RU2552336C1 - Agent for treating septic wounds, pus pockets and trophic ulcers - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention represents an agent for treating septic wounds, pus pockets and trophic ulcers containing betaine hydrochloride, methyluracil, trimecaine, pepsin powder and polyethylene oxide 400 with the ingredients taken in certain proportions, wt %, and polyethylene oxide 400 is taken in an amount of 87.0-84.0 ml.

EFFECT: invention provides fastening necrolysis, intensifies bactericidal action, stimulates regeneration, prevents secondary infection.

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Description

The invention relates to medicine, namely to medicines used for local treatment of infected purulent wounds of various localization and etiology in the first (purulent-necrotic), in the second and partially in the third phases of the wound process, infected burns of the II-IV degree, trophic ulcers and long-term non-healing purulent wounds, suppurative residual cavities of the liver and other organs, prevention of infectious and inflammatory complications after echinococcectomy, postoperative and post-traumatic wounds and fistulas, wounds after opening of purulent-inflammatory diseases of the skin and subcutaneous tissue, pressure sores, etc.

According to the literature in medical practice, many different drugs are known that are used in the form of medicines, suspensions and in ointment, which have necrolytic, bactericidal, analgesic, draining, cytoprotective, buffering and regeneration-stimulating effects, used to treat various purulent-inflammatory processes.

All known drugs differ in chemical structure, mechanism of action and pharmacological activity.

Currently widely used drugs in the form of solutions, suspensions and ointments, the main active components of which are obtained chemically.

Analogs of the invention

The following agents and ointments are known:

1) a tool for dissolving necrotic tissues of the following composition: pepsin 5.0-10.0; ascorbic acid 1.0-5.0; lactic acid (96%) 1.0-3.0; urea 10.0-25.0; water 10.0-16.0; hydrophobic base (anhydrous lanolin + lard in a ratio of 3: 1) - up to 100.0; AC No. 439288, issued August 15, 74, class A61K 9/06 (Leontiev-Tyukina A.A.);

2) a drug for the treatment of purulent wounds and trophic ulcers according to the following recipe: pepsin - 15.0; ascorbic acid - 30.0; glucose - 54.25; hydroperite - 0.75; AS No. 1149977, issued April 15, 1985, class A61K 37/57 (Kaplan A.V. and Feigelman S.S.);

3) suspension for the treatment of trophic ulcers and long-term non-healing purulent wounds according to the following prescription: pepsin - 4.0; ascorbic acid - 1.0; hydroperite - 0.1; methyluracil - 4.0; polyglucin - up to 50.0 ml; Patent No. 2160135, issued December 10, 2000, class A61N 5/06, A61K 38/43 (Magomedov M.G., Khamidov A.I., Ramazanov M.R., Dyuzhikov A.A.);

4) Levosin - an ointment in 100.0 g that contains 1.0 g of chloramphenicol, 4.0 g of sulfadimethoxin and methyluracil, 3.0 g of trimecaine, 88.0 g of polyethylene oxide, has an antimicrobial, local anesthetic, anti-inflammatory and stimulating regeneration action, used to treat purulent wounds of various etiologies. Moshkovsky M.D. "Medicines." - 15th ed., Rev., Rev. and add. - M., 2007. - P.815;

5) levomekol - an ointment in which 100.0 g of which contains 0.75 g of chloramphenicol, 4.0 g of methyluracil, 95.25 g of polyethylene glycol, has an antimicrobial, anti-inflammatory effect. Used to treat purulent wounds. Moshkovsky M.D. "Medicines." - 15th ed., Rev., Rev. and add. - M., 2007. - P.815;

Criticism of analogues

The disadvantages of the above medicines should be recognized:

1. Many chemical antiseptic drugs and antibacterial agents used to treat purulent wounds and suppurating residual organ cavities with purulent-septic complications have side effects and their use is often not recommended due to the possible aggravation of developing dystrophic, metabolic disorders in tissues - dysregenerative processes.

2. It is not effective enough, because the drugs used, which, when used separately, have gained certain positions in purulent surgery and individually have weak necrolytic, anti-inflammatory, local anesthetic and antiseptic properties.

3. In some drugs, the optimum pH for pepsin is not sufficiently created due to the use of weak organic acids, the antibacterial and necrolytic activity of the compositions used is insufficient.

4. In the drugs used, the enzyme activity is limited in time due to the rapid alkalization of the wound, due to the lack of buffer additives that stabilize the pH in the wound.

5. In many cases, substances that are capable of exerting a cytoprotective effect on regenerating tissues, which are active stimulants of regenerative processes, are not used.

6. In these methods, the ability to directly supply plastic material to regenerating tissues is not sufficiently used.

7. Hypersensitivity to the components of the agent in the form of allergic reactions and other side effects may be observed.

8. The use of funds and ointments have limitations, since their activity manifests itself differently in relation to certain diseases.

9. With their use, dermatitis, skin rash, itching and irritation of the skin around the wound are noted.

10. Suppresses local immunity with certain drugs that make up suspensions and ointments.

11. The significant cost of modern antibacterial drugs, proteolytic enzymes, requiring large material costs for this pathology.

Prototype of the invention

As a prototype, the closest to the present invention is the combined tool "Necratsidolizin" for the treatment of trophic ulcers and long-term non-healing purulent wounds, patent RU No. 2278689, issued 10.12.2004, class A61P 17/02, A61K 38/48, A61K 38/39, A61K 38/17 (Emirov G.N.).

Prototype criticism

The essence of the prototype.

Means "Necratsidolizin" contains (g / 100 ml of solution): methyluracil - 0.9-1.1; pepsin - 3.6-4.4; betaine hydrochloride - 3.6-4.4; sodium chloride 9.0-11.0; distilled water - up to 100.0; possesses necrolytic, bactericidal, draining, buffering and regenerative stimulating action. Used to treat purulent wounds and trophic ulcers.

However, during the treatment process, the following disadvantages were noted:

- the tool does not have a sufficiently pronounced therapeutic effect;

- possibly local irritating effect, expressed in redness of the skin or mild itching, burning sensation;

- not effective enough, because it has a weak anti-inflammatory, local anesthetic and drainage property;

- It cannot fully provide all the conditions necessary for regeneration, such as: a balanced moist environment, activation of angiogenesis, the ability to accelerate the formation of collagen fibers, granulations and migration of cell epithelium;

- not effective enough in terms of removing excess exudate, preserving moisture and providing gas exchange.

The purpose of the invention

The aim of the invention is the development of a simple, affordable, cheap and effective drug with a wide range of applications. Moreover, it should be free from negative side effects, and the use should not have contraindications and should be affordable and easy to use.

SUMMARY OF THE INVENTION

The essence of the invention lies in the fact that as components of drugs used (g / 100 ml of solution): pepsin - 4.0-4.5; betaine hydrochloride - 4.0-4.5; methyluracil - 3.0-4.0; trimecaine 2.0-3.0; polyethylene oxide-400 87.0-84.0 ml.

The technical problem solved by the proposed drug is to provide effective treatment of purulent wounds, trophic ulcers, suppurative residual organ cavities with purulent-septic complications, etc.

The technical result obtained by the implementation of the proposed drug in the treatment of purulent wounds, trophic ulcers, suppurating residual organ cavities with purulent-septic complications is achieved by accelerating necrolysis, enhancing bactericidal effects, stimulating regeneration, delivering nutrients necessary for anabolic processes directly to regenerating tissues, ensuring the protection of regenerating tissues from local pain and external influences, ensuring the prevention of secondary infection.

Achievement of the indicated technical result consists in local application in the first phase of the wound healing process of the newly proposed agent, conditionally called “Bemetrim", in the following ratio (g / 100 ml of solution): pepsin - 4.0-4.5; betaine hydrochloride - 4.0-4.5; methyluracil - 3.0-4.0; trimecaine 2.0-3.0; polyethylene oxide-400 87.0-84.0 ml.

The method of application of the proposed tool

After standard treatment of wounds and burns, the drug is applied directly to the wound surface with a thin layer (after which a sterile gauze dressing is applied) or on a gauze dressing, followed by application to the lesion. Impregnated tampons loosely fill the cavity of purulent wounds after their surgical treatment, and gauze turundas with the agent are introduced into the fistulous passages. In the presence of a festering residual cavity, a means is introduced into the cavity through the drainage tube in an amount corresponding to the size of the cavity. In the treatment of infected burns, the drug is used daily or 2-3 times a week, depending on the amount of purulent discharge. In the second and partially third phases of the wound healing process, this composition on a gauze dressing is used in conjunction with collagen preparations (most often with a finely chopped medical catgut).

The most effective ratio of drug components in the composition of Bemetrim was determined by experimental studies and numerous clinical observations.

All components of the product are approved for use by the Ministry of Health of the Russian Federation. Moshkovsky M.D. "Medicines." - 15th ed., Rev., Rev. and add. - M., 2007 .-- 1206 p.

The ingredients of the proposed composition when dissolved do not enter into a chemical relationship with each other, which is proved by spectrophotometric method.

Pepsin is a gastric enzyme with the highest proteolytic activity among all other enzymes in the body.

This enzyme belongs to one of the most numerous groups of enzymes - proteolytic enzymes (proteases). They belong to the class of hydrolases, to the subclass of peptide hydrolases and catalyze the breakdown of proteins and polypeptides. Pepsin hydrolyzes peptide bonds and breaks down almost all natural proteins.

As an ingredient of the proposed composition was used the most affordable and cheapest pork pepsin - abomin. In the literature, the authors have not seen data on the possibility of an overdose of pepsin.

Betaine (N-trimethylglycine, oxyneurin, lycine, betafin) is a natural nitrogenous lipotropic substance of plant origin, a derivative of the natural amino acid glycine. It is a readily soluble powder in water. The molecular formula of betaine is C ₅ H ₁₁ NO ₂ , the chemical formula is (CH ₃ ) ₃ N ⁺ -CH ₂ COO ^- (amphoteren preparation).

Betaine molecule contains active methyl groups (CH ^3- ), which are necessary for normal metabolism. The addition of a methyl group (methylation) is an essential step in the most important biochemical reactions.

The human body cannot synthesize methyl groups, but extracts them from food. Due to its direct participation in the methylation reaction, betaine has a great influence, in particular, on lipid metabolism, having a lipotropic effect, since it is close in composition to choline and lecithin. Betaine is involved in the metabolism of methionine.

In addition, betaine acts as an osmoprotector, i.e. helps maintain water balance in cells, tissues and reduces platelet aggregation.

Betaine is used in pharmacology for the treatment of liver pathology, the treatment of alcoholism in toxic poisoning, in the form of nutritional supplements as part of nutraceuticals.

Betaine hydrochloride (or hydrochloride) chemically 1-carboxy-N, N, N-trime-thylmethanaminium chloride. Pure 5% betaine hydrochloride solution has a pH of 1.

Betaine hydrochloride, which dissociates in solution into free betaine and diluted hydrochloric acid with a pH of 2-2.5, is used as part of Acidin-Pepsin tablets for oral administration in order to treat hypacid gastritis in combination with pepsin.

In the literature, data are not known about the possibility of an overdose of betaine and betaine hydrochloride.

Metiuratsil (2,4-dioxi-6-methyl-1,2,3,4-tetrahydropyrimidine). Flavourless white crystalline powder, slightly soluble in water (up to 0.9% at a temperature of 20 ° C) and alcohol. By the chemical structure, methyluracil is a pyrimidine derivative. According to experimental data, a number of drugs of this group (methyluracil, pentoxyl, etc.) have anabolic and anti-catabolic activity. These drugs accelerate cell regeneration processes; accelerate wound healing, stimulate cellular and humoral defense factors. They have anti-inflammatory effects.

Trimecaine is a crystalline powder, white or white with a slight yellowish tint. It is very soluble in water, in alcohol. It is an active local anesthetic. Low toxicity. It does not contain para-aminobenzoic acid, and therefore does not act antisulfanilamide.

Polyethylene oxide-400 - 30% solution for topical treatment of purulent wounds due to high osmotic activity, has a pronounced dehydrating (dehydrating) effect, easily penetrates deep into the tissues, transporting the related drugs that are part of the combined agent. Due to the high hydration activity of the composition in a short time (2-3 days), it usually eliminates perifocal edema and cleanses the wound from purulent-necrotic contents. When used locally on the wound surface they have a bacteriostatic effect, accelerates the healing and healing of the wound. Applied externally, the polyethylene oxide-400 solution does not have a general resorption toxic or locally irritating effect.

For the use of Bemetrim in clinical practice, collagen preparations are added to the composition in the second and partially third phases of the wound healing process.

Collagen is the most common protein in the human body. It is easily lysed by tissue and bacterial proteases with a prolonged release of the preparations contained in them. Decomposing on the wound surface into simpler compounds, collagen metabolites take an active part in metabolism at the cellular level and stimulate reparative processes, and liquid collagen containing collagen hydrolyzate (gelatin) is introduced into the purulent cavity. Collagen contains a large amount of glycine (33%) and proline (10%) - two amino acids, which are the main components of the collagen and elastin molecules that form the connective tissue organs in the human body. Collagen and collagen-containing materials do not have toxic, irritating, antigenic, carcinogenic effects.

The treatment method for this method is developed.

For direct treatment, Bemetrim is prepared ex tempore by mixing weighed portions of the ingredients in a flask followed by the addition of polyethylene oxide-400 - a 30% solution under normal conditions, and does not require sterilization, since it itself has a pronounced bactericidal activity.

According to the proposed method, in the first phase of the wound healing process, in the first 3-5 days after the corresponding toilet of the wound surface or after washing the purulent cavity with an antiseptic under aseptic conditions, 3-4 layer gauze wipes are applied, abundantly moistened with Bemetrim or the agent is introduced into the cavity in an amount of 2/3 of the volume of the washed antiseptic solution in a preferred embodiment: pepsin 4.0; betaine hydrochloride 4.0; methyluracil 3.0; trimecaine 3.0 g; polyethylene oxide-400 86.0 (pH 2.0). The frequency of changing dressings or the introduction of a purulent cavity means is carried out 1 time per day.

Subsequently, after cleansing the purulent wounds or purulent cavities from the necrotic discharge, under aseptic conditions, finely chopped collagen (catgut) or other official collagen-containing dressings are applied to its surface with a layer of 3 mm thick or Liquid collagen is injected into the cavity. The first layer of a gauze dressing (cut according to the contours of the wound surface) of 3-4 layers is superimposed on the collagen layer, abundantly moistened with Bemetrim. A many-hole micro-irrigator is superimposed ring-shaped on top of the napkin, covered by another 3-4 layer dry sterile napkin.

A small amount of Bemetrim, diluted in a ratio of 1: 2, is fed through a microirrigator to the dressing with a frequency of 1-2 times a day, and the purulent cavity before the introduction of Bemetrim in the amount of 2/3 of the volume of the residual cavity with the preliminary addition of Liquid collagen , washed with an ordinary antiseptic solution through a drainage tube with a microirrigator, followed by their closure for 2 hours. Bandages are changed at intervals of 4-5 days.

If a trophic ulcer or purulent wound heals without the use of autodermoplasty, then with the next dressing after soaking the dressing layers in 3% hydrogen peroxide, if necessary, you can add collagen (catgut) finely chopped under aseptic conditions or other offical collagen-containing dressings without removing the collagen film completely remaining on the granulation surface.

In the treatment of infected burns, the drug is used daily or 2-3 times a week, depending on the amount of purulent discharge.

Bemetrim is an effective combination drug for the local treatment of many diseases: infected and purulent wounds of various localization and etiology in all phases of the wound process, infected burns of the II-IV degree, trophic ulcers and long-term non-healing purulent wounds, suppurable residual cavities of the liver and other organs , prevention of infectious and inflammatory complications after echinococcectomy, postoperative and post-traumatic wounds and fistulas, wounds after opening a purulent-inflammatory disease s skin and subcutaneous tissue, decubitus et al., requiring removal of pain, inflammatory reactions and regenerations stimulator. The effectiveness of the tool is ensured by the selection of components that make up its active part, and their quantity.

The terms of treatment compared with well-known drugs are sharply reduced and are only an average of 15 days per course. In this case, there are no side effects, in connection with which the contingent of patients and patients has expanded.

When using this tool, a marked improvement in the general and local clinical status is observed.

The tool can be used both for treatment and for the prevention of purulent-inflammatory reaction of the wound.

The proposed drug "Bemetrim" was tested in the clinic number 6, Makhachkala, the surgical department of the Veterans Hospital of the RMC MH RD, the burn department of the RCH MH RD.

A clinical study of the drug was conducted on 45 patients. With all indications, a positive therapeutic effect was noted. Negative side effects were not observed in any of the cases.

The technical result is achieved through the combined use of the components included in the "Bemetrim", which together allowed to obtain a therapeutic drug with necrolytic, bactericidal, analgesic, draining, cytoprotective, buffering and stimulating regeneration action, which is the basis of its widespread use in treatment many diseases. The authors found that the Bemetrim product contains components in such quantities that, when used together, provide the most pronounced therapeutic effect, and the liquid base used contributes to the effective maintenance of an optimal environment for good wound healing.

The difference between the proposed tool from the prototype is that the tool contains components of drugs known in pharmacology that are used in everyday medical practice. As the components of the drugs used polyethylene oxide-400 - 30% solution, pepsin powder, betaine hydrochloride, methyluracil, trimecain powder and when combined in the proposed combination due to the synergy of their action, a pronounced clinical effect appears, which dramatically reduces the treatment time compared to the known medicines for local treatment.

An example of a specific implementation of the method

The tool proposed as an invention is used in the treatment of infected and purulent wounds of various localization and etiology, infected burns of the II-IV degree, trophic ulcers and long-term non-healing purulent wounds, purulent residual cavities of the liver and other organs, postoperative and post-traumatic wounds and fistulas, wounds after opening of purulent-inflammatory diseases of the skin and subcutaneous tissue, etc., 45 patients in the surgical department of the Veterans Hospital of the RMC MH RD, the burn department of the RCH MH RD, surgical ward an Internet clinic number 6 in Makhachkala. With all indications, a positive therapeutic effect was noted. Negative side effects were not observed in any of the cases.

Example 1. Patient K., 72 years old, came with an extensive purulent wound on his right leg in the lower leg to the surgical department of the Veterans Hospital of the RMC MH RD. Within a week, after a toilet of the wound, a patient with a 3% solution of hydrogen peroxide was put a gauze napkin with Bemetrim according to the procedure adopted in the clinic. At the same time, the dressing was changed once every 5 days, in the subsequent dressing was carried out after the toilet of the wound with a 1.5% solution of hydrogen peroxide on day 6. Dressings were performed without pain of the patient. After 12 days, the wound healed. The patient was discharged for outpatient treatment. Upon repeated examination after a month, the wound healed completely with a tender scar.

Example 2. Patient B., 59 years old, turned to a hospital with long-term non-healing wounds in the region of the lower third of both legs after a car accident. The duration of the wound is 12 months. Before treatment, the patient was treated in the clinic at the place of residence. Upon examination of the patient, it was found that in the lower third of the left lower leg there is a wound with an area of 82 cm ² . On the right lower leg in its lower third there is a wound with an area of 30 cm ² . The bottom of the ulcers is covered with necrotic films, the edges of the wound are saped and hyperemic. During bacteriological examination of the wound discharge, Staphylococcus aureus, sensitive to cefotaxime, ampioks, was found. After the wound's toilet, the patient was put on a gauze napkin with Bemetrim according to the procedure adopted by the clinic for 10 days. On day 11, according to planimetric data, the wound area on the right foot was 13 cm ² , and on the left - 41 cm ² . The patient was discharged for outpatient treatment. Complete wound healing according to follow-up data occurred on the 24th day.

Example 3. Patient M., 62 years old, was admitted to the hospital for planned treatment for a long non-healing wound in the region of the right lower limb against varicose veins of the lower extremities. The duration of the ulcer is 8 years. Before treatment, she was repeatedly treated on an outpatient basis. On examination, the patient found that in the lower third of the right lower leg there is an ulcer with an area of 26 cm ² with profuse purulent discharge; the bottom of the ulcer is filled with flaccid granulations, covered with necrotic films, the edges of the wound are undermined, the skin around with hyperpigmentation phenomena.

The patient was treated according to the claimed drug. On the 10th day of treatment, the wound area was 13 cm ² , on the 20th day there was an almost complete healing of the wound.

Example 4. Patient T., 69 years old, was admitted to the hospital with a diagnosis of venous trophic ulcer in the lower third of the right lower leg along the anteromedial surface measuring 62 cm ² , hyperpigmentation in the lower third of the right lower leg. Local treatment with Bemetrim was carried out for a week. A patient after a wound toilet with a 3% solution of hydrogen peroxide was put a napkin with Bemetrim according to the procedure adopted in the clinic and external elastic compression was performed. At the same time, the dressing changed once a week. Subsequent dressings were carried out after the toilet wounds with 1.5% hydrogen peroxide solution after 4 days. Dressings were performed without pain. After 12 days, the trophic ulcer healed. The patient was discharged for outpatient treatment on day 18 with an almost completely healed ulcer. Upon re-examination after 6 months, the trophic ulcer healed completely with a tender scar.

Thus, as the treatment shows, Bemetrim has a local anti-inflammatory effect, promotes resorption of the inflammatory process, exhibits analgesic and wound healing effects, which with ease of use and the absence of side effects allows the drug to be widely used in outpatient and inpatient settings.

Features of the invention, distinctive from the prototype

1. Means "Bemetrim" has a fairly pronounced therapeutic effect.

2. There is no locally irritating effect on the wound.

3. The drug has a pronounced anti-inflammatory, local anesthetic, antiseptic and wound healing effect.

4. When using the proposed combination of drugs provides all the necessary conditions for regeneration (balanced moist environment, activation of angiogenesis, helps to accelerate the formation of collagen fibers, granulation and migration of cell epithelium).

5. The tool increases lymphatic drainage of tissues (it is proved that increasing the acidity of tissues from 7.35 to 5.9 increases its exudation volume by 20% due to lymph flow, while a 30% polyethylene oxide-400 solution in the mixture stimulates the outflow of tissue fluid with toxic elements and microflora in a bandage).

The positive effect of the application of the invention

The effectiveness of the drug is confirmed by numerous clinical observations.

The proposed tool, unlike other currently known drugs, can improve the results of treatment of patients with purulent wounds of various localization and etiology in all phases of the wound process, infected burns of the II-IV degree, trophic ulcers and long-healing purulent wounds, festering residual cavities of the liver and other organs, postoperative and post-traumatic wounds and fistulas, etc.

The results obtained from the use of this tool allow you to accelerate 1.5-2 times the cleaning of the wound from a purulent-necrotic process; provide rapid elimination of pathogenic microflora due to the bactericidal action of the drug; to activate the wound healing processes due to stimulation of regeneration by multiplying agents and to provide optimal conditions for the mechanism of wound contraction due to the components that make up the drug. The advantage of the proposed tool is confirmed bacteriologically, cytomorphologically, clinically.

The combined use of the components of the composition and collagen preparations in this method leads to a pronounced synergistic effect on the healing of purulent wounds.

Given the low cost of the ingredients used in the composition of the product, one can expect significant economic efficiency from its introduction into clinical practice.

Information sources

Emirov G.N. Combined remedy "Necratsidolizin" for the treatment of trophic ulcers and long non-healing purulent wounds. Patent RU No. 2278689, issued December 10, 2004, class A61P 17/02, A61K 38/48, A61K 38/39, A61K 38/17 - prototype.

Claims (1)

A tool for the treatment of purulent wounds, purulent cavities and trophic ulcers, containing antiseptic drugs and a liquid base, characterized in that it consists of drugs in the following ratios of components, wt. %:
betaine hydrochloride 4.0-4.5 methyluracil 3.0-4.0 trimecaine 2.0-3.0 pepsin powder 4.0-4.5 liquid base polyethylene oxide-400 87.0-84.0 ml