WO2016080942A1

WO2016080942A1 - Method for obtaining a pasty form of sorbent based on hydrogel o methylsilicic acid

Info

Publication number: WO2016080942A1
Application number: PCT/UA2016/000003
Authority: WO
Inventors: Yuriy Zakharovych TOLCHEYEV
Original assignee: Individual
Current assignee: Individual
Priority date: 2014-11-20
Filing date: 2016-01-12
Publication date: 2016-05-26
Anticipated expiration: 2017-05-20
Also published as: UA112474C2; RU2014151576A

Abstract

The invention relates to methods of obtaining pasty sorbents based on methylsilicic acid hydrogel, which can be used to eliminate organic and toxic metabolites, preferably having high molecular weight. The proposed method provides additional mechanical processing of synthesized methylsilicic acid hydrogel preferably in a rotor-type homogenizer, in a solvent for grinding particles contained in the product to the desired size, preferably 10-200 μm. Water or sugar syrup can be used as the solvent.

Description

METHOD FOR OBTAINING A PASTY FORM OF SORBENT BASED ON HYDROGEL OF METHYLSILICIC ACID

FIELD OF THE INVENTION

The invention relates to a medical industry and refers to a method of obtaining organosilicon adsorbent in the form of paste, which can be used in medicine as enterosorbent to eliminate organic and toxic metabolites, in particularly having high molecular weight.

BACKGROUND OF THE INVENTION

Interest in the use of sorbents for medical purposes has increased sharply since the 1980-s. This was preceded by studies of the Greek scientists, who revealed that activated carbon could be used to effectively eliminate from the body (by purifying blood) toxic products, formed in the body as a result of diseases.

Activated charcoal has been widely used as sorbent. (VIDAL Guideline. Medicinal products in Russia. - M.: OVPEE - Astra Pharm Service, 2000. - P.E-8). It is convenient to use, as it is produced in the form of tablets and powder and is used in chemical, food, pharmaceutical industry, as well as medicine.

However, activated charcoal has significant deficiencies: small sorption activity and low selectivity of the sorption action, e.g., to cholesterol, bilirubin, urea, uric acid, which are usually removed from the body by excretory organs.

In addition, the tablet form is convenient, but does not allow the intake of the required amount of sorbent per single administration: achievement of a therapeutic effect requires doses of 5-15 g, which corresponds to 25-75 tablets, which is naturally difficult for the patient to take at a time.

The use of activated charcoal in powder form is also difficult because it is dewetting or insoluble in water.

Additionally, its use may cause constipation, vomiting, inhalation of coal dust into the lungs; and under long-term usage - hypovitaminosis, malabsorption of nutrients in the gastrointestinal tract.

Activated charcoal is contraindicated in ulcerative lesions of the gastrointestinal tract, stomach bleeding, for children.

It is also known enterosorbent of microcrystalline cellulose (MCC) - "Microcel" (Marketing Authorization of the Ministry of Health of the Russian Federation P 97.128.5, State Registry of Medicinal Products, M., 2000, p. 102).

Deficiencies: unpleasant taste, gastrointestinal discomfort (constipation).

Silicon dioxide powder has certain sorptive abilities . There is a known drug, named Polysorb, inorganic multifunctional enterosorbent based on a highly dispersed silicon dioxide.

The powder is used to prepare a suspension for oral administration. However, the use of drugs or food supplements in powder form is usually associated with great inconvenience compared with their use in a tablet form.

RU,2234931 discloses an enterosorbent containing silicon dioxide in a tablet form. In addition to silicon dioxide, this enterosorbent contains lignin hydrolyzed and microcrystalline cellulose, which also have adsorption properties, as well as excipients used to obtain tablets, such as pectin, starch, and magnesium or calcium stearate.

Furthermore, it is also known an enterosorbent as a product of nonlinear condensation of methylsilicic acid ( the chemical name - polymethylsiloxane polyhydrate), known under the trademark name- "Enterosgel" produced in a gel form. Various raw materials can be used as a source for gel synthesis.

It is disclosed by WO2011/075095 a method of obtaining methylsilicic acid hydrogel from methylethoxy silane (MTES) and aqueous ethanol with a volume portion of ethyl alcohol of 60 to 96.5%, which is treated with a hydro lyzing blend of hydrochloric acid and purified water.

However, this method has certain deficiencies. Hydrolysis requires sufficient volumes of alcohol, it is characterized by a long-term "maturation" process of the gel, large consumption of water during washing, and possibility of alcohol content in the pores of the finished product, which restricts the medical use of the sorbent.

RU 2111979 discloses a method of obtaining an enterosorbent based on methylsilicic acid hydrogel as an adsorbent of medium molecular weight metabolites.

Medium molecular weight metabolites are substances with a molecular weight of about 500-5000 Da; usually these are protein decomposition products that play an important role in intoxication phenomena.

However, high molecular weight compounds, such as bacterial toxins and viruses, are even more important factors of intoxication.

According to the author's experiments, the ability of methylsilicic acid compounds to have affinity for substances of a particular mass depends on the physical state and particle size of the sorbent, as well as the solvent itself.

Unexpectedly, it was found that the paste form of the sorbent adsorbs high molecular weight toxins better than gel form.

WO 2008/036056 discloses a method of obtaining a sorbent based on methylsilicic acid hydrogel, where the sorbent with the general formula

{(CH ₃SiOi.5)-nH₂0} can be produced as paste by varying n ratio, but the concrete Examples for obtaining such form are not described.

According to the experiments, mere dissolution of the sorbent having gel form in water does not produce paste or suspension convenient for administration.

In connection with the above, there is a need for new forms of sorbents based on methylsilicic acid, which would increase their adsorption activity and product output, and improve the convenience of dosing.

SUMMARY OF THE INVENTION

The main object of the invention is obtaining a pasty form of the sorbent based on hydrogel of methylsilicic acid having a pronounced sorption properties in relation to high molecular weight substances.

This object is achieved by the method wherein the synthesized hydrogel of methylsilicic acid is subjected to an additional mechanical processing, preferably in a rotor-type homogenizer, in a solvent for grinding of particles contained in the product to the desired size, preferably to the size of 10-200 μαι.

In the preferred embodiments of the claimed invention water or sugar syrup may be used as the solvent.

THE BEST MODE OF CARRYING OUT THE INVENTION

As a result of the proposed additional mechanical processing of a synthesized hydrogel of methylsilicic acid providing a grinding of particles contained in the produc to a desired size , preferably to 10-200 μι^η, the target product in a pasty form was obtained with the following physical and chemical properties, shown in Table 1 and Table. 2 Table 1

Table 2

Comparative experimental data on properties of the product obtained by the known method (prototype) and the product

obtained by the claimed method

o. Name of compared Value Value (claimed

parameters (prototype) invention)

Blending time - 20-60 sec

Adsorption activity, 3.3-4.6 3.2-4.6 μπιοΐ/g

Average particle size Not specified 10-200

Average pore radius Not specified 31.9 A

Specific surface Not specified More than 600

m³

Target product output, 36.7 70-85 %

pH 5.0-7.0 5.0-7.0

Gel to solvent ratio Not specified 2-5: 1

Adsorption activity (A) of the product, μηιοΐ/g, was calculated by the formula:

(D₀ - D) · m₀ ■ 5■ 50 · 100■ 1000000 _ (D₀ - D)■ m₀ · 50000 D₀ - m - 1000 - 100 - 5 - M D₀ · m^■ M

DO - optical density of Congo red stock solution (solution Kl);

D - optical density of Congo red solution after contact with the product; mO - sample weight Congo red, g; m - mass of sample preparation, g;

1000, 50 - dilution, ml;

M - molecular weight of Congo red solution (696.7). Optical density of the resulting solution was measured in a spectrophotometer at maximum absorption at a wavelength of 464 nm in a cuvette with layer thickness of 10 mm, using 0.02 M sodium chloride solution as a reference solution.

Optical density of DO methyl orange stock solution was measured at the same time (solution M l).

Adsorption activity for high molecular weight substances - immunoglobulin G (more than 100 000 Da) and bacterial toxin (more than 10 000 Da) was measured similarly).

Results are given in Table 3.

Table 3

According to the data in Table 3, the pasty sorbent shows more marked activity in relation to high molecular weight compound, exceeding that of the gel in 1.5-1.83 times.

Further on, the summary of the invention is explained more detailed by the Examples of the preferred embodiments of the claimed method/ Example 1.

300 ml of water was added to 1000 g of methylsilicic acid hydrogel, placed in a 21 - blender, and mechanical processing at 6000 rpm for 15 minutes was provided. This resulted in a pasty product.

Average particle size and adsorption activity was determined under the microscope.

Particle size was 200 μηι, adsorption activity by methylene blue - 3.2 μηιοΐ/g, immunoglobulin G - 330.1 mg/g.

When dissolved in water, the paste yielded stable water suspension.

Example 2.

300 1 of water was added to 100 kg of methylsilicic acid hydrogel, placed in a 200 1 -blender, and mechanical processing at 2000 rpm for 30 minutes was provided. This resulted in a pasty product.

Particle size was 10 μιη, adsorption activity by methylene blue - 3.6 μηιοΐ/g, immunoglobulin G - 333.2 mg/g.

Example 3.

150 ml of water and 150 ml of sugar syrup was added to 1000 g of methylsilicic acid hydrogel, placed in a 2 1- blender, and mechanical processing at 4000 rpm for 15 minutes was provided. This resulted in a pasty product. Average particle size and adsorption activity was determined under the microscope.

Particle size was 10 μηι, adsorption activity by methylene blue - 3.0 μιιιοΐ/g, immunoglobulin G - 330.1 mg/g.

When dissolved in water, the paste yielded stable water suspension

Example 4.

250 ml of sugar syrup was added to 1000 g of methylsilicic acid hydrogel, placed in a 2 1- blender, and mechanical processing at 4000 rpm for 15 minutes was provided. This resulted in a pasty product.

Particle size was 10 μιη, adsorption activity by methylene blue - 2.7 μπιοΐ/g, immunoglobulin G - 318.1 mg/g.

When dissolved in water, the paste yielded stable water suspension

Thus, the pasty form of the sorbent based on methylsilicic acid hydrogel and obtained by the claimed method additionally has pronounced sorption properties in relation to high molecular weight substances.

Claims

1. A method for obtaining a pasty form of sorbent based on hydrogel of methylsilicic acid characterized in that the synthesized hydrogel of methylsilicic acid is subjected to an additional mechanical processing, preferably in a rotor-type homogenizer, in a solvent for grinding particles contained in the product to a desired size, preferably 10-200 μπι.

2. The method according to claim 1 characterized in that the sorbent is water.

3. The method according to claim 1 characterized in that the sorbent is sugar syrup.