RU2220724C1 - Antibacterial and wound-healing agent "ultrakol" - Google Patents

Abstract

FIELD: medicine, pharmacy. SUBSTANCE: invention relates to antibacterial and wound-healing agents. Invention proposes the preparation comprising collagen, methyluracil, metronidazole, sanguiritrin taken in the definite ratio. Agent elicits antibacterial and wound-healing activity and provides reducing wound healing times. EFFECT: enhanced effectiveness of agent, valuable medicinal properties.

Description

 The invention relates to medicine, in particular to antimicrobial and wound healing agents, and can be used in clinical practice for the treatment of infected wounds.

 The main disadvantage of most drugs for the prevention and treatment of purulent wounds is the unidirectionality of their action.

 Prospects for increasing the effectiveness of medical treatment of purulent wounds are determined by the possibility of using a number of different drugs in one dosage form, each of which should activate the development of various phases of the wound process, contributing to the rapid healing of the wound.

 So, it is known antimicrobial agent for the treatment of wounds and burns based on collagen and sanguirytrin (RF patent 2014089, A 61 L 15/32, 1994).

 The disadvantage of this known tool is the relatively low antimicrobial activity and the absence of wound healing activity.

 The objective of the invention is the development of tools with higher antimicrobial activity in combination with wound healing activity, which reduces the healing time of wounds.

This task is achieved by a means containing collagen, methyluracil, metronidazole, sanguirytrin, while the components are taken in the following quantitative proportions, wt. %:
Collagen - 86.5-91.2
Methyluracil - 4.0-6.0
Metronidazole - 4.0-6.0
Sanguirythrin - 0.8-1.5
To obtain funds "Ultracol" use freeze-drying of a collagen solution in a mixture with methyluracil, metronidazole and sanguiritrin.

 After preparing a mixture of collagen, methyluracil, metronidazole and sanguirytrin, it is poured into cuvettes for an hour, frozen and freeze-dried.

 The dry finished product is optionally further structured in formaldehyde vapor. When structuring collagen, intermolecular bonds are formed that increase its resistance to the action of biofluids and cells. Collagen resorption occurs within 2-15 days, depending on the state of the wound.

 Biomedical tests performed in vitro and in vivo on models of infected wounds showed high material efficiency.

 Example 1

To 1 kg of a 2% acetic acid collagen solution, 1 l of water is added, in which 0.92 g of methyluracil, 0.92 g of metronidazole, 0.18 g of sanguirytrin are dissolved and thoroughly mixed. The mixture is poured into flat cuvettes with a layer thickness of (6 ± 2) mm and frozen to -35 ^o C. The cuvette with the frozen composition is transferred to a freeze-drying apparatus and dried in a vacuum of 100 mm RT. Art. The drying is carried out at 40 ^o C. The total drying time is 20 hours. The dry product is ventilated, cut into wafers of a given size, packaged in plastic bags and sterilized by radiation sterilization.

 Example 2

 To 1 kg of a 2% acetic acid collagen solution, 1 l of water is added in which 1.32 g of methyluracil, 1.32 g of metronidazole, 0.32 g of sanguirytrin are dissolved, further, as in example 1.

 Example 3

To 1 kg of a 2% acetic acid collagen solution, 1 l of water is added in which 1 g of methyluracil, 1 g of metronidazole, 0.23 g of sanguirytrin are dissolved and thoroughly mixed. The mixture is poured into flat cuvettes with a layer thickness of (8 ± 2) mm and frozen to -35 ^o C. The cuvettes with frozen product are transferred to a freeze-drying apparatus and dried in a vacuum of 100 mm Hg. at 40 ^o C. The total drying time of 20 hours. The dry product is kept in an atmosphere saturated with water vapor for 16 hours, pressed to a thickness of 1 mm, sterilized in formaldehyde vapor for 6 hours at room temperature, ventilated, cut into wafers of specified sizes, packaged in plastic bags and sterilized by radiation sterilization .

 The study of the biological activity of the drug "Ultracol".

 We conducted a series of in vitro and in vivo experiments for microbiological evaluation of the complex antimicrobial and wound healing agent "Ultracol". At the preliminary stage, we studied the effect of the drug on the clinical strains of microorganisms: S.aureus, E.coli, Klebsiella oxytoca, C.sordelii, as well as on cultures obtained from patients with purulent-septic complications. These studies showed a wide range of high antimicrobial activity of Ultracol in relation to gram-positive, gram-negative microbial strains, as well as in relation to anaerobes.

Previously, on 80 male rats, the healing of full-layer planar wounds under the scab (control group) and using the Ultracol (experimental group) was studied. A model of a planar musculocutaneous wound was reproduced by excision in the interscapular region of skin with round-shaped subcutaneous tissue of ~ 400 mm ² , followed by crushing of muscle tissue into which a pathogenic culture of S. aureus and P. aerygmosa was introduced in an amount of 1.5 • 10 ⁵ microbial bodies in 1 ml of physiological saline. The bottom of the wound was crushed by Kocher clamp. A ring with a diameter of 20 mm was sutured from synthetic material to the edges of the wound (to prevent contraction), which was removed on the 9th day after the start of the experiment. Histological studies were performed on 3, 6, 9, 12 days after surgery.

 A morphological study showed that the healing of purulent wounds under the scab (control group) is characterized by prolonged inflammatory changes that develop against the background of disorders of the microcirculation system, which significantly inhibits the repair process. At the same time, microabscesses and signs of secondary necrotizing persist for a long time in the newly formed granulation tissue. When using the "Ultracol" means (experimental group), the formation of a less pronounced leukocyte-fibrinous layer occurs, weakening of microbial contamination, neutrophilic infiltration and swelling of the tissue, a decrease in the severity of hemorrhage, signs of slug phenomenon and vasculitis, secondary necrotizing of the newly formed tissue, which indicates a weakening of the inflammatory reaction and microcirculatory disorders and contributes to the earlier formation, maturation and remodeling of granulation tissue and its epithelialization tion.

 Clinical example.

 Tarakhtunov OA, 63 g., Diagnosis: severe combined trauma, closed craniocerebral trauma, compression of the brain, fracture of 2-8 ribs on both sides. Fracture of the sternum. Bilateral hematorx. Closed comminuted fracture of the left femur in the upper and middle thirds with the displacement of fragments. Closed fracture of the left patella. Closed fracture of the inner ankle with subluxation of the foot outside. Bruised wounds of the area n / 3 of the left thigh and in / 3 of the right lower leg.

 The injury was received on April 13, 2002 as a result of a car accident. First aid and treatment in a hospital in Lobnya. PHO of wounds was made, a skeletal traction system was applied. A course of drug therapy was conducted. When the general condition improved, the patient was hospitalized in the intensive care unit of the CITO on 13.04.02. After the preoperative preparation, the patient performed an operation on April 17, 2002: thoracoscopy on the right, removal of hematoma, drainage of the right pleural cavity, osteosynthesis of the left femur with the PFN (AO) system with blocking, osteosynthesis of the left patella with the AO screw, manual simultaneous reposition of the inner ankle, elimination of subluxation feet outside, deep plaster cast.

 The postoperative period was uneventful. The wounds healed by primary intention. The seams are removed. Due to the inferior primary surgical treatment of the wounds of the left knee joint and in / 3 of the right lower leg, their inflammation and suppuration occurred. In this connection, the seams were removed. Taken microbiological cultures from wounds showed a high titer of microbial seeding. It was decided to conduct local treatment of wounds through the use of the antimicrobial and wound healing agent "Ultracol". The treatment was carried out by applying to the wound surface of this product 4 times a week (every other day) for 2 weeks. After 3 procedures, purification of wounds from purulent detritus and the appearance of islands of marginal epithelization and a significant decrease in microbial contamination of the surface of the wounds were noted. Complete epithelialization of wounds occurred after 7 procedures. In satisfactory condition, the patient was discharged for outpatient treatment.

 The drug was used in 5 patients and allowed to achieve complete epithelization, on average at the 2-3rd week of treatment, depending on the size of the wounds and the degree of microbial contamination.

Claims (1)

Antimicrobial and wound healing agent based on collagen and sanguirytrin, characterized in that it additionally contains methyluracil and metronidazole in the following ratio of components, wt.%: Collagen 86.5-91.2 Methyluracil 4.0-6.0 Metronidazole 4.0-6.0 Sanguirythrin 0.8-1.5