RU2324499C2 - Method of prevention of purulent process in post-operational osseous defect - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention can be used in prevention of purulent process in the area of the post-operational osseous defects. 3% poviargol is added to the bioactive glass-ceramic spongeous byositall implant, at 18° ÷ 3°C by use of electrophoresis within 30 min at current intensity 50 mA; the saturation of implants with antiseptic is performed under the load until the hydrophilic gasket is firmly adhered to the implants.

EFFECT: long-lasting antibacterial effect is provided inside infected osseous wound.

3 dwg, 3 tbl

Description

The invention relates to medicine, namely to traumatology and orthopedics, and can be used to prevent the development of purulent processes in the field of postoperative bone defects.

The pathomorphological basis of chronic purulent infection of bone tissue is sequestra, pathological granulation, bone foci of necrosis and osteomyelitis bone tissue defect (cavity) [2]. The most difficult and not completely resolved question is the treatment of abdominal forms of chronic osteomyelitis [6, 11].

In accordance with modern views, antimicrobial agents can be effective and promote healing only against the background of radical surgical intervention that eliminates a bone defect [3, 4, 5]. Good long-term results were obtained by surgeons who used biological materials such as muscle and bone autografts and demineralized bone matrix for plastic filling of cavities [8, 7]. However, paying tribute to these techniques, it can be noted that plastic surgery with its own blood-supplying tissues is not always applicable due to the size and shape of the bone defect or in connection with its localization. This statement becomes especially relevant in cases of significant cicatricial degeneration of soft tissues. In these cases, in our opinion, the use of various alternative osteosubstitution materials of a synthetic nature is justified.

The ease of use of such methods, an unlimited amount of plastic material, various types and sizes of implants, the ability to replace bone defects at any location and shape of the osteomyelitis cavity allow the use of these methods in all surgical hospitals. In addition, a number of fundamentally new bioceramic materials have been recently created that can optimize the conditions of osteoregeneration in the area of a bone defect [9, 10].

Our proposed method for the prevention of recurrence of purulent processes in the field of postoperative bone defects combines the use of osteo-substituting glass-crystal implants as a bone cavity filler with a local antibacterial effect, achieved by introducing an antiseptic (poviargol) into the biositall.

The analogues of our proposed technique include methods for filling bone defects with synthetic polymer materials based on ceramics. In Western countries, industrial production has begun and biodegradable materials based on natural polymers, such as Bioos, Interpor, OsteoSet, are widely used. A number of synthetic bioceramic materials have already been created and tested on animals, capable of not only filling bone defects, but also having pronounced osteoinductive properties. However, the high commercial cost of these drugs, the lack of antiseptic properties of these materials does not allow their use for plastic bone defects in conditions of purulent infection. These disadvantages are partially resolved by the use of the Septopal preparation manufactured by Biomet Merck (Germany). Septopal implants are used to fill infected bone defects in traumatology and orthopedics, as the implants include an antibiotic (gentamicin).

However, this technique has several disadvantages. First of all, the fact that the main chemical component of Septopal is a copolymer of methyl methacrylate, methyl acrylate and aminoacetic acid, which are cytotoxic drugs, can be attributed to them. In this regard, the chains of Septopal implanted in bone defects are usually removed 2 weeks after the operation, that is, after the end of the action of the antibiotic introduced into the implants. The absence of osteoinductive properties in Septopal, the cytotoxicity of methyl methacrylate compounds, the need to remove implants in the early postoperative period significantly limits the scope of this drug in surgical practice.

These deficiencies are partially resolved by the use of demineralized bone grafts (VCT) for bone grafting. They are valuable biological material, however, having osteoinductive properties, these grafts do not in themselves have antimicrobial properties.

The closest invention (prototype) to our proposed method is a method of sterilizing tubular VCT [1]. According to the method proposed by the authors, sterilization of such grafts is carried out by electrophoresis of antiseptics (3% silver nitrate solution for 2 hours at a current strength of 50 mA). When studying antimicrobial activity, it was found that in VCT saturated with silver nitrate by this method, it turned out to be significantly higher than in the control. The authors concluded that this method is very promising, including for purulent osteology, due to the fact that the bone graft, acquiring pronounced antimicrobial properties, does not lose its osteoinductive properties. However, the use of VCT is limited due to the sensitization of some patients to a bone antigen that causes rejection, and ultimately, suppuration of the graft.

Unlike VCT, biositall is inert in relation to the surrounding tissues of the body. In the available literature, we did not find information about allergic reactions to the implantation of synthetic glass-crystalline materials. At the same time, the proven positive osteogenic activity of bio-metal is noteworthy, which makes it possible to widely use the material in traumatology and orthopedics, as well as in maxillofacial surgery. However, the lack of antimicrobial properties in biositall does not allow the use of this material in conditions of wound infection. Our proposed method allows us not only to sterilize porous biositall implants, but also to give them pronounced antibacterial properties and thereby provide a long-term local antimicrobial effect in the area of the bone wound.

The technical result of the invention is a long-term local antibacterial effect in the area of a bone wound (22 days or more), the absence of allergic reactions to implants, a decrease in the time for saturation of implants with antiseptics (up to 30 minutes), unlimited scope in surgical practice, the general availability of the method, lower commercial cost of the proposed way.

The result of the invention is achieved by the fact that a bioactive glass crystalline porous implant (bio-glass) at a temperature of 18 ° ± 3 ° C is introduced by electrophoresis into a 3% solution of poviargol for 30 minutes at a current strength of 50 mA, and the implants are saturated with an antiseptic under a load of 5 kg .

The drawings show:

figure 1 - diagram of the method of saturation of cylindrical biositall implants using electrophoresis;

figure 2 - diagram of the method of electrophoretic saturation of the granules of biositall with a solution of poviargol.

The tables show:

Table 1. The values of zones of growth inhibition of microorganisms depending on the concentration of poviargol (in the control and main groups), where * - p <0.05;

Table 2. The values of zones of growth inhibition of microorganisms depending on the exposure time (in the control and main groups), where * - p <0.05;

Table 3. The level of residual antibacterial activity of the implants, depending on the timing of elimination (by the size of the growth inhibition zone on Petri dishes), where * - p <0.05.

The diagram shows a graphical representation of the data in table 3.

The method is as follows. Porous vitreous glass bio-ceramic implants in the form of cylinders and granules are saturated by electrophoresis with a 3% solution of poviargol (a highly dispersed metallic silver stabilized by low molecular weight gulivinylpyrrolidone medical, reg. No. MZ RF: 97/167/7). Saturation is carried out in non-sterile conditions at room temperature (18 ° ± 3 ° C) using galvanic devices widely used in physiotherapy (Potok-1, Elfor-prof, etc.). Electrophoresis exposure time 30 minutes.

Cylinders of biositall (Fig. 1), usually 4-5 pieces, are placed vertically between the electrode gaskets. The gasket on the bottom electrode is impregnated with a 3% solution of poviargol and connected to the positive pole (anode) of the galvanic apparatus. The upper pad is moistened with distilled water, tightly pressed to the implants using a load of 5 kg and connected to the negative pole (cathode). Such an arrangement of the electrodes provides a uniform distribution of electric field lines over the entire area of the implants, which ensures uniform antiseptic impregnation of the entire thickness of the porous glass-crystal biositall implant. The use of a load (5 kg) ensures a tight fit of hydrophilic pads to the implants, which allows reducing the saturation rate of the implants with antiseptic ions and thereby reducing the saturation time (up to 30 minutes).

For electrophoretic saturation of the granulate using a special device (figure 2). A rectangular plate is made from a dielectric. In different parts of it, through holes with a diameter of 1 cm are made. The plate is laid on top of a pad moistened with a 3% solution of poviargol. Biosital granules are poured into the holes. A gasket soaked in distilled water is placed on top of the plate. The system created in this way is placed under a press (5 kg). Poviargol is administered from the positive pole (anode).

Implants made of glass-crystalline material do not conduct electric current, since they are dielectric. After impregnation of the implants with a solution of poviargol, which is an electrolyte, the bio-metal acquires the ability to pass an electric current through itself. Due to its porous structure, biositall implants are able to be easily saturated with any liquid preparations. We determined that the current in the electric network appears when the biositall is impregnated with a 0.3% solution of poviargol. As the concentration of pivargolum solution increases, the strength of the current passing through the material also increases proportionally. Probably, this phenomenon is directly related to the number of particles of ionized silver, the osmolarity of the solution of poviargol. An ion current arises inside the pores of the ceramic product, which contributes to a faster and deeper saturation of the implants with silver ions.

Significant sorption capacity and pore volume of bone-substituting glass-crystalline material allow large amounts of an active antiseptic to be introduced into its composition. In addition, in our opinion, under electrokinetic influences, the ability to change the surface zetopotential is manifested due to the recharging of the SiO ^- and SiOH ^- groups ^, which are always present on the surface of the bio ^- metal. This ability to retain the adsorbed compounds and complexes formed by polyvinylpyrrolidone and Ag ⁺ ensures the duration of the drug release over time and the process dynamics different from the dynamics of removal of poviargol from ceramic implants saturated by simple diffusion. Thus, when porous biositall implants are impregnated with solutions of poviargol in a concentration of more than 0.3%, the glass crystalline material acquires relative conductive properties, which allows the use of electrophoresis to sterilize the material and impart antimicrobial properties to these osteo-substituting glass crystalline porous implants. During the microbiological series of experiments, the results are obtained, which are shown in tables 1 and 2.

As can be seen from the data in the tables, with an increase in the time of exposure of electrophoresis (experimental group), biositall acquires the maximum bacteriostatic effect much faster than with the diffusion method of saturation (control group).

The most effective way of imparting antimicrobial properties to biositall implants is the electrophoretic method of saturation with a 3% solution of poviargol for 30 minutes. With a further increase in exposure time, the strength of the antibacterial effect remains virtually unchanged.

We also studied the dynamics of the elimination of antiseptics from porous glass-crystal implants (table 3 and diagram). In the experimental series, the residual antibacterial activity of biositall granules saturated with an antiseptic by electrophoresis was studied. In the control group, the properties of granules saturated with the diffusion method were studied.

From table 3 and the diagram shows that in the control group there is a much sharper decrease in antibacterial activity in the period from the first to six days. In the experimental group, this indicator decreased more smoothly and by 22 days remained at the level significantly higher (1.4 times) than in the control group.

At the end of the experiment, all implants used in the study were tested for residual bactericidal activity and bacteriostaticity. We determined that even at these times the implants from the experimental group retain pronounced antibacterial activity and completely inhibit the growth of microbes at a microbial load of 1 × 10 ⁵ CFU / cm ² .

Thus, we have proved the effectiveness of saturation of porous glass-crystal implants with poviargol using the electrophoresis method. In the study of antimicrobial activity, it was found that in a bio-glass saturated with pivargol according to the proposed method, it was significantly higher than in control, that is, for implants saturated by the infusion method.

The most effective is the use of a 3% solution of poviargol with an electrophoresis exposure of 30 minutes or more. The use of biositall implants saturated with povargol using electrophoresis allows creating a long-lasting antibacterial effect inside an infected bone wound for 22 days or more, which allows us to consider our proposed technique as a way of preventing purulent processes inside infected bone defects.

Table 1 No. p / p Poviargol Concentration (%) Exposure Time (min) The size of the zone of growth inhibition of microorganisms (mm) Experience The control one one thirty 13.10 ± 0.48 * 8.30 ± 0.42 2 60 13.00 ± 0.58 * 11.40 ± 0.60 3 120 13.30 ± 0.17 * 12.20 ± 0.45 four 3 thirty 15.80 ± 1.04 * 9.30 ± 0.38 5 60 14.30 ± 0.62 * 11.70 ± 0.50 6 120 13.60 ± 0.85 13.00 ± 0.33 7 5 thirty 12.00 ± 0.44 10.70 ± 0.50 8 60 14.10 ± 0.46 13.20 ± 0.37 9 120 13.70 ± 0.37 13.80 ± 0.45 table 2 No. p / p Exposure Time (min) Poviargol Concentration (%) The size of the zone of growth inhibition of microorganisms (mm) Experience The control one thirty one 13.10 ± 0.48 * 8.30 ± 0.42 2 3 15.80 ± 1.04 * 9.30 ± 0.38 3 5 12.00 ± 0.44 10.70 ± 0.50 four 60 one 13.00 ± 0.58 * 11.40 ± 0.60 5 3 14.30 ± 0.62 * 11.70 ± 0.50 6 5 14.10 ± 0.45 13.20 ± 0.37 7 120 one 13.30 ± 0.17 * 12.20 ± 0.45 8 3 13.60 ± 0.85 13.00 ± 0.33 9 5 13.70 ± 0.37 13.80 ± 0.45

Table 3 No. p / p Elimination dates (day) The size of the zone of growth inhibition of microorganisms (mm) Experience The control one one 14.83 ± 0.44 * 13.17 ± 0.65 2 3 11.75 ± 0.36 * 10.17 ± 0.28 3 6 13.00 ± 0.31 * 8.33 ± 0.46 four 9 12.25 ± 0.19 * 8.50 ± 0.52 5 12 12.75 ± 0.19 * 8.00 ± 0.34 6 16 11.75 ± 0.19 * 8.00 ± 0.48 7 22 11.75 ± 0.19 * 8.67 ± 0.39

Information sources

1. Zhirnov V.A., Savelyev V.I., Afinogenov G.E. The method of sterilization of a demineralized bone graft of a tubular shape // A.S. USSR No. 1701324. - Discoveries, inventions. - 1991. - No. 48. - S.33.

2. Kanorsky I.D. Principles of the pathogenetic treatment of chronic osteomyelitis: Abstract. Diss ... Dr. Sc. - M., 1983. - 36 p.

3. Kuzin M.I., Kostyuchenok B.M. Wounds and wound infection. - M-: Medicine. - 1990. - 592 p.

4. Kulik V.I., Mamontov V.D., Afinogenov G.E., Gryaznukhin E.G. Treatment of complications of open diaphyseal fractures of the lower leg bones // Diagnosis, prevention and treatment of wound infections in traumatology and orthopedics. - SPb., - 1994. - P.68-76.

5. Mamontov V.D., Kulik V.I., Afinogenov G.E. Early surgical treatment of "small forms" of suppuration in traumatology and orthopedics as a method for the prevention of postoperative osteomyelitis: Methodical. recommended - SPb. - 1993. - 10 p.

6. Markov B.I. The choice of the method of surgical treatment of chronic osteomyelitis of the tubular bones: Abstract. diss ... cand. sciences. - Saratov, 1987 .-- 21 p.

7. Cancer A.V., Linnik S.A., Nikitin G.D., Pavlov O.A. Osteomyelitis of the humerus and features of its treatment // Sat. scientific works "Diagnosis, prevention and treatment of wound infections in traumatology and orthopedics." - 1994. - S.132-135.

8. Saveliev V.I. Bone tissue transplantation: achievements and prospects // Actual issues of orthopedics. - L., 1987. - S.131-154.

9. Schepetkin I.A. Calcium phosphate materials in biological media // Successes in modern biology. - 1995. - T. 115 No. 1 - S.58-73.

10. Hench L.L. Bioceramics: From Concept to clinic. // J. Amer. Ceramic. Soc. - 1991, vol. 74, No. 7, - P.1487-1510.

11. Kiene S., Lenz P., Brinckman W., Weichteilplastiken im operativen Behand lungsprogram der ostemyelitis // Lbl. Chir. - 1978. - Bd. 103, M.13. - S.854-865.

Claims (1)

A method for preventing the development of purulent processes in the field of postoperative bone defects by filling them with osteosubstituting implants, characterized in that a 3% solution of poviargol is introduced into the bioactive glassy-crystalline porous implant from bio-metal at a temperature of 18 ° ± 3 ° C for 30 minutes at a current strength of 50 mA, and saturation of the implants with an antiseptic is carried out under load until the hydrophilic gaskets fit snugly against the implants.

Images