Bone cement capable of resisting drug-resistant bacteria

Abstract

The invention discloses drug-resistant bacteria resistant bone cement, and belongs to the field of medical materials. By adding the novel antibacterial agent, namely the Sortase A inhibitor, the use of antibiotics is avoided, the conditions of common bacteria, drug-resistant bacteria infection and the like can be effectively handled, and the antibacterial property is good. Benefited from the unique antibacterial mechanism of the Sortase A inhibitor, the drug-resistant bacteria resistant bone cement not only has good antibacterial property on staphylococcus aureus, but also has good antibacterial property on methicillin-resistant staphylococcus aureus, and in addition, the mechanical property of the bone cement is good.

Description

Technical Field

[0001] The present invention belongs to the field of medical materials, and particularly relates to an anti-drug-resistant bacteria bone cement. Background Art

[0002] As a medical material, bone cement plays an important role in orthopedic treatment and is widely used in treatment methods such as prosthesis replacement and bone defect repair. Among them, acrylic bone cement, especially polymethyl methacrylate (PMMA) bone cement, has gradually become the gold standard due to its excellent performance in mechanical properties, biocompatibility, etc. PMMA is often composed of a solid phase agent and a liquid phase agent. The solid phase agent includes PMMA powder, a developer, a free radical initiator, etc., and the liquid phase agent is composed of MMA, an accelerator, an inhibitor of polymerization, etc. In order to prevent and treat bacterial infections, heat-stable antibiotics are usually added to PMMA bone cement to prepare antibiotic-loaded bone cement (ALBC).

[0003] However, due to the extensive use of antibiotics, bacterial drug resistance has increased significantly, and methicillin-resistant Staphylococcus aureus (MRSA) has become a serious clinical challenge. The antibiotics added in traditional ALBC are insufficient in dealing with MRSA infections. To prevent postoperative bacterial infections, especially drug-resistant bacteria infections, it is urgent to develop new antibacterial bone cements. Summary of the Invention

[0004] Aiming at the problem of antibiotic resistance in existing ALBC, the present invention provides an anti-drug-resistant bacteria bone cement containing a new antibacterial agent. By adding a Sortase A inhibitor with antibacterial activity, the present invention obtains a new antibacterial bone cement with good anti-drug-resistant bacteria activity and mechanical properties.

[0005] The anti-drug-resistant bacteria bone cement of the present invention includes a solid phase agent and a liquid phase agent.

[0006] The solid phase agent includes an inhibitor with antibacterial effects.

[0007] Further, the inhibitor is a Sortase A inhibitor.

[0008] Furthermore, the inhibitor is 1-(3,4-dichlorophenyl)-3-(dimethylamino)propan-1-one hydrochloride (hereinafter referred to as "inhibitor"), and its structure is shown as follows:

[0009]

[0010] The drug-resistant bacteria are methicillin-resistant Staphylococcus aureus (MRSA).

[0011] The mass proportion of the inhibitor in the solid phase agent is 0.5%-25%, preferably 2.5%-10%, such as 2.5%, 5%, 10%, and more preferably 5%.

[0012] The solid phase agent is composed of an inhibitor and a commercially available bone cement solid phase agent; or is composed of a raw material comprising the following components: PMMA powder, an inhibitor, benzoyl peroxide, barium sulfate or zirconium dioxide.

[0013] The liquid phase agent is a commercially available bone cement liquid phase agent, or is a compound of raw materials including the following components: methyl methacrylate, dimethyl paratoluidine, etc.

[0014] Furthermore, the components are composed of the following by mass:

[0015] Solid phase agent: PMMA powder 45-52 parts, inhibitor 1.5-6.5 parts, barium sulfate or zirconium dioxide 10 parts, benzoyl peroxide 0.5 parts.

[0016] Liquid phase agent: 36 parts of methyl methacrylate, 0.2 parts of dimethyl p-toluidine.

[0017] The solid phase agent and the liquid phase agent are usually mixed in a mass ratio of 2:1 to form bone cement.

[0018] Application of the antibacterial bone cement of the present invention in preparing bone repair materials.

[0019] The bone cement of the invention contains an inhibitor and has good antibacterial activity, mechanical properties and biocompatibility.

[0020] The beneficial effects of the present invention are embodied in:

[0021] 1. The present invention adds a new antibacterial agent (Sortase A inhibitor, 1-(3,4-dichlorophenyl)-3-(dimethylamino)propan-1-one hydrochloride), avoids the use of antibiotics, can effectively deal with common bacteria and drug-resistant bacteria infections, and has good antibacterial properties.

[0022] 2. Thanks to the unique antibacterial mechanism of Sortase A inhibitor, the increase of bacterial resistance is effectively avoided. In addition, it has good mechanical properties. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is the antibacterial zone diameter test data. Figure 1 It can be seen that the inhibitor-added bone cement has a significantly larger antibacterial zone diameter for MRSA than gentamicin bone cement, and its sustained antibacterial ability is also better than gentamicin; for common Staphylococcus aureus, the inhibitor bone cement's sustained antibacterial ability is also better than gentamicin. Another Sortase A inhibitor, phenyl vinyl sulfone, is ineffective.

[0024] Figure 2 These are the mechanical strength test data of the bone cement before and after being soaked for 7 days. Figure 2 It can be seen that the mechanical properties of each group of bone cement decreased to a certain extent after soaking. Compared with the pure PMMA bone cement, the mechanical strength of the bone cement added with inhibitor and gentamicin did not decrease, and it was higher than the 70 MPa required by the ISO5833 standard.

[0025] Figure 3 These are the scanning electron microscope (SEM) images of the bone cement. Figure 3 It can be seen that there are no obvious differences in each group of bone cement after brittle fracture, and the hemispherical cavities that appear under the same conditions conform to the signs of PMMA bone cement. Specific implementation mode

[0026] Next, in combination with the embodiments of the present invention, the technical solutions of the present invention will be described. The described embodiments are part of the embodiments of the present invention, rather than all of the embodiments.

[0027] 1-(3,4-Dichlorophenyl)-3-(dimethylamino)propan-1-one hydrochloride used in the examples was obtained commercially.

[0028] Examples:

[0029] The bone cement includes a solid phase agent and a liquid phase agent, and its composition is as follows:

[0030]

[0031] Preparation method of antibacterial bone cement: Mix the solid phase agent and the liquid phase agent according to the ratio in the above table, and form a cylinder with a height of 12 mm and a diameter of 6 mm in a mold. 1 in the table is conventional PMMA bone cement, and 2, 3, and 4 are antibacterial bone cements with inhibitor addition amounts of 2.5%, 5%, and 10% respectively based on the mass of the solid phase agent.

[0032] The antibacterial activity evaluation of the inhibitor is as follows: Resuscitate and passage Staphylococcus aureus (ACTT 25923) and MRSA to restore their activity. Synthesize bone cement samples with a preferred drug concentration of 5% (height 3 mm, diameter 6 mm) one day before the experiment. On the day of the experiment, prepare Staphylococcus aureus and MRSA bacterial suspensions with a concentration of 0.5×10 8 CFU / mL respectively. Dip a disposable sterile swab into the bacterial suspension, evenly smear it in the culture dish, place each group of bone cement in a suitable position in the culture dish, and make marks. Place the culture dish in CO 2Incubate in an incubator at 37°C for one day and measure the diameter of the inhibition zone. Replace the culture dish every day for 7 consecutive days to measure its sustained antibacterial performance, and count the diameter of the inhibition zone every day to calculate the antibacterial release effect of bone cements containing different drugs against two types of bacteria. Prepare 5% gentamicin bone cement using the same method for experimental comparison of antibacterial performance. Each concentration of bone cement is tested in triplicate. We also tried other types of inhibitors such as phenyl vinyl sulfone, but there was no antibacterial effect. The results are shown in Figure 1 .

[0033] The mechanical strength test is as follows: Polish the bone cement samples (5 in each group) with 1000-mesh sandpaper until the top and bottom surfaces are parallel. Incubate some samples at 37°C and 100% humidity for 7 days to compare the mechanical strength before and after treatment. At room temperature, use a materials testing machine (MTS809, Bose Corporation, USA) to plot the deformation-load curves of the bone cement samples at a loading rate of 20 mm / min. Calculate the compressive strength and elastic modulus of each bone cement sample from these curves. Prepare 5% gentamicin bone cement using the same method for experiments. All operations are carried out in accordance with the requirements and standards of ISO 5833. The results are shown in Figure 2 .

[0034] Figure 3 is the scanning electron microscope image of the bone cement prepared according to the examples in the table after being treated by liquid nitrogen embrittlement.

Claims

1. A bone cement for resisting drug-resistant bacteria, characterized in that: The anti-drug-resistant bacteria bone cement comprises a solid phase agent and a liquid phase agent; The solid phase agent includes an inhibitor having an antibacterial effect, and the inhibitor is a Sortase A inhibitor.

2. The anti-drug-resistant bacteria bone cement according to claim 1, characterized in that: The inhibitor is 1-(3,4-dichlorophenyl)-3-(dimethylamino)propan-1-one hydrochloride, and its structure is shown below: 。 3. The anti-drug-resistant bacteria bone cement according to claim 1, characterized in that: The drug-resistant bacteria is methicillin-resistant Staphylococcus aureus.

4. The anti-drug-resistant bacteria bone cement according to claim 1 or 2, characterized in that: The mass proportion of the inhibitor in the solid phase agent is 0.5%-25%.

5. The anti-drug-resistant bacteria bone cement according to claim 4, characterized in that: The mass proportion of the inhibitor in the solid phase agent is 2.5%-10%.

6. The anti-drug-resistant bacteria bone cement according to claim 5, characterized in that: The mass proportion of the inhibitor in the solid phase agent is 5%.

7. The anti-drug-resistant bacteria bone cement according to claim 1, characterized in that: The mass ratio of the solid phase agent to the liquid phase agent is 2:

1.

8. Use of the anti-resistant bacteria bone cement according to any one of claims 1 to 7 in the preparation of bone repair materials.

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