(1) Background: Tannacomp^® is a drug consisting of tannin albuminate, a complex of tannic acid (TA) and ethacridine lactate (Eta) used for treating acute and traveler’s diarrhea. TA is thought to modulate gastrointestinal barrier function, but the underlying mechanisms and whether Eta has similar effects remains unclear. (2) Methods: to investigate the effects of TA and Eta on the intestinal barrier, stress responses were induced in murine intestinal organoids by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GF_Red). Further, organoids were exposed to either TA (0.01 mg/mL) or Eta (0.002 mg/mL) and markers of inflammatory response and gut barrier function were assessed. (3) Results: TA and Eta reduced several inflammatory markers such as interleukin 6, interleukin 1β, tumor necrosis factor α, and myeloid differentiation primary response 88 in stressed organoids. In addition, TA and Eta attenuated LPS- and GF_Red-mediated gut barrier dysfunctions, with normalization of tight junction, adherent junction and mucin gene expression and reduction of Nod2- and matrix metalloproteinase 7-dependent activation of antimicrobial peptides. (4) Conclusions: our data show that TA and Eta modulate markers of inflammation and the intestinal barrier and suggest novel mechanisms of action of this drug that could broaden its treatment indications.

Objective: To review the efficacy and safety of tannin albuminate and ethacridine lactate monohydrate in the treatment and prevention of diarrhea. Design: Narrative review. Data sources: A systematic literature search was conducted in MEDLINE and Embase from inception to September 2022. The search was restricted to English and German language publications. Eligibility criteria for selecting studies: Randomized controlled trials, non-interventional studies, and meta-analyses assessing tannin and/or ethacridine for the treatment or prevention of diarrhea. Results: Of 366 titles identified, a total of 13 studies were included in this review. Five randomized controlled trials and four noninterventional trials demonstrate the efficacy and safety of the fixed combination of tannin albuminate and ethacridine lactate monohydrate in treating acute diarrhea and preventing traveler's diarrhea. The fixed combination reduced acute diarrhea duration by improving stool frequency, consistency, and weight and reduced the risk of traveler's diarrhea. Two pilot studies indicate efficacy in chronic diarrhea. Safety and tolerability were very good in all included studies. Two meta-analyses investigated the efficacy of gelatin tannate in children with acute gastroenteritis. Conclusion: The efficacy and safety of tannin albuminate and ethacridine lactate monohydrate for the treatment of acute diarrhea and the prevention of traveler's diarrhea are proven in randomized controlled trials. Several noninterventional studies substantiate the real-world effectiveness and tolerability of the fixed combination. Both active ingredients combine antidiarrheal, antimicrobial, mucosal protection, and spasmolytic properties. However, existing clinical data should be updated with larger, well-designed, placebo-controlled trials in adult and pediatric patient populations.

Objectives: Saccharomyces boulardii CNCM I-745, a probiotic yeast, is effectively used for the treatment of acute diarrhea as well as for the prevention and treatment of traveller‘s diarrhea and diarrhea under tube feeding. The underlying mechanisms are not fully elucidated. Both antitoxic and regulatory effects on the intestinal barrier, mediated either by the yeast or yeast-derived substrates, have been discussed. Methods: To examine the effects of Saccharomyces boulardii released substrates (S.b.S) on gastrointestinal (GI) barrier function, a murine small intestinal organoid cell model under stress was used. Stress was induced by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GF_Red). Stressed organoids were treated with S.b.S (200 µg/mL), and markers of GI barrier and inflammatory response were assessed. Results: GF_Red-induced stress was characterized by disturbances in selected tight junction (TJ) (p < 0.05), adherent junction (AJ) (p < 0.001), and mucin (Muc) formation (p < 0.01), measured by gene expressions, whereby additional S.b.S treatment was found to reverse these effects by increasing Muc2 (from 0.22 to 0.97-fold change, p < 0.05), Occludin (Ocln) (from 0.37 to 3.5-fold change, p < 0.0001), and Claudin (Cldn)7 expression (from 0.13 ± 0.066-fold change, p < 0.05) and by decreasing Muc1, Cldn2, Cldn5, and junctional adhesion molecule A (JAM-A) expression (all p < 0.01). Further, S.b.S normalized expression of nucleotide binding oligomerization domain (Nod)2- (from 44.5 to 0.51, p < 0.0001) and matrix metalloproteinase (Mmp)7-dependent activation (from 28.3 to 0.02875 ± 0.0044 ** p < 0.01) of antimicrobial peptide defense and reduced the expression of several inflammatory markers, such as myeloid differentiation primary response 88 (Myd88) (p < 0.01), tumor necrosis factor α (Tnfα) (p < 0.01), interleukin (IL)-6 (p < 0.01), and IL-1β (p < 0.001). Conclusions: Our data provide new insights into the molecular mechanisms by which Saccharomyces boulardii CNCM I-745-derived secretome attenuates inflammatory responses and restores GI barrier function in small intestinal organoids.

Topical hydrocortisones are commonly used for the self-treatment of allergic or mild inflammatory skin reactions. Post-market data analyzing usage, safety and effectiveness of hydrocortisone creams in a real-world setting are scarce. This non-interventional, observational, pharmacy-based study analyzes the usage patterns and patient-perceived effectiveness and tolerability of Soventol Hydrocortisonacetat 0.5% (Soventol HCA) in a real-world setting. Adult participants with a moderately pronounced reddened, inflammatory or allergic skin disease for which a weak, low-concentration corticosteroid was indicated filled an online questionnaire parallel to product application for a maximum of 7 days. Severity of symptoms, frequency of application and the occurrence of adverse events were documented daily. The study was reported to the German Federal Institute for Drugs and Medical Devices (NIS-nr 7793). Data from 2,561 participants were received. Most participants used Soventol HCA for the treatment of insect bites (62.3%; N = 2,557). Almost all participants were "very satisfied" or "satisfied" with the effectiveness (97.7%; N = 2,106) and tolerability (99.1%; N = 2,106) of Soventol HCA. The vast majority of participants assessed the speed of itching relief (87.0%; N = 2,045), speed of cooling effect (90.5%; N = 2,073), pain relief (93.9%; N = 1,760), redness relief (90.2%; N = 2,033), and swelling relief (92.9%; N = 1,901) as "fast" to "very fast" or "good" to "very good." 61 non-serious adverse reactions were documented. This non-interventional study provides valuable real-world insights about the patient-perceived effectiveness and tolerability of Soventol HCA in treating insect bites, but also other inflammatory or allergic skin reactions as e.g. sunburn, allergies or eczema in adults. Patient satisfaction with effectiveness and tolerability was high in all application fields, especially regarding itch reduction of insect bites.