RU2330685C2 - Method of antibiotics fixation within porous implants - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method of antibiotics fixation within porous implants is described. Result of method application lies in possibility of reliable fixation of antibiotic solution within porous implant and arrangement of favourable conditions for haemostasis in operative wound due to application of 10% gelatine solution as antibiotic carrier. Specified result is achieved by filling porous implants with antibiotic solution in liquid gel. For this purpose implant is dipped in solution by 3/4. Filling occurs under the influence of capillary forces. After solution cooled to form dense gel, antibiotic is fixed in implant pores and gradually released after installation to bone defect area.

EFFECT: reliable fixation of antibiotic solution within porous implant and arrangement of favourable conditions for haemostasis in operative wound.

3 cl, 1 ex

Description

The invention relates to medicine, namely to traumatology, orthopedics and neurosurgery, is intended for the treatment of osteomyelitis of the spine and the prevention of purulent complications during reconstructive surgery using porous implants, for example titanium nickelide.

A known method of applying an antibiotic to nickel-titanium wire elements, in which for applying a drug to the surface of a substrate, electrochemical oxidation of nickel-titanium samples is used, followed by “sewing” of the antibiotic due to the occurrence of chemical (hydrogen) bonds between the functional groups of the substrate and the drug, of this, before applying the antibiotic, it is necessary to activate the implant by forming active functional groups on its surface by increasing changes on the surface of the implant oxide layer (Biocompatible materials with shape memory and new technologies in medicine. / Ed. by Prof. V.E. Gunther. - Tomsk: IAP; Publishing House NTL, 2004. - P.227-229).

However, in the known method using wire elements in which there are no interconnected micropores, while the active substance is located only on the surface.

A known method of soaking a porous titanium nickelide implant in an antibiotic solution (Biocompatible materials with shape memory and new technologies in medicine / Ed. By prof. V.E. Gunther. - Tomsk: IAP; Publishing House NTL, 2004. - P.66 -74).

However, the installation of an implant prepared in a known manner in a formed bed is accompanied by the appearance of a layer of air and blood between it and the implant. In addition, further immersion of the implant in the bed is accompanied by the displacement of the antibiotic solution from the implant into the wound.

A known method of applying an antibiotic coating on materials with interconnected microcavities, in which an aqueous solution 1 is introduced into the microcavities, containing at least one component which is readily soluble in water from the groups of aminoglycoside antibiotics, tetracycline antibiotics, lincosamide antibiotics, 4-quinolone antibiotics and chlorhexidines, and aqueous solution 2 containing at least one water-soluble component from the groups of alkyl sulfates, alkyl sulfonates, alkyl aryl sulfates, dialkyl aryl sulfates, alkyl aryl sulfo atoms, dialkyl aryl sulfonates, cycloalkyl sulfates, cycloalkyl sulfonates, alkyl cycloalkyl sulfates, while between the introduction of solutions 1 and 2, water is mainly removed from the components of solutions 1 and 2, a coating is formed in microcavities, which consists of a poorly soluble precipitate in water (RF patent 2236871, publ. 2004.03.03. .twenty).

However, in the known method, two solutions are used to obtain a coating in microcavities, while water is previously removed from them, which leads to the formation of a poorly soluble precipitate, which includes an antibiotic, the bioavailability of the latter is reduced due to poor solubility.

An object of the present invention is to provide a method for fixing antibiotics in porous implants.

The problem is solved in that in the method of fixing antibiotics in porous implants, including filling the implant micropores with an antibiotic solution, a sterile solution of antibiotic and liquid gel is preliminarily prepared, then the porous implant is placed at 3/4 of its height, which is kept in the solution up to the formation of a dense gel with zero fluidity, the implant is removed from it and used to replace bone defects.

In an embodiment of the invention, high molecular weight compounds (IUDs) are used as a liquid gel, capable of forming a dense gel at room temperature that is firmly fixed in the pores of the implant.

To reduce costs when performing the method, it is advisable to use a gelatin solution as an IUD.

It is advisable to uniformly dissolve the antibiotic in the IUD to use preliminary dissolution of the antibiotic in sterile water for injection.

To form a strong implant - bone block - it is advisable to use a porous titanium nickelide implant.

The present invention is illustrated in the detailed description, exemplary embodiments, and tables.

The method is as follows.

For the preparation of a liquid gel using high molecular weight compounds (IUDs), such as gelatin, collagen.

Under aseptic conditions, gelatin is weighed to produce a 12.5% solution, and water is injected for swelling. Then, in a water bath, the gelatin container is heated to 40 ° C, thereby achieving complete dissolution, that is, a liquid gel. Sterilized by heating three times to 105 ° C for 30 minutes for three days in a row. One serving is poured into Petri dishes to control sterility. After cooling to 35-40 ° C, the second solution is poured with a solution of the antibiotic - cefotaxime, achieving its maximum concentration. For this, a 1 g dose of antibiotic is dissolved in 2 ml of water for injection under aseptic conditions and added to 8 ml of a 12.5% gelatin solution. After thorough mixing, cork. Subsequently, within 7 days, samples of the antibiotic solution are taken to evaluate the activity of the drug, which is evaluated biologically, comparing the zone of growth inhibition of microorganisms.

After controlling the sterility and confirming the preservation of the activity of the antibacterial drug in the gel, the porous implants are filled with a solution of the antibiotic in a solution of liquid gel.

Then the porous implants are filled with the resulting solution.

For this, the implant is sterilized and immersed under aseptic conditions, leaving 1/4 of the implant height free of liquid in a vessel containing a 10% solution of a water-soluble antibiotic in a 10% sterile gelatin solution.

In this case, a solution of a liquid gel with an antibiotic is heated to a temperature of 37.0-40.0 ° C. Micropore filling occurs due to capillary forces of the implant. It is advisable not to completely immerse the implant in the solution, since due to the high viscosity of the solution, not all air is forced out of it. Maximum absorption is noted when immersed in 2/3 or 3/4 of a horizontally oriented implant. After filling the pores of the implant (at least 5 min) and subsequent cooling of the solution until a dense gel is formed, the implant is removed from the container with the solution.

If the implant is not completely immersed in the gelatin solution, the air is forced out of the implant gradually and completely replaced by the solution until it appears directly on the implant surface. Implant filling control is carried out by weighing.

The amount of antibiotic in the micropores of the implant depends on the active pore capacity, the size of the implant itself and the solubility of a particular antibacterial drug in water.

Example 1. The mass of the implant 9.55 g

Under aseptic conditions, gelatin was weighed to produce a 12.5% solution; it was poured for injection with water for swelling. After that, in a water bath, the gelatin container was heated to 40 ° C — complete dissolution. They were sterilized by heating three times to 105 ° C for 30 minutes for three consecutive days. One serving was poured into Petri dishes to control sterility. After cooling to 35–40 ° C, a solution of the antibiotic cefotaxime in 2 ml of water for injection was poured into the second. A 1 g dose of antibiotic was dissolved in 2 ml of water for injection under aseptic conditions and added to 8 ml of a 12.5% gelatin solution. After thorough mixing, they were corked. Subsequently, with an interval of two days, a sample of the antibiotic solution in a 10% gelatin gel was taken to evaluate the activity of the drug, which was tested biologically, comparing the zone of growth inhibition of microorganisms. There were no significant differences within 1 week.

After controlling sterility and confirming the preservation of the activity of the antibacterial drug in the gel, the porous implants were filled with a solution of an antibiotic in a gelatin solution.

The filling of porous implants with this solution was carried out as follows.

The implant is sterilized and immersed under aseptic conditions, leaving 1/4 of the implant surface free of liquid in a vessel containing a 10% solution of a water-soluble antibiotic in a 10% sterile gelatin solution. When preparing a gelatin solution, water is taken taking into account the water used to dissolve the antibiotic.

A 10% solution of the antibiotic in a 10% solution of gelatin was heated to a temperature close to body temperature, 37.0-40.0 ° C. Filling occurs due to the capillary forces of the implant. It is advisable not to completely immerse the implant in the solution, since due to the high viscosity of the solution, not all air is forced out of it. Maximum absorption was observed when immersed in 2/3 or 3/4 of a horizontally oriented implant. After filling the pores of the implant (at least 5 min) and subsequent cooling of the solution to the formation of a dense gel, the implant was removed from the container with the solution.

If the implant is not completely immersed in the gelatin solution, the air is forced out of the implant gradually and completely replaced by the solution until it appears directly on the implant surface. Implant filling was monitored by weighing.

The proposed method of antibiotic fixation is highly effective when using porous implants to replace bone defects formed after removal of the affected bone tissue during injuries and inflammatory bone diseases against the background of radical rehabilitation of the foci of infection. Promotes the implementation of hemostasis in the surgical wound and the prolonged action of the antibacterial drug in the focus of infection.

Experimental data show that for the prevention of purulent complications when using porous titanium nickelide implants to replace bone defects, including spinal osteomyelitis, it is advisable to fill the implants with an antibiotic gel solution. In this case, the implant has antibacterial activity, as the drug is released gradually after the gel solution enters the liquid phase. In addition, the gelatin solution has a hemostatic effect, which facilitates the implementation of hemostasis in the surgical wound.

The proposed method allows for the prolonged action of an antibiotic. In this case, the activity of the antibacterial drug persists for seven days, then gradually decreases over the course of a week.

This method of antibiotic fixation was used in the clinic of the Department of Traumatology, Orthopedics and VPH of the Tyumen State Medical Academy. Implants prepared by this method, with a fixed antibiotic in them, were used in the treatment of spinal osteomyelitis in eight patients with good long-term treatment results (observation periods of more than two years).

Claims (3)

1. A method of fixing antibiotics in porous implants, comprising filling the micropores of the implant with an antibiotic solution, characterized in that a sterile solution of the antibiotic in a liquid gel is preliminarily prepared, which is a biocompatible high molecular weight gel-forming compound such as gelatin or collagen into which the porous implant is placed 3/4 of its height and kept in solution until a dense gel is formed in the interconnected microcavities of the implant and used to replace bone defects at. 2. The method according to claim 1, characterized in that the preliminary dissolution of the antibiotic in sterile water for injection is used. 3. The method according to PP.1 and 2, characterized in that they use a porous implant made of titanium nickelide.