Colloidal Silicon Dioxide in Tablet form (Carbowhite) Efficacy in Patients with Acute Diarrhea: Results of Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study

Abstract

the acute diarrhea is a wide-spread disease. the prescription of enterosorbents is appropriate as a primary measure for the treatment of the acute diarrhea for effective prevention of the fluid and electrolyte loss, as well as method for symptom relief of the attack of the disease. Aim of the study -the antidiarrheal efficacy and safety study of high-dispersion silicon dioxide enterosorbent in tablet dosage form in patients with acute diarrhea. This was randomized, double-blind, placebo-controlled, 4-center study. Acute diarrhea was defined as three and more episodes of watery stool per day either during 48 hours or less before study entry in the patients having normal stool recently. It has been postulated that symptoms and signs of acute diarrhea have to be caused by direct infection of the gastrointestinal tract and did not associated with moderate-to-severe systemic states. 144 patients with established acute diarrhea were randomized into treatment group (enterosorbent "carbowhite", n = 120) or placebo group. Date collection including severity diarrhea, systemic symptoms was performed at baseline and daily during 7 days. Stool examination and serological assay were performed at baseline. The primary end points were declared as time to complete recovery from acute diarrhea. It has been found that the use of the siliceous enterosorbent ("carbowhite") allowed to reduce (p < 0.001) the treatment period averagely for 0.9 days (95% confidence interval 0.5-1.2 days) in comparison with placebo. Data of safety monitoring has revealed that both patient groups had negative stool culture, while initiation of antibiotic treatment was run more frequently in placebo group (8.3%) compared to investigational product group (4.1%, P = 0.044). The siliceous enterosorbent "Carbowhite" was well tolerated and reduced the recovery time of the acute episode of the diarrhea in the clinically significant form.The acute infectious diarrhea is a challenge for the contemporary medicine, although the leading factors contributing in the pathogenesis of the disease is well known 1 . However, there is a large body of evidence regarding higher rate of morbidity and mortality in developing countries due to diarrheal diseases 2,3 . Moreover, the acute diarrheal diseases are also wide-spread in the countries with high sanitary-hygienic level 3 . Foodborne Disease Burden Epidemiology Reference Group finds that the global burden of diarrheal diseases is comparable to those of the major infectious diseases, as HIV/AIDS, malaria and tuberculosis 4 .

Silicon-containing water intake confers antioxidant effect, gastrointestinal protection, and gut microbiota modulation in the rodents

“…In contrast, several probiotics and their metabolites may depress the proliferation of pathogenic bacteria, and increase the intestinal barrier function [ 12 , 13 ]. Previous research using administration of colloidal silicon dioxide in tablet form in patients with acute diarrhea revealed that the high-dispersion silicon dioxide enterosorbent exhibited antidiarrheal effect [ 14 ]. Moreover, it is reported that silicon dioxide blocks the receptors of mucous membrane that is responsible for pathogens adhesion and toxins binding, and accelerates the adsorption of active substances in intestine [ 15 ].…”

Current status of silica-based nanoparticles as therapeutics and its potential as therapies against viruses

“…Most adverse events were mild and were gastrointestinal in origin Mesoporous silica ( Bukara et al, 2016 ) (500 nm ( Jammaer et al, 2009 )) Open-label, randomized, two-way cross-over Enhanced delivery of fenofibrate using mesoporous silica compared to micronized fenofibrate Route: Oral No serious adverse events reported and no relevant differences in clinical laboratory tests between the subjects in the treatment and the reference groups Porous silica-lipid nanoparticles ( Tan et al, 2014 ) (15.20 μm with 3–20 nm pores) Randomized, double-blinded, one-period single oral dose (Phase I) Enhanced delivery of ibuprofen using silica to improve solubility compared to commercial tablet Route: Oral Negligible acute side effects related to the administration of both the investigational and reference formulations. Colloidal silica ( Tieroshyn et al, 2020 ) (Size NR) Randomized, double-blind, placebo-controlled, 4-center (Phase II) Silica as an anti-diarrheal agent compared to placebo Route: Oral “Carbowhite” Carbowhite was well tolerated and no adverse effects were reported Silica Shells ( van Zuuren et al, 2021 ) (Size NR) Multi-centered randomized, double blind, vehicle controlled parallel group (Phase II) – Recently FDA Approved ( Randles-Friedman, Iwaniuk ) Prolonged release of benzoyl peroxide using silica shells Route: Topical 52-week long-term safety study, side effects mostly mild Silicic acid anhydride ( Zschocke et al, 2008 ) (Size NR) Randomized, open‐label, comparator‐controlled Comparison of silica vs Topical acyclovir for the treatment of recurrent herpes labialis Route: Topical No serious adverse events …”

Malabsorption syndrome after gastroenteritis in children, optimization of therapy

“…Ця властивість лежить в основі його застосування для видалення екзотоксинів, ендотоксинів, а також для фіксування мікроорганізмів, міцел, ліпопротеїдів. Завдяки наявності на поверхні мікроорганізмів різноманітних білкових структур, високодисперсний діоксид кремнію активно сорбує патогенну мікрофлору (до 10 10 мікробних тіл на 1 грам речовини) та виводить її з кишечника, а це забезпечує виражений протимікробний ефект [13,16].…”

“…Експериментальні дослідження показали, що високодисперсний діоксид кремнію має також виражені антидіарейні властивості, що пояснюється блокуванням дії стимуляторів секреції рідини в кишечнику (дезоксихолатів натрію, цАМФ і серотоніну) шляхом впливу на відповідні рецептори та вираженими гідрофільними властивостями діоксиду кремнію, що забезпечує структурування кишкового вмісту [13,15].…”

“…Клінічними дослідженнями підтверджено високу ефективність застосування ентеросорбентів на основі діоксиду кремнію за наявності захворювань ШКТ (ГКІ, синдром подразненого кишечника, функціональна диспепсія тощо), у тому числі в педіатричній практиці [5,12,13]. У ряді робіт показано, що додавання ентеросорбції до комплексу лікування бактеріальних та вірусних кишкових інфекцій у дітей сприяє швидкому усуненню основних гастроентерологічних симптомів і скороченню тривалості захворювання [7].…”