RU2302866C2 - Enterosorbent and method for its preparing - Google Patents

Abstract

FIELD: medicinal industry, sorbents, medicine.

SUBSTANCE: invention relates to a method for preparing lignin-base enterosorbent. Lignin-containing enterosorbent comprises additionally iodine bound with lignin in the amount 0.4% to the preparation mass, not less. For preparing sorbent hydrolytic lignin is treated with alkali, washed out with water followed by neutralization, condensing suspension to the required content of solid phase and its disintegration and prepared intermediate product is treated with alcoholic or aqueous iodine solution. Treatment with aqueous or alcoholic iodine solution can be carried out before disintegration stage. Treatment with aqueous or alcoholic iodine solution is carried out at temperature 10-80°C for 10-120 min. Using the invention provides preparing enterosorbent in different medicinal formulations with the content of iodine in the preparation 0.4%, not less, and this preparation possesses bactericidal properties. Invention shows simple technology and without using additional expensive equipment and large energetic consumptions. The broad time and temperature intervals in carrying out the process provides developing the necessary technological schedule for the main steps in preparing enterosorbent successively and with regard to specific conditions of manufacturing. Proposed enterosorbent can be used as an agent in treatment of exogenous and endogenous intoxications in surgery, dermatology, therapy, stomatology, gynecology and in veterinary science also.

EFFECT: improved preparing method, valuable medicinal properties of enterosorbent.

3 cl, 12 ex

Description

The invention relates to the medical industry, in particular to the production of an enterosorbent based on lignin, which can be used as a tool for the treatment of exogenous and endogenous intoxications in surgery, dermatology, therapy, dentistry, gynecology, as well as in veterinary medicine.

Known medical enterosorbent based on lignin called lignosorb (analogue polyphepan) and methods for its preparation. The drug is used to treat acute and chronic infectious diseases, metabolic disorders and other disorders of the body, by oral administration, as well as in the form of applications, tampons, using probes, enemas, etc. The therapeutic properties of the drug are due to its ability to adsorb pathogens, various toxins, firmly hold them on its surface and remove from the body in a natural way.

The disadvantage of this drug is that it only adsorbs pathogens, not suppressing their vital functions, which reduces the therapeutic effect due to possible re-infection.

A number of methods are known for producing a medical enterosorbent based on hydrolytic lignin (GL) (A.S. USSR No. 556811, 1977; A.S. USSR No. 803157, 1980; RF Patent No. 919186, 1981; RF Patent No. 1290583, 1985; RF Patent No. 2026078, 1991; RF Patent No. 2116080, 1997) All known methods for producing a medical enterosorbent from hydrolytic lignin are based on the treatment of the latter with an alkali solution followed by washing, neutralizing, and grinding operations aqueous suspensions, dehydration them to various water contents by filtration, centrifugation, and t also possible drying, with the preparation of enterosorbent in various dosage forms: in the form of a powder with a dry particle content of lignin from 20 to 100%, a water-based suspension with a content of 14-20% dry particles of lignin, and in the form of an aqueous suspension containing a dry substance of 8-10 to 13%. The resulting preparation in the form of various dosage forms is subjected to sterilization by one of the known methods: steam, thermal, radiation.

The disadvantages of the methods of obtaining should include the fact that they do not allow to obtain a drug with the necessary microbiological purity and require the introduction of an additional operation - sterilization, carried out in harsh conditions necessary to meet the requirements for microbiological purity, namely, that in 1 g of the finished product with its subsequent use and storage allowed the presence of not more than 10,000 bacterial cells and not more than 100 fungal cells. To achieve such indicators, special equipment for sterilization and high energy costs per unit of production are required.

Also, to preserve the indicated indicators of microbiological purity, preparations must be stored and transported under special conditions at a temperature of no higher than 10 ° C, and in some cases at temperatures from 2 to 5 ° C, which is associated with additional energy and material costs.

The objective of the invention is the creation of an enterosorbent based on lignin, which has an increased therapeutic effect and the necessary microbiological purity due to giving it bactericidal properties. In addition, the task was to develop an economical method for obtaining such a bactericidal enterosorbent.

The problem is solved in that the enterosorbent containing lignin, according to the invention additionally contains associated with lignin iodine in an amount of not less than 0.4% by weight of the drug.

The problem is also solved by the fact that in the method for producing enterosorbent, which includes treating hydrolytic lignin with alkali, washing with water, neutralizing, thickening the suspension to a predetermined solid phase content, disintegrating it, according to the invention, the obtained intermediate is treated with an alcohol or aqueous iodine solution.

Treatment with an aqueous or alcoholic solution of iodine can be carried out before the disintegration operation.

Treatment with an aqueous or alcoholic solution of iodine is carried out at a temperature of 10-80 ° C for 10-120 minutes.

The inventive method differs from the known introduction of a new additional operation - processing the enterosorbent in the form of a suspension, paste or powder with an aqueous or alcohol solution containing elemental iodine, the conditions for its implementation and the exclusion of the stage of sterilization of the final product.

The possibility of obtaining the drug in various dosage forms with the content of iodine associated with lignin in the amount of at least 0.4% by weight of the drug completely ensures the bactericidal effect of the drug and is economically feasible.

Processing the enterosorbent with iodine solutions at a given temperature of 10-80 ° C for 10-120 minutes ensures that almost 100% of the iodine taken to the reaction is attached to the polymer lignin molecule. In this case, the temperature and duration of the reaction are inversely proportional. Lowering the temperature below 10 ° C and increasing the reaction time of more than 120 minutes slow down the process and is impractical and economically disadvantageous.

Obtained according to the claimed technical solution, the drug is a complex compound in which iodine is in a bound state with the polymer molecules of the sorbent - lignin. In contact with the internal environment of the body, with a wound surface, etc. iodine in various conditions is gradually released from the drug - a positively charged ion, molecular iodine, a negatively charged ion, and compounds of iodine with oxygen; all of the above compounds have strong antiseptic properties and a wide range of antimicrobial and fungicidal effects.

Thanks to the additional processing of the enterosorbent with an iodine solution under the claimed conditions, it is possible to obtain a new drug based on lignin, which, along with adsorption, also has bactericidal properties.

Obtaining an enterosorbent containing iodine provides the emergence of qualitatively new properties of the drug, the use of which in the treatment of intoxication allows not only to adsorb pathogens, but also to suppress their biological activity, significantly reducing the likelihood of secondary infection, thereby increasing the therapeutic effect of using enterosorbent.

Another distinctive property of the drug obtained by the claimed technical solution is that it provides a prolonged action of iodine.

The next positive feature of the new drug is that, having bactericidal properties, it can have a different consistency: in the form of an aqueous suspension, paste and powder, which allows to expand the spectrum of its use, especially in surgery, dentistry, gynecology.

An important difference of the proposed technical solution is that as a result of processing the sorbent with iodine, the resulting preparation is already sterile, which allows us to exclude the stage of steam, heat or radiation sterilization from the compared sorbent production technology and thereby reduce the technological cycle, on the one hand, and energy costs - on the other hand.

Also, due to the considerable stability of the drug, the possibility of its storage under ordinary conditions at room temperature is shown, which eliminates the need for refrigeration chambers for storage and transportation, and thereby significantly reduces the material and energy costs of the preparation.

The method is as follows.

Hydrolysis lignin is loaded into the reactor with a mixing device, filled with an alkali solution in an amount of 2-7 hydromodules (the amount of alkali solution in liters relative to the mass of dry lignin in kilograms) so that its working concentration in solution after neutralizing the acid contained in the raw material and diluting it water was 0.5-2.0%. The mixture is heated to 20-100 ° C and maintained for 30-180 minutes, after which the lignin is separated from the alkaline solution, washed thoroughly with water, neutralized with residual alkali with acid, the suspension is concentrated to a dry matter content of lignin to 10-20% by weight and ground to particles ranging in size from 0.005 to 0.25-0.5 mm to obtain an intermediate in the form of a suspension (dry lignin content 10–13%) or water-suspension paste (dry lignin content 14–20%).

To obtain a powder, a suspension of various humidity after grinding is dehydrated by filtration, centrifugation or by drying to a dry matter content of from 20 to 100%.

The obtained intermediates are treated at 10-80 ° C for 10-120 min with alcohol or aqueous solutions containing elemental iodine in an amount that provides a relative content of lignin-bound iodine in the preparation of at least 0.4%.

Obtaining a bactericidal enterosorbent is possible when treated with an aqueous or alcoholic solution of iodine before grinding the suspension with a solids concentration of 10 to 20%.

The invention is illustrated by the following examples.

Example 1. 140 kg of hydrolysis lignin with a moisture content of 65% is poured with 7 hydraulic modules (980 l) of a 1% sodium hydroxide solution, heated with stirring to 80 ° C and kept at this temperature for 30 minutes. Then the lignin is separated from the alkali solution and the components dissolved in it, the remainder is washed with water, the residual alkali is neutralized with 0.5% acetic acid, washed again with water to a normal medium (pH 5-7) and 11% aqueous suspension, which is subjected to grinding to a particle size of 0.01-0.5 mm

10 l of an Iodine solution of 5% concentration obtained by dissolving 0.5 kg of metal iodine in water in the presence of 1.5 kg of potassium iodide (hereinafter, the ratio of iodine: potassium iodide is maintained equal to 1: 3), make in 100 l of suspension with constant stirring. The mixture is heated to 80 ° C, incubated for 10 minutes, then cooled and poured into appropriate containers. The preparation in the form of a suspension with a solids content of 10.45% is subjected to analysis for the content of iodine bound to lignin, which is 4.3% by weight of absolutely dry lignin contained in the suspension, or 0.45% by weight of the preparation. The drug has a bactericidal effect.

Example 2. The method is carried out in the same way as in example 1, only iodine treatment is carried out before grinding the suspension, and the iodine solution is prepared with a concentration of 10%. To do this, 1 kg of metallic iodine is dissolved in the presence of potassium iodide in 8 l of water, the volume is adjusted to 10 l and the resulting solution is mixed with the suspension. The mixture is stirred, the temperature is brought to 30 ° C and held for 80 minutes, after which it is subjected to grinding. The preparation in the form of a 10.9% suspension contains 8.3% of iodine bound to lignin to the mass of absolutely dry lignin, which corresponds to a concentration of iodine in the preparation equal to ≈0.9%. The drug has bactericidal properties.

Example 3. The method is carried out as in example 1, only the suspension is concentrated to a content of 16% of the particles and disintegrated to a particle size in the range of 0.005-0.25 mm to obtain a paste preparation. 100 kg of paste are mixed with 5 l of an aqueous solution containing 0.42 kg of iodine, the mixture is brought to a temperature of 40 ° C and held for 70 minutes. The resulting preparation in the form of a paste contains 2.55% of iodine bound to lignin to the mass of absolutely dry lignin, which corresponds to its concentration in the preparation equal to 0.4%. The drug has bactericidal properties.

Example 4. The method is carried out as in example 3, only the iodine solution for mixing with the paste is prepared not in water but in ethanol, for which 1 kg of iodine is dissolved in 5 l of alcohol. The alcohol solution is mixed with 100 kg of 16% paste and kept at 20 ° C for 100 minutes. The resulting preparation in the form of a 16.2% paste contains 5.9% of iodine bound to lignin to the mass of absolutely dry lignin, which corresponds to its concentration in the preparation equal to 0.95%. The drug has bactericidal properties.

Example 5. The method is carried out as in example 1, only the suspension for disintegration is concentrated to a content of 20% solids, and iodine treatment is carried out before grinding the suspension. For this, 20.0 l of a 10% aqueous solution of iodine is added to a suspension weighing 100 kg, the mixture is thoroughly mixed, kept at 10 ° C for 120 min, and then subjected to grinding. The resulting preparation in the form of an 18.3% paste contains 9.1% of iodine bound to lignin to the mass of absolutely dry lignin, which corresponds to its concentration in the preparation equal to 1.66%. The paste has bactericidal properties.

Example 6. The method is carried out as in example 3, only the suspension is first thickened to contain 20% lignin, and then subjected to grinding to obtain enterosorbent in the form of 20% paste with particle sizes in the range of 0.005-0.25 mm. 5 l of a 20% aqueous solution containing 1 kg of iodine is introduced into the obtained enterosorbent weighing 100 kg with stirring. The mixture was heated to 30 ° C and held for 80 minutes. The resulting paste with a dry matter content of 20% and 4.76% of iodine bound to lignin to the mass of absolutely dry lignin, which corresponds to its concentration in the preparation equal to 0.95%, has bactericidal activity.

Example 7. The method is carried out as in example 1, only a 10% suspension after wet grinding is concentrated by filtration or centrifugation until it contains 40% solids. A part of the 100 kg powder obtained in this way is mixed with 10 L of an aqueous solution containing 0.44 kg of iodine, heated to 50 ° C and held for 60 minutes. The preparation in the form of a wet powder (solids content of 37.6%) contains 1.09% of iodine bound to lignin to the mass of absolutely dry lignin, which corresponds to its concentration of 0.4%. The drug has bactericidal properties.

Example 8. The method is carried out as in example 7, but 100 kg of powder with a content of 40% solids are mixed with 10 l of a 20% alcohol solution of iodine. The mixture is stirred and kept at 20 ° C for 100 minutes.

The preparation in the form of a wet powder (humidity 62%) contains 4.76% of iodine bound to lignin to the mass of absolutely dry lignin, which corresponds to its concentration in the preparation equal to 1.8%. It exhibits bactericidal properties.

Example 9. The method is carried out in the same manner as in example 7, but the obtained wet powder is additionally dried to 80% solids. 20 l of a 20% alcohol solution of iodine are added to 100 kg of such a powder, mixed thoroughly, heated to 70 ° C and held for 40 minutes. The preparation in the form of a powder (humidity 30%) contains 4.76% of iodine bound to lignin to the mass of absolutely dry lignin, which corresponds to its concentration in the preparation equal to 3.34%. The drug exhibits bactericidal properties.

Example 10. The method is carried out as in example 9, but 10 l of an aqueous solution containing 1 kg of iodine is added to the powder. The mixture is stirred and kept at 30 ° C for 80 minutes.

The resulting preparation in the form of a wet powder (humidity 26.4%) contains 1.23% of iodine bound to lignin to the mass of absolutely dry lignin, which corresponds to its concentration in the preparation equal to 0.9%. The drug exhibits bactericidal properties.

Example 11. The method is carried out as in example 9, but the wet powder is dried to 90% solids. Dry powder in an amount of 100 kg is mixed after cooling to 80 ° C with 30 l of an aqueous solution of iodine of 20% concentration and incubated for 10 minutes.

The resulting preparation with a moisture content of 26.2% contains 6.25% of iodine bound to lignin to the mass of absolutely dry lignin, which corresponds to its concentration in the preparation equal to 4.6%. It exhibits bactericidal properties.

Example 12. The method is carried out as in example 11, but the dry powder is cooled to 10 ° C, mixed with 30 l of a 10% alcohol solution of iodine. The mixture was kept at 10 ° C for 120 minutes.

The resulting preparation with a moisture content of 28.5% contains 3.2% of iodine bound to lignin to the mass of absolutely dry lignin, which corresponds to its concentration in the preparation equal to 2.3%. It has bactericidal properties.

In vitro studies have found that iodine-containing enterosorbent showed the greatest activity in relation to crops:

Saccharomyces cerevisiae,

Saccharomyces werneckii,

Aspergillus niger,

Trichophiton mentographytes var. gypseum

Staphylococcus aureus,

Pseudomonas aeruginosa,

Escherichia coli

Salmonella typhi suis

Salmonella cholera suis

Giving enterosorbent based on hydrolytic lignin new bactericidal and fungicidal properties allows its effective use in various fields of medicine, in particular:

- in surgery in the form of paste and powder using the method of application adsorption (vulnerosorption) in the treatment of traumatic, gunshot, purulent, burn wounds, trophic ulcers, etc .; in suspension for washing wounds, cuts, etc .;

- in gynecology in the form of vaginal suppositories, for the treatment of non-specific and fungal vaginitis, trichomoniasis, genital herpes, etc.

- in dentistry and otolaryngology in the form of a suspension, paste for rinsing and lubricating the mouth and throat during infection; after dental interventions;

- in therapy for the treatment of infectious diseases, the gastrointestinal tract, as well as for the replenishment of iodine deficiency in the body in the form of capsules containing 50-100 μg of iodine.

The above examples do not exhaust all the possible uses of the bactericidal enterosorbent.

A toxicological evaluation of iodinated samples of enterosorbent from hydrolytic lignin with a content of 0.5% to 10% iodine in the solid phase carried out on white mice showed that the preparations, when inhaled, contact with the skin and enteric seed, do not have a toxic effect on the organism of warm-blooded animals.

The harmlessness of the iodine-containing enterosorbent in tests on calves and piglets, as well as a high effect in the treatment of acute gastrointestinal diseases in calves and piglets, has also been established: the duration of the disease has decreased by 1.7 times compared with the control where treatment was carried out with antibiotics.

Iodine-containing enterosorbent is recommended for use in the prevention of acute gastrointestinal diseases of young farm animals.

Using the invention allows to obtain enterosorbent in various dosage forms with an iodine content in the preparation of from 0.4%, which has additionally new, namely bactericidal properties. The production technology is simple, does not require the installation of additional complex expensive equipment and high energy costs. The wide time and temperature intervals of the process allow you to develop the necessary technological schedule of the sequentially conducted basic operations for the production of enterosorbent in relation to the conditions of a particular production.

Claims (3)

1. Enterosorbent based on lignin, characterized in that it additionally contains iodine associated with lignin in an amount of not less than 0.4% by weight of the drug. 2. A method of producing enterosorbent, including treatment of hydrolysis lignin with alkali, washing with water, neutralization, thickening the suspension to a predetermined dry lignin content, disintegrating it, characterized in that the intermediate in the form of a suspension or a water-suspension paste or powder is treated at a temperature of 10-80 ° C during 10-120 minutes with an aqueous or alcoholic solution of iodine in an amount that ensures the content of iodine bound to lignin in the target product is not less than 0.4%. 3. The method according to claim 2, characterized in that the treatment with an aqueous or alcoholic solution of iodine is carried out before the disintegration operation.