Scientific Evidence

Background/Objectives: Irritable Bowel Syndrome (IBS) is a widely prevalent chronic disorder of brain–gut interaction which represents a clinical challenge due to its complex underlying causes and the lack of a standardized treatment approach. This cross-sectional research collected real-world data (RWD) on the effectiveness, safety, and usage pattern of a natural substance-based medical device, Colilen IBS, indicated for the treatment of IBS. Methods: Surveys were conducted both in Italy and Germany with 6101 participants, including 4425 patients, 1014 pharmacists, and 662 physicians using a structured GxP web platform that allows voluntary participants to share their experiences with the device. The validated platform was designed to comply with post-market surveillance requirements of EU Regulation 2017/745. Statistical analyses included descriptive evaluations of responses to gauge overall effectiveness and safety of the device. Results: The effectiveness reported with the medical device was judged extreme or great by 79.2% of patients, with 89.2% of whom observed symptom improvement within one month. Both safety and tolerability were rated extreme or great by 90.7% of patients. Healthcare professionals reported a similar rate on the overall effectiveness, with 94.9% of pharmacists and 95.9% of physicians indicating it extreme or great. Similarly, the safety profile was corroborated by nearly all pharmacists (97.0%) and physicians (98.2%) reporting extreme or great satisfaction with both safety and tolerability of the medical device. Conclusions: This research provides RWD supporting the effectiveness and safety of the product for treating IBS. The strong coherence among patients, pharmacists, and physicians in positively rating the device’s performance suggests that this medical device represents a therapeutic option that effectively addresses patient needs while minimizing safety concerns. Continuous RWD collection is essential, as it offers insights into real-world practice and ensures ongoing confirmation of the product’s safety and effectiveness. Ultimately, this will advance IBS patient care by integrating real-world evidence into clinical management.

Background: Hemorrhoidal disease (HD) is a common anorectal condition characterized by symptoms such as bleeding, pain, discomfort and itching. While often underdiagnosed due to patient reluctance to seek care, HD significantly impacts quality of life (QoL). Conservative treatments are preferred for low-grade HD, with increasing interest in natural substance-based therapies. Materials and Methods: A large-scale survey was conducted using a digital platform to collect real-world data (RWD) from patients, pharmacists and physicians. The research assessed perceived effectiveness, safety, tolerability, quality of life (QoL) and usage patterns of NeoFitoroid BioOintment. Quantitative analysis was also performed using a global score (GS) based on Likert scale ratings and their distribution. Results: A total of 2618 participants were included. A strong concordance across the three participating cohorts in the answers provided for all items of the questionnaire was observed. The descriptive analysis revealed high grades of effectiveness, safety and tolerability. Indeed, over 90% of respondents rated the product as “good” or “excellent” in terms of effectiveness and safety. Conclusions: These findings underscore the treatment’s effectiveness, safety, tolerability and positive influence on QoL in HD patients.

When the protective mechanisms of the gastroesophageal mucosa are overwhelmed by injurious factors, the structural and functional mucosal integrity is compromised, resulting in a wide spectrum of disorders. Poliprotect has recently been shown to be non-inferior to standard-dose omeprazole for the treatment of endoscopy-negative patients with heartburn and/or epigastric pain or burning. Here, we provide preclinical data describing the mechanism of action of the Poliprotect formulation, a 100% natural, biodegradable, and environmental friendly medical device according to EU 2017/745 and containing UVCB (unknown or variable composition, complex-reaction products, or biological materials) substances of botanical and mineral origin, according to the REACH and European Chemical Agency definitions. Different in vitro assays demonstrated the capability of Poliprotect to adhere to mucus-secreting gastric cells and concomitantly deliver a local barrier with buffering and antioxidant activity. In studies conducted in accordance with systems biology principles, we evaluated the effects of this barrier on human gastric cells exposed to acidic stress. Biological functions identified via Ingenuity Pathway Analysis highlighted the product’s ability to create a microenvironment that supports the mucosal structural and functional integrity, promotes healing, and restores a balanced mucosal inflammatory status. Additionally, transepithelial electrical resistance and an Ussing chamber showed the product’s capability of preserving the integrity of the gastric and esophageal epithelial barriers when exposed to an acid solution. Two in vivo models of erosive gastropathy further highlighted its topical protection against ethanol- and drug-induced mucosal injury. Overall, our findings sustain the feasibility of a paradigm shift in therapeutics R&D by depicting a very innovative and desirable mode of interaction with the human body based on the emerging biophysical, rather than the pharmacological properties of these therapeutic agents.

The integrity of esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD) or GERD-like symptoms is the first mechanism of protection to decrease the sensitivity to gastric reflux and heartburn symptoms. We investigated the protective effects of Poliprotect^® (PPRO), a CE-marked medical device, on esophageal epithelial integrity using in vitro and ex vivo models. In vitro, the protective effects of PPRO were tested on Caco-2 cells. PPRO demonstrated safety and protection against oxidative damage induced by hydrogen peroxide. It also preserved epithelial integrity by maintaining transepithelial electrical resistance (TEER) against damage from calcium removal or bile acid exposure (taurodeoxycholic acid, TDCA). Ex vivo, esophageal biopsies from patients subjected to endoscopy were mounted in Ussing chambers and exposed to damaging agents (HCl or HCl + TDCA). Untreated biopsies (control) showed significant loss of epithelial resistance (up to -33%). In contrast, low concentrations of PPRO (50–100 µg/mL) provided strong protection against these damages (p < 0.001), even after 60 min of washing. Histological analysis confirmed the barrier-enhancing effect of PPRO. Overall, PPRO effectively protected the esophageal epithelium from damage in both models, suggesting its potential role in alleviating GERD or GERD-like symptoms by strengthening mucosal barriers and reducing epithelial sensitivity to reflux.

Pharmaceutical products have contributed to improving the expectancy and quality of life of millions of patients and their role in our society is undisputed. However, many active pharmaceutical ingredients have been found in rivers, lakes, seas, drinking water and can cause damage to the environment and ecosystems. Environmental contamination is known to affect biodiversity and health. From a "One Health" perspective, human health is safeguarded by preserving the environment and ecosystems. Italy is at the forefront on the issue of protecting biodiversity, having included it among the fundamental principles of the Constitution. At the same time the European Commission launched the strategy to protect biodiversity by 2030. To map and limit the environmental effect of drugs, it has been proposed the topic of ecopharmacovigilance and eco-directed sustainable prescribing.

It's in this context that this work on the ready biodegradability of a drug-based on loperamide and a medical device made of complex natural matrix, Lenodiar-Pediatric®, was carried out for the first time. The products, indicated to treat diarrhoea, were found to be readily biodegradable. For Lenodiar-Pediatric® the biodegradation isn't surprising, while for the drug-based on loperamide it was due to the degradation of excipients. Indeed, the UHPLC-qToF investigation highlighted that loperamide was present at the end of the test and is therefore potentially persistent in the environment, confirming the most relevant literature.

In conclusion, therapeutic products made of natural complex matrix which efficacy and safety have been proven according to Evidence-Based Standards may play an important role in safeguarding biodiversity.

Diarrhea continues to be a global health problem as acute diarrhea carries the risk of dehydration, while both acute and chronic diarrhea can significantly affect patients’ quality of life and reduce productivity. The innovative medical device Actitan, which consists of a complex of natural molecules, could be an effective option for the treatment of diarrhea from various causes. The aim of this post-market cross-sectional study was to evaluate the perceived efficacy, safety and usage pattern of the two formulations for adults (Actitan-P) and children (Actitan-F) among patients/child caregivers, physicians and pharmacists. Participants completed online questionnaires with closed multiple-choice questions that were rated on a verbal 5-point Likert scale. These surveys were conducted via the online platform Real World Data, which provides digital questionnaires for patients, doctors and pharmacists. Two separate surveys were conducted for the two formulations, with a total of 2630 participants (1488 participants for Actitan-P and 1142 participants for Actitan-F). Overall, the results indicate a high level of efficacy and safety of the product. In the case of Actitan-F, more than 96% of caregivers rated safety as good or excellent, and over 92% rated efficacy as good or excellent. Actitan-P also received positive feedback: nearly 86% of patients reported good/excellent efficacy, and more than 93% rated safety as good or excellent. These positive evaluations were confirmed by physicians and pharmacists, who also did not report adverse effects. In summary, this study confirms the role of Actitan as a safe and effective option for the treatment of diarrhea of different causes and in different patient groups, including young children.

Suspect screening and untargeted analysis using UHPLC-qToF are two advanced analytical approaches now used to achieve an extensive chemical profile of samples, which are then typically confirmed through targeted analysis. These techniques can detect a large number of chemical features simultaneously and are currently being introduced into the study of contaminants of emerging concern (CECs) and into the study of the extent of human chemical exposure (the exposome). Here is described the use of these techniques to characterize chemical mixtures derived from the OECD 301F ready biodegradability test (RBT) of a chemical and natural formulation currently used to treat reflux disease and functional dyspepsia. Untargeted analysis clearly evidenced a different behavior between formulations containing only natural products with respect to that containing synthetic and non-naturally occurring substances. Suspect screening analysis improved the untargeted analysis of the omeprazole-based medicine, leading to the tentative identification of a number of omeprazole-derived transformation products, thereby enabling their preliminary quali-quantitative evaluation. Targeted analysis was then performed to confirm the preliminary data gained from the suspect screening approach. The validation of the analytical method for the quantitative determination of omeprazole and its major metabolite, omeprazole sulphide, has provided robust data to evaluate the behavior of omeprazole during the OECD 301F test. Using advanced analytical approaches, the RBT performed on the two products under investigation confirmed that omeprazole is not readily biodegradable, while the medical device made of natural substances has proven to be readily biodegradable.

INTRODUCTION: In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure.

METHODS: In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed.

RESULTS: A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8–5.0; omeprazole 8.2, 4.8–11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm.

DISCUSSION: Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).

Aim of this Real World (RW) research was to investigate the effectiveness and safety of the vegetal molecular complex ActiMucin in Irritable Bowel Syndrome (IBS) patients with diarrhea predominant (IBS-D), constipation predominant (IBS-C) and mixed (IBS-M) clinical subtypes.

Background: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) are very common in the general population. GERD prevalence is considerably high in pregnant women, and it increases at a young age, alongside obesity. Mucosal protective agents (MPAs) are over-the-counter (OTC) treatments for FD and GERD commonly used alone or as add-on therapy to proton pump inhibitors (PPIs). Real-world data through surveys allow a clinical evaluation of marketed products that also complies with the new regulation on substance-based medical devices (SBMDs).

Aim: The study aimed to evaluate perceived effectiveness, safety, and pattern of usage among patients, physicians, and pharmacists of the natural MPA Poliprotect, as assessed by a validated survey methodology.

Methods: Questionnaire repeatability was first assessed, resulting in the intraclass correlation coefficient agreement level >0.9 in the three validation cohorts of physicians, pharmacists, and patients. All questions were closed multiple-choice, allowing measuring variations in frequency, quality, or magnitude of effect on a 5-point Likert-like verbal scale.

Results: Three different surveys were performed in Italy and Spain on a total of 3,471 physicians, including 77 gastroenterologists, 848 patients, and 146 pharmacists who had an experience with Poliprotect in the previous year. Over 90% of general practitioners (GPs) rated Poliprotect effectiveness as good/excellent in controlling pyrosis, 80% for epigastric pain, and approximately 70% for digestion difficulties. GPs reported Poliprotect as very or extremely useful as an alternative to PPIs (73%) and for pregnancy-associated GERD symptoms (61%), almost unanimously (99.5%) reporting an excellent to good tolerability; 79% of the gastroenterologists answered to be extremely or very satisfied with the improvement of typical GERD symptoms, whereas improvement of dyspepsia and pregnancy- and breast-feeding-associated GERD symptoms was rated as highly satisfactory for 69, 52, and 62%, respectively, among GI specialists. Its use because of painful dyspeptic symptoms was reported by over 80% of patients, who rated symptom relief as excellent/good, and reported a marked quality-of-life improvement in 73% and in 65% of their answers, respectively. The product was used as monotherapy by 63% of patients. 

Conclusion: Large-scale, validated surveys support the safety and effectiveness of Poliprotect in the treatment of common functional upper GI disorders.