Chapter Executive Summarys


Chapter Executive Summaries

Table of Contents

Chapter 1

Chapter 1 introduces (a) the multibillion dollar annual magnitude of the common cold problem, (b) new evidence showing rhinoviruses as the cause of 60 to 70 percent of colds, (c) the immune system's response to viruses as cause of common cold symptoms, (d) the universal failure of existing commercial treatments to reduce common cold duration, (e) the beneficial effects of zinc gluconate lozenges containing 23 mg zinc used every two hours while awake in reducing symptom severity and the average duration of common colds by seven days, (f) applicable scientific and mathematical concepts, and (g) the solution chemistry determination of a 30 percent hydrated Zn2+ ion release from zinc gluconate at physiologic pH 7.4.
Chapter 1 References

Chapter 2

Chapter 2 describes in vitro beneficial effects of Zn2+ ions in (a) virology, with special attention to rhinoviruses, (b) bacteriology, (c) astringency, and Zn2+ ion's beneficial effects in stabilizing and protecting secretory cell membranes, (d) prevention of release of histamine, perforin, other common cold biochemicals, mucus, and serous fluids, (e) stimulation of primary T-cell lymphocyte immunity, (f) induction of interferon release from T-cell lymphocytes, and (g) reduction of inflammation in nasal tissues. In each case, the beneficial effects of Zn2+ ions from zinc lozenges are at nontoxic concentrations achievable in human throat and nasal tissues.
Chapter 2 References

Chapter 3

Chapter 3 discusses the rationale for application of hydrated Zn2+ ions to the oral cavity, rather than the nose. The biologically closed electric circuit (BCEC) between the interior of the mouth and the interior of the nose is described. The mouth-nose BCEC transports Zn2+ ions one-way only; from the mouth into virally infected tissues of the nose, and explains why zinc applied directly to nasal tissues is ineffective. Once within infected nasal tissues, Zn2+ ions produce beneficial effects that shorten common colds.

The zinc ion availability (ZIA) concept is introduced. ZIA is crucial to understanding the variations in results reported in the clinical trials described in Chapter 4. Zinc lozenge efficacy depends totally upon lozenge ZIA, which in turn depends upon the concentration of hydrated Zn2+ ions in saliva over the time of lozenge dissolution and treatments per day. The ZIA concept is an application of Fick's laws of permeability as they are extended to include flow of charged particles in bioelectric fields.
Chapter 3 References

Chapter 4

Chapter 4 describes three possible effects of zinc lozenges upon common colds. Lozenges containing very weak complexes of zinc release positively charged zinc (hydrated Zn2+ ions) at pH 7.4, resulting in positive ZIA values. As the concentration of Zn2+ ions and the time over which they are applied are increased, duration of colds and severity of cold symptoms are proportionately reduced. Use of lozenges having a ZIA value of 25 reduced the average duration of colds by 1.6 days. Use of lozenges having a ZIA value of 44 reduced the mean clinical score and average duration and nasal secretion weights of colds by 4.8 days. Use of lozenges having a ZIA value of 100 reduced the duration and severity of common colds by 7 days.

Lozenges containing strongly complexed zinc release neutrally charged zinc complexes (ZnL0) at pH 7.4, resulting in a ZIA value of zero. Lozenges having zero ZIA values have no effect upon either symptom severity or duration of common colds.

Lozenges containing strongly complexed zinc with strong ligands in molar excess release negatively charged zinc complexes (ZnLN-) at pH 7.4, resulting in negative ZIA values. Lozenges having negative ZIA values increase both the severity and duration of common colds.

Divergence in results between clinical trials of the eight distinctly different proprietary zinc lozenges reviewed is completely reconciled when zinc ion availability (ZIA) values are considered.

Negative ZIA values are possible only because zinc ions are released by the human immune system in its natural fight against common colds, and lozenges releasing negatively charged zinc species at physiologic pH such as zinc and 30% extramolar citric acid neutralize them.

This strongly suggests that zinc ions from ZIA positive lozenges amplify nature's means of terminating common colds, and consequently they are the natural cure for common colds.
Chapter 4 References

Chapter 5

Chapter 5 presents the central finding of linear relationship between zinc ion availability (ZIA) values and reductions in the duration of common colds. Linearity is an important discovery made possible only from rigorous analyses of the physical and chemical properties of the eight distinctly different proprietary lozenges studied. Critical ZIA factors, ZIA values, and comparative taste tests of lozenges are presented. Data show a relationship between ZIA and efficacy but no relation between ZIA and other factors.
Chapter 5 References

Chapter 6

Chapter 6 describes flavor masking techniques for zinc gluconate lozenges. One method, chelation by strong ligands such as 30% extramolar citric acid, or 10-fold extramolar glycine eliminates Zn2+ ions at physiologic pH and destroys efficacy. Addition of strong chelators to zinc gluconate lozenges was erroneously believed to be necessary by others, because dextrose and all carbohydrates based upon dextrose react with zinc gluconate in solid state reactions resulting in bitterness upon lozenge aging.

Fructose, the isomer of dextrose, does not adversely react with zinc gluconate and is the only suitable sweetener for use in flavor masked zinc gluconate lozenges. Either flavor masked zinc gluconate lozenges, or zinc gluconate lozenges having positive ZIA values are each possible separately, but not together (unless the tablet base is fructose with no other soluble carbohydrates). Zinc gluconate lozenges having a ZIA value greater than 50 are not possible without undesirable increases in zinc content.
Chapter 6 References

Chapter 7

Chapter 7 describes zinc acetate lozenges as the successor to zinc gluconate lozenges. Zinc acetate is an outstanding source of hydrated Zn2+ ions, as 100 percent of zinc in zinc acetate solutions is available as Zn2+ ion at physiologic pH 7.4. Zinc acetate lozenges are pleasant tasting, and flavor stable for years. The tablet base can be any carbohydrate sweetener such as fructose, sucrose, dextrose, or other directly compressible, sweet carbohydrate pharmaceutical carriers. None complexes with zinc acetate to cause bitterness in compressed tablets.

Zinc acetate lozenges having ZIA values of up to 280 using 25 mg of zinc can be readily manufactured. Zinc acetate lozenges having a ZIA value of 100 when used 9 times per day can shorten the duration of rhinovirus common colds by an average of 7 days. Lozenges can have any flavor, although preference is given to peppermint. Pharmaceutical characteristics of standard and advanced design lozenges, including Zn2+ ion salivary concentrations, ZIA values by dosage strength, ZIA values and dissolution rates by compressive forces applied, and lozenge taste test results are shown.
Chapter 7 References

Chapter 8

Chapter 8 discusses fundamentals of the biochemistry of zinc. Zinc is an essential element in all cells of every species. Zinc deficiency impairs growth, and proper function of the immune system. Zinc is required in DNA and in its synthesis, and is vital to the function of zinc fingers in transcription factors, or gene-regulating proteins. Life could not have started billions of years ago without the unique ability of zinc to function as a nonenzymatic polymerase, suggesting a riddle with a Zn2+ twist -- which came first, the chicken or the egg? A role for zinc in the management of HIV and AIDS is discussed. Zinc, zinc gluconate, and zinc acetate are Generally Recognized as Safe (GRAS) substances. No evidence of toxicity of short term administration of therapeutic dosages of zinc has been found.
Chapter 8 References

Chapter 9

Chapter 9 draws conclusions and makes recommendations. Hydrated Zn2+ ions have potent antirhinoviral effects, powerful cell membrane protective actions, instantaneous cell pore-closing abilities, strong interferon-inducing properties, outstanding drying effects on secretory cells in nasal tissues, and effective anti-inflammatory action. Zn2+ ions have been shown highly useful in shortening the duration of common colds when used in specific lozenge treatment protocols. A serious difference of opinion concerning efficacy of zinc lozenges tested from 1984 through 1992 existed.

The unifying ZIA method of analysis presented in this handbook provides complete reconciliation. All eight clinical zinc lozenge for common cold studies reviewed are equally valid, but each study portrays only a small facet of the over-all picture. Each of the studies represented responses from lozenges having greatly different ZIA values, as a result of greatly differing chemical compositions. Seven day reductions in average duration of common colds is possible and highly likely using lozenges with a ZIA 100 value.

Recommendations for research on zinc acetate lozenge formulations, placebo matching, and common cold treatment protocols are also given. Methods found helpful to improve clinical results are given.

Related uses for zinc acetate lozenges in allergy and mononucleosis, possible side effects, and contraindications are discussed.
Chapter 9 References

How "Handbook for Curing the Common Cold - The Zinc Lozenge Story" was conceived

The medical symbol.

Journal of Pharmacy Technology peer reviewed article, "Linearity in Dose-Response from Zinc Lozenges in Treatment of Common Colds"

Annals of Pharmacotheraphy invited opinion, "Zinc Lozenges as Cure for Common ColdsColds"

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