RU2203061C1 - Method for treating wounds and cutaneous wound infection - Google Patents

Abstract

FIELD: medicine, surgery. SUBSTANCE: at phase of inflammation one should cover the wound with sterile gauze napkins, impregnate with combined chemotherapeutic preparation containing, g: quinosol, 0.5; streptomycin, 1.5; polyethylenoxide-400, 753.0; polyethylenoxide-500, 187.0; sterilized distilled water, 58.0. Bandages should be carried out daily till complete purification against purulent-necrotic masses. Then wound surface is treated with combined chemotherapeutic preparation containing, g: quinosol, 0.5; streptomycin, 1.5; and water-free lanolin, 500.0; sterile distilled water, 498.0; applied under the bandage. At phases of regeneration and epithelization wound surface should be treated with combined chemotherapeutic preparation named "Butol". The latter should be applied onto granulating wounds by using collagen sponge, placenta or amniotic liquid. Bandages are carried out as biomaterial resolution takes place. EFFECT: higher efficiency of therapy. 1 cl

Description

 The invention relates to medicine, in particular, can be used to treat wound surfaces, including long-term non-healing wounds, trophic ulcers, wounds after a burn injury, including extensive ones.

 The most important provision of the modern treatment of wounds and wound infections is the proven fact of the common biological laws of wound healing of any genesis and localization (Wounds and wound infection: a Guide for doctors. / Ed. By M.I. Kuzin, B.M. Kostyuchenok. - 2nd ed., rev. and add. - M .: Medicine, 1990. - S. 38-82).

 All wounds, regardless of etiology, heal according to general laws (unity of pathogenesis), which can be schematically represented as phases of the wound healing process: 1 - inflammation (vascular changes, cleansing), 2 - regeneration, 3 - scar reorganization and epithelization.

 Medicines used in the 1st phase should have antimicrobial, dehydrating, necrolytic and possibly analgesic effects, i.e., help suppress microflora and speedy wound cleansing, thereby creating conditions for subsequent repair.

 The experience of using the most common preparations for topical treatment of wounds under a dressing (antiseptics, chemotherapy, antibiotics, dehydrating and necrolytic agents) in manufactured dosage forms (powders, aqueous solutions, ointments based on grease, aerosols) in the 1st phase of healing showed their insufficient effectiveness .

 The second phase of the wound process, or the phase of regeneration, is characterized by the development of granulation tissue, gradually filling the wound defect. It begins to form in the form of separate sections at the bottom of the wound, while the main value during the proliferation period is acquired by the capillary endothelium and fibroblasts. Forming collagen fibers, they provide wound healing. Formulating the basic requirements for dressings for the phases of regeneration and epithelization, it should be noted first of all that they should provide conditions for the growth of granulation tissue and epithelium, exclude secondary infection and suppress the microflora growing in the wound, ensure normal vapor exchange of wound tissues, and adhere tightly to the wound surface create an environment for migration and differentiation of cellular elements.

 The treatment of wounds in the third phase (epithelization) has tasks similar to those in the second phase, which are to protect against the harmful effects of granulation tissue and stimulate the epithelization process.

 There is a method of treating trophic ulcers and non-healing wounds based on autodermoplasty - transplanting your own skin on the wound surface (Grigoryan A.V., Gostishchev V.K. Tolstykh P.I. Trophic ulcers. - M.: Medicine, 1972. - 207 p.). However, this method is not without drawbacks such as causing additional trauma when taking a graft, necrotization and resorption of the skin flap, since in the area of trophic disorders, due to impaired vascular tissue permeability, squeezing of capillaries with scar tissue and other manifestations of disorders of vascular and nervous trophism, unfavorable conditions for the engraftment of skin grafts are created. The percentage of failures ranges from 2.7 to 20. Often contraindications for surgical intervention are advanced age and concomitant diseases, as well as patients' disagreement for surgery.

 The closest in technical essence and the achieved result is a method of treating trophic ulcers and long-term non-healing wounds (Collagenoplasty in medicine. Edited by VV Kovanov and IA Sychenikov. - M.: Medicine, 1978, pp. 50-83 , 92-180). In the inflammation phase, this method used the enzymes trypsin, chymotrypsin, as well as lotions from a 2% solution of boric acid. Dressings were performed every other day until ulcers cleansed and inflammation disappeared.

 In the phase of regeneration and epithelization, collagen films and collagen sponges were used. Films were obtained by drying in air a thin layer of a collagen solution. Prepared collagen films after washing the ulcer surface with a solution of hydrogen peroxide were applied to the granulating surface, covered with wet wipes moistened in an isotonic sodium chloride solution to prevent drying of the wound surface. Dressings were performed after 2-3 days, during which the dressing was re-wetted with an isotonic sodium chloride solution. As the collagen was resorbed, a new preparation was applied. The use of collagen films in the clinic has shown their effectiveness in the treatment of trophic ulcers and long-term non-healing wounds of various etiologies. Collagen preparations help cleanse the ulcer surface, reduce inflammation and enhance reparative processes, thereby accelerating wound healing.

 However, in this method, treatment with collagen films required the systematic wetting of the dressing, since when applied to the wet surface of the ulcer, the dressing subsequently dried up, especially with scanty discharge, and lagged from the surface of the ulcer, causing unpleasant pain. In addition, a constantly wet dressing in some cases, in violation of the trophism of surrounding tissues, caused maceration of the skin around the ulcer. It is important to note that the need to wet the dressing also created certain difficulties for using elastic compression.

 The use of collagen sponges in the known method did not require re-wetting of the dressing with an isotonic sodium chloride solution, and also due to its hydrophilicity, the sponges sucked off ulcers. Collagen sponges absorbed by 4-5 days. To prevent secondary infection in a known method, collagen preparations were mixed with antibiotics (monomycin, tetracycline, mycerin, oxacillin). Collagen films with the antibiotic monomycin possessed the greatest antibacterial activity in the experiment. In clinical practice, collagen sponges containing furacilin and boric acid as antiseptics were used. The average duration of ulcer healing in patients who used collagen preparations as local treatment was 30 days, while in the control group of patients with traditional treatment it was 43 days.

However, the use of collagen sponges without the content of antiseptics often causes a secondary infection. And in cases where collagen preparations were used together with antiseptics, the method of conventional mixing of collagen with antibiotics and antiseptics before drying in air (in the case of a film) and by lyophilization (in the case of a sponge) is time-consuming, does not provide the formation of stable intermolecular bonds and thus the prolongation of the directed action of the drugs is very relative. The use of antibacterial monopreparations does not always allow affecting the entire spectrum of diverse flora in the wound. The antibiotic monomycin, which is actively used in the experiment, is discontinued. In addition, the treatment of extensive trophic ulcers and long-term non-healing wounds of the skin (wound area is more than 50 cm ² ), including using collagen coatings, remains an unresolved problem. The treatment of patients with trophic ulcers and non-healing wounds in combination with diabetic angiopathy due to poor effectiveness is a very urgent problem.

 Developed by Academician D.S. Sarkisov et al. biotechnologies based on the use of fibroblast cultures, which are the main cellular unit of the dermis and intimate relationships associated with the epidermis, have achieved good results in the treatment of burn injury (Sarkisov D.S., Glushchenko E.V., Morozov S.S. et al. / / Bulletin of experimental biology. - 1991. - 5. - S. 542-544).

 The use of fibroblasts is based on the fact that they proliferate and synthesize collagen, fibronectin, which stimulates the adhesion of keratinocytes and the proliferation of these cells. In addition, fibroblasts are a factor in the differentiation of keratinocytes and the formation of their intercellular connections. However, the treatment of wound surfaces with trophic ulcers and long-term non-healing wounds using a culture of fibroblasts is an unresolved problem.

 The technical result, the achievement of which the creation of this invention is directed, is to increase the efficiency of treatment of patients with wound surfaces and expand functionality by treating non-healing wounds, trophic ulcers, wounds after burn injury, including extensive ones, and shortening the length of hospital stay of patients .

 The technical result is achieved by the fact that in the method of treating wounds and wound infections of the skin, based on the use of combined antimicrobial agents, collagen preparations and cell culture on the wound process, depending on its phase, degree of damage and the area of the wound surface, in the phase of inflammation of the wound process the wound is covered with sterile gauze napkins impregnated with a combined chemotherapeutic agent containing quinosol 0.5 g, streptomycin 1.5 g, polyethylene oxide-400 753.0 g, ietilenoksid-1500 187.0 g, distilled water of 58.0 g of sterile, producing ligation daily until purification from necrotic masses; then, on a wound surface of the skin, once every 2-3 days, a combined chemotherapeutic agent is applied, evenly under a bandage, consisting of quinosol 0.5 g, streptomycin 1.5 g, anhydrous lanolin 500.0 g, distilled sterile water 498.0 g and in the phases of regeneration and epithelization after treatment of the wound surface with the combined chemotherapeutic agent “Butol”, collagen-containing preparations, for example, collagen sponges, placentas or amniotic membranes, saturated combined, are applied to granulating wounds with chemotherapeutic agent Butol, performing dressings as the biomaterial is absorbed, and with extensive wound surfaces in the phases of regeneration and epithelization, a culture of fibroblasts and keratinocytes is applied to the wound surface. Cell culture transplantation is carried out independently, or in combination with collagen-containing preparations, or in combination with autodermoplasty.

 A method of treating wounds and wound infections is as follows. In the phase of inflammation of the wound healing process, the wound is covered with sterile gauze napkins impregnated with a combined chemotherapeutic agent containing quinosol 0.5 g, streptomycin 1.5 g, polyethylene oxide-400 753.0 g, polyethylene oxide-1500 187.0 g, distilled sterile water 58, 0 g. This tool has a pronounced antibacterial, anti-inflammatory, dehydrating properties, good penetration into the tissue, prolonged action. Dressings to patients are performed daily until the wound is cleansed of purulent-necrotic masses. Then, in the late stages of the transition of the wound healing process to the regeneration phase and to chronic skin defects without any obvious signs of inflammation of the skin, a combined chemotherapeutic agent consisting of 0.5 g of quinosol and 1.5 g of streptomycin is applied once every 2–3 days. , anhydrous lanolin 500.0 g, distilled sterile water 498.0 g to completely clean the wound surface, eliminate inflammation in the wound and start an active regenerative process in the wound. This chemotherapeutic agent has a high antibacterial and anti-inflammatory activity, prolonged action, high penetration into tissues, stimulating regeneration. In the phases of regeneration and epithelization, after treatment of the wound surface with the combined chemotherapeutic agent Butol, collagen-containing preparations are applied to granulating wounds, for example collagen sponges, amniotic membranes, placenta, saturated with ultrasonic vibrations with the combined chemotherapeutic agent Butol, completely covering the granulating wounds and from above applying an aseptic dressing. Collagen sponges, amniotic membranes absorbed by 3-4 days, the placenta by 6-7 days. Dressings in these phases are performed as the biomaterial is resorbed. Collagen-containing preparations (collagen sponges, amniotic membranes, placenta), saturated with the combined chemotherapeutic agent Butol (RF patent 2115418, MKI 6 A 61 K 31/47, 31/71, published in IPM Bulletin 20 July 20, 1998), made on the basis of the Central Research Laboratory of Samara State Medical University. And with extensive wound surfaces with trophic ulcers, non-healing wounds in the regeneration and epithelialization phases, a culture of fibroblasts and keratinocytes, cultured in the cell culture department of the Central Research Laboratory of the Samara State Medical University, is applied to the wound surface. Cell culture transplantation is carried out independently or in combination with collagen-containing preparations (collagen sponge, amniotic membrane, placenta) or in combination with autodermoplasty.

 The average duration of treatment of patients with trophic ulcers and long-term non-healing wounds according to our method was 23.3 ± 5.2 days, while in patients who used traditional local treatment, 47.1 ± 6.8 days.

 Local treatment of patients with trophic ulcers resulting from chronic obliterating diseases of the arteries, according to the proposed method, was carried out after reconstructive operations on the affected vessels in combination with pathogenetic general therapy.

 In the treatment of superficial wounds of the skin, which are small in size, “clean” (without detachable, odorless), with smooth edges, and having a short period from the moment of appearance, it was enough to use only collagen-containing preparations with the antiseptic “Butol”.

 Separately, I wanted to highlight the good effect obtained by treating patients with trophic ulcers and long-term non-healing wounds in combination with diabetic angiopathy in this way.

 The proposed method for treating wounds and wound infections was used in the treatment of burn surfaces in the same sequence as preparing a wound for an autoskin transplant. An infected burn in the inflammatory phase was treated with combined antimicrobial agents as described above until the wound was cleaned. In the regeneration phase, collagen-containing preparations saturated with Butol antiseptic until juicy granulations appeared were used. Then, autodermoplasty of the cleaned granulating wound surface was performed.

 Our proposed method for the treatment of wounds and wound infections, including trophic ulcers, long-term non-healing wounds, burn surfaces, including extensive ones, based on the differentiated use of combined antimicrobial agents, collagen-containing drugs and cell culture for the wound process, depending on its phase and flow characteristics , the degree of damage and the area of the wound surfaces, allowed to significantly improve the effectiveness of treatment and reduce the length of hospital stay by 2 times. None of the clinical observations revealed any complications to our treatment algorithm.

 Example 1. Patient S., 43 years old, medical history 124367/1387 was admitted to the hospital for treatment with a diagnosis of Varicose disease in the pool of both saphenous veins, loose type, complicated form, stage of decompensation. Chronic venous insufficiency III Art. Ulcer of the lower third of the right lower leg. On examination: both lower extremities are edematous (the diameter is segmentwise identical), the trunks of both saphenous veins are expanded at the tibia level, small venous network, hyperpigmentation. On the right lower leg in the lower third on the medial surface there is an ulcer of 9 • 7 cm with scalloped edges, covered with masses of fibrin, with purulent discharge, undermined edges, about 4 mm deep. From the anamnesis - he is sick for about 4 years, during which he notes the presence of an ulcer on his lower leg. She was treated in the clinic at the place of residence, in the hospital - without a clear effect. Ultrasound dopplerography of the veins of the lower extremities revealed the failure of safeno-femoral anastomoses on both sides, the expansion and insufficiency of the valves of the superficial veins at the level of the lower legs of both lower extremities, the insufficiency of perforating veins of the Dodd group on the right. In microbiological culture from an ulcer, the growth of Pseudomonas aeruginosa, Staphilococcus aureus, Proteus was revealed. Local treatment was carried out according to our proposed method. On the first day, we ligated with the combination agent we proposed, containing quinosol 0.5 g, streptomycin 1.5 g, polyethylene oxide-400 753.0 g, polyethylene oxide-1500 187.0 g, distilled sterile water 58.0 g. Already on the next day, the patient noted a decrease in pain in the ulcer, the dressing ceased to get wet wound discharge. On the 2nd day, the dressing was repeated with the same agent. On day 3, a decrease in edema and the number of fibrinous deposits in the ulcer was noted. According to the method of treatment used, they switched to dressings with the combination agent proposed by us, consisting of quinosol 0.5 g, streptomycin 1.5 g, anhydrous lanolin 500.0 g, distilled sterile water 498.0 g. Next, the dressings were performed after 2 days. On examination, a decrease in fibrinous deposits, wound cleansing was noted. On day 10, the ulcer surface is clean, the wound surface is pink, juicy granulation is visible. In the microbiological culture of growth of Pseudomonas aeruginosa, Staphilococcus aureus, Proteus - no. A culture of allofibroblasts fixed on a lyophilized amniotic membrane was placed on the wound surface. Control ligation was performed after 2-3 days, replacing the collagen coating in the areas of its lysis. Complete ulcer epithelization was achieved on day 19 from the start of treatment. The patient is restored to work capacity. After 3 months, there are no signs of ulcer recurrence. It should be noted that previous treatment for this disease did not have an effect.

Example 2. Patient P., 78 years old, medical history 10145/964 was admitted to the hospital for treatment with a diagnosis of Phlegmon superficial and deep palmar, dorsal fascial sheaths, 3 metacarpal spaces, purulent tendovaginitis 3 flexor tendons on the right. Diabetes mellitus, first detected, type II, decompensated, severe course, ketoacidosis. From the anamnesis - about 2 months ago after a minor injury (pricked with a splinter in the palm of the hand), there was swelling, hyperemia and severe pain in the palmar surface of the hand, body temperature increased to 37.5 ^o C. Within a week, it was treated independently at home with lotions of potassium permanganate - without effect. He was hospitalized in a purulent surgical department, where on the day of admission, an abscess was opened on the palmar surface of the right hand, about 6 ml of thick pus was released. After the operation - a short improvement, after 3 days the body temperature rose again, pain appeared on the back of the hand. The pus nodule was opened on the back surface, through drainage was put through 3 intercarpal spaces. Local treatment consisted of washing the wound with a solution of furatsilin, chlorhexidine, boric acid, and dressings with sintomycin emulsion, Levomekol ointment, and iodoform gauze were placed locally. Thus, the patient was treated for 5 weeks. Despite the fact that pus stains were not found during dressings, that systemic antibiotic therapy was carried out, there was no local improvement in the patient. From the wound, the expiration of purulent discharge with an unpleasant odor continued, there was no tendency to healing. The body temperature in the evening reached 38 ^o C, blood sugar did not respond to correction and had a value of 11-12 mmol / l, the phenomena of ketoacidosis practically did not stop (the value of acetone in the urine + / +++). Treatment using the method developed by us was started on the 36th day of hospitalization. In microbiological culture from the wound in large numbers revealed the growth of colonies of Str. faecalis, E. coli, Ps. aeruginosa, Proteus mirabilis. After revision, a minimal necrectomy was performed in the wound. The wound was washed with Butol solution, after which a dressing was applied with the combination agent proposed by us, containing quinosol 0.5 g, streptomycin 1.5 g, polyethylene oxide-400 753.0 g, polyethylene oxide-1500 187.0 g, distilled sterile water 58 , 0 g. On the 2nd day, the disappearance of the fetid odor from the wound, a decrease in purulent discharge, was noted. Dressings with the specified tool were performed daily for 6 days. By the 6th day, it was possible to achieve almost complete cleansing of the wound from necrotic masses, to reduce local inflammatory changes, the appearance of juicy granulations, normalization of body temperature, relief of ketoacidosis and hyperglycemia (acetone-negative, glycemia of 8.2 mmol / l). In microbiological culture from the wound - single colonies of S. epidermidis, E. coli. Then we continued dressings with the combination agent proposed by us, consisting of quinosol 0.5 g, streptomycin 1.5 g, anhydrous lanolin 500.0 g, distilled sterile water 498.0 g. A rapid increase in granulation was noted. On the 14th day, the wound was almost completely healed, only residual defects were noted on the back and palmar surfaces of the right hand. After treating the wound surfaces with Butol, the defects are filled with a lyophilized collagen sponge saturated with the Butol chemotherapeutic agent. Complete wound healing on the 19th day from the start of treatment according to our proposed method. The patient was examined a month after treatment, recurrence of the disease was not noted. I would like to note that the treatment of the patient with traditional local treatment did not bring a positive result and the prognosis of the disease, given the concomitant pathology, duration of the course and age of the patient, was initially regarded as unfavorable.

 A search by the applicant for scientific, technical and patent sources of information on the fund of the patent and technical department of the Samara Regional Technical Library and analysis of the prior art, the identification of sources containing information about the closest analogue of the claimed invention, made it possible to establish that no signs characterized by identical signs were not found ( identical) to all the essential features of the claimed invention "Method for the treatment of wounds and wound infections of the skin."

 Therefore, the claimed invention meets the criterion of "novelty."

 To verify the compliance of the claimed invention with the condition "inventive step", the applicant conducted an additional search for known solutions to identify signs that match the distinctive essential features of the claimed invention.

 The search results showed that the claimed invention "A method for the treatment of wounds and wound infections of the skin" does not follow explicitly from the prior art as determined by the applicant, the effect of the envisaged essential features of the claimed invention on the achievement of the set technical result is not revealed.

 Therefore, the claimed invention meets the criterion of "inventive step".

 The criteria of the invention "industrial applicability" is confirmed by the fact that the proposed invention "Method for the treatment of wounds and wound infections of the skin" can be successfully and effectively, without significant material costs, used in various fields of clinical practice for the treatment of trophic ulcers, non-healing wounds, burns, including extensive.

Claims (2)

 1. A method of treating wounds and wound infections of the skin, including the use of combined antimicrobial agents, a collagen sponge depending on the phase of the wound process, the degree of damage and the area of the wound surface, characterized in that in the phase of inflammation of the wound process, the wound is covered with sterile gauze napkins soaked in a combination chemotherapeutic agent containing quinosole 0.5 g, streptomycin 1.5 g, polyethylene oxide-400 753.0 g, polyethylene oxide-1500 187.0 g, distilled sterile water 58.0 g, producing revyazki daily until purification from necrotic masses; then, on a wound surface of the skin, once every 2-3 days, a combined chemotherapeutic agent is applied, evenly under a bandage, consisting of quinosol 0.5 g, streptomycin 1.5 g, anhydrous lanolin 500.0 g, distilled sterile water 498.0 g and in the phases of regeneration and epithelization after treatment of the wound surface with the combined chemotherapeutic agent Butol, a collagen sponge, or placenta, or amniotic membrane saturated with Butol is applied to granulating wounds, performing dressings as they resorb and material.  2. The method according to p. 1, characterized in that with extensive wound surfaces, with trophic ulcers, long non-healing wounds in the phases of regeneration and epithelization, a culture of fibroblasts and keratinocytes is applied to the wound surface.