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INVENTION
Patent of the Russian Federation RU2185155
ANTISEPTIC ANTI-AGE ADHESIVE
The name of the inventor: Krivoshein Yury Semenovich; Rudko Adolina Petrovna
The name of the patent holder: Krivoshein Yuri Semenovich; Rudko Adolina Petrovna
Address for correspondence: 103045, Moscow, Daev per., 2, ap. 32, Y. Krivosheinu
Date of commencement of the patent: 2000.04.27
The invention relates to medicine and relates to an antiseptic wound healing glue which includes miramistin, ethyl alcohol and BF-6 glue in a certain ratio. The glue has no toxic, irritating and allergic effect on the skin. The adhesive has a pronounced antibacterial, antifugal effect, enhances regenerative processes in the wound and protects clean wounds from infection.
DESCRIPTION OF THE INVENTION
The invention relates to the field of medicine and veterinary medicine, in particular to glues used in surgery, traumatology and everyday life. They are used as a non-bandage dressing that isolates the damaged skin from the environment, or for gluing disjointed and cut areas of the body tissue after surgery or trauma.
It is known to use in medicine and veterinary medicine glue BF-6, which is an alcohol solution of modified phenol-formaldehyde resin, polyvinylbutyrol and rosin, plasticized (FS 42-1221-87). The main disadvantage of this technical solution is its low antiseptic properties, which are manifested to the same only at the time of application and do not have a prolonged action.
It is an object of the present invention to provide a glue for medicine and veterinary medicine having pronounced antiseptic and wound healing properties, as well as a sustained action.
The goal is achieved by adding an antiseptic to the known BF-6 glue, which uses miramistin in the form of an alcoholic solution, with the following ratio of components, mass%:
- Miramistin 0.1-0.0
- Ethyl alcohol - 5.0 - 10.0
- Glue BF-6 - Up to 100
Miramistin is known and approved for use as a means for the prevention of sexually transmitted diseases in the form of 0.01% aqueous solution (VFS 42-2048-91).
The declared antiseptic and wound healing adhesive (KAP) shows a significant antiseptic effect, which persists even if it dries and a film forms.
The effectiveness and properties of the claimed KAP are illustrated by the following specific examples.
Five samples of CAR were prepared for the study (Table 1). The BF-6 glue was used as the prototype. All the samples were a clear, viscous liquid from yellow to reddish color, depending on the color of the BF-6 glue used.
On air the samples quickly thickened, forming a transparent elastic film. Viewing films in polarized light showed their amorphousness (homogeneity) in all cases.
Adhesive properties of CAR according to the claimed technical solution and the mechanical strength of the film formed during its drying did not differ statistically from the corresponding properties of the BF-6 adhesive for its various series.
Antimicrobial properties of CAR
The antimicrobial activity of the samples was investigated by diffusion to agar, the reference strains Staphylococcus aureus 209P, Escherichia coli and Candida albicans were used as test cultures. Staphylococcus and E. coli were inoculated into standard Petri dishes for meat-peptone agar, Candida - for a dense Saburo environment.
In the first series of experiments, KAP and the prototype were injected into the agar with injections with a sterile loop. For the second series of experiments, disks with a diameter of 6 mm were made from glue films which were prepared under sterile conditions by uniformly applying the samples to the polyethylene surface at a rate of 0.125 ml / Cm, followed by drying for 24 hours at room temperature and separating from polyethylene. Adhesive discs were placed on microorganisms sown with nutrient media. Petri dishes, seeded with staphylococcus and E. coli, were incubated at 37 ° C for 24 hours, candida at 22 ° C for 48 hours. Antimicrobial activity was assessed by measuring the growth inhibition zones of microorganisms around injections and discs (Tables 2 and 3).
It was established that KAP samples possess antibacterial and antifugal activity. This applies to both the actual glue and the films formed when it dries. The higher the myramistin concentration, the more pronounced the antimicrobial effect of the prototypes. The best effect was possessed by CAR, containing 0.5% miramistin. The difference between its activity and prototype activity is statistically significant.
It is important that the antimicrobial activity of KAP persists even when it dries out, which is not characteristic of the prototype. The second feature of CAR is its high antikandid activity.
The wound healing properties of CAR and its ability to prevent infection of wounds.
The study of wound healing properties of CAR was carried out in two series of experiments on male Vistar white rats.
In 38 animals of the 1st series, anesthetized with diethyl ether for 2-4 min, on the dorsal side of the body, a 2x2 cm skin site was shaved behind the right scapula. Having seized the skin with tweezers and pulled it, a flap of about 1 sq. The resulting polygonal wound with non-contiguous edges was drained with a sterile gauze pad. Then the animals of the 1 st and 2 nd groups (10 each) were applied to the wound with experimental samples of KAP with a myramistin concentration of 0.01 and 0.1%, respectively. Wounds of rats of the third group (8 animals) were treated with a prototype, the 4th control group consisted of 10 rats whose wounds were not treated.
The drugs were applied in such a way that the glue covered the entire wound and the intact skin area around it. After the glue dries, each animal is released into a separate cage. After 3, 6, 9, 11 and 13 days from the beginning of the experiment (before the healing of wounds in animals of all groups), a planimetric study was performed, which allowed to judge the features of the course of reparative processes. Measurement of the wound area was carried out as follows. On the celluloid film applied to the wound, its contours were applied, after which the area of the wound surface was determined using millimeter paper.
The results of the first series of experiments (Table 4) showed that under the influence of KAP and the prototype, the healing of wounds at the early stages of the study (1-6 days) was somewhat accelerated. In addition, the period between 9 and 11 days, reparative changes were statistically significantly more pronounced in rats treated with KAP (group 1), compared to the animals treated with the prototype.
In the second series of experiments 47 rats, prepared similarly to the previous ones, a linear skin wound 1 cm long and 2 mm deep was applied with a scalpel. All manipulations were carried out in compliance with the rules of asepsis. To the drained wounds of the animals of the 1st (9 rats), the 2nd (9), the 3rd (10) and the 4th (10) groups, samples of KAP with a myramistin concentration of 0.01, 0.1, 0, 2, and 0.5%. The wounds of the rats of the 5th group (9) were covered with a prototype. After 15-20 minutes after the formation of the adhesive film, 0.5 ml of 1 billion of a suspension of the daily culture of S. aureus 209P was applied to it. After 1, 2, 3, 4 and 5 days, the state of the wound was determined, the presence of an adhesive film and perifocal inflammatory reaction (hyperemia) was taken into account.
A local inflammatory response was noted in only three rats whose wounds had been treated with a prototype, and none of the rats treated with CAR with a myramistin concentration of 0.01%; Hyperemia was determined only during the first two days. In animals of the 2 nd, 3 rd and 4 th groups (at higher concentrations of miramistin), there were no signs of inflammation.
Thus, some KAP samples when applied to clean dry wounds of the skin not only promote faster healing, but also prevent infection, creating a permanent elastic membrane that hinders the penetration of bacteria and has an anti-inflammatory effect. These properties of CAR are generally more pronounced than in the prototype (medical glue BF-6).
STUDY OF TOXIC PROPERTIES OF CARS
Based on the data on the specific effect of CAR, the maximum period of its application is two weeks (14 days). In accordance with the order 1509 of the Ministry of Health of the USSR of 30.12.1983, the period of study of chronic toxicity for such drugs is 1 month.
Methods of research. The experiments were performed on 8 rats and 7 rabbits, which were applied to shaved areas of the skin equal to 0.1 body areas with a thin layer of CAR twice a week for 1 month.
All the animals took into account the following parameters: general condition, mass, composition of peripheral blood, functional state of the liver, morphological structure of organs.
Results of experiments . Visual observations of the general condition of experimental animals for a month did not reveal any deviations in the behavior, appearance and consumption of feed. Weighing of animals, which was carried out once a week, did not reveal any deviations.
Analysis of data characterizing the composition of peripheral blood in rats and rabbits during a one-month experiment showed that CAR with a 0.5% miramistin had no significant effect on the hemoglobin content (8.49 ± 0.29 mmol / L before the experiment, 8, 31 ± 0.33 mmol / L in a month), ESR (1.23 ± 0.15 mm before the experiment, 1.26 ± 0.29 mm after 1 month), erythrocytes (5.2 ± 0.23 T / l - before the experiment, 5,9 ± 0,27 t / l - after 1 month), leukocytes (13,7 ± 2,2 t / l - before the experiment, 15,2 ± 1,9 t / l - 1 month), platelets (371.5 ± 113.3 t / l before the experiment, 430.0 ± 97.3 t / l - after 1 month), and a leukogram of blood of rats. The observed deviations were of the same type and did not differ statistically from the control.
To assess the functional state of the liver, a protein-synthetic function was examined for the content of the total protein of the blood by a refractometric method, and a thymol sample was placed. Analysis of the obtained data showed that during the whole observation of the rats that were in the experiment, the values of the total protein (77.3 ± 1.59 g / L before the experiment, 73.4 ± 1.97 g / L - through months) and Thymol test (0.258 ± 0.12 units - before the experiment, 0.237 ± 0.11 units - after 1 month) are within physiological norms.
There were no significant deviations in behavior and weight, eating fodder in 7 rabbits used in the experiments. The composition of peripheral blood, studied before the beginning of the experiment and after 1 month, was not statistically different: hemoglobin (6.93 ± 0.25 mmol / L - before the experiment, 7.21 ± 0.29 mmol / L through month), ESR ( 2,13 ± 0,47 - before the experiment, 1,93 ± 0,49 - after 1 month), erythrocytes (4.23 ± 0.21 t / l - before the experiment, 4.41 ± 0.23 t / l - 1 month), leukocytes (1.96 ± 1.85 t / l - before the experiment, 12.3 ± 1.9 t / l - after 1 month), platelets (469.43 ± 59.3 - before the experiment , 397.65 ± 51.3 t / l - after 1 month). There was no difference in the leukogram.
Beloxinetic liver function in rabbits for 1 month of the experiment, and the indices of thymol test were within the limits of physiological norm: total protein (69.27 ± 2.19 g / l - before the experiment, 71.23 ± 1.9 g / l - After 1 month), thymol test (0 units - before the experiment, 0 units - after 1 month).
Thus, the obtained data make it possible to conclude that the claimed preparation - 0.5% KAP when applied to the skin by experimental animals for 1 month does not cause functional disorders on the part of blood and internal organs.
Pathomorphological and histological changes in internal organs in experimental animals killed after the end of the experiments were not revealed.
Based on the data obtained, it can be concluded that 0.5% of CAR according to the current classification of toxic substances refers to substances of the IV hazard class (low toxicity).
Effect of CAR on the skin of experimental animals
Local irritant effect on the skin of rabbits and rats was studied during the application of 0.5% CAR to shaved areas of the skin for 1 month visually, as well as for histological studies of skin preparations stained with hematoxylin-eosin.
The obtained data showed that skin application of 0.5% CAR within 1 month did not cause either visual or histological changes on the skin side.
STUDY OF THE ALLERGY ACTION OF CARS
The experiments were performed on 10 guinea pigs weighing 300-400 g in accordance with the Methodological Recommendations of the USSR Ministry of Health
"Detection of the hypersensitivity of the skin to ointment and viscous substances in the experiment" (1976), representing a modification of two known methodical schemes of experimental dermatology.
The results of the study showed that, both on the primary contact and on the secondary contact areas of the skin, the irritation reaction was not visually observed during the observation period. Histological examination of skin sites exposed to KAP did not reveal inflammatory micro-reactions.
Thus, in experiments on experimental animals, it was shown that KAP does not possess a skin irritating and allergic effect.
On the basis of the data obtained, it can be concluded that the claimed formulation of KAR in its properties is superior to the prototype. It has a pronounced antibacterial, antifungal action, enhances regenerative processes in the wound and protects clean wounds from infection. The ratio of components in KAP is optimal within the limits claimed in the formula.
CLAIM
Antiseptic wound healing glue, including BF-6 glue, characterized in that it additionally contains an alcohol solution of myramistin at the following proportions of components, wt. %:
- Miramistin 0.3-0.0
- Ethyl alcohol is 5.0 - 10,
- Glue BF-6 - Other
print version
Date of publication 08.11.2006gg
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