds using zinc complexes with excesses of these ligands is important to common cold research, and perhaps virology in general, and needs careful consideration and explanation.
Figure 15. Letter from R. J. E. Williams showing procedure and method for producing effervescence in zinc acetate lozenges.
A suggestion that zinc chelators in lozenges bound endogenous zinc from oral and nasal tissues worsening common colds does not appear to be supported, as a similar lengthening by the placebos did not occur. However, negatively charged zinc species would bind endogenous zinc worsening colds in a linear dose-response manner.
Figure 14. Estimated effect of ZIA -55 zinc acetate-tartarate- carbonate lozenges and placebo.
Zinc Ion Availability
