Research & Development

Formulations containing Hydroxytyrosol from Olive Extract carried in Italian Organic Extra Virgin Olive Oil.

P&P Farma collaborates with top-tier partners in Research and Development to perfect advanced Hydroxytyrosol-based formulations.

The olive extract, delivered in Italian Organic Extra Virgin Olive Oil, is at the heart of a supply chain dedicated to quality control and the clinical validation of the FENOLIA® line.

Clinical Overview: Capsules and Topicals

Health Effects of Hydroxytyrosol from FENÒLIA® Capsules

Hydroxytyrosol (HT) is administered in 15 mg/day doses, delivered in organic extra virgin olive oil within gastro-resistant capsules to optimize intestinal absorption.

Reductions

(Risk Factors)

  • Triglycerides: -9%.
  • Cholesterol Indices: Total cholesterol/HDL (3.5%) and triglycerides/HDL (11.7%).
  • Body Composition: Significant reduction in body fat percentage (p=0,01).
  • Lipid Peroxidation: Improvement in biomarkers such as MDA and nitrites/nitrates.

Improvements

(Endogenous Defense)

  • Antioxidant Enzymes: SOD1 increased by 3.7 times.
  • Total Antioxidant Status (TAS): General improvement in the body's antioxidant capacity.
  • Cellular Protection: Increased Thiol groups for enhanced cell defense.
Liver Health and Systemic Inflammation (NAFLD)

A study involving 80 children with fatty liver (treated with 7.5 mg/day for 4 months) demonstrated:

  • Reduction in steatosis, triglycerides, and transaminases (AST/ALT).
  • Reduction in fibrosis markers (PIIINP) and NADPH oxidase (NOX2) activation.
  • Reduction in pro-inflammatory cytokines (IL-6, IL-1β, TNF-α)
  • Significant increase in Interleukin-10 (IL-10).
  • Improvement in insulin sensitivity (HOMA-IR index).
  • DNA damage recovery and reduction of 8-OHdG

Dermal Repair and Protection: FENÒLIA® Creams

Topical action works on the epidermis and dermis to facilitate skin repair:

  • Erythema: Reduction up to 28% and decrease in acute toxicity from radiotherapy (radiodermatitis).
  • Environmental Damage: Reduction of DNA damage induced by UV rays and cellular senescence.
  • Pathogens: Viral inactivation and reduction of bacterial biofilm.
  • Regeneration: Acceleration of re-epithelialization and angiogenesis.
  • Cellular Proliferation: Increased keratinocyte proliferation.
  • Skin Barrier: Deep hydration and restoration of the skin barrier.

Clinical Synthesis Matrix: Hydroxytyrosol

Capsules

Reductions

  • Lipids & Weight: Triglycerides, LDL Cholesterol, Body Fat, and Body Weight.
  • Inflammation: Systemic Inflammation (IL-6, IL-1β).
  • Liver: Steatosis and Hepatic Fibrosis (PIIINP).

Improvements

  • Antioxidants: Antioxidant Enzymes (SOD1, TAS).
  • Immunomodulation: Anti-inflammatory Response (IL-10).
  • Repair: DNA Repair and Insulin Sensitivity.

Creams

Reductions

  • Clinical Therapy: Radiodermatitis from radiotherapy (-28%).
  • Environmental Damage: Oxidative damage from UV and cellular senescence (beta-galactosidase).
  • Pathogens: Bacterial and viral load

Improvements

  • Regeneration: Wound re-epithelialization and angiogenesis (new vessels).
  • Skin Barrier: Deep hydration and keratinocyte proliferation.

Scientific Validation

Direct links to conducted clinical studies.

  1. “Antioxidant Effects of a Hydroxytyrosol-Based Pharmaceutical Formulation on Body Composition, Metabolic State, and Gene Expression: A Randomized Double-Blinded, Placebo-Controlled Crossover Trial”, pubblicato 09-Ago-17 su Hindawi Oxidative Medicine and Cellular Longevity.
  2. “A hydroxytyrosol-based pharmaceutical formulation for the prevention of cardiovascular disease: a randomized controlled crossover trial”, pubblicato 2017 pubblicato su Biomedicine & Preventions.
  3. “The Antioxidant Effects of Hydroxytyrosol and Vitamin E on Pediatric Nonalcoholic Fatty Liver Disease, in a Clinical Trial: A New Treatment ?”, pubblicato 11-Feb-19 su Antioxidants & Redox Signaling e Comunicato Stampa dell’Ospedale Pediatrico Bambino Gesù di Roma del 07-Gen-19.
  4. “Antioxidant activity of Hydroxytyrosol and Vitamin E reduces systemic inflammation in children with paediatric NAFLD”, pubblicato 13-Ott-20 su Digestive and Liver Disease.
  5. “Hydroxytyrosol Recovers SARS-CoV-2-PLpro-Dependent Impairment of Interferon Related Genes in Polarized Human Airway, Intestinal and Liver Epithelial Cells”, pubblicato 27-Lug-22 su Antioxidants.
  6. “Combination Treatment with Hydroxytyrosol and-Vitamin E Improves NAFLD-Related-Fibrosis”, pubblicato 14-Set-22 su Nutrients.
  7. “The Pharmaceutical Formulation Plays a Pivotal Role in Hydroxytyrosol-Pharmacokinetics”, pubblicato 23-Feb-23 su Pharmaceutics.
  8. “Lifestyle Intervention Improves Metabolic Dysfunction-Associated Steatotic Liver Disease in Children with Down Syndrome”, pubblicato 16-Lug-25 su Nutrients.
  9. “Safety and efficacy of Hydroxytyrosol-based formulation on skin inflammation: in vitro evaluation on reconstructed human epidermis model”, pubblicato 26-Mag-19 su DARU Journal of Pharmaceutical Sciences.
  10. “Development and Validation of RP-HPLC-DAD Method to Quantify Hydroxytyrosol Content in a Semi-Solid Pharmaceutical Formulation”, 2161-0444-1000298”, pubblicato 07-Ott-2015 su Medicinal Chemistry Journal.
  11. “Nitrogen Headspace Improves the Extra Virgin Olive Oil Shelf-Life, Preserving Its Functional Properties”, pubblicato 22-Ago-19 su Antioxidants.
  12. “Fenòlia Radiodermite Case Report”, riportato Ottobre 2018

Strategic Partners

Formulation R&D and Advanced Capsule Manufacturing

Formulation development, production, and final packaging of FENÒLIA® Enteric Coated Capsules 7.5 carried out at Laboratori Truffini e Reggè , Milan. Enteric coating process on filled capsules developed and implemented at Laboratori Rofarma Italia, Gaggiano (Milan).

Formulation development, production, and final packaging of the FENÒLIA® Cosmetic Line carried out at Reynaldi Srl, Pianezza (Turin)

Quality control for verifying the Hydroxytyrosol assay in formulation ingredients and finished products, conducted at the Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm) of the University of Messina. An analytical method for determining the Hydroxytyrosol assay in semi-solid formulations (FENÒLIA® Eudermic Cream 15 and FENÒLIA® Eutrophic Oil-Cream 25), unavailable at the time of product development, was specifically developed and validated. Methodology published in the Medicinal Chemistry Journal.

In-vivo Pharmacokinetic study of Hydroxytyrosol released after taking FENÒLIA® Enteric Coated Capsules 7.5, conducted at the University of Rome “Tor Vergata” and the University of Messina. Results published in Pharmaceutics.

Clinical Nutritional Genomics Study on FENÒLIA® Enteric Coated Capsules 7.5 conducted at the University of Rome Tor Vergata, Clinical Nutrition and Nutrigenomics Section. Results published in the scientific journals Hindawi Oxidative Medicine and Cellular Longevity and Biomedicine & Preventions

Clinical Study evaluating the combined efficacy and tolerability of Hydroxytyrosol and Vitamin E (via FENÒLIA® Enteric Coated Capsules) in the treatment of children with Non-Alcoholic Steatohepatitis (NASH), conducted at the Bambino Gesù Children’s Hospital in Rome. Results published in the scientific journals Antioxidants & Redox Signaling, Digestive and Liver Disease and Nutrients.

Clinical Study evaluating the effectiveness of an intervention promoting a healthy lifestyle on the severity of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in children with Down Syndrome (DS), using FENÒLIA® Enteric Coated Capsules 7.5, conducted at the Bambino Gesù Children’s Hospital in Rome. Results published in the scientific journal Nutrients.

In-vitro Pharmacological Study on a reconstructed human epidermis model to evaluate the efficacy of FENÒLIA® Eudermic Cream 15 in counteracting Atopic Dermatitis, conducted at the University of Messina. Results published in the scientific journal DARU Journal of Pharmaceutical Sciences.

Patch Test on healthy volunteers to verify the tolerability of FENÒLIA® Eudermic Cream 15 and FENÒLIA® Oil Bath 45, conducted by Chelab S.r.l., a Mérieux NutriSciences Company, a spin-off of the University of Padua.

Photopatch Test on healthy volunteers to verify the photosensitivity of FENÒLIA® Eudermic Cream 15, conducted by ISPE S.r.l., Institute for Skin and Product Evaluation, Milan.

Patch Test on healthy volunteers to verify the tolerability of FENÒLIA® Eutrophic Oil-Cream 25, conducted by Bio Basic Europe S.r.l., Milan.

HET-CAM Test on healthy volunteers to verify the ocular irritancy of FENÒLIA® Oil Shampoo 40, conducted by ISPE S.r.l., Institute for Skin and Product Evaluation, Milan.