Polymethylsiloxane polyhydrate (PMSPH), or methylsilicic acid hydrogel (brand name Enterosgel), is an enterosorbent used for binding and removing various toxic substances, infectious agents and metabolites from the gastrointestinal tract. It is available in the form of a white or almost white homogeneous pasty mass. It is odorless and tasteless.
History This product was synthesized in the late 1970s to early 1980s in the USSR by I. B. Slinyakova and I. М. Samodumova of L. B. Pisarzhevskiy Institute of Physical Chemistry (Kyiv), where the theoretical foundations for the formation of the porous structure of organosilicon adsorbents with an adjustable porous structure and a pre-defined chemical nature of the surface were established; there were also efforts to synthesize organosilicon adsorbents, namely porous polymers polyorganosiloxanes. Industrial production of the preparation began in early 1991. In 1994, a medicinal drug with methylsilicic acid hydrogel as the active ingredient, marketed under the brand name Enterosgel, was registered in Ukraine and Russia, and active sales of the new product began.
Currently, the product is already available in 40 countries.
The study of the use of the preparation was conducted in cooperation with the Medical Service of Krasnoznamennyi Kiev Military District (Medical Service Colonel Professor F. G. Novikov, Medical Service Colonel N. P. Bezlyuda). Since, many clinical trials investigating the preparation have been conducted by Ukrainian and Russian companies in the CIS.
A large-scale study of its effect was conducted in the United Kingdom between 2019 and 2022. It established a proven base of effectiveness of the preparation in the treatment of irritable bowel syndrome with diarrhea, help in relieving bloating, abdominal pain and urgency.
The preparation is registered in Russia and the CIS countries as a medicinal drug, and in the countries of the European Union, Serbia, New Zealand, Africa as a medical device, since the product is not absorbed into the bloodstream and acts as an adsorbent only in the gastrointestinal tract, it fits the relevant definition according to the Classification of the European Commission.
The medical device Enterosgel is produced in a factory in Jeseník, Czech Republic, from where it is exported to all countries of the world, except Russia and the CIS countries. This region supplies production in Russia, where a factory is situated in the city of Dankov.
Structure PMSPH is a polymeric gelatinous organosilicon compound. The gel is dispersed in water to a particle size of no more than 300 microns. The preparation is a suspension which is taken orally.
Microstructure Electron microscopic studies have shown that its gel-forming matrix has a globular structure and consists of an ensemble of fused globules. These globules, bound together by siloxane bonds, form pores. The pores are the spaces between the globules. They are filled with water. Pore size is restricted. The presence of methyl groups on the surface ensures its hydrophobic properties. PMSPH particles tend to form a continuous network in a suspension to reduce the interaction of hydrophobic SiCH3 with water. These particles can be viewed as two-dimensional sheets rather than three-dimensional solid particles. Aqueous suspensions of polymethylsiloxane polyhydrate are characterized by high viscosity.
Mechanism of action The physical and chemical characteristics of PMSPH define its absorptive and protective properties:
The solid porous structure of the gel-forming matrix determines absorption capacity by the molecular adsorption mechanism and allows predominantly adsorbing medium molecular weight toxic substances and metabolites (e.g. bilirubin and products of protein breakdown). Due to its gel-like consistency: it absorbs high-molecular-weight toxic substances by the mechanism of co-precipitation in the gel (e.g. bacterial toxins);Nikolaev, 2010, с. 45. it shows protective properties—its elastic gel-like particles form a layer on the surface of mucous membranes. This layer protects mucous membranes from various damaging factors, and its protective properties are manifested universally—in the intestine, and on the surface of the mucous membranes of other organs.1. Авалуева Е.Б., Данилова И.А., Сказываева Е.В. и др. Влияние препарата Энтеросгель®» на патоморфологическую картину у пациентов с Н.pylory-ассоциированными заболеваниями верхних отделов пищеварительного тракта] // Гастроэнтерология Санкт-Петербурга. — 2014. — No. 3-4. — С. M1-M1a. — ISSN 1727-7906. Архивировано 7 февраля 2022 года.
It absorbs toxic substances produced in the gastrointestinal tract, as well as toxic substances entering the gastrointestinal tract from the environment (e.g., ethyl alcohol).Хабибулин М.Е., Гармашова И.В., Кононов В.Н. Анализ сорбционной активности активированного угля и Энтеросгеля при сорбции ими спиртосодержащих жидкостей // Известия Российской Военно-медицинской Академии. — 2019. — Т. 2, No. 1. — С. 234-238. — ISSN 2713-2315. It also prevents reabsorption of toxic substances and metabolites excreted into the intestinal lumen from the blood, as well as getting into the intestine with bile.
In an in vitro experiment, it reduced the production of staphylococcal enterotoxin and inhibited the growth of Staphylococcus aureus.Флуер Ф.С., Кудрявцева А.В., Титарев С.И., Быкова И.Б. Средство для ингибирования продукции стафилококковых энтеротоксинов и удаления их из биологических субстратов // Журнал микробиологии, эпидемиологии и иммунобиологии. — 2017. — No. 3. — С. 71-77. — ISSN 0372-9311. Архивировано 9 февраля 2022 года.
It reduced malonic dialdehyde formation and increased integral antiradical activity in toxic liver damage in vivo.Плаксен Н.В., Устинова Л.В., Степанов С.В. и др. Гепатопротекторный эффект композиции энтеросорбента и природного антиоксиданта // Тихоокеанский медицинский журнал. — 2015. — Т. 60, No. 2. — С. 73-75. — ISSN 1609-1175. Архивировано 7 февраля 2022 года.
Due to adsorption in the gastrointestinal tract, it helps reduce blood sugar and glycated hemoglobin levels, eliminate lipid distress syndrome, including diabetic dyslipidemia, improves energy processes in liver tissues in experimental diabetes.Черняшова В.В., Гнатюк М.С., Олещук О.М. и др. Изучение эффективности использования энтеросорбента Энтеросгель в лекарственной форме паста для перорального применения на модели экспериментального стрептозотоцинового диабета // Международный эндокринологический журнал. — 2011. — Т. 33, No. 1. — С. 64-67. — ISSN 2224-0721. Архивировано 7 февраля 2022 года.
PMSPH firmly binds and excretes pathogenic bacteriaГригорьев A. B., Знаменский В. М., Бондаренко Л. Г. и соавторы. Адгезия патогенной микрофлоры на кремнийорганических сорбентах // Иммуно-биологические препараты нового поколения и методы их контроля. — НИИЭМ им. Н.Ф. Гамалеи АМН СССР, Киевский государственный институт усовершенствования врачей. Москва, 1988. — С. 114—120. and rotaviruses.Зб. наук. праць, 1997, с. 48—51 Дзюблик И.В., Шунько Е.Е., Барбова А.И. Применение энтеросгеля для лечения ротавирусной инфекции.Зб. наук. праць, 1997, с. 25—27 Гирин В.Н., Дзюблик И.В., Барбова А.И. Адсорбционная активность гидрогелей метилкремниевой кислоты в отношении ротавирусов.
Legend intestinal lumen intestinal mucosa metabolites and toxic substances metabolites and toxic substances are bound by Enterosgel Highly viscous PMSPH particles cover mucosal areas and protect them from the damaging effects of bacterial toxins and various active chemical compounds (e.g., deconjugated bile salts that damage the mucosa of the gastrointestinal tract).
PMSPH has a pronounced ability to absorb lipopolysaccharide (LPS) molecules. Large molecules of lipopolysaccharide are co-precipitated in the gel and excreted from the body. A daily dose of PMSPH (Enterosgel paste) binds 410 mg of LPS.Nikolaev, 2010, с. 39.
LPS, which has extremely high biological activity, can be found in the outer wall of all Gram-negative bacteria and is released only when the bacterium is destroyed, and is also known as endotoxin (the prefix endo- means inside, inside the bacterium). The distal section of the intestine is the main reservoir of Gram-negative microflora and lipopolysaccharides. Normally, only a small amount of endotoxin enters the bloodstream because the intestinal wall works as a barrier and limits the inflow of endotoxin into the bloodstream. Most (94%) of the endotoxin entering the bloodstream undergoes detoxification in the liver. However, a small amount of endotoxin bypasses the liver and enters the systemic bloodstream, maintaining physiological concentration of endotoxin in the blood (physiological endotoxinemia).
The process of endotoxin entering the bloodstream can be intensified by various lesions of the intestinal mucosa and by dysbacteriosis, which is accompanied by translocation of bacteria and products of their life activity into the small intestineЛиходед В.Г. Ющук Н.Д. Яковлев М.Ю., 1996. and as a result of antibiotic-induced death of Gram-negative microflora and the release of large amounts of endotoxin. It should be particularly emphasized that various stressful situations (severe seizures, burns, trauma, etc.) cause damage to the mucous membrane of the gastrointestinal tract. This damage occurs due to redistribution of energy and structural resources of the body, i.e. transfer from systems not involved in adaptation to the stress factor to systems providing adaptation.Газенко О.Г., Меерсон Ф.З., 1986, с. 77—124. An increase in the concentration of endotoxin in the blood exceeding the physiological norm leads to a pathological condition known as endotoxin aggression. Endotoxin aggression is a universal factor in the pathogenesis of human diseases, the development of which is caused by an excess of endotoxin entering the general bloodstream and a lack of endotoxin-binding systems.Яковлев М.Ю., 2003.Таболин В.А. и др., 2003.Таболин В.А. и др., 1999.Таболин В.А., Лазарева С.И., Яковлев М.Ю., 2001.Таболин В.А., Яковлев М.Ю. и др., 2002.Таболин В.А., Бельчик Ю.Ф. и др., 2002. Excess endotoxin causes endothelial damageЯковлев М.Ю. Лиходед В.Г. Аниховская И.А. и др., 1996. in the microcirculatory vessels of the intestinal mucosa and leads to the development of mucosal ischemia. This, in turn, causes further damage to the mucosa and a weakening of the intestinal barrier.
Reduction of endotoxin back to physiological levels in the blood prevents damage to the vascular wall and restores impaired blood supply to the intestinal mucosa and eliminates mucosal ischemia. The latter, in turn, contributes to its regeneration and restoration of the barrier function of the intestinal mucosa. The positive effect of using PMSPH is primarily aimed at preserving/restoring the intestinal barrier, restoring the physiological level of endotoxin and breaking the vicious circle caused by damage to the mucous membrane. This inhibits the development of endotoxin aggression.
Legend
From the left: As a result of intestinal barrier insufficiency, there is an increase in the concentration of LPS in the mucosal bloodstream, which leads to impaired microcirculation and ischemia of the mucosa, its damage and further development of intestinal barrier insufficiency. Endotoxin aggression develops.
From the right: The use of PMSPH reverses the course of events: the level of LPS is reduced, microcirculation processes in the intestinal mucosa are restored, the intestinal mucosa is restored, and the function of the intestinal barrier is restored (more details). Notes
Figure 1: As a result of insufficiency of the intestinal barrier, the concentration of LPS in the blood flow of the mucous membrane increases, which leads to disruption of microcirculation and ischemia of the mucous membrane, its damage and further development of intestinal barrier insufficiency. Endotoxin aggression develops.