Research

The research behind Ion Biotechnology is a family of therapeutic applications using ions including ionic metals. These ionic technologies are researched to promote the IAF Mission.

Oxidative Stress

research of free radicalsIn all living organisms, including humans, takes place a delicate equilibrium between the production and the elimination – by antioxidant defense system – of the so-called “free radicals”. The breaking of this balance, frequently named “oxidative stress”, may induce cellular damage with differencing degrees of severity, leading ultimately, over time, to early aging and to many diseases.

IAF has created a topical product using Ion Biotechnology to reduce oxidative stress. The reduction of oxidative stress by definition is “prevention”.

Research across the globe has determined that oxidative stress is the precursor for many diseases.

Oxidative stress is a pathological condition triggered by the damaging action on the cells and tissues of the body, caused by abnormally increased amounts of free radicals. Free radicals are single or grouped atoms having at least one external orbital “occupied” by one single electron “unpaired” instead of a couple of electrons “lone pair”.

The first use of IAF funding will be used towards proof of concept through an independent clinical trial on humans. A third-party study design will measure the current levels of oxidative stress in the study subject’s blood. The Carratelli’s pannel for oxidative stress assessment uses reactive oxygen metabolites (d-ROMs test) and the plasma antioxidant barrier (BAP test). This test will be taken before the application of the product and after different timeliness and amounts of application to determine the reduced levels of oxidative stress.

Oxygen Free Radicals - Research

A Ligand Bond of Cationic Minerals and Ionic Salts

A short explanation of a very technical formula having multiple modes of action. We use a unique delivery system that moves cations, such as Zinc, Copper, Magnesium, Amine, Sulfur, and Hydrogen through the epidermal layers across semi-permeable membranes very quickly to immediately be absorbed by diseased or healthy tissues at very low concentrations.

The Krebs cycle is a charting of the metabolic pathways that healthy plant or animal cells must follow to perform all functions supporting life. There are approximately thirty-two (32) steps in the process. The steps allow healthy cells to expel excessive amounts of toxic materials continuously, including minerals and other nutrients unless totally overwhelmed.

Diseased and/or mutated cells (such as cancer cells) do not follow the Krebs cycle. Rather they follow an alternative anaerobic metabolic pathway with only about eighteen (18) steps and absorb all foods (particularly sugars). The diseased cells will also take up excessive amounts of minerals such as Zinc and Copper (in our formulation) in amounts that are toxic to them, causing the diseased cells to die. The surrounding healthy tissues (following the Krebs cycle’s 32 steps) take up only the amounts of cations needed to function and excrete the excess nutrients.

Following the Krebs 32 steps versus the 18 steps that most anaerobic cells and other diseases follow saves normal healthy tissue while killing the diseased cells. Additional ions can be added to the ligand system such as the Magnesium cation which provides ATP (energy) to regulate cellular metabolism, pain relief, and detox benefits towards normal mitochondrial production.

In summary, we are able to transport our highly available cations to our target diseased cells (including cancer cells) and kill ONLY the diseased and/or mutated cells, leaving the healthy normal cells surrounding them functioning without disruption. Further, a sheath of bacterial cells (also non-Krebs cycle) or biofilm often surrounds a mass of mutated cells. The highly bio-available cations will penetrate and kill the bacterial cells in this shield. The mass of mutated cells are then exposed to the immune system, destroyed, and removed.

We have developed several theories towards the formulas “Modes of Actions” which require additional study. Several scientifically validated and many already published on specific components of the formula.

  • MoA 1 – A nontoxic nutrient uptake to the aerobic cell and a toxic overload to the anaerobic cell.
  • MoA 2 – Redox potential at a minimum of 450 Mv. reducing radical electrons and oxidation (inflammation)
  • MoA 3 – Antioxidant ORAC value of 1026 microM TE (oxygen radical absorbance capacity)
  • MoA 4 – Highly systemic pH of under 1 having ionic polarity movement in living species.
  • MoA 5 – Topical permeability dispersed through interstitial fluids and absorbed at the cellular level.
  • MoA 6 – Precursor to the production of the enzymatic version of Zn +2 Cu +2 Superoxide Dismutase.
  • MoA 7 – Increases the metabolic pathway of apoptosis and normal cell signaling.
  • MoA 8 – Mimicking reactive oxygen species, reactive nitrogen species, and reactive sulfur species.

○ The Reactive Species Interactome – Evolutionary Emergence, Biological Significance, and Opportunities for Redox Metabolomics and Personalized Medicine

Clinical studies and lab research on MoA’s, ionic combinations, and formulations to combat disease.

Human Diseases

  • Oncology
  • Autoimmune Diseases
  • Lyme Disease
  • Infection
  • Rebox Biology

Animals Diseases

  • Oncology
  • Infection
  • Swine Flu Virus
  • Rebox Biology

Current Studies

Human Clinical Studies

Clinical Phase 1 Human Safety Study

  • Ion Gel ZCM25 as a topical drug candidate.
  • This project is being funded by the Mexican Federation.
  • 2019 Study Design and Ethics Review Completed.
  • The project is in progress and submitted for regulatory approval.

Clinical Phase 2 Human Efficacy Study

  • Ion Gel ZCM25 as a topical drug candidate.
  • This project is being funded by the Mexican Federation.
  • 2019 Study Design and Ethics Review Completed.
  • The project is in progress and submitted for regulatory approval.
  • Clinical topical application to increase wound healing and infection prevention post-surgical procedures.

Completed Studies

Preclinical Antimicrobial Efficacy Studies

Ion Gel ZCM-25 In-vitro Antimicrobial Efficacy Study

  • Completed in 2019 by FDA Certified ARJ Labs, Mexico
  • Ion Gel ZCM-25 had a 100% kill rate in 30 seconds on these human pathogens:
    • Aerobic Mesophilic
    • Fungi and Yeasts
    • Staphylococcus Aureus
    • Pseudomonas Aeruginosa

ION-ZCM1 Redox Potential Assay

  • Completed in 2018 by Exova, USA
  • Oxidation-Reduction Potential was measured at 453.2 mV using method SM2580B

ION-ZC1 Redox Potential Assay

  • Completed in 2018 by Exova, USA
  • Oxidation-Reduction Potential was measured at 532.1 mV using method SM2580B

Ion-ZCM1 Oxygen Radical Absorbance Capacity ORAC Activity Assay

  • Completed in 2018 by the University of Debrecen, Hungary
  • ION-ZCM1 has a TOTAL ORAC = H-ORAC value of 1138 μM TE /100 g
  • Total ORAC value for ION-ZCM1 is 1025 μM TE/ml when measured at a dilution of 12.5%
  • Total ORAC value for ION-ZCM1 is 740 μM TE/ml when measured at a dilution of 6.25%
  • Total ORAC value for Vitamin E is 580 to 585 μmol TE/g at 1:1
  • Total ORAC value for Vitamin C is 128 to 133 μmol TE/g at 1:1
  • Total ORAC value for Pepper Leaf Extract is 64.47 μmol TE/g at 1:50 or approx a 2% solution

ION-ZC1 In Vitro Antimicrobial Study On 12 Hospital Acquired Pathogens Gram-Negative And Gram-Positive Bacterias And Fungus

  • Completed in 2016 by the University of Debrecen, Hungary
  • A non-biofilm antimicrobial assays using broth microdilution-based sensitivity method.
  • All fungal and bacterial strains tested with ION-ZC1 concentrations below 2.125 % v/v observed a 50% turbidity within the 24-hour testing period.

ION-ZC1 In Vitro Antimicrobial Study On MRSA

  • Completed in 2017 by the University of Debrecen, Hungary
  • A non-biofilm antimicrobial assays using broth microdilution-based sensitivity method.
  • The results showed that MIC values for ION-ZC1 against the 10-methicillin-resistant Staphylococcus aureus isolate tested were in the range of 0.212 – 0.85% (v/v).
  • The Control for Vancomycin, MIC values were in the range of 4-16 mg/L.

ION-ZC1 In Vitro Antimicrobial Study On Biofilm

  • Completed in 2018 by the University of Debrecen, Hungary
  • An antimicrobial assays using a microtiter dish sensitivity method.
  • Minimum inhibitory concentrations (MICs) were determined after 24 hours at which a prominent decrease of 50% (average) of biofilm mass was observed over 36 isolates.

Preclinical Anticancer Efficacy Studies

Preliminary Evaluation Of ION-ZC1 As A Potential Anticancer Agent In Vitro

  • Completed in 2018 by Brooklyn College and The City University of New York, USA.
  • The ION-ZC1 solution is a responsive cytotoxic agent against:
    • Renal carcinoma cell line Caki-1 (IC50 36.12 ± 1.00 μM),
    • Triple-Negative Breast Cancer (MDA-MB-231),
    • and Melanoma cancer cell line A375 (IC50 95.20 ± 1.01 μM)
  • Highly selective when compared to the cytotoxicity of ION-ZC1 on control cells IMR-90 (IC50 142.6 ± 6.65 μM).
  • The ION-ZC1 solution induces apoptotic death in 92% of renal carcinoma cell line Caki-1 at dose IC50 36.12 ± 1.00 μM.

ION-ZC1 Topical Cream Anti-Tumor Efficacy Study Using A Syngeneic Mouse Melanoma Model (B16F0 – C57BL/6J), Study Design Of 30 Mice.

  • Completed in 2017 by the University of Debrecen, Hungary.
  • The main conclusion drawn from the study is that ION-ZC1 Topical Cream (17%) is:
    • Significantly efficacious against metastatic mouse melanoma as tested in a subcutaneous syngeneic mouse model (B16-F0 in C57BL/6J mice).
    • More efficacious than the Imiquimod Topical Cream (5%).
    • Tumor volumes recorded over the treatment period in the three groups support that tumor growth was slower as inhibited by ION-ZC1 Topical Cream (17%), and its effect was more pronounced as compared to the inhibitory effect of ALDARA (5% Imiquimod) Positive Control substance on tumor growth.
  • Conclusively, ION-ZC1 Topical Cream (17%) treatment extended survival time.

ION-ZC1 Anti-Tumor Efficacy Study By Intravenous Injection (Parenteral) Route, Using A Syngeneic Mouse Xenograft Model, More Specifically A Subcutaneous B16 Mouse Melanoma Model In C57BL/6J, Study Design Of 30 Mice.

  • Completed in 2016 by the University of Debrecen, Hungary.
  • Safety abnormalities compared to control tumor mice were not noted for any of the animals when necropsied at the conclusion of the 14-day observation period. As the most important results from the histopathological analysis, we can state that:
    • Tumors isolated from mice treated with various concentrations of ION-ZC1 IV injections show massive necrosis, which is not pronounced as much in tumors isolated from control tumor mice;
    • Blood vessels are much less frequent, less developed in the ION-ZC1 treated mice compared to control tumor mice.
    • ION-ZC1 injection results in spleen enlargement, which is remarkably (2-3 times) bigger in extent than that of the spleen of control (untreated) tumor mice, and consistent with ION-ZC1 inducing a strong anti-tumor immune response.

Preclinical Safety Studies

Ion Gel ZCM-25 – Dermo Absorbancy Test Rabbits – Chronic Dose 14 Day.

  • In Progress 2020 by UNAM – Preclinical Unit – Mexico.
  • Blood evaluation of dermo absorption in 3 groups with control.

Ion Gel ZCM-25 Skin Irritability Test Rabbits – Chronic Dose 14 Day

  • Completed in 2019 by UNAM – Preclinical Unit – Mexico.
  • No Irritability on the test animals at human dosing levels.

Ion Gel ZCM-25 Skin Irritability Test Rabbits – Single Dose

  • Completed in 2018 by CIATEJ – Medical and Pharmaceutical Biotechnology Unit, Mexico.
  • No irritability on test animal at 5 times human dosing level.

ION-ZCM1 – Cell-Based In Vitro Toxicity Study

  • Completed in 2018 by the University of Debrecen, Hungary.
  • By a HACAT cell line based MTT Cytotoxicity test method established a safety profile for topical use at 25% concentration.

ION-ZC1 – Acute Intravenous Toxicity In Mice

  • Completed in 2015 by the University of Debrecen, Hungary.
  • Test methods established a safety profile of Intravenously administered ION-ZC1 which is non-toxic at the dose of 667 mg/kg body weight on mice.

ION-ZC1 – Topical Skin Irritation On Humans

  • Completed in 2014 by Cencon Labs, Mexico.
  • No irritation detected on 10 human applications of a cream-based formula at 10% concentration of ION-ZC1.

ION-ZC1 – 6 Pack Safety Study – Biosimilar Product Safety Study At 100% Concentration.

  • Completed in 2014 by Product Safety Labs, USA.
  • Minor irritability in the eye irritation study, No irritability in other studies:
    • Acute Dermal Toxicity in Rats
    • Primary Skin Irritation in Rabbits
    • Dermal Sensitization Test in Guinea Pigs – Buehler Method Study
    • Acute Inhalation Toxicity in Rats
    • Primary Eye Irritation in Rabbits
    • Acute Oral Toxicity – Up and Down Procedure in Rats