clays and binders, microbiomes

Enterosgel and alumina

Polymethylsiloxane is a silcon polyer with rheological properties. Because we were interested in fixing the gut to fix the liver, a PubMed search was performed on enterosgel and liver.

MedSilica is the maker of Entrerosol. Enterosgel® – the original silicone Medical Device intended for the elimination of toxic substances, correction of intestinal microbiocenosis and restoration of gastrointestinal mucosa epithelium.

Two Russian papers explored the mixture of immunosgel with alumina and melatonin for liver therapies. This sort of makes sense as a way of preventing the alumina from clumping up and the slow release of meltonin. The images from the first paper were of poor quality and will not be represented.

Russian paper #1

The effects of melatonin, aluminum oxide, and polymethylsiloxane complex on the expression of LYVE-1 (lymphatic vessel endothelial hyaluronan receptor) in the liver were studied in db/db mice with experimental obesity and type 2 diabetes mellitus. The complex or placebo was administered daily by gavage from week 8 to week 16 of life. The animals receiving the complex exhibited enhanced, in comparison with the placebo group, immunohistochemical LYVE-1+ staining of endothelial cells in sinusoids. Enhanced expression of LYVE-1 was associated with less pronounced dilatation of interlobular arteries, veins, and lymphatic vessels. Thee findings suggest a protective effect of the complex towards structural changes in the liver of mice with obesity and type 2 diabetes.

  • Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) that binds hyaluronic acid.
  • HA is a glucosaminoglycan consisting of D-glucuronic acid and N-acetyl-D-glucosamine disaccharide units that is a component of connective tissue, skin, vitreous humour, umbilical cord, synovial fluid and the capsule of certain microorganisms contributing to adhesion, elasticity, and viscosity of extracellular substances.

The duration of experiment was 56 days. The
animals were distributed into groups at random. Animals of the main group (n=8) received CM (white
powder with 40-μ particles releasing melatonin upon
contact with liquid medium) dissolved in 200 μl distilled water through a gastric tube.

Aluminum oxide and polymethylsiloxane (CM components) formed a hydrophilic-hydrophobic matrix compatible with biological tissues. The adsorption characteristics of CM allowed stimulation of the drainage function of the lymphatic system. The animals received CM from week 8 to week 16 of life in a daily dose of0.665 g/kg. Controls (n=8) received 200 μl distilledwater according to the same protocol.


These authors hand some interesting comments on Enterosgel

  • polymethylsiloxane polyhydrate (PMSPH)
  • microglobules which contain porous space filled with water
  • larger particles (<250 µm in size) forming a hydrogel.
  • amorphous and insoluble in water.
  • specific surface area of 150–250 m2/g dry weighIt
  • pores in the microporous range (below 2 nm in diameter) but mostly wide mesopores and small macropores in the range from 2 nm up to 100 nm in diameter
  • Enterosgel is composed of PMSPH and water in the ratio of 70/30 by weight, which has been found experimentally to have the highest pore volume ca. 1.5–1.6 cm3/g

Russian abstract #2

We studied the effects of a melatonin-aluminum oxide-polymethylsiloxane complex (complex M) on the expression of apoptosis regulators Bcl-2 and Bad in the liver of homozygous db/db BKS.Cg-Dock7m+/+Leprdb/J mice with obesity and type 2 diabetes. Complex M or placebo was administered daily through the gastric tube during weeks 8-16 of life. In mice with type 2 diabetes mellitus receiving placebo, enhanced immunohistochemical reactions for proapoptotic Bad protein and weak response for anti-apoptotic Bcl-2 protein were observed. Administration of complex M shifted the ratio of apoptosis regulators: the area of Bcl-2 expression significantly increased and against the background of reduced Bad expression area. These findings attest to antiapoptotic effect of complex M in the liver on the model of type 2 diabetes mellitus.

No effort was made to track this paper down. It is interesting hat they are looking a GI slow released melatonin via enterosgel/alumin and liver health.

Russian paper #3

This is a Russian language publication with an English abstract. Google Translate was used to obtain an English laznguage version of materials and methods.

It is known that the circadian rhythm of melatonin production depends on the intensity of illumination. Violation of the light regime leads to suppression of me-latonin synthesis and the development of desynchronosis, which increases the risk of developing a number of pathologies. In this regard, it is relevant to search for opportunities to restore disturbed circadian rhythms and, especially, to correct immune
dysfunctions that occur in these situations. The aim of this study was to examine the effect of a complex of melatonin, aluminum oxide and polymethylsiloxane on the lymphocytes of the spleen of mice kept under round-the-clock lighting.

Materials and methods. Mice of the C57Bl/6J line were kept under round-the-clock lighting for 14 days, against which they were intragastrically injected with distilled water, aluminum oxide with polydimethylsiloxane, melatonin and a complex of melatonin, aluminum oxide and polymethylsiloxane (a new drug developed by the Re-search Institute of Clinical and Experimental Lymphology – Branch of the Federal Research Center Institute of Cytology and Genetics SB RAS; Patent of Russian Federation No. 2577580, 2016), represented by a complex of porous material (aluminum oxide with polydimethylsiloxane) and melatonin, immobilized in the pores, from which it is gradually released in a liquid medium. Intact animals kept under the light regime of ST 12/12 and under round-the-clock lighting served as a control. Immunophe-notyping of spleen B- and T-lymphocytes was performed on a flow cytofluorimeter with monoclonal antibodies APC CD3 and FITC CD19. For studying the distribution of cells by stages of the cell cycle in splenocytes, the amount of intracellular DNA was measured by the level of inclusion of propidium iodide.

Results. Flow cytometry of the distribution of B- and T-lymphocytes of the spleen in male mice of the C57Bl/6J line kept under round-the-clock lighting conditions (KO 24/0 h) revealed a decrease in the percentage of B-lymphocytes and an increase in the number of T-lymphocytes, compared with animals kept under standard lighting conditions (the light/dark photoperiod – 14/10 hours). The ratio of CD19+/ CD3+ lymphocytes of the spleen in mice under the conditions of KO significantly decreases (1.5 times) compared to intact animals (p ≤ 0.001). The administration of pure and modified melatonin (Complex M) to animals kept under round-the-clock lighting conditions has an equally pronounced normalizing effect on the cellular composition of B- (CD19) and T- (CD3) lymphocytes of the spleen, bringing the values of the studied parameters to the control values of the intact animals (p ≤ 0.001). Round-the-clock lighting affects the proliferative potential of splenocytes, reducing the number of cells in the G2/M phase, compared with animals treated with melatonin (p ≤ 0.050). The introduction of melatonin leads to an increase in the percentage of cells in the G2/M phase relative to the placebo group (p ≤ 0.050). In the group
of mice treated with Complex M, the greatest increase in cells at the S + G2/M phases and the highest percentage of cells at the G2/M phase were revealed compared to the placebo control group (p ≤ 0.050).

Conclusion. The complex of melatonin, aluminum oxide and polymethylsiloxane has additional immunotropic properties in relation to the modifier molecule, which,apparently, are due to the joint immunostimulating effect of melatonin and the lympho stimulating effect of the sorbent. Melatonin in the composition of the complex shows its properties more stably

The following groups were formed:

  1. Intact animals (n = 6) were kept at standard lighting mode – photoperiod light / darkness: 14/10 h, while the light phase of the day is related to whether a smooth increase in illumination to daylight readings for 1 hour (dawn) and a gradual decrease values of illumination until complete shutdown during 1 hour (sunset);
  2. Mice of the KO group (n = 6) were kept for 14 days in conditions of round-the-clock lighting (foto period light/darkness – 24/0 h, model of light desynchronosis);
  3. Mice of the “KO + WATER” group (n = 6) were kept with round-the-clock lighting and daily inside distilled water was received through a probe in a volume of 200 μl (placebo control);
  4. Group “KO + C” (n = 6) included mice containing – shihsya with round-the-clock lighting, which inside- an aqueous suspension “C” was injected through the stomach through a tube (aluminum oxide with polydimethylsiloxane) from the calculation and 0.664 g/kg of animal body weight;
  5. Mice of the “KO + M” group were kept at 24-hour illumination and received intragastrically through a melatonin probe (CAT No 102254, MP Biomedical, LLC, France) at a dose of 1 mg/kg of body weight in 200 µl of water(n=6);
  6. The group “KO + S + M” (n = 6) included mice, kept under round-the-clock illumination, which melatonin, aluminum oxide and polymethylsiloxane from theeven 0.664 g/kg of animal body weight. Enter the procedure measurements were carried out at 16:00 local time (with the onset ofI eat the dark phase of the day). .

All experiments were carried out in compliance with principles of humanity and carried out in accordance with in accordance with the “Rules for working with experimental animals” votnymi” (Appendix to the Order of the Ministry of Health of the USSR No 755 of 08/12/1977) and the directive of the European Union society (86/609/EEC). The experiments were approved by the local ethics committee (protocol No. 128from 15.03.2017) This paper is hard follow, here is the order of the box and whisker plots going left to right

  1. Normal light cycle
  2. KO +H2O constant light, gastric water injection
  3. KO + C, constant light plus alumina/Enterosgel NO melatonin
  4. KO+C + M, constant light plus alumina/enterosgel/melatonin
  5. KO + M, constant light, just melatonin
  6. KO just constant light.
FIG. 2.
Cell composition of B- (CD19) and T- (CD3) spleen lymphocytesin intact C57Bl/6J mice, under 24-hour illumination (KO), with the introduction of water (KO + ВОДА), aluminum oxide and poly-methylsiloxane (KO + C), melatonin (KO + M) and a complex of me-latonin, aluminum oxide and polymethylsiloxane (KO + C + M): KO – round-the-clock lighting; C – composition of aluminum oxide and polydimethylsiloxane; M – melatonin. Statistically significant differences: * – from intact animals; & – from KO + C + M group(*, & – p ≤ 0.050; ** – p ≤ 0.010; Mann –Whitney test)
FIG. 3.
The ratio of CD19+/CD3+-lymphocytes of the spleen of C57Bl/6Jmice, under round-the-clock lighting, with the introduction of water, aluminum oxide and polymethylsiloxane, melatonin (KO + M)and a complex of melatonin, aluminum oxide and polymethylsilox-ane: KO – round-the-clock lighting; C – a composition of aluminumoxide and polydimethylsiloxane; M – melatonin. Statistically significant differences: * – from intact animals; # – from КО + ВОДА group; $ – from КО + C group (#, $ – p ≤ 0,050; **, ## – p ≤ 0.010;
*** – p ≤ 0.001; Mann – Whitney test)

“Complex M”

  • containing Melatonin is a white powder, content of melatonin in Complex M -0.15%
  • particle size of up to 0.1 mm
  • bulk density close to unity
  • average pore volume up to 0.26 cm3/g
  • specific surface area up to 160 m2/g.
  • The . meso-, macroporous structurec pore size of 10–100 nm,
  • surface is characterized by a set of hydrophilic areas due to the matrix of aluminum oxide
  • hydrophobic areas due to silicon-containing polymer that creates the conditions for multipoint communication analysis of various medium and high molecular weight toxic agents on the surface of Complex M and subsequent removing them from the body in a natural way, which provides a detoxifying effect.
  • Complex aluminum oxide with polydimethylsiloxane has static sorption capacity.
  • Preset parameters structure and chemical nature of the surface created by the possibility of a gradual release of hormones on melatonin, which allows you to achieve the effect of “prothesis” of the melatonin-producing function of the epi-physiology, i.e. the peak of increased concentration of melatonin in the blood is not short-term, but distribution lazy throughout the night, subject to the reception of pre-couple in the evening.
  • Composition creates conditions for modeling the physiological daily rhythm ma content of melatonin in the body, exhibits de-toxic and anti-edematous effect due to refluctuations in tissue fluid balance. At the same time, it is shown almost complete safety of the drug (RF PatentNo 2577580, 2016).

Russian and British Paper #4

This paper compared enterosgel with charcodote. Note that the publication date is after the enterosgel/alumina papers. The first, second, and fourth authors of this paper are from the UK, the third from National Medical University, Almaty, Kazakhstan, and the fourth from a Russian company called TNK SILMA LLC, Shipilovskaya, Moscow, Russia.

Oral intestinal adsorbents (enterosorbents) are orally administered materials which pass through the gut where they bind (adsorb) various substances. The enterosorbent Enterosgel (Polymethylsiloxane polyhdrate) is recommended as a symptomatic treatment for acute diarrhoea and chronic diarrhoea associated with irritable bowel syndrome (IBS). Since 1980’s there have been many Enterosgel clinical trials, however, the detailed mechanism of Enterosgel action towards specific toxins and interaction with concomitantly administered medications has not been fully investigated. Our in vitro study assessed the adsorption capacity of Enterosgel for bacterial enterotoxins and endotoxin, bile acids and interaction with the pharmaceutical drugs; Cetirizine and Amitriptyline hydrochloride. Our data demonstrate the good adsorption capacity of Enterosgel for bacterial toxins associated with gastrointestinal infection, with a lower than the comparator charcoal Charcodote capacity for bile acids whose levels can be raised in IBS patients. Adsorption capacity for the two drugs varied but was significantly lower than Charcodote. These findings suggest that the mechanism of Enterosgel action in the treatment of gastrointestinal infection or IBS is adsorption of target molecules followed by removal from the body. This therapy offers a drug free approach to prevention and treatment of infectious and chronic non-infectious diseases, where intestinal flora and endotoxemia play a role.

SorbentEnterosgel (single dose 22.5 g)Charcodote (single dose 25–50 g)
C. difficile TcdA (ng)739.12819–5638
C. difficile TcdB (µg)764.01073–2146
Shiga toxin Stx2-B (µg)151.03375–6750
Endotoxin (mg)3.739.1–78.2
Taurocholic acid (mg)13.5 (1.3%)172.3 (17.2%)
Glycocholic acid (mg)38.2 (3.8%)349.6 (34.9%)
Taurochenodeoxycholic acid (mg)32.3(3.2%)390.9 (39.0%)
Glycochenodeoxycholic acid (mg)104.9 (10.5%)404.6 (40.5%)
Table 1 Quantity of each bacterial toxin and bile acid that can be removed by the recommended single dose of Enterosgel and Charcodote (Enterosgel 3 doses daily, Charcodote every 4–6 hours).


  1. Michurina SV, Ishchenko IY, Arkhipov SA, Klimontov VV, Rachkovskaya LN, Konenkov VI, Zavyalov EL. Effects of Melatonin, Aluminum Oxide, and Polymethylsiloxane Complex on the Expression of LYVE-1 in the Liver of Mice with Obesity and Type 2 Diabetes Mellitus. Bull Exp Biol Med. 2016 Dec;162(2):269-272. PubMed free article
  2. Michurina SV, Ischenko IY, Arkhipov SA, Klimontov VV, Cherepanova MA, Korolev MA, Rachkovskaya LN, Zav’yalov EL, Konenkov VI. Melatonin-Aluminum Oxide-Polymethylsiloxane Complex on Apoptosis of Liver Cells in a Model of Obesity and Type 2 Diabetes Mellitus. Bull Exp Biol Med. 2017 Dec;164(2):165-169. PubMed
  3. Shurlygina А.V et al The effect of a complex of melatonin, aluminum oxide and polymethylsiloxan on the cellular composition of mice spleen kept in round the clock lighting conditions. ACTA BIOMEDICA SCIENTIFICA, 2021, Vol. 6, N 4 free article
  4. Howell CA, Mikhalovsky SV, Markaryan EN, Khovanov AV. Investigation of the adsorption capacity of the enterosorbent Enterosgel for a range of bacterial toxins, bile acids and pharmaceutical drugs. Sci Rep. 2019 Apr 4;9(1):5629. PMC free article

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