UA65716A - Complex antibacterial sorption composition "benegol forte" for preventing anaerobic infection and treating purulent wounds, neurepathic eschar, and burns, method for its manufacture and application - Google Patents

Abstract

The complex antibacterial sorption composition "Benegol Forte" for preventing the anaerobic infection and treating the purulent wounds, the neurepathic eschar, and the burns is based on the fine pyrogenic silica - aerosil (known under the brands of Sillard P, Polysorb) with immobilized potassium permanganate (èînO4) at the following mass ratio (in %): aerosil (Sillard P, Polysorb) 49.2-98.0 potassium permanganate (èînO4) 2.0-50.8. Upon application to the wound, the preparation is periodically moistened with 3% solution of hydrogen peroxide (ì2O2) until the foamy substance is generated.

Description

The invention relates to new substances based on highly dispersed fumed silica - Aerosil (pharmaceutical trade name Sillard P), containing potassium permanganate (KMpoOx) immobilized on it. After applying the mixture to a purulent wound, trophic ulcer, burn surface and applying a gauze bandage, to increase the effectiveness of the sorbent and better oxygenation of the tissues, the latter is abundantly irrigated with hydrogen peroxide (HgOg). Such a mixture actively inhibits anaerobic and aerobic pathogenic microorganisms, cleans the surface of the wound , improves blood supply to tissues, reduces hypoxia, eliminates unpleasant rotten smell, especially in case of anaerobic infection, has an anesthetic, anti-edematous and anti-tumor effect.

Known commercial drugs used for the treatment of wound anaerobic infection, for example, derivatives of nitroimidazole (metronidazole, tinidazole), dioxidin, clindamycin. Anaerobic gram-positive cocci, Vas.tadiiii5, Vas.teiiIapipodepisivye, and others are sensitive to them (1). Among domestic drugs, nitazol (2-acetylamino-5-nitrothiazole) is very effective in anaerobic infection, which, in addition, shows activity against spore-forming anaerobes (clostridia) (21.

However, all of them do not show an antihypoxic effect, do not have a prolonged effect and therefore do not give a lasting effect in the treatment of anaerobic infection, which in current medical practice is the cause of most complications, which often leads to a fatal outcome in wounds, peritonitis and serial surgical interventions. The closest in terms of technical essence and therapeutic effect is the drug "Imosgent" (ZI, which is a composition that contains a xerogel of methylsilicic acid with the antibiotic gentamicin I4Y1 immobilized on it. This drug exhibits a prolonged antimicrobial effect against pathogenic aerobic microorganisms and is effective for the treatment burns and purulent wounds. At the same time, this drug also has insufficient effectiveness in the treatment of anaerobic and gram-positive infections, does not improve tissue blood supply, does not have an antihypoxic effect. In addition, most microorganisms have developed acquired resistance to the main active ingredient of the drug, gentamicin, which makes the drug is ineffective in many cases. The drug Imosgent is prepared by impregnating a xerogel of methyl silicic acid with a solution of gentamicin, followed by drying the composition at temperatures below 502C, in order to prevent the deactivation of the antimicrobial action of the active component - the antibiotic gentamicin (4).

The purpose of this invention is a composition based on highly dispersed fumed silica - Aerosil (pharmaceutical trade name Sillard P) and potassium permanganate (KMpO4) immobilized on it for the treatment of aerobic and anaerobic infection, which would have an increased preventive and curative effect, clean the wound surface, improve blood supply tissues, eliminated the unpleasant putrid smell, especially in anaerobic infection, had an anesthetic and anti-edematous effect, which is achieved by enhancing the effect of the sorbent by treating the latter after applying it to the wound with a solution of hydrogen peroxide (HgO), as well as the method of obtaining the composition and its application using hydrogen peroxide ( NgOg) as a wetting and activating agent.

The set goal is achieved by the fact that the composition (Benegol Forte), which includes highly dispersed fumed silica - Aerosil (trade pharmaceutical name Sillard P), contains potassium permanganate (KMpoO»x) immobilized on it with the following composition of components in 9% by weight:

Aerosil (Sillard P,

Polysorb) from 49.2 to 98.0

Potassium permanganate (KMpOa) from 2.0 to 50.8

Hydrogen peroxide (HgOg) Omapsht Zayiv

After applying the mixture to the wound and applying a gauze bandage, the latter is constantly or periodically moistened

With a solution of hydrogen peroxide (HgO") until the formation of a foamy mass.

Such a composition was not known before.

Aerosil is highly dispersed pyrogenic silica consisting of hydrated spherical particles. . . - I'm sorry. with an average radius of 4.35 nm, an airgel of polysilicate acid composition, the water content can reach 10 wt.9o. Aerosil is approved for oral use as an enterosorbent and as a matrix for the immobilization of drugs.

The composition is prepared in the following way: 1) preparation of a solution of potassium permanganate from 0.1 to tOmas.9o; 2) mixing Aerosil powder with permanganate solution, which are taken in appropriate quantities; 3) maturation of the mixture at a temperature of 15-2570 for 20-30 minutes; 4) drying the mixture at a temperature of 90-1007C until a dry loose powder is formed; 5) after applying the composition to the wound surface, it is periodically or constantly moistened with a solution of hydrogen peroxide (HgOg) until a foamy mass is formed.

Below are examples of specific preparation of Benegol Forte.

Example 1 "Benegol Forte 1". Add 100 ml of 0.295% potassium permanganate (KM) solution to 10 g of aerosol (Sillard P), stir the mixture for 15 minutes until a homogeneous substance is formed and leave to mature for 20 minutes at a temperature of 20 "C. The resulting mixture was transferred to a glass plate or cup Petri dish and dried at a temperature of -90-100"C in a drying cabinet until a dry loose powder of pink color is formed.

The resulting powdery preparation was transferred to a glass jar with a capacity of 25 ml and tightly closed with a polyethylene lid.

The yield of the drug is 10.2 g.

After applying the mixture to the wound and applying a gauze bandage, the latter is constantly or periodically moistened

With a solution of hydrogen peroxide (HO) until the formation of a foamy mass. It is used for the treatment of second-stage burns, superficial wounds, trophic ulcers, does not cause pain.

Example 2

"Benegol Forte 1". Add 20 ml of a 0.595% potassium permanganate (KM) solution to 2 g of aerosol (Sillard P). The mixture was stirred for 10 minutes until a homogeneous substance was formed and left to mature for 30 minutes at a temperature of 20 "C. The resulting mixture was transferred to a glass plate or cup Petri dishes and dried at a temperature of 90-1007C in a drying cabinet until a dry loose powder of violet color was formed.

The resulting powdery preparation was transferred to a glass jar with a capacity of 10 ml and tightly closed with a polyethylene lid.

The output of the drug is 21 g.

After applying the mixture to the wound and applying a gauze bandage, the latter is constantly or periodically moistened

So-called solution of hydrogen peroxide (HO) until the formation of a foamy mass.

It is used for the treatment of second-stage burns, superficial wounds, trophic ulcers, does not cause pain.

Example From "Benegol Forte 1". Add 100 ml of 1.095% potassium permanganate (KM) solution to 9.0 g of aerosil (Sillard P). The mixture was stirred for 15 minutes until a homogeneous substance was formed and left to mature for 30 minutes at a temperature of 20 "C. The resulting mixture was transferred to a glass plate or a Petri dish and dried at a temperature of -90-1007"С in a drying cabinet until the formation of a dry loose powder of a dark violet color.

The resulting powdery preparation was transferred to a glass jar with a capacity of 25 ml and tightly closed with a polyethylene lid.

The output of the drug is 10.Og.

After applying the mixture to the wound and applying a gauze bandage, the latter is constantly or periodically moistened

So-called solution of hydrogen peroxide (HO) until the formation of a foamy mass.

It is used for the treatment of second-stage burns, superficial wounds, trophic ulcers, does not cause pain.

Example 4 "Benegol Forte 2". To 8.0 g of aerosol (Sillard P) add 8 Oml of a 2.095 solution of potassium permanganate (KM). The mixture was stirred for 20 minutes until a homogeneous substance was formed and left to mature for 20 minutes at a temperature of 23"C. The resulting mixture was transferred to a glass plate or a Petri dish and dried at a temperature of -90-1007"С in a drying cabinet until the formation of a dry loose powder of a dark violet color.

The resulting powdery preparation was transferred to a glass jar with a capacity of 25 ml and tightly closed with a polyethylene lid.

The output of the drug is 10.Og.

After applying the mixture to the wound and applying a gauze bandage, the latter is constantly or periodically moistened

So-called solution of hydrogen peroxide (HO) until the formation of a foamy mass.

It is used for the treatment of second-stage burns, superficial wounds, trophic ulcers, does not cause pain.

Example 5 "Benegol Forte 2". Add 52 ml of 5.095% potassium permanganate (KM) solution to 5.0 g of aerosol (Sillard P). The mixture was stirred for 20 minutes until a homogeneous substance was formed and left to ripen for 30 minutes at a temperature of 2570. The resulting mixture was transferred to a glass plate or cup Petri dishes and dried at a temperature of -90-1007"C in a drying cabinet until a dry loose powder of dark violet color was formed.

The resulting powdery preparation was transferred to a glass jar with a capacity of 10 ml and tightly closed with a polyethylene lid.

The output of the drug is 7, bg.

After applying the mixture to the wound and applying a gauze bandage, the latter is constantly or periodically moistened

So-called solution of hydrogen peroxide (HO) until the formation of a foamy mass.

It is used for the treatment of purulent wounds, burns of the P-IM stage of necrotic trophic ulcers. Destroys the smell, cleans the wound from pus, necrotic tissues.

Example 6 "Benegol Forte 2". Add 52 ml of 10.095% potassium permanganate (KM) solution to 5.0 g of aerosol (Sillard P), stir the mixture for 20 minutes until a homogeneous substance is formed and leave to mature for 30 minutes at a temperature of 20"C. The resulting mixture was transferred to a glass plate or a Petri dish and dried at a temperature of -90-1007"С in a drying cabinet until the formation of a dry loose powder of a dark violet color.

The resulting powdery preparation was transferred to a glass jar with a capacity of 25 ml and tightly closed with a polyethylene lid.

The yield of the drug is 10.0 g

After applying the mixture to the wound and applying a gauze bandage, the latter is constantly or periodically moistened

So-called solution of hydrogen peroxide (HgOg) until the formation of a foamy mass.

They are used for the treatment of very purulent wounds, burns of the PI-IM stage of necrotic trophic ulcers. Destroys the smell, cleans the wound from pus, necrotic tissues.

Description of chemical reagents Hydrogen peroxide: Ngog reducer and oxidizer with the formation of free oxygen in tissues, a weak antiseptic, used in the form of a 395 aqueous solution, has a weak bactericidal effect. Cleans purulent wounds mechanically from pus, dead tissues, blood clots, and bacteria. In a fresh wound, it accelerates blood clotting, is used for hemostatic purposes. It is especially widely used in the treatment of wounds caused by anaerobic infection. In large concentrations, more than 3905, it is not used because it causes tissue necrosis.

Potassium permanganate: KMpO4 is an oxidant, an antiseptic, its crystals are well soluble in water. When reduced, it forms manganese oxide MpO", which forms albuminates with tissue proteins, as a result of which, in small doses and concentrations, it has a viscous and caustic effect. It is used in the treatment of burns - 295-595 solution, rinsing of the oral cavity, bladder - 0.595-195 solution. It is a means that destroys unpleasant odors. Bactericidal activity is characteristic only of strong solution 295-595.

Aerosil (Sillard P) is a highly dispersed pyrogenic silica consisting of hydrated spherical particles with an average radius of 4.35 nm, an airgel of polysilicic acid with a composition of ЖИ хНГО, the water content can reach 1Omas.9o. Adsorbent of destructive protein substances. Aerosil is approved for oral use as an enterosorbent and as a matrix for the immobilization of drugs.

Description of the chemical reaction of the proposed complex composition. p. . . oh, oh, BUT" ; KMpO in . ry mixing aqueous solutions of 395-595 hydrogen peroxide ( ) with potassium permanganate ( ) in powder, - - KMpO, nyo" formed during adsorption, on sorbents followed by irrigation of the wound with hydrogen peroxide ( ), or in bathtubs, by draining these solutions - a multi-stage process takes place , a redox chemical reaction with the formation of intermediate reaction products, chemically active oxygen.

The chemical reaction takes place in three stages:

NgO» -2MpO4 - 2MpO»o -2OH 202 and 2NeO»z (MpOzg) -22H20 05 T in 2HgO2 catalase -» 2H20 2 t p HO»: - . hydrogen peroxide ( ) enters into these reactions with the formation of a reactive form of oxygen (singlet, etc.) and water in a neutral environment. Potassium permanganate (КМпОа) is an oxidizing agent and is reduced to manganese dioxide (MO), which is a catalyst for the following reaction: 2НгО02 МпОо -з3 НгО 4 О2

It follows from this reaction that to increase the effectiveness of this solution, an excess of hydrogen peroxide (H2O2) and an optimal ratio of potassium permanganate (KMpod and Ngog hydrogen peroxide 1:8.

Mechanism of chemical reaction in a wound

The use of one potassium permanganate in a purulent wound has a weak bactericidal effect due to the small formation of oxygen, and large concentrations cannot be used due to the coagulating effect on the tissue

Private sector". This does not happen in the "popsicle" suspension (agerosyl-KMpO4-H2gO»2), even when using high contents in the composition of KMpOd due to the dilution of the latter with a 339% solution of hydrogen peroxide and mutual neutralization of the components.

In neutral and alkaline solutions, hydrogen peroxide reduces permanganate to Mp, which falls as a brown precipitate: IbI: 2МпОХд - НО» -252mМпО» 4205 -2ОоН

The ratio of solutions of hydrogen peroxide 395 and potassium permanganate on the adsorbent in the applied reaction can reach 8:1 or more. This ratio has high bactericidal and biological activity, does not cause damage to the wound, approved by the Pharmacocommittee of the Ministry of Health of Ukraine.

Method of obtaining

Benegol Forte I synonyms :(Agnosil Forte I) 5 g of Aerosil (Sillard P, Polysorb) pour 50 ml of a solution containing 0.2 g of potassium permanganate (KMpOa) and thoroughly mix the resulting mushy mass, which is then dried at 100-1107С for 12 hours to the formation of a dry loose powder of a dark violet color.

Benegol Forte 2 synonyms: (Agnosil Forte 2) 5 g of Aerosil (Sillard P, Polysorb) are poured into 50 ml of a solution containing 1 g of potassium permanganate (KMpoh) and the resulting slurry is thoroughly mixed, which is then dried at 4100-1107 for 12 hours until a dry loose powder is formed dark fawn color.

We have established that for the preparation of the drug "Benegol Forte 1", which is used for the treatment of burns of the second stage, superficial wounds, trophic ulcers, solutions of potassium permanganate (KMpoh) no more than 195 can be used. For "Benegol Forte 2", which used for the treatment of very purulent wounds, burns PI-

IM stage of necrotic trophic ulcer - no more than 1095 potassium permanganate solution (КМпО4). The advantage of the drug when used together with hydrogen peroxide over the individual components is: - firstly, in the use of the beneficial properties of each of the components - potassium permanganate and hydrogen peroxide as antimicrobial disinfectants, in addition to permanganate as an odor killer and aerosol as an adsorbent of pathogenic residues bacteria and products of destruction of rotten and necrotic tissues; - secondly, in reducing the effective concentration of permanganate in the contact solution to prevent burns of healthy tissues (permanganate consumption is regulated by interaction with hydrogen peroxide and slow desorption from the adsorbent on which it is immobilized);

- thirdly, in reducing the effective concentration of hydrogen peroxide due to its oxidation with permanganate and, as a result, preventing burns of healthy tissues with peroxide; - fourthly, in the peroxidation of lipid membranes of pathogenic bacteria and their effective destruction by active forms of oxygen (singlet oxygen, peroxide radical, etc.), which are formed as a result of the reaction of permanganate and hydrogen peroxide, as well as abundant oxygenation of tissues, which saves healthy tissues from harmful anaerobes (b|.

In the invention, by oxidizing it with potassium permanganate, the previously used oxygenating properties of hydrogen peroxide are enhanced as a result of its decomposition with the release of oxygen under the action of the blood peroxidase enzyme.

Moreover, the consumption of permanganate practically does not affect the rate of its decomposition, since as a result of the reaction of permanganate with peroxide, manganese oxide (IM) is formed, which also decomposes hydrogen peroxide with the release of oxygen, being the catalyst of this reaction.

As a result of the reaction of pharmaceutical solutions used in medicine, in particular in surgery: 3-590 solution of hydrogen peroxide (H2O2 and 1-595 solution of potassium permanganate (KMpOg), when mixed with the help of a sorbent, a chemical multistage redox reaction occurs, depending on acidity of the environment (pH), with the formation of intermediate reaction products, biologically active substances, including chemical radicals: oxygen (Og2 - singlet oxygen, OH - hydroxyl radical, HO" - superoxide radical, and Mn" - singlet manganese).

Biologically active forms of oxygen cause processes in the wound and in the patient's body, which contribute to the rapid cleaning of the wound, the destruction of the infection, accelerated healing and recovery.

The antimicrobial effect of the composite drug "Benegol Forte" (origin of the abbreviation: Belyaeva,

Nevzglyad, Golub) were studied in relation to microorganisms that are in the wound, and specifically their number per 1g of tissue. After one procedure, the number of microorganisms in the wound is significantly reduced below the critical level, and after using the specified drug for 2 days, in 6395 cases, microorganisms were not obtained in the patient's wound, which indicates the high antimicrobial effect of Benegol.

Drug for external use in the form of a red-purple powder, used for intensive therapy of purulent wounds, burns and trophic ulcers in a composition with a 396th solution of hydrogen peroxide (HO

Composition: 1 g of the drug contains:

Potassium permanganate (KMpOa) 0.5-0.02 g

Aerosil (Sillard P) 0.5-0.98 g

Hydrogen peroxide (202 ) Otsapsht vzaiyev

The drug is an adsorption mixture of substances known in medical practice. "Benegol Forte 1" was used in 11 patients with superficial trophic ulcers, burns of the 1st stage, purulent wounds in the granulation stage. "Benegol Forte 2" was used in 9 patients with purulent wounds in the stage of necrosis, gangrene in diabetes, abscesses, trophic ulcers with necrosis, etc. After applying the mixture to the wound and applying a gauze bandage, the latter is constantly or periodically moistened with a 3-6b95 solution of hydrogen peroxide (Neo) until a foamy mass is formed.

Example 1

Patient A, born in 1936, was hospitalized for a 2nd degree thermal burn of the lower extremities. After surgical treatment of the burn surface, a powdered mixture of Benegol Forte 1 was applied to the wound surface. After applying the mixture to the wound and applying a gauze bandage, the latter was constantly applied (for the first hour to relieve the painful syndrome), and then it was periodically moistened 3-6b9u5o with a solution of hydrogen peroxide ( ) until the formation of a foamy mass with subsequent repetition during the day up to 6-8 times a day.

On the second day, a culture was made from the wound surface - no microorganisms were obtained. The wounds healed completely on the 10th day. Recovery.

Example 2

Patient N., born in 1934, was hospitalized for chronic venous insufficiency of the lower extremities, complicated by a huge trophic ulcer covered with necrotic tissues, with an unpleasant odor. V. MeIapipodepisiv, 5Y, was obtained during microbiological research. Ashgai5. Benegol is applied to the wound surface

Forte 2 with periodic wetting 8-10 times a day with a solution of hydrogen peroxide. After 3 days, the unpleasant smell disappeared, the temperature decreased. The patient's condition gradually improved, Benegol Forte 2 was repeatedly applied to the wound. The ulcer healed after 25 days. Previously, the patient was treated several times, but the ulcer did not heal. Recovery.

In connection with the above, the new drugs Benegol Forte 1 and Benegol Forte 2 can be used for the prevention and local treatment of aerobic and anaerobic infections in complicated wounds of various genesis.

Literature. 1. Blatun L.A., Yakovlev V.P. Modern aspects of general and local antibacterial therapy of anasrobes infection of soft tissues // Tez. acc. All-Union symposium "Anaerobic non-clostridial infection in purulent surgery. - Ternopil - 1989. - P. 6-8. 2. Mashkovsky M.D. Medicines, - Kharkiv, Izd. Thorsing -1997. - 1 volume, p. 268; Afinogenov G.E.,

Elinov I.P. - Antiseptics in surgery. - L.: Medicine. - 1987 -1446 b.

Z. Znamensky V.A. and others. Use of therapeutic and prophylactic drugs made on the basis of organosilicon adsorbents. Methodological recommendations. - K.: UKOTStsaANDYSI. -1992. -16 b. 4. A.A. Shalimov and others. Method of treatment of purulent wounds // A.s. USSR Me1144699 with priority dated November 15, 1984 (prototype) 5. Chemistry and technology of hydrogen peroxide, edited by G. F. Serisheva, Leningrad. - "Khimiya". - 1984 - p. I5-16. b. Botsipai-U/aisnp R. Oesotrovziop de Geatsy ohudepee rag Ie reppapdapaiye tiiiie Basidie. -). sleep Voi., 1953, my.

BOLYO, r/ 527-544.

Claims (3)

1. A complex antimicrobial sorption preparation for the prevention of anaerobic infection and the treatment of purulent wounds, trophic ulcers and burns, which is a silica sorbent with a drug immobilized on it, which differs in that aerosol is used as a sorbent, and potassium is used as a drug immobilized on it permanganate (KMpO»x) with the following composition of components, wt. 90: Aerosil (Sillard P, Polysorb) 49.2 - 98.0 potassium permanganate (KMpOkha) 2.0 - 50.8. 2. The method of obtaining a complex sorption preparation for the prevention of anaerobic infection and the treatment of purulent wounds, trophic ulcers and burns, which differs in that 0.2 to 10.0 wt.9% potassium permanganate solution (KMpoOzh) is added to the aerosol powder with thorough mixing , mix 10 g of powder and from 80 to 100 g of a solution in a solvent indifferent to potassium permanganate (КМпО4), with a content of potassium permanganate (КМпОх) from 0.2 to 10 g, until a homogeneous substance is obtained, the obtained substance is kept for ripening at a temperature of 15 to 25"C for 20-30 minutes followed by drying at a temperature of 90 to 1007C. 3. The method of using a complex sorption preparation for the prevention of anaerobic infection and the treatment of purulent wounds, trophic ulcers and burns, which differs in that, after applying to the wound, the dry aerosol powder with immobilized potassium permanganate (KMpOyh) is constantly or periodically moistened with a 395 solution hydrogen peroxide (HgOg) to form a foamy mass.